Fatemeh Dadkhah Tehrani, Michael D O'Toole, David J Collins
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.
{"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, David J Collins","doi":"10.1039/d4lc00882k","DOIUrl":"10.1039/d4lc00882k","url":null,"abstract":"<p><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":" ","pages":""},"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}
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.
{"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}
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 in vitro 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% vs. 6 ± 6%, p < 0.01). Compared to day 0 of differentiation, stretching the myotubes induced MHC and Titin colocalization (0.66 ± 0.13 vs. 0.93 ± 0.05, p < 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.
{"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}
Enas Osman, Jonathan L'Heureux-Hache, Phoebe Li, Leyla Soleymani
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. In silico 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.
{"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}
Kongchang Wei, Wuchao Wang, Giorgia Giovannini, Khushdeep Sharma, René M Rossi, Luciano F Boesel
Hydrogel fibers are promising biomaterials for a broad range of biomedical applications, including biosensing, drug delivery, and tissue engineering. Different types of microfluidic devices have been developed for hydrogel fiber spinning, however, they often require skillful fabrication procedures with special instruments such as 3D printers and clean-room facilities. On the other hand, microfluidic devices with predetermined and fixed configurations are susceptible to clotting, contamination, and damage, thereby creating a significant barrier for potential users. Herein, we describe a plug-and-play (PnP) microfluidic device for hydrogel fiber spinning. The PnP device was designed to be assembled in a modular manner based on simple mounting of PDMS elastomers on commercial Lego® blocks. Easy disassembly and re-assembly make the device user-friendly, since cleaning or replacing individual modules is convenient. We demonstrated the application of our PnP microfluidic device in alginate (Alg) hydrogel fiber spinning by using a single-module or double-module device. Moreover, thanks to the PnP approach, multi-layered fibers can be produced by using a triple-module device. As proof-of-principle, we fabricated pH-sensitive multi-layered fibers that could be used for monitoring biological environments, showcasing the potential of such a PnP device in advancing biomedical research related to functional fibers.
{"title":"A plug-and-play microfluidic device for hydrogel fiber spinning.","authors":"Kongchang Wei, Wuchao Wang, Giorgia Giovannini, Khushdeep Sharma, René M Rossi, Luciano F Boesel","doi":"10.1039/d4lc00783b","DOIUrl":"10.1039/d4lc00783b","url":null,"abstract":"<p><p>Hydrogel fibers are promising biomaterials for a broad range of biomedical applications, including biosensing, drug delivery, and tissue engineering. Different types of microfluidic devices have been developed for hydrogel fiber spinning, however, they often require skillful fabrication procedures with special instruments such as 3D printers and clean-room facilities. On the other hand, microfluidic devices with predetermined and fixed configurations are susceptible to clotting, contamination, and damage, thereby creating a significant barrier for potential users. Herein, we describe a plug-and-play (PnP) microfluidic device for hydrogel fiber spinning. The PnP device was designed to be assembled in a modular manner based on simple mounting of PDMS elastomers on commercial Lego® blocks. Easy disassembly and re-assembly make the device user-friendly, since cleaning or replacing individual modules is convenient. We demonstrated the application of our PnP microfluidic device in alginate (Alg) hydrogel fiber spinning by using a single-module or double-module device. Moreover, thanks to the PnP approach, multi-layered fibers can be produced by using a triple-module device. As proof-of-principle, we fabricated pH-sensitive multi-layered fibers that could be used for monitoring biological environments, showcasing the potential of such a PnP device in advancing biomedical research related to functional fibers.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397622","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}
Marsel Lino, Henrik Persson, Mohammad Paknahad, Alisa Ugodnikov, Morvarid Farhang Ghahremani, Lily E Takeuchi, Oleg Chebotarev, Caleb Horst, Craig A Simmons
Biological barriers formed by the endothelium and epithelium regulate nutrient exchange, disease development, and drug delivery. Organ-on-chip (OOC) systems effectively model these barriers by incorporating key biophysical cues like microscale dimensions, co-culture, and fluid flow-induced shear stress. The majority of microfluidic OOC platforms, however, require syringe and pump systems which are hindered by several limitations, including large footprints, elaborate designs, long setup times, and a high rate of failure (contamination, leakage, etc.). Here we describe VitroFlo, a pump-free microfluidic device designed for in vitro biological barrier modeling with 12 independent co-culture modules that can be simultaneously subjected to tunable, unidirectional flow with physiological shear stresses ranging from 0.01-10 dyn/cm2. We demonstrate application of the device to model vascular endothelial, blood-brain, and intestinal epithelial barriers, and confirm shear stress-dependent cell alignment, tight junction protein expression, barrier maturation, permeability, and paracrine signaling between co-cultured cells. The VitroFlo platform enables scalable and cost-effective modeling of physiological barriers to facilitate the translation of findings from in vitro systems to preclinical models.
{"title":"A pumpless microfluidic co-culture system to model the effects of shear flow on biological barriers.","authors":"Marsel Lino, Henrik Persson, Mohammad Paknahad, Alisa Ugodnikov, Morvarid Farhang Ghahremani, Lily E Takeuchi, Oleg Chebotarev, Caleb Horst, Craig A Simmons","doi":"10.1039/d4lc00835a","DOIUrl":"https://doi.org/10.1039/d4lc00835a","url":null,"abstract":"<p><p>Biological barriers formed by the endothelium and epithelium regulate nutrient exchange, disease development, and drug delivery. Organ-on-chip (OOC) systems effectively model these barriers by incorporating key biophysical cues like microscale dimensions, co-culture, and fluid flow-induced shear stress. The majority of microfluidic OOC platforms, however, require syringe and pump systems which are hindered by several limitations, including large footprints, elaborate designs, long setup times, and a high rate of failure (contamination, leakage, <i>etc.</i>). Here we describe VitroFlo, a pump-free microfluidic device designed for <i>in vitro</i> biological barrier modeling with 12 independent co-culture modules that can be simultaneously subjected to tunable, unidirectional flow with physiological shear stresses ranging from 0.01-10 dyn/cm<sup>2</sup>. We demonstrate application of the device to model vascular endothelial, blood-brain, and intestinal epithelial barriers, and confirm shear stress-dependent cell alignment, tight junction protein expression, barrier maturation, permeability, and paracrine signaling between co-cultured cells. The VitroFlo platform enables scalable and cost-effective modeling of physiological barriers to facilitate the translation of findings from <i>in vitro</i> systems to preclinical models.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381248","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}
Daina V Baker, Jasmine Bernal-Escalante, Christine Traaseth, Yihao Wang, Michael V Tran, Seth Keenan, W Russ Algar
Over the past 15 years, smartphones have had a transformative effect on everyday life. These devices also have the potential to transform molecular analysis over the next 15 years. The cameras of a smartphone, and its many additional onboard features, support optical detection and other aspects of engineering an analytical device. This article reviews the development of smartphones as platforms for portable chemical and biological analysis. It is equal parts conceptual overview, technical tutorial, critical summary of the state of the art, and outlook on how to advance smartphones as a tool for analysis. It further discusses the motivations for adopting smartphones as a portable platform, summarizes their enabling features and relevant optical detection methods, then highlights complementary technologies and materials such as 3D printing, microfluidics, optoelectronics, microelectronics, and nanoparticles. The broad scope of research and key advances from the past 7 years are reviewed as a prelude to a perspective on the challenges and opportunities for translating smartphone-based lab-on-a-chip devices from prototypes to authentic applications in health, food and water safety, environmental monitoring, and beyond. The convergence of smartphones with smart assays and smart apps powered by machine learning and artificial intelligence holds immense promise for realizing a future for molecular analysis that is powerful, versatile, democratized, and no longer just the stuff of science fiction.
{"title":"Smartphones as a platform for molecular analysis: concepts, methods, devices and future potential.","authors":"Daina V Baker, Jasmine Bernal-Escalante, Christine Traaseth, Yihao Wang, Michael V Tran, Seth Keenan, W Russ Algar","doi":"10.1039/d4lc00966e","DOIUrl":"https://doi.org/10.1039/d4lc00966e","url":null,"abstract":"<p><p>Over the past 15 years, smartphones have had a transformative effect on everyday life. These devices also have the potential to transform molecular analysis over the next 15 years. The cameras of a smartphone, and its many additional onboard features, support optical detection and other aspects of engineering an analytical device. This article reviews the development of smartphones as platforms for portable chemical and biological analysis. It is equal parts conceptual overview, technical tutorial, critical summary of the state of the art, and outlook on how to advance smartphones as a tool for analysis. It further discusses the motivations for adopting smartphones as a portable platform, summarizes their enabling features and relevant optical detection methods, then highlights complementary technologies and materials such as 3D printing, microfluidics, optoelectronics, microelectronics, and nanoparticles. The broad scope of research and key advances from the past 7 years are reviewed as a prelude to a perspective on the challenges and opportunities for translating smartphone-based lab-on-a-chip devices from prototypes to authentic applications in health, food and water safety, environmental monitoring, and beyond. The convergence of smartphones with smart assays and smart apps powered by machine learning and artificial intelligence holds immense promise for realizing a future for molecular analysis that is powerful, versatile, democratized, and no longer just the stuff of science fiction.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363153","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}
Sena Yaman, Tessa Devoe, Ugur Aygun, Ugur Parlatan, Madhusudhan Reddy Bobbili, Asma H Karim, Johannes Grillari, Naside Gozde Durmus
Biological nanomaterials have unique magnetic and density characteristics that can be employed to isolate them into subpopulations. Extracellular nanovesicles (EVs) are crucial for cellular communication; however, their isolation poses significant challenges due to their diverse sizes and compositions. We present EV-Lev, a microfluidic magnetic levitation technique for high-throughput, selective isolation of small EVs (<200 nm) from human plasma. EV-Lev overcomes the challenges posed by the subtle buoyancy characteristics of EVs, whose small size and varied densities complicate traditional magnetic levitation techniques. It employs antibody-coated polymer beads of varying densities, integrating immuno-affinity and microfluidics to isolate EVs from sub-milliliter plasma volumes efficiently. It facilitates rapid, simultaneous sorting of EV subpopulations based on surface markers, such as CD9, CD63, and CD81, achieving high yield and purity. Subsequent size and morphology analyses confirmed that the isolated EVs maintain their structural integrity. EV-Lev could help uncover the cargo and function of EV subpopulations associated with multiple diseases including cancer, infectious diseases and help to discover potential biomarkers in small volume samples, while offering a portable, cost-effective, and straightforward assay scheme.
{"title":"EV-Lev: extracellular vesicle isolation from human plasma using microfluidic magnetic levitation device.","authors":"Sena Yaman, Tessa Devoe, Ugur Aygun, Ugur Parlatan, Madhusudhan Reddy Bobbili, Asma H Karim, Johannes Grillari, Naside Gozde Durmus","doi":"10.1039/d4lc00830h","DOIUrl":"https://doi.org/10.1039/d4lc00830h","url":null,"abstract":"<p><p>Biological nanomaterials have unique magnetic and density characteristics that can be employed to isolate them into subpopulations. Extracellular nanovesicles (EVs) are crucial for cellular communication; however, their isolation poses significant challenges due to their diverse sizes and compositions. We present EV-Lev, a microfluidic magnetic levitation technique for high-throughput, selective isolation of small EVs (<200 nm) from human plasma. EV-Lev overcomes the challenges posed by the subtle buoyancy characteristics of EVs, whose small size and varied densities complicate traditional magnetic levitation techniques. It employs antibody-coated polymer beads of varying densities, integrating immuno-affinity and microfluidics to isolate EVs from sub-milliliter plasma volumes efficiently. It facilitates rapid, simultaneous sorting of EV subpopulations based on surface markers, such as CD9, CD63, and CD81, achieving high yield and purity. Subsequent size and morphology analyses confirmed that the isolated EVs maintain their structural integrity. EV-Lev could help uncover the cargo and function of EV subpopulations associated with multiple diseases including cancer, infectious diseases and help to discover potential biomarkers in small volume samples, while offering a portable, cost-effective, and straightforward assay scheme.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363151","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}
Koki Yoshida, Masahiro Tanakinoue, Hiroaki Onoe, Michinao Hashimoto
Soft actuators have developed over the last decade for diverse applications including industrial machines and biomedical devices. Integration of chemical sensors with soft actuators would be beneficial in analyzing chemical and environmental conditions, but there have been limited devices to achieve such sensing capabilities. In this work, we developed a thin-film soft actuator integrated with a paper-based chemical sensor, termed a microfluidic paper-based analytical soft actuator (μPAC). μPAC consists of (1) a silicone thin film with a 3D-printed pneumatic chamber and (2) a cellulose paper. This cellulose paper offers dual functions: the strain-limiting layer of a soft actuator and the substrate for the chemical sensor for a paper-based analytical device (μPAD). We characterized the design parameters of the actuators-namely, (1) thickness of silicone thin film, (2) chamber length, and (3) Young's modulus of silicone thin film-to evaluate the actuation performance. These characterizations suggested that the cellulose paper served as a suitable self-straining layer of the actuator, making μPAC a chemical sensor that can actuate simultaneously. Highlighting the unique capability of μPAC, we demonstrated the local detection of pH on the curved target surface. Overall, this research demonstrated the rapid fabrication of actuating chemical sensors with a unique design by combining soft actuators and μPAD, enabling chemical sensing on various surface topologies by dynamically making conformal contact.
{"title":"Microfluidic paper-based analytical soft actuators (μPAC).","authors":"Koki Yoshida, Masahiro Tanakinoue, Hiroaki Onoe, Michinao Hashimoto","doi":"10.1039/d4lc00602j","DOIUrl":"https://doi.org/10.1039/d4lc00602j","url":null,"abstract":"<p><p>Soft actuators have developed over the last decade for diverse applications including industrial machines and biomedical devices. Integration of chemical sensors with soft actuators would be beneficial in analyzing chemical and environmental conditions, but there have been limited devices to achieve such sensing capabilities. In this work, we developed a thin-film soft actuator integrated with a paper-based chemical sensor, termed a microfluidic paper-based analytical soft actuator (μPAC). μPAC consists of (1) a silicone thin film with a 3D-printed pneumatic chamber and (2) a cellulose paper. This cellulose paper offers dual functions: the strain-limiting layer of a soft actuator and the substrate for the chemical sensor for a paper-based analytical device (μPAD). We characterized the design parameters of the actuators-namely, (1) thickness of silicone thin film, (2) chamber length, and (3) Young's modulus of silicone thin film-to evaluate the actuation performance. These characterizations suggested that the cellulose paper served as a suitable self-straining layer of the actuator, making μPAC a chemical sensor that can actuate simultaneously. Highlighting the unique capability of μPAC, we demonstrated the local detection of pH on the curved target surface. Overall, this research demonstrated the rapid fabrication of actuating chemical sensors with a unique design by combining soft actuators and μPAD, enabling chemical sensing on various surface topologies by dynamically making conformal contact.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254396","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}
Terry Ching, Abraham C I van Steen, Delaney Gray-Scherr, Jessica L Teo, Anish Vasan, Joshua Jeon, Jessica Shah, Aayush Patel, Amy E Stoddard, Jennifer L Bays, Jeroen Eyckmans, Christopher S Chen
A longstanding challenge in microfluidics has been the efficient delivery of fluids from macro-scale pumping systems into microfluidic devices, known as the "world-to-chip" problem. Thus far, the entire industry has accepted the use of imperfect, rigid tubing and connectors as the ecosystem within which to operate, which, while functional, are often cumbersome, labor-intensive, prone to errors, and ill-suited for high-throughput experimentation. In this paper, we introduce TapeTech microfluidics, a flexible and scalable solution designed to address the persistent "world-to-chip" problem in microfluidics, particularly in organ-on-a-chip (OoC) applications. TapeTech offers a streamlined alternative, utilizing adhesive tape and thin-film polymers to create adaptable, integrated multi-channel ribbon connectors that simplify fluidic integration with pumps and reservoirs. Key features of TapeTech include reduced pressure surges, easy priming, rapid setup, easy multiplexing, and broad compatibility with existing devices and components, which are essential for maintaining stable fluid dynamics and protecting sensitive cell cultures. Furthermore, TapeTech is designed to flex around the lids of Petri dishes, enhancing sterility and transportability by enabling easy transfer between incubators, biosafety cabinets (BSCs), and microscopes. The rapid design-to-prototype iteration enabled by TapeTech allows users to quickly develop connectors for a wide range of microfluidic devices. Importantly, we showcase the utility of TapeTech in OoC cultures requiring fluid flow. We also highlight other utilities, such as real-time microscopy and a well-plate medium exchanger. The accessibility of this technology should enable more laboratories to simplify design and setup of microfluidic experiments, and increase technology adoption.
{"title":"TapeTech microfluidic connectors: adhesive tape-enabled solution for organ-on-a-chip system integration.","authors":"Terry Ching, Abraham C I van Steen, Delaney Gray-Scherr, Jessica L Teo, Anish Vasan, Joshua Jeon, Jessica Shah, Aayush Patel, Amy E Stoddard, Jennifer L Bays, Jeroen Eyckmans, Christopher S Chen","doi":"10.1039/d4lc00970c","DOIUrl":"10.1039/d4lc00970c","url":null,"abstract":"<p><p>A longstanding challenge in microfluidics has been the efficient delivery of fluids from macro-scale pumping systems into microfluidic devices, known as the \"world-to-chip\" problem. Thus far, the entire industry has accepted the use of imperfect, rigid tubing and connectors as the ecosystem within which to operate, which, while functional, are often cumbersome, labor-intensive, prone to errors, and ill-suited for high-throughput experimentation. In this paper, we introduce TapeTech microfluidics, a flexible and scalable solution designed to address the persistent \"world-to-chip\" problem in microfluidics, particularly in organ-on-a-chip (OoC) applications. TapeTech offers a streamlined alternative, utilizing adhesive tape and thin-film polymers to create adaptable, integrated multi-channel ribbon connectors that simplify fluidic integration with pumps and reservoirs. Key features of TapeTech include reduced pressure surges, easy priming, rapid setup, easy multiplexing, and broad compatibility with existing devices and components, which are essential for maintaining stable fluid dynamics and protecting sensitive cell cultures. Furthermore, TapeTech is designed to flex around the lids of Petri dishes, enhancing sterility and transportability by enabling easy transfer between incubators, biosafety cabinets (BSCs), and microscopes. The rapid design-to-prototype iteration enabled by TapeTech allows users to quickly develop connectors for a wide range of microfluidic devices. Importantly, we showcase the utility of TapeTech in OoC cultures requiring fluid flow. We also highlight other utilities, such as real-time microscopy and a well-plate medium exchanger. The accessibility of this technology should enable more laboratories to simplify design and setup of microfluidic experiments, and increase technology adoption.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187800","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}