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Mar 2023 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XX …, 2023

Bioimaging, pH sensing, and fluorescence lifetime imaging microscopy using polyethyleneimine coated carbon dots and gold nanoparticles

Shweta Pawar, Hamootal Duadi, Dror Fixler

The unique fluorescent nanomaterials known as carbon dots (CDs) are highly resistant to photobleaching, have low toxicity, and are well soluble in water. Polyethyleneimine (PEI) coated CDs are a novel fluorophore with good biocompatibility and pH sensing ability. Here, p-phenylenediamine (p-PD) is used as a carbon source and hyperbranched PEI is used as a surface passivation agent in a simple, one-step hydrothermal synthesis process. The CDs optical characteristics are pH-responsive due to the presence of different amine groups on PEI, which is functional polycationic polymer. The limits of techniques based on fluorescence intensity can be overcome by fluorescent lifetime imaging microscopy (FLIM), a very sensitive method for detecting a microenvironment. In this study, FLIM was used to measure pH with pH-sensitive CDs. These molecules are nontoxic to the cells, and the positively charged CDs have …

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Mar 2023 • Real-time Measurements, Rogue Phenomena, and Single-Shot Applications VIII …, 2023

Quantum temporal optics

Moti Fridman

Temporal optics, and specifically time-lenses and time-stretch systems, revolutionized the field of ultrafast measurements. Over the last years, we utilized time-lenses to measure different quantum schemes and studied the temporal modes of correlated photons with high temporal resolution. We developed temporal schemes based on quantum light, for realizing quantum tomography in the time-domain. We developed low-resolution time-lenses for weak quantum measurements. Finally, we suggest how quantum time-lens can lead to optical deep learning systems. In the talk, I will give an overview of the different types of quantum temporal schemes, elaborate on the future challenges in the field, and discuss the prospects and future applications which may be possible.

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Mar 2023 • High Contrast Metastructures XII, PC124320D, 2023

Deep subwavelength light localization in ultra-high index topological insulator nanostructures

Tomer Lewi

In nanophotonic, small mode volumes, narrow resonance linewidths and field enhancements, fundamentally scales with refractive index values and are key for many implementations involving light-matter interactions. Topological insulators (TI) are a class of insulating materials that host topologically protected surface states, some of which exhibit very high permittivity values. In this talk, I will discuss our latest results on Bi2Te3 and Bi2Se3 TI nanostructures. Using polarized far-field and near field nanospectroscopy we reveal that Bi2Se3 nanobeams exhibit mid-infrared resonant modes with 2π phase shifts across the resonance. We further demonstrate that Bi2Te3 metasurfaces exhibit deep subwavelength resonant modes utilizing their record high index value peaking at n~11.

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Mar 2023 • Multiphoton Microscopy in the Biomedical Sciences XXIII 12384, 53-60, 2023

NIR fluorescence lifetime macroscopic imaging with a novel time-gated SPAD camera

Xavier Michalet, Arin C Ulku, Michael A Wayne, Shimon Weiss, Claudio Bruschini, Edoardo Charbon

SwissSPAD3 is the latest of a family of widefield time-gated SPAD imagers developed for fluorescence lifetime imaging (FLI) applications. Its distinctive features are (i) the ability to define shorter gates than its predecessors (width W < 1 ns), (ii) support for laser repetition rates up to at least 80 MHz and (iii) a dual-gate architecture providing an effective duty cycle of 100%. We present widefield macroscopic FLI measurements of short lifetime NIR dyes, analyzed using the phasor approach. The results are compared with those previously obtained with SwissSPAD2 and to theoretical predictions.

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Mar 2023 • Molecular Therapy-Nucleic Acids

Multiplex HDR for disease and correction modeling of SCID by CRISPR genome editing in human HSPCs

Ortal Iancu, Daniel Allen, Orli Knop, Yonathan Zehavi, Dor Breier, Adaya Arbiv, Atar Lev, Yu Nee Lee, Katia Beider, Arnon Nagler, Raz Somech, Ayal Hendel

Severe combined immunodeficiency (SCID) is a group of disorders caused by mutations in genes involved in the process of lymphocyte maturation and function. CRISPR-Cas9 gene editing of the patient’s own hematopoietic stem and progenitor cells (HSPCs) ex vivo could provide a therapeutic alternative to allogeneic hematopoietic stem cell transplantation, the current gold standard for treatment of SCID. To eliminate the need for scarce patient samples, we engineered genotypes in healthy donor (HD)-derived CD34+ HSPCs using CRISPR-Cas9/rAAV6 gene-editing, to model both SCID and the therapeutic outcomes of gene-editing therapies for SCID via multiplexed homology-directed repair (HDR). First, we developed a SCID disease model via biallelic knockout of genes critical to the development of lymphocytes; and second, we established a knockin/knockout strategy to develop a proof-of-concept single …

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Mar 2023 • 2023 Optical Fiber Communications Conference and Exhibition (OFC), 1-3, 2023

Incoherent Fiber-based Optical Neuromorphic Computing Circuit

Maya Yevnin, Alon Harel, Or Arbel-Arenfrid, Zeev Zalevsky, Eyal Cohen

We present novel photonic neuromorphic computing scheme working with incoherent light while capable implementing negative weighting for the neural network and obtaining reliable/accurate computing of the linear multiply-accumulate function necessary for neural networks applications.

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Mar 2023 • Journal of Biophotonics

Fluorescence attenuated by a thick scattering medium: theory, simulations and experiments

Yitzchak Weber, Hamootal Duadi, Pavitra Sokke Rudraiah, Inbar Yariv, Gilad Yahav, Dror Fixler, Rinat Ankri

Fluorescence‐based imaging has an enormous impact on our understanding of biological systems. However, in vivo fluorescence imaging is greatly influenced by tissue scattering. A better understanding of this dependance can improve the potential of non‐invasive in vivo fluorescence imaging. In this paper we present a diffusion model, based on an existing master‐slave model, of isotropic point sources imbedded in a scattering slab, representing fluorophores within a tissue. The model was compared to Monte Carlo simulations and measurements of a fluorescent slide measured through tissue‐like phantoms with different reduced scattering coefficients (0.5 to 2.5mm‐1) and thicknesses(0.5 to 5mm). Results show a good correlation between our suggested theory, simulations and experiments; while the fluorescence intensity decays as the slab's scattering and thickness increase, the decay rate decreases as the …

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Mar 2023 • Journal of Biophotonics

Fluorescence attenuated by a thick scattering medium: Theory, Simulations and Experiments

Yitzchak Weber, Hamootal Duadi, Pavitra Sokke Rudraiah, Inbar Yariv, Gilad Yahav, Dror Fixler, Rinat Ankri

Fluorescence‐based imaging has an enormous impact on our understanding of biological systems. However, in vivo fluorescence imaging is greatly influenced by tissue scattering. A better understanding of this dependance can improve the potential of non‐invasive in vivo fluorescence imaging. In this paper we present a diffusion model, based on an existing master‐slave model, of isotropic point sources imbedded in a scattering slab, representing fluorophores within a tissue. The model was compared to Monte Carlo simulations and measurements of a fluorescent slide measured through tissue‐like phantoms with different reduced scattering coefficients (0.5 to 2.5mm‐1) and thicknesses(0.5 to 5mm). Results show a good correlation between our suggested theory, simulations and experiments; while the fluorescence intensity decays as the slab's scattering and thickness increase, the decay rate decreases as the …

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Mar 2023 • Microsystems & Nanoengineering

Femtosecond laser-assisted fabrication of piezoelectrically actuated crystalline quartz-based MEMS resonators

John Linden, Neta Melech, Igor Sakaev, Ofer Fogel, Slava Krylov, David Nuttman, Zeev Zalevsky, Marina Sirota

A novel technology for the precise fabrication of quartz resonators for MEMS applications is introduced. This approach is based on the laser-induced chemical etching of quartz. The main processing steps include femtosecond UV laser treatment of a Cr-Au-coated Z-cut alpha quartz wafer, followed by wet etching. The laser-patterned Cr-Au coating serves as an etch mask and is used to form electrodes for piezoelectric actuation. This fabrication approach does not alter the quartz’s crystalline structure or its piezo-electric properties. The formation of defects, which is common in laser micromachined quartz, is prevented by optimized process parameters and by controlling the temporal behavior of the laser-matter interactions. The process does not involve any lithography and allows for high geometric design flexibility. Several configurations of piezoelectrically actuated beam-type resonators were fabricated using …

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Mar 2023 • Proc. of SPIE Vol 12394, 1239408-1, 2023

pH sensing, bioimaging, and Fluorescence lifetime imaging microscopy using polyethyleneimine coated carbon dots and gold nanoparticles

Shweta Pawar, Hamootal Duadi, Dror Fixler

The unique fluorescent nanomaterials known as carbon dots (CDs) are highly resistant to photobleaching, have low toxicity, and are well soluble in water. Polyethyleneimine (PEI) coated CDs are a novel fluorophore with good biocompatibility and pH sensing ability. Here, p-phenylenediamine (p-PD) is used as a carbon source and hyperbranched PEI is used as a surface passivation agent in a simple, one-step hydrothermal synthesis process. The CDs optical characteristics are pH-responsive due to the presence of different amine groups on PEI, which is functional polycationic polymer. The limits of techniques based on fluorescence intensity can be overcome by fluorescent lifetime imaging microscopy (FLIM), a very sensitive method for detecting a microenvironment. In this study, FLIM was used to measure pH with pH-sensitive CDs. These molecules are nontoxic to the cells, and the positively charged CDs have …

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Mar 2023

A ‘golden’alternative for prevention of cisplatin nephrotoxicity in bladder cancer

Yoray Sharon, Menachem Motiei, Chen Tzror-Azankot, Tamar Sadan, Rachela Popovtzer, Eli Rosenbaum

Cisplatin (CP) is the rst-line standard of care for bladder cancer. However, a signi cant percentage of advanced bladder cancer patients are ineligible to receive standard CP treatment, due to the drug’s toxicity, and in particular its nephrotoxicity. These patients currently face suboptimal therapeutic options with lower e cacy. To overcome this limitation, here we designed CP-conjugated gold nanoparticles (GNPs) with speci c properties that prevent renal toxicity, and concurrently preserve the therapeutic e cacy of CP. Safety and e cacy of the particles were studied in bladder tumor-bearing mice, using clinically-relevant fractionated or non-fractionated dosing regimens. A non-fractionated high dose of CPGNP showed long-term intratumoral accumulation, blocked tumor growth, and nulli ed the lethal effect of CP. Treatment with fractionated lower doses of CP-GNP was also superior to an equivalent treatment with free CP, demonstrating both anti-tumor e cacy and prolonged mouse survival. Moreover, as opposed to free drug, CP-conjugated GNPs did not cause brosis or necrosis in kidney. These results indicate that conjugating CP to GNPs can serve as an effective, combined anti-cancer and renoprotective approach, and thus has potential to widen the range of patients eligible for CP-based therapy.

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Mar 2023 • The Journal of Physical Chemistry Letters

Protein Orientation Defines Rectification of Electronic Current via Solid-State Junction of Entire Photosystem-1 Complex

Jerry A Fereiro, Tatyana Bendikov, Andreas Herrmann, Israel Pecht, Mordechai Sheves, David Cahen

We demonstrate that the direction of current rectification via one of nature’s most efficient light-harvesting systems, the photosystem 1 complex (PS1), can be controlled by its orientation on Au substrates. Molecular self-assembly of the PS1 complex using four different linkers with distinct functional head groups that interact by electrostatic and hydrogen bonds with different surface parts of the entire protein PS1 complex was used to tailor the PS1 orientation. We observe an orientation-dependent rectification in the current–voltage characteristics for linker/PS1 molecule junctions. Results of an earlier study using a surface two-site PS1 mutant complex having its orientation set by covalent binding to the Au substrate supports our conclusion. Current–voltage–temperature measurements on the linker/PS1 complex indicate off-resonant tunneling as the main electron transport mechanism. Our ultraviolet photoemission …

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Feb 2023 • Angewandte Chemie (International ed. in English)

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon‐Induced Excitation

Ori Licht, Dario Barreiro-Lage, Patrick Rousseau, Alexandre Giuliani, Aleksandar Milosavljevic, Avinoam Isaak, Yitzhak Mastai, Amnon Albeck, Raj Singh, Vy Nguyen, Laurent Nahon, Lara Martinez, Sergio Díaz-Tendero, Yoni Toker

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the eV range. Moreover, the comparison of photon induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by {\it ab initio} molecular dynamics and exploration of several excited state potential energy surfaces, unravelling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.

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Feb 2023 • arXiv preprint arXiv:2302.00705

Quantum circuits measuring weak values and Kirkwood-Dirac quasiprobability distributions, with applications

Rafael Wagner, Zohar Schwartzman-Nowik, Ismael L Paiva, Amit Te'eni, Antonio Ruiz-Molero, Rui Soares Barbosa, Eliahu Cohen, Ernesto F Galvão

Weak values and Kirkwood--Dirac (KD) quasiprobability distributions have been independently associated with both foundational issues in quantum theory and advantages in quantum metrology. We propose simple quantum circuits to measure weak values, KD distributions, and density matrix spectra without the need for post-selection. This is achieved by measuring unitary-invariant, relational properties of quantum states, as functions of Bargmann invariants. Our circuits also enable direct experimental implementation of various applications of KD distributions, such as out-of-time-ordered correlators (OTOCs) and the quantum Fisher information in post-selected parameter estimation, among others. This results in a unified view of nonclassicality in all those tasks. In particular, we discuss how negativity and imaginarity of Bargmann invariants relate to set coherence.

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Feb 2023 • Biophysical Journal

Towards precise optical measurements of steady state of and small changes in resting membrane potentials

Debjit Roy, Xavier Michalet, Kiran Bharadwaj, Evan W Miller, Yijie Wang, Arjun Deb, Michael A Wayne, Claudio Bruschini, Edoardo Charbon, Mahbanoo Vakili, Robert Gunsalus, Robert T Clubb, Shimon Weiss

While great progress has been achieved in developing optical methods for measuring fast changes in membrane potential (like action potentials) in excitable cells, less progress has been made in precise (and calibrated) measurements of steady state resting membrane potentials (RMPs) and small changes in RMPs (in excitable or non-excitable cells). In excitable cells, small changes in RMPs are associated with multiple physiological processes such as sub-threshold events in neuronal signaling and in synaptic plasticity. They also play an important role in cell differentiation and proliferation of cardiomyocytes. In non-excitable cells, such as bacterial colonies, RMP changes play important roles in intercellular communication, coordination, metabolism, and stress response. Accurate and precise recordings of minute RMP changes require noise-immune optical tools. We have been developing an RMP (calibrated …

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Feb 2023 • Pharmaceutics 15 (2), 686, 2023

Bioimaging probes based on magneto-fluorescent nanoparticles

Sayan Ganguly, Shlomo Margel

Novel nanomaterials are of interest in biology, medicine, and imaging applications. Multimodal fluorescent-magnetic nanoparticles demand special attention because they have the potential to be employed as diagnostic and medication-delivery tools, which, in turn, might make it easier to diagnose and treat cancer, as well as a wide variety of other disorders. The most recent advancements in the development of magneto-fluorescent nanocomposites and their applications in the biomedical field are the primary focus of this review. We describe the most current developments in synthetic methodologies and methods for the fabrication of magneto-fluorescent nanocomposites. The primary applications of multimodal magneto-fluorescent nanoparticles in biomedicine, including biological imaging, cancer treatment, and drug administration, are covered in this article, and an overview of the future possibilities for these technologies is provided.

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Feb 2023 • Physical Review E

Brownian particles in periodic potentials: Coarse-graining versus fine structure

Lucianno Defaveri, Eli Barkai, David A Kessler

We study the motion of an overdamped particle connected to a thermal heat bath in the presence of an external periodic potential in one dimension. When we coarse-grain, ie, bin the particle positions using bin sizes that are larger than the periodicity of the potential, the packet of spreading particles, all starting from a common origin, converges to a normal distribution centered at the origin with a mean-squared displacement that grows as 2 D* t, with an effective diffusion constant that is smaller than that of a freely diffusing particle. We examine the interplay between this coarse-grained description and the fine structure of the density, which is given by the Boltzmann-Gibbs (BG) factor e− V (x)/k B T, the latter being nonnormalizable. We explain this result and construct a theory of observables using the Fokker-Planck equation. These observables are classified as those that are related to the BG fine structure, like the …

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Feb 2023 • arXiv preprint arXiv:2302.00705

Quantum circuits measuring weak values and Kirkwood-Dirac quasiprobability distributions, with applications

Rafael Wagner, Zohar Schwartzman-Nowik, Ismael L Paiva, Amit Te'eni, Antonio Ruiz-Molero, Rui Soares Barbosa, Eliahu Cohen, Ernesto F Galvão

Weak values and Kirkwood--Dirac (KD) quasiprobability distributions have been independently associated with both foundational issues in quantum theory and advantages in quantum metrology. We propose simple quantum circuits to measure weak values, KD distributions, and density matrix spectra without the need for post-selection. This is achieved by measuring unitary-invariant, relational properties of quantum states, as functions of Bargmann invariants. Our circuits also enable direct experimental implementation of various applications of KD distributions, such as out-of-time-ordered correlators (OTOCs) and the quantum Fisher information in post-selected parameter estimation, among others. This results in a unified view of nonclassicality in all those tasks. In particular, we discuss how negativity and imaginarity of Bargmann invariants relate to set coherence.

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Feb 2023 • ImmunoInformatics

AIRR community curation and standardised representation for immunoglobulin and T cell receptor germline sets

William D Lees, Scott Christley, Ayelet Peres, Justin T Kos, Brian Corrie, Duncan Ralph, Felix Breden, Lindsay G Cowell, Gur Yaari, Martin Corcoran, Gunilla B Karlsson Hedestam, Mats Ohlin, Andrew M Collins, Corey T Watson, Christian E Busse, The AIRR Community

Analysis of an individual's immunoglobulin or T cell receptor gene repertoire can provide important insights into immune function. High-quality analysis of adaptive immune receptor repertoire sequencing data depends upon accurate and relatively complete germline sets, but current sets are known to be incomplete. Established processes for the review and systematic naming of receptor germline genes and alleles require specific evidence and data types, but the discovery landscape is rapidly changing. To exploit the potential of emerging data, and to provide the field with improved state-of-the-art germline sets, an intermediate approach is needed that will allow the rapid publication of consolidated sets derived from these emerging sources. These sets must use a consistent naming scheme and allow refinement and consolidation into genes as new information emerges. Name changes should be minimised, but …

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Feb 2023 • npj Quantum Information

Fundamental quantum limits of magnetic nearfield measurements

Chen Mechel, Jonathan Nemirovsky, Eliahu Cohen, Ido Kaminer

Major advances in the precision of magnetic measurements bring us closer to quantum detection of individual spins at the single-atom level. On the quest for reducing both classical and quantum measurement noise, it is intriguing to look forward and search for precision limits arising from the fundamental quantum nature of the measurement process itself. Here, we present the limits of magnetic quantum measurements arising from quantum information considerations, and apply these limits to a concrete example of magnetic force microscopy (MFM). We show how such microscopes have a fundamental limit on their precision arising from the theory of imperfect quantum cloning, manifested by the entanglement between the measured system and the measurement probe. We show that counterintuitively, increasing the probe complexity decreases both the measurement noise and back action, and a judicious design …

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Feb 2023 • Cold Spring Harbor Protocols

Probing acoustic communication during fly reproductive behaviors

Anne C von Philipsborn, Galit Shohat-Ophir, Carolina Rezaval

During reproduction, male and female flies use wing vibration to generate different acoustic signals. Males produce a courtship song before copulation that is easily recognized by unilateral wing vibration. In copula, females produce a distinct sound pattern (copulation song) with both wings. Sexual rejection of immature virgins and aggressive encounters between males are also accompanied by sound pulses generated by wing flicks. Fly song has frequency ranges audible to the human ear and can be directly listened to after appropriate amplification. When displayed in an oscillogram, audio recordings can be mapped on wing-movement patterns and thus provide a fast and precise method to sample and quantify motor behaviors with high temporal resolution. After recording different fly sounds, their effect on behavior can be tested in playback experiments.

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