{"title":"High-throughput and multimodal profiling of antigen-specific T cells with a droplet-based cell-cell interaction screening platform","authors":"","doi":"10.1016/j.bios.2024.116815","DOIUrl":"10.1016/j.bios.2024.116815","url":null,"abstract":"<div><div>Identifying antigen-specific T cells from tumor-infiltrating lymphocytes is essential for designing effective T cell immunotherapies. Traditional methods can detect antigen-specific T cells but struggle with high-throughput screening and multimodal profiling simultaneously. To address this issue, we developed DropCCI, a new strategy that transfers antigen information to co-incubated T cells for high-throughput, non-contaminated multimodal profiling. In DropCCI, droplets encapsulated DNA barcodes and antigen-loaded antigen-presenting cells (APCs), while click chemistry-modified T cells were injected into these droplets to capture free barcodes and acquire the corresponding antigen information. Following cell-cell interaction, APCs were removed via streptavidin-biotin conjugation, to prevent contamination. The resulting T cells underwent single-cell omics sequencing for comprehensive profiling of their antigen specificity, transcriptome, and genomics accurately. This click-chemistry method allowed detection of antigen-specific T cells without lysing APCs, avoiding cross-cell contamination and enabling low-noise multimodal profiling of primary T cells. With a completion time within 12 h and no requirement for complex equipment, DropCCI provides unbiased single-cell sequencing results that offer a comprehensive understanding of anti-tumor T cell responses. The concept of DropCCI holds great promise not only for advancing the field of T cell immunotherapy but also for its potential application in studying other cell-cell interactions.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A light-addressable potentiometric sensor-based extracellular calcium dynamic monitoring and imaging platform for cellular calcium channel drug evaluation","authors":"","doi":"10.1016/j.bios.2024.116814","DOIUrl":"10.1016/j.bios.2024.116814","url":null,"abstract":"<div><div>Disruption and dysregulation of cellular calcium channel function can lead to diseases such as ischemic stroke, heart failure, and arrhythmias. Corresponding calcium channel drugs typically require preliminary efficacy evaluations using in vitro models such as cells and simulated tissues before clinical testing. However, traditional detection and evaluation methods often encounter challenges in long-term continuous monitoring and lack calcium specificity. In this study, a dynamic monitoring system based on ion-sensitive membranes for light-addressable potentiometric sensor (LAPS) was developed to meet the demand for monitoring changes in extracellular calcium ion (Ca<sup>2+</sup>) concentration in live cells. The effects of Ca<sup>2+</sup> channel agonists and blockers on 2D and 3D HL-1 cells were investigated, with changes in extracellular Ca<sup>2+</sup> concentration reflecting cellular calcium metabolism, facilitating drug evaluation. Additionally, calcium imaging technology with optical addressing capability complemented the LAPS system's ability to perceive 3D cell morphology, enhancing its drug evaluation capabilities. This work provides a novel, label-free, specific, and stable technique for monitoring cellular calcium metabolism. It achieves both continuous monitoring at single points and custom sensing area calcium imaging, holding significant implications for drug screening and disease treatment related to human calcium homeostasis.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utilizing a high-throughput visualization screening technology to develop a genetically encoded biosensor for monitoring 5-aminolevulinic acid production in engineered Escherichia coli","authors":"","doi":"10.1016/j.bios.2024.116806","DOIUrl":"10.1016/j.bios.2024.116806","url":null,"abstract":"<div><div>5-Aminolevulinic acid (5-ALA) is a non-protein amino acid widely used in agriculture, animal husbandry and medicine. Currently, microbial cell factories are a promising production pathway, but the lack of high-throughput fermentation strain screening tools often hinders the exploration of engineering strategies to increase cell factory yields. Here, mutant AC<sup>103</sup><sup><sup>-</sup></sup><sup>3</sup>H was screened from libraries of saturating mutants after response-specific engineering of the transcription factor AsnC of L-asparagine (Asn). Based on mutant AC<sup>103</sup><sup>-</sup><sup>3</sup>H, a whole-cell biosensor EAC<sup>103</sup><sup>-</sup><sup>3</sup>H with a specific response to 5-ALA was constructed, which has a linear dynamic detection range of 1–12 mM and a detection limit of 0.094 mM, and can be used for in situ screening of potential high-producing 5-ALA strains. With its support, overexpression of the C5 pathway genes using promoter engineering assistance resulted in a 4.78-fold enhancement of 5-ALA production in the engineered <em>E. coli</em>. This study provides an efficient strain screening tool for exploring approaches to improve the 5-ALA productivity of engineered strains.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual action electrochemical bandage operated by a programmable multimodal wearable potentiostat","authors":"","doi":"10.1016/j.bios.2024.116791","DOIUrl":"10.1016/j.bios.2024.116791","url":null,"abstract":"<div><div>We have developed electrochemical bandage (e-bandage) prototypes that generate the reactive oxygen species hypochlorous acid (HOCl) or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) for potential use to treat biofilm-infected wounds in humans. We have shown that both e-bandage-generated HOCl and H<sub>2</sub>O<sub>2</sub> kill biofilms <em>in vitro</em> and in infected wounds on mice, with the former being more active <em>in vitro</em>. The H<sub>2</sub>O<sub>2</sub>-generating e-bandage, more so than the HOCl-generating e-bandage, was associated with improved healing of infected wounds. Here, a strategy in which H<sub>2</sub>O<sub>2</sub> and HOCl are alternately generated—for dual action—was explored. The goal was to develop a programmable multimodal wearable potentiostat [PMWP] that can generate HOCl or H<sub>2</sub>O<sub>2</sub>, as needed. An ultralow-power microcontroller unit was developed to manage operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 g, making it suitable for future small animal experiments (and ultimately, potential evaluation in humans). As assessed using electrochemical parameters, the device functioned comparably to a commercial benchtop potentiostat. To confirm antimicrobial activity, PMWP-controlled e-bandages were tested <em>in vitro</em> against clinical isolates of methicillin-resistant <em>Staphylococcus aureus</em>, <em>Pseudomonas aeruginosa</em>, <em>Acinetobacter baumannii</em>, <em>Enterococcus faecium</em>, and <em>Candida auris</em>. When programmed to deliver HOCl followed by H<sub>2</sub>O<sub>2</sub>, PMWP-controlled e-bandages exhibited activity against biofilms of all study isolates tested. Finally, we demonstrated the PMWP's usability in a murine wound infection model.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrospray deposition of starch-containing laccase: A green technique for low-cost and eco-friendly biosensors","authors":"","doi":"10.1016/j.bios.2024.116758","DOIUrl":"10.1016/j.bios.2024.116758","url":null,"abstract":"<div><div>Recently a laccase-based biosensors with unprecedented reuse and storage capabilities in the detection of catechol compound has been manufactured using ambient Electrospray Deposition (ESD) technique. These biosensors showed to be reused up to 63 measurements on the same electrode just prepared at room temperature and pressure. In this new work the reasons behind such a high-performance functioning have been investigated by analysing the commercial sample of laccase with different chemical physics methods: Electrophoresis, Fourier Transform Infrared Spectroscopy, X-ray Fluorescence and Nuclear Magnetic Resonance Spectroscopy. The analyses reveal the presence of the starch in the sample and its essential role as stabilizing agent. Indeed, comparing the performance of starch/laccase-based biosensors with starch-free/laccase-based biosensors, both produced via ESD, showed that the starch-free biosensors lost about 40% of their performance after just the first wash. This suggests that the presence of starch in the laccase sample is a key factor in providing the high wash and storage resistance, which are essential for the fabrication of such devices.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innovations in one-step point-of-care testing within microfluidics and lateral flow assays for shaping the future of healthcare","authors":"","doi":"10.1016/j.bios.2024.116795","DOIUrl":"10.1016/j.bios.2024.116795","url":null,"abstract":"<div><div>Point-of-care testing (POCT) technology, using lateral flow assays and microfluidic systems, facilitates cost-effective diagnosis, timely treatment, ongoing monitoring, and prevention of life-threatening outcomes. Aside from significant advancements demonstrated in academic research, implementation in real-world applications remains frustratingly limited. The divergence between academic developments and practical utility is often due to factors such as operational complexity, low sensitivity and the need for trained personnel. Taking this into consideration, our objective is to present a critical and objective overview of the latest advancements in fully integrated one-step POCT assays for home-testing which would be commercially viable. In particular, aspects of signal amplification, assay design modification, and sample preparation are critically evaluated and their features and medical applications along with future perspective and challenges with respect to minimal user intervention are summarized. Associated with and very important for the one-step POCT realization are also readout devices and fabrication processes. Critical analysis of available and useful technologies are presented in the SI section.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing cardiovascular health monitoring: Simultaneous multi-artery cardiac markers recording with flexible and bio-compatible AlN piezoelectric sensors","authors":"","doi":"10.1016/j.bios.2024.116790","DOIUrl":"10.1016/j.bios.2024.116790","url":null,"abstract":"<div><div>Continuous monitoring of cardiovascular parameters like pulse wave velocity (PWV), blood pressure wave (BPW), stiffness index (SI), reflection index (RI), mean arterial pressure (MAP), and cardio-ankle vascular index (CAVI) has significant clinical importance for the early diagnosis of cardiovascular diseases (CVDs). Standard approaches, including echocardiography, impedance cardiography, or hemodynamic monitoring, are hindered by expensive and bulky apparatus and accessibility only in specialized facilities. Moreover, noninvasive techniques like sphygmomanometry, electrocardiography, and arterial tonometry often lack accuracy due to external electrical interferences, artifacts produced by unreliable electrode contacts, misreading from placement errors, or failure in detecting transient issues and trends. Here, we report a bio-compatible, flexible, noninvasive, low-cost piezoelectric sensor for continuous and real-time cardiovascular monitoring. The sensor, utilizing a thin aluminum nitride film on a flexible Kapton substrate, is used to extract heart rate, blood pressure waves, pulse wave velocities, and cardio-ankle vascular index from four arterial pulse sites: carotid, brachial, radial, and posterior tibial arteries. This simultaneous recording, for the first time in the same experiment, allows to provide a comprehensive cardiovascular patient's health profile. In a test with a 28-year-old male subject, the sensor yielded the SI = 7.1 ± 0.2 m/s, RI = 54.4 ± 0.5 %, MAP = 86.2 ± 1.5 mmHg, CAVI = 7.8 ± 0.2, and seven PWVs from the combination of the four different arterial positions, in good agreement with the typical values reported in the literature. These findings make the proposed technology a powerful tool to facilitate personalized medical diagnosis in preventing CVDs.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances of lipid droplet-targeted AIE-active materials for imaging, diagnosis and therapy","authors":"","doi":"10.1016/j.bios.2024.116802","DOIUrl":"10.1016/j.bios.2024.116802","url":null,"abstract":"<div><div>Lipid droplets (LDs) are cellular organelles specialized in the storage and regulating the release of lipids critical for energy metabolism. As investigation on LDs deepens, the complex biological functions of LDs are revealed and their relationships with various diseases such as atherosclerosis, fatty liver, obesity, and cancer are uncovered. Fluorescence-based techniques with simple operations, visible results and high non-invasiveness are ideal tools for investigating LD-related biological processes and diseases. Materials with aggregation-induced emission (AIE) characteristics have emerged as promising candidates for investigating LDs due to their high signal-to-noise ratio (S/N), strong photostability, and large Stokes shift. This review discusses the principles and advantages of LD-targeting AIE probes for imaging LDs, diagnosis of LD-associated diseases including atherosclerotic plaques, liver diseases, acute kidney diseases and cancer, therapies with LD-targeting AIE-active photosensitizers and other relevant fields in the past five years. Through typical examples, we illustrate the status of investigating LD-related imaging, diagnosis of diseases and therapy with AIE materials. This review is expected to attract attentions from scientists with different research backgrounds and contribute to the further development of LD-targeting AIE materials.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bridging basic science and applied diagnostics: Comprehensive viral diagnostics enabled by graphene-based electronic biosensor technology advancements","authors":"","doi":"10.1016/j.bios.2024.116807","DOIUrl":"10.1016/j.bios.2024.116807","url":null,"abstract":"<div><div>This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-enzymatic g-C3N4 supported CuO derived-biochar based electrochemical sensors for trace level detection of malathion","authors":"","doi":"10.1016/j.bios.2024.116808","DOIUrl":"10.1016/j.bios.2024.116808","url":null,"abstract":"<div><div>Malathion (MALA), a widely used insecticide, even at trace levels exhibits deleterious effects towards respiratory tracts, and nervous system, necessitating its detection. Herein, we have offered non-enzymatic trace level monitoring of MALA using g-C<sub>3</sub>N<sub>4</sub> supported CuO-derived biochar. The present B-CuO/g-C<sub>3</sub>N<sub>4</sub> based electrochemical sensor is synthesized using hydrothermal approach followed by calcination at high temperature. The result unveiled the strong <pi-pi> interactions, high charge separation efficiency, significant porosity leading to excellent electrochemically active surface area 9.88 × 10<sup>−5</sup> cm<sup>2</sup> with least charge transfer resistance (R<sub>CT</sub>) value of 35.2 K Ω. The B-CuO/g-C<sub>3</sub>N<sub>4</sub> based nanocomposite offered excellent complex formation ability with MALA and square wave anodic stripping voltametric method (SWASV) generates an enhanced electrochemical signal due to oxidation of MALA. Following all necessary optimizations, the sensor was capable to exhibit limit of detection (LOD) value of 1.2 pg mL<sup>−1</sup> with R<sup>2</sup> = 0.968. The modified biosensor offered its potential towards detection of MALA in apple and tomato samples with a recovery ranging from 87.64 to 120.59%. This novel B-CuO/g-C<sub>3</sub>N<sub>4</sub> ternary nanocomposite provides non-enzymatic detection of MALA having excellent electrochemical properties and hence opens new pathways for exploring the use of biochar in other electrochemical applications.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}