Microfluidic probes (MFPs) are an emerging class of open microfluidic devices that use hydrodynamic flow confinement (HFC) to enable precise, contact-free delivery and removal of fluids on biological surfaces. Unlike closed-channel microfluidics, MFPs operate in open environments, allowing localized chemical and biological interactions with high spatial and temporal resolution. Since their introduction in 2005, MFPs have advanced through major innovations, including multipolar flow designs, vertical configurations, 3D printing, and structural enhancements such as herringbone mixers. This review presents a comprehensive overview of MFP technologies, covering core physical principles, flow dynamics, operating modes, and the influence of geometric and hydrodynamic design. We examine fabrication techniques such as photolithography, soft lithography, and 3D printing, highlighting their trade-offs in precision, scalability, and cost. We also explore biological applications of MFPs, including tissue assays, cellular manipulation, molecular patterning, and single-cell biopsy. Emerging integrations with heating, dielectrophoresis, and real-time feedback are expanding the utility of MFPs for adaptive, high-throughput workflows. By tracing two decades of development, this review positions MFPs as transformative tools in open-space microfluidics and outlines opportunities for future progress.
{"title":"Twenty Years of Microfluidic Probes and Open-Space Microfluidics: From Origins to Emerging Directions","authors":"Dima Samer Ali, Ayoub Glia, Mohammad Qasaimeh","doi":"10.1039/d5lc00879d","DOIUrl":"https://doi.org/10.1039/d5lc00879d","url":null,"abstract":"Microfluidic probes (MFPs) are an emerging class of open microfluidic devices that use hydrodynamic flow confinement (HFC) to enable precise, contact-free delivery and removal of fluids on biological surfaces. Unlike closed-channel microfluidics, MFPs operate in open environments, allowing localized chemical and biological interactions with high spatial and temporal resolution. Since their introduction in 2005, MFPs have advanced through major innovations, including multipolar flow designs, vertical configurations, 3D printing, and structural enhancements such as herringbone mixers. This review presents a comprehensive overview of MFP technologies, covering core physical principles, flow dynamics, operating modes, and the influence of geometric and hydrodynamic design. We examine fabrication techniques such as photolithography, soft lithography, and 3D printing, highlighting their trade-offs in precision, scalability, and cost. We also explore biological applications of MFPs, including tissue assays, cellular manipulation, molecular patterning, and single-cell biopsy. Emerging integrations with heating, dielectrophoresis, and real-time feedback are expanding the utility of MFPs for adaptive, high-throughput workflows. By tracing two decades of development, this review positions MFPs as transformative tools in open-space microfluidics and outlines opportunities for future progress.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021973","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}
Daniel B. Rodrigues, Daniela Cruz-Moreira, Luca Gasperini, Mariana Jarnalo, Ricardo Horta, Rui Reis, Rogério Pirraco
As studies continue to bring forward data on both the complexity and heterogeneity behind the tumor microenvironment, new strategies to understand and unravel the cellular interactions that regulate tumor progression and tumor cell invasion are required. Here, we present a novel and tailorable 4-well 3D culture chamber design capable of studying chemotaxis between several distinct cell types and a cancer cell population of interest. The use of a type I collagen hydrogel as the 3D substrate allowed for a differential molecule diffusion, in which rate of diffusion was associated with molecular weight. When culturing different human stromal cells (hASCs, hDMECs and hDFbs) in the outer wells while keeping VMM15 melanoma cells within the central well it was observed that hASCs and hDFbs presented directional migration throughout the collagen matrix towards the tumor cells. Further analysis revealed a higher area of migration present in the hDFbs when compared to the hASCs, supporting the potential of this system to study the recruitment of supporting cells by cancer cells and how this may impact tumor invasion.
{"title":"A 3D model to evaluate cell chemotaxis within a heterogenic tumor microenvironment","authors":"Daniel B. Rodrigues, Daniela Cruz-Moreira, Luca Gasperini, Mariana Jarnalo, Ricardo Horta, Rui Reis, Rogério Pirraco","doi":"10.1039/d5lc00763a","DOIUrl":"https://doi.org/10.1039/d5lc00763a","url":null,"abstract":"As studies continue to bring forward data on both the complexity and heterogeneity behind the tumor microenvironment, new strategies to understand and unravel the cellular interactions that regulate tumor progression and tumor cell invasion are required. Here, we present a novel and tailorable 4-well 3D culture chamber design capable of studying chemotaxis between several distinct cell types and a cancer cell population of interest. The use of a type I collagen hydrogel as the 3D substrate allowed for a differential molecule diffusion, in which rate of diffusion was associated with molecular weight. When culturing different human stromal cells (hASCs, hDMECs and hDFbs) in the outer wells while keeping VMM15 melanoma cells within the central well it was observed that hASCs and hDFbs presented directional migration throughout the collagen matrix towards the tumor cells. Further analysis revealed a higher area of migration present in the hDFbs when compared to the hASCs, supporting the potential of this system to study the recruitment of supporting cells by cancer cells and how this may impact tumor invasion.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"194 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001584","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}
Ming Cao, Xiaoshan Jin, Meirong Yi, Xiaoxiao Chen, Fangsheng Huang, Zhiqiang Zhu, Shengyun Ji, Ke Li, Yichuan Dai and Jianfeng Chen
In confined spaces where early fire detection and suppression are particularly challenging, failures in fire prevention and control can lead to severe personal injury and property loss. In such scenarios, the structured encapsulation and controlled release of fire-extinguishing agents are especially critical. However, systematic studies on the structural design of extinguishing agents and their fire-suppression mechanisms remain notably insufficient. Based on non-planar microfluidic technology, this study designed a novel PDMS microfluidic device for the highly efficient preparation of thermally responsive water-based fire-extinguishing microcapsules. Through rational design of the microcapsule structure and substrates, we achieved not only controllable adjustment of the agent dosage but also precise regulation over the release direction and coverage area of fine water mist. In accordance with the UL94 V-0 standard, the optimal microcapsule size was determined to be 550 μm in diameter with a shell thickness of 35 μm. Furthermore, integration of the microcapsules into a thermally responsive patch enabled effective flame suppression within 3 seconds. The water-based microcapsule system is environmentally benign, highly efficient, and cost-effective, offering a high-performance microencapsulated fire-extinguishing technology with directional release capability for early fire prevention and control in confined spaces, showing promising application potential.
{"title":"Size optimization of fire-extinguishing microcapsules fabricated via non-planar microfluidics and their performance study","authors":"Ming Cao, Xiaoshan Jin, Meirong Yi, Xiaoxiao Chen, Fangsheng Huang, Zhiqiang Zhu, Shengyun Ji, Ke Li, Yichuan Dai and Jianfeng Chen","doi":"10.1039/D5LC01058F","DOIUrl":"10.1039/D5LC01058F","url":null,"abstract":"<p >In confined spaces where early fire detection and suppression are particularly challenging, failures in fire prevention and control can lead to severe personal injury and property loss. In such scenarios, the structured encapsulation and controlled release of fire-extinguishing agents are especially critical. However, systematic studies on the structural design of extinguishing agents and their fire-suppression mechanisms remain notably insufficient. Based on non-planar microfluidic technology, this study designed a novel PDMS microfluidic device for the highly efficient preparation of thermally responsive water-based fire-extinguishing microcapsules. Through rational design of the microcapsule structure and substrates, we achieved not only controllable adjustment of the agent dosage but also precise regulation over the release direction and coverage area of fine water mist. In accordance with the UL94 V-0 standard, the optimal microcapsule size was determined to be 550 μm in diameter with a shell thickness of 35 μm. Furthermore, integration of the microcapsules into a thermally responsive patch enabled effective flame suppression within 3 seconds. The water-based microcapsule system is environmentally benign, highly efficient, and cost-effective, offering a high-performance microencapsulated fire-extinguishing technology with directional release capability for early fire prevention and control in confined spaces, showing promising application potential.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 735-749"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021671","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}
Xinying Xie, Qining Leo Wang, Runxiao Shi, Tengteng Lei, Chang-Jin "CJ" Kim, Man Wong
Based on electro-wetting mechanism, digital microfluidics (DMF) today utilizes both direct-drive and active-matrix (AM) control of electrodes. Recently, DMF with surfactant-mediated electro-dewetting that electrically induces hydrophobic repulsion of droplets containing ionic surfactant has also been demonstrated. However, the existing electro-dewetting DMF devices are on a direct-drive controlled electrode array, which limits the number of independent electrodes. Reported in this work is an electro-dewetting DMF device on an AM array by providing the continuous current needed for electrodewetting. Indium-tin-zinc oxide top-gate self-aligned thin-film transistors are employed in the cell circuit to address and drive droplets with low voltage. The resulting AM electro-dewetting DMF devices are confirmed to transport, split, and merge droplets by using low voltage, opening the path for electro-dewetting DMF that offers a large number of independent electrodes.
{"title":"Active-Matrix Digital Microfluidic Device Based on Surfactant-Mediated Electro-Dewetting","authors":"Xinying Xie, Qining Leo Wang, Runxiao Shi, Tengteng Lei, Chang-Jin \"CJ\" Kim, Man Wong","doi":"10.1039/d5lc00992h","DOIUrl":"https://doi.org/10.1039/d5lc00992h","url":null,"abstract":"Based on electro-wetting mechanism, digital microfluidics (DMF) today utilizes both direct-drive and active-matrix (AM) control of electrodes. Recently, DMF with surfactant-mediated electro-dewetting that electrically induces hydrophobic repulsion of droplets containing ionic surfactant has also been demonstrated. However, the existing electro-dewetting DMF devices are on a direct-drive controlled electrode array, which limits the number of independent electrodes. Reported in this work is an electro-dewetting DMF device on an AM array by providing the continuous current needed for electrodewetting. Indium-tin-zinc oxide top-gate self-aligned thin-film transistors are employed in the cell circuit to address and drive droplets with low voltage. The resulting AM electro-dewetting DMF devices are confirmed to transport, split, and merge droplets by using low voltage, opening the path for electro-dewetting DMF that offers a large number of independent electrodes.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"60 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995948","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}
Dear Editor, Thank you very much for your work and time on our manuscript entitled as “Wearable Biosensors for Disease Diagnostics and Health Monitoring: Recent Progress and Emerging Technologies”. This is a revision for LC-CRV-09-2025-000892. We also sincerely thank reviewers for their constructive comments. The manuscript has been thoroughly revised accordingly. Please find the attached revised manuscript, supporting information, and response to reviewers. Our responses have been made point by point according to the Reviewers' comments (blue text). All corrections were marked with red in the text. We do hope that the revised manuscript will be taken into consideration for publication in Lab on a Chip. Should you have any questions, please feel free to contact me. Sincerely, Yue Cui
{"title":"Wearable Biosensors for Disease Diagnostics and Health Monitoring: Recent Progress and Emerging Technologies","authors":"Zixuan Ren, Yue Cui","doi":"10.1039/d5lc00892a","DOIUrl":"https://doi.org/10.1039/d5lc00892a","url":null,"abstract":"Dear Editor, Thank you very much for your work and time on our manuscript entitled as “Wearable Biosensors for Disease Diagnostics and Health Monitoring: Recent Progress and Emerging Technologies”. This is a revision for LC-CRV-09-2025-000892. We also sincerely thank reviewers for their constructive comments. The manuscript has been thoroughly revised accordingly. Please find the attached revised manuscript, supporting information, and response to reviewers. Our responses have been made point by point according to the Reviewers' comments (blue text). All corrections were marked with red in the text. We do hope that the revised manuscript will be taken into consideration for publication in Lab on a Chip. Should you have any questions, please feel free to contact me. Sincerely, Yue Cui","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"222 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993165","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}
Elham Akbari, Jason Paul Beech, Johannes Kumra Ahnlide, Sebastian Wrighton, Pontus Nordenfelt, Jonas Olof Tegenfeldt
Group A Streptococcus (GAS) forms highly deformable aggregates with broad variations in size and morphology, complicating controlled separation and biological analysis. Reliable methods to isolate fractions of GAS clusters with defined properties are essential for studying host–pathogen interactions that depend on cluster size. Here, we present a simple deterministic lateral displacement (DLD) microfluidic device to separate complex suspensions of bacterial aggregates into two size-enriched fractions. We use a DLD with a small displacement angle to accommodate the large range of particle sizes above the critical size. We introduce an intermediate outlet, in addition to the conventional zigzag and displacement outlets, to collect the aggregates which exhibit a large dispersion due to their broad variety in shape and sizes close to the device critical diameter. In this way, we can demonstrate fractionation of GAS clusters with >90% purity based on effective size while causing minimal fragmentation or additional aggregation, as demonstrated by image analysis and dual-colour experiments. Finally, we show biological relevance through a live immune-cell assay, where human immune cells migrate more rapidly in the presence of larger GAS clusters than in smaller clusters or single bacteria. These results demonstrate that DLD-based separation provides biologically meaningful fractions of bacterial aggregates and enables new analyses of how cluster size influences immune responses.
{"title":"Size-based sorting of dynamic bacterial clusters","authors":"Elham Akbari, Jason Paul Beech, Johannes Kumra Ahnlide, Sebastian Wrighton, Pontus Nordenfelt, Jonas Olof Tegenfeldt","doi":"10.1039/d5lc01111f","DOIUrl":"https://doi.org/10.1039/d5lc01111f","url":null,"abstract":"Group A Streptococcus (GAS) forms highly deformable aggregates with broad variations in size and morphology, complicating controlled separation and biological analysis. Reliable methods to isolate fractions of GAS clusters with defined properties are essential for studying host–pathogen interactions that depend on cluster size. Here, we present a simple deterministic lateral displacement (DLD) microfluidic device to separate complex suspensions of bacterial aggregates into two size-enriched fractions. We use a DLD with a small displacement angle to accommodate the large range of particle sizes above the critical size. We introduce an intermediate outlet, in addition to the conventional zigzag and displacement outlets, to collect the aggregates which exhibit a large dispersion due to their broad variety in shape and sizes close to the device critical diameter. In this way, we can demonstrate fractionation of GAS clusters with >90% purity based on effective size while causing minimal fragmentation or additional aggregation, as demonstrated by image analysis and dual-colour experiments. Finally, we show biological relevance through a live immune-cell assay, where human immune cells migrate more rapidly in the presence of larger GAS clusters than in smaller clusters or single bacteria. These results demonstrate that DLD-based separation provides biologically meaningful fractions of bacterial aggregates and enables new analyses of how cluster size influences immune responses.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972348","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}
Abdullah-Bin Siddique,Shaghayegh Mirhosseini,Nathan S Swami
Precise manipulation of small sample volumes through enrichment, metering, routing, and selective sorting defines the analytical performance of microfluidic systems. While passive approaches such as deterministic lateral displacement and inertial microfluidics offer robust geometry-encoded separations and field-based techniques like dielectrophoresis, magnetophoresis, and acoustofluidics provide dynamic control, they are limited by inability for tuning, susceptibility to sample media properties, and hardware complexity. Diaphragm-based actuation overcomes these constraints by introducing deformable membranes that dynamically reconfigure channel geometry to achieve sub-second fluidic control without direct exposure to external fields. This review consolidates diaphragm-actuated microfluidic strategies as a unified framework for active sample manipulation, spanning two key functions, enrichment (analyte/cell trapping, ion-transport focusing, and nanoconfinement) and activated sorting (label-based, label-free, and hybrid modalities). Diaphragm materials, geometries, and actuation schemes (pneumatic, piezoelectric, electrostatic, electromagnetic, thermo-pneumatic, and shape-memory) are benchmarked against quantitative performance metrics like pressure-deflection transfer, latency, enrichment efficiency, selectivity, and gating accuracy. Emerging directions include smart fatigue-resistant diaphragm materials, sensor-integrated feedback control, real-time programmable gating, scalable fabrication, and artificial intelligence (AI) to process multimodal data to trigger actuation. By bridging sample enrichment and activated sorting within a single mechanical paradigm, diaphragm-based actuation provides a versatile route towards autonomous, label-free, and high-content lab-on-a-chip systems for next-generation diagnostics, single-cell analytics, and biomanufacturing workflows.
{"title":"Diaphragm-based microfluidic platforms for reconfigurable sample manipulation: from enrichment to activated sorting.","authors":"Abdullah-Bin Siddique,Shaghayegh Mirhosseini,Nathan S Swami","doi":"10.1039/d5lc00984g","DOIUrl":"https://doi.org/10.1039/d5lc00984g","url":null,"abstract":"Precise manipulation of small sample volumes through enrichment, metering, routing, and selective sorting defines the analytical performance of microfluidic systems. While passive approaches such as deterministic lateral displacement and inertial microfluidics offer robust geometry-encoded separations and field-based techniques like dielectrophoresis, magnetophoresis, and acoustofluidics provide dynamic control, they are limited by inability for tuning, susceptibility to sample media properties, and hardware complexity. Diaphragm-based actuation overcomes these constraints by introducing deformable membranes that dynamically reconfigure channel geometry to achieve sub-second fluidic control without direct exposure to external fields. This review consolidates diaphragm-actuated microfluidic strategies as a unified framework for active sample manipulation, spanning two key functions, enrichment (analyte/cell trapping, ion-transport focusing, and nanoconfinement) and activated sorting (label-based, label-free, and hybrid modalities). Diaphragm materials, geometries, and actuation schemes (pneumatic, piezoelectric, electrostatic, electromagnetic, thermo-pneumatic, and shape-memory) are benchmarked against quantitative performance metrics like pressure-deflection transfer, latency, enrichment efficiency, selectivity, and gating accuracy. Emerging directions include smart fatigue-resistant diaphragm materials, sensor-integrated feedback control, real-time programmable gating, scalable fabrication, and artificial intelligence (AI) to process multimodal data to trigger actuation. By bridging sample enrichment and activated sorting within a single mechanical paradigm, diaphragm-based actuation provides a versatile route towards autonomous, label-free, and high-content lab-on-a-chip systems for next-generation diagnostics, single-cell analytics, and biomanufacturing workflows.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"267 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961258","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}
Jingjin Ge,Chenhao Bai,Zhuo Chen,Toshio Fukuda,Tatsuo Arai,Xiaoming Liu
Traditional microfluidic chips for single-cell mechanical characterization face challenges such as cell aggregation and low throughput, limiting their clinical applicability. While fluid-driven methods such as constricted extrusion, pipette aspiration, and shear-induced or stretch-induced deformation have demonstrated laboratory success, they require improvements in accuracy and scalability. To overcome these limitations, integration of external physical fields, including acoustic, optical, electrical, and magnetic, enables non-contact, high-throughput cell operations and analysis. Acoustic waves and magnetic fields provide precise control over cell deformation, optical tweezers enable contact-free trapping, and electric fields facilitate dielectrophoretic manipulation. These techniques improve measurement sensitivity and throughput, making them more suitable for clinical applications, but also increase follow-up processing time. Artificial intelligence (AI) further enhances microfluidic automation across all these methodologies by enabling real-time image processing, parameter optimization, and data analysis to shorten processing time. This review particularly explores how AI is poised to solve fundamental, long-standing problems in cell mechanics that are intractable for conventional methods. Future microfluidic systems will integrate multiple physical fields controlled with AI, improving precision and scalability. The convergence of microfluidics, external fields, and AI is expected to revolutionize single-cell mechanobiology, advancing both fundamental research and clinical applications.
{"title":"On-chip characterization of cell mechanics assisted by external physical fields and artificial intelligence.","authors":"Jingjin Ge,Chenhao Bai,Zhuo Chen,Toshio Fukuda,Tatsuo Arai,Xiaoming Liu","doi":"10.1039/d5lc00855g","DOIUrl":"https://doi.org/10.1039/d5lc00855g","url":null,"abstract":"Traditional microfluidic chips for single-cell mechanical characterization face challenges such as cell aggregation and low throughput, limiting their clinical applicability. While fluid-driven methods such as constricted extrusion, pipette aspiration, and shear-induced or stretch-induced deformation have demonstrated laboratory success, they require improvements in accuracy and scalability. To overcome these limitations, integration of external physical fields, including acoustic, optical, electrical, and magnetic, enables non-contact, high-throughput cell operations and analysis. Acoustic waves and magnetic fields provide precise control over cell deformation, optical tweezers enable contact-free trapping, and electric fields facilitate dielectrophoretic manipulation. These techniques improve measurement sensitivity and throughput, making them more suitable for clinical applications, but also increase follow-up processing time. Artificial intelligence (AI) further enhances microfluidic automation across all these methodologies by enabling real-time image processing, parameter optimization, and data analysis to shorten processing time. This review particularly explores how AI is poised to solve fundamental, long-standing problems in cell mechanics that are intractable for conventional methods. Future microfluidic systems will integrate multiple physical fields controlled with AI, improving precision and scalability. The convergence of microfluidics, external fields, and AI is expected to revolutionize single-cell mechanobiology, advancing both fundamental research and clinical applications.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"233 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961257","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}
Je Hyun Lee, Taesoo Jang, Soeun Park, Su-Bin Shin, Jaemoon Lee, Yoon-Ho Hwang, Hyomin Lee
3D printing is reshaping droplet microfluidics by converting digital designs into sealed, volumetric devices that integrate non-planar droplet generators and junctions, as well as embedded distributors. This Critical Review distills design rules that link geometry, key dimensionless groups (Ca, φ, λ), and wetting control to the robust production of single and multiple emulsions. We compare 3D printing modalities using criteria specific to droplet microfluidics, attainable feature size, optical clarity, chemical resistance, surface roughness, native wettability, and cleanability, and provide practical guidance on material–fluid compatibility, extractables, and long-run stability. We formalize scale-up via hydraulic balancing and unit-resistor strategies that preserve monodispersity across arrays, and outline selective surface treatments and multi-material printing approaches for achieving durable wettability patterns. Finally, we highlight AI/digital-twin workflows for predictive design and adaptive control, and map pathways toward standardized, manufacturable devices. These principles offer a conservative, application-oriented blueprint for 3D-printed droplet microfluidic devices.
{"title":"3D Printing of Droplet Microfluidic Devices: Principles, Wetting Control, Scale-Up, and Beyond","authors":"Je Hyun Lee, Taesoo Jang, Soeun Park, Su-Bin Shin, Jaemoon Lee, Yoon-Ho Hwang, Hyomin Lee","doi":"10.1039/d5lc01011j","DOIUrl":"https://doi.org/10.1039/d5lc01011j","url":null,"abstract":"3D printing is reshaping droplet microfluidics by converting digital designs into sealed, volumetric devices that integrate non-planar droplet generators and junctions, as well as embedded distributors. This Critical Review distills design rules that link geometry, key dimensionless groups (Ca, φ, λ), and wetting control to the robust production of single and multiple emulsions. We compare 3D printing modalities using criteria specific to droplet microfluidics, attainable feature size, optical clarity, chemical resistance, surface roughness, native wettability, and cleanability, and provide practical guidance on material–fluid compatibility, extractables, and long-run stability. We formalize scale-up via hydraulic balancing and unit-resistor strategies that preserve monodispersity across arrays, and outline selective surface treatments and multi-material printing approaches for achieving durable wettability patterns. Finally, we highlight AI/digital-twin workflows for predictive design and adaptive control, and map pathways toward standardized, manufacturable devices. These principles offer a conservative, application-oriented blueprint for 3D-printed droplet microfluidic devices.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"50 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972349","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}
Hongxia Li, Xuhui Chen, Du Qiao, Xue Zhang, Jiang Zhang, Jianan Zou, Danyang Zhao, Xuhong Qian, Honglin Li
Precise spatiotemporal manipulation of particles in complex microfluidic channel networks (MCNs) underlies numerous advanced applications, but remains constrained by the difficulty of rapidly translating prescribed trajectories into manufacturable device designs. In this work, we introduce a modular deep learning framework that overcomes these limitations by decomposing MCNs into standardized, reusable functional modules with well-characterized fluidic and structural properties. For each module, a dedicated neural network predicts the full spatiotemporal particle state—including position, velocity, and transit time—under diverse flow conditions. A multi-module reconfiguration algorithm (MMRA) assembles these local predictions into continuous, device-scale trajectories while rigorously preserving physical state continuity. This approach enables deterministic port routing and precise spatiotemporal scheduling on “DUT” and “grid” chips, with a mean absolute timing error below 0.031 s. Integrated into PathChip, our user-friendly end-to-end design platform, the proposed approach enables users to specify target particle behaviors and automatically generate optimized module sequences, geometries, and control parameters, producing fabrication-ready device blueprints. Using this reverse design workflow, the integration of 5,000 modules can be completed in as little as 18 s. This work establishes a structurally scalable pathway toward programmable, device-level spatiotemporal particle manipulation in microfluidics, with broad implications for lab-on-a-chip automation, high-throughput screening, and adaptive microfluidic systems.
{"title":"Deep learning-driven microfluidic chip architecture design for intelligent particle motion control","authors":"Hongxia Li, Xuhui Chen, Du Qiao, Xue Zhang, Jiang Zhang, Jianan Zou, Danyang Zhao, Xuhong Qian, Honglin Li","doi":"10.1039/d5lc01185j","DOIUrl":"https://doi.org/10.1039/d5lc01185j","url":null,"abstract":"Precise spatiotemporal manipulation of particles in complex microfluidic channel networks (MCNs) underlies numerous advanced applications, but remains constrained by the difficulty of rapidly translating prescribed trajectories into manufacturable device designs. In this work, we introduce a modular deep learning framework that overcomes these limitations by decomposing MCNs into standardized, reusable functional modules with well-characterized fluidic and structural properties. For each module, a dedicated neural network predicts the full spatiotemporal particle state—including position, velocity, and transit time—under diverse flow conditions. A multi-module reconfiguration algorithm (MMRA) assembles these local predictions into continuous, device-scale trajectories while rigorously preserving physical state continuity. This approach enables deterministic port routing and precise spatiotemporal scheduling on “DUT” and “grid” chips, with a mean absolute timing error below 0.031 s. Integrated into PathChip, our user-friendly end-to-end design platform, the proposed approach enables users to specify target particle behaviors and automatically generate optimized module sequences, geometries, and control parameters, producing fabrication-ready device blueprints. Using this reverse design workflow, the integration of 5,000 modules can be completed in as little as 18 s. This work establishes a structurally scalable pathway toward programmable, device-level spatiotemporal particle manipulation in microfluidics, with broad implications for lab-on-a-chip automation, high-throughput screening, and adaptive microfluidic systems.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"5 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993166","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}
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