Lab on a Chip最新文献

{"title":"Development and evaluation of a microfluidic human testicular tissue chip: a novel in vitro platform for reproductive biology and pharmacology studies.","authors":"Jiaming Shen,Xinlong Wang,Chenghua Yang,Guanyu Ren,Lei Wang,Shuguang Piao,Boyang Zhang,Weihao Sun,Xie Ge,Jun Jing,Yijian Xiang,Zhaowanyue He,Linhui Wang,Bing Yao,Zhiyong Liu","doi":"10.1039/d4lc00780h","DOIUrl":"https://doi.org/10.1039/d4lc00780h","url":null,"abstract":"Organ-on-a-chip culture systems using human organ tissues provide invaluable preclinical insights into systemic functions in vitro. This study aimed to develop a novel human testicular tissue chip within a microfluidic device employing computer-aided design software and photolithography technology. Polydimethylsiloxane was used as the primary material to ensure marked gas permeability and no biotoxicity, enabling effective mimicry of the in vivo testicular microenvironment. This biochip preserved the structural integrity and cellular composition of human testicular tissue, as well as part of its functionality, over an extended period in vitro. Moreover, compared to traditional static culture methods, it more effectively maintained tissue viability and endocrine function. The chip maintained cellular components, histological morphology, and an ultrastructure similar to those in vivo. Notably, the addition of gonadotropins to the human testis tissue on the chip resulted in consistent and steady in vitro production of testosterone and inhibin B. Additionally, the chip displayed sensitivity to the reproductive toxicity of the chemotherapeutic drug busulfan. The results demonstrate the successful establishment of a novel human testicular tissue chip culture system, providing a novel in vitro approach enabling the exploration of human reproductive biology, reproductive pharmacology, toxicology, individual diagnosis, and treatment strategies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"574 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989076","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":"A single microfluidic device for multi-omics analysis sample preparation.","authors":"Ranjith Kumar Ravi Kumar, Iman Haddad, Massamba Mbacké Ndiaye, Martial Marbouty, Joëlle Vinh, Yann Verdier","doi":"10.1039/d4lc00919c","DOIUrl":"https://doi.org/10.1039/d4lc00919c","url":null,"abstract":"<p><p>Combining different \"omics\" approaches, such as genomics and proteomics, is necessary to generate a detailed and complete insight into microbiome comprehension. Proper sample collection and processing and accurate analytical methods are crucial in generating reliable data. We previously developed the ChipFilter device for proteomic analysis of microbial samples. We have shown that this device coupled to LC-MS/MS can successfully be used to identify microbial proteins. In the present work, we have developed our workflow to analyze concomitantly proteins and nucleic acids from the same sample. We performed lysis and proteolysis in the device using cultures of <i>E. coli</i>, <i>B. subtilis</i>, and <i>S. cerevisiae</i>. After peptide recovery for LC-MS/MS analysis, DNA from the same samples was recovered and successfully amplified by PCR for the 3 species. This workflow was further extended to a complex microbial mixture of known compositions. Protein analysis was carried out, enabling the identification of more than 5000 proteins. The recovered DNA was sequenced, performing comparable to DNA extracted with a commercial kit without proteolysis. Our results show that the ChipFilter device is suited to prepare samples for parallel proteomic and genomic analyses, which is particularly relevant in the case of low-abundant samples and drastically reduces sampling bias.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996440","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":"An all-in-one microfluidic cryopreservation system and protocols with gradually increasing CPA concentration.","authors":"Tianhang Yang, Xinbei Lv, Yuqiao Bai, Huabin Jiang, Xiaoran Chang, Jinxian Wang, Gangyin Luo","doi":"10.1039/d4lc00888j","DOIUrl":"https://doi.org/10.1039/d4lc00888j","url":null,"abstract":"<p><p>In regular biosample cryopreservation operations, dropwise pipetting and continuous swirling are ordinarily needed to prevent cell damage (<i>e.g.</i> sudden osmotic change, toxicity and dissolution heat) caused by the high-concentration cryoprotectant (CPA) addition process. The following CPA removal process after freezing and rewarming also requires multiple sample transfer processes and manual work. In order to optimize the cryopreservation process, especially for trace sample preservation, here we present a microfluidic approach integrating CPA addition, sample storage, CPA removal and sample resuspension processes on a 30 × 30 × 4 mm³ three-layer chip. The sample solution could be added into CPA solution with pre-generated increasing concentration to decrease possible osmotic damage. Utilizing specially designed microfluidic structure and fluid field analysis, on-chip sample enrichment and CPA removal were achieved. A novel dead-end micro valve strategy with a simplified control module was applied and evaluated to assist on-chip mixing and sample pellet resuspension. The entire biosample cryopreservation process was also performed that verified the functions of the integrated microfluidic platform. Altogether, this developed platform could be an effective approach to realize automatic, all-in-one, low-damage cryopreservation operation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996446","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":"A universal framework for design and manufacture of deterministic lateral displacement chips.","authors":"Aryan Mehboudi, Shrawan Singhal, S V Sreenivasan","doi":"10.1039/d4lc00838c","DOIUrl":"https://doi.org/10.1039/d4lc00838c","url":null,"abstract":"<p><p>Despite being a high-resolution separation technique, deterministic lateral displacement (DLD) technology is facing multiple challenges with regard to design, manufacture, and operation of pertinent devices. This work specifically aims at alleviating difficulties associated with design and manufacture of DLD chips. The process of design and production of computer-aided design (CAD) mask layout files that are typically required for computational modeling analysis, optimization, as well as for manufacturing DLD-based micro/nanofluidic chips is complex, time-consuming, and often necessitates a high level of expertise in the field. Herein, we report a universal framework to automate the process of designing DLD and producing layout CAD files for various systems spanning from simply a single DLD unit to complex parallelized DLD structures with/without additional upstream/downstream components, <i>e.g.</i>, inlet filter, preload, collection channels, and through-wafer vias. In addition, to the best of our knowledge, for the first time, we adopt imprint lithography (IL) into fabrication process flow to define fine features of parallelized DLD arrays, while avoiding problems in connection with accessibility and cost of advanced photolithography tools. With regard to parallelized DLD architectures, we also report a new fabrication process flow aiming at mitigating the problems related to creating through-silicon vias at high yield. We demonstrate some use cases of our developed design and manufacture framework by designing and fabricating multiple devices to separate microspheres (0.6 μm and 1.3 μm) from aqueous media. We believe that our design automation package offers a user-friendly workflow, significantly alleviating the hurdles associated with design and optimization of DLD structures, while our fabrication process flow can provide an accessible solution to manufacturing micron- and submicron-scale DLD chips. These innovations should enable a larger community to adopt the DLD technology into their research, particularly for lab-on-a-chip applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976974","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":"An integrated paper-based microfluidic platform for screening of early-stage Alzheimer's disease by detecting Aβ42.","authors":"Sixuan Duan, Tianyu Cai, Lizhe Chen, Xiaoyan Wang, Shuailong Zhang, Bing Han, Eng Gee Lim, Kai Hoettges, Yong Hu, Pengfei Song","doi":"10.1039/d4lc00748d","DOIUrl":"https://doi.org/10.1039/d4lc00748d","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia worldwide, and the development of early screening methods can address its significant health and social consequences. In this paper, we present a rotary-valve assisted paper-based immunoassay device (RAPID) for early screening of AD, featuring a highly integrated on-chip rotary micro-valve that enables fully automated and efficient detection of the AD biomarker (amyloid beta 42, Aβ42) in artificial plasma. The microfluidic paper-based analytical device (μPAD) of the RAPID pre-stores the required assay reagents on a μPAD and automatically controls the liquid flow through a single valve. Once the test sample is added, the test reagents are sequentially transferred to the test area in the order set by the enzyme-linked immunosorbent assay (ELISA) protocol. In addition, the RAPID can remotely control the operation of the μPAD valve via a micro-servomotor, quantify the signals generated, display the results, and wirelessly transmit the data to a smartphone. To calibrate the RAPID, we performed a sandwich ELISA for Aβ42 in artificial plasma, and obtained a low limit of detection (LOD) of 9.6 pg mL^-1, a coefficient of determination (COD) of 0.994, and an individual assay time of ∼30 minutes. In addition, we simulated 24 artificial samples to quantify Aβ42 protein concentrations in artificial plasma samples. The results show good consistency between the conventional ELISA and RAPID detection. The experimental results demonstrate that the RAPID is expected to promote further popularization of the screening of early-stage AD.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968747","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":"Rapid microfluidic perfusion system enables controlling dynamics of intracellular pH regulated by Na⁺/H⁺ exchanger NHE1.","authors":"Quang D Tran, Yann Bouret, Xavier Noblin, Gisèle Jarretou, Laurent Counillon, Mallorie Poët, Céline Cohen","doi":"10.1039/d4lc00884g","DOIUrl":"https://doi.org/10.1039/d4lc00884g","url":null,"abstract":"<p><p>pH regulation of eukaryotic cells is of crucial importance and influences different mechanisms including chemical kinetics, buffer effects, metabolic activity, membrane transport and cell shape parameters. In this study, we develop a microfluidic system to rapidly and precisely control a continuous flow of ionic chemical species to acutely challenge the intracellular pH regulation mechanisms and confront predictive models. We monitor the intracellular pH dynamics in real-time using pH-sensitive fluorescence imaging and establish a robust mathematical tool to translate the fluorescence signals to pH values. By varying flow rate across the cells and duration for the rinsing process, we manage to tweak the dynamics of intracellular pH from a smooth recovery to either an overshooting state, where the pH goes excitedly to a maximum value before decreasing to a plateau, or an undershooting state, where the pH is unable to recover to ∼7. We believe our findings will provide more insight into intracellular regulatory mechanisms and promote the possibility of exploring cellular behavior in the presence of strong gradients or fast changes in homogeneous conditions.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968707","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":"Selective adsorption of unmethylated DNA on ZnO nanowires for separation of methylated DNA.","authors":"Marina Musa, Zetao Zhu, Hiromi Takahashi, Wataru Shinoda, Yoshinobu Baba, Takao Yasui","doi":"10.1039/d4lc00893f","DOIUrl":"https://doi.org/10.1039/d4lc00893f","url":null,"abstract":"<p><p>DNA methylation is a crucial epigenetic modification used as a biomarker for early cancer progression. However, existing methods for DNA methylation analysis are complex, time-consuming, and prone to DNA degradation. This work demonstrates selective capture of unmethylated DNAs using ZnO nanowires without chemical or biological modifications, thereby concentrating methylated DNA, particularly those with high methylation levels that can predict cancer risk. We observe varying affinities between methylated and unmethylated DNA on ZnO nanowires, which may be influenced by differences in hydrogen bonding strength, potentially related to the effects of methylation on DNA strand behavior, including self-aggregation and stretching inhibition. As a result, the nanowire-based microfluidic device effectively collects unmethylated DNA, leading to a significantly increased ratio of methylated to unmethylated DNA, particularly for collecting low-concentration methylated DNA. This simplified microfluidic device, composed of ZnO nanowires, enables direct separation of specific methylated DNA, offering a potential approach for DNA methylation mapping in clinical disease diagnostics.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941588","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":"Time-resolved single-cell secretion analysis <i>via</i> microfluidics.","authors":"Ying Xu, Mei Tsz Jewel Chan, Ming Yang, Heixu Meng, Chia-Hung Chen","doi":"10.1039/d4lc00904e","DOIUrl":"https://doi.org/10.1039/d4lc00904e","url":null,"abstract":"<p><p>Revealing how individual cells alter their secretions over time is crucial for understanding their responses to environmental changes. Key questions include: When do cells modify their functions and states? What transitions occur? Insights into the kinetic secretion trajectories of various cell types are essential for unraveling complex biological systems. This review highlights seven microfluidic technologies for time-resolved single-cell secretion analysis: 1. Microwell real-time electrical detection: uses microelectrodes for precise, cell-specific, real-time measurement of secreted molecules. 2. Microwell real-time optical detection: employs advanced optical systems for real-time, multiplexed monitoring of cellular secretions. 3. Microvalve real-time optical detection: dynamically analyzes secretions under controlled <i>in situ</i> stimuli, enabling detailed kinetic studies at the single-cell level. 4. Droplet real-time optical detection: provides superior throughput by generating droplets containing single cells and sensors for high-throughput screening. 5. Microwell time-barcoded optical detection: utilizes sequential barcoding techniques to facilitate scalable assays for tracking multiple secretions over time. 6. Microvalve time-barcoded optical detection: incorporates automated time-barcoding <i>via</i> micro-valves for robust and scalable analysis. 7. Microwell time-barcoded sequencing: captures and labels secretions for sequencing, enabling multidimensional analysis, though currently limited to a few time points and extended intervals. This review specifically addresses the challenges of achieving high-resolution timing measurements with short intervals while maintaining scalability for single-cell screening. Future advancements in microfluidic devices, integrating innovative barcoding technologies, advanced imaging technologies, artificial intelligence-powered decoding and analysis, and automations are anticipated to enable highly sensitive, scalable, high-throughput single-cell dynamic analysis. These developments hold great promise for deepening our understanding of biosystems by exploring single-cell timing responses on a larger scale.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941595","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":"A fluidic device for continuous on-line inductive sensing of proteolytic cleavages.","authors":"Fan Li, Leif Sieben, Johannes Büchler, Manuel Strahm, Pascal Poc, Matej Vizovišek, Michael G Christiansen, Simone Schuerle","doi":"10.1039/d4lc00657g","DOIUrl":"10.1039/d4lc00657g","url":null,"abstract":"<p><p>Proteases, an important class of enzymes that cleave proteins and peptides, carry a wealth of potentially useful information. Devices to enable routine and cost effective measurement of their activity could find frequent use in clinical settings for medical diagnostics, as well as some industrial contexts such as detecting on-line biological contamination. In particular, devices that make use of readouts involving magnetic particles may offer distinct advantages for continuous sensing because material they release can be magnetically captured downstream and their readout is insensitive to optical properties of the sample. Bioassays based on giant magnetoresistance sensors that detect the binding or release of magnetic materials have been widely explored for these reasons, but they typically require expensive consumables. Here, we develop a simpler protease sensor based on inductive detection of particle release with pulsed magnetic fields, leveraging a design that incorporates both the pulse coil and gradiometer coils into a printed circuit board. Our fluidic chips are formed from casts of 3D printed molds, such that both the sensor and the consumable components could be relatively easy to mass produce. Using pulses ranging up to 10 s of mT, we show that our device has a limit of detection below 1 μg of iron and that its duty cycle can be varied to control temperature through Joule heating. By chemically functionalizing the glass surface of our fluidic chips with zwitterionic polymer and incorporating a PEG block co-polymer into the PDMS component, we are able to suppress the nonspecific binding of albumin by 7.8 times inside the chips. We demonstrate a layer-by-layer approach for covalently linking magnetic nanoparticles to the chips <i>via</i> cleavable peptide substrates. Finally, we observe the release of the magnetic particles from the chips under conditions of proteolytic cleavage and measure resulting changes in inductive signals, demonstrating a detection sensitivity for chymotrypsin in the hundreds of nM. The methods we establish here have the potential to aid progress toward sensors comprised of disposable fluidic chips measured by inexpensive detection devices that may one day facilitate ubiquitous protease activity monitoring.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941754","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":"Repackable microfluidic molecularly imprinted solid-phase extraction coupled with mass spectrometry (μMISPE-MS) for rapid analysis of mycotoxin in agri-foods: an example of zearalenone.","authors":"Marti Z Hua, Jinxin Liu, Tianqi Li, David R McMullin, Yaxi Hu, Xiaonan Lu","doi":"10.1039/d4lc00760c","DOIUrl":"https://doi.org/10.1039/d4lc00760c","url":null,"abstract":"<p><p>Mycotoxins are detectable in 60-80% of food crops, posing significant threats to human health and food security, and causing substantial economic losses. Most mitigation approaches focus on detecting mycotoxins with standard methods based on liquid chromatography coupled with mass spectrometry (LC-MS). Typical MS methods require extensive sample preparation and clean-up due to the matrix effect, followed by time-consuming LC separation, complicating the analysis process and limiting analytical throughput. This study reports the development of a repackable microfluidic molecularly imprinted solid-phase extraction coupled with mass spectrometry (μMISPE-MS) method for rapid detection of zearalenone in agri-food samples. Silica microspheres coated with molecularly imprinted polymers were synthesized as the sorbent for analyte enrichment and sample clean-up. A cost-effective microfluidic chip was designed and fabricated as the μMISPE platform with fully automated operation, including on-line microcolumn packing and unpacking. With optimized solvent conditions and on-chip μMISPE protocol, the entire analytical process from sample to answer was completed within 15 min and achieved high recoveries (71-94%) for corn and rice samples at residue levels of 0.05-0.5 ppm (within Canadian regulatory limits of 0.2-10 ppm). This μMISPE-MS method provides a promising tool for improving mycotoxin monitoring in agri-food systems and is generalizable to other rapid analyses of targeted chemicals in complex matrices.</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":"142941583","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}