Lab on a Chip最新文献

{"title":"Real-time and regional analysis of the efficacy of anticancer drugs in a patient-derived intratumoral heterogeneous tumor microenvironment.","authors":"Ya-Hui Lin, Chiao-Min Lin, Kee-Ming Man, Chih-Chiang Hung, Hsin-Ling Hsu, Yunching Chen, Hsuan-Yu Mu, Tzu-Hung Hsiao, Jen-Huang Huang","doi":"10.1039/d4lc00990h","DOIUrl":"https://doi.org/10.1039/d4lc00990h","url":null,"abstract":"<p><p>Preclinical evaluation of anticancer drug efficacy utilizes 2D cell culture systems, tumoroids or experimental animal models, but it suffers from limitations such as inaccurate simulation of tumor microenvironments in living tumors, difficulty in regional analysis, and low throughput. Therefore, in this study, we developed a system named tumor-microenvironment-on-chip (TMoC) comprising a 3D dynamic tumor tissue culture system, which recreated diverse and heterogeneous cellular tumor microenvironments. In addition to the culture with a dynamic circulation, TMoC allowed users to perform real-time regional analysis, independently assessing the drug response from the normoxic area to the hypoxic area in a gradient manner. Through cell composition analysis and gene analysis, we proved that TMoC has a tumor environment with close resemblance to the original tumor environment. By comparing 15 drug testing results with animal experiments, we proved that TMoC is 93% consistent with the response results of animal experiments. In addition, we confirmed that either mouse- or patient-derived tumor cell lines can be cultured and tested in TMoC, indicating its immense potential for all aspects of preclinical drug evaluation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Acoustic modulation and non-contact atomization of droplets based on the Fabry-Pérot resonator.","authors":"Jingjun Li, Xiukun Wang, Fan Yang, Yadong Sun, Lei Zhang","doi":"10.1039/d5lc90020d","DOIUrl":"https://doi.org/10.1039/d5lc90020d","url":null,"abstract":"<p><p>Correction for 'Acoustic modulation and non-contact atomization of droplets based on the Fabry-Pérot resonator' by Jingjun Li <i>et al.</i>, <i>Lab Chip</i>, 2024, <b>24</b>, 2418-2427, https://doi.org/10.1039/D4LC00071D.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A digital microfluidic approach to increasing sample volume and reducing bead numbers in single molecule array assays.","authors":"Alinaghi Salari, Jose Gilberto Camacho Valenzuela, Nguyen Le, Joshua Dahmer, Alexandros A Sklavounos, Cheuk W Kan, Ryan Manning, David C Duffy, Nira R Pollock, Aaron R Wheeler","doi":"10.1039/d4lc01002g","DOIUrl":"10.1039/d4lc01002g","url":null,"abstract":"<p><p>We report methods that improve the manipulation of magnetic beads using digital microfluidics (DMF) that can enhance the performance of single molecule array (Simoa) digital protein assays in miniaturized analytical systems. Despite significant clinical and biomedical applications for digital protein detection, the development of miniaturized Simoa systems has been limited by the requirements for use of large sample volumes (∼100 μL) and low numbers of beads (∼5000) for high sensitivity tests. To address these challenges, we improved the integration of DMF with Simoa-based assays by developing strategies for loading mixtures of sample and beads into DMF networks using methods relying on either virtual channels or small liquid segments that were applied either in parallel or in a stepwise manner. We have also demonstrated a dedicated densifying electrode technique that captures low numbers of beads within a droplet, allowing high bead retention with minimal residual volumes of liquid. Based on these improvements, we optimized the front-end assay processing of beads using DMF and demonstrated a method to detect tumor necrosis factor α (TNF-α) by Simoa that showed equivalent performance to a microtitre plate assay. The new strategies described here form a step toward integrating DMF and Simoa for a wide range of applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances of dual-organ and multi-organ systems for gut, lung, skin and liver models in absorption and metabolism studies.","authors":"Konstanze Brandauer, Sophie Schweinitzer, Alexandra Lorenz, Judith Krauß, Silvia Schobesberger, Martin Frauenlob, Peter Ertl","doi":"10.1039/d4lc01011f","DOIUrl":"https://doi.org/10.1039/d4lc01011f","url":null,"abstract":"<p><p>Drug development is a costly and timely process with high risks of failure during clinical trials. Although <i>in vitro</i> tissue models have significantly advanced over the years, thus fostering a transition from animal-derived models towards human-derived models, failure rates still remain high. Current cell-based assays are still not able to provide an accurate prediction of the clinical success or failure of a drug candidate. To overcome the limitations of current methods, a variety of microfluidic systems have been developed as powerful tools that are capable of mimicking (micro)physiological conditions more closely by integrating physiological fluid flow conditions, mechanobiological cues and concentration gradients, to name only a few. One major advantage of these biochip-based tissue cultures, however, is their ability to seamlessly connect different organ models, thereby allowing the study of organ-crosstalk and metabolic byproduct effects. This is especially important when assessing absorption, distribution, metabolism, and excretion (ADME) processes of drug candidates, where an interplay between various organs is a prerequisite. In the current review, a number of <i>in vitro</i> models as well as microfluidic dual- and multi-organ systems are summarized with a focus on absorption (skin, lung, gut) and metabolism (liver). Additionally, the advantage of multi-organ chips in identifying a drug's on and off-target toxicity is discussed. Finally, the potential high-throughput implementation and modular chip design of multi-organ-on-a-chip systems within the pharmaceutical industry is highlighted, outlining the necessity of reducing handling complexity.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soft, wearable, microfluidic system for fluorometric analysis of loss of amino acids through eccrine sweat.","authors":"Seunghee H Cho, Soongwon Cho, Zengyao Lv, Yurina Sekine, Shanliangzi Liu, Mingyu Zhou, Ravi F Nuxoll, Evangelos E Kanatzidis, Roozbeh Ghaffari, Donghwan Kim, Yonggang Huang, John A Rogers","doi":"10.1039/d4lc00734d","DOIUrl":"https://doi.org/10.1039/d4lc00734d","url":null,"abstract":"<p><p>Amino acids are essential for protein synthesis and metabolic processes in support of homeostatic balance and healthy body functions. This study quantitatively investigates eccrine sweat as a significant channel for loss of amino acids during exercise, to improve an understanding of amino acid turnover and to provide feedback to users on the need for supplement intake. The measurement platform consists of a soft, skin-interfaced microfluidic system for real-time analysis of amino acid content in eccrine sweat. This system relies on integrated fluorometric assays and smartphone-based imaging techniques for quantitative analysis, as a simple, cost-effective approach that does not require electrochemical sensors, electronics or batteries. Human subject studies reveal substantial amino acid losses in sweat from working muscle regions during prolonged physical activities, thereby motivating the need for dietary supplementation. The findings suggest potential applications in healthcare, particularly in athletic and clinical settings, where maintaining amino acid balance is critical for ensuring proper homeostasis.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimensional analysis meets AI for non-Newtonian droplet generation.","authors":"Farnoosh Hormozinezhad, Claire Barnes, Alexandre Fabregat, Salvatore Cito, Francesco Del Giudice","doi":"10.1039/d4lc00946k","DOIUrl":"10.1039/d4lc00946k","url":null,"abstract":"<p><p>Non-Newtonian droplets are used across various applications, including pharmaceuticals, food processing, drug delivery and material science. However, predicting droplet formation using such complex fluids is challenging due to the intricate multiphase interactions between fluids with varying viscosities, elastic properties and geometrical constraints. In this study, we introduce a novel hybrid machine-learning architecture that integrates dimensional analysis with machine learning to predict the flow rates required to generate droplets with specified sizes in systems involving non-Newtonian fluids. Unlike previous approaches, our model is designed to accommodate shear-rate-dependent viscosities and a simple estimate of the elastic properties of the fluids. It provides accurate predictions of the dispersed and continuous phases flow rates for given droplet length, height, and viscosity curves, even when the fluid properties deviate from those used during training. Our model demonstrates strong predictive power, achieving <i>R</i>² values of up to 0.82 for unseen data. The significance of our work lies in its ability to generalize across a broad range of non-Newtonian systems having different viscosity curves, offering a powerful tool for optimizing droplet generation. This model represents a significant advancement in the application of machine learning to microfluidics, providing new opportunities for efficient experimental design in complex multiphase systems.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tutorial on impedance and dielectric spectroscopy for single-cell characterisation on microfluidic platforms: theory, practice, and recent advances","authors":"Fatemeh Dadkhah Tehrani, Michael D. O'Toole and David J. Collins","doi":"10.1039/D4LC00882K","DOIUrl":"10.1039/D4LC00882K","url":null,"abstract":"<p >Cell analysis plays an important role in disease diagnosis. However, many characterisation techniques are labour intensive, expensive and time-consuming. Impedance and dielectric spectroscopy (IDS) offers a new approach by using varying electrical current and electric field propagation responses to probe cell physiology. This review aims to explore the theoretical foundations, practical applications, and advancements in IDS for single-cell analysis, particularly when integrated with microfluidic technologies. It highlights recent developments in electrode configurations, calibration techniques, and data analysis methodologies, emphasising their importance in enhancing sensitivity and selectivity. The review identifies key trends, including the shift towards high-throughput and precise single-cell analysis, and discusses the challenges and potential solutions in this field. The implications of these findings suggest significant near-future advances in biomedical research, diagnostics, and therapeutic monitoring. This paper serves as a comprehensive reference for researchers in different fields to make a bridge between theoretical research and practical implementation in single-cell analysis.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 5","pages":" 837-855"},"PeriodicalIF":6.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iDEP-based single-cell isolation in a two-dimensional array of chambers addressed by easy-to-align wireless electrodes.","authors":"Thilini N Rathnaweera, Robbyn K Anand","doi":"10.1039/d4lc00976b","DOIUrl":"10.1039/d4lc00976b","url":null,"abstract":"<p><p>Platforms capable of selective single-cell capture and enclosure in a fluidically isolated volume for subsequent analysis are crucial for unmasking cellular heterogeneity. Our research group has previously reported an approach that employs wireless bipolar electrodes (BPEs) to facilitate individual isolation of cells in large arrays of pico- to nanoliter scale chambers by dielectrophoresis (DEP). This device was leveraged for a single-cell enzymatic assay and the isolation of circulating tumor cells (CTCs) from patient-derived blood samples, which takes advantage of the selectivity of DEP. However, alignment of BPEs to the microchamber openings is nontrivial, and augmentation of the array dimensions accumulates alignment error, thereby disrupting the uniformity of cell capture across the device. Thus, tolerance-forgiving designs that are simultaneously expandable are in demand. To address this demand, we present an approach that combines BPEs with insulator DEP (iDEP) to drastically expand alignment tolerance. This iDEP-BPE device offers a vertical tolerance (the distance the BPE is recessed within each microchamber) of 80 μm while the horizontal tolerance is nearly infinite. Further, the iDEP-BPE device decreases the exposure of cells to electrode surfaces and reactive oxygen species, thereby preserving their viability. Finally, this iDEP approach can be carried out with BPEs that are easy to fabricate, lacking features that require high-resolution lithography. These advancements potentiate the broad adoption of the iDEP-BPE approach for selective single-cell capture and on-chip analysis and potentiate its commercialization upon deployment of appropriate thermoplastic materials.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new biofunctionalized and micropatterned PDMS is able to promote stretching induced human myotube maturation.","authors":"Théo Regagnon, Fabrice Raynaud, Gilles Subra, Gilles Carnac, Gerald Hugon, Aurélien Flatres, Vincent Humblot, Laurine Raymond, Julie Martin, Elodie Carretero, Margaux Clavié, Nathalie Saint, Sylvie Calas, Cécile Echalier, Pascal Etienne, Stefan Matecki","doi":"10.1039/d4lc00911h","DOIUrl":"https://doi.org/10.1039/d4lc00911h","url":null,"abstract":"<p><p>Inter-individual variability in muscle responses to mechanical stress during exercise is poorly understood. Therefore, new cell culture scaffolds are needed to gain deeper insights into the cellular mechanisms underlying the influence of mechanical stress on human myogenic progenitor cells behavior. To this end, we propose the first <i>in vitro</i> model involving uniaxial mechanical stress applied to aligned human primary muscle-derived cells, employing a biocompatible organic-inorganic photostructurable hybrid material (OIPHM) covalently attached to a stretchable PDMS support. Using a laser printing technique with an additive photolithographic process, we optimally micropatterned the PDMS support to create longitudinal microgrooves, achieving well-aligned muscle fibers without significantly affecting their diameter. This support was biofunctionalized with peptide sequences from the ECM, which interact with cellular adhesion receptors and prevent myotube detachment induced by stretching. X-ray photoelectron spectroscopy (XPS) of biofunctionalized PDMS with RGD-derived peptide deposition revealed a significant increase in nitrogen compared to silicon, associated with the presence of a 380 nm thick layer measured by atomic force microscopy (AFM). Upon cell culture, we observed that functionalization with an RGD peptide had a beneficial impact on cell fusion rate and myotube area compared to bare PDMS. At the initiation of the stretching protocol, we observed a three-fold rapid and transient increase in RNA expression for the mechanosensitive ion channel protein piezo and a decrease in the ratio of nuclei expressing myogenin relative to the total nuclei count (43 ± 16% <i>vs.</i> 6 ± 6%, <i>p</i> < 0.01). Compared to day 0 of differentiation, stretching the myotubes induced MHC and Titin colocalization (0.66 ± 0.13 <i>vs.</i> 0.93 ± 0.05, <i>p</i> < 0.01), favoring sarcomere organization and maturation. In this study, we propose and validate an optimized protocol for culturing human primary muscle-derived cells, allowing standardized uniaxial mechanical stress with a biocompatible OIPHM covalently linked to PDMS biofunctionalized with an ECM-derived peptide, to better characterize the behavior of myogenic progenitor cells under mechanical stress in future studies.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and simulation of biomimetic microfluidic designs to achieve uniform flow and DNA capture for high-throughput multiplexing.","authors":"Enas Osman, Jonathan L'Heureux-Hache, Phoebe Li, Leyla Soleymani","doi":"10.1039/d4lc01023j","DOIUrl":"https://doi.org/10.1039/d4lc01023j","url":null,"abstract":"<p><p>High-throughput multi-analyte point-of-care detection is often constrained by the limited number of analytes that can be effectively monitored. This study introduces bio-inspired microfluidic designs optimized for multi-analyte detection using 38-42 biosensors. Drawing inspiration from the human spinal cord and leaf vein networks, these perfusion-oriented designs ensure uniform flow velocity and consistent molecular capture while maintaining spatial separation to prevent cross-talk. <i>In silico</i> optimizations achieved velocity profile uniformity with coefficients of variance of 0.89% and 0.86% for the spine- and leaf-inspired designs, respectively. However, simulations revealed that velocity uniformity alone is insufficient for accurate molecular capture prediction without consistent reaction site channel dimensions. The bio-inspired designs demonstrated superior performance, stabilizing-coefficient of variance below 20%-in DNA capture within 10 minutes, compared to 68 minutes for a simple branched design. This work underscores the potential of bio-inspired microfluidics to enable scalable, uniform, and high-performance systems for multi-analyte detection.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}