Rapid and on-site wireless immunoassay of respiratory virus aerosols via hydrogel-modulated resonators.

Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.

Hydrogel-based radio frequency H2S sensor for in situ periodontitis monitoring and antibacterial treatment.

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.

Berberine inhibits intracellular Ca2+ signals in mouse pancreatic acinar cells through M3 muscarinic receptors: Novel target, mechanism, and implication.

Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca2+ oscillations, mediated through an inhibition of the muscarinic subtype 3 (M3) receptor. Patch-clamp recordings and confocal Ca2+ imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M3 receptors, further confirmed by evidence of the interaction between berberine and M3 receptors in pancreatic acinar cells.

Deep Learning-Based Culture-Free Bacteria Detection in Urine Using Large-Volume Microscopy.

Bacterial infections, increasingly resistant to common antibiotics, pose a global health challenge. Traditional diagnostics often depend on slow cell culturing, leading to empirical treatments that accelerate antibiotic resistance. We present a novel large-volume microscopy (LVM) system for rapid, point-of-care bacterial detection. This system, using low magnification (1-2×), visualizes sufficient sample volumes, eliminating the need for culture-based enrichment. Employing deep neural networks, our model demonstrates superior accuracy in detecting uropathogenic Escherichia coli compared to traditional machine learning methods. Future endeavors will focus on enriching our datasets with mixed samples and a broader spectrum of uropathogens, aiming to extend the applicability of our model to clinical samples.

Gated Photochromism of Dithienylethene-Embedded Expanded Calixphyrins.

Dithienylethene (DTE)-embedded expanded porphyrins were synthesized and confirmed to be photochemically inactive due to the lowest excited state of the expanded porphyrins. On the other hand, DTE-embedded expanded calixphyrins exhibited reversible photochromism upon UV-irradiation to form colored closed forms, which reverted to colorless open forms upon red-light irradiation. The closed forms were oxidized with DDQ or the air to lock the recorded information by converting to photochemically inactive expanded porphyrins. This was unlocked by reduction with NaBH4 to restore expanded calixphyrins with photochromism activity. These gated photochromic behaviors were demonstrated in PMMA (polymethyl methacrylate) film.

Smartphone-based portable photoelectrochemical biosensing system for point-of-care detection of urine creatinine and albumin.

Creatinine and albumin are crucial biomarkers for health monitoring and their ratio in urine is an effective approach for albuminuria assessment. Herein, to address the challenges of point-of-care and efficient analysis of the biomarkers simultaneously, we developed a fully integrated handheld smartphone-based photoelectrochemical biosensing system. A miniaturized printed circuit board included a potentiostat for photocurrent measurements and single-wavelength light-emitting diodes (LEDs) for photo-excitation, which was controlled with a Bluetooth-enabled smartphone. Graphitic carbon nitride (g-C3N4)/chitosan nanocomposites were modified on a transparent indium tin oxide (ITO) electrode as photoactive materials. Creatinine was detected through chelate formation with copper ion probes, while albumin was recognized specifically by an antigen-antibody reaction based on immunoassay. The biosensing system demonstrated good linearity and high sensitivity, with detection ranges of 100 µg mL-1 to 1500 µg mL-1 for creatinine, and 9.9 µg mL-1 to 500 µg mL-1 for albumin. Spiked artificial urine samples with different concentrations were tested to confirm the practical validity of the biosensing system, where an acceptable recovery rate ranged from 98.7% to 105.3%. This portable photoelectrochemical biosensing platform provides a convenient and cost-effective method for biofluid analysis, which has an extensive prospect in point-of-care testing (POCT) for mobile health.

A Multimodal Sensing CMOS Imager Based on Dual-Focus Imaging.

Advanced machine intelligence is empowered not only by the ever-increasing computational capability for information processing but also by sensors for collecting multimodal information from complex environments. However, simply assembling different sensors can result in bulky systems and complex data processing. Herein, it is shown that a complementary metal-oxide-semiconductor (CMOS) imager can be transformed into a compact multimodal sensing platform through dual-focus imaging. By combining lens-based and lensless imaging, visual information, chemicals, temperature, and humidity can be detected with the same chip and output as a single image. As a proof of concept, the sensor is equipped on a micro-vehicle, and multimodal environmental sensing and mapping is demonstrated. A multimodal endoscope is also developed, and simultaneous imaging and chemical profiling along a porcine digestive tract is achieved. The multimodal CMOS imager is compact, versatile, and extensible and can be widely applied in microrobots, in vivo medical apparatuses, and other microdevices.

All-MXene-Printed RF Resonators as Wireless Plant Wearable Sensors for In Situ Ethylene Detection.

Printed flexible electronics have emerged as versatile functional components of wearable intelligent devices that bridge the digital information networks with biointerfaces. Recent endeavors in plant wearable sensors provide real-time and in situ insights to study phenotyping traits of crops, whereas monitoring of ethylene, the fundamental phytohormone, remains challenging due to the lack of flexible and scalable manufacturing of plant wearable ethylene sensors. Here the all-MXene-printed flexible radio frequency (RF) resonators are presented as plant wearable sensors for wireless ethylene detection. The facile formation of additive-free MXene ink enables rapid, scalable manufacturing of printed electronics, demonstrating decent printing resolution (2.5% variation), ≈30000 S m-1 conductivity and mechanical robustness. Incorporation of MXene-reduced palladium nanoparticles (MXene@PdNPs) facilitates 1.16% ethylene response at 1 ppm with 0.084 ppm limit of detection. The wireless sensor tags are attached on plant organ surfaces for in situ and continuously profiling of plant ethylene emission to inform the key transition of plant biochemistry, potentially extending the application of printed MXene electronics to enable real-time plant hormone monitoring for precision agriculture and food industrial management.

Visual-Olfactory Synergistic Perception Based on Dual-Focus Imaging and a Bionic Learning Architecture.

The synergistic interaction of vision and olfaction is critical for both natural and artificial intelligence systems to recognize and adapt to complex environments. However, current bioinspired systems with visual and olfactory sensations are mostly assembled with separate and heterogeneous sensors, inevitably leading to bulky systems and incompatible datasets. Here, we demonstrate on-chip integration of visual and olfactory sensations through a dual-focus imaging approach. By combining lens-based visual imaging and lensless colorimetric imaging, a target object and its odor fingerprint can be captured with a single complementary metal-oxide-semiconductor imager, and the obtained multimodal images are analyzed with a bionic learning architecture for information fusion and perception. To demonstrate the capability of this system, we adapted it to food detection and achieved 100% accuracy in identifying meat freshness and category with a 10 s sampling time. In addition to the highly integrated sensor design, our approach exhibits superior accuracy and efficiency in object recognition, providing a promising approach for robotic sensing and perception.

MXene-based wireless facemask enabled wearable breath acetone detection for lipid metabolic monitoring.

Breath acetone (BrAC) detection presents a promising scheme for noninvasive monitoring of metabolic health due to its close correlation to diets and exercise-regulated lipolysis. Herein, we report a Ti3C2Tx MXene-based wireless facemask for on-body BrAC detection and real-time tracking of lipid metabolism, where Ti3C2Tx MXene serves as a versatile nanoplatform for not only acetone detection but also breath interference filtration. The incorporation of in situ grown TiO2 and short peptides with Ti3C2Tx MXene further improves the acetone sensitivity and selectivity, while TiO2-MXene interfaces facilitate light-assisted response calibration. To further realize wearable breath monitoring, a miniaturized flexible detection tag has been integrated with a commercially available facemask, which enables facile BrAC detection and wireless data transmission. Through the hierarchically designed filtration-detection-calibration-transmission system, we realize BrAC detection down to 0.31 ppm (part per million) in breath. On-body breath tests validate the facemask in dynamically monitoring of lipid metabolism, which could guide dieter, athletes, and fitness enthusiasts to arrange diets and exercise activities. The proposed wearable platform opens up new possibility toward the practice of breath analysis as well as daily lipid metabolic management.

m-Benziporphyrin(1.1.0.0)s as a Rare Example of Ring-Contracted Carbaporphyrins with Metal-Coordination Ability: Distorted Coordination Structures and Small HOMO-LUMO Gaps.

m-Benziporphyrin(1.1.0.0) and m-pyreniporphyrin(1.1.0.0) were prepared as ring-contracted carbaporphyrins. While m-Benziporphyrin(1.1.0.0) was unstable, m-pyreniporphyrin(1.1.0.0) was fairly stable. Both of their PdII complexes showed distorted coordination structures with extremely short Pd-C bonds. As compared with the reported m-benziporphyrin PdII complexes, these PdII complexes showed considerably small HOMO-LUMO gaps, despite their smaller molecular size. PdII metalation of the m-pyreniporphyrin(1.1.0.0) dimer gave the corresponding PdII complex, which showed similar distorted coordination and a smaller HOMO-LUMO gap. Finally, PdII metalation of a pyrene-sharing formal p-benziporphyrin(1.1.1.1) dimer gave a nonaromatic PdII dimer, which rearranged to an aromatic PdII complex upon treatment with alumina.

Multiplexed Chemical Sensing CMOS Imager.

A miniaturized and multiplexed chemical sensing technology is urgently needed to empower mobile devices and robots for various new applications such as mobile health and Internet of Things. Here, we show that a complementary metal-oxide-semiconductor (CMOS) imager can be turned into a multiplexed colorimetric sensing chip by coating micron-scale sensing spots on the CMOS imager surface. Each sensing spot contains nanocomposites of colorimetric sensing probes and silica nanoparticles that enhance sensing signals by several orders of magnitude. The sensitivity is spot-size-invariant, and high-performance gas sensing can be achieved on sensing spots as small as ∼10 µm. This great scalability combined with millions of pixels of a CMOS imager offers a promising platform for highly integrated chemical sensors. To prove its compatibility with mobile electronics, we have built a smartphone accessory based on this chemical CMOS sensor and demonstrated that personal health management can be achieved through the detection of gaseous biomarkers and pollutants. We anticipate that this new platform will pave the way for the widespread application of chemical sensing in mobile electronics and wearable devices.

Electronically powered drug delivery devices: considerations and challenges.

INTRODUCTION: Electronically powered drug delivery devices enable a controlled drug release route for a more convenient and painless way with reduced side effects. The current advances in microfabrication and microelectronics have facilitated miniaturization and intelligence with the integration of sensors and wireless communication modules. These devices have become an essential component of commercialized on-demand drug delivery. AREAS COVERED: This review aims to provide a concise overview of current progress in electronically powered drug devices, focusing on delivery strategies, manufacturing techniques, and control circuit design with specific examples. EXPERT OPINION: The application of electronically powered drug delivery systems is now considered a feasible therapeutic approach with improved drug release efficiency and increased patient comfort. It is anticipated that these technologies will gradually fulfill clinical needs and resolve commercialization challenges in the future. This review discusses the current advances in electronic drug delivery devices, especially focusing on designing strategies to achieve an effective drug release, as well as the perspectives and challenges for future applications in clinical therapy.

Rapid Detection of Urinary Tract Infection in 10 min by Tracking Multiple Phenotypic Features in a 30 s Large-Volume Scattering Video of Urine Microscopy.

Rapid point-of-care (POC) diagnosis of bacterial infection diseases provides clinical benefits of prompt initiation of antimicrobial therapy and reduction of the overuse/misuse of unnecessary antibiotics for nonbacterial infections. We present here a POC compatible method for rapid bacterial infection detection in 10 min. We use a large-volume solution scattering imaging (LVSi) system with low magnifications (1-2×) to visualize bacteria in clinical samples, thus eliminating the need for culture-based isolation and enrichment. We tracked multiple intrinsic phenotypic features of individual cells in a short video. By clustering these features with a simple machine learning algorithm, we can differentiate Escherichia coli from similar-sized polystyrene beads, distinguish bacteria with different shapes, and distinguish E. coli from urine particles. We applied the method to detect urinary tract infections in 104 patient urine samples with a 30 s LVSi video, and the results showed 92.3% accuracy compared with the clinical culture results. This technology provides opportunities for rapid bacterial infection diagnosis at POC settings.

Label-Free Quantification of Molecular Interaction in Live Red Blood Cells by Tracking Nanometer Scale Membrane Fluctuations.

Molecular interactions in live cells play an important role in both cellular functions and drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, while the in situ quantification of molecular interaction with surface plasmon resonance (SPR) imaging mainly worked with fixed cells due to the micro-motion related noises of live cells. Here, an optical imaging method is presented to measure the molecular interaction with live red blood cells by tracking the nanometer membrane fluctuations. The membrane fluctuation dynamics are measured by tracking the membrane displacement during glycoprotein interaction. The data are analyzed with a thermodynamic model to determine the elastic properties of the cell observing reduced membrane fluctuations under fixatives, indicating cell fixations affect membrane mechanical properties. The binding kinetics of glycoprotein to several lectins are obtained by tracking the membrane fluctuation amplitude changes on single live cells. The binding kinetics and strength of different lectins are quite different, indicating the glycoproteins expression heterogeneity in single cells. It is anticipated that the method will contribute to the understanding of mechanisms of cell interaction and communication, and have potential applications in the mechanical assessment of cancer or other diseases at the single-cell level, and screening of membrane protein targeting drugs.

Elimination of oxygen interference in the photoelectrochemical sensor with ferricyanide shield oxygen reduction for point of care testing.

As a sensitive and promising detection method, photoelectrochemical (PEC) sensor has been widely used in biochemical analysis field. However, the interferences from environment, especially dissolved oxygen, often impact the stability and precision of PEC sensors, which limit its practical applications. Here, we report a dissolved oxygen insensitive PEC sensor based on a proposed indirect electron transfer model. Through the detailed study of the charge transfer process, we determined that the photocurrent mainly comes from the electrochemical reaction between the photochemical products and the electrode, rather than direct charge transfer between the photoelectric materials and the electrode. The newly designed PEC sensor used ferricyanide to shield oxygen reduction and eliminated the influence from variable oxygen solubility. This sensor maintained robust responses over an extremely wide range (1.0-7.5 mg/L) of dissolved oxygen concentrations. To further demonstrate its capability, a smartphone based portable immunosensor was constructed for the detection of human serum albumin (HSA), which exhibited excellent stability and accuracy. The relative error of current was reduced by 81.3% over traditional electron donor solution. This work effectively improves the stability of PEC sensors, and lays the foundation for the subsequently practical applications of PEC sensor in point-of-care testing.

Smartphone-based label-free photoelectrochemical sensing of cysteine with cadmium ion chelation.

As an important amino acid, cysteine is related to the development of various diseases. The quantitative detection of cysteine is of great significance for both disease diagnosis and treatment. The current labeling methods mainly rely on fluorescent probes, making it difficult for quantitative cysteine detection in point-of-care testing (POCT). In this study, we proposed a label-free method for cysteine quantification by novel photoelectrochemical (PEC) sensing using a specific ion chelation probe. An indium tin oxide electrode loaded with nanoscale graphitic carbon nitride (g-C3N4) was used as the PEC electrode and gold nanoparticle modification was performed to further promote the charge transfer efficiency for enhanced photocurrent detection. Cadmium ions (Cd2+) were employed as the specific ion chelation probe for cysteine detection, and the formed Cd2+/cysteine chelate complex served as the electron acceptor for sensitive PEC sensing under low-power LED illumination. A portable PEC system was developed for quantitative detection of cysteine by integrating the PEC sensor, a self-designed detection circuit and a smartphone. The detected photocurrents changed linearly with the cysteine concentrations ranging from 0 µM to 40 µM, and the limit of detection is calculated to be 9.2 µM. To demonstrate the capability of this system, cysteine in spiked urine samples was quantified with a recovery rate of 96.1%-100.57%. This system provides high portability, sufficient accuracy and sensitivity, and greatly reduces the complexity and cost of point-of-care cysteine detection.

Bio-electron transfer modulated localized surface plasmon resonance biosensing with charge density monitoring.

The analysis of reactant at different regions of the bioreaction interface is significant for the study on the influence of interface condition on bioreaction. In this study, we proposed a localized surface plasmon resonance (LSPR) biosensing platform for local charge density monitoring and corresponding analytes detection based on the bio-electron transfer modulation of plasmon resonance. Core-shell nanocomposites of polyaniline coated gold nanoparticles were synthesized for the enhanced sensitivity of plasmon resonance to applied electric potential. Tin-doped indium oxide (ITO) substrates modified with the nanocomposites were used as LSPR chip for optical and electrochemical measurements simultaneously. The charge sensitivity of LSPR was verified with external electric potential modulation theoretically and experimentally. Through layer-by-layer self-assembly immobilization of glucose oxidase (GOD) on the LSPR chips, the charge transfer monitoring during the bioreaction of glucose catalysis was further demonstrated based on the bio-electron transfer modulation of LSPR. By equivalent circuit method, the charge density of the LSPR chip were detected with optical extinction peak shifts, and the limit of detection was about 0.51 µC/cm2. This bio-electron transfer modulated LSPR provides a promising approach for the detection of spatial charge densities and the evaluation of bioreaction substances at different region of single chip.

Rapid Antimicrobial Susceptibility Testing on Clinical Urine Samples by Video-Based Object Scattering Intensity Detection.

To combat the ongoing public health threat of antibiotic-resistant infections, a technology that can quickly identify infecting bacterial pathogens and concurrently perform antimicrobial susceptibility testing (AST) in point-of-care settings is needed. Here, we develop a technology for point-of-care AST with a low-magnification solution scattering imaging system and a real-time video-based object scattering intensity detection method. The low magnification (1-2×) optics provides sufficient volume for direct imaging of bacteria in urine samples, avoiding the time-consuming process of culture-based bacterial isolation and enrichment. Scattering intensity from moving bacteria and particles in the sample is obtained by subtracting both spatial and temporal background from a short video. The time profile of scattering intensity is correlated with the bacterial growth rate and bacterial response to antibiotic exposure. Compared to the image-based bacterial tracking and counting method we previously developed, this simple image processing algorithm accommodates a wider range of bacterial concentrations, simplifies sample preparation, and greatly reduces the computational cost of signal processing. Furthermore, development of this simplified processing algorithm eases implementation of multiplexed detection and allows real-time signal readout, which are essential for point-of-care AST applications. To establish the method, 130 clinical urine samples were tested, and the results demonstrated an accuracy of ∼92% within 60-90 min for UTI diagnosis. Rapid AST of 55 positive clinical samples revealed 98% categorical agreement with both the clinical culture results and the on-site parallel AST validation results. This technology provides opportunities for prompt infection diagnosis and accurate antibiotic prescriptions in point-of-care settings.

A Robust Porphyrin-Stabilized Triplet Carbon Diradical.

The synthesis of robust high-spin carbon radicals is an important topic in organic chemistry. Toward this end, several porphyrin-stabilized radicals have been systematically explored. A singly naphthalene-fused porphyrin radical was synthesized by a reaction sequence consisting of a Suzuki-Miyaura coupling of ß-borylated porphyrin with 2-bromobenzaldehyde, addition of mesityl Grignard reagent, intramolecular Friedel-Crafts alkylation, and final oxidation with DDQ or tBuOK/O2 . This strategy was also used to synthesize doubly naphthalene-fused porphyrins and syn- and anti-fused-anthracene-bridged porphyrin dimers. While singly naphthalene-fused porphyrin radical has been shown to be a stable monoradical, doubly naphthalene-fused porphyrins and anti-fused-anthracene-bridged porphyrin dimers have been shown to be closed-shell molecules. Finally, the syn-dimer was characterized as a surprisingly stable radical (t1/2 =28 days under ambient air and at 80 °C) that is storable for more than several months, despite its high-spin triplet ground-state carbon diradical.