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Feb 2019 • International Society for Optics and Photonics

Bio-sensor based on multiclass support vector machine with a reject option

Stav Buchsbaum, Yossi Keshet, Nisan Ozana, Zeev Zalevsky

In this work we explore the problem of multiclass classification where the classifier may abstain from classifying on some observation. We derivate a new surrogate loss function and a multiclass decision rule by using a reject threshold on posterior probabilities in the Bayes decision rule, known as Chow's rule. The goal of the decision rule is to minimize the value of given misprediction and rejection cost functions specified by the user. We suggest a general training algorithm by plug-in the surrogate loss in to Support Vector Machine (SVM) structure. We then test the algorithm on various real -life problem in the photonic medical sensing field where accuracy is critical. We present an example of a non-invasive way of detecting glucose level in blood to help patients with Diabetes mellitus diseases while the sensing is performed with speckle-based approach to analyze remote sensing of biomedical parameters. The …

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Jan 2019 • Materials

Genetic Algorithm-Based Design for Metal-Enhanced Fluorescent Nanostructures

Dror Fixler, Chen Tzur, Zeev Zalevsky

In this paper, we present our optimization tool for fluorophore-conjugated metal nanostructures for the purpose of designing novel contrast agents for multimodal bioimaging. Contrast agents are of great importance to biological imaging. They usually include nanoelements causing a reduction in the need for harmful materials and improvement in the quality of the captured images. Thus, smart design tools that are based on evolutionary algorithms and machine learning definitely provide a technological leap in the fluorescence bioimaging world. This article proposes the usage of properly designed metallic structures that change their fluorescence properties when the dye molecules and the plasmonic nanoparticles interact. The nanostructures design and evaluation processes are based upon genetic algorithms, and they result in an optimal separation distance, orientation angles, and aspect ratio of the metal nanostructure. View Full-Text

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Jan 2019 • bioRxiv

In Depth Flow Inspection Using Dynamic Laser Speckle Temporal Statistics

Mark Golberg, Ran Califa, Sagi Polani, Javier Garcia, Zeev Zalevsky

We present novel optical approach based on statistical analysis of temporal laser speckle patterns for tissue in-depth flow characteristics. An ability to distinguish between Brownian motion of particles and laminar flow is well proved. The main steps in the post processing algorithm and the in-vivo and in-vitro experimental results are presented and demonstrated.

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Jan 2019 • bioRxiv

Characterization of splice isoform switching during human kidney development

Yishay Wineberg, Itamar Kanter, Nissim Ben-Haim, Naomi Pode-Shakked, Efrat Bucris, Tali Hana Bar-Lev, Sarit Oriel, Yishai Yehuda, Rotem Gershon, Rachel Shukrun, Dekel Dov Bar-Lev, Achia Urbach, Benjamin Dekel, Tomer Kalisky

Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme – a transient kidney-specific progenitor state – undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms’ tumor that mimics normal kidney development. While kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. We therefore performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms’ tumor patient-derived xenografts. We identified a set of transcripts that are alternatively spliced between the different developmental stages. Moreover, we found that cells from the earliest developmental stage have a mesenchymal splice-isoform profile that is similar to that of blastemal-predominant Wilms’ tumors. RNA binding motif enrichment analysis suggests that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate mRNA splice isoform switching during human kidney development. These findings illuminate new molecular mechanisms involved in kidney development and pediatric kidney tumors.HIGHLIGHTS During fetal kidney development, kidney progenitor cells undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the …

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Jan 2019 • bioRxiv

The hunger games: sensing host arginine is essential for Leishmania parasite virulence

Adele Goldman-Pinkovich, Sriram Kannan, Roni Nitzan-Koren, Madhu Puri, Yael Bar-Avraham, Jacqueline A McDonald, Aakash Sur, Wen-Wei Zhang, Greg Matlashewski, Rentala Madhubala, Shulamit Michaeli, Peter J Myler, Dan Zilberstein

Arginine homeostasis in lysosomes is critical for growth and metabolism of mammalian cells. They employ a specific sensor (SLC38A9) that monitors intra-lysosome arginine sufficiency and subsequently up-regulates cellular mTORC1 activity. Lysosomes of macrophages (phagolysosomes) are the niche where the parasitic protozoan Leishmania resides and causes important human disease. Several years ago, we discovered that upon arginine starvation, cultured Leishmania parasites promptly activate a MAPK2-mediated Arginine Deprivation Response (ADR) pathway, resulting in up-regulation of the Leishmania arginine transporter (AAP3), as well as a small group of other transporters. Significantly, ADR is also activated during macrophage infection, implying that the intracellular parasite actively depletes arginine within the host phagolysosome, likely to prevent mTORC1 activation and enhance intracellular development. We hypothesize that ADR-mediated up-regulation of AAP3 activity is necessary to withstand the resultant arginine starvation. Both copies of the AAP3 genes are located (in tandem) on a tetrasomic chromosome (chr31), but only one (AAP3.2) is responsive to arginine deprivation. CRISPR/Cas9-mediated disruption of the AAP3 locus yielded mutants that retain a basal level of arginine transport (mediated by AAP3.1), but lack a functional copy of AAP3.2 and are therefore not responsive to arginine starvation. While these mutants grow normally in culture as promastigotes, they were impaired in their ability to develop inside THP1 macrophages grown under physiological concentrations of arginine (0.1 mM). However, flooding …

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Jan 2019 • ACS Energy Letters 4 (2), 436-446, 2019

Metal–sulfur batteries: overview and research methods

Michael Salama, Rosy, Ran Attias, Reut Yemini, Yosef Gofer, Doron Aurbach, Malachi Noked

Rechargeable metal–sulfur batteries (RMSBs) represent one of the most attractive electrochemical systems in terms of energy density and cost. In most of the proposed systems, the anode side is metallic and the cathode side is elemental sulfur impregnated in a porous matrix. Despite the relatively low voltage of these systems, they attract a lot of attention and are considered to be very promising as next-generation batteries for the following reasons: (1) utilization of active metal anodes enables a leap in specific energy due to the high capacity of metal anodes in comparison to intercalation compounds, (2) sulfur as a cathode exhibits high theoretical specific capacity (1675 mAh/g), and (3) system components make RMSBs low-cost, less toxic batteries. Nevertheless, the high reactivity of metallic anodes (e.g., Li, Na, Mg, and Al) and the solubility of sulfur species in the electrolyte render these batteries unstable and …

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A 512× 512Gating for Widefield FLIMSPAD Image Sensor With Integrated

Arin Can Ulku, Claudio Bruschini, Ivan Michel Antolovic, Yung Kuo, Rinat Ankri, Shimon Weiss, Xavier Michalet, Edoardo Charbon

In this paper, we report on SwissSPAD2, an image [2],[3]. In addition, the sensitivity of fluorescence lifetime on sensor with 512× 512 photon-counting pixels, each comprising a various environmental parameters such as oxygen levels or pH single-photon avalanche diode (SPAD), a 1-b memory, and a gating makes it a useful tool in functional imaging. Finally, FLIM mechanism capable of turning the SPAD ON and OFF, with a skew of 250 and 344 ps, respectively, for a minimum duration of 5.75 ns. permits rejection of background fluorescence by gating, when

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Jan 2019 • International journal of molecular sciences

Unraveling the impact of cysteine-to-serine mutations on the structural and functional properties of Cu (I)-binding proteins

Matic Pavlin, Zena Qasem, Hila Sameach, Lada Gevorkyan-Airapetov, Ida Ritacco, Sharon Ruthstein, Alessandra Magistrato

Appropriate maintenance of Cu (I) homeostasis is an essential requirement for proper cell function because its misregulation induces the onset of major human diseases and mortality. For this reason, several research efforts have been devoted to dissecting the inner working mechanism of Cu (I)-binding proteins and transporters. A commonly adopted strategy relies on mutations of cysteine residues, for which Cu (I) has an exquisite complementarity, to serines. Nevertheless, in spite of the similarity between these two amino acids, the structural and functional impact of serine mutations on Cu (I)-binding biomolecules remains unclear. Here, we applied various biochemical and biophysical methods, together with all-atom simulations, to investigate the effect of these mutations on the stability, structure, and aggregation propensity of Cu (I)-binding proteins, as well as their interaction with specific partner proteins. Among Cu (I)-binding biomolecules, we focused on the eukaryotic Atox1-ATP7B system, and the prokaryotic CueR metalloregulator. Our results reveal that proteins containing cysteine-to-serine mutations can still bind Cu (I) ions; however, this alters their stability and aggregation propensity. These results contribute to deciphering the critical biological principles underlying the regulatory mechanism of the in-cell Cu (I) concentration, and provide a basis for interpreting future studies that will take advantage of cysteine-to-serine mutations in Cu (I)-binding systems. View Full-Text

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Jan 2019 • Nature Photonics

Ultra-narrowband integrated brillouin laser

Hilel Hagai Diamandi, Avi Zadok

Optomechanics is a fascinating topic of study. Researchers have been exploring the rich interplay between optical and elastic waves in a medium ever since the first studies in the area by Mandelstam and Brillouin nearly 100 years ago1. Light waves can stimulate mechanical (acoustic) oscillations through electrostriction and radiation pressure. Likewise, acoustic waves can scatter and modulate light via photoelasticity. One interaction between light and acoustic waves that is of considerable importance is stimulated Brillouin scattering (SBS). In this situation, the interaction between an optical pump and an acoustic wave2 leads to the amplification of a second optical wave (called the Stokes wave) that is down-frequency-shifted from the pump by a few gigahertz. With appropriate feedback, this gain mechanism can be used to create a Brillouin laser. Since SBS is inherently a narrowband process due to phase …

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Jan 2019 • Journal of the Electrochemical Society

New insights related to rechargeable lithium batteries: Li metal anodes, Ni rich LiNixCoyMnzO2 cathodes and beyond them

Elena Markevich, Gregory Salitra, Pascal Hartmann, Joern Kulisch, Doron Aurbach, Kang-Joon Park, Chong S Yoon, Yang-Kook Sun

The electro-mobility revolution challenges the batteries community to develop rechargeable batteries with the highest energy density, including the use of Li metal anodes. Relevant cathode materials include sulfur and molecules with the general formula LiNi x Co y Mn z O 2, denoted as Ni rich NCM (x+ y+ z= 1; x> 0.5). We discuss herein new insights obtained from our recent work with cells comprising Li metal anodes, LiNi 0.6 Co 0.2 Mn 0.2 O 2 and LiNiO 2 cathodes with practical charge density higher than 3 mAh/cm 2. Highly stable behavior of Li metal anodes was realized in solutions containing mono-fluorinated ethylene carbonate (FEC) as a co-solvent. We found that the same solutions stabilize Ni rich NCM cathodes as well. We discuss herein the limiting factor of Li-LiNiO 2 cells in terms of cycle life and have gained new understandings related to failure and stabilization mechanisms of Ni rich NCM cathodes …

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Jan 2019 • Academic Press, 2019

Inorganic Nanowires for Sensing Applications

Guy Rahamim, Sokhrab B Aliev, David Zitoun

Nanowires are defined as wires with diameters of up to 100 nm and lengths of up to several millimeters. Their high surface-to-volume ratios provide them a high sensitivity to any external stimulus. In particular, the nanometric scale of the diameter enhances their sensitivity to the chemical surface state, which makes them appealing as building blocks for gas sensing.In a first part, we detail the fabrication of nanowires by bottom-up approaches with a special focus on the semi-conductor and metallic materials which are relevant for sensing. In a second part, we report the state-of-the-art in device fabrication with special emphasis on the nanowires-based gas sensors.

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Jan 2019 • Journal of the Electrochemical Society

Multifunctional separators: a promising approach for improving the durability and performance of Li-ion batteries

Anjan Banerjee, Baruch Ziv, Yuliya Shilina, Joseph M Ziegelbauer, Hanshuo Liu, Kristopher J Harris, Gianluigi Botton, Gillian R Goward, Shalom Luski, Doron Aurbach, Ion C Halalay

Electrified vehicles require Li-ion batteries (LIBs) with 10-year useful life. We review herein our progress since 2016 in the understanding of dissolved Mn species and LIB performance degradation by multifunctional materials. Multifunctional separators (MFSs), can trap Mn cations, scavenge acid species, and/or dispense alkali metal ions, with significant battery performance benefits: increased capacity retention during electrochemical cycling and improved rate performance. Cells with LiMn 2 O 4 (LMO), LiNi 0.6 Mn 0.2 Co 0.2 O 2 (NCM622), or LiNi 0.5 Mn 1.5 O 4 (LNMO) positive electrodes, graphite negative electrodes, and LiPF 6/mixed organic carbonate solutions were investigated. XRD, ICP-OES, XANES, HR-SEM, FIB-SEM, and MAS-NMR on harvested cell components complemented and aided the interpretation of electrochemical test results. While in LIBs with positive electrodes affected by Mn dissolution …

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Jan 2019 • ACS energy letters

Structural and Electrochemical Aspects of LiNi0.8Co0.1Mn0.1O2 Cathode Materials Doped by Various Cations

Tina Weigel, Florian Schipper, Evan M Erickson, Francis Amalraj Susai, Boris Markovsky, Doron Aurbach

Ni-rich materials of layered structure LiNixCoyMnzO2, x > 0.5, are promising candidates as cathodes in high-energy-density Li-ion batteries for electric vehicles. The structural and cycling stability of Ni-rich cathodes can be remarkably improved by doping with a small amount of extrinsic multivalent cations. In this study, we examine development of a fast screening methodology for doping LiNi0.8Co0.1Mn0.1O2 with cations Mg2+, Al3+, Si4+, Ti4+, Zr4+, and Ta5+ by a “top-down” approach. The cathode material is coated by a precursor layer that contains the dopant, which then is introduced into the particles by diffusion during heat treatment at elevated temperatures. The methodology described herein can be applied to Ni-rich cathode materials and allows relatively easy and prompt identification of the most promising dopants. Then further optimization work can lead to development of high-capacity stable cathode …

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Jan 2019 • Comprehensive Nanoscience and Nanotechnology

1.11 Inorganic Nanowires for Sensing Applications☆

Guy Rahamim, Sokhrab B Aliev, David Zitoun

In bottom-up syntheses, compounds are created from nanoscale building blocks, which may be varied and optimized depending on the synthetic conditions. This is the most widely used approach in modern chemistry; it is becoming more and more sophisticated and plays a key role in materials chemistry.The most developed and popular bottom-up method for growing one-dimensional structures, such as nanowires (NWs), is the vapor–liquid–solid (VLS) method [1]. The VLS technique has several benefits, such as controllable tuning of different crystal structures [2], alloys [3], dopant concentrations [4], and isotope distributions [5]. The typical VLS procedure of NW growth includes three main stages: metal alloying, crystal nucleation, and axial growth [6]. It starts from dissolution of gaseous precursors into nanosized catalytic liquid particles followed by quick adsorption of the vapor of a precursor of NW material. As a result, a liquid metal alloy of the catalyst and the target material is formed. The ensuing nucleation and growth of single-crystalline NWs happens on the surface of the silicon substrate. The nucleated dots play the role of crystallization centers of NWs on the liquid–solid surface. The 1D growth is conditioned by the nature of liquid droplets that play the role of soft template for the NW growth. For the first time, this methodology was proposed in 1964 by Wagner and Ellis to explain silicon whisker growth from the gas phase on silicon substrate in the presence of liquid gold situated on the surface of the substrate [7]. Metal-organic compounds, such as diphenyl silane and diphenyl germane, are commonly used for synthesis of NWs by metal …

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Jan 2019 • Batteries & Supercaps

Cover Picture: The Electrochemical Sodiation of FeSb2: New Insights from Operando 57Fe Synchrotron Mössbauer and X‐Ray Absorption Spectroscopy (Batteries …

Marcus Fehse, Dimitrios Bessas, Ali Darwiche, Abdelfattah Mahmoud, Guy Rahamim, Camille La Fontaine, Raphael P Hermann, David Zitoun, Laure Monconduit, Lorenzo Stievano, Moulay T Sougrati

The Front Cover shows how synchrotron radiation is important to study battery materials for many different applications. In this work, operando synchrotron‐based characterisation techniques, specifically X‐ray absorption and Mössbauer spectroscopy, were applied to elucidate the FeSb 2 charge–discharge mechanism. More information can be found in the article by M. Fehse et al.(DOI: 10.1002/batt. 201800075).

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Jan 2019 • bioRxiv

Feasibility analysis of semiconductor voltage nanosensors for neuronal membrane potential sensing

Anastasia Ludwig, Pablo Serna, Lion Morgenstein, Gaoling Yang, Omri Bar-Elli, Gloria Ortiz, Evan Miller, Dan Oron, Asaf Grupi, Shimon Weiss, Antoine Triller

In the last decade, optical imaging methods have significantly improved our understanding of the information processing principles in the brain. Although many promising tools have been designed, sensors of membrane potential are lagging behind the rest. Semiconductor nanoparticles are an attractive alternative to classical voltage indicators, such as voltage-sensitive dyes and proteins. Such nanoparticles exhibit high sensitivity to external electric fields via the quantum-confined Stark effect. Here we report the development of lipid-coated semiconductor voltage-sensitive nanorods (vsNRs) that self-insert into the neuronal membrane. We describe a workflow to detect and process the photoluminescent signal of vsNRs after wide-field time-lapse recordings. We also present data indicating that vsNRs are feasible for sensing membrane potential in neurons at a single-particle level. This shows the potential of vsNRs for detection of neuronal activity with unprecedentedly high spatial and temporal resolution.

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Jan 2019 • Journal of Controlled Release

Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy

Tivadar Feczkó, Albrecht Piiper, Saema Ansar, Frank W Blixt, Mukul Ashtikar, Susanne Schiffmann, Thomas Ulshöfer, Michael J Parnham, Yifat Harel, Liron Limor Israel, Jean-Paul Lellouche, Matthias G Wacker

For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared …

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Jan 2019 • Small

Improving the sensitivity of fluorescence‐based immunoassays by photobleaching the autofluorescence of magnetic beads

Shira Roth, Orr Hadass, Meir Cohen, Jasenka Verbarg, Jennifer Wilsey, Amos Danielli

In fluorescence‐based assays, usually a target molecule is captured using a probe conjugated to a capture surface, and then detected using a second fluorescently labeled probe. One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical performance of the assay. Here, several widely used magnetic beads are photobleached and their autofluorescence is reduced to 1% of the initial value. Their autofluorescence properties, including their photobleaching decay rates and autofluorescence spectra pre‐ and post‐photobleaching, and the stability of the photobleaching over a period of two months are analyzed. The photobleached beads are stable over time and their surface functionality is retained. In a high‐sensitivity LX‐200 system using photobleached …

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Jan 2019 • Journal of Physics D: Applied Physics

Layer by layer deposition of alternate carbon nanotubes and Ni films for efficient multilayer thin film temperature gauges

Shrutidhara Sarma, Ilias Fekas, Kyriakos Filintoglou, J Arvanitidis, Dimitris Christofilos, Euripides Hatzikraniotis, Ortal Lidor, Yitzhak Mastai, Aynur Unal, P Patsalas

This study reports a novel approach for growing multilayer thin films consisting of alternate layers of carbon nanotubes (CNT) and nickel on Si (1 0 0) substrates and justifies their use in thin film temperature sensors. A low pressure chemical vapor deposition system was employed for synthesizing CNT films, while Ni films were deposited by electrodeposition. Porous-Si was used as substrate to increase adhesion between the layers of the multilayer structure. The structure of the multilayer films and the quality of the CNT grown were analyzed using several characterization methods, including scanning electron microscopy, x-ray photoelectron spectroscopy, x-ray auger electron spectroscopy and Raman spectroscopy. The electrical characteristics were investigated using a van der Pauw setup and the effect of the increasing number of CNT layers in the multilayer structure was studied. The sensitivity of the multilayer …

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Jan 2019 • APL Photonics

Distributed opto-mechanical analysis of liquids outside standard fibers coated with polyimide

Hilel Hagai Diamandi, Yosef London, Gil Bashan, Avi Zadok

The analysis of surrounding media has been a long-standing challenge of optical fiber sensors. Measurements are difficult due to the confinement of light to the inner core of standard fibers. Over the last two years, new sensor concepts have enabled the analysis of liquids outside the cladding boundary, where light does not reach. Sensing is based on opto-mechanical, forward stimulated Brillouin scattering (F-SBS) interactions between guided light and sound waves. In most previous studies, however, the protective polymer coating of the fiber had to be removed first. In this work, we report the opto-mechanical analysis of liquids outside commercially available, standard single-mode fibers with polyimide coating. The polyimide layer provides mechanical protection but can also transmit acoustic waves from the fiber cladding toward outside media. The comprehensive analysis of opto-mechanical coupling in coated …

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Jan 2019 • Small

Photobleaching: improving the sensitivity of fluorescence‐based immunoassays by photobleaching the autofluorescence of magnetic beads (Small 3/2019)

Shira Roth, Orr Hadass, Meir Cohen, Jasenka Verbarg, Jennifer Wilsey, Amos Danielli

In fluorescence-based assays, the autofluorescence of capture surfaces produces strong background noise. In article number 1803751, Amos Danielli and co-workers use photobleaching as a method to reduce the autofluorescence of magnetic beads, a commonly used capture surface. The technique yields a 3-fold improvement in the limit of detection and signal-to-noise ratio of a fluorescence-based immunoassay.

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