Lab on a Chip最新文献

{"title":"Liquid metal electrodes enabled cascaded on-chip dielectrophoretic separation of large-size-range particles.","authors":"Huichao Chai, Liang Huang, Junwen Zhu, Jialu Tian, Wenhui Wang","doi":"10.1039/d4lc00942h","DOIUrl":"https://doi.org/10.1039/d4lc00942h","url":null,"abstract":"<p><p>The separation of large-size-range particles of complex biological samples is critical but yet well resolved. As a label-free technique, dielectrophoresis (DEP)-based particle separation faces the challenge of how to configure DEP in an integrated microfluidic device to bring particles of various sizes into the effective DEP force field. Herein, we propose a concept that combines the passive flow fraction mechanism with the accumulative DEP deflection effect in a cascaded manner. This concept places DEP deflection segments and bypass outlets alternately. Each DEP deflection segment is configured with an array of side-wall liquid metal electrodes to exert effective DEP forces on the particles of a suitable size range. After each DEP deflection segment, the passive bypass flow fraction mechanism diverts part of the sample flow and target range of particles through the bypass outlet. Simultaneously, this flow fraction brings the remaining particles closer to the electrodes in the subsequent DEP deflection segment, causing the next size range of particles to deflect under effective DEP forces and thus making them separable. Repeating this process, particles would be separated from the bypass outlets one by one in the order of reducing size ranges. We present the concept design and modeling, and prove the concept through separating five different particles ranging from 16-0.5 μm mixed together to mimic blood composition, providing a powerful platform for separating multiple particles in diverse biomedical applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875534","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":"An intimal-lumen model in a microfluidic device: potential platform for atherosclerosis-related studies.","authors":"Fahima Akther, Dimple Sajin, Shehzahdi S Moonshi, Jessica Pickett, Yuao Wu, Jun Zhang, Nam-Trung Nguyen, Hang Thu Ta","doi":"10.1039/d4lc00868e","DOIUrl":"https://doi.org/10.1039/d4lc00868e","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory vascular disorder driven by factors such as endothelial dysfunction, hypertension, hyperlipidemia, and arterial calcification, and is considered a leading global cause of death. Existing atherosclerosis models have limitations due to the absence of an appropriate hemodynamic microenvironment <i>in vitro</i> and interspecies differences <i>in vivo</i>. Here, we develop a simple but robust microfluidic intimal-lumen model of early atherosclerosis using interconnected dual channels for studying monocyte transmigration and foam cell formation at an arterial shear rate. To the best of our knowledge, this is the first study that creates a physiologically relevant microenvironment under an arterial shear rate to modulate lipid-laden foam cells on a microfluidic platform. As a proof of concept, we use murine endothelial cells to develop a vascular lumen in one channel and collagen-embedded murine smooth muscle cells to mimic the subendothelial intimal layer in another channel. The model successfully triggers endothelial dysfunction upon TNF-α stimulation, initiating monocyte adhesion to the endothelial monolayer under the arterial shear rate. Unlike existing <i>in vitro</i> models, native low-density lipoprotein (LDL) is added in the culture media instead of ox-LDL to stimulate subendothelial lipid accumulation, thereby mimicking more accurate physiology. The subendothelial transmigration of adherent monocytes and subsequent foam cell formation is also achieved under flow conditions in the model. The model also investigates the inhibitory effect of aspirin in monocyte adhesion and transmigration. The model exhibits a significant dose-dependent reduction in monocyte adhesion and transmigration upon aspirin treatment, making it an excellent tool for drug testing.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851733","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":"High-throughput microfluidic spheroid technology for early detection of colistin-induced nephrotoxicity with gradient-based analysis.","authors":"Yugyeong Lee, Yunsang Choi, Ju Lan Chun, Hong Bin Kim, Sejoong Kim, Eu Suk Kim, Sungsu Park","doi":"10.1039/d4lc00782d","DOIUrl":"https://doi.org/10.1039/d4lc00782d","url":null,"abstract":"<p><p>Colistin is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Traditional approaches for studying colistin's nephrotoxicity are challenged by the rapid metabolism of its prodrug, colistin methanesulfonate and the difficulty of obtaining adequate plasma from critically ill patients. To address these challenges, we developed the Spheroid Nephrotoxicity Assessing Platform (SNAP), a microfluidic device that efficiently detects colistin-induced toxicity in renal proximal tubular epithelial cell (RPTEC) spheroids within 48 hours using just 200 μL of patient plasma. Our findings demonstrate that SNAP not only promotes higher expression of kidney-specific markers aquaporin-1 (AQP1) and low-density lipoprotein receptor-related protein 2 (LRP2) compared to traditional two-dimensional (2D) cultures, but also exhibits increased sensitivity to colistin, with significant toxicity detected at concentrations of 50 μg ml^-1 and above. Notably, SNAP's non-invasive method did not identify nephrotoxicity in plasma from healthy donors, thereby confirming its physiological relevance and showcasing superior sensitivity over 2D cultures, which yielded false-positive results. In clinical validation, SNAP accurately identified patients at risk of colistin-induced nephrotoxicity with 100% accuracy for both early and late onset and demonstrated a 75% accuracy rate in predicting the non-occurrence of nephrotoxicity. These results underline the potential of SNAP in personalized medicine, offering a non-invasive, precise and efficient tool for the assessment of antibiotic-induced nephrotoxicity, thus enhancing the safety and efficacy of treatments against resistant bacterial infections.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845342","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":"3D-printed acoustic metasurface with encapsulated micro-air-bubbles for frequency-selective manipulation.","authors":"Miaomiao Ji, Yukai Liu, Zheng Zhang, Rui Xu, Fanyun Pan, Ya Zhang, Rouyu Su, Minghui Lu, Xiujuan Zhang, Guanghui Wang","doi":"10.1039/d4lc00890a","DOIUrl":"https://doi.org/10.1039/d4lc00890a","url":null,"abstract":"<p><p>Acoustic waves provide an effective method for object manipulation in microfluidics, often requiring high-frequency ultrasound in the megahertz range when directly handling microsized objects, which can be costly. Micro-air-bubbles in water offer a solution toward low-cost technologies using low-frequency acoustic waves. Owing to their high compressibility and low elastic modulus, these bubbles can exhibit significant expansion and contraction in response to even kilohertz acoustic waves, leading to resonances with frequencies determined and tuned by air-bubble size. The resonances amplify vibrational amplitude and generate localized turbulence, enabling selective, non-invasive, and high-precision manipulation of microsized objects. However, conventional bubble formation relies on the shear force of the liquid flow and bubble surface tension, facing challenges of instability and random vibration that can impair manipulation precision and performance. To address these issues, we propose a coupled vibration structure with 3D-printed circular microsized air holes encapsulated by a PDMS film. These airholes act as artificial micro-air-bubbles, with their expansion and contraction stabilized by acoustic hard boundaries. The PDMS film further regulates vibration modes through the interaction between air movement and the film's vibration, eliminating randomness. Compared to conventional air-bubbles held by surface tension, these artificial air-bubbles are mechanically stable, allowing for enhanced gas volume changes and stronger forces for object manipulation. We experimentally confirm the stable vibration modes and their frequency-dependent behavior using laser Doppler vibrometry. Precise aggregation, rotation, and separation of micro-objects are demonstrated by adjusting the film's vibration mode. Furthermore, we propose a metasurface design featuring a multi-size microbubble array for frequency-selective manipulation, enabling flexible control of sample trajectory by changing the exciting frequency of an embedded piezoelectric transducer. Our low-frequency acoustic metasurface device offers a versatile, cost-effective solution for drug screening and automated sample handling.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845340","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":"Real-time cell barrier monitoring by spatial transepithelial electrical resistance measurement on a microelectrode array integrated Transwell.","authors":"Yimin Shi, Sheng Sun, Hui Liu, Mingda Zhao, Meiyan Qin, Jinlong Liu, Jingfang Hu, Yang Zhao, Mingxiao Li, Lingqian Zhang, Chengjun Huang","doi":"10.1039/d4lc00817k","DOIUrl":"https://doi.org/10.1039/d4lc00817k","url":null,"abstract":"<p><p>Transepithelial electrical resistance (TEER) measurement is a label free, rapid and real-time technique, which is commonly used to evaluate the integrity of cell barriers. TEER characterization is important for applications, such as tissue (brain, intestines, lungs) barrier modeling, drug screening, and cell growth monitoring. Traditional TEER methods usually only show the average impedance of the whole cell layer, and lack accuracy and the characterization of internal spatial differences within cell layer regions. Here, we introduce a new spatial TEER strategy that utilizes microelectrode arrays (MEA) integrated in a Transwell to dynamically monitor TEER. A new electrical model which could reveal spatial impedance non-uniformity was proposed to extract accurate resistance from the measured data. Based on our method, the TEER signals from 16 different regions were successfully monitored in real time. The mapped impedance hotspots in different regions closely correlate with both fluorescence cell staining signals and calculated cell coverage, indicating the effectiveness of the developed spatial TEER system in monitoring local cell growth <i>in vitro</i>. The real-time spatial TEER responses to ethylene glycol-bis(β-aminoethylether)-<i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>'-tetraacetic acid (EGTA) and cisplatin were studied, which could either reduce barrier integrity or inhibit cellular growth. The obtained results demonstrated the spatial TEER's applicability for cell barrier function and cell growth monitoring. Our approach provides accurate spatial electrical information of cell barriers and holds potential applications in drug development and screening.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833103","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":"Sheath-enhanced concentration and on-chip detection of bacteria from an extremely low-concentration level.","authors":"Xinye Chen, Ruonan Peng, Ruo-Qian Wang, Ke Du","doi":"10.1039/d4lc00698d","DOIUrl":"https://doi.org/10.1039/d4lc00698d","url":null,"abstract":"<p><p>Microfluidic-based sheath flow focusing methods have been widely used for efficiently isolating, concentrating, and detecting pathogenic bacteria for various biomedical applications due to their enhanced sensitivity and exceptional integration. However, such a microfluidic device usually needs complicated device fabrication and sample dilution, hampering the efficient and sensitive identification of target bacteria. In this study, we develop and fabricate a sheath-assisted and pneumatic-induced nano-sieve device for achieving the improved on-chip concentration and sensitive detection of <i>Staphylococcus aureus</i> (MRSA). The optimized nanochannel design with diverging configuration is beneficial to the regulation of the hydrodynamic flow while the sheath flow is focusing the sample to the confined region as expected. Per the experimental finding, a high flow ratio (sheath flow/sample flow) presents enhanced target concentration by comparing with a low flow ratio. With this setup, MRSA bacteria with an extremely low concentration of ∼100 CFU mL^-1 are successfully and sensitively detected under a fluorescence microscope, less than 30 min, demonstrating a reliable sheath-enhanced concentration and on-chip detection for target bacteria. Additionally, the theoretical model introduced here further rationalizes the working principle of our nano-sieve device, potentially guiding the optimization of next generation devices for highly sensitive and accurate on-chip bacteria detection at a much lower concentration level below 100 CFU mL^-1.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833109","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":"An agarose fluidic chip for high-throughput <i>in toto</i> organoid imaging.","authors":"Sarah De Beuckeleer, Andres Vanhooydonck, Johanna Van Den Daele, Tim Van De Looverbosch, Bob Asselbergh, Hera Kim, Coen Campsteijn, Peter Ponsaerts, Regan Watts, Winnok H De Vos","doi":"10.1039/d4lc00459k","DOIUrl":"https://doi.org/10.1039/d4lc00459k","url":null,"abstract":"<p><p>Modern cell and developmental biology increasingly relies on 3D cell culture systems such as organoids. However, routine interrogation with microscopy is often hindered by tedious, non-standardized sample mounting, limiting throughput. To address these bottlenecks, we have developed a pipeline for imaging intact organoids in flow, utilizing a transparent agarose fluidic chip that enables efficient and consistent recordings with theoretically unlimited throughput. The chip, cast from a custom-designed 3D-printed mold, is coupled to a mechanically controlled syringe pump for fast and precise sample positioning. We benchmarked this setup on a commercial digitally scanned light sheet microscope with cleared glioblastoma spheroids. Spheroids of varying sizes were positioned in the field of view with micrometer-level stability, achieving a throughput of 40 one-minute recordings per hour. We further showed that sample positioning could be automated through online feedback microscopy. The optical quality of the agarose chip outperformed FEP tubing, glass channels and PDMS casts for the clearing agents used, as demonstrated by image contrast profiles of spheroids stained with a fluorescent nuclear counterstain and further emphasized by the resolution of fine microglial ramifications within cerebral organoids. The retention of image quality throughout 500 μm-sized spheroids enabled comprehensive spatial mapping of live and dead cells based on their nuclear morphology. Finally, imaging a batch of <i>LMNA</i> knockout <i>vs.</i> wildtype astrocytoma spheroids revealed significant differences in their DNA damage response, underscoring the system's sensitivity and throughput. Overall, the fluidic chip design provides a cost-effective, accessible, and efficient solution for high-throughput organoid imaging.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833100","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":"Highly efficient combination of multiple single cells using a deterministic single-cell combinatorial reactor.","authors":"Mina Yoshida, Saori Tago, Kunihiko Iizuka, Teruo Fujii, Soo Hyeon Kim","doi":"10.1039/d4lc00951g","DOIUrl":"https://doi.org/10.1039/d4lc00951g","url":null,"abstract":"<p><p>Compartmentalization of multiple single cells and/or single microbeads holds significant potential for advanced biological research including single-cell transcriptome analysis or cell-cell interactions. To ensure reliable analysis and prevent misinterpretation, it is essential to achieve highly efficient pairing or combining of single objects. In this paper, we introduce a novel microfluidic device coupled with a multilayer interconnect Si/SiO² control circuit, named the deterministic single-cell combinatorial reactor (DSCR) device, for the highly efficient combination of multiple single cells. The deterministic combination of multiple single cells is realized by sequentially introducing and trapping each cell population into designated trap-wells within each DSCR. These cell-sized trap-wells, created by etching the SiO₂ passivation layer, generate a highly localized electric field that facilitates deterministic single-cell trapping. The device's multilayer interconnection of electrodes enables the sequential operation of each trap-well, allowing precise trapping of each cell population into designated trap-wells within an array of combinatorial reactors. We demonstrated the feasibility of the DSCR by sequentially trapping three distinct groups of PC3 cells, each stained with a different fluorescent dye (blue, green, or red). This method achieved a 93 ± 2% pairing efficiency for two cell populations and an 82 ± 7% combination efficiency for three cell populations. Our innovative system offers promising applications for analyzing multiple cell-cell communications and combinatorial indexing of single cells.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826744","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 of a magnetically responsive artificial cilia array platform for microsphere transport.","authors":"Yan Qiu, Xinwei Cai, Xin Bian, Guoqing Hu","doi":"10.1039/d4lc00981a","DOIUrl":"https://doi.org/10.1039/d4lc00981a","url":null,"abstract":"<p><p>We present an innovative platform designed to mimic the mucociliary clearance system, an essential defense mechanism in the respiratory tract. Our system utilizes PDMS and iron powder to fabricate micro-ciliary arrays that dynamically respond to alternating magnetic fields. The cilia exhibit an asymmetric beating pattern under a cyclically varying magnetic field, which propels microspheres directionally in a fluid medium, simulating the movement of mucus. We use both experimental setups and numerical simulations to investigate factors that influence the efficiency of particle transport, such as cilia beating frequency, microsphere size, cilia density, and fluid viscosity. Our results elucidate the role of artificial cilia in surface cleaning processes and provide insights that enhance our understanding of mucociliary clearance. This novel experimental platform holds great promise for advancing research in respiratory health and microchannel cleaning technologies, and contributes to our ability to model and study human respiratory function <i>in vitro</i>.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826741","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":"Reusable EWOD-based microfluidic system for active droplet generation.","authors":"Suhee Park, Jaewook Ryu, Ki-Ho Han","doi":"10.1039/d4lc00744a","DOIUrl":"https://doi.org/10.1039/d4lc00744a","url":null,"abstract":"<p><p>Droplets are essential in a wide range of microfluidic applications, but traditional passive droplet generation methods suffer from slow response speed and the need for precise flow rate adjustment. Here, we present an active droplet generation method through electrowetting-on-dielectric (EWOD). Electrowetting is a technique that uses an electric field to change the wettability of a surface. In our method, we apply an electric field to the laminar flow of the dispersed and continuous phases in a microchannel, which induces the discretization of the dispersed thread and leads to droplet formation. A key feature of the proposed active droplet-generating microfluidic device is the reusability of the EWOD actuation substrate, dramatically reducing operational costs. In addition, this approach offers significant advantages over passive methods, including fast response speeds, a wider range of droplet sizes, and greater control over droplet size. In addition, the ultrathin polymer film used in this device allows for a low electrowetting voltage, which helps to prevent damage to encapsulated cells. We believe that our active droplet generation method is a promising new method for generating droplets in microfluidic applications. It is faster, more versatile, and more precise than passive methods, making it ideal for a wide range of applications, including single-cell genomics and drug discovery.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816635","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}