Lab on a Chip最新文献

{"title":"Developing 3D bioprinting for organs-on-chips.","authors":"Zhuhao Wu, Rui Liu, Ning Shao, Yuanjin Zhao","doi":"10.1039/d4lc00769g","DOIUrl":"https://doi.org/10.1039/d4lc00769g","url":null,"abstract":"<p><p>Organs-on-chips (OoCs) have significantly advanced biomedical research by precisely reconstructing human microphysiological systems with biomimetic functions. However, achieving greater structural complexity of cell cultures on-chip for enhanced biological mimicry remains a challenge. To overcome these challenges, 3D bioprinting techniques can be used in directly building complex 3D cultures on chips, facilitating the <i>in vitro</i> engineering of organ-level models. Herein, we review the distinctive features of OoCs, along with the technical and biological challenges associated with replicating complex organ structures. We discuss recent bioprinting innovations that simplify the fabrication of OoCs while increasing their architectural complexity, leading to breakthroughs in the field and enabling the investigation of previously inaccessible biological problems. We highlight the challenges for the development of 3D bioprinted OoCs, concluding with a perspective on future directions aimed at facilitating their clinical translation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941475","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 microfluidic platforms for tumor cell phenotyping: from bench to bedside.","authors":"Rutwik Joshi, Hesaneh Ahmadi, Karl Gardner, Robert K Bright, Wenwen Wang, Wei Li","doi":"10.1039/d4lc00403e","DOIUrl":"https://doi.org/10.1039/d4lc00403e","url":null,"abstract":"<p><p>Heterogeneities among tumor cells significantly contribute towards cancer progression and therapeutic inefficiency. Hence, understanding the nature of cancer through liquid biopsies and isolation of circulating tumor cells (CTCs) has gained considerable interest over the years. Microfluidics has emerged as one of the most popular platforms for performing liquid biopsy applications. Various label-free and labeling techniques using microfluidic platforms have been developed, the majority of which focus on CTC isolation from normal blood cells. However, sorting and profiling of various cell phenotypes present amongst those CTCs is equally important for prognostics and development of personalized therapies. In this review, firstly, we discuss the biophysical and biochemical heterogeneities associated with tumor cells and CTCs which contribute to cancer progression. Moreover, we discuss the recently developed microfluidic platforms for sorting and profiling of tumor cells and CTCs. These techniques are broadly classified into biophysical and biochemical phenotyping methods. Biophysical methods are further classified into mechanical and electrical phenotyping. While biochemical techniques have been categorized into surface antigen expressions, metabolism, and chemotaxis-based phenotyping methods. We also shed light on clinical studies performed with these platforms over the years and conclude with an outlook for the future development in this field.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941759","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":"Recent advances in centrifugal microfluidics for point-of-care testing.","authors":"Huijuan Yuan, Zeyu Miao, Chao Wan, Jingjing Wang, Jinzhi Liu, Yiwei Li, Yujin Xiao, Peng Chen, Bi-Feng Liu","doi":"10.1039/d4lc00779d","DOIUrl":"https://doi.org/10.1039/d4lc00779d","url":null,"abstract":"<p><p>Point-of-care testing (POCT) holds significant importance in the field of infectious disease prevention and control, as well as personalized precision medicine. The emerging microfluidics, capable of minimal reagent consumption, integration, and a high degree of automation, play a pivotal role in POCT. Centrifugal microfluidics, also termed lab-on-a-disc (LOAD), is a significant subfield of microfluidics that integrates crucial analytical steps onto a single chip, thereby optimizing the process and enabling high-throughput, automated analysis. By utilizing rotational mechanics to precisely control fluid dynamics without external pressure sources, centrifugal microfluidics facilitates swift operations ideal for urgent medical and field settings. This review provides a comprehensive overview of the latest advancements in centrifugal microfluidics for POCT, covering both theoretical principles and practical applications. We begin by introducing the fundamental operational principles, fluidic control mechanisms, and signal output detection methods. Subsequently, we delve into the typical applications of centrifugal microfluidic platforms in immunoassays, nucleic acid testing, antimicrobial susceptibility testing, and other tests. We also discuss the strengths and potential limitations of centrifugal microfluidic platforms, underscoring their transformative impact on traditional conventional procedures and their significant role in diagnostic practices.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941582","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":"Demystifying EV heterogeneity: emerging microfluidic technologies for isolation and multiplexed profiling of extracellular vesicles.","authors":"Guihua Zhang, Xiaodan Huang, Sinong Liu, Yiling Xu, Nan Wang, Chaoyong Yang, Zhi Zhu","doi":"10.1039/d4lc00777h","DOIUrl":"https://doi.org/10.1039/d4lc00777h","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are heterogeneous lipid containers carrying complex molecular cargoes, including proteins, nucleic acids, glycans, <i>etc.</i> These vesicles are closely associated with specific physiological characteristics, which makes them invaluable in the detection and monitoring of various diseases. However, traditional isolation methods are often labour-intensive, inefficient, and time-consuming. In addition, single biomarker analyses are no longer accurate enough to meet diagnostic needs. Routine isolation and molecular analysis of high-purity EVs in clinical applications is even more challenging. In this review, we discuss a promising solution, microfluidic-based techniques, that combine efficient isolation and multiplex detection of EVs, to further demystify EV heterogeneity. These microfluidic-based EV multiplexing platforms will hopefully facilitate development of liquid biopsies and offer promising opportunities for personalised therapy.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941469","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":"Microsensor systems for cell metabolism - from 2D culture to organ-on-chip (2019-2024).","authors":"Johannes Dornhof, Jochen Kieninger, Stefan J Rupitsch, Andreas Weltin","doi":"10.1039/d4lc00437j","DOIUrl":"https://doi.org/10.1039/d4lc00437j","url":null,"abstract":"<p><p>Cell cultures, organs-on-chip and microphysiological systems become increasingly relevant as <i>in vitro</i> models, <i>e.g.</i>, in drug development, disease modelling, toxicology or cancer research. It has been underlined repeatedly that culture conditions and metabolic cues have a strong or even essential influence on the reproducibility and validity of such experiments but are often not appropriately measured or controlled. Here we review microsensor systems for cell metabolism for the continuous measurement of culture conditions in microfluidic and lab-on-chip platforms. We identify building blocks, features and essential advantages to underline the relevance of these systems and to derive appropriate requirements for development and practical use. We discuss different formats and geometries of cell culture, microfluidics and the resulting consequences for sensor placement, as the prerequisite for understanding the various approaches and classification of the systems. The major chemical and biosensors based on electrochemical and optical principles are discussed for general understanding and to contextualize current developments. We then review selected recent sensor systems with real-world implementations of sensing in cell cultures and organs-on-chip, employing a helpful characterization. That includes formats and cell models, microfluidic systems and sensor types applied in static and dynamic monitoring of 2D and 3D cell cultures, as well as single spheroids. We discuss notable advances, particularly with respect to sensor performance and the demonstration of long-term continuous measurements. We outline current approaches to system fabrication technologies, material choice, and interfacing, and comment on recent trends. Finally, we conclude with critical remarks on the current state of sensors in cell culture monitoring and identify avenues for future improvements for both developers and users of such systems, which will lead to better and more predictive <i>in vitro</i> models.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941531","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":"Synergizing microfluidics and plasmonics: advances, applications, and future directions.","authors":"C Escobedo, A G Brolo","doi":"10.1039/d4lc00572d","DOIUrl":"https://doi.org/10.1039/d4lc00572d","url":null,"abstract":"<p><p>In the past decade, interest in nanoplasmonic structures has experienced significant growth, owing to rapid advancements in materials science and the evolution of novel nanofabrication techniques. The activities in the area are not only leading to remarkable progress in specific applications in photonics, but also permeating to and synergizing with other fields. This review delves into the symbiosis between nanoplasmonics and microfluidics, elucidating fundamental principles on nanophotonics centered on surface plasmon-polaritons, and key achievements arising from the intricate interplay between light and fluids at small scales. This review underscores the unparalleled capabilities of subwavelength plasmonic structures to manipulate light beyond the diffraction limit, concurrently serving as fluidic entities or synergistically combining with micro- and nanofluidic structures. Noteworthy phenomena, techniques and applications arising from this synergy are explored, including the manipulation of fluids at nanoscopic dimensions, the trapping of individual nanoscopic entities like molecules or nanoparticles, and the harnessing of light within a fluidic environment. Additionally, it discusses light-driven fabrication methodologies for microfluidic platforms and, contrariwise, the use of microfluidics in the fabrication of plasmonic nanostructures. Pondering future prospects, this review offers insights into potential future developments, particularly focusing on the integration of two-dimensional materials endowed with exceptional optical, structural and electrical properties, such as goldene and borophene, which enable higher carrier densities and higher plasmonic frequencies. Such advancements could catalyze innovations in diverse applications, including energy harvesting, advanced photothermal cancer therapies, and catalytic processes for hydrogen generation and CO₂ conversion.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941592","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":"Micro- and milli-fluidic sample environments for <i>in situ</i> X-ray analysis in the chemical and materials sciences.","authors":"Mark A Levenstein, Corinne Chevallard, Florent Malloggi, Fabienne Testard, Olivier Taché","doi":"10.1039/d4lc00637b","DOIUrl":"https://doi.org/10.1039/d4lc00637b","url":null,"abstract":"<p><p>X-ray-based methods are powerful tools for structural and chemical studies of materials and processes, particularly for performing time-resolved measurements. In this critical review, we highlight progress in the development of X-ray compatible microfluidic and millifluidic platforms that enable high temporal and spatial resolution X-ray analysis across the chemical and materials sciences. With a focus on liquid samples and suspensions, we first present the origins of microfluidic sample environments for X-ray analysis by discussing some alternative liquid sample holder and manipulator technologies. The bulk of the review is then dedicated to micro- and milli-fluidic devices designed for use in the three main areas of X-ray analysis: (1) scattering/diffraction, (2) spectroscopy, and (3) imaging. While most research to date has been performed at synchrotron radiation facilities, the recent progress made using commercial and laboratory-based X-ray instruments is then reviewed here for the first time. This final section presents the exciting possibility of performing <i>in situ</i> and <i>operando</i> X-ray analysis in the 'home' laboratory and transforming microfluidic and millifluidic X-ray analysis into a routine method in physical chemistry and materials research.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941525","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":"Amplification-free CRISPR/Cas based dual-enzymatic colorimetric nucleic acid biosensing device.","authors":"Guodong Tong, Pabitra Nath, Yuki Hiruta, Daniel Citterio","doi":"10.1039/d4lc01039f","DOIUrl":"https://doi.org/10.1039/d4lc01039f","url":null,"abstract":"<p><p>Nucleic acid testing (NAT) is widely considered the gold standard in analytical fields, with applications spanning environmental monitoring, forensic science and clinical diagnostics, among others. However, its widespread use is often constrained by complicated assay procedures, the need for specialized equipment, and the complexity of reagent handling. In this study, we demonstrate a fully integrated 3D-printed biosensensing device employing a CRISPR/Cas12a-based dual-enzymatic mechanism for highly sensitive and user-friendly nucleic acid detection. A plastic probe stick was designed to host small-sized gold nanoparticles, enhancing enzyme labeling density. Alkaline phosphatase (ALP) was then conjugated <i>via</i> single-stranded DNA, requiring only a single enzyme substrate addition to generate a simple visual signal change. This approach eliminates the need for amplification or centrifugation steps, achieving a limit of detection (LOD) as low as 10 pM - among the highest sensitivities reported for amplification-free colorimetric nucleic acid detection. Furthermore, we developed a device that incorporates this probe stick, integrates all necessary reagents, and features a smartphone-compatible accessory for quantitative analysis. This allows end-users to perform visual or quantitative DNA analysis with simple operations, achieving a visual detection limit of approximately 100 pM, comparable to other CRISPR-based non-amplified nucleic acid detection methods. Additionally, the system successfully distinguished perfectly matched from mismatched nucleic acid sequences, demonstrating its specificity and versatility. Although certain design limitations affected the sensitivity of the integrated device compared to the probe stick alone, the simplicity and portability of this device make it a promising tool for rapid nucleic acid screening in clinical diagnostics, environmental monitoring, and food safety control. This study paves the way for the development of practical biosensors for point-of-care testing (POCT) applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941722","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":"Challenges in blood fractionation for cancer liquid biopsy: how can microfluidics assist?","authors":"Robert Salomon, Sajad Razavi Bazaz, Kirk Mutafopulos, David Gallego-Ortega, Majid Warkiani, David Weitz, Dayong Jin","doi":"10.1039/d4lc00563e","DOIUrl":"https://doi.org/10.1039/d4lc00563e","url":null,"abstract":"<p><p>Liquid biopsy provides a minimally invasive approach to characterise the molecular and phenotypic characteristics of a patient's individual tumour by detecting evidence of cancerous change in readily available body fluids, usually the blood. When applied at multiple points during the disease journey, it can be used to monitor a patient's response to treatment and to personalise clinical management based on changes in disease burden and molecular findings. Traditional liquid biopsy approaches such as quantitative PCR, have tended to look at only a few biomarkers, and are aimed at early detection of disease or disease relapse using predefined markers. With advances in the next generation sequencing (NGS) and single-cell genomics, simultaneous analysis of both circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) is now a real possibility. To realise this, however, we need to overcome issues with current blood collection and fractionation processes. These include overcoming the need to add a preservative to the collection tube or the need to rapidly send blood tubes to a centralised processing lab with the infrastructure required to fractionate and process the blood samples. This review focuses on outlining the current state of liquid biopsy and how microfluidic blood fractionation tools can be used in cancer liquid biopsy. We describe microfluidic devices that can separate plasma for ctDNA analysis, and devices that are important in isolating the cellular component(s) in liquid biopsy, <i>i.e.</i>, individual CTCs and CTC clusters. To facilitate a better understanding of these devices, we propose a new categorisation system based on how these devices operate. The three categories being 1) solid Interaction devices, 2) fluid Interaction devices and 3) external force/active devices. Finally, we conclude that whilst some assays and some cancers are well suited to current microfluidic techniques, new tools are necessary to support broader, clinically relevant multiomic workflows in cancer liquid biopsy.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941466","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":"Sample-to-answer microfluidic device towards the point-of-need detection of <i>Staphylococcus aureus</i> enterotoxin genes in ruminant milk.","authors":"Maha Shalaby, Valentina Busin, Xiaoxiang Yan, Seyda Cengiz, Mehmet Cemal Adiguzel, Jonathan M Cooper, Taya Forde, Julien Reboud","doi":"10.1039/d4lc00907j","DOIUrl":"https://doi.org/10.1039/d4lc00907j","url":null,"abstract":"<p><p>Milk is commonly screened both for indicators of animal disease and health, but also for foodborne hazards. Included in these analyses is the detection of <i>Staphylococcus aureus</i>, that can produce an enterotoxin, causing staphylococcal food poisoning (SFP), which often leads to sudden onset of significant gastrointestinal symptoms in humans. Epidemiological data on SFP are limited, particularly in low- and middle-income countries. Many conventional assays for the detection of staphylococcal enterotoxins rely on the detection of the genes coding for them, either directly in food samples or after bacterial culture. Currently, many of the nucleic acid-based methods used require specific expertise and equipment, whilst bacterial culture takes 24-48 hours; both are contributory factors that limit efforts either during food safety emergencies or routine screening. Here we present the development of a \"sample-to-answer\" isothermal nucleic acid loop-mediated amplification (LAMP) assay in a microfluidic device for the detection of <i>Staphylococcus aureus</i> enterotoxin genes in ruminant milk. A multiplex LAMP assay targeting two of the most prevalent <i>S. aureus</i> enterotoxin-encoding genes (A and B) was integrated into a microfluidic device combining simple 1 : 10 dilution for sample preparation and a lateral flow assay for easy readout. We achieved a limit of detection of 10⁴ colony forming units per ml in spiked cow and goat milk samples, an order of magnitude more sensitive than the European recommendation for the maximum allowable presence of coagulase-positive staphylococci in raw milk. The assay showed no cross-reactivity in detecting other tested non-enterotoxigenic <i>S. aureus</i> strains or associated foodborne pathogens. The test integrated the simplicity of use of microfluidic devices with the sensitivity, specificity and rapidity of a nucleic acid-based assay, and a simple lateral flow readout to provide an appropriate device to ensure the safety of milk for human consumption. To illustrate its potential for point-of-need practical applications, the test was performed in agricultural settings in rural Turkey in a limited feasibility exercise.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941585","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}