Lab on a Chip最新文献

{"title":"Organ-on-a-chip: key industry insights, challenges, and opportunities from 100+ NSF I-Corps interviews","authors":"Ronin-Mae Komarnisky, Shaun Wootten, Nathan Friedman and Mehdi Nikkhah","doi":"10.1039/D5LC00426H","DOIUrl":"10.1039/D5LC00426H","url":null,"abstract":"<p >Organ-on-a-chip (OoC) is a rapidly advancing technology with significant potential to revolutionize healthcare, drug discovery, and personalized medicine. OoC technologies offer cost-effective and ethical platforms that enable the acquisition of physiologically relevant data and enhance our understanding of human disease mechanisms and drug responsiveness. Over the past decade, numerous academic start-ups and spin-offs have sought to translate foundational research on OoC platforms from the lab bench to commercial and real-world applications. However, industry adoption of these systems has been limited, resulting in a marginal impact on personalized medicine and drug discovery – two key application areas for OoC technology. The U.S. National Science Foundation Innovation Corps (NSF I-Corps™) program, an entrepreneurial training program, provides a means to assess the commercialization potential of academically developed technologies, such as, for instance, OoC, by encouraging in-depth discussions with over 100 key stakeholders and potential customers within relevant areas. Our research group participated in the Fall 2024 cohort of the NSF I-Corps program, conducting 100+ (<em>i.e.</em> 102) interviews with OoC experts, clinicians, and professionals across the pharmaceutical and biotech industries. This perspective article summarizes our collective effort and the insights gained from this program, offering valuable knowledge for the OoC community. Overall, the vision of our NSF I-Corps interviewees highlighted the urgent need for OoC standardization, reproducibility, reliability, scalability, as well as ease of usability along with regulatory acceptance. Moreover, these interviews highlighted a critical gap between academic innovations and commercial applications, emphasizing the importance of bridging collaboration between the two entities. This perspective further explores the current commercialization potential of OoC technologies and outlines the key hurdles that must be addressed for OoC technologies to achieve broader adoption in drug discovery and personalized medicine.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 19","pages":" 4828-4843"},"PeriodicalIF":5.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962748","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":"Tunable cell separation using a thermo-responsive deterministic lateral displacement device","authors":"Ze Jiang, Yusuke Kanno, Takasi Nisisako","doi":"10.1039/d5lc00783f","DOIUrl":"https://doi.org/10.1039/d5lc00783f","url":null,"abstract":"Tunability in isolating target cells of varying sizes from complex heterogeneous samples is essential for biomedical research and diagnostics. However, conventional deterministic lateral displacement (DLD) systems lack flexibility due to their fixed critical diameters (Dc). Here, we present a thermo-responsive DLD micropillar array that enables tunable cell separation by dynamically modulating Dc through temperature control. Our device integrates poly(N-isopropylacrylamide) (PNIPAM) hydrogel micropillars within a PDMS-silicon microfluidic chip mounted on a Peltier element, enabling precise Dc adjustments from 0.8 to 29.0 μm within a temperature range of 20–40 °C. Transient and steady-state simulations confirmed that the silicon substrate enhances thermal performance, ensuring rapid and uniform temperature regulation. Using blood samples containing human breast adenocarcinoma cells (MCF-7), we demonstrated three separation modes: (i) major separation at 25°C, isolating MCF-7 cells (average size: 17.6 μm) with 100% purity; (ii) selective separation at 26°C, targeting larger MCF-7 subpopulations (average size: 18.7 μm); (iii) minimal separation at 37°C. All processes preserved cell viability. These findings highlight the potential of our thermo-responsive DLD platform for precise, temperature-controlled cell selection, offering broad applications in biomedical research and diagnostics.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987577","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":"Concussive injuries induce neuronal stress-dependent tau mislocalization to dendritic spines with acrolein and functional network alteration in TBI-on-a-chip","authors":"Edmond A. Rogers, Tyler C. Diorio, Timothy Beauclair, Jhon Martinez, Shatha J. Mufti, David Kim, Nikita Krishnan, Vitaliy Rayz and Riyi Shi","doi":"10.1039/D5LC00067J","DOIUrl":"10.1039/D5LC00067J","url":null,"abstract":"<p >Traumatic brain injuries (TBIs) are a risk factor for Alzheimer's disease (AD), and share several important pathological features including the development of neurofibrillary tangles (NFT) of tau protein. While this association is well established, the underlying pathogenesis is poorly defined and current treatment options remain limited, necessitating novel methods and approaches. In response we developed “TBI-on-a-chip”, an <em>in vitro</em> trauma model utilizing murine cortical networks on microelectrode arrays (MEAs), capable of reproducing clinically relevant impact injuries while providing simultaneous morphological and electrophysiological readout. Here, we incorporate a digital twin of the TBI-on-a-chip model to resolve cell-scale mechanical deformation <em>via</em> shear stresses and demonstrate direct connections between impact forces with aberrations in tau and synaptic deficits, and correlate these changes with elevations of oxidative stress, a suspected key contributor to both trauma and neurodegeneration. This multi-disciplinary investigation combines computational modeling, electrophysiology, and imaging, to explore tau mislocalization and functional deficits as a function of force, in the context of a potential mechanism <em>via</em> acrolein. We hope that this novel, integrative approach will help improve our mechanistic understanding of trauma and neurodegeneration, solo and in concert, and ultimately assist in generating more effective treatment options.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 20","pages":" 5203-5220"},"PeriodicalIF":5.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00067j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesion-based cell sorting platform using on-chip centrifugation","authors":"Mao Otake, Takaaki Abe, Yoshiaki Ukita and Hiromi Miyoshi","doi":"10.1039/D5LC00578G","DOIUrl":"10.1039/D5LC00578G","url":null,"abstract":"<p >Cell sorting is an important fundamental process for the selection and purification of target cell types for cell analysis in the life sciences and medical fields. In particular, demand is increasing for high-throughput cell sorting technology for the analysis of rare cells. Toward this end, we developed a centrifugal force-based cell sorting technique that relies on the adhesion force of cells as a marker. We constructed a real-time observation device to observe the cell detachment behavior during centrifugation and identify the centrifugation conditions effective for cell sorting, such as rotation speed and application time. Furthermore, the usefulness of precoating the substrate surface with a blocking reagent to control cell adhesiveness was evaluated by image analysis of the focal adhesion combined with observation of the detaching behavior in malignant fibrosarcoma and non-cancer fibroblasts. The analysis revealed that the average size of the focal adhesions was a dominant parameter for centrifugal detachment behavior of both malignant fibrosarcoma and noncancerous fibroblasts. These findings will be applicable not only for cancer cell analysis but also in the field of regenerative medicine as a minimally invasive, high-throughput cell sorting technique.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 20","pages":" 5367-5378"},"PeriodicalIF":5.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919107","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":"Mechanical actuation on surface (MAOS) microfluidics: compression for preparation in next-generation sequencing.","authors":"Parimala Nagaraja, Rohit Lal, Cheng-Chang Lee, Eduardo Cervantes, Foteini Christodoulou, Mais J Jebrail","doi":"10.1039/d5lc00625b","DOIUrl":"https://doi.org/10.1039/d5lc00625b","url":null,"abstract":"<p><p>We present mechanical actuation on surface (MAOS), a programmable microfluidic platform that manipulates droplets <i>via</i> localized mechanical compression-eliminating the need for embedded electronics or fixed microchannel geometries. MAOS integrates essential fluidic operations-including droplet transport, magnetic bead-based purification, and thermal cycling-within a benchtop instrument and single-use cartridge. The system accommodates droplet volumes from nL to μL, enabling precise control over sequential biochemical processes. By studying the dynamic behavior of diverse fluids under compression, we identified the key physical variables-surface tension, contact angle, and viscosity-that dictate the onset of droplet motion. We observed sharp transitions in mobility around specific thresholds and validated interfacial encapsulation as a general strategy to overcome resistive pinning. We validated MAOS by first implementing and testing miniaturized next-generation sequencing (NGS) library preparation sub-processes. Magnetic bead-based cleanup showed DNA recovery and fragment size selection comparable to manual methods, and PCR amplification was carried out reliably in low-volume (5 μL) reactions with minimal evaporation. Subsequently, the full NGS library preparation workflow was executed in a plexed format, processing eight libraries in parallel on a single disposable cartridge using as little as 10% of standard reagent volumes. Short- and long-read sequencing outputs from MAOS libraries aligned with manual protocols across key quality metrics. These results establish MAOS as a scalable and user-friendly alternative to conventional microfluidics, suitable for diverse applications in molecular biology, chemistry, and high-throughput workflows.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936618","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":"Advances in large-scale electrophysiology with high-density microelectrode arrays","authors":"Manuel Schröter, Fernando Cardes, Cat-Vu H. Bui, Lorenzo Davide Dodi, Tobias Gänswein, Julian Bartram, Lorenca Sadiraj, Philipp Hornauer, Sreedhar Kumar, Maria Pascual-Garcia and Andreas Hierlemann","doi":"10.1039/D5LC00058K","DOIUrl":"10.1039/D5LC00058K","url":null,"abstract":"<p >A detailed functional characterization of electrogenic cells, such as neurons and cardiomyocytes, by means of high-density microelectrode arrays (HD-MEAs) has emerged as a powerful approach for inferring cellular phenotypes and elucidating fundamental mechanisms underlying cellular function. HD-MEAs have been applied across a range of disciplines, including neurodevelopmental research, stem cell biology, and pharmacology, and more recently in interdisciplinary work at the intersection of biomedical engineering, computer science, and artificial intelligence (AI). Innovations in chip design, fabrication, recording capabilities, and data processing have significantly advanced the functionality of HD-MEAs. Today's chips allow the study of cellular function across scales and at high throughput. They enable the analysis of multi-parametric functional phenotypes over extended time and facilitate monitoring the effects of targeted perturbations on cellular behavior. In this <em>Tutorial Review</em>, we will first survey the advances in HD-MEA design and their readout and stimulation capabilities. We will then abstract studies that used HD-MEAs in combination with other experimental techniques to probe biologically relevant cellular and subcellular features, with an emphasis on <em>in vitro</em> applications of HD-MEAs. Thereafter, we will cover analytical techniques that are essential for analyzing and characterizing HD-MEA data. Finally, we will address current limitations of HD-MEAs and discuss potential future developments.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 19","pages":" 4844-4885"},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00058k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking microfluidic and immunomagnetic platforms for isolating circulating tumor cells in pancreatic cancer","authors":"Celine Macaraniag, Ifra Khan, Alexandra Barabanova, Valentina Valle, Jian Zhou, Pier C. Giulianotti, Alain Borgeat, Gina Votta-Velis and Ian Papautsky","doi":"10.1039/D5LC00512D","DOIUrl":"10.1039/D5LC00512D","url":null,"abstract":"<p >Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the US., with poor prognosis due to late-stage diagnosis and high recurrence rates following surgery. Circulating tumor cells (CTCs) are thought to contribute to post-surgical metastasis, while circulating epithelial cells (CECs) have been detected in up to 33% of patients with premalignant pancreatic cysts, offering a potential window for early intervention. Despite their promise as prognostic biomarkers, the clinical utility of CTCs and CECs in pancreatic cancer remains underexplored. Microfluidic technologies offer label-free isolation of rare cells, but few have been benchmarked against clinically validated systems. In this study, we conducted a direct comparison of our inertial microfluidic system with a widely used immunomagnetic negative selection platform (EasySep™). Using matched experimental conditions, we quantified target cell recovery and enrichment to evaluate performance. The inertial microfluidic system demonstrated higher recovery and enrichment, particularly at low cell concentrations, compared to EasySep™, supporting its potential for clinical translation. These findings highlight the advantages of label-free microfluidic isolation and its promise for early detection, prognostic assessment, and therapeutic monitoring in pancreatic cancer.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 20","pages":" 5292-5301"},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00512d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modular RCA-CRISPR/Cas12a amplification on a multi-volume SlipChip for ultrafast, single-copy quantification of circRNA and miRNA in ovarian cancer.","authors":"Lingxi Tian, Yan Gao, Yang Lu, Feng Xu, Zirui Feng, Lihan Zi, Zaian Deng, Jun Yang","doi":"10.1039/d5lc00585j","DOIUrl":"https://doi.org/10.1039/d5lc00585j","url":null,"abstract":"<p><p>The aberrant expression of RNAs in ovarian cancer (OC) progression highlights their potential as clinical biomarkers. However, rapid and accurate quantification of these RNAs in biosamples remains a significant challenge. In this study, we develop a modular isothermal rolling circle amplification (RCA)-activated Cas12a loop-enhanced (MIRACLE) amplification method for circRNA and miRNA quantification without the need of reverse transcription. In this design, isothermal amplification of modular DNA can be initiated by target-specific RCA primers or miRNAs, with the amplification products subsequently recognized by the Cas12a system to generate measurable signals. When integrated with a multi-volume sliding chip (SlipChip) platform, this MIRACLE method enables portable, rapid and ultra-sensitive quantification of these two types of RNA. Under optimized conditions, this platform exhibits detection limits of 0.125 copies per μL for circRNA and 0.326 copies per μL for miRNA, covering a 5-log dynamic range from 10^-1 to 10³ copies per μL within 35 min. The platform was validated using OC cell lines and clinical blood samples. It successfully profiled OC RNA biomarkers (hsa_circ_0049101 and hsa-miR-338-3p) and effectively distinguished between early and advanced stages of OC. These results show a strong correlation with RT-qPCR (<i>R</i>² = 0.953 for circRNA and <i>R</i>² = 0.947 for miRNA). This work establishes a versatile CRISPR-microfluidic platform for cancer diagnosis. Its modular design allows for adaptation to detect other cancer-related RNA biomarkers, thereby addressing critical needs in precision oncology.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936589","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":"Trapping nanoscale particles <i>via</i> quasi-Scholte mode in acoustofluidics.","authors":"Jiaqi Liu, Yuan Yu, Rujun Zhang, Yanru Chen, Yanlong Guo, Yi Zhang, Ran Tao, Jingting Luo, Hairong Zheng, Pingfa Feng, Yongqing Fu, Jianjian Wang, Feiyan Cai","doi":"10.1039/d5lc00490j","DOIUrl":"https://doi.org/10.1039/d5lc00490j","url":null,"abstract":"<p><p>Non-contact and label-free acoustic manipulation of particles is crucial for various applications ranging from cell separation and tissue engineering to micromachining and nanofabrication. Surface acoustic waves (SAWs) have been widely used for microscale particle manipulation; their leaky nature in liquid often generates significant bulk acoustic streaming that undermines stable trapping of nanoscale particles. To address this challenge, we introduce an acoustofluidic device comprising a zinc oxide (ZnO) thin film deposited on aluminum foil with one-sided water loading. This design excites quasi-Scholte waves, a specialized nonleaky mode confined to the fluid-solid interface, which effectively suppresses bulk streaming and enables stable nanoparticle trapping. Both theoretical modeling and experiments confirm that the resulting strongly evanescent field operated at 5.11 MHz generates negative vertical forces and strong lateral (in-plane) trapping forces, successfully trapping 250 nm-radius particles on the foil surface. As the particle radius decreases to 150 nm, streaming-induced drag becomes the dominant manipulation mechanism. Operable at low frequencies with a simple and scalable design, our platform offers a versatile route for precise nanoscale particle trapping, with significant potential for bioengineering and nanofabrication applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936611","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":"On-chip near-infrared gas sensing based on slow light mode multiplexing in photonic crystal waveguides","authors":"Zihang Peng, Yuting Min, Mingquan Pi, Kaiyuan Zheng, Fang Song, Lei Liang, Yiding Wang, Yu Zhang, Xue Bai and Chuantao Zheng","doi":"10.1039/D5LC00403A","DOIUrl":"10.1039/D5LC00403A","url":null,"abstract":"<p >Photonic crystal slow light waveguides present a breakthrough in the manipulation of optical signals and enhancing the interaction between light and matter. In particular, two-dimensional (2D) photonic crystal waveguides (PCWs) on silicon photonic chips hold promise in improving the sensitivity of on-chip gas sensors. However, the development of the gas sensors based on 2D PCWs suffers from a high propagation loss and a narrow slow light bandwidth. In this study, our focus was on designing a one-dimensional (1D) PCW with lower propagation loss and tailored group indices across dual distinct frequency bands. To achieve this, a mode converter was employed to effectively stimulate both odd and even modes of the 1D PCW with odd modes ranging from 1520 to 1555 nm and even modes spanning 1615–1665 nm. Remarkably, we pioneered the application of slow light mode multiplexing to demonstrate the potential of the 1D PCW as an on-chip multi-gas sensor, specifically targeting acetylene (C<small>₂</small>H<small>₂</small>) and methane (CH<small>₄</small>). At 1533 nm, the odd mode exhibited an impressive interaction factor of 0.836; while at 1654 nm, the even mode achieved an even higher interaction factor of 1.308, and both retain relatively low propagation losses. This research not only introduces innovative strategies for expanding slow light bandwidth, but also presents a promising avenue for on-chip multi-gas detection.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 20","pages":" 5318-5328"},"PeriodicalIF":5.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906324","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}