Despite intense interests in developing blood measurements of Alzheimer’s disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we present a dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins – exosome-bound vs. unbound – directly from blood. The technology, termed a mplified p lasmonic ex osome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.

atomically thin 2D layered materials, such as monolayer transition metal dichalcogenides (TMDs), [5][6][7][8] hexagonal boron nitride (hBN). [9,10] and gallium selenide, [11] are attractive alternative hosts to overcome such fundamental limitations of bulk counterparts.Following the initial reports on single photon emitters observed in naturally occurring defects in as-grown and as-exfoliated 2D TMDs, [5][6][7][8] various strain and crystal defect engineering approaches have been developed to deterministically generate these quantum emitters. While local strain introduced by nano-pillars/ holes or nano-indents commonly results in single photon emitters in a variety of 2D materials including hBN, WS 2 , WSe 2 , and MoSe 2 , [12][13][14][15][16][17] creation of point defects by ion [10,18] and electron [9,19] beam irradiation has proved to be a viable route to inducing similar quantum emitters. Further, direct writing of quantum emitter arrays on monolayer MoS 2 with precisely controlled positions has been demonstrated using a focused helium ion beam. [20][21][22] Chalcogen vacancies (V X , X = S/Se), which are commonly present in TMDs, are known to introduce in-gap states. [23][24][25][26] Studies on helium-ion treated MoS 2 (Refs. [18,(20)(21)(22)27,28]) found that transitions involving such in-gap states can be optically bright and yield anti-bunched photons at sufficiently low-density defects. However, emission peaks commonly attributed to chalcogen vacancies in other TMDs are often broad (FWHM > 100 meV), lacking typical features of quantum emitters. [26,29,30] Defect engineering of atomically thin semiconducting crystals is an attractive route to developing single-photon sources and valleytronic devices. For these applications, defects with well-defined optical characteristics need to be generated in a precisely controlled manner. However, defect-induced optical features are often complicated by the presence of multiple defect species, hindering the identification of their structural origin. Here, we report systematic generation of optically active atomic defects in monolayer MoS 2 , WS 2 , MoSe 2 , and WSe 2 via proton-beam irradiation. Defect-induced emissions are found to occur ≈100 to 200 meV below the neutral exciton peak, showing typical characteristics of localized excitons such as saturation at high-excitation rates and long lifetime. Using scanning transmission electron microscopy, it is shown that freshly created chalcogen vacancies are responsible for the localized exciton emission. Density functional theory and ab initio GW plus Bethe-Salpeter-equation calculations reveal that the observed emission can be attributed to transitions involving defect levels of chalcogen vacancy and the valence band edge state.

Accurate and accessible nucleic acid diagnostics is critical to reducing the spread of COVID-19 and resuming socioeconomic activities. Here, we present an integrated platform for the direct detection of SARS-CoV-2 RNA targets near patients. Termed e lectrochemical s ystem i ntegrating r econfigurable e nzyme-DNA n anostructures ( eSIREN ), the technology leverages responsive molecular nanostructures and automated microfluidics to seamlessly transduce target-induced molecular activation into an enhanced electrochemical signal. Through responsive enzyme-DNA nanostructures, the technology establishes a molecular circuitry that directly recognizes specific RNA targets and catalytically enhances signaling; only upon target hybridization, the molecular nanostructures activate to liberate strong enzymatic activity and initiate cascading reactions. Through automated microfluidics, the system coordinates and interfaces the molecular circuitry with embedded electronics; its pressure actuation and liquid-guiding structures improve not only analytical performance but also automated implementation. The developed platform establishes a detection limit of 7 copies of RNA target per μl, operates against the complex biological background of native patient samples, and is completed in <20 min at room temperature. When clinically evaluated, the technology demonstrates accurate detection in extracted RNA samples and direct swab lysates to diagnose COVID-19 patients.

Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state—the transition state—that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/μl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples.

Figure 4. a) A microscope image of the patterned irradiated hBN flake. b) PL mapping of the same area in (a), there are 8 different regions marked with different irradiation conditions. c) PL spectra of the four circled emitters marked in (b). d) ODMR spectra of the four emitters in (b) and (c).