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Smart city and innovative building strategies are becoming increasingly more necessary because advancing a sustainable building system is regarded as a promising solution to overcome the depleting water and energy. However, current sustainable building systems mainly focus on energy saving and miss a holistic integration of water regeneration and energy generation. Here, we present a theoretical study of a solar optics-based active panel (SOAP) that enables both solar energy storage and photothermal disinfection of greywater simultaneously. Solar collector efficiency of energy storage and disinfection rate of greywater have been investigated. Due to the light focusing by microlens, the solar collector efficiency is enhanced from 25% to 65%, compared to that without the microlens. The simulation of greywater sterilization shows that 100% disinfection can be accomplished by our SOAP for different types of bacteria including Escherichia coli. Numerical simulation reveals that our SOAP as a lab-on-a-wall system can resolve the water and energy problem in future sustainable building systems.

The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

We present a simple, ultra-rapid and robust method to create sharp nanostructures-nanopetals-in a shape memory polymer substrate demonstrating unprecedented enhancements for surface enhanced sensing over large surface areas. These bimetallic nanostructures demonstrate extremely strong surface plasmon resonance effects due to the high density multifaceted petal structures that increase the probability of forming nanogaps. We demonstrate that our nanopetals exhibit extremely strong surface plasmons, confining the emission and enhancing the fluorescence intensity of the nearby high-quantum yield fluorescein by >4000×. The enhancements are confined to the extremely small volumes at the nanopetal borders. This enables us to achieve single molecule detection at relatively high and physiological concentrations. © 2010 American Institute of Physics.

(Figure Presented) Controllable biaxial and uniaxial nanowrinkles (see figure) are fabricated by a simple two-step approach - metal deposition and subsequent heating - based on shape memory polymer (prestressed polystyrene) sheets. The wavelengths of the wrinkles can be tuned by controlling the thickness of deposited metal. The ready integration of the nanowrinkles into microchannels and their effectiveness in surface enhanced sensing is demonstrated. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Precise and rapid disease detection is critical for controlling infectious diseases like COVID-19. Current technologies struggle to simultaneously identify viral RNAs and host immune antibodies due to limited integration of sample preparation and detection. Here, we present acoustofluidic integrated molecular diagnostics (AIMDx) on a chip, a platform enabling high-speed, sensitive detection of viral immunoglobulins [immunoglobulin A (IgA), IgG, and IgM] and nucleic acids. AIMDx uses acoustic vortexes and Gor'kov potential wells at a 1/10,000 subwavelength scale for concurrent isolation of viruses and antibodies while excluding cells, bacteria, and large (>200 nanometers) vesicles from saliva samples. The chip facilitates on-chip viral RNA enrichment, lysis in 2 minutes, and detection via transcription loop-mediated isothermal amplification, alongside electrochemical sensing of antibodies, including mucin-masked IgA. AIMDx achieved nearly 100% recovery of viruses and antibodies, a 32-fold RNA detection improvement, and an immunity marker sensitivity of 15.6 picograms per milliliter. This breakthrough provides a transformative tool for multiplex diagnostics, enhancing early infectious disease detection.

The emergence of antibiotic resistance has become a global health crisis, and everyone must arm themselves with wisdom to effectively combat the "silent tsunami" of infections that are no longer treatable with antibiotics. However, the overuse or inappropriate use of unnecessary antibiotics is still routine for administering them due to the unavailability of rapid, precise, and point-of-care assays. Here, a rapid antimicrobial-resistance point-of-care identification device (RAPIDx) is reported for the accurate and simultaneous identification of bacterial species (genotype) and target enzyme activity (phenotype). First, a contamination-free active target enzyme is extracted via the photothermal lysis of preconcentrated bacteria cells on a nanoplasmonic functional layer on-chip. Second, the rapid, precise identification of pathogens is achieved by the photonic rolling circle amplification of DNA on a chip. Third, the simultaneous identification of bacterial species (genotype) and target enzyme activity (phenotype) is demonstrated within a sample-to-answer 45 min operation via the RAPIDx. It is believed that the RAPIDx will be a valuable method for solving the bottleneck of employing on-chip nanotechnology for antibiotic-resistant bioassay and other infectious diseases., (© 2024 Wiley‐VCH GmbH.)

Acoustic manipulation has emerged as a valuable tool for precision controls and dynamic programming of cells and particles. However, conventional acoustic manipulation approaches lack the finesse necessary to form intricate, configurable, continuous, and 3D patterning of particles. Here, this study reports acoustography by Beam Engineering and Acoustic Control Node (BEACON), which delivers intricate, configurable patterns by guiding particles along custom paths with independent phase modulation. Leveraging analytical methods of orbital angular momentum beam via iterative Wirtinger hologram algorithm, this study accomplish acoustography by facilitating orbital angular momentum traps, enabling continuous 2D and 3D acoustic manipulation of microparticles in any desired geometry, with phase modulation independent of intensity. Utilizing on-chip acoustography, the BEACON platform markedly increases the space-bandwidth product to 31 000 while attaining an enhanced resolution with a pixel size of ≈25 µm, surpassing the typical resolution of over 200 µm in previous holographic particle manipulation methods. The capabilities of BEACON are demonstrated in creating intricate triple helical tracing structures using microdroplets (20 µm in diameter) and those carrying DNA to validate the effectiveness of the acoustography and phase control methods. This study offers new particle manipulation opportunities, paving the way for next-generation biomedical systems and the future of contact-free precision manufacturing., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Laboratory automation technologies have revolutionized biomedical research. However, the availability of automation solutions at the single-cell level remains scarce, primarily owing to the inherent challenges of handling cells with such small dimensions in a precise, biocompatible manner. Here, we present a single-cell-level laboratory automation solution that configures various experiments onto standardized, microscale test-tube matrices via our precise ultrasonic liquid sample ejection technology, known as PULSE. PULSE enables the transformation of titer plates into microdroplet arrays by printing nanodrops and single cells acoustically in a programmable, scalable, and biocompatible manner. Unlike pipetting robots, PULSE enables researchers to conduct biological experiments using single cells as anchoring points (e.g., 1 cell vs. 1000 cells per "tube"), achieving higher resolution and potentially more relevant data for modeling and downstream analyses. We demonstrate the ability of PULSE to perform biofabrication, precision gating, and deterministic array barcoding via preallocated droplet-addressable primers. Single cells can be gently printed at a speed range of 5-20 cell⋅s -1 with an accuracy of 90.5-97.7%, which can then adhere to the substrate and grow for up to 72 h while preserving cell integrity. In the deterministic barcoding experiment, 95.6% barcoding accuracy and 2.7% barcode hopping were observed by comparing the phenotypic data with known genotypic data from two types of single cells. Our PULSE platform allows for precise and dynamic analyses by automating experiments at the single-cell level, offering researchers a powerful tool in biomedical research., Competing Interests: Conflict of interest: The authors declare competing financial interests: T.J.H. has co-founded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers. All the other authors declare that they have no competing interests. Details are available in the online version of the paper. Ethical declarations: This study does not involve any direct interaction with human participants or collection of personal information. Model organisms were acquired in fixed format from Duke Z-Core and Meyer’s Lab. All experiments were performed in compliance with the relevant laws and the guidelines of Institutional Animal Care and Use Committee (IACUC) at Duke University., (© 2024. The Author(s).)

Advanced biofabrication techniques can create tissue-like constructs that can be applied for reconstructive surgery or as in vitro three-dimensional (3D) models for disease modeling and drug screening. While various biofabrication techniques have recently been widely reviewed in the literature, acoustics-based technologies still need to be explored. The rapidly increasing number of publications in the past two decades exploring the application of acoustic technologies highlights the tremendous potential of these technologies. In this review, we contend that acoustics-based methods can address many limitations inherent in other biofabrication techniques due to their unique advantages: noncontact manipulation, biocompatibility, deep tissue penetrability, versatility, precision in-scaffold control, high-throughput capabilities, and the ability to assemble multilayered structures. We discuss the mechanisms by which acoustics directly dictate cell assembly across various biostructures and examine how the advent of novel acoustic technologies, along with their integration with traditional methods, offers innovative solutions for enhancing the functionality of organoids. Acoustic technologies are poised to address fundamental challenges in biofabrication and tissue engineering and show promise for advancing the field in the coming years., Competing Interests: Conflict of interest T.J.H. has co-founded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers., (© 2024. The Author(s).)

Quantum mechanics is applied to create numerous electronic devices, including lasers, electron microscopes, magnetic resonance imaging, and quantum information technology. However, the practical realization of cavity quantum electrodynamics (QED) in various applications is limited due to the demanding conditions required for achieving strong coupling between an optical cavity and excitonic matter. Here, we present biological cavity QED with self-aligned nanoring doublets: QED-SANDs, which exhibit robust room-temperature strong coupling with a biomolecular emitter, chlorophyll- a . We observe the emergence of plasmon-exciton polaritons, which manifest as a bifurcation of the plasmonic scattering peak of biological QED-SANDs into two distinct polariton states with Rabi splitting up to ∼200 meV. We elucidate the mechanistic origin of strong coupling using finite-element modeling and quantify the coupling strength by employing temporal coupled-mode theory to obtain the coupling strength up to approximately 3.6 times the magnitude of the intrinsic decay rate of QED-SANDs. Furthermore, the robust presence of the polaritons is verified through photoluminescence measurements at room temperature, from which strong light emission from the lower polariton state is observed, while emission from the upper polariton state is quenched. QED-SANDs present significant potential for groundbreaking insights into biomolecular behavior in nanocavities, especially in the context of quantum biology.

Thioesterase superfamily member 2 (Them2), a long-chain fatty acyl-CoA thioesterase that is highly expressed in oxidative tissues, interacts with phosphatidylcholine transfer protein (PC-TP) to regulate hepatic lipid and glucose metabolism and to suppress insulin signaling. High-fat diet-fed mice lacking Them2 globally or specifically in skeletal muscle, but not liver, exhibit reduced hepatic steatosis and insulin resistance. Here, we report that the capacity of Them2 in skeletal muscle to promote hepatic steatosis and insulin resistance depends on both its catalytic activity and interaction with PC-TP. Two residues of Them2 catalytic site were mutated (N50A/D65A) to produce the inactive enzyme while maintaining its homotetrameric structure and interaction with PC-TP. Restoration of skeletal muscle expression in Them2 -/- mice using recombinant adeno-associated virus revealed that WT, but not N50A/D65A Them2, promoted high-fat diet-induced weight gain and hepatic steatosis. This was accompanied by greater impairment of insulin sensitivity in WT than N50A/D65A Them2. Pharmacological inhibition or genetic ablation of PC-TP attenuated these effects. In reductionist experiments, conditioned medium collected from WT primary cultured myotubes promoted excess lipid accumulation in oleic acid-treated primary cultured hepatocytes relative to Them2 -/- myotubes, which was attributable to secreted extracellular vesicles. Reconstitution of Them2 expression in Them2 -/- myotubes affirmed the requirements for catalytic activity and PC-TP interactions for extracellular vesicles to promote lipid accumulation in hepatocytes. These studies provide valuable mechanistic insights, whereby Them2 in skeletal muscle promotes hepatic steatosis and establish both Them2 and PC-TP as attractive targets for managing metabolic dysfunction-associated steatotic liver disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Kidney organoids, replicating human development, pathology, and drug responses, are a promising model for advancing bioscience and pharmaceutical innovation. However, reproducibility, accuracy, and quantification challenges hinder their broader utility for advanced biological and pharmaceutical applications. Herein, we present a dynamic kidney organoid microphysiological analysis platform (MAP), designed to enhance organoid modeling and assays within physiologically relevant environments, thereby expanding their utility in advancing kidney physiology and pathology research. First, precise control of the dynamic microenvironment in MAP enhances the ability to fine-tune nephrogenic intricacies, facilitating high-throughput and reproducible human kidney organoid development. Also, MAP's miniaturization of kidney organoids significantly advances pharmaceutical research by allowing for detailed analysis of entire nephron segments, which is crucial for assessing the nephrotoxicity and safety of drugs. Furthermore, the MAP's application in disease modeling faithfully recapitulates pathological development and functions as a valuable testbed for therapeutic exploration in polycystic kidney diseases. We envision the kidney organoid MAP enhancing pharmaceutical research, standardizing processes, and improving analytics, thereby elevating the quality and utility of organoids in biology, pharmacology, precision medicine, and education.

Monitoring the health conditions of the environment and humans is essential for ensuring human well-being, promoting global health, and achieving sustainability. Innovative biosensors are crucial in accurately monitoring health conditions, uncovering the hidden connections between the environment and human well-being, and understanding how environmental factors trigger autoimmune diseases, neurodegenerative diseases, and infectious diseases. This review evaluates the use of nanoplasmonic biosensors that can monitor environmental health and human diseases according to target analytes of different sizes and scales, providing valuable insights for preventive medicine. We begin by explaining the fundamental principles and mechanisms of nanoplasmonic biosensors. We investigate the potential of nanoplasmonic techniques for detecting various biological molecules, extracellular vesicles (EVs), pathogens, and cells. We also explore the possibility of wearable nanoplasmonic biosensors to monitor the physiological network and healthy connectivity of humans, animals, plants, and organisms. This review will guide the design of next-generation nanoplasmonic biosensors to advance sustainable global healthcare for humans, the environment, and the planet.

Lateral flow assay (LFA) systems use metal nanoparticles for rapid and convenient target detection and are extensively studied for the diagnostics of various diseases. Gold nanoparticles (AuNPs) are often used as probes in LFAs, displaying a single red color. However, there is a high demand for colorimetric LFAs to detect multiple biomarkers, requiring the use of multicolored NPs. Here, we present a highly sensitive multiplexed colorimetric lateral flow immunoassay by multicolored Plasmon-controlled metal-silica Isoform Nanocomposites (PINs). We utilized the localized surface plasmon resonance effect to create multi-colored PINs by precisely adjusting the distance between the NPs on the surface of PINs through the controlled addition of reduced gold and silver precursors. Through simulations, we also confirmed that the distance between nanoparticles on the surface of PINs significantly affects the color and colorimetric signal intensity of the PINs. We achieved multicolored PINs that exhibit stronger colorimetric signals, offering a new solution for LFA detection with high sensitivity and a 33 times reduced limit of detection (LOD) while maintaining consistent size deviations within 5%. We expect that our PINs-based colorimetric LFA will facilitate the sensitive and simultaneous detection of multiple biomarkers in point-of-care testing., (© 2024. The Author(s).)

Preeclampsia is a hypertensive disorder of pregnancy that can lead to stillbirth and preterm birth if not treated promptly. Currently, the diagnosis of preeclampsia relies on clinical symptoms such as hypertension and proteinuria, along with invasive blood tests. Here, we investigate the role of soluble proteins and exosomes in noninvasive diagnosing preeclampsia non-invasively using maternal urine and urine-derived exosomes. We quantified the levels of particles and the presence of TSG101 and CD63 in urine and urinary exosomes via the biologically intact exosome separation technology (BEST) platform. Then, we obtained higher levels of soluble proteins such as fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) from urine as it was than urinary exosomes. Compared to commercial blood tests, the sensitivity of the sFlt-1/PlGF ratio was found to be 4.0 times higher in urine tests and 1.5 times higher in tests utilizing urine-derived exosomes. Our findings offer promising possibilities for the early and non-invasive identification of high-risk individuals at risk of preeclampsia, allowing for comprehensive preventive management., (© 2024. The Author(s).)

Background: Membranous nephropathy (MN) is a specific autoimmune disease affecting kidneys. It is characterized by the accumulation of immune complexes in the glomerular basement membrane. Renal biopsy is currently the standard procedure to confirm the diagnosis, although the presence of autoantibodies against the phospholipase A2 receptor (PLA2R) can also help diagnose. In this study, we aimed to investigate the potential of urinary exosomes as noninvasive markers for diagnosing MN., Methods: Exosomes were extracted from urine samples of five patients with MN and four healthy controls. The concentration of PLA2R was measured in both urine and isolated exosomes using enzyme-linked immunosorbent assay techniques. The measurements were adjusted based on the urine creatinine (UCr) level of each participant., Results: The levels of PLA2R/UCr were investigated in urine and urine-derived exosomes from patients and controls. Results of the analysis revealed significantly higher expression of PLA2R/UCr in patients compared to the control group (p < 0.05). Furthermore, the expression level of PLA2R/UCr was higher in urine-derived exosomes than in urine samples. Additionally, a positive correlation was observed between the expression levels of PLA2R/UCr and the urine protein-to-creatinine ratio, with urine-derived exosomes exhibiting a stronger correlation than urine samples., Conclusion: Studies have indicated that measuring exosomal PLA2R/UCr levels in urine could be a noninvasive method for diagnosing MN. Using urine-derived exosomes could also reduce the burden of performing a biopsy on patients and facilitate follow-up treatment, such as monitoring for future recurrence.

Mycobacterium tuberculosis (MTB) is a pathogen that is known for its ability to persist in harsh environments and cause chronic infections. Understanding the regulatory networks of MTB is crucial for developing effective treatments. Small regulatory RNAs (sRNAs) play important roles in gene expression regulation in all kingdoms of life, and their classification based solely on genomic location can be imprecise due to the computational-based prediction of protein-coding genes in bacteria, which often neglects segments of mRNA such as 5'UTRs, 3'UTRs, and intercistronic regions of operons. To address this issue, our study simultaneously discovered genomic features such as TSSs, UTRs, and operons together with sRNAs in the M. tuberculosis H37Rv strain (ATCC 27294) across multiple stress conditions. Our analysis identified 1,376 sRNA candidates and 8,173 TSSs in MTB, providing valuable insights into its complex regulatory landscape. TSS mapping enabled us to classify these sRNAs into more specific categories, including promoter-associated sRNAs, 5'UTR-derived sRNAs, 3'UTR-derived sRNAs, true intergenic sRNAs, and antisense sRNAs. Three of these sRNA candidates were experimentally validated using 3'-RACE-PCR: predictedRNA&#95;0240, predictedRNA&#95;0325, and predictedRNA&#95;0578. Future characterization and validation are necessary to fully elucidate the functions and roles of these sRNAs in MTB. Our study is the first to simultaneously unravel TSSs and sRNAs in MTB and demonstrate that the identification of other genomic features, such as TSSs, UTRs, and operons, allows for more accurate and specific classification of sRNAs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification and quantification in diverse fields such as life sciences, global health, medicine, agricultural science, forensic science, and environmental science for global sustainability. However, implementing a cost-effective PCR remains challenging for rapid preventive medical action to the widespread pandemic diseases due to the absence of highly efficient and low-cost PCR chip-based POC molecular diagnostics. Here, this work reports an ultrafast metaphotonic PCR chip as a solution of a cost-effective and low-power-consumption POC device for the emerging global challenge of sustainable healthcare. This work designs a near-perfect photonic meta-absorber using ring-shaped titanium nitride to maximize the photothermal effect and realize rapid heating and cooling cycles during the PCR process. This work fabricates a large-area photonic meta-absorber on a 6-inch wafer cost-effectively using simple colloidal lithography. In addition, this work demonstrates 30 thermocycles from 65 (annealing temperature) to 95 °C (denaturation temperature) within 3 min 15 s, achieving an average 16.66 °C s -1 heating rate and 7.77 °C s -1 cooling rate during thermocycling, succeeding rapid metaphotonic PCR. This work believes a metaphotonic PCR chip can be used to create a low-cost, ultrafast molecular diagnostic chip with a meta-absorber., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

The isolation of viruses from complex biological samples is essential for creating sensitive bioassays that assess the efficacy and safety of viral therapeutics and vaccines, which have played a critical role during the COVID-19 pandemic. However, existing methods of viral isolation are time-consuming and labor-intensive due to the multiple processing steps required, resulting in low yields. Here, we introduce the rapid, efficient, and high-resolution acoustofluidic isolation of viruses from complex biological samples via Bessel beam excitation separation technology (BEST). BEST isolates viruses by utilizing the nondiffractive and self-healing properties of 2D, in-plane acoustic Bessel beams to continuously separate cell-free viruses from biofluids, with high throughput and high viral RNA yield. By tuning the acoustic parameters, the cutoff size of isolated viruses can be easily adjusted to perform dynamic, size-selective virus isolation while simultaneously trapping larger particles and separating smaller particles and contaminants from the sample, achieving high-precision isolation of the target virus. BEST was used to isolate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from human saliva samples and Moloney Murine Leukemia Virus from cell culture media, demonstrating its potential use in both practical diagnostic applications and fundamental virology research. With high separation resolution, high yield, and high purity, BEST is a powerful tool for rapidly and efficiently isolating viruses. It has the potential to play an important role in the development of next-generation viral diagnostics, therapeutics, and vaccines.

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

In some patients, COVID-19 can trigger neurological symptoms with unclear pathogenesis. Here we describe a microphysiological system integrating alveolus and blood-brain barrier (BBB) tissue chips that recapitulates neuropathogenesis associated with infection by SARS-CoV-2. Direct exposure of the BBB chip to SARS-CoV-2 caused mild changes to the BBB, and infusion of medium from the infected alveolus chip led to more severe injuries on the BBB chip, including endothelial dysfunction, pericyte detachment and neuroinflammation. Transcriptomic analyses indicated downregulated expression of the actin cytoskeleton in brain endothelium and upregulated expression of inflammatory genes in glial cells. We also observed early cerebral microvascular damage following lung infection with a low viral load in the brains of transgenic mice expressing human angiotensin-converting enzyme 2. Our findings suggest that systemic inflammation is probably contributing to neuropathogenesis following SARS-CoV-2 infection, and that direct viral neural invasion might not be a prerequisite for this neuropathogenesis. Lung-brain microphysiological systems should aid the further understanding of the systemic effects and neurological complications of viral infection., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Small-reactor-based polymerase chain reaction (PCR) has attracted considerable attention. A significant number of tiny reactors must be prepared in parallel to capture, amplify, and accurately quantify few target genes in clinically relevant large volume, which, however, requires sophisticated microfabrication and longer sample-to-answer time. Here, single plasmonic cavity membrane is reported that not only enriches and captures few nucleic acids by taking advantage of both capillarity and hydrodynamic trapping but also quickly amplifies them for sensitive plasmonic detection. The plasmonic cavity membrane with few nanoliters in a void volume is fabricated by self-assembling gold nanorods with SiO 2 tips. Simulations reveal that hydrodynamic stagnation between the SiO 2 tips is mainly responsible for the trapping of the nucleic acid in the membrane. Finally, it is shown that the plasmonic cavity membrane is capable of enriching severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes up to 20 000-fold within 1 min, amplifying within 3 min, and detecting the trace genes as low as a single copy µL -1 . It is anticipated that this work not only expands the utility of PCR but also provides an innovative way of the enrichment and detection of trace biomolecules in a variety of point-of-care testing applications., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Extracellular vesicles (EVs) are promising tools for the early diagnosis of diseases, and bacterial membrane vesicles (MVs) are especially important in health and environment monitoring. However, detecting EVs or bacterial MVs presents significant challenges for the clinical translation of EV-based diagnostics. In this Review, we provide a comprehensive discussion on the basics of nanoplasmonic sensing and emphasize recent developments in nanoplasmonics-based optical sensors to effectively identify EVs or bacterial MVs. We explore various nanoplasmonic sensors tailored for EV or bacterial MV detection, emphasizing the application of localized surface plasmon resonance through gold nanoparticles and their multimers. Additionally, we highlight advanced EV detection techniques based on surface plasmon polaritons using plasmonic thin film and nanopatterned structures. Furthermore, we evaluate the improved detection capability of surface-enhanced Raman spectroscopy in identifying and classifying these vesicles, aided by plasmonic nanostructures. Nanoplasmonic sensing techniques have remarkable precision and sensitivity, making them a potential tool for accurate EV detection in clinical applications, facilitating point-of-care molecular diagnostics. Finally, we summarize the challenges associated with nanoplasmonic EV or bacterial MV sensors and offer insights into potential future directions for this evolving field., (© 2024. The Author(s).)

Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Soap bubbles exhibit abundant fascinating phenomena throughout the entire life of evolution with different fundamental physics governing them. Nevertheless, the complicated dynamics of small objects in soap films are still unrevealed. Here, we report the first observation of spontaneous particle ordering in a complicated galaxy of soap films without any external energy. The balance of interfacial tension at two liquid-gas interfaces is theoretically predicted to govern belted wetted particles (BWPs) traveling along a specified path spontaneously. Such spontaneous particle path-finding is found to depend on the particle size and hydrophilic properties. Spontaneous particle sorting is directly realized via these discrete and distinctive paths for different particles. The deformation of the soap membrane facilitates 1D/2D particle organization along the path. This observation represents the discovery of a new spontaneous order phenomenon in soap film systems and provides a new energy-free approach for particle separation and soft colloidal crystal assembly.

Hybridization of microbial cells with inorganic nanoparticles that could dramatically improve cellular functions such as electron transfer has been realized by the random attachment or stochastic entry of the nanoparticles. Clearly, the selective growth of inorganic nanoparticles on target functional organelles is ideal for such hybridization. Here, we report the selective growth of gold nanocrystals in the intermembrane space (IMS) of Escherichia coli by exploiting the electron transport chain (ETC). We systematically show that gold ions are permeated through porins in the outer membrane of E. coli and further reduced to gold nanocrystals by the ETC in live E. coli . We directly observe that the resulting gold nanocrystals exist only in the IMS by transmission electron microscopy measurements of cross-sectioned E. coli . Molecular dynamics simulations suggest that once gold ions are reduced to small nuclei by the ETC, the nuclei can be stably physisorbed onto ETC complexes, further supporting the ETC-mediated growth. Finally, we show that the ATP synthesis of E. coli where gold nanocrystals are formed in the IMS is up to 9 times higher than that of E. coli alone. We believe that our work can significantly contribute to not only improving microbial metabolic functions for biological energy conversion but also restoring physiological dysfunctions of microbial cells for biomedicine.

Alzheimer's disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/μL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aβ EVs at different time courses, and compared them with intraneuronal Aβ cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer's and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.

Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs., (© 2024. The Author(s).)

Efficient isolation and analysis of exosomal biomarkers hold transformative potential in biomedical applications. However, current methods are prone to contamination and require costly consumables, expensive equipment, and skilled personnel. Here, we introduce an innovative spaceship-like disc that allows Acoustic Separation and Concentration of Exosomes and Nucleotide Detection: ASCENDx. We created ASCENDx to use acoustically driven disc rotation on a spinning droplet to generate swift separation and concentration of exosomes from patient plasma samples. Integrated plasmonic nanostars on the ASCENDx disc enable label-free detection of enriched exosomes via surface-enhanced Raman scattering. Direct detection of circulating exosomal microRNA biomarkers from patient plasma samples by the ASCENDx platform facilitated a diagnostic assay for colorectal cancer with 95.8% sensitivity and 100% specificity. ASCENDx overcomes existing limitations in exosome-based molecular diagnostics and holds a powerful position for future biomedical research, precision medicine, and point-of-care medical diagnostics.

A PCR- and sequencing-free mutation detection assay facilitates cancer diagnosis and reduces over-reliance on specialized equipment. This benefit was highlighted during the pandemic when high demand for viral nucleic acid testing often sidelined mutation analysis. This shift led to substantial challenges for patients on targeted therapy in tracking mutations. Here, we report a 30-minute DNA mutation detection technique using Cas12a-loaded liposomes in a microplate reader, a fundamental laboratory tool. CRISPR-Cas12a complex and fluorescence-quenching (FQ) probes are introduced into tumor-derived extracellular vesicles (EV) through membrane fusion. When CRISPR-RNA hybridizes with the DNA target, activated Cas12a can trans -cleave FQ probes, resulting in fluorescence signals for the quantification of DNA mutation. Future advancements in multiplex and high-throughput mutation detection using this assay will streamline self-diagnosis and treatment monitoring at home., Competing Interests: Competing interests The authors declare no conflict of interest.

Rapid, sensitive, inexpensive point-of-care molecular diagnostics are crucial for the efficient control of spreading viral diseases and biosecurity of global health. However, the gold standard, polymerase chain reaction (PCR) is time-consuming and expensive and needs specialized testing laboratories. Here, we report a low-cost yet fast, selective, and sensitive Plasmonic Optical Wells-Based Enhanced Rate PCR: POWER-PCR. We optimized the efficient optofluidic design of 3D plasmonic optical wells via the computational simulation of light-to-heat conversion and thermophoretic convection in a self-created plasmonic cavity. The POWER-PCR chamber with a self-passivation layer can concentrate incident light to accumulate molecules, generate rapid heat transfer and thermophoretic flow, and minimize the quenching effect on the naked Au surface. Notably, we achieved swift photothermal cycling of nucleic acid amplification in POWER-PCR on-a-chip in 4 min 24 s. The POWER-PCR will provide an excellent solution for affordable and sensitive molecular diagnostics for precision medicine and preventive global healthcare.

Extracellular vesicles (EVs) have been identified as promising biomarkers for the noninvasive diagnosis of various diseases. However, challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities. Here, we report a high-yield ( > 90%) and rapid ( < 10 min) EV isolation method called FLocculation via Orbital Acoustic Trapping (FLOAT). The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets. By adding a thermoresponsive polymer flocculant, nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet. We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein, addressing a significant obstacle in the development of EV-based liquid biopsies. Due to its high-yield nature, FLOAT reduces biofluid starting volume requirements by a factor of 100 (from 20 mL to 200 µL), demonstrating its promising potential in point-of-care diagnostics., Competing Interests: Conflict of interestT.J.H. has co-founded a startup company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers. All other authors declare that they have no competing interests., (© The Author(s) 2024.)

The study of molecular mechanisms at the single-cell level holds immense potential for enhancing immunotherapy and understanding neuroinflammation and neurodegenerative diseases by identifying previously concealed pathways within a diverse range of paired cells. However, existing single-cell pairing platforms have limitations in low pairing efficiency, complex manual operation procedures, and single-use functionality. Here, we report a multiparametric cellular immunity analysis by a modular acoustofluidic platform: CIAMAP. This platform enables users to efficiently sort and collect effector-target (i.e., NK92-K562) cell pairs and monitor the real-time dynamics of immunological response formation. Furthermore, we conducted transcriptional and protein expression analyses to evaluate the pathways that mediate effector cytotoxicity toward target cells, as well as the synergistic effect of doxorubicin on the cellular immune response. Our CIAMAP can provide promising building blocks for high-throughput quantitative single-cell level coculture to understand intercellular communication while also empowering immunotherapy by precision analysis of immunological synapses.

While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine., (© 2023. The Author(s).)

Polymerase chain reaction (PCR) in small fluidic systems not only improves speed and sensitivity of deoxyribonucleic acid (DNA) amplification but also achieves high-throughput quantitative analyses. However, air bubble trapping and growth during PCR has been considered as a critical problem since it causes the failure of DNA amplification. Here we report bubble-free diatom PCR by exploiting a hierarchically porous silica structure of single-celled algae. We show that femtoliters of PCR solution can be spontaneously loaded into the diatom interior without air bubble trapping due to the surface hydrophilicity and pore structure of the diatom. We discover that a large pressure gradient between air bubbles and nanopores rapidly removes residual air bubbles through the periodically arrayed nanopores during thermal cycling. We demonstrate the DNA amplification by diatom PCR without air bubble trapping and growth. Finally, we successfully detect DNA fragments of SARS-CoV-2 with as low as 10 copies/μl by devising a microfluidic device integrated with diatoms assembly. We believe that our work can be applied to many PCR applications for innovative molecular diagnostics and provides new opportunities for naturally abundant diatoms to create innovative biomaterials in real-world applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The COVID-19 outbreak has caused public and global health crises. However, the lack of on-site fast, reliable, sensitive, and low-cost reverse transcription polymerase chain reaction (RT-PCR) testing limits early detection, timely isolation, and epidemic prevention and control. Here, the authors report a rapid mobile efficient diagnostics of infectious diseases via on-chip -RT-quantitative PCR (RT-qPCR): MEDIC-PCR. First, the authors use a roll-to-roll printing process to accomplish low-cost carbon-black-based disposable PCR chips that enable rapid LED-induced photothermal PCR cycles. The MEDIC-PCR can perform RT (3 min), and PCR (9 min) steps. Further, the cohort of 89 COVID-19 and 103 non-COVID-19 patients testing is completed by the MEDIC-PCR to show excellent diagnostic accuracy of 97%, sensitivity of 94%, and specificity of 98%. This MEDIC-PCR can contribute to the preventive global health in the face of a future pandemic., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

During the last decade, organs-on-chips or organoids microphysiological analysis platforms (MAP) have garnered attention in the practical applications of disease models, drug discovery, and developmental biology. Research on pregnant women has firm limitations due to ethical issues; thus, remodelling human pregnancy in vitro is highly beneficial for treatment modality development via disease remodelling or drug monitoring. This review highlights current efforts in bioengineering devices to reproduce human pregnancy and emphasises the significant convergence of biology, engineering, and maternal-foetal medicine. First, we review recent achievements in culturing cells from tissues involved in pregnancy; specifically, trophoblasts from the placenta. Second, we highlight developments in the reconstitution of pregnancy-related female reproductive organs across several structural and functional interpretations. Last, we examine research on the fundamental comprehension of pregnancy-associated diseases to find bioengineering solutions. Recreating human pregnancy through an engineered model is naturally complex; nevertheless, challenges are inevitable to progress precision medicine., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acoustic tweezers provide an effective means for manipulating single cells and particles in a high-throughput, precise, selective and contact-free manner. The adoption of acoustic tweezers in next-generation cellular assays may advance our understanding of biological systems. Here we present a comprehensive set of instructions that guide users through device fabrication, instrumentation setup and data acquisition to study single cells with an experimental throughput that surpasses traditional methods, such as atomic force microscopy and micropipette aspiration, by several orders of magnitude. With acoustic tweezers, users can conduct versatile experiments that require the trapping, patterning, pairing and separation of single cells in a myriad of applications ranging across the biological and biomedical sciences. This procedure is widely generalizable and adaptable for investigations in materials and physical sciences, such as the spinning motion of colloids or the development of acoustic-based quantum simulations. Overall, the device fabrication requires ~12 h, the experimental setup of the acoustic tweezers requires 1-2 h and the cell manipulation experiment requires ~30 min to complete. Our protocol is suitable for use by interdisciplinary researchers in biology, medicine, engineering and physics., (© 2023. Springer Nature Limited.)

Obtaining single-molecular-level fingerprints of biomolecules and electron-transfer dynamic imaging in living cells are critically demanded in postgenomic life sciences and medicine. However, the possible solution called plasmonic resonance energy transfer (PRET) spectroscopy remains challenging due to the fixed scattering spectrum of a plasmonic nanoparticle and limited multiplexing. Here, multiplexed metasurfaces-driven PRET hyperspectral imaging, to probe biological light-matter interactions, is reported. Pixelated metasurfaces with engineered scattering spectra are first designed over the entire visible range by the precision nanoengineering of gap plasmon and grating effects of metasurface clusters. Pixelated metasurfaces are created and their full dark-field coloration is optically characterized with visible color palettes and high-resolution color printings of the art pieces. Furthermore, three different biomolecules (i.e., chlorophyll a, chlorophyll b, and cytochrome c) are applied on metasurfaces for color palettes to obtain selective molecular fingerprint imaging due to the unique biological light-matter interactions with application-specific biomedical metasurfaces. This metasurface-driven PRET hyperspectral imaging will open up a new path for multiplexed real-time molecular sensing and imaging methods., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine., (© 2023. The Author(s).)

The occurrence of acute pancreatitis (AP) is increasing significantly worldwide. However, current diagnostic methods of AP do not provide a clear clinical stratification of severity, and the prediction of complications in AP is still limited. Here, we present a robust AP identification and diagnosis (RAPIDx) method by the proteomic fingerprinting of intact nanoscale extracellular vesicles (EVs) from clinical samples. By tracking analysis of circulating biological nanoparticles released by cells ( i.e. , EVs) via bottom-up proteomics, we obtain close phenotype connections between EVs, cell types, and multiple tissues based on their specific proteomes and identify the serum amyloid A (SAA) proteins on EVs as potential biomarkers that are differentially expressed from AP patients significantly. We accomplish the quantitative analysis of EVs fingerprints using MALDI-TOF MS and find the SAA proteins (SAA1-1, desR-SAA1-2, SAA2, SAA1-2) with areas under the curve (AUCs) from 0.92 to 0.97, which allows us to detect AP within 30 min. We further realize that SAA1-1 and SAA2, combined with two protein peaks (5290.19, 14032.33 m / z ), can achieve an AUC of 0.83 for classifying the severity of AP. The RAPIDx platform will facilitate timely diagnosis and treatment of AP before severity development and persistent organ failure and promote precision diagnostics and the early diagnosis of pancreatic cancer.

The global outbreaks of infectious diseases have significantly driven an imperative demand for rapid and accurate molecular diagnostics. Nucleic acid amplification tests (NAATs) feature high sensitivity and high specificity; however, the labor-intensive sample preparation and nucleic acid amplification steps remain challenging in order to carry out rapid and precision molecular diagnostics at home. This review discusses the advances and challenges of automatic solutions of sample preparation integrated with on-chip nucleic acid amplification for effective and accurate molecular diagnostics at home. The sample preparation methods of whole blood, urine, saliva/nasal swab, and stool on chip are examined. Then, the repurposable integrated sample preparation on a chip using various biological samples is investigated. Finally, the on-chip NAATs that can be integrated with automated sample preparation are evaluated. The user-friendly approaches with combined sample preparation and NAATs can be the game changers for next-generation rapid and precision home diagnostics., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Snakebite envenoming is a medical emergency requiring urgent and specific treatment. Unfortunately, snakebite diagnostics are scarce, time-consuming and lacking specificity. Hence, this study aimed to develop a simple, quick and specific snakebite diagnostic assay using animal antibodies. Anti-venom horse immunoglobulin G (IgG) and chicken immunoglobulin Y (IgY) were produced against the venoms of four major medically important snake species in Southeast Asia, i.e., the Monocled Cobra (Naja kaouthia), Malayan Krait (Bungarus candidus), Malayan Pit Viper (Calloselasma rhodostoma), and White-lipped Green Pit Viper (Trimeresurus albolabris). Different capture:detection configurations of double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) were constructed using both immunoglobulins, and the horse IgG:IgG-HRP configuration was found to be most selective and sensitive in detecting the corresponding venoms. The method was further streamlined to develop a rapid immunodetection assay, which is able to produce a visual color change within 30 min for discrimination between different snake species. The study shows it is feasible to develop a simple, quick and specific immunodiagnostic assay using horse IgG, which can be derived directly from antisera prepared for antivenom production. The proof-of-concept indicates it is a sustainable and affordable approach in keeping with on-going antivenom manufacturing activities for specific species in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

2D transition-metal dichalcogenides (TMDs) have been successfully developed as novel ubiquitous optoelectronics owing to their excellent electrical and optical characteristics. However, active-matrix image sensors based on TMDs have limitations owing to the difficulty of fabricating large-area integrated circuitry and achieving high optical sensitivity. Herein, a large-area uniform, highly sensitive, and robust image sensor matrix with active pixels consisting of nanoporous molybdenum disulfide (MoS 2 ) phototransistors and indium-gallium-zinc oxide (IGZO) switching transistors is reported. Large-area uniform 4-inch wafer-scale bilayer MoS 2 films are synthesized by radio-frequency (RF) magnetron sputtering and sulfurization processes and patterned to be a nanoporous structure consisting of an array of periodic nanopores on the MoS 2 surface via block copolymer lithography. Edge exposure on the nanoporous bilayer MoS 2 induces the formation of subgap states, which promotes a photogating effect to obtain an exceptionally high photoresponsivity of 5.2 × 10 4 A W -1 . A 4-inch-wafer-scale image mapping is successively achieved using this active-matrix image sensor by controlling the device sensing and switching states. The high-performance active-matrix image sensor is state-of-the-art in 2D material-based integrated circuitry and pixel image sensor applications., (© 2023 Wiley-VCH GmbH.)

Discovering the secrets of diseases from tear extracellular vesicles (EVs) is well-recognized and appreciated. However, a precise understanding of the interaction network between EV populations and their biogenesis from our body requires more in-depth and systematic analysis. Here, we report the biological profiles of different-size tear EV subsets from healthy individuals and the origins of EV proteins. We have identified about 1800 proteins and revealed the preferential differences in the biogenesis among distinct subsets. We observe that eye-related proteins that maintain retinal homeostasis and regulate inflammation are preferentially enriched in medium-size EVs (100 to 200 nm) fractions. Using universal analysis in combination with the Human Protein Atlas consensus dataset, we found the genesis of tear EV proteins with 37 tissues and 79 cell types. The proteins related to retinal neuronal cells, glial cells, and blood and immune cells are selectively enriched among EV subsets. Our studies in heterogeneous tear EVs provide building blocks for future transformative precision molecular diagnostics and therapeutics.

Prompt on-site diagnosis of SARS-CoV-2 with other respiratory infections will have minimized the global impact of the COVID-19 pandemic through rapid, effective management. However, no such multiplex point-of-care (POC) chip has satisfied a suitable sensitivity of gold-standard nucleic acid amplification tests (NAATs). Here, a rapid multiplexed ultrasensitive sample-to-answer loop-mediated isothermal amplification (MUSAL) chip operated by simple LED-driven photothermal amplification to detect six targets from single-swab sampling is presented. First, the MUSAL chip allows ultrafast on-chip sample preparation with ≈500-fold preconcentration at a rate of 1.2 mL min -1 . Second, the chip enables contamination-free amplification using autonomous target elution into on-chip reagents by photothermal activation. Finally, the chip accomplishes multiplexed on-chip diagnostics of SARS-CoV-2 and influenza viruses with a limit of detection (LoD) of 0.5 copies µL -1 . The rapid, ultrasensitive, cost-effective sample-to-answer chip with a multiplex capability will allow timely management of various pandemics situations that may be faced shortly., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine., (© 2023. The Author(s).)