• 6 Oct 2021 Journal Article iScience

    Leaders of the field: What does the future hold for single molecule technology?

    Chirlmin Joo, Amit Meller
    In recent years, single molecule technology has experienced a rapid growth, with exciting developments in fundamental research and real-world applications. Detecting and studying biological phenomena on the single molecule level requires a unique synergy between researchers working on instrumentation, physics, and the life sciences. In the iScience special issue ‘‘Single… show more
  • 27 Sep 2021 Preprint medRxiv

    Descriptive characteristics of continuous oximetry measurement in moderate to severe COVID-19 patients

    Jonathan A Sobel, Jeremy Levy, Ronit Almog, Anat Reiner Benaim, Asaf Miller, Danny Eytan
    Background Non-invasive oxygen saturation (SpO2) measurement is a central vital sign that supports the management of COVID-19 patients. However, reports on SpO2 characteristics (patterns and dynamics) are scarce and none, to our knowledge, has analysed high resolution continuous SpO2 in COVID-19. Methods SpO2 signal sampled at 1Hz and clinical data were collected from… show more
  • 24 Sep 2021 Journal Article Journal of Biomechanics

    Mechanical interactions of invasive cancer cells through their substrate evolve from additive to synergistic


    Non-contacting, adjacent cancer cells can mechanically interact through their substrate to increase their invasive and migratory capacities that underly metastases-formation. Such mechanical interactions may induce additive or synergistic enhancement of invasiveness, potentially indicating different underlying force-mechanisms. To identify cell–cell-gel interactions

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  • 16 Sep 2021 Journal Article Bioengineering & Translational Medicine

    Biophysical targeting of high-risk cerebral aneurysms

    Mark Epshtein, Moran Levi, Afif M Kraitem, Hikaia Zidan, Robert M King, Meinrad Gawaz, Matthew J Gounis, Netanel Korin

    Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured

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  • 14 Sep 2021 Preprint Research Square

    Synthetic neuromorphic computing in living cells

    Biological regulatory networks in cells and neuronal networks employ complex circuit topologies with highly interconnected nodes to perform sophisticated information processing. Despite the complexity of neuronal networks, their information processing and computational capabilities can be recapitulated using simplified models comprising repeated connected nodes, e.g.… show more
  • 12 Sep 2021 Journal Article Advanced Functional Materials

    Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects

    Idan Redenski, Shaowei Guo, Majd Machour, Ariel A Szklanny, Shira Landau, Ben Kaplan, Roberta I Lock, Yankel Gabet, Dana Egozi, Gordana Vunjak-Novakovic, Shulamit Levenberg
    Functional regeneration of complex large‐scaled defects requires both soft‐ and hard‐tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and metabolism during the engraftment. Soft‐tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue‐harvest required for the… show more
  • 12 Sep 2021 Journal Article Advanced Materials

    3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion

    Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized… show more
  • 8 Sep 2021 Journal Article Frontiers in Physiology

    Ca2+ and Membrane Potential Transitions During Action Potentials Are Self-Similar to Each Other and to Variability of AP Firing Intervals Across the Broad Physiologic Range of AP Intervals During Autonomic Receptor Stimulation

    Dongmei Yang, Christopher H Morrell, Alexey E Lyashkov, Syevda Tagirova Sirenko, Ihor Zahanich, Yael Yaniv, Tatiana M Vinogradova, Bruce D Ziman, Victor A Maltsev, Edward G Lakatta
    Ca2+ and Vm transitions occurring throughout action potential (AP) cycles in sinoatrial nodal (SAN) cells are cues that (1) not only regulate activation states of molecules operating within criticality (Ca2+ domain) and limit-cycle (Vm domain) mechanisms of a coupled-clock system that underlies SAN cell automaticity, (2) but are also regulated by the activation states… show more
  • 6 Sep 2021 Preprint medRxiv

    Development of a machine-learning model to assess terminal ileum Endoscopic healing in pediatric Crohn's disease from Magnetic Resonance Enterography data

    Itai Guez, Gili Focht, Mary-Louise C Greer, Ruth Cytter-Kuint, Li-tal Pratt, Denise A Castro, Dan Turner, Anne M Griffiths, Moti Freiman
    Background and Aims Endoscopic healing (EH), is a major treatment goal for Crohn’s disease (CD). However, terminal ileum (TI) intubation failure is common, especially in children. We evaluated the added-value of machine-learning models in imputing a TI Simple Endoscopic Score for CD (SES-CD) from Magnetic Resonance Enterography (MRE) data of pediatric CD patients. Methods… show more
  • 1 Sep 2021 Preprint arXiv

    Fabrication of diffractive optical elements by programmable thermocapillary shaping of thin liquid films

    Diffractive optical elements (DOEs) enable precise manipulation of wavefronts and are widely used in a variety of optical systems. However, their fabrication relies on lithography or high precision machining processes that are long, expensive, and infrastructure-heavy. We here present a one-step rapid fabrication method that leverages the thermocapillary effect to shape… show more
  • 1 Sep 2021 Journal Article Current Opinion in Biotechnology

    Advances in vascularization and innervation of constructs for neural tissue engineering

    A growing number of technologies are being developed to promote vascularization and innervation in engineered tissues. Organ-on-a-chip, organoid and 3D printing technologies, as well as pre-vascularized and oriented scaffolds, have been employed for vascularization and innervation of engineered tissues both in vivo and in vitro. Both vascularization and innervation are… show more
  • 27 Aug 2021 Journal Article Science

    Airborne transmission of respiratory viruses

    Chia C Wang, Kimberly A Prather, Josué Sznitman, Jose L Jimenez, Seema S Lakdawala, Zeynep Tufekci, Linsey C Marr
    The COVID-19 pandemic has revealed critical knowledge gaps in our understanding of and a need to update the traditional view of transmission pathways for respiratory viruses. The long-standing definitions of droplet and airborne transmission do not account for the mechanisms by which virus-laden respiratory droplets and aerosols travel through the air and lead to… show more
  • 26 Aug 2021 Journal Article Frontiers in Molecular Biosciences

    The Dynamics of Lamin a During the Cell Cycle

    Lamin proteins play an essential role in maintaining the nuclear organization and integrity; and lamin A, in particular, plays a major role in the whole volume of the nuclear interior. Although the nucleus is highly organized, it is rather dynamic, it affects crucial nuclear processes and its organization must change as cells progress through the cell cycle. Although… show more
  • 24 Aug 2021 Journal Article Bioengineering & Translational Medicine

    Biophysical Targeting of High-Risk Cerebral Aneurysms

    Mark Epshtein, Moran Levi, Afif M Kraitem, Hikaia Zidan, Robert M King, Meinrad Gawaz, Matthew J Gounis, Netanel Korin
    Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured… show more
  • 15 Aug 2021 Preprint arXiv

    NPBDREG: A Non-parametric Bayesian Deep-Learning Based Approach for Diffeomorphic Brain MRI Registration

    Quantification of uncertainty in deep-neural-networks (DNN) based image registration algorithms plays an important role in the safe deployment of real-world medical applications and research-oriented processing pipelines, and in improving generalization capabilities. Currently available approaches for uncertainty estimation, including the variational encoder-decoder… show more
  • 5 Aug 2021 Journal Article European Heart Journal - Digital Health

    Atrial fibrillation risk prediction from the 12-lead ECG using digital biomarkers and deep representation learning

    Shany Biton, Sheina Gendelman, Antônio H Ribeiro, Gabriela Miana, Carla Moreira, Antonio Luiz P Ribeiro, Joachim Behar
    Aims This study aims to assess whether information derived from the raw 12-lead electrocardiogram (ECG) combined with clinical information is predictive of atrial fibrillation (AF) development. Methods We use a subset of the Telehealth Network of Minas Gerais (TNMG) database consisting of patients that had repeated 12-lead ECG measurements between 2010-2017 that is… show more
  • 3 Aug 2021 Journal Article PNAS

    Investigating lymphangiogenesis in vitro and in vivo using engineered human lymphatic vessel networks

    The lymphatic system is involved in various biological processes, including fluid transport from the interstitium into the venous circulation, lipid absorption, and immune cell trafficking. Despite its critical role in homeostasis, lymphangiogenesis (lymphatic vessel formation) is less widely studied than its counterpart, angiogenesis (blood vessel formation). Although… show more
  • 1 Aug 2021 Journal Article American Journal of Hematology

    Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy

    Diane M Tshikudi, Olivier Simandoux, Dongkyun Kang, Elizabeth M Van Cott, Michael N Andrawes, Dvir Yelin, Seemantini K Nadkarni

    During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients

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  • 29 Jul 2021 Journal Article Advanced Drug Delivery Reviews

    Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

    Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant… show more
  • 26 Jul 2021 Preprint Social Science Research Network

    Single-Molecule, Non-Chromatic Discrimination in Binary Fluorophores Mixtures

    SummarySingle biomolecule sensing often involves quantification of multiple fluorescent species, coupled for example to different DNAs or proteins resides. While chromatic separation of the fluorescent species is well-established and broadly used it involves several limitations, particularly when the total photon budget is limited. Here we theoretically and experimentally… show more
  • 23 Jul 2021 Journal Article Cells

    Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

    Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain… show more
  • 19 Jul 2021 Journal Article Optics Express

    Deep-ROCS: from speckle patterns to superior-resolved images by deep learning in rotating coherent scattering microscopy

    Alon Saguy, Felix Jünger, Aviv Peleg, Boris Ferdman, Elias Nehme, Alexander Rohrbach, Yoav Shechtman
    Rotating coherent scattering (ROCS) microscopy is a label-free imaging technique that overcomes the optical diffraction limit by adding up the scattered laser light from a sample obliquely illuminated from different angles. Although ROCS imaging achieves 150 nm spatial and 10 ms temporal resolution, simply summing different speckle patterns may cause loss of sample… show more
  • 16 Jul 2021 Journal Article IEEE Transactions on Biomedical Engineering

    Remote atrial fibrillation burden estimation using deep recurrent neural network

    Armand Chocron, Julien Oster, Shany Biton, Franck Mandel, Meyer Elbaz, Yehoshua Y Zeevi, Joachim Behar
    OBJECTIVE The atrial fibrillation burden (AFB) is defined as the percentage of time spent in atrial fibrillation (AF) over a long enough monitoring period. Recent research has suggested the added prognostic value of using the AFB compared to a binary diagnosis. We evaluate, for the first time, the ability to estimate the AFB over long-term continuous recordings, using… show more
  • 16 Jul 2021 Preprint In Review

    P-selectin Targeting Stimulates Caveolin-1-Mediated Endothelial Transcytosis in Medulloblastoma

    Daniel Tylawsky, Hiro Kiguchi, Jake Vaynshteyn, Jeffrey Gerwin, Janki Shah, Taseen Islam, Matija Snuderl, Matthew B Greenblatt, Daniel Boué, Yosi Shamay, Praveen Raju, Daniel A Heller
    Medulloblastoma (MB) is the most common malignant pediatric brain tumor with ~30% mediated by Sonic hedgehog (SHH) signaling. While SHH effector Smoothened inhibition is promising, therapeutic index is reduced by high systemic doses required for sufficient intracranial drug concentrations. Treatment-related toxicities associated with radiation therapy result in lifelong… show more
  • 12 Jul 2021 Conference Paper IEEE International Workshop on Medical Measurement and Applications (MEMEA)

    Measurement of Enhanced Photothermal Effects of CuO-encapsulated Polymeric Nanospheres

    Sanzhar Korganbayev, Somayeh Asadi, Inbal Maor, Emiliano Schena, Haim Azhari, Iris S Weitz, Paola Saccomandi
    Copper oxide nanoparticles (CuO-NPs) have the potential of serving as an anticancer theranostic agent with photothermal capabilities. In order to control their toxicity and release, the CuO NPs were encapsulated within polymeric nanospheres composed of poly(lactic-co-glycolic acid) (PLGA) core and polydopamine (PDA)/polyethylene glycol (PEG) shell. After the characterization… show more
  • 5 Jul 2021 Journal Article ACS Nano

    Fast and Deterministic Fabrication of Sub-5 Nanometer Solid-State Pores by Feedback-Controlled Laser Processing

    Nanopores are single-molecule sensors capable of detecting and quantifying a broad range of unlabeled biomolecules including DNA and proteins. Nanopores’ generic sensing principle has permitted the development of a vast range of biomolecular applications in genomics and proteomics, including single-molecule DNA sequencing and protein fingerprinting. Owing to their… show more
  • 2 Jul 2021 Journal Article Nano Letters

    Multiplexed PSF Engineering for Three-Dimensional Multicolor Particle Tracking

    Three-dimensional spatiotemporal tracking of microscopic particles in multiple colors is a challenging optical imaging task. Existing approaches require a trade-off between photon efficiency, field of view, mechanical complexity, spectral specificity, and speed. Here, we introduce multiplexed point-spread-function engineering that achieves photon-efficient, 3D multicolor… show more
  • 1 Jul 2021 Journal Article IEEE Transactions on Pattern Analysis and Machine Intelligence

    Learning Optimal Wavefront Shaping for Multi-Channel Imaging

    Fast acquisition of depth information is crucial for accurate 3D tracking of moving objects. Snapshot depth sensing can be achieved by wavefront coding, in which the point-spread function (PSF) is engineered to vary distinctively with scene depth by altering the detection optics. In low-light applications, such as 3D localization microscopy, the prevailing approach is… show more
  • 1 Jul 2021 Journal Article Advanced Functional Materials

    Injectability of Biosynthetic Hydrogels: Consideration for Minimally Invasive Surgical Procedures and 3D Bioprinting

    Injectable hydrogels are often preferred when designing carriers for cell therapy or developing new bio-ink formulations. Biosynthetic hydrogels, which are a class of materials made with a hybrid design strategy, can be advantageous for endowing injectability while maintaining biological activity of the material. The chemical modification required to make these gels… show more
  • 30 Jun 2021 Journal Article Frontiers in Physiology

    Opening the Schrödinger Box: Short- and Long-Range Mammalian Heart Rate Variability

    Background: The interactions between the autonomic nervous system (ANS), intrinsic systems (e.g., endocrine), and internal pacemaker mechanisms govern short (milliseconds–seconds)- and long (seconds–minutes)-range heart rate variability (HRV). However, there is a debate regarding the identity of the mechanism underlying HRV on each time scale. We aim to design a general… show more
  • 22 Jun 2021 Preprint bioRxiv

    Computational neural network provides naturalistic solution for recovery of finger dexterity after stroke

    Finger dexterity is a fundamental movement skill of humans and the ability to individuate fingers imparts high motor flexibility. Disruption of dexterity due to brain injury imposes a detriment to quality of life, and thus understanding the neurological mechanisms responsible for recovery is imperative for neurorehabilitation. Two neuronal pathways have been proposed… show more
  • 21 Jun 2021 Conference Paper 2021 Conference on Lasers and Electro-Optics Europe (CLEO/Europe)

    Photon-efficient three-dimensional simultaneous multicolor particle tracking by multiplexed PSF engineering


    Real-time microscopic tracking of multicolor fluorescent probes in 3D is of key importance for understanding a variety of biological processes. Point-Spread-Function (PSF) engineering is an effective tool for such tasks – by modulating the PSF of the optical system, emitters can be tracked with nm-scale resolution in 3D by means of computational analysis [1] . Existing

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  • 21 Jun 2021 Conference Paper 2021 Conference on Lasers and Electro-Optics Europe (CLEO/Europe)

    Liquid immersion enables 3D printable diffractive optical elements


    Diffractive optical elements, used to shape the wavefront of incident light, are ubiquitous in optics thanks to the high flexibility in design and compactness that they offer [1]. However, the nanoscale-precision requirements typically necessitates a complicated fabrication process, e.g. nanolithography. Here we present the liquid immersed DOE. By immersing the DOE in

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  • 15 Jun 2021 Journal Article PNAS

    Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis

    Despite their great promise, artificial intelligence (AI) systems have yet to become ubiquitous in the daily practice of medicine largely due to several crucial unmet needs of healthcare practitioners. These include lack of explanations in clinically meaningful terms, handling the presence of unknown medical conditions, and transparency regarding the system’s limitations… show more
  • 12 Jun 2021 Journal Article Biomechanics and Modeling in Mechanobiology

    Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay

    Sally Kortam, Yulia Merkher, Aviv Kramer, Issa Metanes, Dean Ad-El, Judit Krausz, Yaron Har-Shai, Daphne Weihs
    Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors… show more
  • 9 Jun 2021 Journal Article Journal of Biomechanics

    Towards homogenization of liquid plug distribution in reconstructed 3D upper airways of the preterm infant

    Liquid plug therapies are commonly instilled in premature babies suffering from infant respiratory distress syndrome (IRDS) by a procedure called surfactant replacement therapy (SRT) in which a surfactant-laden bolus is instilled endotracheally in the neonatal lungs, dramatically reducing mortality and morbidity in neonatal populations. Since data are frequently limited… show more
  • 9 Jun 2021 Journal Article Vascularization for Tissue Engineering and Regenerative Medicine

    Co-culture systems for vasculogenesis

    Vascularization is a fundamental aspect of tissue engineering and is one of the main challenges in the field when trying to construct thick tissues. Co-culture systems have demonstrated promising potential in construction of vascularized tissues, and in enhancing graft viability and persistence in vivo. In this chapter, we discuss pivotal studies integrating co-cultures… show more
  • 7 Jun 2021 Journal Article Nature Methods

    The emerging landscape of single-molecule protein sequencing technologies

    Javier Antonio Alfaro, Peggy Bohländer, Mingjie Dai, Mike Filius, Cecil J Howard, Xander F van Kooten, Shilo Ohayon, Adam Pomorski, Sonja Schmid, Aleksei Aksimentiev, Eric V Anslyn, Georges Bedran, Chan Cao, Mauro Chinappi, Etienne Coyaud, Cees Dekker, Gunnar Dittmar, Nicholas Drachman, Rienk Eelkema, David Goodlett, Sébastien Hentz, Umesh Kalathiya, Neil L Kelleher, Ryan T Kelly, Zvi Kelman, Sung Hyun Kim, Bernhard Kuster, David Rodriguez-Larrea, Stuart Lindsay, Giovanni Maglia, Edward M Marcotte, John P Marino, Christophe Masselon, Michael Mayer, Patroklos Samaras, Kumar Sarthak, Lusia Sepiashvili, Derek Stein, Meni Wanunu, Mathias Wilhelm, Peng Yin, Amit Meller, Chirlmin Joof
    Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry… show more
  • 5 Jun 2021 Journal Article International Journal of Molecular Sciences

    Photo-Polymerization Damage Protection by Hydrogen Sulfide Donors for 3D-Cell Culture Systems Optimization

    Silvia Buonvino, Matteo Ciocci, Dror Seliktar, Sonia Melino
    Photo-polymerized hydrogels are ideally suited for stem-cell based tissue regeneration and three dimensional (3D) bioprinting because they can be highly biocompatible, injectable, easy to use, and their mechanical and physical properties can be controlled. However, photo-polymerization involves the use of potentially toxic photo-initiators, exposure to ultraviolet light… show more
  • Jun 2021 Journal Article Journal of Aerosol Medicine and Pulmonary Drug Delivery

    Surfactant foam therapy for severe COVID-19 patients with acute respiratory distress syndrome (ARDS)

    The SARS-CoV-2 virus enters primarily through the respiratory tract and penetrates epithelial cells. In severe cases, the disease deteriorates to a form of acute respiratory distress syndrome (ARDS) and is accountable for most deaths. To date, there is no effective pharmacological treatment in ARDS in adults with mortality rates around 40%. One of the hallmarks of ARDS… show more
  • 30 May 2021 Journal Article International Journal of Molecular Sciences

    Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes

    Maila Chirivì, Fabio Maiullari, Marika Milan, Dario Presutti, Chiara Cordiglieri, Mariacristina Crosti, Maria Lucia Sarnicola, Andrea Soluri, Marina Volpi, Wojciech Swieszkowski, Daniele Prati, Marta Rizzi, Marco Costantini, Dror Seliktar, Chiara Parisi, Claudia Bearzi, Roberto Rizzi

    The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of

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  • 27 May 2021 Preprint bioRxiv

    Separation of multiple motor memories through implicit and explicit processes

    Acquisition of multiple motor skills without interference is a remarkable ability in sport and daily life. During adaptation to opposing perturbations, a common paradigm to study this ability, each perturbation can be successfully learned when a dynamical contextual cue, such as a follow-through movement, is associated with the direction of the perturbation. It is still… show more
  • 27 May 2021 Journal Article Journal of Physical Chemistry B

    Automated Analysis of Fluorescence Kinetics in Single-Molecule Localization Microscopy Data Reveals Protein Stoichiometry

    Alon Saguy, Tim N Baldering, Lucien E Weiss, Elias Nehme, Christos Karathanasis, Marina S Dietz, Mike Heilemann, Yoav Shechtman
    Understanding the function of protein complexes requires information on their molecular organization, specifically, their oligomerization level. Optical super-resolution microscopy can localize single protein complexes in cells with high precision, however, the quantification of their oligomerization level, remains a challenge. Here, we present a Quantitative Algorithm… show more
  • 25 May 2021 Journal Article Nature Communications

    Synthetic neural-like computing in microbial consortia for pattern recognition

    Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial… show more
  • 25 May 2021 Journal Article Scientific Reports

    Alginate hydrogel beads embedded with drug-bearing polycaprolactone microspheres for sustained release of paclobutrazol

    Alexandra Mun, Haneen Simaan Yameen, Giora Edelbaum, Dror Seliktar
    In recent years there has been a growing demand for the development of agrochemical controlled release (CR) technologies. In the present study, we aimed to create a novel agricultural CR device using two polymeric systems that have been predominantly employed in biomedical applications: beads of alginate hydrogel embedded with drug-bearing Polycaprolactone (PCL)… show more
  • 24 May 2021 Journal Article Nature Communications

    3D printable diffractive optical elements by liquid immersion Associated Content

    Diffractive optical elements (DOEs) are used to shape the wavefront of incident light. This can be used to generate practically any pattern of interest, albeit with varying efficiency. A fundamental challenge associated with DOEs comes from the nanoscale-precision requirements for their fabrication. Here we demonstrate a method to controllably scale up the relevant… show more
  • 21 May 2021 Preprint bioRxiv

    Bioluminescent Synthetic Cells Communicate with Natural Cells and Self-Activate Light-Responsive Proteins

    Development of regulated cellular processes and signaling methods in synthetic cells is essential for their integration with living materials. Light is an attractive tool to achieve this, but the limited penetration depth into tissue of visible light restricts its usability for in-vivo applications. Here, we describe the synthesis and application of blue-light-generating… show more
  • 21 May 2021 Journal Article Nucleic Acids Research

    Topologies of synthetic gene circuit for optimal fold change activation

    Computations widely exist in biological systems for functional regulations. Recently, incoherent feedforward loop and integral feedback controller have been implemented into Escherichia coli to achieve a robust adaptation. Here, we demonstrate that an indirect coherent feedforward loop and mutual inhibition designs can experimentally improve the fold change of promoters… show more
  • 14 May 2021 Journal Article frontiers in Medicine

    Comparing COVID-19 and Influenza Presentation and Trajectory

    Anat Reiner Benaim, Jonathan A Sobel, Ronit Almog, Snir Lugassy, Tsviel Ben Shabbat, Alistair E W Johnson, Danny Eytan, Joachim Behar
    Background: COVID-19 is a newly recognized illness with a predominantly respiratory presentation. It is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis and help in guiding treatment. Methods: Data from… show more
  • 14 May 2021 Journal Article Physiological Measurement

    From sleep medicine to medicine during sleep - a clinical perspective

    Nitai Bar, Jonathan A Sobel, Thomas Penzel, Yosi Shamay, Joachim Behar
    Objective. In this perspective paper, we aim to highlight the potential of sleep as an auspicious time for diagnosis, management and therapy of non-sleep-specific pathologies. Approach. Sleep has a profound influence on the physiology of body systems and biological processes. Molecular studies have shown circadian-regulated shifts in protein expression patterns across… show more
  • 5 May 2021 Journal Article IEEE Transactions on Nanobioscience

    Formation of Large Intracellular Actin Networks Following Plasmonic Cell Fusion


    Following fusion between two or more individual cells, the resulting cellular entity must undergo extensive restructuring of its plasma membrane and cytoskeleton in order to maintain its mechanical and physiological function. In artificial cell fusion that is executed by external triggering, such restructuring could be problematic due to the absence of preconditioning

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  • 5 May 2021 Journal Article Arteriosclerosis, Thrombosis, and Vascular Biology

    Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes

    Ronen Siman-Tov, Natalie Zelikson, Michal Caspi, Yakir Levi, Chava Perry, Fayhaa Khair, Hagit Stauber, Josué Sznitman, Rina Rosin-Arbesfeld
    Objective: The deformation ability of erythrocytes is critical for their function and affects their mobility in the circulation. To circulate and travel through narrow vessels, erythrocytes must continuously alter their shape by modifying their cytoskeleton, which controls their elasticity and stability. Erythrocytes lack nuclei and other major organelles, and thus most… show more
  • 3 May 2021 Journal Article JACC: Cardiovascular Imaging

    Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia

    Pepijn A van Diemen, Michiel J Bom, Roel S Driessen, Stefan P Schumacher, Henk Everaars, Ruben W de Winter, Peter M van de Ven, Moti Freiman, Liran Goshen, Dennis Heijtel, Eran Langzam, James K Min, Jonathon A Leipsic, Pieter G Raijmakers, Albert C van Rossum, Ibrahim Danad, Paul Knaapen
    Objectives This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. Background Inflammation plays a crucial role in atherosclerosis. PCATa has been shown… show more
  • 2 May 2021 Preprint bioRxiv

    Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with anti-inflammatory therapeutics

    Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite maintenance of blood homeostasis. The biotrauma hypothesis advances that mechanical forces from invasive ventilation trigger immunological factors that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here we show that flow-induced… show more
  • 1 May 2021 Journal Article Gait & Posture

    Intermittent vibrational stimulation enhances mobility during stair navigation in patients with knee pain

    Arielle G Fischer, Jennifer C Erhart-Hledik, Jessica L Asay, Thomas P Andriacchi
    Background Reduced quadriceps function and proprioception can cause decreased mobility during stair navigation in patients with knee pain. Patients can benefit from interventions to mitigate pain and restore quadriceps function. Activating the somatosensory system via intermittent vibrational stimulation has the potential to improve stair navigation mobility in patients… show more
  • 1 May 2021 Journal Article American Journal of Respiratory and Critical Care Medicine

    Nicotine in e-Cigarettes Dysregulates Interferon Beta, Tumor Necrosis Factor Alpha, and Matrix Metalloproteinase 12 Expression, Without Effecting Respiratory Syncytial Virus Virulence in Mice

    Brais Perez Gandara, Jessica Perez Perez, Hannah Goldenberg, Andrew Bramante, Robert F Foronjy, Abdoulaye J Dabo, Edward Eden, Josué Sznitman, Patrick Geraghty
    Introduction/rationale for the study: The safety of electronic cigarettes (e-cigarettes) is a major topic of discussion, especially with the recent vaping-associated pulmonary injury (EVALI) outbreak and growing evidence of potential harmful effects of vaping. The key goals of this study were to determine if components of e-cigarette vapor alter inflammatory responses… show more
  • 29 Apr 2021 Preprint bioRxiv

    Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions

    Glorieux L, Sapala A, David Willnow, Moulis M, Shlomit Edri, Darrigrand J, Schonblum A, Lina Sakhneny, Schaumann L, Harold F Gómez, Lang C, Conrad L, Guillemot F, Shulamit Levenberg, Limor Landsman, Dagmar Iber, Pierreux C, Francesca M Spagnoli
    Generating comprehensive image maps, while preserving spatial 3D context, is essential to quantitatively assess and locate specific cellular features and cell-cell interactions during organ development. Despite the recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is… show more
  • 28 Apr 2021 Journal Article APL Bioengineering

    Transforming a well into a chip: A modular 3D-printed microfluidic chip

    Rossana Rauti, Adi Ess, Baptiste Le Roi, Yevgeniy Kreinin, Mark Epshtein, Netanel Korin, Ben M Maoz
    Organ-on-a-Chip platforms provide rich opportunities to observe interactions between different cell types under in vivo-like conditions, i.e., in the presence of flow. Yet, the costs and know-how required for the fabrication and implementation of these platforms restrict their accessibility. This study introduces and demonstrates a novel Insert-Chip: a microfluidic… show more
  • 28 Apr 2021 Journal Article ACS Synthetic Biology

    A Whole-Cell Bacterial Biosensor for Blood Markers Detection in Urine

    The early detection of blood in urine (hematuria) can play a crucial role in the treatment of serious diseases (e.g., infections, kidney disease, schistosomiasis, and cancer). Therefore, the development of low-cost portable biosensors for blood detection in urine has become necessary. Here, we designed an ultrasensitive whole-cell bacterial biosensor interfaced with an… show more
  • 27 Apr 2021 Journal Article Journal of Visualized Experiments

    Continuous Measurement of Biological Noise in Escherichia Coli Using Time-lapse Microscopy

    The protocol developed here offers a tool to enable computer tracking of Escherichia coli division and fluorescent levels over several hours. The process starts by screening for colonies that survive on minimal media, assuming that only Escherichia coli harboring the correct plasmid will be able to thrive in the specific conditions. Since the process of building large… show more
  • 23 Apr 2021 Journal Article Biomechanics and Modeling in Mechanobiology

    A formalism for modelling traction forces and cell shape evolution during cell migration in various biomedical processes

    Qiyao Peng, Fred J Vermolen, Daphne Weihs
    The phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity… show more
  • 23 Apr 2021 Book Chapter The Science, Etiology and Mechanobiology of Diabetes and its Complications

    The mechanobiology of adipocytes in the context of diabetes: much more than a fat depot

    We describe the mechanobiology of adipocytes in varying stages of their development, from mesenchymal stem cells, to lineage-committed preadipocytes, through the adipogenesis to adipocytes, and conditions that may relate to diabetes development. Cells in the different stages exhibit varying mechanical interactions with the substrate, related to changes in interactions… show more
  • 21 Apr 2021 Journal Article JACC: Clinical Electrophysiology

    Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species

    Syevda Tagirova Sirenko, Kenta Tsutsui, Kirill V Tarasov, Dongmei Yang, Ashley N Wirth, Victor A Maltsev, Bruce D Ziman, Yael Yaniv, Edward G Lakatta
    Objectives The purpose of this study was to discover regulatory universal mechanisms of normal automaticity in sinoatrial nodal (SAN) pacemaker cells that are self-similar across species. Background Translation of knowledge of SAN automaticity gleaned from animal studies to human dysrhythmias (e.g., “sick sinus” syndrome [SSS]) requiring electronic pacemaker insertion… show more
  • 20 Apr 2021 Journal Article Cell Death and Disease

    A hydrogel reveals an elusive cancer stem cell

    Sonia Melino, Dror Seliktar
    Biomaterials made from polymers have helped to revolutionize the medical industry through innovative designs of implants and biosensors. Now, materials in the form of hydrogels are making headway in cancer research, where an ever-expanding tool-chest of sophisticated in vitro cell culture platforms is helping scientists to unravel the mysteries of cancer stem cells… show more
  • 16 Apr 2021 Conference Paper Novel Techniques in Microscopy 2021

    Liquid immersion enables 3D-printing of diffractive optical elements

    We show that immersing a diffractive optical element (DOE) in a near-index-matched solution significantly simplifies its fabrication process thanks to scaling-up of its axial dimensions, enabling adaptable and 3D printable DOEs.
  • 16 Apr 2021 Conference Paper OSA Biophotonics Congress: Optics in the Life Sciences

    Multiplexed PSF engineering - photon-efficient simultaneous multicolor 3D particle tracking

    We demonstrate photon-efficient, multicolor, large FOV 3D localization microscopy with high spatiotemporal resolution by multiplexing spectrally-defined, single-channel PSFs. This is accomplished by encoding spectral and 3D information into the PSFs.
  • 15 Apr 2021 Journal Article Nature Communications

    Democratising deep learning for microscopy with ZeroCostDL4Mic

    Lucas von Chamier, Romain F Laine, Johanna Jukkala, Christoph Spahn, Daniel Krentzel, Elias Nehme, Martina Lerche, Sara Hernández-Pérez, Pieta K Mattila, Eleni Karinou, Seamus Holden, Ahmet Can Solak, Alexander Krull, Tim-Oliver Buchholz, Martin L Jones, Loic Royer, Christophe Leterrier, Yoav Shechtman, Florian Jug, Mike Heilemann, Guillaume Jacquemet, Ricardo Henriques
    Deep Learning (DL) methods are powerful analytical tools for microscopy and can outperform conventional image processing pipelines. Despite the enthusiasm and innovations fuelled by DL technology, the need to access powerful and compatible resources to train DL networks leads to an accessibility barrier that novice users often find difficult to overcome. Here, we present… show more
  • 15 Apr 2021 Journal Article Journal of Biomechanics

    A converging artery-sized model for shear adhesion mapping of particles

    Drug carriers for targeting cardiovascular diseases have been gaining a respectable attention, however, designing such carriers is challenging due to the biophysical complexity of the vascular system. Wall shear stress (WSS), exerted by blood flow on the endothelium surface, is a crucial factor in the circulatory system. WSS affects the adhesion and preferential accumulation… show more
  • 7 Apr 2021 Journal Article Physiological Measurement

    Machine learning for nocturnal diagnosis of chronic obstructive pulmonary disease using digital oximetry biomarkers

    Jeremy Levy, Daniel Alvarez, Felix del Campo, Joachim Behar
    Objective Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic condition. COPD is a major cause of morbidity, mortality and healthcare costs globally. Spirometry is the gold standard test for a definitive diagnosis and severity grading of COPD. However, a large proportion of individuals with COPD are undiagnosed and untreated. Given the high… show more
  • 14 Mar 2021 Journal Article Journal of Visualized Experiments

    In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow

    The use of three-dimensional (3D) models of human arteries, which are designed with the correct dimensions and anatomy, enables the proper modeling of various important processes in the cardiovascular system. Recently, although several biological studies have been performed using such 3D models of human arteries, they have not been applied to study vascular targeting… show more
  • 12 Mar 2021 Journal Article Science and Technology of Advanced Materials

    Laser-induced thermal response and controlled release of copper oxide nanoparticles from multifunctional polymeric nanocarriers

    Inbal Maor, Somayeh Asadi, Sanzhar Korganbayev, Daniel Dahis, Yosi Shamay, Emiliano Schena, Haim Azhari, Paola Saccomandi, Iris S Weitz

    Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows

    show more
  • 12 Mar 2021 Journal Article Nano Letters

    Stimulating Extracellular Vesicles Production from Engineered Tissues by Mechanical Forces

    Extracellular vesicles (EVs) have emerged as a promising strategy to promote tissue regeneration. However, overcoming the low EV production yield remains a big challenge in translating EV-based therapies to the clinical practice. Current EV production relies heavily on 2D cell culture, which is not only less physiologically relevant to cells but also requires substantial… show more
  • 8 Mar 2021 Journal Article Biomechanics and Modeling in Mechanobiology

    Modeling force application configurations and morphologies required for cancer cell invasion

    Yaniv Ben-David, Daphne Weihs
    We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in invasive cancer cells, while in-plane traction forces alone reproduce observations in non-cancer/noninvasive cells. Mechanobiological interactions of cells with their microenvironment drive migration and cancer invasion… show more
  • 5 Mar 2021 Conference Paper High-Speed Biomedical Imaging and Spectroscopy VI

    3D microscopy in extreme conditions: in-flow or at high density

    Attaining three-dimensional data at high throughput is a grand challenge in microscopy. I will discuss two recent contributions to 3D microscopy utilizing point-spread-function (PSF) engineering: 1.a new method that extends the capabilities of flow-based imaging to 3D co-localization microscopy, and 2. efficient and fast localization of dense molecules in volumetric… show more
  • 4 Mar 2021 Journal Article Cell

    Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis

    Alexander Heyde, David Rohde, Cameron S McAlpine, Shuang Zhang, Friedrich Felix Hoyer, Jeffrey M Gerold, David Cheek, Yoshiko Iwamoto, Maximilian J Schloss, Katrien Vandoorne, Oriol Iborra-Egea, Christian Muñoz-Guijosa, Antoni Bayes-Genis, Johannes G Reiter, Morgan Craig, Filip K Swirski, Matthias Nahrendorf, Martin A Nowak, Kamila Naxerova
    Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis… show more
  • 1 Mar 2021 Journal Article Journal of Applied Physiology

    Anatomical variability in the upper tracheobronchial tree: sex-based differences and implications for personalized inhalation therapies

    Simoni Christou, Thanasis Chatziathanasiou, Stelios Angeli, Pantelis Koullapis, Fotos Stylianou, Josué Sznitman, Haiwei Henry Guo, Stavros C Kassinos
    The morphometry of the large conducting airways is presumed to have a strong effect on the regional deposition of inhaled aerosol particles. Nevertheless, sex-based differences have not been fully quantified and are still largely ignored in designing inhalation therapies. To this end, we retrospectively analyzed high-resolution computer-tomography scans for 185 individuals… show more
  • 19 Feb 2021 Journal Article eLife

    LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior

    Nana Naetar, Konstantina Georgiou, Christian Knapp, Irena Bronshtein, Elisabeth Zier, Petra Fichtinger, Thomas Dechat, Yuval Garini, Roland Foisner
    Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2α. Here, we show that loss of LAP2α… show more
  • 18 Feb 2021 Journal Article Frontiers in Physiology

    Visualizing and Quantifying Irregular Heart Rate Irregularities to Identify Atrial Fibrillation Events

    Background: Screening the general public for atrial fibrillation (AF) may enable early detection and timely intervention, which could potentially decrease the incidence of stroke. Existing screening methods require professional monitoring and involve high costs. AF is characterized by an irregular irregularity of the cardiac rhythm, which may be detectable using an… show more
  • 17 Feb 2021 Journal Article Frontiers in Neuroscience

    Beating Rate Variability of Isolated Mammal Sinoatrial Node Tissue: Insight Into Its Contribution to Heart Rate Variability

    Background: Because of the complexity of the interaction between the internal pacemaker mechanisms, cell interconnected signals, and interaction with other body systems, study of the role of individual systems must be performed under in vivo and in situ conditions. The in situ approach is valuable when exploring the mechanisms that govern the beating rate and rhythm of… show more
  • 15 Feb 2021 Journal Article Embo Molecular Medicine

    Biofabricating murine and human myo‐substitutes for rapid volumetric muscle loss restoration

    Marco Costantini, Stefano Testa, Ersilia Fornetti, Claudia Fuoco, Carles Sanchez Riera, Minghao Nie, Sergio Bernardini, Alberto Rainer, Jacopo Baldi, Carmine Zoccali, Roberto Biagini, Luisa Castagnoli, Libero Vitiello, Bert Blaauw, Dror Seliktar, Wojciech Swieszkowski, Piotr Garstecki, Shoji Takeuchi, Gianni Cesareni, Stefano Cannata, Cesare Gargioli
    The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly… show more
  • 8 Feb 2021 Journal Article European Journal of Echocardiography

    Pericoronary adipose tissue attenuation leads to improved prognostication beyond atherosclerotic burden and high-risk plaques in patients with suspected coronary artery disease

    Pepijn A van Diemen, Michiel J Bom, Roel S Driessen, Henk Everaars, Ruben W de Winter, Peter M van de Ven, Moti Freiman, Liran Goshen, Eran Langzam, James K Min, Jonathon A Leipsic, Pieter G Raijmakers, Albert C van Rossum, Ibrahim Danad, Paul Knaapen
    Background Inflammation is a key component in the atherosclerotic process, initiating and sustaining plaques and serving as a trigger for plaque rupture leading to myocardial infarction. Coronary computed tomography angiography (CCTA) derived pericoronary adipose tissue attenuation (PCATa) has been proposed as surrogate marker for coronary inflammation and might improve… show more
  • 5 Feb 2021 Book Chapter Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches

    In silico methods to model dose deposition

    Pantelis Koullapis, Fotos Stylianou, Ching-Long Lin, Stavros C Kassinos, Josué Sznitman
    In this chapter, we review the current state of in silico tools for lung deposition applications and discuss how knowledge gathered from recent studies can be purposefully leveraged to design efficient hybrid multiscale lung models. We firstly address the different roles of in silico methods when applied to the human lung airways. We then discuss the variability of… show more
  • 2 Feb 2021 Journal Article Nature Reviews Materials

    Targeted drug delivery strategies for precision medicines

    Mandana Taghizadeh Manzari, Yosi Shamay, Hiroto Kiguchi, Neal Rosen, Maurizio Scaltriti, Daniel A Heller
    Progress in the field of precision medicine has changed the landscape of cancer therapy. Precision medicine is propelled by technologies that enable molecular profiling, genomic analysis and optimized drug design to tailor treatments for individual patients. Although precision medicines have resulted in some clinical successes, the use of many potential therapeutics… show more
  • 1 Feb 2021 Journal Article Journal of Thrombosis and Haemostasis

    Wall shear rates in human and mouse arteries: Standardization of hemodynamics for in vitro blood flow assays: Communication from the ISTH SSC subcommittee on biorheology

    Mikhail A Panteleev, Netanel Korin, Koen D Reesink, David L Bark, Judith M E M Cosemans, Elizabeth E Gardiner, Pierre Mangin
    Hemodynamics play a central role in hemostasis and thrombosis by affecting all aspects linked to platelet functions and coagulation. In vitro flow devices are extensively used in basic research, pharmacological studies, antiplatelet agent screening, and development of diagnostic tools. Because hemodynamic conditions vary tremendously throughout the vascular tree and… show more
  • 31 Jan 2021 Journal Article Journal of Thrombosis and Haemostasis

    In vitro flow-based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis

    Pierre Mangin, Keith B Neeves, Wilbur A Lam, Judith M E M Cosemans, Netanel Korin, Steven W Kerrigan, Mikhail A Panteleev
    In vitro flow‐based assays are widely used to investigate the role of platelets and coagulation in hemostasis and thrombosis. Their main advantage over other assays relies on the fact that they integrate blood flow that regulates many aspects of platelet function, including adhesion, activation, and aggregation. Blood flow is also central in the regulation of coagulation… show more
  • 28 Jan 2021 Journal Article Journal of Visualized Experiments

    Silicon Nanowires and Optical Stimulation for Investigations of Intra- and Intercellular Electrical Coupling

    Menahem Y Rotenberg, Erik N Schaumann, Aleksander Prominski, Bozhi Tian
    Myofibroblasts can spontaneously internalize silicon nanowires (SiNWs), making them an attractive target for bioelectronic applications. These cell-silicon hybrids offer leadless optical modulation capabilities with minimal perturbation to normal cell behavior. The optical capabilities are obtained by the photothermal and photoelectric properties of SiNWs. These hybrids… show more
  • 28 Jan 2021 Journal Article Journal of Biomechanics

    Focused targeting of inhaled magnetic aerosols in reconstructed in vitro airway models

    Yan Ostrovski, Simon Dorfman, Wilson Poh, Say Chye Joachim Loo, Josué Sznitman
    The pulmonary tract is an attractive route for topical treatments of lung diseases. Yet, our ability to confine the deposition of inhalation aerosols to specific lung regions, or local airways, remains still widely beyond reach. It has been hypothesized that by coupling magnetic particles to inhaled therapeutics the ability to locally target airway sites can be… show more
  • 28 Jan 2021 Patent

    Device And Method For Spectral Imaging

    Yuval Garini, Irena Bronshtein, Iris Barshack
    A spectral imaging device includes an imager, a scanning stage to establish relative motion between the imager and a sample in a scanning direction and an optical system controlling a light characteristic of a light beam constituting an image of the sample to the imager. The optical system includes a light varying element to receive the light beam and provide an output… show more
  • 26 Jan 2021 Journal Article Clinical Chemistry

    Nanopore Identification of Single Nucleotide Mutations in Circulating Tumor DNA by Multiplexed Ligation

    Nitza Burck, Tal Gilboa, Abhilash Gadi, Michelle Patkin Nehrer, Robert J Schneider, Amit Meller
    Background Circulating tumor DNAs (ctDNAs) are highly promising cancer biomarkers, potentially applicable for noninvasive liquid biopsy and disease monitoring. However, to date, sequencing of ctDNAs has proven to be challenging primarily due to small sample size and high background of fragmented cell-free DNAs (cfDNAs) derived from normal cells in the circulation… show more
  • 22 Jan 2021 Journal Article Annals of Biomedical Engineering

    Machine-Learning Provides Patient-Specific Prediction of Metastatic Risk Based on Innovative, Mechanobiology Assay

    Cancer mortality is mostly related to metastasis. Metastasis is currently prognosed via histopathology, disease-statistics, or genetics; those are potentially inaccurate, not rapidly available and require known markers. We had developed a rapid (~ 2 h) mechanobiology-based approach to provide early prognosis of the clinical likelihood for metastasis. Specifically… show more
  • 22 Jan 2021 Journal Article Frontiers in Oncology

    Use of Simvastatin, Fibrin Clots, and Their Combination to Improve Human Ovarian Tissue Grafting for Fertility Restoration After Anti-Cancer Therapy

    Roei Magen, Yoel Shufaro, Yair Daykan, Galia Oron, Elena Tararashkina, Shulamit Levenberg, Eli Anuka, Avi Ben-Haroush, Benjamin Fisch, Ronit Abir
    Anticancer treatments, particularly chemotherapy, induce ovarian damage and loss of ovarian follicles. There are limited options for fertility restoration, one of which is pre-chemotherapy cryopreservation of ovarian tissue. Transplantation of frozen-thawed human ovarian tissue from cancer survivors has resulted in live-births. There is extensive follicular loss… show more
  • 15 Jan 2021 Patent

    Vesicles Comprising a Pten Inhibitor and Uses of Same

    Shulamit Levenberg, Shaowei Guo, Daniel Offen, Nisim Perets
    The present invention provides pharmaceutical compositions comprising membrane vesicles, including extracellular vesicles including those referred to as exosomes, loaded with an exogenous Phosphatase and tensin homolog (PTEN) inhibitor. Methods of treating neurological diseases, disorders or conditions using the extracellular vesicles are provided. Isolated extracellular… show more
  • 14 Jan 2021 Journal Article Journal of Respiration

    Nicotine in E-Cigarettes Dysregulates Pulmonary Inflammation and MMP-12 Expression without Effecting Respiratory Syncytial Virus Virulence

    Hannah Goldenberg, Brais Perez Gandara, Jessica Perez Perez, Andrew Bramante, Robert F Foronjy, Abdoulaye J Dabo, Edward Eden, Josué Sznitman, Patrick Geraghty
    The safety of electronic cigarettes (e-cigarettes) is a major topic of discussion. The key goals of this study were to examine the contents of e-cigarette vapor and determine if nicotine altered inflammatory responses against respiratory syncytial virus (RSV) infection. E-cigarette vapor was passed through a hollow 3D-model of an adult lung, and gas chromatography… show more
  • 14 Jan 2021 Journal Article Journal of Visualized Experiments

    Stepwise Cell Seeding on Tessellated Scaffolds to Study Sprouting Blood Vessels

    Ariel A Szklanny, Dylan B Neale, Joerg Lahann, Shulamit Levenberg
    The cardiovascular system is a key player in human physiology, providing nourishment to most tissues in the body; vessels are present in different sizes, structures, phenotypes, and performance depending on each specific perfused tissue. The field of tissue engineering, which aims to repair or replace damaged or missing body tissues, relies on controlled angiogenesis… show more
  • 13 Jan 2021 Patent

    Optical coherence tomography systems and methods including fluorescence microscopic imaging of one or more biological structures

    Guillermo J Tearney, Dvir Yelin, Benjamin J Vakoc, Wang-Yuhl Oh, Brett E Bouma
    The present invention generally relates to arrangements and methods for providing multimodality microscopic imaging of one or more biological structures, and particularly to, e.g., conducting reflectance and/or fluorescence microscopy of biological specimens using spectrally encoded confocal microscopy ("SECM"), fluorescence SECM, optical coherence tomography ("OCT")… show more
  • 13 Jan 2021 Patent

    Optical Coherence Tomography Systems And Methods Including Fluorescence Microscopic Imaging Of One Or More Biological Structures

    Guillermo J Tearney, Dvir Yelin, Benjamin J Vakoc, Wang-Yuhl Oh, Brett E Bouma
    An optical coherence tomography system comprising: a wavelength tuning source (700, 800, 805) configured to provide a light signal whose wavelength varies over time; a detector apparatus (755, 852) configured to provide first data associated with a first light signal provided by the wavelength tuning source (700, 800, 805) reflected from at least one region of at least… show more
  • 7 Jan 2021 Patent

    Method For Loading A Multiplexed Array Of Nanoliter Droplet Array Devices

    Microfluidic devices and methods thereof; the devices including: SNDA components; each SNDA component comprising: a primary channel; secondary channels; and nano-wells that are each open to the primary channel and are each connected via vents to the secondary channel; the vents are configured to enable passage of gas solely from the nano-wells to the secondary channel… show more
  • 4 Jan 2021 Journal Article npj Digital Medicine

    Digital oximetry biomarkers for assessing respiratory function: standards of measurement, physiological interpretation, and clinical use

    Pulse oximetry is routinely used to non-invasively monitor oxygen saturation levels. A low oxygen level in the blood means low oxygen in the tissues, which can ultimately lead to organ failure. Yet, contrary to heart rate variability measures, a field which has seen the development of stable standards and advanced toolboxes and software, no such standards and open tools… show more
  • 4 Jan 2021 Journal Article Physiological Measurement

    Editorial on Remote Health Monitoring: from chronic diseases to pandemics

    Joachim Behar, Chengyu Liu, Yaniv Zigel, Pablo Laguna, Gari D Clifford
    With billions of mobile devices worldwide and the relatively low cost of connected medical sensors, recording and transmitting medical data has become easier and faster than ever, and we can now easily obtain continuous and long-term dynamic physiological data. However, this 'wealth' of physiological data has seen very limited successes in being harnessed to provide… show more
  • 30 Dec 2020

    Production Of Extracellular Vesicles From Stem Cells

    The present invention provides methods and systems for enhanced production and/or secretion of extracellular vesicles from at least one three-dimensional porous scaffold having a population of stem cells cultured thereon, utilizing various shear stress conditions on a variety of stem cells.
  • 22 Dec 2020 bioRxiv

    Self-similar synchronization of calcium and membrane potential transitions during AP cycles predict HR across species

    Syevda Tagirova Sirenko, Kenta Tsutsui, Kirill V Tarasov, Dongmei Yang, Ashley N Wirth, Victor A Maltsev, Bruce D Ziman, Yael Yaniv, Edward G Lakatta
    Studies in animal models are an important facet of cardiac arrhythmia research. Because HR differs by over ten-fold between some animals and humans, translation of knowledge about regulatory mechanisms of SAN normal automaticity gleaned from studies in animal models to target human SSS has been sub-optimal. Our findings demonstrating that trans-species self-similarity… show more
  • 7 Dec 2020 Nature Nanotechnology

    Micelle-enabled self-assembly of porous and monolithic carbon membranes for bioelectronic interfaces

    Yin Fang, Aleksander Prominski, Menahem Y Rotenberg, Lingyuan Meng, Héctor Acarón Ledesma, Yingying Lv, Jiping Yue, Erik N Schaumann, Junyoung Jeong, Naomi Yamamoto, Yuanwen Jiang, Benayahu Elbaz, Wei Wei, Bozhi Tian
    Real-world bioelectronics applications, including drug delivery systems, biosensing and electrical modulation of tissues and organs, largely require biointerfaces at the macroscopic level. However, traditional macroscale bioelectronic electrodes usually exhibit invasive or power-inefficient architectures, inability to form uniform and subcellular interfaces, or faradaic… show more
  • 3 Dec 2020

    Single Input Multiplex Decision Systems And Methods Of Using The Same

    The present invention is directed to a single input multiplex decision expression system, and a method of using same, such as for expressing a reporter protein.
  • 1 Dec 2020 Israel Journal of Chemistry

    Nanoinformatics in Drug Delivery

    The use of nanomedicine for targeted drug delivery, though well established, is still a growing and developing field of research with potential benefits to many biomedical problems. There is a plethora of nano‐carriers with myriads of designs of shapes, sizes and composition that involves complex, trial and error based preparation protocols. The digital age brought an… show more
  • 1 Dec 2020 bioRxiv

    Liquid foam therapy (LiFT) for homogenous distribution of exogenous pulmonary surfactant in ARDS

    Lung surfactant dysfunction has a critical role in the pathophysiology of acute respiratory distress syndrome (ARDS). Yet, efforts to treat ARDS patients with liquid instillations of exogenous surfactant have so far failed. One of the ongoing challenges in surfactant therapy is obtaining a homogeneous distribution of surfactant within the lungs despite an inherent… show more
  • 25 Nov 2020 European Heart Journal

    Incremental prognostic value of pericoronary adipose tissue attenuation on top of comprehensive CCTA assessment

    Pepijn A van Diemen, Michiel J Bom, Roel S Driessen, Henk Everaars, Stefan P Schumacher, Ruben W de Winter, Peter M van de Ven, Moti Freiman, Liran Goshen, D Heitel, Eran Langzam, Albert C van Rossum, Ibrahim Danad, Paul Knaapen
    Background Coronary computed tomography angiography (CCTA) derived parameters linked to severity and extent of atherosclerosis are associated with prognosis in patients with coronary artery disease (CAD). Furthermore, coronary inflammation, by determining pericoronary adipose tissue CT-attenuation (PCATa), can be assessed on CCTA as well and has been proposed as promising… show more
  • 22 Nov 2020 medRxiv

    At the dawn of winter: comparing COVID-19and influenza presentation and trajectory

    Anat Reiner Benaim, Jonathan A Sobel, Ronit Almog, Snir Lugassy, Tsviel Ben Shabbat, Alistair E W Johnson, Danny Eytan, Joachim Behar
    Background: COVID-19 is a newly recognized illness with a predominantly respiratory presentation. As winter approaches in the northern hemisphere, it is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis… show more
  • 17 Nov 2020 Circulation

    An Increase in the Respiratory Effort Immediately Intensifies the Hemodynamic Congestion; a Mechanism for Progressive Cardiac Decompensation

    Noa Markovitch, Shmuel Rispler, Yair Feld, Amir Solomonica, Sergey Yalonetsky, Ariel Roguin, Arthur Kerner, Amir Landesberg
    Introduction: An increase in the pulmonary wedge pressure (PCWP) is associated with an increase in the respiratory effort and the sensation of dyspnea. Hypothesis: We investigated the inverse cause and effect relationship, whether an increase in the respiratory effort can by itself aggravate the hemodynamic congestion. Methods: We scrutinized the cardiopulmonary… show more
  • 12 Nov 2020 Circulation

    Quantification of Arterial Stenosis Severity Based on the Changes in the Perfusion Wave Dynamics; a Novel Technology for Monitoring Peripheral Artery Disease

    Tomer Heitner, Amit Livneh, Jonathan Lorber, Ron Karmeli, Amir Landesberg
    Introduction: Current screening modalities for peripheral artery disease (PAD) lack sensitivity especially in the elderly and diabetics, and there is an unmet need for early detection of restenosis after revascularization. Hypothesis: We have hypothesized that arterial stenosis is associated with adaptive arteriolar vasodilatation, which alters the downstream perfusion… show more
  • 11 Nov 2020 Nanotechnology

    Ultrasound-induced and MRI-monitored CuO nanoparticles release from micelle encapsulation

    Roana N Schiopu Aresteanu, Alexander Borodetsky, Haim Azhari, Iris S Weitz
    Copper oxide nanoparticles (CuO NPs) have anticancer and antimicrobial activities. Moreover, they have a contrast enhancing effect in both MRI and Ultrasound. Nonetheless, encapsulation is needed to control their toxic side effects and a mechanism for release on demand is required. A methodology is introduced herein for encapsulating and releasing CuO NPs from micelles… show more
  • 3 Nov 2020 Journal Article Annals of Biomedical Engineering

    Actin as a Target to Reduce Cell Invasiveness in Initial Stages of Metastasis

    We demonstrate the relative roles of the cell cytoskeleton, and specific importance of actin in facilitating mechanical aspects of metastatic invasion. A crucial step in metastasis, the typically lethal spread of cancer to distant body-sites, is cell invasion through dense tissues composed of extracellular matrix and various non-cancerous cells. Cell invasion requires… show more
  • 28 Oct 2020 Science Advances

    Microscopic scan-free surface profiling over extended axial ranges by point-spread-function engineering

    The shape of a surface, i.e., its topography, influences many functional properties of a material; hence, characterization is critical in a wide variety of applications. Two notable challenges are profiling temporally changing structures, which requires high-speed acquisition, and capturing geometries with large axial steps. Here, we leverage point-spread-function… show more
  • 27 Oct 2020 bioRxiv

    Local calcium signals in pacemaker cells heart rate and body mass are self-similar from mice to humans

    Syevda Tagirova Sirenko, Kenta Tsutsui, Dongmei Yang, Bruce D Ziman, Kirill V Tarasov, Yael Yaniv, Edward G Lakatta
    Long-range, power law correlations across species between heart rate (HR) and body mass (BM) have been documented. Heart rate, which varies widely across species, is determined by the frequency and rhythm at which action potentials (APs) are generated by pacemaker cells within the hearts sinoatrial node (SAN). The rate and rhythm of AP firing of SAN pacemaker cells… show more
  • 19 Oct 2020 Biomedical Optics Express

    Rapid imaging of tympanic membrane vibrations in humans

    Matan Hamra, Shadi Shinnawi, Mauricio Cohen Vaizer, Dvir Yelin
    Functional imaging of the human ear is an extremely challenging task because of its minute anatomic structures and nanometer-scale motion in response to sound. Here, we demonstrate noninvasive in vivo functional imaging of the human tympanic membrane under various acoustic excitations, and identify unique vibration patterns that vary between human subjects. By combining… show more
  • 8 Oct 2020 Nanotechnology

    Roadmap on nanomedicine

    Paolo Decuzzi, Dan Peer, Daniele Di Mascolo, Anna Lisa Palange, Purnima Naresh Manghnani, S Moein Moghimi, Z Shadi Farhangrazi, Kenneth A Howard, Daniel Rosenblum, Tingxizi Liang, Zhaowei Chen, Zejun Wang, Jun-Jie Zhu, Zhen Gu, Netanel Korin, Didier Letourneur, Cédric Chauvierre, Roy van der Meel, Fabian Kiessling, Twan Lammers
    Since the launch of the Alliance for Nanotechnology in Cancer by the National Cancer Institute in late 2004, several similar initiatives have been promoted all over the globe with the intention of advancing the diagnosis, treatment and prevention of cancer in the wake of nanoscience and nanotechnology. All this has encouraged scientists with diverse backgrounds to team… show more
  • 23 Sep 2020 ACS Nano

    Quantification of mRNA Expression Using Single-Molecule Nanopore Sensing

    RNA quantification methods are broadly used in life science research and in clinical diagnostics. Currently, real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most common analytical tool for RNA quantification. However, in cases of rare transcripts or inhibiting contaminants in the sample, an extensive amplification could bias the copy number… show more
  • 16 Sep 2020 Journal of Materials Science

    In vitro evaluation of copper release from MRI-visible, PLGA-based nanospheres

    Iris S Weitz, Or Perlman, Haim Azhari, Sarit Sara Sivan
    Copper nanostructures offer remarkable therapeutic potential. In particular, copper oxide nanoparticles (CuO NPs) are increasingly studied for diagnostic and therapeutic purposes. Their anticancer potential, as well as contrast-enhancing capabilities for magnetic resonance imaging (MRI) and ultrasound (US), were previously demonstrated. To further exploit their unique… show more
  • 26 Aug 2020 Neurorehabilitation and Neural Repair

    Pushing the Rehabilitation Boundaries: Hand Motor Impairment Can Be Reduced in Chronic Stroke

    Firas Mawase, Kendra M Cherry-Allen, Jing Xu, Manuel Anaya, Shintaro Uehara, Pablo Celnik
    Background. Stroke is one of the most common causes of physical disability worldwide. The majority of survivors experience impairment of movement, often with lasting deficits affecting hand dexterity. To date, conventional rehabilitation primarily focuses on training compensatory maneuvers emphasizing goal completion rather than targeting reduction of motor impairment… show more
  • 26 Aug 2020 Methods of Molecular Biology

    Photocurable Biopolymers for Coaxial Bioprinting

    Marco Costantini, Andrea Barbetta, Wojciech Swieszkowski, Dror Seliktar, Cesare Gargioli, Alberto Rainer
    Thanks to their unique advantages, additive manufacturing technologies are revolutionizing almost all sectors of the industrial and academic worlds, including tissue engineering and regenerative medicine. In particular, 3D bioprinting is rapidly emerging as a first-choice approach for the fabrication-in one step-of advanced cell-laden hydrogel constructs to be used for… show more
  • 23 Jul 2020 International Journal of Cancer

    Lung mechanics modifications facilitating metastasis are mediated in part by breast cancer-derived extracellular vesicles

    Tamar Barenholz-Cohen, Yulia Merkher, Jozafina Haj, Dvir Shechter, Daniela Kirchmeier, Yuval Shaked, Daphne Weihs
    Tumor microenvironment-mechanics greatly affect tumor-cell characteristics such as invasion and proliferation. We and others have previously shown that after chemotherapy, tumor cells shed more extracellular vesicles (EVs), leading to tumor growth and even spread, via angiogenesis and the mobilization of specific bone-marrow-derived cells contributing to metastasis… show more
  • 26 Jun 2020 Neuron

    Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

    Or A Shemesh, Changyang Linghu, Kiryl D Piatkevich, Daniel Goodwin, Orhan T Celiker, Howard J Gritton, Michael Romano, Ruixuan Gao, Chi-Chieh (Jay) Yu, Hua-an Tseng, Seth Bensussen, Sujatha Narayan, Chao-Tsung Yang, Limor Freifeld, Cody A Siciliano, Ishan Gupta, Joyce Wang, Nikita Pak, Young-Gyu Yoon, Jeremy F P Ullmann, Burcu Guner-Ataman, Habiba Noamany, Zoe R Sheinkopf, Won Min Park, Shoh Asano, Amy E Keating, James S Trimmer, Jacob Reimer, Andreas S Tolias, Mark F Bear, Kay M Tye, Xue Han, Misha B Ahrens, Edward S Boyden
    Summary Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual… show more
  • 15 Jun 2020 Nature Methods

    DeepSTORM3D: dense 3D localization microscopy and PSF design by deep learning

    An outstanding challenge in single-molecule localization microscopy is the accurate and precise localization of individual point emitters in three dimensions in densely labeled samples. One established approach for three-dimensional single-molecule localization is point-spread-function (PSF) engineering, in which the PSF is engineered to vary distinctively with emitter… show more
  • 1 Jun 2020 The Cerebellum

    Locomotor Adaptation Is Associated with Microstructural Properties of the Inferior Cerebellar Peduncle

    Sivan Jossinger, Firas Mawase, Michal Ben-Shachar, Lior Shmuelof
    In sensorimotor adaptation paradigms, participants learn to adjust their behavior in response to an external perturbation. Locomotor adaptation and reaching adaptation depend on the cerebellum and are accompanied by changes in functional connectivity in cortico-cerebellar circuits. In order to gain a better understanding of the particular cerebellar projections involved… show more
  • 25 May 2020 Gait & Posture

    Utilizing the somatosensory system via vibratory stimulation to mitigate knee pain during walking: Randomized clinical trial

    Arielle G Fischer, Jennifer C Erhart-Hledik, Jessica L Asay, Constance R Chu, Thomas P Andriacchi
    Background Pain and proprioception deficits are often associated with knee pathologies and resultant quadriceps muscle inhibition. There is a need for new approaches to mitigate active knee pain and restore muscle function during walking. Activating properties of the somatosensory system with common pain and sensory pathways offers a novel opportunity to enhance quadriceps… show more
  • 20 Apr 2020 Nature Nanotechnology

    Three-dimensional localization microscopy in live flowing cells Associated Content


    Capturing the dynamics of live cell populations with nanoscale resolution poses a significant challenge, primarily owing to the speed-resolution trade-off of existing microscopy techniques. Flow cytometry would offer sufficient throughput, but lacks subsample detail. Here we show that imaging flow cytometry, in which the point detectors of flow cytometry are replaced

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  • 18 Dec 2019 Scientific Reports

    Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy

    Maaike van den Boomen, Hanne B Kause, Hans C van Assen, Patricia Y W Dankers, Carlijn V C Bouten, Katrien Vandoorne
    Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. Yet, noninvasive evaluation of their efficacy has been lagging behind. Here, we report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy… show more
  • 26 Feb 2018 Nature Chemical Biology

    A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

    Kiryl D Piatkevich, Erica E Jung, Christoph Straub, Changyang Linghu, Demian Park, Ho-Jun Suk, Daniel Hochbaum, Daniel Goodwin, Eftychios A Pnevmatikakis, Nikita Pak, Takashi Kawashima, Chao-Tsung Yang, Jeffrey L Rhoades, Or A Shemesh, Shoh Asano, Young-Gyu Yoon, Limor Freifeld, Jessica L Saulnier, Clemens Riegler, Florian Engert, Thomas E Hughes, Mikhail Drobizhev, Bálint Szabó, Misha B Ahrens, Steven W Flavell, Bernardo L Sabatini, Edward S Boyden
    We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library… show more