Modulational instability and spectral broadening of vortex modes in chiral photonic crystal fibers

Paul Roth, Philip Russell, Michael Frosz, Yang Chen, Gordon Wong

We report on intra- and inter-modal four-wave-mixing (FWM) in N-fold rotationally symmetric (C_N) single- and multi-core chiral photonic crystal fiber (PCF), created by spinning the preform during fiber drawing. The non-circular modal field is forced to rotate as it propagates along the fiber, resulting in circular birefringence and robust maintenance of circular polarization state. Multi-core chiral C_N PCF supports vortex-carrying helical Bloch modes (HBMs) in which the degeneracy between clockwise and counter-clockwise vortices is lifted. This makes possible new kinds of intermodal polarization modulational instability (PMI). We develop PMI theory for vortex HBMs, and illustrate the results by a series of experiments in which two or more PMI sidebands with different vorticities and polarization states are selectively generated by adjusting the polarization state and topological charge of the pump light. In every case both the topological charge and the spin of the pump light are conserved. We also report generation of a broadband supercontinuum in a single circularly polarized vortex mode.

Confocal Interferometric Scattering Microscopy Reveals 3D Nanoscopic Structure and Dynamics in Live Cells

Michelle Küppers, David Albrecht, Anna D. Kashkanova, Jennifer Lühr, Vahid Sandoghdar

Bright-field light microscopy and related techniques continue to play a key role in life sciences because they provide a facile and label-free insight into biological specimen. However, lack of three-dimensional imaging and low sensitivity to nanoscopic features hamper their application in high-end quantitative studies. Here, we remedy these shortcomings by employing confocal interferometric scattering (iSCAT) microscopy. We demonstrate the performance of this label-free technique in a selection of case studies in live cells and benchmark our findings against simultaneously acquired fluorescence images. We reveal the nanometric topography of the nuclear envelope, quantify the dynamics of the endoplasmic reticulum, detect single microtubules, and map nanoscopic diffusion of clathrin-coated pits undergoing endocytosis. Furthermore, we introduce the combination of confocal and wide-field iSCAT modalities for simultaneous imaging of cellular structures and high-speed tracking of nanoscopic entities such as single SARS-CoV2 virions. Confocal iSCAT can be readily implemented as an additional contrast mechanism in existing laser scanning microscopes.

Quantum Efficiency of Single Dibenzoterrylene Molecules in para-Dichlorobenzene at Cryogenic Temperatures

Mohammad Musavinezhad, Alexey Shkarin, Dominik Rattenbacher, Jan Renger, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

We measure the quantum efficiency (QE) of individual dibenzoterrylene (DBT)<br>molecules embedded in para-dichlorobenzene at cryogenic temperatures. To achieve<br>this, we apply two distinct methods based on the maximal photon emission and on<br>the power required to saturate the zero-phonon line. We find that the outcome of<br>the two approaches are in good agreement, reporting a large fraction of molecules<br>with QE values above 50 %, with some exceeding 70 %. Furthermore, we observe<br>no correlation between the observed lower bound on the QE and the lifetime of the<br>molecule, suggesting that most of the molecules have a QE exceeding the established<br>lower bound. This confirms the suitability of DBT for quantum optics experiments.<br>In light of previous reports of low QE values at ambient conditions, our results hint at<br>the possibility of a strong temperature dependence of the QE.

Multiphoton non-local quantum interference controlled by an undetected photon

Kaiyi Qian, Kai Wang, Leizhen Chen, Hou Zhaohua, Mario Krenn, Shining Zhu, Xiao-Song Ma

The interference of quanta lies at the heart of quantum physics. The multipartite generalization<br>of single-quanta interference creates entanglement, the coherent superposition of states shared by several quanta. Entanglement allows non-local correlations between many quanta and hence is a key resource for quantum information technology. Entanglement is typically considered to be essential for creating non-local correlations, manifested by multipartite interference. Here, we show that this is not the case and demonstrate multiphoton non-local quantum interference without entanglement of any intrinsic properties of the photons. We harness the superposition of the physical origin of a four-photon product state, which leads to constructive and destructive interference of the photons’ mere existence. With the intrinsic indistinguishability in the generation process of photons, we realize four-photon frustrated quantum interference. We furthermore establish non-local control of multipartite quantum interference, in which we tune the phase of one undetected photon and observe the interference of the other three photons. Our work paves the way for fundamental studies of non-locality and potential applications in quantum technologies.

Impact of crowding on the diversity of expanding populations

Carl F. Schreck, Diana Fusco, Yuya Karita, Stephen Martis, Jona Kayser, Marie-Cécilia Duvernoy, Oskar Hallatschek

Crowding effects critically impact the self-organization of densely packed cellular assemblies, such as biofilms, solid tumors, and developing tissues. When cells grow and divide, they push each other apart, remodeling the structure and extent of the population’s range. Recent work has shown that crowding has a strong impact on the strength of natural selection. However, the impact of crowding on neutral processes, which controls the fate of new variants as long as they are rare, remains unclear. Here, we quantify the genetic diversity of expanding microbial colonies and uncover signatures of crowding in the site frequency spectrum. By combining Luria–Delbrück fluctuation tests, lineage tracing in a novel microfluidic incubator, cell-based simulations, and theoretical modeling, we find that the majority of mutations arise behind the expanding frontier, giving rise to clones that are mechanically “pushed out” of the growing region by the proliferating cells in front. These excluded-volume interactions result in a clone-size distribution that solely depends on where the mutation first arose relative to the front and is characterized by a simple power law for low-frequency clones. Our model predicts that the distribution depends on a single parameter—the characteristic growth layer thickness—and hence allows estimation of the mutation rate in a variety of crowded cellular populations. Combined with previous studies on high-frequency mutations, our finding provides a unified picture of the genetic diversity in expanding populations over the whole frequency range and suggests a practical method to assess growth dynamics by sequencing populations across spatial scales.

Quench-drive spectroscopy and high-harmonic generation in BCS superconductors

Matteo Puviani, Rafael Haenel, Dirk Manske

In pump-probe spectroscopies, THz pulses are used to quench a system, which is subsequently probed by either a THz or optical pulse. In contrast, third-harmonic generation experiments employ a single multicycle driving pulse and measure the induced third harmonic. In this work, we analyze a spectroscopy setup where both a quench and a drive are applied and two-dimensional spectra as a function of time and quench-drive delay are recorded. We calculate the time evolution of the nonlinear current generated in the superconductor within an Anderson-pseudospin framework and characterize all experimental signatures using a quasiequilibrium approach. We analyze the superconducting response in Fourier space with respect to both the frequencies corresponding to the real time and the quench-drive delay time. In particular, we show the presence of a transient modulation of higher harmonics, induced by a wave mixing process of the drive with the quench pulse, which probes both quasiparticle and collective excitations of the superconducting condensate.

Stimulated Raman transition in a single molecule

Johannes Zirkelbach, Burak Gürlek, Masoud Mirzaei, Alexey Shkarin, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

The small cross section of Raman scattering has hampered the direct study of this eect at the<br>single molecule level. By exploiting the high Franck-Condon factor of a common-mode resonance,<br>choosing a large vibrational frequency dierence in electronic ground and excited states, and operation<br>at T < 2K, we succeed at driving a coherent stimulated Raman transition in a single molecule.<br>We observe and model a spectral splitting that serves as a characteristic signature of the coherent<br>phenomenon at hand. Our study sets the ground for exploiting the intrinsically ecient coupling<br>of the vibrational and electronic degrees of freedom in molecules for quantum optical operations in<br>the solid state.

Self-supervised machine learning pushes the sensitivity limit in label-free detection of single proteins below 10 kDa

Mahyar Dahmardeh, Houman Mirzaalian Dastjerdi, Hisham Mazal, Harald Köstler, Vahid Sandoghdar

Interferometric scattering (iSCAT) microscopy is a label-free optical method capable of detecting single proteins, localizing<br>their binding positions with nanometer precision, and measuring their mass. In the ideal case, iSCAT is limited by shot noise<br>so that collection of more photons should allow its detection sensitivity to biomolecules of arbitrarily low mass. However, a<br>number of technical noise sources combined with speckle-like background fluctuations have restricted the detection limit in<br>iSCAT. Here, we show that an unsupervised machine learning isolation forest algorithm for anomaly detection pushes the<br>mass sensitivity limit by a factor of four to below 10 kDa. We implement this scheme both with a user-defined feature matrix<br>and a self-supervised FastDVDNet and validate our results with correlative fluorescence images recorded in total internal<br>reflection mode. Our work opens the door to the optical detection of small traces of disease markers such as alpha-synuclein,<br>chemokines, and cytokines.

Topological phase diagrams of exactly solvable non-Hermitian interacting Kitaev chains

Sharareh Sayyad, Jose L. Lado

Many-body interactions give rise to the appearance of exotic phases in Hermitian physics. Despite their importance, many-body effects remain an open problem in non-Hermitian physics due to the complexity of treating many-body interactions. Here, we present a family of exact and numerical phase diagrams for non-Hermitian interacting Kitaev chains. In particular, we establish the exact phase boundaries for the dimerized Kitaev-Hubbard chain with complex-valued Hubbard interactions. Our results reveal that some of the Hermitian phases disappear as non-Hermiticty is enhanced. Based on our analytical findings, we explore the regime of the model that goes beyond the solvable regime, revealing regimes where non-Hermitian topological degeneracy remains. The combination of our exact and numerical phase diagrams provides an extensive description of a family of non-Hermitian interacting models. Our<br>results provide a stepping stone toward characterizing non-Hermitian topology in realistic interacting quantum many-body systems.

Crystal superlattices for versatile and sensitive quantum spectroscopy

Zi S. D. Toa, Maria V. Chekhova, Leonid A. Krivitsky, Anna V. Paterova

Nonlinear interferometers with quantum correlated photons have been demonstrated to improve optical characterization and metrology. These interferometers can be used in gas spectroscopy, which is of particular interest for monitoring greenhouse gas emissions, breath analysis and industrial applications. Here, we show that gas spectroscopy can be further enhanced via the deployment of crystal superlattices. This is a cascaded arrangement of nonlinear crystals forming interferometers, allowing the sensitivity to scale with the number of nonlinear elements. In particular, the enhanced sensitivity is observed via the maximum intensity of interference fringes that scales with low concentration of infrared absorbers, while for high concentration the sensitivity is better in interferometric visibility measurements. Thus, a superlattice acts as a versatile gas sensor since it can operate by measuring different observables, which are relevant to practical applications. We believe that our approach offers a compelling path towards further enhancements for quantum metrology and imaging using nonlinear interferometers with correlated photons.

Selective phase filtering of charged beams with laser-driven antiresonant hollow-core fibers

Luca Genovese, Max Kellermeier, Frank Mayet, Klaus Floettmann, Gordon Wong, Michael Frosz, Ralph Assmann, Philip Russell, Francois Lemery

Emerging accelerator concepts increasingly rely on the combination of high-frequency electromagnetic radiation with electron beams, enabling longitudinal phase space manipulation which supports a variety of advanced applications. The handshake between electron beams and radiation is conventionally provided by magnetic undulators which unfortunately require a balance between the electron beam energy, undulator parameters, and laser wavelength. Here we propose a scheme using laser-driven large-core antiresonant optical fibers to manipulate electron beams. We explore two general cases using TM01 and HE11 modes. In the former, we show that large energy modulations O(100 keV). can be achieved while maintaining the overall electron beam quality. Further, we show that by using larger field strengths O(100 MV/m) the resulting transverse forces can be exploited with beam-matching conditions to filter arbitrary phases from the modulated electron bunch, leading to the production of ≈100 attosecond FWHM microbunches. Finally, we also investigate the application of the transverse dipole HE11 mode and find it suitable for supporting time-resolved electron beam measurements with sub-attosecond resolution. We expect the findings to be widely appealing to high-charge pump-probe experiments, metrology, and accelerator science.

Deep learning of many-body observables and quantum information scrambling

Naeimeh Mohseni, Junheng Shi, Tim Byrnes, Michael Hartmann

Machine learning has shown significant breakthroughs in quantum science, where in particular deep neural networks exhibited remarkable power in modeling quantum many-body systems. Here, we explore how the capacity of data-driven deep neural networks in learning the dynamics of physical observables is correlated with the scrambling of quantum information. We train a neural network to find a mapping from the parameters of a model to the evolution of observables in random quantum circuits for various regimes of quantum<br>scrambling and test its \textit{generalization} and \textit{extrapolation} capabilities in applying it to unseen circuits. Our results show that a particular type of recurrent neural network is extremely powerful in generalizing its predictions within the system size and time window that it has been trained on for both, localized and scrambled regimes. These include<br>regimes where classical learning approaches are known to fail in sampling from a representation of the full wave function. Moreover, the considered neural network succeeds in \textit{extrapolating} its predictions beyond the time window and system size that it has been trained on for models that show localization, but not in scrambled regimes.

Engineering Arbitrary Hamiltonians in Phase Space

Lingzhen Guo, Vittorio Peano

We introduce a general method to engineer arbitrary Hamiltonians in the Floquet phase space of a periodically driven oscillator, based on the non-commutative Fourier transformation (NcFT) technique. We establish the relationship between an arbitrary target Floquet Hamiltonian in phase space and the periodic driving potential in real space. We obtain analytical expressions for the driving potentials in real space that can generate novel Hamiltonians in phase space, e.g., rotational lattices and sharp-boundary well. Our protocol<br>can be realised in a range of experimental platforms for nonclassical states generation and bosonic quantum computation.

Recent advances in the Self-Referencing Embedding Strings (SELFIES) library

Alston Lo, Robert Pollice, AkshatKumar Nigam, Andrew D. White, Mario Krenn, Alán Aspuru-Guzik

String-based molecular representations play a crucial role in cheminformatics applications, and with the growing success of deep learning in chemistry, have been readily adopted into machine learning pipelines. However, traditional<br>string-based representations such as SMILES are often prone to syntactic and semantic errors when produced by generative models. To address these problems, a novel representation, SELF-referencIng Embedded Strings (SELFIES), was proposed that is inherently 100% robust, alongside an accompanying open-source implementation. Since then, we have generalized SELFIES to support a wider range of molecules and semantic constraints and streamlined its underlying grammar. We have implemented this updated representation in subsequent versions<br>of \selfieslib, where we have also made major advances with respect to design, efficiency, and supported features. Hence, we present the current status of \selfieslib (version 2.1.1) in this manuscript.

Linear optical elements based on cooperative subwavelength emitter arrays

Nico S. Baßler, Michael Reitz, Kai P. Schmidt, Claudiu Genes

We describe applications of two-dimensional subwavelength quantum emitter<br>arrays as efficient optical elements in the linear regime. For normally<br>incident light, the cooperative optical response, stemming from emitter-emitter<br>dipole exchanges, allows the control of the array's transmission, its resonance<br>frequency, and bandwidth. Operations on fully polarized incident light, such as<br>generic linear and circular polarizers as well as phase retarders can be<br>engineered and described in terms of Jones matrices. Our analytical approach<br>and accompanying numerical simulations identify optimal regimes for such<br>operations and reveal the importance of adjusting the array geometry and of the<br>careful tuning of the external magnetic fields amplitude and direction.<br>

Shear rheology of methyl cellulose based solutions for cell mechanical measurements at high shear rates

Beyza Büyükurganci, Santanu Kumar Basu, Markus Neuner, Jochen Guck, Andreas Wierschem, Felix Reichel

Methyl cellulose (MC) is a widely used material in various microfluidic applications in biology. Due to its biocompatibility, it has become a popular crowding agent for microfluidic cell deformability measurements, which usually operate at high shear rates (>10 000 s−1). However, a full rheological characterization of methyl cellulose solutions under these conditions has not yet been reported. With this study, we provide a full shear-rheological description for solutions of up to 1% MC dissolved in phosphate-buffered saline (PBS) that are commonly used in real-time deformability cytometry (RT-DC). We characterized three different MC-PBS solutions used for cell mechanical measurements in RT-DC with three different shear rheometer setups to cover a range of shear rates from 0.1–150 000 s−1. We report viscosities and normal stress differences in this regime. Viscosity functions can be well described using a Carreau–Yasuda model. Furthermore, we present the temperature dependency of shear viscosity and first normal stress difference of these solutions. Our results show that methyl cellulose solutions behave like power-law liquids in viscosity and exhibit first normal stress difference at shear rates between 5000–150 000 s−1. We construct a general viscosity equation for each MC solution at a certain shear rate and temperature. Furthermore, we investigated how MC concentration influences the rheology of the solutions and found the entanglement concentration at around 0.64 w/w%. Our results help to better understand the viscoelastic behavior of MC solutions, which can now be considered when modelling stresses in microfluidic channels.

Optical Vortex Brillouin Laser

Xinglin Zeng, Philip Russell, Yang Chen, Zheqi Wang, Gordon Wong, Paul Roth, Michael Frosz, Birgit Stiller

Optical vortices, which have been extensively studied over the last decades, offer an additional degree of freedom useful in many applications, such as optical tweezers and quantum control. Stimulated Brillouin scattering (SBS), providing a narrow linewidth and a strong nonlinear response, has been used to realize quasi-continuous wave lasers. Here, stable oscillation of optical vortices and acoustic modes in a Brillouin laser based on chiral photonic crystal fiber (PCF) is reported, which robustly supports helical Bloch modes (HBMs) that carry circularly polarized optical vortex and display circular birefringence. A narrow-linewidth Brillouin fiber laser that stably emits 1st- and 2nd-order vortex-carrying HBMs is implemented. Angular momentum conservation selection rules dictate that pump and backward Brillouin signals have opposite topological charge and spin. Additionally, it is shown that when the chiral PCF is placed within a laser ring cavity, the linewidth-narrowing associated with lasing permits the peak of the Brillouin gain that corresponds to acoustic mode to be measured with resolution of 10 kHz and accuracy of 520 kHz. The results pave the way to a new generation of vortex-carrying SBS systems with applications in optical tweezers, quantum information processing, and vortex-carrying nonreciprocal systems.

From Dyson Models to Many-Body Quantum Chaos

Alexei Andreanov, Matteo Carrega, Jeff Murugan, Jan Olle, Dario Rosa, Ruth Shir

Understanding the mechanisms underlying many-body quantum chaos is one of the big challenges in theoretical physics. We tackle this problem by considering a set of perturbed quadratic Sachdev-Ye-Kitaev (SYK) Hamiltonians defined on graphs. This allows to disambiguate between operator growth and<br>\emph{delocalization}, showing that the latter is the dominant process in the single-particle to many-body chaotic transition. Our results are verified numerically with state-of-the-art numerical techniques, capable of extracting<br>eigenvalues in a desired energy window of very large Hamiltonians, in this case up to dimension $2^{19}\times 2^{19}$. Our approach essentially provides a new way of viewing many-body chaos from a single-particle perspective.

A quantum trajectory analysis of singular wave functions

Angel S. Sanz, Luis Sanchez-Soto, Andrea Aiello

The Schrödinger equation admits smooth and finite solutions that spontaneously evolve into a singularity, even for a free particle. This blowup is generally ascribed to the intrinsic dispersive character of the associated time evolution. We resort to the notion of quantum trajectories to reinterpret this singular behavior. We show that the blowup can be directly related to local phase variations, which generate an underlying velocity field responsible for driving the quantum flux toward the singular region.

Embracing the diversity of model systems to deconstruct the basis of regeneration and tissue repair

Aldine Amiel, Stephanie Tsai, Daniel Wehner

The eighth EMBO conference in the series ‘The Molecular and Cellular Basis of Regeneration and Tissue Repair’ took place in Barcelona (Spain) in September 2022. A total of 173 researchers from across the globe shared their latest advances in deciphering the molecular and cellular basis of wound healing, tissue repair and<br>regeneration, as well as their implications for future clinical applications. The conference showcased an ever-expanding diversity of model organisms used to identify mechanisms that promote regeneration. Over 25 species were discussed, ranging from invertebrates to humans. Here, we provide an overview of the exciting topics presented at the conference, highlighting novel discoveries in regeneration and perspectives for regenerative medicine.

An optofluidic antenna for enhancing the sensitivity of single-emitter measurements

Luis Morales-Inostroza, Julian Folz, Ralf Kühnemuth, Suren Felekyan, Franz Wieser, Claus A.M. Seidel, Stephan Götzinger, Vahid Sandoghdar

Many single-molecule investigations are performed in fluidic environments, e.g., to avoid unwanted consequences of contact with surfaces. Diffusion of molecules in this arrangement limits the observation time and the number of collected photons, thus, compromising studies of processes with fast or slow dynamics. Here, we introduce a planar optofluidic antenna (OFA), which enhances the fluorescence signal from molecules by about 5 times per passage, leads to about 7-fold more frequent returns to the observation volume, and significantly lengthens the diffusion time within one passage. We use single-molecule multi-parameter fluorescence detection (sm-MFD), fluorescence correlation spectroscopy (FCS) and Förster resonance energy transfer (FRET) measurements to characterize our OFAs. The antenna advantages are showcased by examining both the slow (ms) and fast (50μs) dynamics of DNA four-way (Holliday) junctions with real-time resolution. The FRET trajectories provide evidence for the absence of an intermediate conformational state and introduce an upper bound for its lifetime. The ease of implementation and compatibility with various microscopy modalities make OFAs broadly applicable to a diverse range of studies.

On-chip interference of scattering from two individual molecules in plastic

Dominik Rattenbacher, Alexey Shkarin, Jan Renger, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

Integrated photonic circuits offer a promising route for studying coherent cooperative effects of a controlled collection of quantum emitters. However, spectral inhomogeneities, decoherence and material incompatibilities in the solid state make this a nontrivial task. Here, we demonstrate efficient coupling of a pair of organic molecules embedded in a plastic film to a TiO2 microdisc resonator on a glass chip. Moreover, we tune the resonance frequencies of the molecules with respect to that of the microresonator by employing nanofabricated electrodes. For two molecules separated by a distance of about 8μm and an optical phase difference of about π/2, we report on a large collective extinction of the incident light in the forward direction and the destructive interference of its scattering in the backward direction. Our work sets the ground for the coherent coupling of several molecules via a common mode and the realization of polymer-based hybrid quantum photonic circuits.

AI-discovery of a new charging protocol in a micromaser quantum battery

Carla Rodríguez, Dario Rosa, Jan Olle

We propose a general computational framework for optimizing model-dependent<br>parameters in quantum batteries (QB). We apply this method to two different<br>charging scenarios in the micromaser QB and we discover a new charging protocol<br>for stabilizing the battery in upper-laying Hilbert space chambers in a<br>controlled and automatic way. This protocol is found to be stable and robust,<br>and it leads to an improved charging efficiency in micromaser QBs. Moreover,<br>our optimization framework is highly versatile and efficient, holding great<br>promise for the advancement of QB technologies at all scales.<br>

No-Collapse Accurate Quantum Feedback Control via Conditional State Tomography

Sangkha Borah, Bijita Sarma

The effectiveness of measurement-based feedback control (MBFC) protocols is hindered by the presence of measurement noise, which impairs the ability to accurately infer the underlying dynamics of a quantum system from noisy continuous measurement records. To circumvent this limitation, a real-time stochastic state estimation approach is proposed in this work, that enables noise-free monitoring of the conditional dynamics, including the full density matrix of the quantum system, despite using noisy measurement data. This, in turn, enables the development of precise MBFC strategies that leads to effective control of quantum systems by essentially mitigating the constraints imposed by measurement noise, and has potential applications in various feedback quantum control scenarios. This approach is particularly important for machine learning-based control, where the AI controller can be trained with arbitrary conditional averages of observables, including the full density matrix, to quickly and accurately learn control strategies.

On-chip quantum interference between the origins of a multi-photon state

Lan-Tian Feng, Ming Zhang, Di Liu, Yu-Jie Cheng, Guo-Ping Guo, Dao-Xin Dai, Guang-Can Guo, M. Krenn, Xi-Feng Ren

Quantum mechanically, multiple particles can jointly be in a coherent superposition of two or more different states at the same time. This property is called quantum entanglement, and gives rise to characteristic nonlocal interference and stays at the heart of quantum information process. Here, rather than interference of different intrinsic properties of particles, we experimentally demonstrated coherent superposition of two different birthplaces of a four-photon state. The quantum state is created in four probabilistic photon-pair sources, two combinations of which can create photon quadruplets. Coherent elimination and revival of distributed 4-photons can be fully controlled by tuning a phase. The stringent coherence requirements are met by using a silicon-based integrated photonic chip that contains four spiral waveguides for producing photon pairs via spontaneous four-wave mixing. The experiment gives rise to peculiar nonlocal phenomena without any obvious involvement of entanglement. Besides several potential applications that exploit the new on-chip technology, it opens up the possibility for fundamental studies on nonlocality with spatially separated locations.

Roadmap on structured waves

K. Y. Bliokh, E. Karimi, M. J. Padgett, M. A. Alonso, M. R. Dennis, A. Dudley, A. Forbes, S. Zahedpour, S. W. Hancock, et al.

Structured waves are ubiquitous for all areas of wave physics, both classical and quantum, where the wavefields are inhomogeneous and cannot be approximated by a single plane wave. Even the interference of two plane waves, or a single inhomogeneous (evanescent) wave, provides a number of nontrivial phenomena and additional functionalities as compared to a single plane wave. Complex wavefields with inhomogeneities in the amplitude, phase, and polarization, including topological structures and singularities, underpin modern nanooptics<br>and photonics, yet they are equally important, e.g., for quantum matter waves, acoustics, water waves, etc. Structured waves are crucial in optical and electron microscopy, wave propagation and scattering, imaging, communications, quantum optics, topological and non-Hermitian wave systems, quantum<br>condensed-matter systems, optomechanics, plasmonics and metamaterials, optical and acoustic manipulation, and so forth. This Roadmap is written collectively by prominent researchers and aims to survey the role of structured waves in various areas of wave physics. Providing background, current research, and anticipating future developments, it will be of interest to a wide cross-disciplinary audience.

Quantum coherent control in pulsed waveguide optomechanics

Junyin Zhang, Changlong Zhu, Christian Wolff, Birgit Stiller

Coherent control of traveling acoustic excitations in a waveguide system is an interesting way to manipulate and transduce classical and quantum information. So far, these interactions, often based on optomechanical resonators or Brillouin scattering, have been studied in the steady-state regime using continuous waves. However, waveguide experiments are often based on optical pump pulses, which require treatment in a dynamic framework. In this paper, we present an effective Hamiltonian formalism in the dynamic regime using optical pulses that links waveguide optomechanics and cavity optomechanics, which can be used in the classical and quantum regime including quantum noise. Based on our formalism, a closed solution for coupled-mode equation under the undepleted assumption is provided and we found that the strong coupling regime is already accessible in current Brillouin waveguides by using pulses. We further investigate several possible experiments within waveguide optomechanics, including Brillouin-based coherent transfer, Brillouin cooling, and optoacoustic entanglement.

Image-based cell sorting using focused travelling surface acoustic waves

Ahmad Ahsan Nawaz, Despina Soteriou, Catherine Xu, Ruchi Goswami, Maik Herbig, Jochen Guck, Salvatore Girardo

Sorting cells is an essential primary step in many biological and clinical applications such as high-throughput drug screening, cancer research and cell transplantation. Cell sorting based on their mechanical properties has long been considered as a promising label-free biomarker that could revolutionize the isolation of cells from heterogeneous populations. Recent advances in microfluidic image-based cell analysis combined with subsequent label-free sorting by on-chip actuators demonstrated the possibility of sorting cells based on their physical properties. However, the high purity of sorting is achieved at the expense of a sorting rate that lags behind the analysis throughput. Furthermore, stable and reliable system operation is an important feature in enabling the sorting of small cell fractions from a concentrated heterogeneous population. Here, we present a label-free cell sorting method, based on the use of focused travelling surface acoustic wave (FTSAW) in combination with real-time deformability cytometry (RT-DC). We demonstrate the flexibility and applicability of the method by sorting distinct blood cell types, cell lines and particles based on different physical parameters. Finally, we present a new strategy to sort cells based on their mechanical properties. Our system enables the sorting of up to 400 particles per s. Sorting is therefore possible at high cell concentrations (up to 36 million per ml) while retaining high purity (>92%) for cells with diverse sizes and mechanical properties moving in a highly viscous buffer. Sorting of small cell fraction from a heterogeneous population prepared by processing of small sample volume (10 μl) is also possible and here demonstrated by the 667-fold enrichment of white blood cells (WBCs) from raw diluted whole blood in a continuous 10-hour sorting experiment. The real-time analysis of multiple parameters together with the high sensitivity and high-throughput of our method thus enables new biological and therapeutic applications in the future.

Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation

Luz del Carmen Martínez-Sánchez, Phuong Anh Ngo, Rashmita Pradhan, Lukas-Sebastian Becker, David Boehringer, Despina Soteriou, Markéta Kubánková, Christine Schweitzer, Tatyana Koch, et al.

Objective: Increased apoptotic shedding has been linked to intestinal barrier dysfunction and development of inflammatory bowel diseases (IBD). In contrast, physiological cell shedding allows the renewal of the epithelial monolayer without compromising the barrier function. Here, we investigated the role of live cell extrusion in epithelial barrier alterations in IBD.<br><br>Design: Taking advantage of conditional GGTase and RAC1 knockout mice in intestinal epithelial cells (Pggt1biΔIEC and Rac1iΔIEC mice), intravital microscopy, immunostaining, mechanobiology, organoid techniques and RNA sequencing, we analysed cell shedding alterations within the intestinal epithelium. Moreover, we examined human gut tissue and intestinal organoids from patients with IBD for cell shedding alterations and RAC1 function.<br><br>Results: Epithelial Pggt1b deletion led to cytoskeleton rearrangement and tight junction redistribution, causing cell overcrowding due to arresting of cell shedding that finally resulted in epithelial leakage and spontaneous mucosal inflammation in the small and to a lesser extent in the large intestine. Both in vivo and in vitro studies (knockout mice, organoids) identified RAC1 as a GGTase target critically involved in prenylation-dependent cytoskeleton dynamics, cell mechanics and epithelial cell shedding. Moreover, inflamed areas of gut tissue from patients with IBD exhibited funnel-like structures, signs of arrested cell shedding and impaired RAC1 function. RAC1 inhibition in human intestinal organoids caused actin alterations compatible with arresting of cell shedding.<br><br>Conclusion: Impaired epithelial RAC1 function causes cell overcrowding and epithelial leakage thus inducing chronic intestinal inflammation. Epithelial RAC1 emerges as key regulator of cytoskeletal dynamics, cell mechanics and intestinal cell shedding. Modulation of RAC1 might be exploited for restoration of epithelial integrity in the gut of patients with IBD.

Photon pairs bi-directionally emitted from a resonant metasurface

Changjin Son, Vitaliy Sultanov, Tomas Santiago-Cruz, Aravind P. Anthur, Haizhong Zhang, Ramon Paniagua-Dominguez, Leonid Krivitsky, Arseniy I. Kuznetsov, Maria V. Chekhova

Metasurfaces are artificially structured surfaces able to control the properties of light at subwavelength scales. While, initially, they have been proposed as means to control classical optical fields, they are now emerging as nanoscale sources of quantum light, in particular of entangled photons with versatile properties. Geometric resonances in metasurfaces have been recently used to engineer the frequency spectrum of entangled photons, but the emission directivity was so far less studied. Here, we generate photon pairs via spontaneous parametric down conversion from a metasurface supporting a quasi-bound state in the continuum (BIC) leading to remarkable emission directivities. The pair generation rate is enhanced 67 times compared to the case of an unpatterned film of the same thickness and material. At the wavelength of the quasi-BIC resonance, photons are mostly emitted backwards, while their partners, spectrally detuned by only 8 nm, are emitted forwards. This behavior demonstrates fine spectral splitting of entangled photons and their bi-directional emission, never before observed in nanoscale sources. We expect this work to be a starting point for the efficient demultiplexing of photons in nanoscale quantum optics.

Artificial Intelligence and Machine Learning for Quantum Technologies

Mario Krenn, Jonas Landgraf, Thomas Fösel, Florian Marquardt

In recent years the dramatic progress in machine learning has begun to impact many areas of science and technology significantly. In the present perspective article, we explore how quantum technologies are benefiting from this revolution. We showcase in illustrative examples how scientists in the past few years have started to use machine learning and more broadly methods of artificial intelligence to analyze quantum measurements, estimate the parameters of quantum devices, discover new quantum experimental setups, protocols, and feed- back strategies, and generally improve aspects of quantum computing, quantum communication, and quantum simulation. We highlight open challenges and future possibilities and conclude with some speculative visions for the next decade.

Cooling microwave fields into general multimode Gaussian states

Nahid Yazdi, Juan José García-Ripoll, Diego Porras, Carlos Navarrete-Benlloch

We show that a collection of lossy multi-chromatically modulated qubits can be used to dissipa- tively engineer arbitrary Gaussian states of a set of bosonic modes. Our ideas are especially suited to superconducting-circuit architectures, where all the required ingredients are experimentally avail- able. The generation of such multimode Gaussian states is necessary for many applications, most notably measurement-based quantum computation. We build upon some of our previous proposals, where we showed how to generate single-mode and two-mode squeezed states through cooling and lasing. Special care must be taken when extending these ideas to many bosonic modes, and we discuss here how to overcome all the limitations and hurdles that naturally appear. We illustrate our ideas with a fully worked out example consisting of GHZ states, but have also tested several other examples such as cluster states. All these examples allow us to show that it is possible to use a set of N lossy qubits to cool down a bosonic chain of N modes to any desired Gaussian state.

Protection of all nondefective twofold degeneracies by antiunitary symmetries in non-Hermitian systems

Sharareh Sayyad

Non-Hermitian degeneracies are classified as defective exceptional points (EPs) and nondefective de- generacies. While in defective EPs, both eigenvalues and eigenvectors coalesce, nondefective degeneracies are characterized merely by the emergence of degenerate eigenvalues. It is also known that all degeneracies are either symmetryprotected or accidental. In this paper, I prove that antiunitary symmetries protect all nondefective twofold degeneracies. By developing a 2D non-Hermitian tight-binding model, I have demonstrated that these symmetries comprise various symmetry operations, such as discrete or spatial point-group symmetries and Wick’s rotation in the non-Hermitian parameter space. Introducing these composite symmetries, I present the protection of nondefective degeneracies in various parameter regimes of my model. This work paves the way to stabilizing nondefective degeneracies and offers a new perspective on understanding non-Hermitian band crossings.

Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations

Serhii Aif, Nico Appold, Lucas Kampman, Oskar Hallatschek, Jona Kayser

Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, many resistance mutations have a substantial fitness cost and are subject to purifying selection. How emerging resistant lineages may escape purifying selection via subsequent compensatory mutations is still unclear due to the difficulty of tracking such evolutionary rescue dynamics in space and time. Here, we introduce a system of fluorescence-coupled synthetic mutations to show that the probability of evolutionary rescue, and the resulting long-term persistence of drug resistant mutant lineages, is dramatically increased in dense microbial populations. By tracking the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies we uncover an underlying quasi-stable equilibrium between the opposing forces of radial expansion and natural selection, a phenomenon we term inflation-selection balance. Tailored computational models and agent-based simulations corroborate the fundamental nature of the observed effects and demonstrate the potential impact on drug resistance evolution in cancer. The described phenomena should be considered when predicting multi-step evolutionary dynamics in any mechanically compact cellular population, including pathogenic microbial biofilms and solid tumors. The insights gained will be especially valuable for the quantitative understanding of response to treatment, including emerging evolution-based therapy strategies.

Caveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system

Fidel-Nicolás Lolo, Nikhil Walani, Eric Seemann, Dobryna Zalvidea, Dácil María Pavón, Gheorghe Cojoc, Moreno Zamai, Christine Varis de Lesegno, Fernando Martínez de Benito, et al.

In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations—dolines—capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.

Spectral theorem for dummies: A pedagogical discussion on quantum probability and random variable theory

Andrea Aiello

John von Neumann's spectral theorem for self-adjoint operators is a cornerstone of quantum mechanics. Among other things, it also provides a connection between expectation values of self-adjoint operators and expected values of real-valued random variables. This paper presents a plain-spoken formulation of this theorem in terms of Dirac's bra and ket notation, which is based on physical intuition and provides techniques that are important for performing actual calculations. The goal is to engage students in a constructive discussion about similarities and differences in the use of random variables in classical and quantum mechanics. Special emphasis is given on operators that are simple functions of noncommuting self-adjoint operators. The presentation is self-contained and includes detailed calculations for the most relevant results.

Deep learning of spatial densities in inhomogeneous correlated quantum systems

Alex Blania, Sandro Herbig, Fabian Dechent, Evert van Nieuwenburg, Florian Marquardt

Machine learning has made important headway in helping to improve the treatment of quantum many-body systems. A domain of particular relevance are correlated inhomogeneous systems. What has been missing so far is a general, scalable deep-learning approach that would enable the rapid prediction of spatial densities for strongly correlated systems in arbitrary potentials. In this work, we present a straightforward scheme, where we learn to predict densities using convolutional neural networks trained on random potentials. While we demonstrate this approach in 1D and 2D lattice models using data from numerical techniques like Quantum Monte Carlo, it is directly applicable as well to training data obtained from experimental quantum simulators. We train networks that can predict the densities of multiple observables simultaneously and that can predict for a whole class of many-body lattice models, for arbitrary system sizes. We show that our approach can handle well the interplay of interference and interactions and the behaviour of models with phase transitions in inhomogeneous situations, and we also illustrate the ability to solve inverse problems, finding a potential for a desired density.

Interferometric nanoparticle tracking analysis enables label-free discrimination of extracellular vesicles from large lipoproteins

Anna D. Kashkanova, Martin Blessing, Marie Reischke, Andreas S. Baur, Vahid Sandoghdar, Jan Van Deun

Complex decoherence-free interactions between giant atoms

Lei Du, Lingzhen Guo, Yong Li

Giant atoms provide a promising platform for engineering decoherence-free interactions which <br><br><br>is a major task in modern quantum technologies. Here we study systematically how to implement <br><br><br>complex decoherence-free interactions among giant atoms resorting to periodic coupling modulations and suitable arrangements of coupling points. We demonstrate that the phase of the modulation, which is tunable in experiments, can be encoded into the decoherence-free interactions, and thus <br><br><br>enables the Aharonov-Bohm effect of photons when the giant atoms constitute an effective closed loop. In particular, we consider the influence of non-Markovian retardation effect arising from large separations of the coupling points and study its dependence on the modulation parameters.

Realizing a deep reinforcement learning agent discovering real-time feedback control strategies for a quantum system

Kevin Reuer, Jonas Landgraf, Thomas Fösel, James O'Sullivan, Liberto Beltrán, Abdulkadir Akin, Graham J. Norris, Ants Remm, Michael Kerschbaum, et al.

To realize the full potential of quantum technologies, finding good strategies to control quantum information processing devices in real time becomes increasingly important. Usually these strategies require a precise understanding of the device itself, which is generally not available. Model-free reinforcement learning circumvents this need by discovering control strategies from scratch without relying on an accurate description of the quantum system. Furthermore, important tasks like state <br><br>preparation, gate teleportation and error correction need feedback at time scales much shorter than the coherence time, which for superconducting circuits is in the microsecond range. Developing and training a deep reinforcement learning agent able to operate in this real-time feedback regime has been an open challenge. Here, we have implemented such an agent in the form of a latency-optimized deep neural network on a field-programmable gate array (FPGA). We demonstrate its use to efficiently initialize a superconducting qubit into a target state. To train the agent, we use <br><br>model-free reinforcement learning that is based solely on measurement data. We study the agent’s performance for strong and weak measurements, and for three-level readout, and compare with simple strategies based on thresholding. This demonstration motivates further research towards adoption of <br><br>reinforcement learning for real-time feedback control of quantum devices and more generally any physical system requiring learnable low-latency feedback control.

Helicity, chirality, and spin of optical fields without vector potentials

Andrea Aiello

Helicity H, chirality C, and spin angular momentum S are three physical observables that play an important role in the study of optical fields. These quantities are closely related, but their connection is hidden by the use of four different vector fields for their representation, namely, the electric and magnetic fields E and B, and the two transverse potential vectors C⊥ and A⊥. Helmholtz's decomposition theorem restricted to solenoidal vector fields entails the introduction of a bona fide inverse curl operator, which permits one to express the above three quantities in terms of the observable electric and magnetic fields only. This yields clear expressions for H,C, and S, which are automatically gauge invariant and display electric-magnetic democracy.

Identification of a Distinct Monocyte-Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells

Alexandru-Emil Matei, Markéta Kubánková, Liyan Xu, Andrea-Hermina Györfi, Evgenia Boxberger, Despina Soteriou, Maria Papava, Julia Prater, Xuezhi Hong, et al.

Objective<br>Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc.<br><br>Methods<br>We performed biophysical phenotyping of circulating immune cells by real-time fluorescence and deformability cytometry (RT-FDC) in 63 SSc patients, 59 rheumatoid arthritis (RA) patients, 28 antineutrophil cytoplasmic antibody–associated vasculitis (AAV) patients, and 22 age- and sex-matched healthy donors.<br><br>Results<br>We identified a specific signature of biophysical properties of circulating immune cells in SSc patients that was mainly driven by monocytes. Since it is absent in RA and AAV, this signature reflects an SSc-specific monocyte activation rather than general inflammation. The biophysical properties of monocytes indicate current disease activity, the extent of skin or lung fibrosis, and the severity of manifestations of microvascular damage, as well as the risk of disease progression in SSc patients.<br><br>Conclusion<br>Changes in the biophysical properties of circulating immune cells reflect their pathologic activation in SSc patients and are associated with clinical outcomes. As a high-throughput approach that requires minimal preparations, RT-FDC–based biophysical phenotyping of monocytes can serve as a tool for the evaluation and risk stratification of patients with SSc.

Nonreciprocal vortex isolator via topology-selective stimulated Brillouin scattering

Xinglin Zeng, Philip Russell, Christian Wolff , Michael Frosz, Gordon Wong, Birgit Stiller

Optical nonreciprocity, which breaks the symmetry between forward and backward propagating optical waves, has become vital in photonic systems and enables many key applications. So far, all the existing nonreciprocal systems are implemented for linearly or randomly polarized fundamental modes. Optical vortex modes, with wavefronts that spiral around the central axis of propagation, have been extensively studied over the past decades and offer an additional degree of freedom useful in many applications. Here, we report a light-driven nonreciprocal isolation system for optical vortex modes based on topology-selective stimulated Brillouin scattering (SBS) in chiral photonic crystal fiber. The device can be reconfigured as an amplifier or an isolator by adjusting the frequency of the control signal. The experimental results show vortex isolation of 22 decibels (dB), which is at the state of the art in fundamental mode isolators using SBS. This device may find applications in optical communications, fiber lasers, quantum information processing, and optical tweezers.

Digital Discovery of a Scientific Concept at the Core of Experimental Quantum Optics

Sören Arlt, Carlos Ruiz-Gonzalez, Mario Krenn

Entanglement is a crucial resource for quantum technologies ranging from quantum communication to quantum-enhanced measurements and computation. Finding experimental setups for these tasks is a conceptual challenge for human scientists due to the counterintuitive behavior of multiparticle interference and the enormously large combinatorial search space. Recently, new possibilities have been opened by artificial discovery where artificial intelligence proposes experimental setups for the creation and manipulation of high-dimensional multi-particle entanglement. While digitally discovered experiments go beyond what has been conceived by human experts, a crucial goal is to understand the underlying concepts which enable these new useful experimental blueprints. Here, we present Halo (Hyperedge Assembly by Linear Optics), a new form of multiphoton quantum interference with surprising properties. Halos were used by our digital discovery framework to solve previously open questions. We -- the human part of this collaboration -- were then able to conceptualize the idea behind the computer discovery and describe them in terms of effective probabilistic multi-photon emitters. We then demonstrate its usefulness as a core of new experiments for highly entangled states, communication in quantum networks, and photonic quantum gates. Our manuscript has two conclusions. First, we introduce and explain the physics of a new practically useful multi-photon interference phenomenon that can readily be realized in advanced setups such as integrated photonic circuits. Second, our manuscript demonstrates how artificial intelligence can act as a source of inspiration for the scientific discoveries of new actionable concepts in physics.

Digital Discovery of 100 diverse Quantum Experiments with PyTheus

Carlos Ruiz-Gonzalez, Sören Arlt, Jan Petermann, Sharareh Sayyad, Tareq Jaouni, Ebrahim Karimi, Nora Tischler, Xuemei Gu, Mario Krenn

Photons are the physical system of choice for performing experimental tests of the foundations of quantum mechanics. Furthermore, photonic quantum technology is a main player in the second quantum revolution, promising the development of better sensors, secure communications, and quantum-enhanced computation. These endeavors require generating specific quantum states or efficiently performing quantum tasks. The design of the corresponding optical experiments was historically powered by human creativity but is recently being automated with advanced computer algorithms and artificial intelligence. While several computer-designed experiments have been experimentally realized, this approach has not yet been widely adopted by the broader photonic quantum optics community. The main roadblocks consist of most systems being closed-source, inefficient, or targeted to very specific use-cases that are difficult to generalize. Here, we overcome these problems with a highly-efficient, open-source digital discovery framework PyTheus, which can employ a wide range of experimental devices from modern quantum labs to solve various tasks. This includes the discovery of highly entangled quantum states, quantum measurement schemes, quantum communication protocols, multi-particle quantum gates, as well as the optimization of continuous and discrete properties of quantum experiments or quantum states. PyTheus produces interpretable designs for complex experimental problems which human researchers can often readily conceptualize. PyTheus is an example of a powerful framework that can lead to scientific discoveries -- one of the core goals of artificial intelligence in science. We hope it will help accelerate the development of quantum optics and provide new ideas in quantum hardware and technology.

Theory of Laser-Assisted Nuclear Excitation by Electron Capture

Pavlo Bilous

The interplay of x-ray ionization and atomic and nuclear degrees of freedom is investigated theoretically in the process of laser-assisted nuclear excitation by electron capture. In the resonant process of nuclear excitation by electron capture, an incident electron recombines into a vacancy in the atomic shell with simultaneous nuclear excitation. Here we investigate the specific scenario in which the free electron and the required atomic shell hole<br>are generated by an x-ray free electron laser pulse. We develop a theoretical description based on the Feshbach projection operator formalism and consider numerically experimental scenarios at the SACLA x-ray free electron laser. Our numerical results for excitation of the 29.2 keV nuclear state in<br>$^{229}\text{Th}$ and the 14.4 keV M\"ossbauer transition in $^{57}\text{Fe}$<br>show low excitation rates but strong enhancement with respect to direct two<br>photon nuclear excitation.<br>

SELFIES and the future of molecular string representations

Mario Krenn, Qianxiang Ai, Senja Barthel, Nessa Carson, Angelo Frei, Nathan C. Frey, Pascal Friederich, Théophile Gaudin, Alberto Alexander Gayle, et al.

Artificial intelligence (AI) and machine learning (ML) are expanding in popularity for broad applications to challenging tasks in chemistry and materials science. Examples include the prediction of properties, the discovery of new reaction pathways, or the design of new molecules. The machine needs to read and write fluently in a chemical language for each of these tasks. Strings are a common tool to represent molecular graphs, and the most popular molecular string representation, SMILES, has powered cheminformatics since the late 1980s. However, in the context of AI and ML in chemistry, SMILES has several shortcomings -- most pertinently, most combinations of symbols lead to invalid results with no valid chemical interpretation. To overcome this issue, a new language for molecules was introduced in 2020 that guarantees 100\% robustness: SELFIES (SELF-referencIng Embedded Strings). SELFIES has since simplified and enabled numerous new applications in chemistry. In this manuscript, we look to the future and discuss molecular string representations, along with their respective opportunities and challenges. We propose 16 concrete Future Projects for robust molecular representations. These involve the extension toward new chemical domains, exciting questions at the interface of AI and robust languages and interpretability for both humans and machines. We hope that these proposals will inspire several follow-up works exploiting the full potential of molecular string representations for the future of AI in chemistry and materials science.

Design of quantum optical experiments with logic artificial intelligence

Alba Cervera-Lierta, Mario Krenn, Alán Aspuru-Guzik

Logic Artificial Intelligence (AI) is a subfield of AI where variables can take two defined arguments, True or False, and are arranged in clauses that follow the rules of formal logic. Several problems that span from physical systems to mathematical conjectures can be encoded into these clauses and solved by checking their satisfiability (SAT). In contrast to machine learning approaches where the results can be approximations or local minima, Logic AI delivers formal and mathematically exact solutions to those problems. In this work, we propose the use of logic AI for the design of optical quantum experiments. We show how to map into a SAT problem the experimental preparation of an arbitrary quantum state and propose a logic-based algorithm, called Klaus, to find an interpretable representation of the photonic setup that generates it. We compare the performance of Klaus with the state-of-the-art algorithm for this purpose based on continuous optimization. We also combine both logic and numeric strategies to find that the use of logic AI significantly improves the resolution of this problem, paving the path to developing more formal-based approaches in the context of quantum physics experiments.

Ultralong Imaging Range Chromatic Confocal Microscopy

Gargi Sharma, Kanwarpal Singh

Confocal microscopy is regularly used in cellular research but unfortunately, the imaging is restricted to a single plane. Chromatic confocal microscopy (CCM) offers the possibility to image multiple planes simultaneously, thus providing a manifold increase in the imaging speed, whereas eliminating the need for z-axis scanning. Standard chromatic confocal systems have a limited imaging range of the order of a few hundreds of micrometers which limits their applications. Herein, using a single zinc selenide lens, a CCM system that has an imaging range of 18 mm (±68 nm) with an average spatial resolution of 2.46 μm (±44 nm) and another system with a 1.55 mm (±14 nm) imaging range with 0.86 μm (±30 nm) average lateral spatial resolution is demonstrated. In doing so, sevenfold increase in the imaging range for the system with 1.55 mm imaging when compared with previously reported systems with similar lateral spatial resolution is achieved. The proposed approach can be a powerful tool for confocal imaging of biological samples or surface profiling of industrial samples.

On scientific understanding with artificial intelligence

Mario Krenn, Robert Pollice, Si Yue Guo, Matteo Aldeghi, Alba Cervera-Lierta, Pascal Friederich, Gabriel dos Passos Gomes, Florian Häse, Adrian Jinich, et al.

An oracle that correctly predicts the outcome of every particle physics experiment, the products of every possible chemical reaction or the function of every protein would revolutionize science and technology. However, scientists would not be entirely satisfied because they would want to comprehend how the oracle made these predictions. This is scientific understanding, one of the main aims of science. With the increase in the available computational power and advances in artificial intelligence, a natural question arises: how can advanced computational systems, and specifically artificial intelligence, contribute to new scientific understanding or gain it autonomously? Trying to answer this question, we adopted a definition of ‘scientific understanding’ from the philosophy of science that enabled us to overview the scattered literature on the topic and, combined with dozens of anecdotes from scientists, map out three dimensions of computer-assisted scientific understanding. For each dimension, we review the existing state of the art and discuss future developments. We hope that this Perspective will inspire and focus research directions in this multidisciplinary emerging field.<br><br><br><br>

Two-photon-absorption measurements in the presence of single-photon losses

Shahram Panahiyan, Carlos Sánchez Muñoz, Maria V. Chekhova, Frank Schlawin

We discuss how two-photon absorption (TPA) of squeezed and coherent states of light can be detected in measurements of the transmitted light fields. Such measurements typically suffer from competing loss mechanisms such as experimental imperfections (i.e., imperfect photodetectors) and other linear scattering losses inside the sample itself, which can lead to incorrect assessments of the two-photon-absorption cross section. We evaluate the sensitivity with which TPA can be detected and find that at sufficiently large photon numbers TPA sensitivity of squeezed vacua or squeezed coherent states can become independent of linear losses that occur after the TPA event has taken place. In particular, this happens for measurements of the photon number or of the antisqueezed field quadrature, where large fluctuations counteract and exactly cancel the degradation caused by single-photon losses.

Investigation of inverse design of multilayer thin-films with conditional invertible Neural Networks

Alexander Luce, Ali Mahdavi, Heribert Wankerl, Florian Marquardt

The task of designing optical multilayer thin-films regarding a given target is currently solved using gradient-based optimization in conjunction with methods that can introduce additional thin-film layers. Recently, Deep Learning and Reinforcement Learning have been been introduced to the task of designing thin-films with great success, however a trained network is usually only able to become proficient for a single target and must be retrained if the optical<br>targets are varied. In this work, we apply conditional Invertible Neural Networks (cINN) to inversely designing multilayer thin-films given an optical target. Since the cINN learns the energy landscape of all thin-film configurations within the training dataset, we show that cINNs can generate a stochastic ensemble of proposals for thin-film configurations that that are reasonably close to the desired target depending only on random variables. By refining the proposed configurations further by a local optimization, we show that the generated thin-films reach the target with significantly greater precision than comparable state-of-the art approaches. Furthermore, we tested the generative capabilities on samples which are outside the training data distribution and found that the cINN was able to predict thin-films for<br>out-of-distribution targets, too. The results suggest that in order to improve the generative design of thin-films, it is instructive to use established and new machine learning methods in conjunction in order to obtain the most<br>favorable results.

Predicting the Future of AI with AI: High-quality link prediction in an exponentially growing knowledge network

Mario Krenn, Lorenzo Buffoni, Bruno Coutinho, Sagi Eppel, Jacob Gates Foster, Andrew Gritsevskiy, Harlin Lee, Yichao Lu, Joao P. Moutinho, et al.

A tool that could suggest new personalized research directions and ideas by taking insights from the scientific literature could significantly accelerate the progress of science. A field that might benefit from such an approach is artificial intelligence (AI) research, where the number of scientific publications has been growing exponentially over the last years, making it challenging for human researchers to keep track of the progress. Here, we use AI techniques to predict the future research directions of AI itself. We develop a new graph-based benchmark based on real-world data -- the Science4Cast benchmark, which aims to predict the future state of an evolving semantic network of AI. For that, we use more than 100,000 research papers and build up a knowledge network with more than 64,000 concept nodes. We then present ten diverse methods to tackle this task, ranging from pure statistical to pure learning methods. Surprisingly, the most powerful methods use a<br>carefully curated set of network features, rather than an end-to-end AI approach. It indicates a great potential that can be unleashed for purely ML approaches without human knowledge. Ultimately, better predictions of new future research directions will be a crucial component of more advanced research suggestion tools.

Label-free monitoring of proteins in optofluidic hollow-core photonic crystal fibres

Jan R. Heck , Ermanno Miele, Ralf Mouthaan, Michael Frosz, Tuomas P J Knowles, Tijmen G Euser

The fluorescent detection of proteins without labels or stains, which affect their behaviour and require additional genetic or chemical preparation, has broad applications to biological research. However, standard approaches require large sample volumes or analyse only a small fraction of the sample. Here we use optofluidic hollow-core photonic crystal fibres to detect and quantify sub-microlitre volumes of unmodified bovine serum albumin (BSA) protein down to 100 nM concentrations. The optofluidic fibre's waveguiding properties are optimised for guidance at the (auto)fluorescence emission wavelength, enabling fluorescence collection from a 10 cm long excitation region, increasing sensitivity. The observed spectra agree with spectra taken from a conventional cuvette-based fluorimeter, corrected for the guidance properties of the fibre. The BSA fluorescence depended linearly on BSA concentration, while only a small hysteresis effect was observed, suggesting limited biofouling of the fibre sensor. Finally, we briefly discuss how this method could be used to study aggregation kinetics. With small sample volumes, the ability to use unlabelled proteins, and continuous flow, the method will be of interest to a broad range of protein-related research.

Deep-learning approach for large atomic structure calculations

Pavlo Bilous, Adriana Pálffy, Florian Marquardt

High-precision atomic structure calculations require accurate modelling of<br>electronic correlations involving large multiconfiguration wave function<br>expansions. Here we develop a deep-learning approach which allows to preselect<br>the most relevant configurations out of large basis sets until the targeted<br>precision is achieved. Our method replaces a large multiconfiguration<br>Dirac-Hartree-Fock computation by a series of smaller ones performed on an<br>iteratively expanding basis subset managed by a convolutional neural network.<br>The results for several examples with many-electron atoms show that deep<br>learning can significantly reduce the required computational memory and running<br>time and renders possible large-scale computations on otherwise unaccessible<br>basis sets.<br>

Tunneling-induced fractal transmission in Valley Hall waveguides

Tirth Shah, Florian Marquardt, Vittorio Peano

The Valley Hall effect provides a popular route to engineer robust waveguides<br>for bosonic excitations such a photons and phonons. The almost complete absence<br>of backscattering in many experiments has its theoretical underpinning in a<br>smooth-envelope approximation that neglects large momentum transfer and is<br>accurate only for small bulk band gaps and/or smooth domain walls. For larger<br>bulk band gaps and hard domain walls backscattering is expected to become<br>significant. Here, we show that in this experimentally relevant regime, the<br>reflection of a wave at a sharp corner becomes highly sensitive on the<br>orientation of the outgoing waveguide relative to the underlying lattice.<br>Enhanced backscattering can be understood as being triggered by resonant<br>tunneling transitions in quasimomentum space. Tracking the resonant tunneling<br>energies as a function of the waveguide orientation reveals a self-repeating<br>fractal pattern that is also imprinted in the density of states and the<br>backscattering rate at a sharp corner.<br>

Analysis of the signal measured in spectral-domain optical coherence tomography based on nonlinear interferometers

Arturo Rojas-Santana, Gerard J. Machado, Maria V. Chekhova, Dorilian Lopez-Mago, Juan P. Torres

We analyze and compare the output signals obtained in three different configurations of optical coherence tomography (OCT). After appropriate processing, these signals are used to retrieve an image of the sample under investigation. One of the configurations considered is the common choice in most OCT applications and is based on the use of a Michelson interferometer. For brevity, here we refer to it as standard OCT. The other two configurations are two types of optical coherence tomography based on the use of so-called nonlinear interferometers, interferometers that contain optical parametric amplifiers inside. The goal is to highlight the differences and similarities between the output signals measured in standard OCT and in these two OCT schemes, with the aim of evaluating if retrieval of information about the sample can be better done in one case over the others. We consider schemes where the optical sectioning of the sample is obtained by measuring the output signal spectrum (spectral or Fourier-domain OCT), since it shows better performance in terms of speed and sensitivity than the counterpart time-domain OCT.

Strong circular dichroism for the HE11 mode in twisted single-ring hollow-core photonic crystal fiber: erratum

Paul Roth, Yang Chen, Mehmet Can Günendi, Ramin Beravat, Nitin Edavalath, Michael Frosz, Goran Ahmed, Gordon Wong, Philip Russell

Recent work has revealed that the dispersion relation, given inOptica 5, 1315 (2018), for helicalBloch modes in a ring of capillaries surrounding a central hollowcore, is incorrect.Herewe correct this error and provide a revised version of Fig. 2. The overall conclusions of the original paper are unaffected.

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Richard Gerum, Elham Mirzahossein, Mar Eroles, Jennifer Elsterer, Astrid Mainka, Andreas Bauer, Selina Sonntag, Alexander Winterl, Johannes Bartl, et al.

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

Erratum to “Bragg Reflection and Conversion Between Helical Bloch Modes in Chiral Three-Core Photonic Crystal Fiber”

Sébastien Loranger, Yang Chen, Paul Roth, Michael Frosz, Gordon Wong, Philip Russell

The dispersion relation for the helical Bloch modes in this paper contains an error, which affects Equation (3) in the original manuscript, as well as Fig. 2. Otherwise the conclusions of the paper are unaffected.

Stern–Volmer analysis of photocatalyst fluorescence quenching within hollow-core photonic crystal fibre microreactors

Alexander S. Gentleman, Takashi Lawson, Matthew G. Ellis, Molly Davis, Jacob Turner-Dore, Alison S. H. Ryder, Michael Frosz, Maria Ciaccia, Erwin Reisner, et al.

We report the use of optofluidic hollow-core photonic crystal fibres as microreactors for Stern–Volmer (SV) luminescence quenching analysis of visible-light photocatalytic reactions. This technology enables measurements on nanolitre volumes and paves the way for automated SV analyses in continuous flow that minimise catalyst and reagent usage. The method is showcased using a recently developed photoredox-catalysed α-C–H alkylation reaction of unprotected primary alkylamines.

Resonant metasurfaces for generating complex quantum states

Tomas Santiago-Cruz, Sylvain D. Gennaro, Oleg Mitrofanov, Sadhvikas Addamane, John Reno, Igal Brener, Maria V. Chekhova

Quantum state engineering, the cornerstone of quantum photonic technologies, mainly relies on spontaneous parametric downconversion and four-wave mixing, where one or two pump photons spontaneously decay into a photon pair. Both of these nonlinear effects require momentum conservation for the participating photons, which strongly limits the versatility of the resulting quantum states. Nonlinear metasurfaces have subwavelength thickness and allow the relaxation of this constraint; when combined with resonances, they greatly expand the possibilities of quantum state engineering. Here, we generated entangled photons via spontaneous parametric downconversion in semiconductor metasurfaces with high–quality factor, quasi-bound state in the continuum resonances. By enhancing the quantum vacuum field, our metasurfaces boost the emission of nondegenerate entangled photons within multiple narrow resonance bands and over a wide spectral range. A single resonance or several resonances in the same sample, pumped at multiple wavelengths, can generate multifrequency quantum states, including cluster states. These features reveal metasurfaces as versatile sources of complex states for quantum information.

Cooperative subwavelength molecular quantum emitter arrays

Raphael Holzinger, Sue Ann Oh, Michael Reitz, Helmut Ritsch, Claudiu Genes

Dipole-coupled subwavelength quantum emitter arrays respond cooperatively to<br>external light fields as they may host collective delocalized excitations (a<br>form of excitons) with super- or subradiant character. Deeply subwavelength<br>separations typically occur in molecular ensembles, where in addition to<br>photon-electron interactions, electron-vibron couplings and vibrational<br>relaxation processes play an important role. We provide analytical and<br>numerical results on the modification of super- and subradiance in molecular<br>rings of dipoles including excitations of the vibrational degrees of freedom.<br>While vibrations are typically considered detrimental to coherent dynamics, we<br>show that molecular dimers or rings can be operated as platforms for the<br>preparation of long-lived dark superposition states aided by vibrational<br>relaxation. In closed ring configurations, we extend previous predictions for<br>the generation of coherent light from ideal quantum emitters to molecular<br>emitters, quantifying the role of vibronic coupling onto the output intensity<br>and coherence.<br>

Recent advances in petahertz electric field sampling

Andreas Herbst, Kilian Scheffter, M.M. Bidhendi, M. Kieker, Anchit Srivastava, Hanieh Fattahi

The ability to resolve the complete electric field of laser pulses from terahertz to mid-infrared spectral ranges has enriched time-domain spectroscopy for decades. Field-resolved measurements in this range have been performed routinely in ambient air by various techniques like electro-optic sampling, photoconductive switching, field-induced second harmonic generation, and time stretch photonics. On the contrary, resolving the electric field of light at the near-infrared spectral range has been limited to attosecond streaking and other techniques that require operation in vacuum. Recent advances are circumventing these<br>shortcomings and extending the direct, ambient air field detection of light to petahertz frequencies. In the first part of this letter, recent field-resolved techniques are reviewed. In the second part, different approaches for temporal scanning are discussed, as the temporal resolution of the time-domain methods is prone to temporal jitter. The review concludes by discussing technological obstacles and emerging applications of such advancements.

Robust Tipless Positioning Device for Near-Field Investigations: Press and Roll Scan (PROscan)

Hsuan-Wei Liu, Michael A. Becker, Korenobu Matsuzaki, Randhir Kumar, Stephan Götzinger, Vahid Sandoghdar

Scanning probe microscopes scan and manipulate a sharp tip in the immediate vicinity of a sample surface. The limited bandwidth of the feedback mechanism used for stabilizing the separation between the tip and the sample makes the fragile nanoscopic tip very susceptible to mechanical instabilities. We propose, demonstrate, and characterize an alternative device based on bulging a thin substrate against a second substrate and rolling them with respect to each other. We showcase the power of this method by placing gold nanoparticles and semiconductor quantum dots on the two opposite substrates and positioning them with nanometer precision to enhance the fluorescence intensity and emission rate. Furthermore, we exhibit the passive mechanical stability of the system over more than 1 h. Our design concept finds applications in a variety of other scientific and technological contexts, where nanoscopic features have to be positioned and kept near contact with each other.<br>a thin substrate against a second substrate and rolling them with respect each other. We showcase the power of this method by placing gold nanoparticles and semiconductor quantum dots on the<br>two opposite substrates and positioning them with nanometer precision to enhance the fluorescence intensity and emission rate. We exhibit the passive mechanical stability of the system over more than<br>one hour. The design concept presented in this work holds promise in a variety of other contexts, where nanoscopic features have to be positioned and kept near contact with each other.

Classical model of spontaneous parametric down-conversion

Girish Kulkarni, Jeremy Rioux, Boris Braverman, Maria V. Chekhova, Robert W. Boyd

We model spontaneous parametric down-conversion (SPDC) as classical difference frequency generation (DFG) of the pump field and a hypothetical stochastic “vacuum” seed field. We analytically show that the second-order spatiotemporal correlations of the field generated from the DFG process replicate those of the signal field from SPDC. Specifically, for low gain, the model is consistent with the quantum calculation of the signal photon’s reduced density matrix; and for high gain, the model’s predictions are in good agreement with our experimental measurements of the far-field intensity profile, orbital angular momentum spectrum, and wavelength spectrum of the SPDC field for increasing pump strengths. We further theoretically show that the model successfully captures second-order SU(1,1) interference and induced coherence effects in both gain regimes. Intriguingly, the model also correctly predicts the linear scaling of the interference visibility with object transmittance in the low-gain regime—a feature that is often regarded as a quintessential signature of the nonclassicality of induced coherence. Our model may not only lead to fundamental insights into the classical-quantum divide in the context of SPDC and induced coherence, but can also be a useful theoretical tool for numerous experiments and applications based on SPDC.

Metasurfaces for quantum technologies

Kai Wang, Maria V. Chekhova, Yuri S. Kivshar

Subwavelength planar structures can generate, reshape, and entangle photons in a compact and stable device.

Control of Yu-Shiba-Rusinov States through a Bosonic Mode

Helene Müller, Martin Eckstein, Silvia Viola-Kusminskiy

We investigate the impact of a bosonic degree of freedom on Yu-Shiba-Rusinov (YSR) states emerging from a magnetic impurity in a conventional superconductor. Starting from the Anderson impurity model, we predict that an additional p-wave conduction band channel opens up if a bosonic mode is coupled to the tunnelling between impurity and host, which implies an additional pair of odd-parity YSR states. The bosonic mode can be a vibrational mode or the electromagnetic field in a cavity. The exchange couplings in the two channels depend sensitively on the state of the bosonic mode (ground state, few quanta or classically driven Floquet state), which opens possibilities for phononics or photonics control of such systems, with a rich variety of ground and excited states.

Protocol for generating an arbitrary quantum state of the magnetization in cavity magnonics

Sanchar Sharma, Victor A. S. V. Bittencourt, Silvia Viola-Kusminskiy

We propose and numerically evaluate a protocol to generate an arbitrary quantum state of the magnetization in a magnet. The protocol involves repeatedly exciting a frequency-tunable superconducting transmon and transferring the excitations to the magnet via a microwave cavity. To avoid decay, the protocol must be much shorter than magnon lifetime. Speeding up the protocol by simply shortening the pulses leads to non-resonant leakage of excitations to higher levels of the transmon accompanied by higher decoherence. We discuss how to correct for such leakages by applying counter pulses to de-excite these higher levels. In our protocol, states with a maximum magnon occupation of up to ∼9 and average magnon number up to ∼4 can be generated with fidelity >0.75.

Curiosity in exploring chemical spaces: Intrinsic rewards for deep molecular reinforcement learning

Luca A. Thiede, Mario Krenn, AkshatKumar Nigam, Alán Aspuru-Guzik

Computer-aided design of molecules has the potential to disrupt the field of drug and material discovery. Machine learning, and deep learning, in particular, have been topics where the field has been developing at a rapid pace. Reinforcement learning is a particularly promising approach since it allows for molecular design without prior knowledge. However, the search space is vast and efficient exploration is desirable when using reinforcement learning agents. In this study, we propose an algorithm to aid efficient exploration. The algorithm is inspired by a concept known in the literature as curiosity. We show on three benchmarks that a curious agent finds better performing molecules. This indicates an exciting new research direction for reinforcement learning agents that can explore the chemical space out of their own motivation. This has the potential to eventually lead to unexpected new molecules that no human has thought about so far.

Direct optical probe of magnon topology in two-dimensional quantum magnets

Emil Viñas Boström, Tahereh S. Parvini, James W. McIver, Angel Rubio, Silvia Viola-Kusminskiy, Michael A. Sentef

Controlling edge states of topological magnon insulators is a promising route to stable spintronics devices. However, to experimentally ascertain the topology of magnon bands is a challenging task. Here we derive a fundamental relation between the light-matter coupling and the quantum geometry of magnon states. This allows to establish the two-magnon Raman circular dichroism as an optical probe of magnon topology in honeycomb magnets, in particular of the Chern number and the topological gap. Our results pave the way for interfacing light and topological magnons in functional quantum devices.

Flat-optics generation of broadband photon pairs with tunable polarization entanglement

Vitaliy Sultanov, José Tomás Santiago-Cruz, Maria V. Chekhova

The concept of “flat optics” is quickly conquering different fields of photonics, but its implementation in quantum optics is still in its infancy. In particular, polarization entanglement, strongly required in quantum photonics, is so far not realized on “flat” platforms. Meanwhile, relaxed phase matching of “flat” nonlinear optical sources enables enormous freedom in tailoring their polarization properties. Here we use this freedom to generate photon pairs with tunable polarization entanglement via spontaneous parametric downconversion (SPDC) in a 400 nm GaP film. By changing the pump polarization, we tune the polarization state of photon pairs from maximally entangled to almost disentangled, which is impossible in a single bulk SPDC source. Polarization entanglement, together with the broadband frequency spectrum, results in an ultranarrow (12 fs) Hong–Ou–Mandel effect and promises extensions to hyperentanglement.

Quantitative phase imaging through an ultra-thin lensless fiber endoscope

Jiawei Sun, Jiachen Wu, Ruchi Goswami, Salvatore Girardo, Liangcai Cao, Jochen Guck, Nektarios Koukourakis, Jürgen W. Czarske

Quantitative phase imaging (QPI) is a label-free technique providing both morphology and quantitative biophysical information in biomedicine. However, applying such a powerful technique to in vivo pathological diagnosis remains challenging. Multi-core fiber bundles (MCFs) enable ultra-thin probes for in vivo imaging, but current MCF imaging techniques are limited to amplitude imaging modalities. We demonstrate a computational lensless microendoscope that uses an ultra-thin bare MCF to perform quantitative phase imaging with microscale lateral resolution and nanoscale axial sensitivity of the optical path length. The incident complex light field at the measurement side is precisely reconstructed from the far-field speckle pattern at the detection side, enabling digital refocusing in a multi-layer sample without any mechanical movement. The accuracy of the quantitative phase reconstruction is validated by imaging the phase target and hydrogel beads through the MCF. With the proposed imaging modality, three-dimensional imaging of human cancer cells is achieved through the ultra-thin fiber endoscope, promising widespread clinical applications.

PNIPAAm microgels with defined network architecture as temperature sensors in optical stretchers

Nicolas Hauck, Timon Beck, Gheorghe Cojoc, Raimund Schlüßler, Saeed Ahmed, Ivan Raguzin, Martin Mayer, Jonas Schubert, Paul Müller, et al.

Stretching individual living cells with light is a standard method to assess their mechanical properties. Yet, heat introduced by the laser light of optical stretchers may unwittingly change the mechanical properties of cells therein. To estimate the temperature induced by an optical trap, we introduce cell-sized, elastic poly(N-isopropylacrylamide) (PNIPAAm) microgels that relate temperature changes to hydrogel swelling. For their usage as a standardized calibration tool, we analyze the effect of free-radical chain-growth gelation (FCG) and polymer-analogous photogelation (PAG) on hydrogel network heterogeneity, micromechanics, and temperature response by Brillouin microscopy and optical diffraction tomography. Using a combination of tailor-made PNIPAAm macromers, PAG, and microfluidic processing, we obtain microgels with homogeneous network architecture. With that, we expand the capability of standardized microgels in calibrating and validating cell mechanics analysis, not only considering cell and microgel elasticity but also providing stimuli-responsiveness to consider dynamic changes that cells may undergo during characterization.

Topologically Protected Transport in Engineered Mechanical Systems

Tirth Shah, Christian Brendel, Vittorio Peano, Florian Marquardt

Mechanical vibrations are being harnessed for a variety of purposes and at many length scales, from the macroscopic world down to the nanoscale. The considerable design freedom in mechanical structures allows to engineer new<br>functionalities. In recent years, this has been exploited to generate setups that offer topologically protected transport of vibrational waves, both in the solid state and in fluids. Borrowing concepts from electronic physics and being cross-fertilized by concurrent studies for cold atoms and electromagnetic waves, this field of topological transport in engineered mechanical systems offers a rich variety of phenomena and platforms. In this review, we provide a unifying overview of the various ideas employed in this area, summarize the different approaches and experimental implementations, and comment on the challenges as well as the prospects.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Charlotte Szewczykowski, Christian Mardin, Marianna Lucio, Gerd Wallukat, Jakob Hoffmanns, Thora Schröder, Franziska Raith, Lennart Rogge, Felix Heltmann, et al.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

A non-separability measure for spatially disjoint vectorial fields

Andrea Aiello, Xiao-Bo Hu, Valeria Rodríguez-Fajardo, Andrew Forbes, Raul I. Hernandez-Aranda, Benjamin Perez-Garcia, Carmelo Rosales-Guzmán

Vectorial forms of structured light that are non-separable in their spatial and polarisation degrees of freedom have become topical of late, with an extensive toolkit for their creation and control. In contrast, the toolkit for quantifying their non-separability, the inhomogeneity of the polarisation structure, is less developed and in some cases fails altogether. To overcome this, here we introduce a new measure for vectorial light, which we demonstrate both theoretically and experimentally. We consider the general case where the local polarisation homogeneity can vary spatially across the field, from scalar to vector, a condition that can arise naturally if the composite scalar fields are path separable during propagation, leading to spatially disjoint vectorial light. We show how the new measure correctly accounts for the local path-like separability of the individual scalar beams, which can have varying degrees of disjointness, even though the global vectorial field remains intact. Our work attempts to address a pressing issue in the analysis of such complex light fields, and raises important questions on spatial coherence in the context of vectorially polarised light.

Deep Reinforcement Learning for Quantum State Preparation with Weak Nonlinear Measurements

Riccardo Porotti, Antoine Essig, Benjamin Huard, Florian Marquardt

Quantum control has been of increasing interest in recent years, e.g. for tasks like state initialization and stabilization. Feedback-based strategies are particularly powerful, but also hard to find, due to the exponentially increased search space. Deep reinforcement learning holds great promise in this regard. It may provide new answers to difficult questions, such as whether nonlinear measurements can compensate for linear, constrained control. Here we show that reinforcement learning can successfully discover such feedback strategies, without prior knowledge. We illustrate this for state reparation in a cavity subject to quantum-non-demolition detection of photon number, with a simple linear drive as control. Fock states can be produced and stabilized at very high fidelity. It is even possible to reach superposition states, provided the measurement rates for different Fock states can be controlled as well.

In vivo assessment of mechanical properties during axolotl development and regeneration using confocal Brillouin microscopy

Camilo Riquelme-Guzmán, Timon Beck, Sandra Edwards-Jorquera, Raimund Schlüßler, Paul Müller, Jochen Guck, Stephanie Möllmert, Tatiana Sandoval-Guzmán

In processes such as development and regeneration, where large cellular and tissue rearrangements occur, cell fate and behaviour are strongly influenced by tissue mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures mechanical parameters optically with high resolution in a contact-free and label-free fashion. In this work, we took advantage of this tool and the transparency of the highly regenerative axolotl to probe its mechanical properties in vivo for the first time. We mapped the Brillouin frequency shift with high resolution in developing limbs and regenerating digits, the most studied structures in the axolotl. We detected a gradual increase in the cartilage Brillouin frequency shift, suggesting decreasing tissue compressibility during both development and regeneration. Moreover, we were able to correlate such an increase with the regeneration stage, which was undetected with fluorescence microscopy imaging. The present work evidences the potential of Brillouin microscopy to unravel the mechanical changes occurring in vivo in axolotls, setting the basis to apply this technique in the growing field of epimorphic regeneration.

Quantum indistinguishability by path identity and with undetected photons

Armin Hochrainer, Mayukh Lahiri, Manuel Erhard, Mario Krenn, Anton Zeilinger

Two processes of photon-pair creation can be arranged such that the paths of the emitted photons are identical. The path information is thereby not erased but rather never born in the first place due to this path identity. In addition to its implications for fundamental physics, this concept has recently led to a series of impactful discoveries in the fields of imaging, spectroscopy, and quantum information science. Here the idea of path identity is presented and a comprehensive review of recent developments is provided. Specifically, the concept of path identity is introduced based on three defining experimental ideas from the early 1990s. The three experiments have in common that they contain two photon-pair sources. The paths of one or both photons from the different sources overlap such that no measurement can recognize from which source they originate. A wide range of noteworthy quantum interference effects (at the single- or two-photon level), such as induced coherence, destructive interference of photon pairs, and entanglement generation, are subsequently described. Progress in the exploration of these ideas has stagnated and has gained momentum again only in the last few years. The focus of the review is the new development in the last few years that modified and generalized the ideas from the early 1990s. These developments are overviewed and explained under the same conceptual umbrella, which will help the community develop new applications and realize the foundational implications of this sleeping beauty.

Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina

Rana Amini, Archit Bhatnagar, Raimund Schlüßler, Stephanie Möllmert, Jochen Guck, Caren Norden

Migration of cells in the developing brain is integral for the establishment of neural circuits and function of the central nervous system. While migration modes during which neurons employ predetermined directional guidance of either preexisting neuronal processes or underlying cells have been well explored, less is known about how cells featuring multipolar morphology migrate in the dense environment of the developing brain. To address this, we here investigated multipolar migration of horizontal cells in the zebrafish retina. We found that these cells feature several hallmarks of amoeboid-like migration that enable them to tailor their movements to the spatial constraints of the crowded retina. These hallmarks include cell and nuclear shape changes, as well as persistent rearward polarization of stable F-actin. Interference with the organization of the developing retina by changing nuclear properties or overall tissue architecture hampers efficient horizontal cell migration and layer formation showing that cell-tissue interplay is crucial for this process. In view of the high proportion of multipolar migration phenomena observed in brain development, the here uncovered amoeboid-like migration mode might be conserved in other areas of the developing nervous system.

Adipose cells and tissues soften with lipid accumulation while in diabetes adipose tissue stiffens

Shada Abuhattum, Petra Kotzbeck, Raimund Schlüßler, Alexandra Harger, Angela Ariza de Schellenberger, Kyoohyun Kim, Joan-Carles Escolano, Torsten Müller, Jürgen Braun, et al.

Adipose tissue expansion involves both differentiation of new precursors and size increase of mature adipocytes. While the two processes are well balanced in healthy tissues, obesity and diabetes type II are associated with abnormally enlarged adipocytes and excess lipid accumulation. Previous studies suggested a link between cell stiffness, volume and stem cell differentiation, although in the context of preadipocytes, there have been contradictory results regarding stiffness changes with differentiation. Thus, we set out to quantitatively monitor adipocyte shape and size changes with differentiation and lipid accumulation. We quantified by optical diffraction tomography that differentiating preadipocytes increased their volumes drastically. Atomic force microscopy (AFM)-indentation and -microrheology revealed that during the early phase of differentiation, human preadipocytes became more compliant and more fluid-like, concomitant with ROCK-mediated F-actin remodelling. Adipocytes that had accumulated large lipid droplets were more compliant, and further promoting lipid accumulation led to an even more compliant phenotype. In line with that, high fat diet-induced obesity was associated with more compliant adipose tissue compared to lean animals, both for drosophila fat bodies and murine gonadal adipose tissue. In contrast, adipose tissue of diabetic mice became significantly stiffer as shown not only by AFM but also magnetic resonance elastography. Altogether, we dissect relative contributions of the cytoskeleton and lipid droplets to cell and tissue mechanical changes across different functional states, such as differentiation, nutritional state and disease. Our work therefore sets the basis for future explorations on how tissue mechanical changes influence the behaviour of mechanosensitive tissue-resident cells in metabolic disorders.

Topological phonon transport in an optomechanical system

Hengjiang Ren, Tirth Shah, Hannes Pfeifer, Christian Brendel, Vittorio Peano, Florian Marquardt, Oskar Painter

Recent advances in cavity-optomechanics have now made it possible to use light not just as a passive measuring device of mechanical motion, but also to manipulate the motion of mechanical objects down to the level of individual quanta of vibrations (phonons). At the same time, microfabrication techniques have enabled small-scale optomechanical circuits capable of on-chip manipulation of mechanical and optical signals. Building on these developments, theoretical proposals have shown that larger scale optomechanical arrays can be used to modify the propagation of phonons, realizing a form of topologically protected phonon transport. Here, we report the observation of topological phonon transport within a multiscale optomechanical crystal structure consisting of an array of over 800 cavity-optomechanical elements. Using sensitive, spatially resolved optical read-out we detect thermal phonons in a 0.325−0.34GHz band traveling along a topological edge channel, with substantial reduction in backscattering. This represents an important step from the pioneering macroscopic mechanical systems work towards topological phononic systems at the nanoscale, where hypersonic frequency (≳GHz) acoustic wave circuits consisting of robust delay lines and non-reciprocal elements may be implemented. Owing to the broadband character of the topological channels, the control of the flow of heat-carrying phonons, albeit at cryogenic temperatures, may also be envisioned.

Learning Interpretable Representations of Entanglement in Quantum Optics Experiments using Deep Generative Models

Daniel Flam-Shepherd, Tony Wu, Xuemei Gu, Alba Cervera-Lierta, M. Krenn, Alan Aspuru-Guzik

Quantum physics experiments produce interesting phenomena such as interference or entanglement, which is a core property of numerous future quantum technologies. The complex relationship between a quantum experiment's structure and its entanglement properties is essential to fundamental research in quantum optics but is difficult to intuitively understand. We present the first deep generative model of quantum optics experiments where a variational autoencoder (QOVAE) is trained on a dataset of experimental setups. In a series of computational experiments, we investigate the learned representation of the QOVAE and its internal understanding of the quantum optics world. We demonstrate that the QOVAE learns an intrepretable representation of quantum optics experiments and the relationship between experiment structure and entanglement. We show the QOVAE is able to generate novel experiments for highly entangled quantum states with specific distributions that match its training data. Importantly, we are able to fully interpret how the QOVAE structures its latent space, finding curious patterns that we can entirely explain in terms of quantum physics. The results demonstrate how we can successfully use and understand the internal representations of deep generative models in a complex scientific domain. The QOVAE and the insights from our investigations can be immediately applied to other physical systems throughout fundamental scientific research.

Learning Quantum Systems

Valentin Gebhart, Raffaele Santagati, Antonio Andrea Gentile, Erik Gauger, David Craig, Natalia Ares, Leonardo Banchi, Florian Marquardt, Luca Pezzè, et al.

Quantum technologies hold the promise to revolutionise our society with<br>ground-breaking applications in secure communication, high-performance<br>computing and ultra-precise sensing. One of the main features in scaling up<br>quantum technologies is that the complexity of quantum systems scales<br>exponentially with their size. This poses severe challenges in the efficient<br>calibration, benchmarking and validation of quantum states and their dynamical<br>control. While the complete simulation of large-scale quantum systems may only<br>be possible with a quantum computer, classical characterisation and<br>optimisation methods (supported by cutting edge numerical techniques) can still<br>play an important role.<br> Here, we review classical approaches to learning quantum systems, their<br>correlation properties, their dynamics and their interaction with the<br>environment. We discuss theoretical proposals and successful implementations in<br>different physical platforms such as spin qubits, trapped ions, photonic and<br>atomic systems, and superconducting circuits. This review provides a brief<br>background for key concepts recurring across many of these approaches, such as<br>the Bayesian formalism or Neural Networks, and outlines open questions.<br>

Deciphering a hexameric protein complex with Angstrom optical resolution

Hisham Mazal, Franz Wieser, Vahid Sandoghdar

Cryogenic optical localization in three dimensions (COLD) was recently shown to resolve up to four binding sites on a single protein. However, because COLD relies on intensity fluctuations that result from the blinking behavior of fluorophores, it is limited to cases, where individual emitters show different brightness. This significantly lowers the measurement yield. To extend the number of resolved sites as well as the measurement yield, we employ partial labeling and combine it with polarization encoding in order to identify single fluorophores during their stochastic blinking. We then use a particle classification scheme to identify and resolve heterogenous subsets and combine them to reconstruct the three-dimensional arrangement of large molecular complexes. We showcase this method (polarCOLD) by resolving the trimer arrangement of proliferating cell nuclear antigen (PCNA) and the hexamer geometry of Caseinolytic Peptidase B (ClpB) of Thermus thermophilus in its quaternary structure, both with Angstrom resolution. The combination of polarCOLD and single-particle cryogenic electron microscopy (cryoEM) promises to provide crucial insight into intrinsic, environmental and dynamic heterogeneities of biomolecular structures. Furthermore, our approach is fully compatible with fluorescent protein labeling and can, thus, be used in a wide range of studies in cell and membrane biology.<br><br>Significance statement Fluorescence super-resolution microscopy has witnessed many clever innovations in the last two decades. Here, we advance the frontiers of this field of research by combining partial labeling and 2D image classification schemes with polarization-encoded single-molecule localization at liquid helium temperature to reach Angstrom resolution in three dimensions. We demonstrate the performance of the method by applying it to trimer and hexamer protein complexes. Our approach holds great promise for examining membrane protein structural assemblies and conformations in challenging native environments. The methodology closes the gap between electron and optical microscopy and offers an ideal ground for correlating the two modalities at the single-particle level. Indeed, correlative light and electron microscopy is an emerging technique that will provide new insight into cell biology.

Theory of phase-adaptive parametric cooling

Alekhya Ghosh, Pardeep Kumar, Fidel Jimenez, Vivishek Sudhir, Claudiu Genes

We propose an adaptive phase technique for the parametric cooling of<br>mechanical resonances. This involves the detection of the mechanical<br>quadratures, followed by a sequence of periodic controllable adjustments of the<br>phase of a parametric modulation. The technique allows the preparation of the<br>quantum ground state with an exponential loss of thermal energy, similarly to<br>the case of cold-damping or cavity self-cooling. Analytical derivations are<br>presented for the cooling rate and final occupancies both in the classical and<br>quantum regimes.<br>

One more time on the helicity decomposition of spin and orbital optical currents

Andrea Aiello

The helicity representation of the linear momentum density of a light wave is well understood for monochromatic optical fields in both paraxial and non-paraxial regimes of propagation. In this note we generalize such representation to nonmonochromatic optical fields. We find that, differently from the monochromatic case, the linear momentum density, aka the Poynting vector divided by c2, does not separate into the sum of right-handed and left-handed terms, even when the so-called electric–magnetic democracy in enforced by averaging the electric and magnetic contributions. However, for quasimonochromatic light, such a separation is approximately restored after time-averaging. This paper is dedicated to Sir Michael Berry on the occasion of his 80th birthday.

Realizing exceptional points of any order in the presence of symmetry

Sharareh Sayyad, Flore K. Kunst

Exceptional points~(EPs) appear as degeneracies in the spectrum of non-Hermitian matrices at which the eigenvectors coalesce. In general, an EP of order n may find room to emerge if 2(n−1) real constraints are imposed. Our results show that these constraints can be expressed in terms of the determinant and traces of the non-Hermitian matrix. Our findings further reveal that the total number of constraints may reduce in the presence of unitary and antiunitary symmetries. Additionally, we draw generic conclusions for the low-energy dispersion of the EPs. Based on our calculations, we show that in odd dimensions the presence of sublattice or pseudo-chiral symmetry enforces nth order EPs to disperse with the (n−1)th root. For two-, three- and four-band systems, we explicitly present the constraints needed for the occurrence of EPs in terms of system parameters and classify EPs based on their low-energy dispersion relations.

Deep Learning of Quantum Many-Body Dynamics via Random Driving

Naeimeh Mohseni, Thomas Fösel, Lingzhen Guo, Carlos Navarrete-Benlloch, Florian Marquardt

Neural networks have emerged as a powerful way to approach many practical problems in quantumphysics. In this work, we illustrate the power of deep learning to predict the dynamics of a quantummany-body system, where the training is based purely on monitoring expectation values of observables under random driving. The trained recurrent network is able to produce accurate predictions for driving trajectories entirely different than those observed during training. As a proof of principle, here we train the network on numerical data generated from spin models, showing that it can learn the dynamics of observables of interest without needing information about the full quantum state.This allows our approach to be applied eventually to actual experimental data generated from aquantum many-body system that might be open, noisy, or disordered, without any need for a detailedunderstanding of the system. This scheme provides considerable speedup for rapid explorations andpulse optimization. Remarkably, we show the network is able to extrapolate the dynamics to times longer than those it has been trained on, as well as to the infinite-system-size limit.

Depth of focus extension in optical coherence tomography using ultrahigh chromatic dispersion of zinc selenide

Maria N. Romodina, Kanwarpal Singh

We report a novel technique to overcome<br>the depth-of-focus limitation in optical coherence tomography (OCT) using chromatic<br>dispersion of zinc selenide lens.<br>OCT is an established method of optical<br>imaging, which found numerous biomedical<br>applications. However, the depth scanning range of high-resolution OCT is limited by its depth of focus. Chromatic dispersion of zinc selenide lens allows to get high lateral resolution along extended depth of focus, because the different spectral components are focused at a different position along axes of light propagation. Test measurements with nanoparticle phantom show 2.8 times extension of the depth of focus compare to the system with a standard achromatic lens. The feasibility of biomedical applications was demonstrated by ex vivo imaging of the pig cornea and chicken fat tissue.

Optimal broad-band frequency conversion via a magnetomechanical transducer

Fabian Engelhardt, Victor A. S. V. Bittencourt, Hans Huebl, Olivier Klein , Silvia Viola-Kusminskiy

Developing schemes for efficient and broad-band frequency conversion of quantum signals is an ongoing challenge in the field of modern quantum information. Especially the coherent conversion between microwave and optical signals is an important milestone towards long-distance quantum communication. In this work, we propose a two-stage conversion protocol, employing a resonant interaction between magnetic and mechanical excitations as a mediator between microwave and optical photons. Based on estimates for the coupling strengths under optimized conditions for yttrium iron garnet, we predict close to unity conversion efficiency without the requirement of matching cooperativities. We predict a conversion bandwidth in the regions of largest efficiency on the order of magnitude of the coupling strengths which can be further increased at the expense of reduced conversion efficiency.

Anomalous Behaviors of Quantum Emitters in Non-Hermitian Baths

Zongping Gong, Miguel Bello, Daniel Malz, Flore K. Kunst

Both non-Hermitian systems and the behaviour of emitters coupled to structured baths have been studied intensely in recent years. Here we study the interplay of these paradigmatic settings. In a series of examples, we show that a single quantum emitter coupled to a non-Hermitian bath displays a number of unconventional behaviours, many without Hermitian counterpart. We first consider a unidirectional hopping lattice whose complex dispersion forms a loop. We identify peculiar bound states inside the loop as a manifestation of the non-Hermitian skin effect. In the same setting, emitted photons may display spatial amplification markedly distinct from free propagation, which can be understood with the help of the generalized Brillouin zone. We then consider a nearest-neighbor lattice with alternating loss. We find that the long-time emitter decay always follows a power law, which is usually invisible for Hermitian baths. Our work points toward a rich landscape of anomalous quantum emitter dynamics induced by non-Hermitian baths.

Bound states and photon emission in non-Hermitian nanophotonics

Zongping Gong, Miguel Bello, Daniel Malz, Flore K. Kunst

We establish a general framework for studying the bound states and the photon-emission dynamics of quantum emitters coupled to structured nanophotonic lattices with engineered dissipation (loss). In the single-excitation sector, the system can be described exactly by a non-Hermitian formalism. We have pointed out in the accompanying letter [Gong \emph{et al}., arXiv:2205.05479] that a single emitter coupled to a one-dimensional non-Hermitian lattice may already exhibit anomalous behaviors without Hermitian counterparts. Here we provide further detail on these observations. We also present several additional examples on the cases with multiple quantum emitters or in higher dimensions. Our work unveils the tip of the iceberg of the rich non-Hermitian phenomena in dissipative nanophotonic systems.

TMM-Fast: A Transfer Matrix Computation Package for Multilayer Thin-Film Optimization: tutorial

Alexander Luce, Ali Mahdavi, Florian Marquardt, Heribert Wankerl

Achieving the desired optical response from a multilayer thin-film structure over a broad range of wavelengths and angles of incidence can be challenging. An advanced thin-film structure can consist of multiple materials with different thicknesses and numerous layers. Design and optimization of complex thin-film structures with multiple variables is a computationally heavy problem that is still under active research. To enable fast and easy experimentation with new optimization techniques, we propose the Python package TMM-Fast which enables parallelized computation of reflection and transmission of light at different angles of incidence and wavelengths through the multilayer thin-film.<br>By decreasing computational time, generating datasets for machine learning becomes feasible and evolutionary optimization can be used effectively. Additionally, the sub-package TMM-Torch allows to directly compute analytical<br>gradients for local optimization by using PyTorch Autograd functionality. Finally, an OpenAi Gym environment is presented which allows the user to train reinforcement learning agents on the problem of finding multilayer thin-film configurations.

Topological interface of light

Flore K. Kunst

Upon combining dissipative and nonlinear effects in a bipartite lattice of cavity polaritons, dissipatively stabilized bulk gap solitons emerge, which create a topological interface.

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Precision size and refractive index analysis of weakly scattering nanoparticles in polydispersions

Anna D. Kashkanova, Martin Blessing, André Gemeinhardt, Didier Soulat, Vahid Sandoghdar

Characterization of the size and material properties of particles in liquid suspensions is in very high demand, for example, in the analysis of colloidal samples or of bodily fluids such as urine or blood plasma. However, existing methods are limited in their ability to decipher the constituents of realistic samples. Here we introduce iNTA as a new method that combines interferometric detection of scattering with nanoparticle tracking analysis to reach unprecedented sensitivity and precision in determining the size and refractive index distributions of nanoparticles in suspensions. After benchmarking iNTA with samples of colloidal gold, we present its remarkable ability to resolve the constituents of various multicomponent and polydisperse samples of known origin. Furthermore, we showcase the method by elucidating the refractive index and size distributions of extracellular vesicles from Leishmania parasites and human urine. The current performance of iNTA already enables advances in several important applications, but we also discuss possible improvements.

Optomagnonics in Dispersive Media: Magnon-Photon Coupling Enhancement at the Epsilon-near-Zero Frequency

V. A. S. V. Bittencourt, I. Liberal, S. Viola-Kusminskiy

Reaching strong light-matter coupling in solid-state systems has long been pursued for the implementation of scalable quantum devices. Here, we put forward a system based on a magnetized epsilon-near-zero (ENZ) medium, and we show that strong coupling between magnetic excitations (magnons) and light can be achieved close to the ENZ frequency due to a drastic enhancement of the magneto-optical response. We adopt a phenomenological approach to quantize the electromagnetic field inside a dispersive magnetic medium in order to obtain the frequency-dependent coupling between magnons and photons. We predict that, in the epsilon-near-zero regime, the single-magnon single-photon coupling can be comparable to the magnon frequency for a small magnetic volume and perfect mode overlap. For state-of-the-art illustrative values, this would correspond to achieving the single-magnon strong coupling regime, where the coupling rate is larger than all the decay rates. Finally, we show that the nonlinear energy spectrum intrinsic to this coupling regime can be probed via the characteristic multiple magnon sidebands in the photon power spectrum.

Tunable and state-preserving frequency conversion of single photons in hydrogen

Rinat Tyumenev, Jonas Hammer, Nicolas Joly, Philip St.J. Russell, David Novoa

In modern quantum technologies, preservation of the photon statistics of quantum optical states upon frequency conversion holds the key to the viable implementation of quantum networks, which often require interfacing of several subsystems operating in widely different spectral regions. Most current approaches offer only very small frequency shifts and limited tunability, while suffering from high insertion loss and Raman noise originating in the materials used. We introduce a route to quantum-correlation–preserving frequency conversion using hydrogen-filled antiresonant-reflecting photonic crystal fibers. Transient optical phonons generated by stimulated Raman scattering enable selective frequency up-conversion by 125 terahertz of the idler photon of an entangled pair, with efficiencies up to 70%. This threshold-less molecular modulation process preserves quantum correlations, making it ideal for applications in quantum information.<br><br>https://www.science.org/stoken/author-tokens/ST-474/full

Observing polarization patterns in the collective motion of nanomechanical arrays

Juliane Doster, Tirth Shah, Thomas Fösel, Philipp Paulitschke, Florian Marquardt, Eva Weig

In recent years, nanomechanics has evolved into a mature field, with wide-ranging impact from sensing applications to fundamental physics, and it has now reached a stage which enables the fabrication and study of ever more elaborate devices. This has led to the emergence of arrays of coupled nanomechanical resonators as a promising field of research, serving as model systems to study collective dynamical phenomena such as synchronization or topological transport. From a general point of view, the arrays investigated so far represent scalar fields on a lattice. Moving to a scenario where these could be extended to vector fields would unlock a whole host of conceptually interesting additional phenomena, including the physics of polarization patterns in wave fields and their associated topology. Here we introduce a new platform, a two-dimensional array of coupled nanomechanical pillar resonators, whose orthogonal vibration directions encode a mechanical polarization degree of freedom. We demonstrate direct optical imaging of the collective dynamics, enabling us to analyze the emerging polarization patterns and follow their evolution with drive frequency.

Ising machines: Hardware solvers for combinatorial optimization problems

Naeimeh Mohseni, Peter McMahon, Tim Byrnes

Ising machines are hardware solvers which aim to find the absolute or approximate ground states of the Ising model. The Ising model is of fundamental computational interest because it is possible to formulate any problem in the complexity class NP as an Ising problem with only polynomial overhead. A scalable Ising machine that outperforms existing standard digital computers could have a huge impact for practical applications for a wide variety of optimization problems. In this review, we survey the current status of various approaches to constructing Ising machines and explain their underlying operational principles. The types of Ising machines considered here include classical thermal annealers based on technologies such as<br>spintronics, optics, memristors, and digital hardware accelerators; dynamical-systems solvers implemented with optics and electronics; and superconducting-circuit quantum annealers. We compare and contrast their performance using standard metrics such as the ground-state success probability and time-to-solution, give their scaling relations with problem size, and<br>discuss their strengths and weaknesses.

Best practices for reporting throughput in biomedical research

Maik Herbig, Akihiro Isozaki, Dino Di Carlo, Jochen Guck, Nao Nitta, Robert Damoiseaux, Shogo Kamikawaji, Eigo Suyama, Hirofumi Shintaku, et al.

mRNA Subtype of Cancer-Associated Fibroblasts Significantly Affects Key Characteristics of Head and Neck Cancer Cells

Barbora Peltanová, Hana Holcová Polanská, Martina Raudenská, Jan Balvan, Jiri Navrátil, Tomás Vicar, Jaromir Gumulec, Barbora Cechová, Martin Kräter, et al.

Head and neck squamous cell carcinomas (HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial cancer cells, as communication between CAFs and epithelial cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different mRNA subtypes influence the proliferation of cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of HNSCC patients to identify a possible gene signature typical for HNSCC progression. We found that the right kind of cooperation between cancer cells and CAFs is needed for tumour growth and progression, and only specific mRNA subtypes can support the growth of primary cancer cells or metastases. Specifically, during coculture, cancer cell colony supporting effect and effect of CAFs on cell stiffness of cancer cells are driven by the mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in cancer cell glycolysis levels and lactate shuttle-related transporters.

Symmetry-protected exceptional and nodal points in non-Hermitian systems

Sharareh Sayyad, Marcus Stålhammar, Lukas Rødland, Flore K. Kunst

One of the unique features of non-Hermitian (NH) systems is the appearance of non-Hermitian degeneracies known as exceptional points~(EPs). The occurrence of EPs in NH systems requires satisfying constraints whose number can be reduced in the presence of some symmetries. This results in stabilizing the appearance of EPs. Even though two different types of EPs, namely defective and non-defective EPs, may emerge in NH systems, exploring the possibilities of stabilizing EPs has been only addressed for defective EPs, at which the Hamiltonian becomes non-diagonalizable. In this letter, we show that certain discrete symmetries, namely parity-time, parity-particle-hole, and pseudo-Hermitian symmetry, may guarantee the occurrence of both defective and non-defective EPs. We extend this list of symmetries by including the non-Hermitian time-reversal symmetry in the two-band systems. <br>We further show that the non-defective EPs manifest themselves by i) the diagonalizability of non-Hermitian Hamiltonian at these points and ii) the non-diagonalizability of the Hamiltonian along certain intersections of non-defective EPs. Two-band and four-band models exemplify our findings. Through an example, we further reveal that ordinary (Hermitian) nodal points may coexist with defective EPs in non-Hermitian models when the above symmetries are relaxed.

A Proposal to Perform High Contrast Imaging of Human Palatine Tonsil with Cross Polarized Optical Coherence Tomography

Gargi Sharma, Asha Parmar, Franziska Hoffmann, Katharina Geißler, Ferdinand von Eggeling, Orlando Guntinas-Lichius, Kanwarpal Singh

The palatine tonsils provide the first line of immune defense against foreign pathogens<br>inhaled or ingested. However, a disruption in the epithelial layer within the tonsil crypts can lead to recurrent acute tonsillitis (RAT). Current imaging techniques suffer from poor resolution and contrast and do not allow a classification of the severity of RAT. We have developed a cross-polarized optical coherence tomography system. The system can detect a change in the polarization of the light after the light-tissue interaction. We demonstrate improved resolution and contrast in tonsil imaging with the developed method. Intensity, as well as retardance images of the excised tonsil tissue, were acquired. Features such as crypt epithelium, lymphoid follicles, and dense connective tissue were observed with improved contrast. Cross polarized optical coherence tomography can be a valuable tool in the clinic to evaluate palatine tonsils as it would allow visualizing common tonsil features without the need for any external contrast agent.

Modern applications of machine learning in quantum sciences

Anna Dawid, Julian Arnold, Borja Requena, Alexander Gresch, Marcin Płodzień, Kaelan Donatella, Kim Nicoli, Paolo Stornati, Rouven Koch, et al.

In these Lecture Notes, we provide a comprehensive introduction to the most<br>recent advances in the application of machine learning methods in quantum<br>sciences. We cover the use of deep learning and kernel methods in supervised,<br>unsupervised, and reinforcement learning algorithms for phase classification,<br>representation of many-body quantum states, quantum feedback control, and<br>quantum circuits optimization. Moreover, we introduce and discuss more<br>specialized topics such as differentiable programming, generative models,<br>statistical approach to machine learning, and quantum machine learning.<br>

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)

Andreas Walther, Anne Mackens-Kiani, Julian Eder, Maik Herbig, Christoph Herold, Clemens Kirschbaum, Jochen Guck, Lucas Wittwer, Katja Beesdo-Baum, et al.

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

Felix Reichel, Martin Kräter, Kevin Peikert, Hannes Glaß, Philipp Rosendahl, Maik Herbig, Alejandro Rivera Prieto, Alexander Kihm, Giel Bosman, et al.

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of five ChAc patients compared to healthy controls during up to 1-year individual off-label treatment with the tyrosine kinase inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results showed that blood cell deformability–including both RBCs and leukocytes - in general was altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observed alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hinted at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc.

Unbiased retrieval of frequency-dependent mechanical properties from noisy time-dependent signals

Shada Abuhattum, Hui-Shun Kuan, Paul Mueller, Jochen Guck, Vasily Zaburdaev

The mechanical response of materials to dynamic loading is often quantified by the frequency-dependent complex modulus. Probing materials directly in the frequency domain faces technical challenges such as a limited range of frequencies, long measurement times, or small sample sizes. Furthermore, many biological samples, such as cells or tissues, can change their properties upon repetitive probing at different frequencies. Therefore, it is common practice to extract the material properties by fitting predefined mechanical models to measurements performed in the time domain. This practice, however, precludes the probing of unique and yet unexplored material properties. In this report, we demonstrate that the frequency-dependent complex modulus can be robustly retrieved in a model-independent manner directly from time-dependent stress-strain measurements. While applying a rolling average eliminates random noise and leads to a reliable complex modulus in the lower frequency range, a Fourier transform with a complex frequency helps to recover the material properties at high frequencies. Finally, by properly designing the probing procedure, the recovery of reliable mechanical properties can be extended to an even wider frequency range. Our approach can be used with many state-of-the-art experimental methods to interrogate the mechanical properties of biological and other complex materials.

Hollow-core optical fibre sensors for operando Raman spectroscopy investigation of Li-ion battery liquid electrolytes

Ermanno Miele, Wesley M. Dose, Ilya Manyakin, Michael Frosz, Zachary Ruff, Michael F. L. De Volder, Clare P. Grey, Jeremy J. Baumberg, Tijmen G. Euser

Improved analytical tools are urgently required to identify degradation and failure mechanisms in Li-ion batteries. However, understanding and ultimately avoiding these detrimental mechanisms requires continuous tracking of complex electrochemical processes in different battery components. Here, we report an operando spectroscopy method that enables monitoring the chemistry of a carbonate-based liquid electrolyte during electrochemical cycling in Li-ion batteries with a graphite anode and a LiNi0.8Mn0.1Co0.1O2 cathode. By embedding a hollow-core optical fibre probe inside a lab-scale pouch cell, we demonstrate the effective evolution of the liquid electrolyte species by background-free Raman spectroscopy. The analysis of the spectroscopy measurements reveals changes in the ratio of carbonate solvents and electrolyte additives as a function of the cell voltage and show the potential to track the lithium-ion solvation dynamics. The proposed operando methodology contributes to understanding better the current Li-ion battery limitations and paves the way for studies of the degradation mechanisms in different electrochemical energy storage systems.

PiSCAT: A Python Package for Interferometric Scattering Microscopy

Houman Mirzaalian Dastjerdi, Reza Gholami Mahmoodabadi, Matthias Bär, Vahid Sandoghdar, Harald Köstler

Interferometric scattering (iSCAT) microscopy allows one to image and track nano-objects with a nanometer spatial and microsecond temporal resolution over arbitrarily long measurement times (Lindfors et al., 2004; Taylor & Sandoghdar, 2019b, 2019a). A key advantage of this technique over the well-established fluorescence methods is the indefinite photostability of the scattering phenomenon in contrast to the photobleaching of fluorophores. This means that one can perform very long measurements. Moreover, scattering processes are linear and thus do not saturate. This leads to larger signals than is possible from a single fluorophore. As a result, one can image at a much faster rate than in fluorescence microscopy. Furthermore, the higher signal makes it possible to localize a nano-object with much better spatial precision.<br>The remarkable sensitivity of iSCAT, however, also brings about the drawback that one obtains a rich speckle-like background from other nano-objects in the field of view.

Introduction to quantum optics

Carlos Navarrete-Benlloch

These are the lecture notes for a course that I am teaching at Zhiyuan College of Shanghai Jiao<br>Tong University (available at www.youtube.com/derekkorg), though the first draft was created for a previous course I taught at the University of Erlangen-Nuremberg in Germany. It has been designed for students who have only had basic training on quantum mechanics, and hence, the course is suited<br>for people at all levels (say, from the end of the bachelor all the way into the PhD). The notes are<br>a work in progress, meaning that some proofs and many figures are still missing. However, I’ve<br>tried my best to write everything in such a way that a reader can follow naturally all arguments<br>and derivations even with these missing bits. Also a few chapters are left to add, including one<br>on mathematical methods to analyze the dynamics of open systems, and another introducing the plethora of current experimental platforms where the tools and ideas developed in these notes are being currently implemented.

Quantum physics in space

Alessio Belenchia, Matteo Carlesso, Ömer Bayraktar, Daniele Dequal, Ivan Derkach, Giulio Gasbarri, Waldemar Herr, Ying Lia Li, Markus Rademacher, et al.

Advances in quantum technologies are giving rise to a revolution in the way fundamental physics questions are explored at the empirical level. At the same time, they are the seeds for future disruptive technological applications of quantum physics. Remarkably, a space-based environment may open many new avenues for exploring and employing quantum physics and technologies. Recently, space missions employing quantum technologies for fundamental or applied studies have been proposed and implemented with stunning results. The combination of quantum physics and its space application is the focus of this review: we cover both the fundamental scientific questions that can be tackled with quantum technologies in space and the possible implementation of these technologies for a variety of academic and commercial purposes.

High-resolution vibronic spectroscopy of a single molecule embedded in a crystal

Johannes Zirkelbach, Masoud Mirzaei, Irena Deperasińska, Boleslaw Kozankiewicz, Burak Gürlek, Alexey Shkarin, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

Vibrational levels of the electronic ground states in dye molecules have not been previously explored at high resolution<br>in solid matrices. We present new spectroscopic measurements on single polycyclic aromatic molecules of dibenzoter-<br>rylene embedded in an organic crystal made of para-dichlorobenzene. To do this, we use narrow-band continuous-wave<br>lasers and combine spectroscopy methods based on fluorescence excitation and stimulated emission depletion (STED)<br>to select individual vibronic transitions at a resolution of ∼30 MHz dictated by the linewidth of the electronic ex-<br>cited state. In this fashion, we identify several exceptionally narrow vibronic levels in the electronic ground state with<br>linewidths down to values around 2 GHz. Additionally, we sample the distribution of vibronic wavenumbers, relax-<br>ation rates, and Franck-Condon factors, both in the electronic ground and excited states for a handful of individual<br>molecules. We discuss various noteworthy experimental findings and compare them with the outcome of DFT cal-<br>culations. The highly detailed vibronic spectra obtained in our work pave the way for studying the nanoscopic local<br>environment of single molecules. The approach also provides an improved understanding of the vibrational relaxation<br>mechanisms in the electronic ground state, which may help to create long-lived vibrational states for applications in<br>quantum technology.

Gradient Ascent Pulse Engineering with Feedback

Riccardo Porotti, Vittorio Peano, Florian Marquardt

Efficient approaches to quantum control and feedback are essential for quantum technologies, from sensing to quantum computation. Pure control tasks have been successfully solved using optimization techniques, including methods like gradient-ascent pulse engineering (GRAPE) , relying on a differentiable model of the quantum dynamics. For feedback tasks, such methods are not directly applicable, since the aim is to discover strategies conditioned on measurement outcomes. There, model-free reinforcement learning (RL) has recently proven a powerful new ansatz. What is missing is a way to combine the best of both approaches for scenarios that go beyond weak measurements. In this work, we introduce feedback-GRAPE, which borrows concepts from model-free RL to incorporate the response to strong stochastic (discrete or continuous) measurements, while still performing direct gradient ascent through the quantum dynamics. We illustrate its power on a Jaynes-Cummings model with feedback, where it yields interpretable feedback strategies for state preparation and stabilization in the presence of noise. This approach could be employed for discovering strategies in a wide range of feedback tasks, from calibration of multi-qubit devices to linear-optics quantum computation strategies, quantum-enhanced sensing with adaptive measurements, and quantum error correction.

An explicit model to extract viscoelastic properties of cells from AFM force-indentation curves

Shada Abuhattum Hofemeier, Dominic Mokbel, Paul Müller, Despina Soteriou, Jochen Guck, Sebastian Aland

Atomic force microscopy (AFM) is widely used for quantifying the mechanical properties of soft materials such as cells. AFM force-indentation curves are conventionally fitted with a Hertzian model to extract elastic properties. These properties solely are, however, insufficient to describe the mechanical properties of cells. Here, we expand the analysis capabilities to describe the viscoelastic behavior while using the same force-indentation curves. Our model gives an explicit relation of force and indentation and extracts physically meaningful mechanical parameters. We first validated the model on simulated force-indentation curves. Then, we applied the fitting model to the force-indentation curves of two hydrogels with different crosslinking mechanisms. Finally, we characterized HeLa cells in two cell cycle phases, interphase and mitosis, and showed that mitotic cells have a higher apparent elasticity and a lower apparent viscosity. Our study provides a simple method, which can be directly integrated into the standard AFM framework for extracting the viscoelastic properties of materials.

Polarization Independent Optical Coherence Tomography

Asha Parmar, Gargi Sharma, Kanwarpal Singh

Optical coherence tomography (OCT) is a well established imaging modality for high-resolution three-dimensional imaging in clinical settings. While imaging, care must be taken to minimize the imaging artifacts related to the polarization differences between the sample and the reference signals. Current OCT systems adopt complicated mechanisms, such as the use of multiple detectors, polarization-maintaining fibers, polarization controllers to achieve polarization artifacts free sample images.<br>Often the polarization controllers need readjustment which is not suitable for clinical settings. In this work, we demonstrate a simple approach that can minimize the polarization-related artifacts in the OCT systems. Polarization artifact-free images are acquired using two orthogonally polarized reference signals where the orthogonal polarization is achieved using a Faraday mirror. In the current approach, only a single detector is required which makes the current approach compatiblewith swept-source or camera-basedOCT systems. Furthermore, no polarization controllers are used in the system which increases the system stability while minimizing the artifacts related to the sample birefringence, polarization change due to the sample scattering, and polarization change due to the optical fiber movements present in the system.

Nonreciprocal and chiral single-photon scattering for giant atoms

Yao-Tong Chen, Lei Du, Lingzhen Guo, Zhihai Wang, Yan Zhang, Yong Li, Jin-Hui Wu

In this work, we investigate the nontrivial single-photon scattering properties of giant atoms cou-<br>pled to waveguides that can be an effective platform for realising nonreciprocal and chiral quantum optics. For the two-level giant-atom setup, we identify the condition for nonreciprocal transmission: the external atomic dissipation is further required other than the breaking of time-reversal symmetry by local coupling phases. Especially, in the non-Markovian regime, unconventional revival peaks periodically appear in the reflection spectrum of such a two-level giant-atom system. To explore more interesting scattering behaviours, we further extend the two-level giant-atom system to ∆-type and<br>∇-type three-level giant atoms coupled to double waveguides without external atomic dissipation.<br>We analyse the different physical mechanisms for the nonreciprocal and chiral scattering properties of the ∆-type and ∇-type giant atoms. Our proposed giant-atom structures have potential applications of high-efficient single-photon targeted router and circulator for quantum information precessing.

Phase Space Crystal Vibrations: Chiral Edge States with Preserved Time-reversal Symmetry

Lingzhen Guo, Vittorio Peano, Florian Marquardt

Chiral transport along edge channels in Chern insulators represents the most robust version of topological transport, but it usually requires breaking of the physical time-reversal symmetry. In this work, we introduce a different mechanism that foregoes this requirement, based on the combination of the symplectic geometry of phase space and interactions. Starting from a honeycomb phase-space crystal of atoms, which can be generated by periodic driving of a one-dimensional interacting quantum gas, we show that the resulting vibrational lattice waves have topological properties. Our work provides a new platform to study topological many-body physics in dynamical systems.

suggested by editors

An exception to the rule? Regeneration of the injured spinal cord in the spiny mouse

Daniel Wehner, Catherina G. Becker

The capacity for long-distance axon regeneration and functional recovery after spinal cord injury in the adult has long been thought to be a unique feature of certain non-mammalian vertebrates. However, in this issue of Developmental Cell, Nogueira-Rodrigues et al. report an astonishingly high regenerative ability in the spiny mouse.

Experimental high-dimensional Greenberger-Horne-Zeilinger entanglement with superconducting transmon qutrits

Alba Cervera-Lierta, Mario Krenn, Alan Aspuru-Guzik, Alexey Galda

Multipartite entanglement is one of the core concepts in quantum information science with broad applications that span from condensed matter physics to quantum physics foundations tests. Although its most studied and tested forms encompass two-dimensional systems, current quantum platforms technically allow the manipulation of additional quantum levels. We report the first experimental demonstration of a high-dimensional multipartite entangled state in a superconducting quantum processor. We generate the three-qutrit Greenberger-Horne-Zeilinger state by designing the necessary pulses to perform high-dimensional quantum operations. We obtain the fidelity of 76 ±1%, proving the generation of a genuine three-partite and three-dimensional entangled state.<br>To this date, only photonic devices have been able to create and manipulate these high-dimensional states. Our work demonstrates that another platform, superconducting systems, is ready to exploit<br>high-dimensional physics phenomena and that a programmable quantum device accessed on the<br>cloud can be used to design and execute experiments beyond binary quantum computation.

Stimulated Brillouin scattering in chiral photonic crystal fiber

Xinglin Zeng, Wenbin He, Michael Frosz, Andreas Geilen, Paul Roth, Gordon Wong, Philip Russell, Birgit Stiller

Stimulated Brillouin scattering (SBS) has many applications; for example, in sensing, microwave photonics, and signal processing. Here, we report the first experimental study of SBS in chiral photonic crystal fiber (PCF), which displays optical activity and robustly maintains circular polarization states against external perturbations. As a result, circularly polarized pump light is cleanly backscattered into a Stokes signal with the orthogonal circular polarization state, as is required by angular momentum conservation. By comparison, untwisted PCF generates a Stokes signal with an unpredictable polarization state, owing to its high sensitivity to external perturbations. We use chiral PCF to realize a circularly polarized continuous-wave Brillouin laser. The results pave the way for a new generation of stable circularly polarized SBS systems with applications in quantum manipulation, optical tweezers, optical gyroscopes, and fiber sensors.

Quantitative imaging of Caenorhabditis elegans dauer larvae during cryptobiotic transition

Kyoohyun Kim, Vamshidhar Gade, Teymuras V. Kurzchalia, Jochen Guck

Upon starvation or overcrowding, the nematode Caenorhabditis elegans enters diapause by forming a dauer larva, which can then further survive harsh desiccation in an anhydrobiotic state. We have previously identified the genetic and biochemical pathways essential for survival—but without detailed knowledge of their material properties, the mechanistic understanding of this intriguing phenomenon remains incomplete. Here we employed optical diffraction tomography (ODT) to quantitatively assess the internal mass density distribution of living larvae in the reproductive and diapause stages. ODT revealed that the properties of the dauer larvae undergo a dramatic transition upon harsh desiccation. Moreover, mutants that are sensitive to desiccation displayed structural abnormalities in the anhydrobiotic stage that could not be observed by conventional microscopy. Our advance opens a door to quantitatively assessing the transitions in material properties and structure necessary to fully understand an organism on the verge of life and death.

Efficient Excitation of High-Purity Modes in Arbitrary Waveguide Geometries

Ralf Mouthaan, Peter J. Christopher, Jonathan Pinnell, Michael Frosz, George Gordon, Timothy D. Wilkinson, Tijmen G. Euser

A general method is presented for exciting discrete modes in waveguides of arbitrary geometry. Guided modes supported by the waveguide are first calculated using a finite difference frequency domain model. High efficiency holograms to excite these discrete modes are then generated using the Direct Search hologram generation algorithm. The Direct Search algorithm is optimised such that the inherent properties of waveguide modes are exploited to give faster execution times. A nodeless antiresonant photonic crystal fibre is considered as a test geometry, in which high-purity modes are experimentally excited and in-coupling efficiencies of up to 32.8% are obtained.

Advances in Magnetics Roadmap on Spin-Wave Computing

A. V. Chumak, P. Kabos, M. Wu, C. Abert, C. Adelmann, A. Adeyeye, J. Åkerman, F. G. Aliev, A. Anane, et al.

Magnonics addresses the physical properties of spin waves and utilizes them for data processing. Scalability down to atomic dimensions, operation in the GHz-to-THz frequency range, utilization of nonlinear and nonreciprocal phenomena, and compatibility with CMOS are just a few of many advantages offered by magnons. Although magnonics is still primarily positioned in the academic domain, the scientific and technological challenges of the field are being extensively investigated, and many proof-of-concept prototypes have already been realized in laboratories. This roadmap is a product of the collective work of many authors, which covers versatile spin-wave computing approaches, conceptual building blocks, and underlying physical phenomena. In particular, the roadmap discusses the computation operations with the Boolean digital data, unconventional approaches, such as neuromorphic computing, and the progress toward magnon-based quantum computing. This article is organized as a collection of sub-sections grouped into seven large thematic sections. Each sub-section is prepared by one or a group of authors and concludes with a brief description of current challenges and the outlook of further development for each research direction.

Cascaded frequency up-conversion of bright squeezed vacuum: spectral and correlation properties

Andrei V. Rasputnyi, Denis A. Kopylov, Tatiana V. Murzina, Maria V. Chekhova

High-gain parametric down-conversion (PDC) is inevitably accompanied by cascaded up-conversion (CUpC) of PDC radiation in a nonlinear crystal even if CUpC is nonphase matched. Here we study experimentally and theoretically the spectral properties of broadband phase-matched and nonphase-matched CUpC radiation in a beta barium borate (BBO) crystal. Our calculations of the normalized second- order correlation function predict the super-bunching of CUpC radiation.

Nonlinear microscopy using impulsive stimulated Brillouin scattering for high-speed elastography

Benedikt Krug, Nektarios Koukourakis, Jochen Guck, Jürgen Czarske

The impulsive stimulated Brillouin microscopy promises fast, non-contact measurements of the elastic properties of biological samples. The used pump-probe approach employs an ultra-short pulse laser and a cw laser to generate Brillouin signals. Modeling of the microscopy technique has already been carried out partially, but not for biomedical applications. The nonlinear relationship between pulse energy and Brillouin signal amplitude is proven with both simulations and experiments. Tayloring of the excitation parameters on the biologically relevant polyacrylamide hydrogels outline sub-ms temporal resolutions at a relative precision of <1%. Brillouin microscopy using the impulsive stimulated scattering therefore exhibits high potential for the measurements of viscoelastic properties of cells and tissues.

Cross-Polarized Optical Coherence Tomography System with Unpolarized Light

Georg R. Hartl, Asha Parmar, Gargi Sharma, Kanwarpal Singh

Cross-polarized optical coherence tomography offers improved contrast for samples which<br>can alter the polarization of light when it interacts with the sample. This property has been utilized to screen pathological conditions in several organs. Existing cross-polarized optical coherence tomography systems require several polarization-controlling elements to minimize the optical fiber movement-related image artifacts. In this work, we demonstrate a cross-polarized optical coherence tomography system using unpolarized light and only two quarter-wave plates, which is free from fiber-induced image artifacts. The simplicity of the approach will find many applications in clinical settings.

Single photon sources for quantum radiometry: a brief review about the current state‑of‑the‑art

Stefan Kück, Marco López, Helmuth Hofer, Hristina Georgieva, Justus Christinck, Beatrice Rodiek, Geiland Porrovecchio, Marek Smid, Stephan Götzinger, et al.

Single-photon sources have a variety of applications. One of these is quantum radiometry, which is reported on in this<br>paper in the form of an overview, specifically of the current state of the art in the application of deterministic single photon<br>sources to the calibration of single photon detectors. To optimize single-photon sources for this purpose, extensive research<br>is currently carried out at the European National Metrology Institutes (NMIs), in collaboration with partners from universi-<br>ties. Single-photon sources of different types are currently under investigation, including sources based on defect centres in<br>(nano-)diamonds, on molecules and on semiconductor quantum dots. We will present, summarise, and compare the current<br>results obtained at European NMIs for single-photon sources in terms of photon flux, single-photon purity, and spectral<br>power distribution as well as the results of single-photon detector calibrations carried out with this type of light sources.

Label-free imaging flow cytometry for analysis and sorting of enzymatically dissociated tissues

Maik Herbig, Karen Tessmer, Martin Nötzel, Ahmad Ahsan Nawaz, Tiago Santos-Ferreira, Oliver Borsch, Sylvia J. Gasparini, Jochen Guck, Marius Ader

Biomedical research relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells’ properties and should be avoided, especially when purifying cells for clinical applications. A promising alternative is the label-free identification of cells based on physical properties. Sorting real-time deformability cytometry (soRT-DC) is a microfluidic technique for label-free analysis and sorting of single cells. In soRT-FDC, bright-field images of cells are analyzed by a deep neural net (DNN) to obtain a sorting decision, but sorting was so far only demonstrated for blood cells which show clear morphological differences and are naturally in suspension. Most cells, however, grow in tissues, requiring dissociation before cell sorting which is associated with challenges including changes in morphology, or presence of aggregates. Here, we introduce methods to improve robustness of analysis and sorting of single cells from nervous tissue and provide DNNs which can distinguish visually similar cells. We employ the DNN for image-based sorting to enrich photoreceptor cells from dissociated retina for transplantation into the mouse eye.

Machine learning assisted real-time deformability cytometry of CD34+ cells allows to identify patients with myelodysplastic syndromes

Maik Herbig, Angela Jacobi, Manja Wobus, Heike Weidner, Anna Mies, Martin Kräter, Oliver Otto, Christian Thiede, Marie-Theresa Weickert, et al.

Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations. Hence, quantitative image analysis could improve the accuracy and reproducibility of MDS diagnosis. We used real-time deformability cytometry (RT-DC) to measure bone marrow biopsy samples of MDS patients and age-matched healthy individuals. RT-DC is a high-throughput (1000 cells/s) imaging flow cytometer capable of recording morphological and mechanical properties of single cells. Properties of single cells were quantified using automated image analysis, and machine learning was employed to discover morpho-mechanical patterns in thousands of individual cells that allow to distinguish healthy vs. MDS samples. We found that distribution properties of cell sizes differ between healthy and MDS, with MDS showing a narrower distribution of cell sizes. Furthermore, we found a strong correlation between the mechanical properties of cells and the number of disease-determining mutations, inaccessible with current diagnostic approaches. Hence, machine-learning assisted RT-DC could be a promising tool to automate sample analysis to assist experts during diagnosis or provide a scalable solution for MDS diagnosis to regions lacking sufficient medical experts.

Mechanical spinal cord transection in larval zebrafish and subsequent whole-mount histological processing

Nora John, Julia Kolb, Daniel Wehner

Zebrafish regenerate their spinal cord after injury, both at larval and adult stages. Larval zebrafish have emerged as a powerful model system to study spinal cord injury and regeneration due to their high optical transparency for in vivo imaging, amenability to high-throughput analysis, and rapid regeneration time. Here, we describe a protocol for the mechanical transection of the larval zebrafish spinal cord, followed by whole-mount tissue processing for in situ hybridization and immunohistochemistry to elucidate principles of regeneration.

Bright squeezed vacuum for two-photon spectroscopy: simultaneously high resolution in time and frequency, space and wavevector

Paula Cutipa, Maria V. Chekhova

Entangled photons offer two advantages for two-photon absorption spectroscopy. One of them, the linear scaling of two-photon absorption rate with the input photon flux, is valid only at very low photon fluxes and is therefore impractical. The other is the overcoming of the classical constraints for simultaneous resolution in time–frequency and in space–wavevector. Here we consider bright squeezed vacuum (BSV) as an alternative to entangled photons. The efficiency increase it offers in comparison with coherent light is modest, but it does not depend on the photon flux. Moreover, and this is what we show in this work, BSV also provides simultaneously high resolution in time and frequency, and in space and wavevector. In our experiment, we measure the widths of the second-order correlation functions in space, time, frequency, and angle and demonstrate the violation of the constraint given by the Fourier transformation, in the case of photon pairs, known as the Mancini criterion of entanglement.

Light propagation and magnon-photon coupling in optically dispersive magnetic media

V. A. S. V. Bittencourt, I. Liberal, S. Viola-Kusminskiy

Achieving strong coupling between light and matter excitations in hybrid systems is a benchmark for the implementation of quantum technologies. We recently proposed (Bittencourt, Liberal, and Viola-Kusminskiy, arXiv:2110.02984) that strong single-particle coupling between magnons and light can be realized in a magnetized epsilon-near-zero (ENZ) medium, in which magneto-optical effects are enhanced. Here we present a detailed derivation of the magnon-photon coupling Hamiltonian in dispersive media both for degenerate and nondegenerate optical modes, and show the enhancement of the coupling near the ENZ frequency. Moreover, we show that the coupling of magnons to plane-wave nondegenerate Voigt modes vanishes at specific frequencies due to polarization selection rules tuned by dispersion. Finally, we present specific results using a Lorentz dispersion model. Our results pave the way for the design of dispersive optomagnonic systems, providing a general theoretical framework for describing and engineering ENZ-based optomagnonic systems.

Correlative all-optical quantification of mass density and mechanics of subcellular compartments with fluorescence specificity

Raimund Schlüßler, Kyoohyun Kim, Martin Nötzel, Anna Taubenberger, Shada Abuhattum, Timon Beck, Paul Müller, Shovamaye Maharana, Gheorghe Cojoc, et al.

Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples − so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epifluorescence imaging for explicitly measuring the Brillouin shift, RI, and absolute density with specificity to fluorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample − a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.

Cooperative quantum phenomena in light-matter platforms

Michael Reitz, Christian Sommer, Claudiu Genes

Quantum cooperativity is evident in light-matter platforms where quantum-emitter ensembles are interfaced<br>with confined optical modes and are coupled via the ubiquitous electromagnetic quantum vacuum.<br>Cooperative effects can find applications, among other areas, in topological quantum optics, in quantum<br>metrology, or in quantum information. This tutorial provides a set of theoretical tools to tackle the behavior<br>responsible for the onset of cooperativity by extending open quantum system dynamics methods, such as<br>the master equation and quantum Langevin equations, to electron-photon interactions in strongly coupled<br>and correlated quantum-emitter ensembles. The methods are illustrated on a wide range of current research<br>topics such as the design of nanoscale coherent-light sources, highly reflective quantum metasurfaces, or<br>low intracavity power superradiant lasers.

Comparison of back focal plane imaging of nitrogen vacancy centers in nanodiamond and core-shell CdSe/CdS quantum dots

Justus Christinck, Beatrice Rodiek, Marco Lopez , Hristina Georgieva, Stephan Götzinger, Stefan Kück

We report on the characterization of the angular-dependent emission of two different <br>single-photon emitters based on nitrogen-vacancy centers in nanodiamond and on core-shell CdSe/CdS quantum dot nanoparticles. The emitters were characterized in a confocal microscope <br>setup by spectroscopy and Hanbury-Brown and Twiss interferometry. The angular-dependent emission is measured using a back focal plane imaging technique. A theoretical model of the angular emission patterns of the 2D dipoles of the emitters is developed to determine their orientation. Experiment and model agree well with each other.