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Abstract The COVID-19 pandemic has profoundly impacted global economies and healthcare systems, revealing critical vulnerabilities in both. In response, our study introduces a sensitive and highly specific detection method for cDNA, leveraging Luminescence Resonance Energy Transfer (LRET) between upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs), and achieves a detection limit of 242 fM for SARS-CoV-2 cDNA. This innovative sensing platform utilizes UCNPs conjugated with one primer and AuNPs with another, targeting the 5′ and 3′ ends of the SARS-CoV-2 cDNA, respectively, enabling precise differentiation of mismatched cDNA sequences and significantly improving detection specificity. Through rigorous experimental analysis, we established a quenching efficiency range from 10.4 % to 73.6 %, with an optimal midpoint of 42 %, thereby demonstrating the superior sensitivity of our method. Our work uses SARS-CoV-2 cDNA as a model system to demonstrate the potential of our LRET-based detection method. This proof-of-concept study highlights the adaptability of our platform for future diagnostic applications. Instrumental validation confirms the synthesis and formation of AuNPs, addressing the need for experimental verification of the preparation of nanomaterial. Our comparative analysis with existing SARS-CoV-2 detection methods revealed that our approach provides a low detection limit and high specificity for target cDNA sequences, underscoring its potential for targeted COVID-19 diagnostics. This study demonstrates the superior sensitivity and adaptability of using UCNPs and AuNPs for cDNA detection, offering significant advances in rapid, accessible diagnostic technologies. Our method, characterized by its low detection limit and high precision, represents a critical step forward in developing next-generation biosensors for managing current and future viral outbreaks. By adjusting primer sequences, this platform can be tailored to detect other pathogens, contributing to the enhancement of global healthcare responsiveness and infectious disease control.more » « lessFree, publicly-accessible full text available March 31, 2026
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Strong quantum correlated sources are essential but delicate resources for quantum information science and engineering protocols. Decoherence and loss are the two main disruptive processes that lead to the loss of nonclassical behavior in quantum correlations. In quantum systems, scattering can contribute to both decoherence and loss. In this work, we present an experimental scheme capable of significantly mitigating the adverse impact of scattering in quantum systems. Our quantum system is composed of a two-mode squeezed light generated with the four-wave-mixing process in hot rubidium vapor and a scatterer is introduced to one of the two modes. An integrating sphere is then placed after the scatterer to recollect the scattered photons. We use mutual information between the two modes as the measure of quantum correlations and demonstrate a 47.5% mutual information recovery from scattering, despite an enormous photon loss of greater than 85%. Our scheme is the very first step toward recovering quantum correlations from disruptive random processes and thus has the potential to bridge the gap between proof-of-principle demonstrations and practical real-world implementations of quantum protocols. Published by the American Physical Society2024more » « less
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The intrinsic fluorescence of bacterial samples has a proven potential for label-free bacterial characterization, monitoring bacterial metabolic functions, and as a mechanism for tracking the transport of relevant components through vesicles. The reduced scattering and axial confinement of the excitation offered by multiphoton imaging can be used to overcome some of the limitations of single-photon excitation (e.g., scattering and out-of-plane photobleaching) to the imaging of bacterial communities. In this work, we demonstrate in vivo multi-photon microscopy imaging of Streptomyces bacterial communities, based on the excitation of blue endogenous fluorophores, using an ultrafast Yb-fiber laser amplifier. Its parameters, such as the pulse energy, duration, wavelength, and repetition rate, enable in vivo multicolor imaging with a single source through the simultaneous two- and three-photon excitation of different fluorophores. Three-photon excitation at 1040 nm allows fluorophores with blue and green emission spectra to be addressed (and their corresponding ultraviolet and blue single-photon excitation wavelengths, respectively), and two-photon excitation at the same wavelength allows fluorophores with yellow, orange, or red emission spectra to be addressed (and their corresponding green, yellow, and orange single-photon excitation wavelengths). We demonstrate that three-photon excitation allows imaging over a depth range of more than 6 effective attenuation lengths to take place, corresponding to an 800 micrometer depth of imaging, in samples with a high density of fluorescent structures.more » « less
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Development of a simple, label-free screening technique capable of precisely and directly sensing interaction-in-solution over a size range from small molecules to large proteins such as antibodies could offer an important tool for researchers and pharmaceutical companies in the field of drug development. In this work, we present a thermostable Raman interaction profiling (TRIP) technique that facilitates low-concentration and low-dose screening of binding between protein and ligand in physiologically relevant conditions. TRIP was applied to eight protein–ligand systems, and produced reproducible high-resolution Raman measurements, which were analyzed by principal component analysis. TRIP was able to resolve time-depending binding between 2,4-dinitrophenol and transthyretin, and analyze biologically relevant SARS-CoV-2 spike-antibody interactions. Mixtures of the spike receptor–binding domain with neutralizing, nonbinding, or binding but nonneutralizing antibodies revealed distinct and reproducible Raman signals. TRIP holds promise for the future developments of high-throughput drug screening and real-time binding measurements between protein and drug.more » « less
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Non-destructive measurements of internal morphological structures in plant materials such as seeds are of high interest in agricultural research. The estimation of pericarp thickness is important to understand the grain quality and storage stability of seeds and can play a crucial role in improving crop yield. In this study, we demonstrate the applicability of fiber-based Bessel beam Fourier domain (FD) optical coherence microscopy (OCM) with a nearly constant high lateral resolution maintained at over ~400 µm for direct non-invasive measurement of the pericarp thickness of two different sorghum genotypes. Whereas measurements based on axial profiles need additional knowledge of the pericarp refractive index, en-face views allow for direct distance measurements. We directly determine pericarp thickness from lateral sections with a 3 µm resolution by taking the width of the signal corresponding to the pericarp at the 1/e threshold. These measurements enable differentiation of the two genotypes with 100% accuracy. We find that trading image resolution for acquisition speed and view size reduces the classification accuracy. Average pericarp thicknesses of 74 µm (thick phenotype) and 43 µm (thin phenotype) are obtained from high-resolution lateral sections, and are in good agreement with previously reported measurements of the same genotypes. Extracting the morphological features of plant seeds using Bessel beam FD-OCM is expected to provide valuable information to the food processing industry and plant breeding programs.more » « less
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We investigate quantum beats by monitoring cooperative emission from rubidium vapor and demonstrate correlated beats via coupled emission channels. We develop a theoretical model, and our simulations are in good agreement with experimental results. The results pave the way for advanced techniques measuring interactions between atoms that are excited to high energy levels.more » « less
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Abstract In a viral pandemic, a few important tests are required for successful containment of the virus and reduction in severity of the infection. Among those tests, a test for the neutralizing ability of an antibody is crucial for assessment of population immunity gained through vaccination, and to test therapeutic value of antibodies made to counter the infections. Here, we report a sensitive technique to detect the relative neutralizing strength of various antibodies against the SARS-CoV-2 virus. We used bright, photostable, background-free, fluorescent upconversion nanoparticles conjugated with SARS-CoV-2 receptor binding domain as a phantom virion. A glass bottom plate coated with angiotensin-converting enzyme 2 (ACE-2) protein imitates the target cells. When no neutralizing IgG antibody was present in the sample, the particles would bind to the ACE-2 with high affinity. In contrast, a neutralizing antibody can prevent particle attachment to the ACE-2-coated substrate. A prototype system consisting of a custom-made confocal microscope was used to quantify particle attachment to the substrate. The sensitivity of this assay can reach 4.0 ng/ml and the dynamic range is from 1.0 ng/ml to 3.2 $$\upmu$$ μ g/ml. This is to be compared to 19 ng/ml sensitivity of commercially available kits.more » « less
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