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.

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.

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.

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.

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.

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.

Direct Antimicrobial Susceptibility Testing on Clinical Urine Samples by Optical Tracking of Single Cell Division Events.

With the increasing prevalence of antibiotic resistance, the need to develop antimicrobial susceptibility testing (AST) technologies is urgent. The current challenge has been to perform the antibiotic susceptibility testing in short time, directly with clinical samples, and with antibiotics over a broad dynamic range of clinically relevant concentrations. Here, a technology for point-of-care diagnosis of antimicrobial-resistant bacteria in urinary tract infections, by imaging the clinical urine samples directly with an innovative large volume solution scattering imaging (LVSi) system and analyzing the image sequences with a single-cell division tracking method is developed. The high sensitivity of single-cell division tracking associated with large volume imaging enables rapid antibiotic susceptibility testing directly on the clinical urine samples. The results demonstrate direct detection of bacterial infections in 60 clinical urine samples with a 60 min LVSi video, and digital AST of 30 positive clinical samples with 100% categorical agreement with both the clinical culture results and the on-site agar plating validation results. This technology provides opportunities for precise antibiotic prescription and proper treatment of the patient within a single clinic visit.

Rapid Antimicrobial Susceptibility Testing of Patient Urine Samples Using Large Volume Free-Solution Light Scattering Microscopy.

The emergence of antibiotic resistance has prompted the development of rapid antimicrobial susceptibility testing (AST) technologies that will enable evidence-based treatment and promote antimicrobial stewardship. To date, many rapid AST methods have been developed, but few are able to be performed on clinical samples directly. Here we developed a large volume light scattering microscopy technique that tracks phenotypic features of single bacterial cells directly in clinical urine samples without sample enrichment or culturing. The technique demonstrated rapid (90 min) detection of Escherichia coli in 24 clinical urine samples with 100% sensitivity and 83% specificity and rapid (90 min) AST in 12 urine samples with 87.5% categorical agreement with two antibiotics, ampicillin and ciprofloxacin.

Quantification of epidermal growth factor receptor expression level and binding kinetics on cell surfaces by surface plasmon resonance imaging.

Epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER-1) is a membrane bound protein that has been associated with a variety of solid tumors and the control of cell survival, proliferation, and metabolism. Quantification of the EGFR expression level in cell membranes and the interaction kinetics with drugs are thus important for cancer diagnosis and treatment. Here we report mapping of the distribution and interaction kinetics of EGFR in their native environment with the surface plasmon resonance imaging (SPRi) technique. The monoclonal anti-EGFR antibody was used as a model drug in this study. The binding of the antibody to EGFR overexpressed A431 cells was monitored in real time, which was found to follow the first-order kinetics with an association rate constant (ka) and dissociation rate constant (kd) of (2.7 ± 0.6) × 10(5) M(-1) s(-1) and (1.4 ± 0.5) × 10(-4) s(-1), respectively. The dissociation constant (KD) was determined to be 0.53 ± 0.26 nM with up to seven-fold variation among different individual A431 cells. In addition, the averaged A431 cell surface EGFR density was found to be 636/µm(2) with an estimation of 5 × 10(5) EGFR per cell. Additional measurement also revealed that different EGFR positive cell lines (A431, HeLa, and A549) show receptor density dependent anti-EGFR binding kinetics. The results demonstrate that SPRi is a valuable tool for direct quantification of membrane protein expression level and ligand binding kinetics at single cell resolution. Our findings show that the local environment affects the drug-receptor interactions, and in situ measurement of membrane protein binding kinetics is important.

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.

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.

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.

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.

Umami evaluation in taste epithelium on microelectrode array by extracellular electrophysiological recording.

Umami is one of the basic tastes along with sweet, bitter, sour and salty. It is often elicited by amino acids and can provide a palatable flavor for food. With taste epithelium as the sensing element, microelectrodes can be used to evaluate umami taste by biological responses of the tissue. The electrophysiological activities to umami stimuli are measured with a 60-channel microelectrode array (MEA). Local field potential (LFP) recorded by a MEA system showed different temporal characteristics respectively with l-glutamic acid (l-Glu), l-aspartic acid (l-Asp), l-monosodium glutamate (l-MSG) and l-monosodium aspartate (l-MSA), while remarkable differences were observed between amino acids and their sodium salts. We also found that a dose-dependent behavior in the increasing concentrations of umami stimulations and a synergistic enhancement between amino acids and purine nucleotides can be detected. The investigation of this evaluation for umami represents a promising approach for distinguishing and evaluating umami tastants.

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.

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.

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.

Olfactory epithelium biosensor: odor discrimination of receptor neurons from a bio-hybrid sensing system.

Bio-hybrid systems provide an opportunity for integrating a living bio-active unit and a proper biosensing system, to employ the unique properties of the bio-active unit. The biological olfactory system can sense and identify thousands of trace odors. The purpose of this study is to combine olfactory epithelium with microelectrode array (MEA) to establish an olfactory epithelium-MEA hybrid system to record the odor-induced electrophysiological activities of the tissue. In our experiments, extracellular potential of olfactory receptor neurons in intact epithelium were measured in the presence of ethyl ether, acetic acid, butanedione, and acetone, respectively. After the odor-induced response signals were analyzed in the time and frequency domain, the temporal characteristics of response signals were extracted. We found that olfactory epithelium-MEA hybrid system can reflect the in vitro odor information of different signal characteristics and firing modes in vitro. The bio-hybrid sensing system can represent a useful instrument to sense and detect the odorant molecules with well recognizing patterns. With the development of sensor technology, bio-hybrid systems will represent emerging and promising platforms for wide applications, ranging from health care to environmental monitoring.