Opening Remarks

• Gerd Leuchs (Max-Planck for the Science of Light)
• Liz Rogan (OSA, CEO)
• Frank Duzaar (DEAN, FAU)

Room: Seminar room

Physics and applications of epsilon-near-zero materials

• Robert Boyd (University of Ottawa)

Room: Seminar room This talk begins with a description of how the properties of light become modified for propagation through a material for which the dielectric permittivity epsilon is nearly vanishing. In such a situation, the refractive index also nearly vanishes, and thus both the wavelength of light and the phase velocity of light become nearly infinite. Radiative processes also are strongly modified, with both the Einstein A and B coefficients being dependent on the refractive index of the material. We have recently found that nonlinear optical properties tend to be strongly enhanced in epsilon-near-zero (ENZ) materials [1]. For the case of indium-tin-oxide (ITO), we measured a huge value (10^6 times larger than that of fused silica) of the nonlinear coefficient n_2. In subsequent work, we have fabricated a metasurface consisting of gold nanorods on an ITO substrate, and we have found that the nonlinear coefficient is further enhanced and can be controlled in both magnitude and sign [2]. The talk then turns to a discussion of the implications of the use of ENZ materials as a platform for applications in the field of nanophotonics. 1. Large optical nonlinearity of indium tin oxide in its epsilon-near-zero region, M. Z. Alam, I. D. Leon, and R. W. Boyd, Science 352, 795 (2016).  2. Large optical nonlinearity of nanoantennas coupled to an epsilon-near-zero material, M. Z. Alam, S. A. Schulz, J. Upham, I. De Leon and R. W. Boyd, Nature Photonics,12 79-83 (2018).

Quantum optics and information science in multi-dimensional photonics networks

• Christine Silberhorn (University of Paderborn)

Room: Seminar room Classical optical networks have been widely used to explore a broad range of transfer phenomena based on coherent interference of waves, which relate to different disciplines in physics, information science, and even biological systems. At the quantum level, the quantized nature of light, this means the existence of photons and entangled states, gives rise to genuine quantum effects. Yet, to date, quantum network experiments typically remain very limited in terms of the number of photons, reconfigurability and, maybe most importantly, network size and dimensionality. Photonic quantum systems, which comprise multiple optical modes as well as highly non-classical and sophisticated quantum states of light, have been investigated intensively in various theoretical proposals over the last decades. However, their implementation requires advanced setups of high complexity, which poses a considerable challenge on the experimental side. The successful realization of controlled quantum network structures is key for many applications in quantum optics and quan- tum information science. Here we present three different approaches to overcome current limitations for the experimental implementation of multi-dimensional quantum networks. Non-linear, integrated quantum devices with multiple channels allow to combine several functionalities on a single monolithic structure, e.g. photon pair generation, circuitry and fast routing. The photon temporal modes of ultrafast pulsed quantum light are defined as sets of field orthogonal superposition states; they span an attractive high-dimensional Hilbert space for quantum communication applications. Finally, pulsed light in combination with designed fibre loop geometries is harnessed for realizing quantum walks as a test-bed for the photonic quantum simulation.

Multi-scale imaging inside and outside the optics lab

• Jan Huisken (University of Wisconsin)

Room: Seminar room Fast multi-scale imaging is needed to study biological processes in single cells across an entire living embryo. Light sheet microscopy (SPIM, LSFM) has changed the field of 3D imaging dramatically by offering a versatile and simple technique to obtain optical sectioning deep inside biological specimens. By illuminating the sample with a thin sheet of light and collecting fluorescence with a fast and sensitive camera, phototoxicity is minimal and high speed acquisitions of long developmental processes have become possible. The ability to custom design an instrument around a sample has empowered many research labs to do experiments that have been impossible with commercial instruments. We have expanded the capabilities of the light sheet microscopy platform by developing optical and computational tools to address fundamental questions in cell and developmental biology. Typically, in order to get access to cutting-edge technology, the biologist visits an engineer’s lab or a facility that offers the technology. However, the experiments may be severely compromised by the fact that living biological samples die or otherwise degrade in transit. Experiments also need to be conducted in a short, predefined amount of time; experiments may be rushed and essential controls skipped. We aim to foster a new model of advanced microscopy, based on shareable, modular instruments configurable to a broad range of applications. Employing modularity in the design facilitates reconfiguration and allows easy upgradability and an expanding functional palette. In turn, shareability provides financial prudent widespread access to cutting edge technologies.

Superresolution by image scanning microscopy and image inversion interferometry

• Rainer Heintzmann (University of Jena)

Room: Seminar room In the past decade revolutionary advances have been made in the field of microscopy imaging, some of which have been honoured by the Nobel prize in Chemistry 2014. Yet some methods are less well known, which will be the topic of this talk. Image scanning microscopy is a linear super-resolution method, which made it to the commercial market. However, image inversion interferometry as realized by the UZ-interferometer (UZI) is relatively unknown and the superresolution aspect is based on an interesting interferometric effect in which the light, in a sense, creates its own pinhole with the advantage of not losing any photons on the detection side. This talk will also present a quantitative signal-to-noise comparison of various linear superresolution methods.

Pushing the limits of fluorescence microscopy with adaptive imaging and deep learning

• Loic Royer (Biohub)

Room: Seminar room Fluorescence microscopy lets biologist see and understand the intricate machinery at the heart of living systems and has led to numerous discoveries. Any technological progress towards improving image quality would extend the range of possible observations and would consequently open up the path to new findings. I will show how modern machine learning and smart robotic microscopes can push the boundaries of observability. One fundamental obstacle in microscopy takes the form of an experiment design trade-offs between imaging speed, spatial resolution, light exposure, imaging depth, and live versus fixed imaging. State of the art machine learning — Deep Learning — can circumvent these limitations: microscopy images can be restored even if 60-fold fewer photons are used during acquisition, isotropic resolution can be achieved even with a 10-fold under-sampling along the axial direction, and diffraction-limited structures can be resolved at 20-times higher frame-rates compared to state-of- the-art methods. Moreover, I will demonstrate how smart microscopy techniques can attain the full optical resolution of light-sheet microscopes — instruments capable of capturing the entire developmental arch of an embryo from a single cell to a fully formed motile organism.  Our adaptive light-sheet microscope improves spatial resolution and signal strength two to five-fold, recovers cellular and sub-cellular structures in many regions otherwise not resolved, adapts to spatiotemporal dynamics of genetically encoded fluorescent markers and robustly optimises imaging performance during large-scale morphogenetic changes in living organisms.

Single plasmonic nanostructure: a playground for nonlinear and quantum optics

• Victor Zadkov (Direktor RAS und U Moskau)

Room: Seminar room In this talk, we will explore quantum and nonlinear optical effects due to interaction of a single quantum emitter with a plasmonic nanostructure in an external electromagnetic field. First, we will discuss our experimental results on nonlinear optical interaction of laser radiation with a single gold nanostructure in the split-hole resonator geometry, which shows several multipole plasmon resonances that will lead to SHG, THG, and light generation at the mixed frequencies. The THG nearfield amplitude reaches 0.6% of the fundamental frequency field amplitude, which enables creation of UV radiation sources with a record high intensity. The UV THG may then find many important applications including biomedical ones. Second, we will overview the mechanisms of modification of the local field and radiative and nonradiative decay rates of a two-level quantum emitter located in close proximity to a plasmonic nanoparticle and will analyze the polarization distribution at the nanoscale around the nanoparticle. We will also analyze the photon-number statistics in resonance fluorescence of the quantum emitter near a metal nanosphere and the antibunching effect of photons from the resonance fluorescence. Acknowledgements: The authors acknowledge financial support from the Russian Foundation for Basic Research (grants Nos. 16-02-00816, 18-52-53040).

Field fluctuations and photon statistics in nonlinear radiation-matter interactions

• Peter Lambropoulos (FORTH Heraklion)

Room: Seminar room Half a century ago, it was shown that “incoherent” light is more efficient than “coherent” light in inducing a non-linear process; which at that time seemed counterintuitive. A limited number of experimental results have been in general agreement with that prediction. Yet, to this day, that statement is greeted with disbelief and not only by students. The story and content of the talk revolves around the quantum stochastic properties of radiation, as reflected in its correlation functions. Correlation functions are important tools in many quantum systems, as they provide information well beyond average (expectation) values of dynamical variables. As such they serve as probes of quantum systems. In the case of radiation, however, they turn out to also be tools for inducing counterintuitive effects in radiation-matter interactions. Some of these effects are discussed in the context of recent developments.

Topological photonics

• Alex Szameit (University of Rostock)

Room: Seminar room In the context of photonics, topology has emerged as an abstract, yet surprisingly powerful, new paradigm for controlling the flow of light. As such, it holds great promise for a wide range of advanced applications, from scatter-free routing and switching of light along arbitrary three-dimensional trajectories to long-distance transmission of slow-light waves. Whereas topological effects in condensed matter originate typically from the fermionic Kramer’s degeneracy or the quantum Hall effect in the presence of strong magnetic fields, these mechanisms cannot be readily adapted due to the bosonic nature of photons and the notoriously weak magnetic interactions at optical frequencies. Recently, a number of approaches for the realization of photonic topological transport have been put forward. Among these, perhaps the most promising one follows the spirit of Floquet topological insulators, in which temporal variations of solid-state systems induce topological edge states. In the context of photonics, temporal modulations serve to break the time-reversal symmetry and thereby give rise to topologically protected one-way edge states. In my talk, I will present an introduction to topology in photonics, with a particular focus on our work on the implementation of photonic Floquet topological insulators. The purpose is to review these and other recent developments, to discuss potential applications and to stimulate new conceptual ideas.

Next generation silicon photonics

• Michal Lipson (Columbia University)

Room: Seminar room In the past decade, silicon photonics has been shown as a platform for high-performance massively integrated optical devices that can be integrated with state-of-the-art microelectronics. The toolbox of integrated nanophotonics today is rich: from the ability to modulate, guide and amplify at GHz bandwidths, to opto-mechanical and nonlinear devices. The explosion of silicon photonics enabled components with unprecedented performance, and opened the door to a vast variety of applications ranging from micro-lidars for self-driving cars to implantable devices for neural activation. In this talk I will review the current challenges and recent achievements in the field of silicon nanophotonics and present recent results.

Microresonator soliton frequency combs

• Tobias Kippenberg (EPFL)

Room: Seminar room Optical frequency combs1,2 provide equidistant markers in the IR, visible and UV and have become a pivotal tool for frequency metrology and are the underlying principle of optical atomic clocks, but are also finding use in other areas, such as broadband spectroscopy or low noise microwave generation. In 2007 a new method to generate optical combs was discovered based on high Q optical microresonators3,4. Such microresonator frequency combs have since then emerged as a new and widely investigated method with which combs can be generated via parametric frequency conversion of a continuous wave (CW) laser inside a high Q resonator via the Kerr nonlinearity. Over the past years the a detailed understanding of the comb formation process has been gained, and regimes identified in which dissipative temporal solitons (DKS) can be generated, that not only provide low noise optical frequency combs but moreover give access to femtosecond pulses. Such DKS have unlocked the full potential of soliton micro-combs by providing access to fully coherent and broadband combs and soliton broadening effects. Dissipative Kerr solitons have now been generated in a wide variety of resonators, including those compatible with photonic integration based on silicon nitride (Si3N4). We will discuss the DKS regime, first discovered in crystalline resonators, and our current understanding including the observation of the breather soliton regime, the influence of avoided mode crossings on breather and the repetition rate, as well as methods to deterministically access the single soliton regime. Taken together this has enabled to reliably access single soliton states in photonic chip based resonators, in particular those utilizing the photonic damascene process. Dissipative Kerr solitons enable to obtain combs that can span more than a full octave using soliton induced Cherenkov radiation, which extends the combs bandwidth and power in the spectral wings via dispersive waves. Such DKS have been enabled to count the cycles of light, allow 2f-3f self referencing. Using such soliton Kerr optical frequency combs in a SiN microresonator we have recently demonstrated with the group of C. Koos (KIT) massively parallel coherent communication, with dual combs for both the source and as massively parallel LO for the coherent receiver. Moreover, we have demonstrated using a pair of photonic chip based frequency combs dual comb distance measurements, with record acquisition rates due to the combs large mode spacing (100 GHz). Recent work moreover has shown that DKS can be extended to the biological imaging window at 1 micron, relevant for e.g. Raman spectral imaging or OCT. Soliton microcombs have the potential to advance timekeeping, metrology or telecommunication by providing a technology amenable to full photonic integration, low power consumption and large comb bandwidth and repetition rate. References 1 Cundiff, S. T. & Ye, J. Colloquium: Femtosecond optical frequency combs. Rev. Mod. Phys. 75, 325-342 (2003). 2 Udem, T., Holzwarth, R. & Hansch, T. W. Optical frequency metrology. Nature 416, 233-237 (2002). 3 Del Haye, P. et al. Optical frequency comb generation from a monolithic microresonator. Nature 450, 1214 (2007 ). 4 Kippenberg, T. J., Holzwarth, R. & Diddams, S. A. Microresonator-based optical frequency combs. Science 332, 555-559, doi:10.1126/science.1193968 (2011). 5 Del’Haye, P. et al. Octave Spanning Tunable Frequency Comb from a Microresonator. Physical Review Letters 107, doi:10.1103/PhysRevLett.107.063901 (2011). 6 Herr, T. et al. Universal formation dynamics and noise of Kerr-frequency combs in microresonators. Nature Photonics 6, 480-487, doi:10.1038/nphoton.2012.127 (2012). 7 Alnis, J. et al. Thermal-noise-limited crystalline whispering-gallery-mode resonator for laser stabilization. Physical Review A 84, doi:10.1103/PhysRevA.84.011804 (2011). 8 Kudryashov, A. V. et al. Terabit/s data transmission using optical frequency combs. 8600, 860009, doi:10.1117/12.2003701 (2013). 9 Wang, C. Y. et al. Mid-infrared optical frequency combs at 2.5 mum based on crystalline microresonators. Nature communications 4, 1345, doi:10.1038/ncomms2335 (2013).10 Herr, T. et al. Temporal solitons in optical microresonators. Nature Photonics 8, 145-152, doi:10.1038/nphoton.2013.343 (2013).

Lithium niobate quantum devices

• Amir Safavi-Naeini (Stanford University)

Room: Seminar room In this talk I will outline our lab's work on fabrication of nanostructures on a thin-films of lithium niobate. Thin-film LiNbO3 has recently gained prominence in the realm of classical optical and radio-frequency systems -- it is an extremely low-loss and nonlinear material with large electro-optic and piezoelectric coefficients. Applications in quantum optomechanics, acoustics, and photonics will be discussed.

Quantum weirdness under control

• Joseph Eberly (University of Rochester)

Room: Seminar room Duality was the first weirdness of quantum mechanics, and one can argue it is the most central. It can't be dodged by mathematical sophistications, and an acceptable wording has never been agreed on for rationalizing the conceptual impossibility of duality. It remains as weird today as in the 1920s. Analytical discussion of the duality dilemma has never stopped [1] and it is accurately referred to as the wave-particle paradox. Attention to the paradox has moved through several stages of increasing sophistication [2], but after ninety years of reflection following Bohr's invention of complementarity, there has been no resolution. Here we are reporting the discovery of a resolution [3,4]. It is noteworthy that the resolution we report reveals itself through the classical analog, the ray-wave dilemma of optics. This is appropriate. The operational foundation of coherence in a physical state lies in the interpretation of interference effects, whether they are quantum or classical wave mechanical.  Since optical physics and single-particle quantum mechanics are theories erected on linear vector spaces, they share almost everything, and in this way optics can be called equally weird. Ironically, in reaching the resolution that we will present, the other conceptually challenging weirdness of quantum theory, i.e., entanglement, will be shown to be in control of duality's weirdness. By control we mean that we establish an identity through which entanglement prescribes exactly the degree of duality (the combined amount of waveness and particleness or waveness and rayness) that is possible to record in a two-path coherence experiment. [1] N. Bohr, Atomic Theory and the Description of Nature (Cambridge Univ. Press. 1934), p. 10, and A. Whitaker, Einstein, Bohr and the Quantum Dilemma, 2nd Edition (Cambridge Univ. Press, 2006). [2] See W.K. Wootters and W.H. Zurek, Phys. Rev. D {19}, 473 (1979); D. M. Greenberger and A. Yasin, Phys. Lett. A {128}, 391 (1988); L. Mandel, Opt. Lett. {16}, 1882 (1991); G. Jaeger, A. Shimony, and L. Vaidman, Phys. Rev. A {51}, 54 (1993); B.-G. Englert, M.O. Scully and H. Walther, Sci. Am. {271}, 86 (1994); S. Dürr and G. Rempe, Am. J. Phys. {68}, 1021 (2000); F. Gori, M. Santarsiero and R. Borghi, Opt. Lett. {31}, 858 (2006); R. Menzel, D. Puhlmann, A. Heuer and W.P. Schleich, PNAS {109}, 9314 (2012); F. De Zela, Phys. Rev. A {89}, 013845 (2014) and Optica {5}, 243 (2018). [3] X.-F. Qian, A.N. Vamivakas and J.H. Eberly (under review, 2018). [4] See hints by P.L. Knight (1998) and Jakob and Bergou (2003).

Divergence-free circuit quantum electrodynamics

• Hakan Tureci (Princeton University)

Room: Seminar room Any quantum-confined electronic system coupled to the electromagnetic continuum is subject to radiative decay and renormalization of its energy levels. When inside a cavity, these quantities can be strongly modified with respect to their values in vacuum. In the planar circuit quantum electrodynamics architecture the radiative decay rate of a Josephson Junction qubit is strongly influenced by far off-resonant modes. A multimode calculation including all cavity modes however leads to divergences unless a cutoff is imposed. It has so far not been identified what the source of divergence is, or whether the divergence is a fundamental issue. I will show that unless gauge invariance is respected, any attempt at the calculation of circuit QED quantities is bound to diverge. I will then discuss an internally consistent theoretical and computational framework based on a Heisenberg-Langevin approach to the calculation of a finite spontaneous emission rate and the Lamb shift in an arbitrarily complex electromagnetic environment, that is free of cutoff.

Plasmon-enhanced single-molecule spectroscopy

• Zhen-Chao Dong (Hefei University)

Room: Seminar room Control of optical properties of single molecules by plasmonic nanostructures is an important issue in nanoplasmonics and nanophotonics, particularly valuable for the development of molecular plasmonic devices and ultrasensitive high-resolution microscopic techniques. The nanocavity defined by the coinage-metal tip and substrate in a scanning tunneling microscope (STM) can provide highly localized and dramatically enhanced electrical fields upon appropriate plasmonic resonant tuning, which can modify the excitation and emission of a single molecule inside and produce interesting new optoelectronic phenomena. In this talk, I shall demonstrate two STM-based phenomena related to single-molecule optical spectroscopy. The first is single-molecule Raman scattering. The spatial resolution of tip enhanced Raman spectromicroscopy has been driven down to sub-nanometer scale for a single porphyrin molecule. I shall demonstrate further applications of this technique to chemically distinguish different adjacent molecules on a surface, from relatively large porphyrin molecules to small DNA-base molecules. The second phenomenon is single-molecule electroluminescence. I shall first demonstrate the realization of electrically driven single-photon emission from a well-defined isolated single molecule. Then, by using STM manipulation to construct a molecular dimer, I shall demonstrate the visualization of coherent intermolecular dipole-dipole coupling in real space through sub-nanometer resolved electroluminescence imaging, together with a demonstration of single-photon superradiance in artificially constructed oligomers. These findings provide unprecedented spatial details about the coherent dipole-dipole coupling in molecular systems, which may open up new research avenues to study molecular interactions and enable rational engineering of light harvesting structures and quantum light sources.

Spatiotemporal dynamics of optical pulse propagation in multimode fibers

• Frank Wise (Cornell University)

Room: Seminar room Optical fibers designed to support multiple transverse modes offer opportunities to study wave propagation in a setting that is intermediate between single-mode fiber and free-space propagation. A variety of qualitatively-new phenomena have been observed recently in multimode fibers. Self-cleaning of a multimode beam is observed at a fraction of the critical power for self-focusing. New instabilities, which are spatiotemporal in nature, occur. By varying the launched spatial modes, it is possible to generate dispersive waves over one octave in frequency, or continua that span multiple octaves. One or two of these new phenomena will be presented along with their connection to multimode soliton dynamics. Recent progress spatiotemporal mode-locking in fiber lasers will then be summarized. Possible directions for studies of new nonlinear wave physics in multimode fibers will be discussed along with potential applications.

Spatiotemporal pulse shaping in multimode nonlinear optical fibers

• Stefan Wabnitz (Università degli Studi di Brescia)

Room: Seminar room Nonlinear multimode optical fibers (MMFs) have recently emerged as easily accessible platform to control complex spatiotemporal beam reshaping phenomena. Light intensity oscillations associated to the self-imaging effect in graded-index (GRIN) MMFs lead, via the Kerr effect, to a dynamic long-period index grating which may phase-match the generation of ultra-broadband sideband series. For relatively short, virtually lossless GRIN fibers, beam self-cleaning activated by the Kerr effect is observed, at lower power thresholds than the Raman beam cleanup. The output highly multimode speckled beam evolves, at high powers, into a high brightness bell-shaped beam sitting on a low-power background of high-order modes. This Kerr beam self-cleaning is shown to be even reinforced in the presence of strong loss or gain, e.g., in a passive or active ytterbium doped MMF, which leads to its possible exploitation in high power multimode fiber laser sources. We shall overview recent experiments, which demonstrate the spatiotemporal pulse break-up and significant temporal compression that accompany the self-cleaning process. At the same time, we shall describe experiments revealing the dependence of the output beam shape and the efficiency of the self-cleaning process on the input beam conditions, such as transverse dimension and incidence angle.

Harnessing multimode propagation for deep-tissue imaging

• Tomas Cizmar (Leibniz-IPHT Jena / ISI CAS Brno)

Room: Seminar room The turbid nature of refractive index distribution within living tissues introduces severe aberrations to light propagation thereby severely compromising image reconstruction using currently available non-invasive techniques. Numerous approaches of endoscopy, based mainly on fibre bundles or GRIN-lenses, allow imaging within extended depths of turbid tissues, however their footprint causes profound mechanical damage to all overlying regions and their imaging performance is very limited. Progress in the domain of complex photonics enabled a new generation of minimally invasive, high-resolution endoscopes by substitution of the Fourier-based image relays with a holographic control of light propagating through apparently randomizing multimode optical waveguides. This form of endo-microscopy became recently a very attractive way to provide minimally invasive insight into hard-to-access locations within living objects. I will review our fundamental and technological progression in this domain and introduce several applications of this concept in bio-medically relevant environments.

Optical tools for large-scale in vivo Interrogation of neuronal activity underlying behavior

• Alipasha Vaziri (Rockefeller University)

Room: Seminar room The combination of optogenetics and high speed functional imaging are providing new opportunities to understand how the collective dynamics of neurons in functional networks leads to behavior. While traditional imaging modalities based on two-photon imaging have relied on the manipulations of light in the spatial domain, multi-photon microscopy via femtosecond optical pulses can also provide a new degree of freedom via the pulse spectrum that can be used to “sculpt” the spatial localization of light within the sample. Using this approach in combination with genetically encoded calcium (Ca2+) indicators we have shown that near-simultaneous recording of whole-brain neuronal activity in C. elegans at single cell resolution is possible. Moreover, the combination of light sculpting microscopy with rapid volumetric scanning has allows for unbiased, high-speed and single-cell resolution volumetric calcium imaging in scattering tissues. Using this technique, we have shown that the activity of thousands of neurons in a mouse cortical column or the hippocampus can be captured in awake behaving animals. Light-field microscopy in combination with 3D deconvolution and other more sophisticated mathematical signal demixing strategies is another highly scalable approach for high-speed volumetric Ca2+ imaging. Using this technique termed Seeded Iterative Demixing (SID), we have recently demonstrated video-rate recoding of neuronal activity within a volume of 0.6mm×0.6 mm×0.2 mm located as deep as 380μm in the scattering mouse during free behavior. These tools combined with high speed optogentic control of neuronal circuits, advanced statistics tools and mathematical modeling and will be crucial to move from an anatomical wiring map towards a dynamic map of neuronal circuits. References: 1. Andrasfalvy, B., et al., Two-photon Single Cell Optogenetic Control of Neuronal Activity by Sculpted Light. PNAS, (2010). 107. 2. Losonczy, A., et al., Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons. Nature Neuroscience, (2010). 13(8): p. 967-72. 3. Schrodel, T., et al., Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light. Nature Methods, (2013). 10(10): p. 1013 4. Prevedel, R., et al., Simultaneous whole-animal 3D-imaging of neuronal activity using light-field microscopy. Nature Methods, (2014) 11. 727–730 5. Prevedel, R., et al., Fast volumetric calcium imaging across multiple cortical layers using sculpted light Nature Methods, (2016) 13, 1021-1028 6. Nöbauer, T. et al., Video rate volumetric Ca2+ imaging across cortex using seeded iterative demixing (SID) microscopy, Nature Methods (2017), 14, 811-818 7. Skocek, O. et al., High-speed volumetric imaging of neuronal activity in freely moving rodents, Nature Methods (2018) AOP, doi:10.1038/s41592-018-0008-0

Brillouin microscopy to image cell and tissue mechanical properties

• Giuliano Scarcelli (University of Maryland)

Room: Seminar room Brillouin spectroscopy has been widely used for decades to characterize material mechanical properties. However, due to the weakness of its signal, it was never considered viable in biomedicine. Developing a spectrometer with million-fold improved throughput and combining it with a confocal microscope, we developed Brillouin microscopy, a 3D imaging modality that uses the longitudinal modulus as contrast mechanism for imaging. Our first area of application has been in ophthalmology: e.g. 1) Lens biomechanics is involved in the loss of accommodation power (presbyopia) and the genesis of cataract but it is difficult to measure lens mechanical properties in vivo. 2) Loss of corneal strength leads to ectasia (thinning and bulging) and is a major risk factor for LASIK surgery; however, current diagnostic tools only rely on morphology, not on biomechanics. To address this issue, we have developed an in vivo Brillouin ophthalmoscope and have measured ~200 subjects so far. Encouraging data show we can differentiate ectatic corneas based on elasticity and characterize the most promising of treatments, collagen crosslinking. Recently we have increased Brillouin microscopy resolution to characterize intracellular modulus and we have now developed a flow cytometry platform to rapidly characterize cells based on their mechanical properties. As cells sense and respond to the mechanical forces of their surrounding microenvironment, cell mechanical signatures are promising as biomarkers and diagnostic indicators for underlying disease or treatment response.

Light-induced intracellular flows to study and guide embryogenesis

• Moritz Kreysing (Max Planck Institute of Molecular Cell Biology and Genetics)

Room: Seminar room Throughout the last decades, genetic perturbations massively advanced our molecular understanding of cell biological processes. At the same time however, the spatio-temporal organization of cells and developing embryos is widely believed to also depend on physical transport processes such as diffusion and directed intracellular flows. Problematically, physical models to unite reaction and transport as drivers of morphogenesis remain difficult to test experimentally. As an example: how would one change direction or temporal persistence of cytoplasmic flows to test their role during embryogenesis? Here we demonstrate focused-light induced cytoplasmic-streaming (FLUCS). FLUCS uses light controlled thermoviscous expansion phenomena to induce well-defined flows in single cells and developing embryos. These non-invasive flows are localized, directed, highly dynamical, probe-free, and non-invasive. By controlling flows inside the cytoplasm of one-cell C. elegans embryos, we directly demonstrate the causal role of flows for the establishment of the head-to-tail body axis (aka PAR-polarization). Specifically, we find that i) cytoplasmic flows transport PAR-2 proteins towards the membrane, thus helping to define the posterior pole. ii) we show that induced flows of the actomyosin cell cortex transport and even invert PAR polarization. This light-controlled re-localization of native proteins reveals iii) the down-stream phenotype of embryos with an inverted body plan, which demonstrates that body axis formation is a bi-stable process. Moreover, we utilize FLUCS for active and probe-free micro-rheology, revealing a fluid-to-solid transition of the cytoplasm in energy-depleted yeast cells. On the subcellular scale, we show how hydrodynamic flows can be reversibly induced within the cell nucleus. We conclude by emphasizing the enormous biomedical potential of FLUCS to study and guide the spatio-temporal organization of cells and embryos by light. References: i) Mittasch et al, Nature Cell Biology 20 (2018) News and Views: Kruse, Chiaruttini, Roux, Nature Cell Biol 20 (2018)

Time-resolved X-ray spectroscopy: towards sub-femtosecond resolution

• Jon Marangos (Imperial College London)

Room: Seminar room X-rays with sub-femtosecond duration are a key tool for future ultrafast probes of matter. The challenge is not only to generate photon pulses of this ultrashort duration but also to develop measurement methodologies that enable the high temporal resolution even in condensed phase systems. X-ray spectroscopy is a promising route that we are investigating using both HHG based and XFEL based sources. I will discuss our recent work on using HHG driven by 800 nm and 1800 nm CEP stable few cycle sources to generate sub-femtosecond pulses from the VUV (20 eV)[1] to the SXR (600 eV)[2], and measurements that have so far been undertaken with these sources[3][4]. This will be compared with recent work at the LCLS that we have undertaken to develop ultrafast X-ray measurement methods[5][6]. [1] D.Fabris et al, Nature Photonics, 9, 383 (2015). [2] A.S.Johnson et al. Science Advances, 4, 3761 (2018). [3] A.S.Johnson et al, Structural Dynamics, 3, 062603 (2016). [4] T.Barrilot et al, Chemical Physics Letters, 683 38 (2017). [5] C.E.Liekhaus-Schmaltz et al, Nature Communications, 6, 8199 (2015. [6] A.Sanchez-Gonzalez et al, Nature Communications, 8, 15461 (2017).

Watching and clocking electrons in condensed matter with visible light

• Eleftherios Goulielmakis (Max-Planck Institute for Quantum Optics)

Room: Seminar room The wavelength of visible light is often assumed to impose fundamental frontiers in optical microscopies and time-resolved spectroscopies. In optical microscopies, it limits the spatial resolution to the nanometer scale while in time-resolved techniques it restricts the temporal resolution to the scale of femtoseconds. I will discuss how recent efforts allow us to push these frontiers. We show that precisely measured and controlled optical fields allow imaging of valence electrons in solids with sub-Angstrom resolution. This enables the establishment of a new kind of optical tomography of solids with a spatial resolution 104 times beyond the abbe limit. Optical fields also provide the required temporal resolution for observing how electronic relaxation occurs deep inside matter with attosecond precision. When used to nonlinearly release and probe free electrons from nanostructures controlled optical fields provide new routes to optical nanoelectronics and light-controlled electron diffraction techniques.

Lightwave-driven quantum dynamics: the molecular selfie

• Jens Biegert (ICFO)

Room: Seminar room Electron recollision in an intense laser field gives rise to a variety of phenomena, ranging from electron diffraction to coherent soft X-ray emission. We have, over the years, developed intense sources of waveform-controlled mid-IR light to exploit ponderomotive scaling, quantum diffusion and quasi-static photoemission. I will describe how we leverage these effects to “teach” electrons to take a selfie of the dynamics of a single molecule. This permits visualizing for the first time, with combined attosecond temporal and atomic spatial resolution, molecular bond breaking and deprotonation. The results provide first insight into the dynamics of molecules with the future possibility to address fundamental and long-standing questions such as molecular isomerization and the connection between molecular structure and function.

Capturing molecular interactions and assembly with a molecular photonic scale

• Philipp Kukura (University of Oxford)

Room: Seminar room The cellular processes underpinning life are orchestrated by proteins and the interactions they make with themselves and other biomolecules. A range of techniques has been developed to characterise these associations, operating from the ensemble all the way to the single molecule level. Structural and dynamic heterogeneity, however, continues to pose a fundamental challenge to existing analytical and structural methodologies, despite being key to protein and drug function. I will present recent developments demonstrating that interferometric scattering mass spectrometry (iSCAMS) can mass-image single biomolecules in solution with simultaneous nanometre precision and mass accuracy comparable to native mass spectrometry in the gas phase. As a result, we can resolve oligomeric distributions at high dynamic range, detect small-molecule binding, and quantitatively mass-image not only biomolecules composed of amino acids, but also heterogeneous species such as glyco- and lipoproteins. These capabilities enable us to determine the equilibrium constants and thereby the molecular mechanisms of homo- and hetero-oligomeric protein assembly, which I will illustrate with heat-shock protein oligomerisation and drug-induced HIV glycoprotein cross-linking. Furthermore, by virtue of the intrinsic nanometre spatial precision, we can mass-monitor the dynamics of mesoscopic objects, such as individual amyloidogenic protein aggregates and actin filaments down to the single molecule level. Coupled with clear routes towards future improvements in mass resolution and precision well below the kDa range and extension towards membrane proteins, these results illustrate how single molecule mass imaging provides universally-applicable and spatially-resolved access to the mechanisms and dynamics of protein assemblies, their interactions and how they form nano- and mesoscopic structures, one molecule at a time.

Enlightening cell mechanics in biological systems using optical tools

• Timo Betz (Institute of Cell Biology Münster)

Room: Seminar room Biophysical methods have revolutionized our understanding of many biological systems, spanning from embryonal development to cancer. The precise experimental and theoretical description of mechanical forces relevant for cell and tissue dynamics was a main driver of these advances. Many cellular functions, like cell division, cell migration and differentiation are closely related to a dynamic restructuring of the intracellular protein networks, leading to changes in the viscoelastic properties and force generation inside cells and tissue. We will discuss how optical methods provide an outstanding toolbox to study and manipulate the forces and mechanical properties of biological systems. Optical tweezers are systematically used to determine the viscoelastic properties of cells, bio-membranes and tissue, while interferometric approaches allow a nanometer and microsecond precise measurement of membrane and particle fluctuations of microscopic living objects. Optogenetic tools allow to directly trigger biochemical signaling cascades by simple illumination and classical bleaching experiments help deciphering reaction rates and dynamics in cells and tissue. But these optical tools do not only allow to study biological systems, they also help in understanding general non-equilibrium physics.

Diamond quantum devices in biology

• Martin Plenio (University of Ulm)

Room: Seminar room Perfect diamond is transparent for visible light but there are famous diamonds, such as the famous Oppenheim Blue or the Pink Panther worth ten's of millions of dollar, which have intense colour. An important source of colour in diamond are lattice defects which emit and absorb light at optical frequencies and may indeed possess a non-vanishing ground state electronic spin. I will explore the physics of one of these defects, the nitrogen vacancy center, and show how we can manipulate its electronic spin to develop nanoscale quantum sensors and sources of nuclear hyperpolarisation. Applications of such devices range from sensing in biology to medical imaging.

Talking about optical forces: what light can and cannot do

• Monika Ritsch-Marte (Med. University of Innsbruck)

Room: Seminar room It has long been known that light does not only carry energy, but also momentum. Yet only recently has the “optical force” been turned into a technology. Optical tweezers enable precise and controllable manipulations of microscopic particles and provide a means to measure forces on the level of mechanical activities in living cells. I will discuss some recent advances, some controversies, and some remaining challenges of optical micro-manipulation in various scenarios from astrophysics to biophotonics