Lab on a Chip最新文献

{"title":"Beveled microneedles with channel for transdermal injection and sampling, fabricated with minimal steps and standard MEMS technology†","authors":"Alvise Bagolini, Nicolò G. Di Novo, Severino Pedrotti, Matteo Valt, Cristian Collini, Nicola M. Pugno and Leandro Lorenzelli","doi":"10.1039/D4LC00880D","DOIUrl":"10.1039/D4LC00880D","url":null,"abstract":"<p >Microneedles hold the potential for enabling shallow skin penetration applications where biomarkers are extracted from the interstitial fluid (ISF) and drugs are injected in a painless and effective manner. To this purpose, needles must have an inner channel. Channeled needles were demonstrated using custom silicon microtechnology, having several needle tip geometries. Nevertheless, all the proposed fabrication sequences are not compatible with mass production based on mature, standard microfabrication techniques. Furthermore, ISF extraction was also demonstrated with channeled needles but under poorly controlled conditions and over long periods of time, the latter being impractical for medical use. A range of factors may impede or slow ISF extraction that require controlled experiments. In this work we address the above tasks in terms of microfabrication sequence design, tip geometry design and experimental validation under controlled conditions. We report the development and fabrication of a silicon channeled microneedle array using conventional, industrial micromechanic processes. With only 2 lithography steps, a hypodermic needle tip profile is achieved. Using the fabricated microneedles, fluid extraction is experimented on chicken skin mockups. Extraction tests are carried out by inducing a controlled pressure gradient between the two ends of the microneedle channels, generated by loading the chip or by applying vacuum to the chip's backside. The extraction of more than 1 μL of fluid in 20 minutes is demonstrated with a maximum applied pressure gradient of 500 mbar. A correlation between the extraction rate efficiency and needles' density is observed, both for short and long extraction times. These results provide the first demonstration of <em>in vitro</em> interstitial fluid collection under controlled experimental conditions using silicon hollow microneedles fabricated with standard micro electro mechanical systems (MEMS) fabrication technology and minimal steps. Based on the obtained data, a comparison is drawn between pressure load and vacuum as drivers for ISF extraction, according to modelling and controlled experiments.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 201-211"},"PeriodicalIF":6.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811411","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":"Liquid metal electrodes enabled cascaded on-chip dielectrophoretic separation of large-size-range particles†","authors":"Huichao Chai, Liang Huang, Junwen Zhu, Jialu Tian and Wenhui Wang","doi":"10.1039/D4LC00942H","DOIUrl":"10.1039/D4LC00942H","url":null,"abstract":"<p >The separation of large-size-range particles of complex biological samples is critical but yet well resolved. As a label-free technique, dielectrophoresis (DEP)-based particle separation faces the challenge of how to configure DEP in an integrated microfluidic device to bring particles of various sizes into the effective DEP force field. Herein, we propose a concept that combines the passive flow fraction mechanism with the accumulative DEP deflection effect in a cascaded manner. This concept places DEP deflection segments and bypass outlets alternately. Each DEP deflection segment is configured with an array of side-wall liquid metal electrodes to exert effective DEP forces on the particles of a suitable size range. After each DEP deflection segment, the passive bypass flow fraction mechanism diverts part of the sample flow and target range of particles through the bypass outlet. Simultaneously, this flow fraction brings the remaining particles closer to the electrodes in the subsequent DEP deflection segment, causing the next size range of particles to deflect under effective DEP forces and thus making them separable. Repeating this process, particles would be separated from the bypass outlets one by one in the order of reducing size ranges. We present the concept design and modeling, and prove the concept through separating five different particles ranging from 16–0.5 μm mixed together to mimic blood composition, providing a powerful platform for separating multiple particles in diverse biomedical applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 308-318"},"PeriodicalIF":6.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875534","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":"Intelligent optoelectrowetting digital microfluidic system for real-time selective parallel manipulation of biological droplet arrays.","authors":"Tianyi Wang, Shizheng Zhou, Xuekai Liu, Jianghao Zeng, Xiaohan He, Zhihang Yu, Zhiyuan Liu, Xiaomei Liu, Jing Jin, Yonggang Zhu, Liuyong Shi, Hong Yan, Teng Zhou","doi":"10.1039/d4lc00804a","DOIUrl":"https://doi.org/10.1039/d4lc00804a","url":null,"abstract":"<p><p>Optoelectrowetting technology generates virtual electrodes to manipulate droplets by projecting optical patterns onto the photoconductive layer. This method avoids the complex design of the physical circuitry of dielectricwetting chips, compensating for the inability to reconstruct the electrode. However, the current technology relies on operators to manually position the droplets, draw optical patterns, and preset the droplet movement paths. It lacks real-time feedback on droplet information and the ability for independent droplet control, which can lead to droplet miscontrol and contamination. This paper presents a combination of optoelectrowetting with deep learning algorithms, integrating software and a photoelectric detection platform, and develops an optoelectrowetting intelligent control system. First, a target detection algorithm identifies droplet characteristics in real-time and automatically generate virtual electrodes to control movement. Simultaneously, a tracking algorithm outputs trajectories and ID information for efficient droplet arrays tracking. The results show that the system can automatically control the movement and fusion of multiple droplets in parallel and realize the automatic arrangement and storage of disordered droplet arrays without any additional electrodes and sensing devices. Additionally, through the automated control of the system, the cell suspension can be precisely cultured in the specified medium according to experimental requirements, and the growth trend is consistent with that observed in the well plate, significantly enhancing the experiment's flexibility and accuracy. In this paper, we propose an intelligent method applicable to the automated manipulation of discrete droplets. This method would play a crucial role in advancing the applications of digital microfluidic technology in biomedicine and other fields.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805626","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":"Retinal organoid chip: engineering a physiomimetic oxygen gradient for optimizing long term culture of human retinal organoids.","authors":"Emma Drabbe, Daniel Pelaez, Ashutosh Agarwal","doi":"10.1039/d4lc00771a","DOIUrl":"10.1039/d4lc00771a","url":null,"abstract":"<p><p>An oxygen gradient across the retina plays a crucial role in its development and function. The inner retina resides in a hypoxic environment (2% O₂) adjacent to the vitreous cavity. Oxygenation levels rapidly increase towards the outer retina (18% O₂) at the choroid. In addition to retinal stratification, oxygen levels are critical for the health of retinal ganglion cells (RGCs), which relay visual information from the retina to the brain. Human stem cell derived retinal organoids are being engineered to mimic the structure and function of human retina for applications such as disease modeling, development of therapeutics, and cell replacement therapies. However, rapid degeneration of the retinal ganglion cell layers are a common limitation of human retinal organoid platforms. We report the design of a novel retinal organoid chip (ROC) that maintains a physiologically relevant oxygen gradient and allows the maturation of inner and outer retinal cell phenotypes for human retinal organoids. Our PDMS-free ROC holds 55 individual retinal organoids that were manually seeded, cultured for extended periods (over 150 days), imaged <i>in situ</i>, and retrieved. ROC was designed from first principles of liquid and gas mass transport, and fabricated from biologically- and chemically inert materials using rapid prototyping techniques such as micromachining, laser cutting, 3D printing and bonding. After computational and experimental validation of oxygen gradients, human induced pluripotent stem cell derived retinal organoids were transferred into the ROC, differentiated, cultured and imaged within the chip. ROCs that maintained active perfusion and stable oxygen gradients were successful in inducing higher viability of RGCs within retinal organoids than static controls, or ROC without oxygen gradients. Our physiologically relevant and higher-throughput retinal organoid culture system is well suited for applications in studying developmental perturbations to primate retinogenesis, including those driven by inherited traits, fetal environmental exposure to toxic agents, or acquired by genetic mutations, such as retinoblastoma.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805628","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":"Injury-on-a-chip for modelling microvascular trauma-induced coagulation†","authors":"Halston Deal, Elizabeth M. Byrnes, Sanika Pandit, Anastasia Sheridan, Ashley C. Brown and Michael Daniele","doi":"10.1039/D4LC00471J","DOIUrl":"10.1039/D4LC00471J","url":null,"abstract":"<p >Blood coagulation is a highly regulated injury response that features polymerization of fibrin fibers to prevent the passage of blood from a damaged vascular endothelium. A growing body of research seeks to monitor coagulation in microfluidic systems but fails to capture coagulation as a response to disruption of the vascular endothelium. Here we present a device that allows compression injury of a defined segment of a microfluidic vascular endothelium and the assessment of coagulation at the injury site. This pressure injury-on-a-chip (PINCH) device allows visualization of coagulation as the accumulation of fluorescent fibrin at injury sites. Quantification of fluorescent fibrin levels upstream of and at injury sites confirm that pre-treating vascular endothelium with fluid shear stress helps capture coagulation as an injury response. We leverage the PINCH devices to demonstrate the limited coagulation response of type A hemophiliacs and evaluate the performance of hemostatic microparticles and fibrinolytic nanoparticles. Our findings and the straightforward fabrication of the PINCH devices make it a promising choice for additional screening of hemostatic therapeutics.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 440-453"},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941512","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":"Reusable EWOD-based microfluidic system for active droplet generation†","authors":"Suhee Park, Jaewook Ryu and Ki-Ho Han","doi":"10.1039/D4LC00744A","DOIUrl":"10.1039/D4LC00744A","url":null,"abstract":"<p >Droplets are essential in a wide range of microfluidic applications, but traditional passive droplet generation methods suffer from slow response speed and the need for precise flow rate adjustment. Here, we present an active droplet generation method through electrowetting-on-dielectric (EWOD). Electrowetting is a technique that uses an electric field to change the wettability of a surface. In our method, we apply an electric field to the laminar flow of the dispersed and continuous phases in a microchannel, which induces the discretization of the dispersed thread and leads to droplet formation. A key feature of the proposed active droplet-generating microfluidic device is the reusability of the EWOD actuation substrate, dramatically reducing operational costs. In addition, this approach offers significant advantages over passive methods, including fast response speeds, a wider range of droplet sizes, and greater control over droplet size. In addition, the ultrathin polymer film used in this device allows for a low electrowetting voltage, which helps to prevent damage to encapsulated cells. We believe that our active droplet generation method is a promising new method for generating droplets in microfluidic applications. It is faster, more versatile, and more precise than passive methods, making it ideal for a wide range of applications, including single-cell genomics and drug discovery.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 225-234"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816635","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":"High-throughput microfluidic spheroid technology for early detection of colistin-induced nephrotoxicity with gradient-based analysis†","authors":"Yugyeong Lee, Yunsang Choi, Ju Lan Chun, Hong Bin Kim, Sejoong Kim, Eu Suk Kim and Sungsu Park","doi":"10.1039/D4LC00782D","DOIUrl":"10.1039/D4LC00782D","url":null,"abstract":"<p >Colistin is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Traditional approaches for studying colistin's nephrotoxicity are challenged by the rapid metabolism of its prodrug, colistin methanesulfonate and the difficulty of obtaining adequate plasma from critically ill patients. To address these challenges, we developed the Spheroid Nephrotoxicity Assessing Platform (SNAP), a microfluidic device that efficiently detects colistin-induced toxicity in renal proximal tubular epithelial cell (RPTEC) spheroids within 48 hours using just 200 μL of patient plasma. Our findings demonstrate that SNAP not only promotes higher expression of kidney-specific markers aquaporin-1 (AQP1) and low-density lipoprotein receptor-related protein 2 (LRP2) compared to traditional two-dimensional (2D) cultures, but also exhibits increased sensitivity to colistin, with significant toxicity detected at concentrations of 50 μg ml<small>⁻¹</small> and above. Notably, SNAP's non-invasive method did not identify nephrotoxicity in plasma from healthy donors, thereby confirming its physiological relevance and showcasing superior sensitivity over 2D cultures, which yielded false-positive results. In clinical validation, SNAP accurately identified patients at risk of colistin-induced nephrotoxicity with 100% accuracy for both early and late onset and demonstrated a 75% accuracy rate in predicting the non-occurrence of nephrotoxicity. These results underline the potential of SNAP in personalized medicine, offering a non-invasive, precise and efficient tool for the assessment of antibiotic-induced nephrotoxicity, thus enhancing the safety and efficacy of treatments against resistant bacterial infections.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 275-284"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845342","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":"Highly efficient combination of multiple single cells using a deterministic single-cell combinatorial reactor†","authors":"Mina Yoshida, Saori Tago, Kunihiko Iizuka, Teruo Fujii and Soo Hyeon Kim","doi":"10.1039/D4LC00951G","DOIUrl":"10.1039/D4LC00951G","url":null,"abstract":"<p >Compartmentalization of multiple single cells and/or single microbeads holds significant potential for advanced biological research including single-cell transcriptome analysis or cell–cell interactions. To ensure reliable analysis and prevent misinterpretation, it is essential to achieve highly efficient pairing or combining of single objects. In this paper, we introduce a novel microfluidic device coupled with a multilayer interconnect Si/SiO<small>²</small> control circuit, named the deterministic single-cell combinatorial reactor (DSCR) device, for the highly efficient combination of multiple single cells. The deterministic combination of multiple single cells is realized by sequentially introducing and trapping each cell population into designated trap-wells within each DSCR. These cell-sized trap-wells, created by etching the SiO<small>₂</small> passivation layer, generate a highly localized electric field that facilitates deterministic single-cell trapping. The device's multilayer interconnection of electrodes enables the sequential operation of each trap-well, allowing precise trapping of each cell population into designated trap-wells within an array of combinatorial reactors. We demonstrated the feasibility of the DSCR by sequentially trapping three distinct groups of PC3 cells, each stained with a different fluorescent dye (blue, green, or red). This method achieved a 93 ± 2% pairing efficiency for two cell populations and an 82 ± 7% combination efficiency for three cell populations. Our innovative system offers promising applications for analyzing multiple cell–cell communications and combinatorial indexing of single cells.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 4","pages":" 476-486"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826744","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":"Correction: Distal renal tubular system-on-a-chip for studying the pathogenesis of influenza A virus-induced kidney injury","authors":"Yueyue Huangfu, Ji Wang, Jiao Feng and Zhi-Ling Zhang","doi":"10.1039/D4LC90105C","DOIUrl":"10.1039/D4LC90105C","url":null,"abstract":"<p >Correction for ‘Distal renal tubular system-on-a-chip for studying the pathogenesis of influenza A virus-induced kidney injury’ by Yueyue Huangfu <em>et al.</em>, <em>Lab Chip</em>, 2023, 23, 4255–4264, https://doi.org/10.1039/D3LC00616F</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 285-286"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d4lc90105c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798648","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":"A gravity-driven microfluidic metering system for automation of multiplexed bioassays†","authors":"Lu Zhang, Johnson Q. Cui and Shuhuai Yao","doi":"10.1039/D4LC00800F","DOIUrl":"10.1039/D4LC00800F","url":null,"abstract":"<p >Automatic and precise fluid manipulation is essential in microfluidic applications. Microfluidic metering, in particular, plays a critical role in achieving the multiplexity of assays, reaction consistency, quantitative analysis, and the scalability of microfluidic operations. However, existing fluid metering techniques often face limitations, such as high complexity, high cost, reliance on external accessories, and lack of precision, which have restricted their use in multiplexed and quantitative analysis, especially in portable applications. In this study, we present a novel portable gravity-driven metering system designed for automated multiplexed fluid metering, multistep fluid control, and multi-chamber signal readout. Our metering chip utilizes gravitational force to dispense sample liquids, allowing for versatile and precise metering. Guided by a series of numerical simulations, we optimized the design of our metering chip to achieve rapid and accurate liquid metering. Furthermore, thermal control valves were employed to facilitate automated and programmable fluid transfer, eliminating the need for external equipment. To enhance user experience, we developed a smartphone-assisted readout pod for seamless integration with the metering chip. We validated the efficacy of our platform through a proof-of-concept multiplexed analysis of urinary biomarkers, demonstrating high sensitivity, specificity, and absolute quantification capabilities. Our gravity-driven metering system shows significant potential for applications in multiplexed diagnostics, drug screening, and material synthesis, effectively addressing critical needs in fluid manipulation and analysis.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 175-186"},"PeriodicalIF":6.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798643","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}