Lab on a ChipPub Date : 2025-08-26DOI: 10.1039/d5lc00673b
Trisna Julian, Tao Tang, Naomi Tanga, Yang Yang, Yoichiroh Hosokawa, Yaxiaer Yalikun
{"title":"A long-term universal impedance flow cytometry platform empowered by adaptive channel height and real-time clogging-release strategy","authors":"Trisna Julian, Tao Tang, Naomi Tanga, Yang Yang, Yoichiroh Hosokawa, Yaxiaer Yalikun","doi":"10.1039/d5lc00673b","DOIUrl":"https://doi.org/10.1039/d5lc00673b","url":null,"abstract":"Impedance flow cytometry is a widely used label-free technique for single-cell analysis; however, its limited sensitivity and lack of universality have hindered its ability to replace conventional flow cytometry. In this study, we propose an adaptive microfluidic channel platform that dynamically adjusts the channel height to improve both measurement performance and system versatility. We found that reducing the channel height by one-third effectively decreases the distance between particles and the sensing electrodes, resulting in an average 3.2-fold amplification of the impedance signal. This approach also reduces signal variability by half, thereby enhancing measurement precision. Enhanced particle discrimination was demonstrated using a mixture of yeast cells and 6 μm beads, while robust cell phenotyping was achieved across multiple cell lines, including A549, C6, and NIH/3T3. By integrating this adaptive channel with an object detection algorithm, we successfully created a self-optimizing system that utilizes intentional, temporary clogging as a strategy to regulate channel height. These findings underscore the potential for a universal, high-performance impedance flow cytometry platform that simple, clog-resistant, and adaptable for a wide range of biomedical applications.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"116 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906326","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":"Disruption and nebulization of lipid vesicles using surface acoustic waves for direct mass spectrometry.","authors":"Yuqi Huang, Qian Ma, Ashton Taylor, Lucas Lienard, Theresa Evans-Nguyen, Venkat Bhethanabotla","doi":"10.1039/d5lc00692a","DOIUrl":"https://doi.org/10.1039/d5lc00692a","url":null,"abstract":"<p><p>Characterizing extracellular vesicles (EVs) using mass spectrometry (MS) provides several advantages. The molecular compositions within EVs can be analyzed at very low concentrations and can also distinguish lipids and molecules with similar structures. However, there are some challenges when analyzing EVs directly using MS, mainly due to their variations in size and biological composition, as well as their tendency to form large clusters. Here, we present a novel surface acoustic wave (SAW) sample preparation system capable of simultaneous disruption and nebulization of liposomes as a model for direct EV analysis by MS. This approach provides a mechanical alternative to traditional chemical methods, which minimizes sample preparation time, volume loss, and chemical interference while enhancing ionization efficiency. We study the influence of frequency on SAW nebulization for MS analysis of DOPC (1,2-dioleoyl-<i>sn-glycero</i>-3-phosphocholine) liposomes as well as liposome mixture. Through high-frequency Rayleigh SAW excitation, we demonstrate improved liposome disruption and enhanced ionization signals during MS analysis when combined with corona discharge ionization. We systematically investigate key parameters of device frequency, input radio frequency (RF) power, nebulization rate, acoustic heating, aerosolized droplet sizes, and surface preparation. The nebulization process was captured by high-speed imaging, which reveals the critical role of surface treatment and jetting dynamics in achieving efficient nebulization at different frequencies. Our findings reveal the frequency-dependent nature of Rayleigh SAW nebulization, highlighting its ability to generate fine, aerosolized particles that enhance MS sampling reliability and ionization efficiency. This work represents a significant advance in MS sample preparation techniques, with broad implications for lipidomics and growing interest in the analysis of biologically relevant vesicles such as EVs.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936626","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}
Lab on a ChipPub Date : 2025-08-22DOI: 10.1039/d5lc00349k
Jose Wippold, Mark Kozlowski, Joe La Fiandra, Jessica Boetticher, Alison Grafton, Justin P. Jahnke, Joshua A. Orlicki
{"title":"kappa(κ)Chip: A modular microfluidic device for analyte screening using a parallelized assays and multiple shear rate approach","authors":"Jose Wippold, Mark Kozlowski, Joe La Fiandra, Jessica Boetticher, Alison Grafton, Justin P. Jahnke, Joshua A. Orlicki","doi":"10.1039/d5lc00349k","DOIUrl":"https://doi.org/10.1039/d5lc00349k","url":null,"abstract":"Polymers are ubiquitous in the modern world, but many have low surface energies, making it difficult to engineer adhesive interactions to them. The large sequence space afforded by biology, and biology’s ability to evolve novel solutions to difficult problems, makes exploring bioinspired materials for novel adhesives attractive. However, the discovery of biologically inspired adhesive modalities requires the development of high-throughput screening methods that require small amounts of material, requirements for which microfluidics are ideally suited. In this work, we present the development of a novel microfluidic chip, the kappa(κ)Chip, which represents a significant leap in testing efficiency. The kappa(κ)Chip’s parallelized design enables 24 simultaneous adhesion tests from a single input stream. This drastically reduces experimental time and reagent consumption, and allows for more comprehensive data sets and the ability to quickly compare the performance of multiple proteins against different substrates – a capability unavailable with current single-test platforms. The chip was used to evaluate the adhesive properties of fungal hydrophobin proteins engineered to display on the surface of cells, using the adhesion of the cells as a proxy for hydrophobins ability to serve as an adhesive. The device combines microfabrication, microfluidics, material sciences, synthetic biology, Multiphysics simulation and ML in a unique way to enable the discovery of strong biological adhesives. Through the rapid screening enabled by the kappa(k)Chip, an informed rank-ordering of potential binding motifs/sequences against arbitrary substrates is achieved, and the device could also potentially be applied to studies of cell adhesion in tissue and organ environments, or marine fouling.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"23 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901288","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}
Lab on a ChipPub Date : 2025-08-22DOI: 10.1039/D5LC90080H
Wei Liu, Yaqian Li, Siyu Feng, Jia Ning, Jingyu Wang, Maling Gou, Huijun Chen, Feng Xu and Yanan Du
{"title":"Correction: Magnetically controllable 3D microtissues based on magnetic microcryogels","authors":"Wei Liu, Yaqian Li, Siyu Feng, Jia Ning, Jingyu Wang, Maling Gou, Huijun Chen, Feng Xu and Yanan Du","doi":"10.1039/D5LC90080H","DOIUrl":"10.1039/D5LC90080H","url":null,"abstract":"<p >Correction for ‘Magnetically controllable 3D microtissues based on magnetic microcryogels’ by Wei Liu <em>et al.</em>, <em>Lab Chip</em>, 2014, <strong>14</strong>, 2614–2625, https://doi.org/10.1039/C4LC00081A.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 18","pages":" 4815-4816"},"PeriodicalIF":5.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc90080h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936631","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}
Lab on a ChipPub Date : 2025-08-22DOI: 10.1039/D5LC00387C
Wen Song
{"title":"Mine-on-a-chip: megascale opportunities for microfluidics in critical materials and minerals recovery","authors":"Wen Song","doi":"10.1039/D5LC00387C","DOIUrl":"10.1039/D5LC00387C","url":null,"abstract":"<p >The rising supply gap for metal resources essential to energy, defense, and consumer technologies—the critical minerals and materials—poses one of the most pressing bottlenecks toward energy and national security. A suite of challenges ranging from resource definition to extraction and refining, however, undergird the economic feasibility and cradle-to-grave sustainability of these technologies. Myriad opportunities exist to leverage the unique advantages of microfluidics – low sample and reagent consumption, parallel processing, and rapid and low-cost testing – to understand and improve existing approaches for materials characterization, extraction, chemical analyses, reagent screening, separation. This perspective identifies key gaps and opportunities in securing the supply of minerals and materials critical to energy sustainability and aims to galvanize the lab on a chip (LoC) community in this crucial research.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 18","pages":" 4461-4472"},"PeriodicalIF":5.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00387c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901068","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}
Lab on a ChipPub Date : 2025-08-21DOI: 10.1039/d4lc00865k
Yazdan Rashidi, Christian Wagner, Steffen M Recktenwald
{"title":"Impact of sequential bifurcations on the cell-free layer of healthy and rigid red blood cells.","authors":"Yazdan Rashidi, Christian Wagner, Steffen M Recktenwald","doi":"10.1039/d4lc00865k","DOIUrl":"https://doi.org/10.1039/d4lc00865k","url":null,"abstract":"<p><p>In the microcirculation, red blood cells (RBCs) tend to move away from vessel walls, creating a central flow of cells and a peripheral cell-free layer (CFL). The CFL significantly affects blood flow and is important for lab-on-a-chip applications, such as cell-plasma separation. This study investigates how the length of the feeding branch before bifurcations affects RBC distribution and CFL formation, especially in sequential T-bifurcations. We conducted experiments to study RBC flow in microfluidic bifurcating channels of different lengths (2.5-7.5 mm) at a fixed hematocrit of 5% using both healthy and artificially rigidified RBCs. Our findings show that a minimum branch length is required before a bifurcation to achieve a steady state in the CFL. If the channel length before a second bifurcation is shorter than this minimum, reaching an equilibrium CFL in sequential bifurcations is impossible. We observe that short channels after the first bifurcation lead to increased CFL asymmetry in the daughter branches after the second bifurcation, while longer channels better maintain symmetry. Additionally, we explored the impact of RBC rigidity on CFL development. Rigid and healthy RBCs showed similar behavior at the first bifurcation, but their CFL development patterns differed significantly by the second bifurcation, affecting RBC partitioning. These results emphasize the importance of considering branch length in the study and design of bifurcations for lab-on-a-chip devices and provide insights into how impaired RBC deformability can affect blood flow.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936621","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}
Lab on a ChipPub Date : 2025-08-20DOI: 10.1039/d5lc00211g
Samantha R Schad, Joan D Beckman, Wilbur A Lam, David K Wood
{"title":"Oxygen-tunable endothelialized microvascular chip to assess hypoxia-reperfusion in sickle cell disease.","authors":"Samantha R Schad, Joan D Beckman, Wilbur A Lam, David K Wood","doi":"10.1039/d5lc00211g","DOIUrl":"https://doi.org/10.1039/d5lc00211g","url":null,"abstract":"<p><p>A better understanding of hypoxia reperfusion (H/R) injury is needed to gain deeper insight into the mechanisms driving sickle cell disease (SCD) pathophysiology. Existing <i>in vivo</i> and <i>in vitro</i> models have yet to fully explain H/R, which is typically associated with harmful inflammatory processes but has also been linked to a protective effect ameliorating subsequent severe vaso-occlusion. To address this need, we developed a novel microfluidic platform that includes three-dimensional endothelial-lined microchannels within an oxygen-tunable environment. These features enable simulation of H/R, red blood cell (RBC) sickling, and vaso-occlusion on-chip. The endothelial network cultured on-chip is physiologically relevant and expresses crucial microvascular features such as 3D lumen structure and expression of functional endothelial markers. We utilized this platform to perform an occlusion assay, evaluating the effects of hypoxic preconditioning on RBC-endothelial interactions contributing to occlusion. Our results demonstrate that both sustained mild hypoxia and cyclic hypoxia endothelial treatment reduce the likelihood of SCD occlusion on-chip. Specifically, average vaso-occlusion rates of 8.89% and 11.78% were observed among endothelialized devices preconditioned to cyclic and sustained hypoxia, respectively, compared to 57.93% and 55.05% for the control groups. Additionally, we leveraged RNA sequencing to identify differential regulation of specific genes contributing to this protective outcome. Of note, hypoxia preconditioning resulted in significant modulation of <i>CYBB</i>, <i>RELN</i>, and <i>SERPINA1</i>. These results offer a better understanding of the mechanistic changes affecting the endothelium during H/R and also offer potential targets for further exploration and therapeutic intervention in SCD.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936662","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}
Lab on a ChipPub Date : 2025-08-19DOI: 10.1039/d5lc00407a
Ludovic Keiser, Loukas Stamoulis, Baptiste Georjon, Philippe Marmottant, Benjamin Dollet
{"title":"Bubble removal in microfluidic channels surrounded by gas-permeable media: experiments and a predictive model.","authors":"Ludovic Keiser, Loukas Stamoulis, Baptiste Georjon, Philippe Marmottant, Benjamin Dollet","doi":"10.1039/d5lc00407a","DOIUrl":"10.1039/d5lc00407a","url":null,"abstract":"<p><p>Controlling the removal of bubbles from channels is crucial in microfluidics, either to eliminate air pockets if they are unwanted, or in pumpless microfluidic applications where receding bubbles is a way to induce liquid flows. To provide a better physical understanding of air removal in microchannels, we study the dynamics of invasion of wetting liquids in dead-end microchannels surrounded by an air-permeable medium. Using polydimethylsiloxane (PDMS)-based devices, we demonstrate that gas permeation through the channel walls drives an exponential decay in trapped air length with time (in marked contrast with the so-called Lucas-Washburn law of imbibition in porous media), providing a straightforward route to bubble elimination. Systematic experiments varying channel width, height, and PDMS thickness reveal how geometric and material factors modulate the refilling timescale. A simple analytical model, coupling capillarity and gas diffusion, captures these results quantitatively. For this purpose, we introduce an explicit expression for the interfacial curvature in microchannels with heterogeneous wettability (<i>e.g.</i>, PDMS-on-glass). This framework offers practical guidelines for microfluidic engineers aiming to prevent or remove trapped bubbles without relying on active pumping.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870412","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}
Lab on a ChipPub Date : 2025-08-19DOI: 10.1039/D5LC00525F
Sanghoon Lee, Won Gi Chung, Enji Kim, Eunmin Kim, Joonho Paek, Dayeon Kim, Seung Hyun An, Taekyeong Lee, Jung Ah Lim and Jang-Ung Park
{"title":"Wearable and implantable microfluidic technologies for future digital therapeutics","authors":"Sanghoon Lee, Won Gi Chung, Enji Kim, Eunmin Kim, Joonho Paek, Dayeon Kim, Seung Hyun An, Taekyeong Lee, Jung Ah Lim and Jang-Ung Park","doi":"10.1039/D5LC00525F","DOIUrl":"10.1039/D5LC00525F","url":null,"abstract":"<p >Microfluidic technology, originally developed for lab-on-a-chip applications, has rapidly expanded into wearable and implantable biomedical systems, enabling precise fluid handling for real-time biosensing, targeted drug delivery, and closed-loop therapeutics. This review provides a comprehensive overview of recent advancements in microfluidic platforms designed for integration with the human body, focusing on both wearable devices and implantable systems. Key design strategies are highlighted, including the integration of microfluidics with soft electronics, wireless communication, and multimodal sensing to enhance mechanical adaptability and functional versatility in dynamic biological environments. In addition, three critical technological directions for advancing digital therapeutics are discussed, particularly focusing on system-level stretchability, multimodal module integration, and artificial intelligence-driven data processing. These capabilities will serve as the foundation for transforming current microfluidic systems into intelligent, autonomous platforms, which will play a pivotal role in shaping future digital therapeutics that are personalized, responsive, and seamlessly integrated into everyday healthcare.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 18","pages":" 4508-4541"},"PeriodicalIF":5.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870437","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}
Lab on a ChipPub Date : 2025-08-15DOI: 10.1039/d5lc00557d
Junyoung Hwang, Siqin Yu, Cynthia M Ross, Ilenia Battiato
{"title":"Integrated Physics-Based Modeling and Microfluidics for Quantifying Multiphase Carbonate Dissolution in Rocks","authors":"Junyoung Hwang, Siqin Yu, Cynthia M Ross, Ilenia Battiato","doi":"10.1039/d5lc00557d","DOIUrl":"https://doi.org/10.1039/d5lc00557d","url":null,"abstract":"Acid dissolution of carbonate formations is critical to the energy transition and relevant to many engineering applications. The dynamics of the dissolution reaction are complex, strongly depend both on the flow properties and sample mineralogy and are further complicated by the production of carbon dioxide gas bubbles from the reactive surface, which renders the system multiphase. Quantifying the impact of multiphase flow conditions on effective reaction rates of carbonate dissolution has challenged experimental methods focused on core-based characterization techniques. In this work, we use microfluidic devices that contain carbonate-rich (86 wt%) rock samples with a cylindrical shape to observe their dissolution upon injection of hydrochloric (HCl) acid under both single and multiphase conditions. The dissolution reaction is visualized and recorded at high temporal resolution using a high-speed camera and is quantified through machine learning (ML)-based image segmentation. First, we combine ML-enabled image analysis with physics-based modeling to estimate the instantaneous reaction rates of carbonate dissolution under single-phase conditions and validate that it follows a first-order reaction rate law. Then, we use the proposed approach to determine the effective dissolution rate under multiphase flow conditions, i.e. when - at higher HCl concentration - the formation of CO$_2$ bubbles shields the adjacent carbonate surface hindering reaction progress. We find that, under such conditions, the effective reaction rate decreases by one order of magnitude, strongly deviating from the reaction rate law previously determined for single-phase conditions and that current models are not able to capture the impact of gas shielding effects on effective reaction rates under multiphase flow conditions. We also find that the natural chemical heterogeneity of rocks leads to the in situ formation of an unreacted mineral porous layer which serves as the substrate for gas bubbles to nucleate and grow, which changes the conceptual model established for calcite systems.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"14 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857980","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}