Lab on a Chip最新文献

{"title":"Roll-to-roll manufacturing of large surface area PDMS devices, and application to a microfluidic artificial lung†","authors":"Andrew Zhang, Kartik Tharwani, Jennifer Wang, Gabriele K. Seilo, Michael A. Atie and Joseph A. Potkay","doi":"10.1039/D4LC00339J","DOIUrl":"10.1039/D4LC00339J","url":null,"abstract":"<p >The ability to cost-effectively produce large surface area microfluidic devices would bring many small-scale technologies such as microfluidic artificial lungs (μALs) from the realm of research to clinical and commercial applications. However, efforts to scale up these devices, such as by stacking multiple flat μALs have been labor intensive and resulted in bulky devices. Here, we report an automated manufacturing system, and a series of cylindrical multi-layer lungs manufactured with the system and tested for fluidic fidelity and function. A roll-to-roll (R2R) system to engrave multiple-layer devices was assembled. Unlike typical applications of R2R, the rolling process is synchronized to achieve consistent radial positioning. This allows the fluidics in the final device to be accessed without being unwrapped. To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer μALs. Gas and blood are engraved in alternating layers and routed orthogonally to each other. The proximity of gas and blood separated by gas permeable PDMS permits CO<small>₂</small> and O<small>₂</small> exchange <em>via</em> diffusion. After manufacturing, they were evaluated using water for pressure drop and CO<small>₂</small> gas exchange. The best performing device was tested with fresh whole bovine blood for O<small>₂</small> exchange. Three μALs were successfully manufactured and passed leak testing. The top performing device had 15 alternating blood and gas layers. It oxygenated blood from 70% saturation to 95% saturation at a blood flow of 3 mL min<small>⁻¹</small> and blood side pressure drop of 234 mmHg. This new roll-to-roll manufacturing system is suitable for the automated construction of multi-layer microfluidic devices that are difficult to manufacture by conventional means. With some upgrades and improvements, this technology should allow for the automatic creation of large surface area microfluidic devices that can be employed for various applications including large-scale membrane gas exchange such as clinical-scale microfluidic artificial lungs.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00339j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755113","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":"3D cellular self-assembly on optical disc-imprinted nanopatterns†","authors":"Jeeyeon Lee and Chwee Teck Lim","doi":"10.1039/D4LC00386A","DOIUrl":"10.1039/D4LC00386A","url":null,"abstract":"<p >Three-dimensional (3D) cellular assemblies, such as cancer spheroids and organoids, are increasingly valued for their physiological relevance, and versatility in biological applications. Nanopatterns that mimic the extracellular matrix provide crucial topological cues, creating a physiologically relevant cellular environment and guiding cellular behaviors. However, the high cost and complex, time-consuming nature of the nanofabrication process have limited the widespread adoption of nanopatterns in diverse biological applications. In this study, we present a straightforward and cost-effective elastomer replica molding method utilizing commercially available optical discs to generate various nanopatterns, such as nanogroove/ridge, nanoposts, and nanopits, varying in spacing and heights. Using the nanopatterned well chips (NW-Chips), we demonstrated the efficient formation of 3D multicellular self-assemblies of three different types of cancer cells. Our findings highlight the accessibility and affordability of optical discs as tools for nanopattern generation, offering promising avenues for modulating cell behaviors and advancing diverse biological applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750327","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 programmable and automated optical electrowetting-on-dielectric (oEWOD) driven platform for massively parallel and sequential processing of single cell assay operations†","authors":"Lawrence G. Welch, Jasper Estranero, Panagiotis Tourlomousis, Robert C. R. Wootton, Valentin Radu, Carlos González-Fernández, Tim J. Puchtler, Claire M. Murzeau, Nele M. G. Dieckmann, Aya Shibahara, Brooke W. Longbottom, Clare E. Bryant and Emma L. Talbot","doi":"10.1039/D4LC00245H","DOIUrl":"10.1039/D4LC00245H","url":null,"abstract":"<p >Recently, there has been an increasing emphasis on single cell profiling for high-throughput screening workflows in drug discovery and life sciences research. However, the biology underpinning these screens is often complex and is insufficiently addressed by singleplex assay screens. Traditional single cell screening technologies have created powerful sets of ‘omic data that allow users to bioinformatically infer biological function, but have as of yet not empowered direct functional analysis at the level of each individual cell. Consequently, screening campaigns often require multiple secondary screens leading to laborious, time-consuming and expensive workflows in which attrition points may not be queried until late in the process. We describe a platform that harnesses droplet microfluidics and optical electrowetting-on-dielectric (oEWOD) to perform highly-controlled sequential and multiplexed single cell assays in massively parallelised workflows to enable complex cell profiling during screening. Soluble reagents or objects, such as cells or assay beads, are encapsulated into droplets of media in fluorous oil and are actively filtered based on size and optical features ensuring only desirable droplets (<em>e.g.</em> single cell droplets) are retained for analysis, thereby overcoming the Poisson probability distribution. Droplets are stored in an array on a temperature-controlled chip and the history of individual droplets is logged from the point of filter until completion of the workflow. On chip, droplets are subject to an automated and flexible suite of operations including the merging of sample droplets and the fluorescent acquisition of assay readouts to enable complex sequential assay workflows. To demonstrate the broad utility of the platform, we present examples of single-cell functional workflows for various applications such as antibody discovery, infectious disease, and cell and gene therapy.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00245h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732887","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":"Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing","authors":"Rohan Palanki, Emily L. Han, Amanda M. Murray, Rohin Maganti, Sophia Tang, Kelsey L. Swingle, Dongyoon Kim, Hannah Yamagata, Hannah C. Safford, Kaitlin Mrksich, William H. Peranteau and Michael J. Mitchell","doi":"10.1039/D4LC00283K","DOIUrl":"10.1039/D4LC00283K","url":null,"abstract":"<p >mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized <em>in vivo</em>, these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms. In this study, we investigated the effect of microfluidic and lipid excipient parameters on LNP gene editing efficacy. Through <em>in vitro</em> screening in liver cells, we discovered distinct trends in delivery based on phospholipid, cholesterol, and lipid-PEG structure in LNP formulations. Combination of top-performing lipid excipients produced an LNP formulation that resulted in 3-fold greater gene editing <em>in vitro</em> and facilitated 3-fold greater reduction of a therapeutically-relevant protein <em>in vivo</em> relative to the unoptimized LNP formulation. Thus, systematic optimization of LNP formulation parameters revealed a novel LNP formulation that has strong potential for delivery of gene editors to the liver to treat metabolic disease.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732888","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":"Studying the impact of geometrical and cellular cues on myogenesis with a skeletal muscle-on-chip†","authors":"M.-L. Nguyen, N. Demri, B. Lapin, F. Di Federico, G. Gropplero, F. Cayrac, K. Hennig, Edgar R. Gomes, C. Wilhelm, W. Roman and S. Descroix","doi":"10.1039/D4LC00417E","DOIUrl":"10.1039/D4LC00417E","url":null,"abstract":"<p >In the skeletal muscle tissue, cells are organized following an anisotropic architecture, which is both required during myogenesis when muscle precursor cells fuse to generate myotubes and for its contractile function. To build an <em>in vitro</em> skeletal muscle tissue, it is therefore essential to develop methods to organize cells in an anisotropic fashion, which can be particularly challenging, especially in 3D. In this study, we present a versatile muscle-on-chip system with adjustable collagen hollow tubes that can be seeded with muscle precursor cells. The collagen acts both as a tube-shaped hollow mold and as an extracellular matrix scaffold that can house other cell types for co-culture. We found that the diameter of the channel affects the organization of the muscle cells and that proper myogenesis was obtained at a diameter of 75 μm. In these conditions, muscle precursor cells fused into long myotubes aligned along these collagen channels, resulting in a fascicle-like structure. These myotubes exhibited actin striations and upregulation of multiple myogenic genes, reflecting their maturation<em>.</em> Moreover, we showed that our chip allowed muscle tissue culture and maturation over a month, with the possibility of fibroblast co-culture embedding in the collagen matrix.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730529","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":"Flow-induced fabrication of ZnO nanostructures in pillar-arrayed microchannels†","authors":"Ruyi Xu, Siyu Li, Sai-Xi Yu, Yan-Jun Liu, Wenhui Xie, Qingfeng Zhan, Zhenjie Zhao and Xin Li","doi":"10.1039/D4LC00328D","DOIUrl":"10.1039/D4LC00328D","url":null,"abstract":"<p >The emergence of microfluidic devices integrated with nanostructures enables highly efficient, flexible and controllable biosensing, among which zinc oxide (ZnO) nanostructure-based fluorescence detection has been demonstrated to be a promising methodology due to its high electrical point and unique fluorescence enhancement properties. The optimization of microfluidic synthesis of ZnO nanostructures for biosensing on chip has been in demand due to its low cost and high efficiency, but still the flow-induced growth of ZnO nanostructures is not extensively studied. Here, we report a simple and versatile strategy that could manipulate the local flow field by creating periodically arranged micropillars within a straight microchannel. We have explored the effects of perfusion speed and flow direction of seed solution, localized flow variation of growth solution and growth time on the morphology of nanostructures. This provided a comprehensive understanding which governs nanostructure fabrication controlled by flow. The results demonstrated that localized flow in microfluidic devices was essential for the initiation and growth of zinc oxide crystals, enabling precise control over their properties and morphology. Furthermore, a model protein was used to demonstrate the intrinsic fluorescence enhancement of ZnO nanostructures as an example to reveal the morphology-related enhancement properties.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722705","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 novel immunoassay technique using principal component analysis for enhanced detection of emerging viral variants†","authors":"Josselyn Mata Calidonio, Arianna I. Maddox and Kimberly Hamad-Schifferli","doi":"10.1039/D4LC00505H","DOIUrl":"10.1039/D4LC00505H","url":null,"abstract":"<p >Rapid diagnostics are critical infectious disease tools that are designed to detect a known biomarker using antibodies specific to that biomarker. However, a way to detect unknown disease variants has not yet been achieved in a paper test format. We describe here a route to make an adaptable paper immunoassay that can detect an unknown biomarker, demonstrating it on SARS-CoV-2 variants. The immunoassay repurposes cross reactive antibodies raised against the alpha variant. Gold nanoparticles of two different colors conjugated to two different antibodies create a colorimetric signal, and machine learning of the resulting colorimetric pattern is used to train the assay to discriminate between variants of alpha and Omicron BA.5. By using principal component analysis, the colorimetric test patterns can pick up and discriminate an unknown variant that it has not encountered before, Omicron BA.1. The test has an accuracy of 100% and a potential calculated discriminatory power of 900. We show that it can be used adaptively and that it can be used to pick up emerging variants without the need to raise new antibodies.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00505h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726277","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":"ElectrochemCap: an integrated detection for loop-mediated isothermal amplification reactions†","authors":"P. Rioboó-Legaspi, E. Costa-Rama and M. T. Fernández-Abedul","doi":"10.1039/D4LC00395K","DOIUrl":"10.1039/D4LC00395K","url":null,"abstract":"<p >Loop-mediated isothermal amplification (LAMP) of genetic materials has emerged as a powerful molecular biology technique with great potential to be a standard point-of-care (POC) technique. This method has found several applications, but it still presents challenges for its direct on-site application, particularly in terms of integrated reaction and detection systems and the risk of carryover contamination. In this work, we propose an innovative solution – an electrochemical microcentrifuge tube cap (ElectrochemCap) based on a screen-printed electrode, a 3D printed adapter and an adhesive layer – which integrates the amplification reaction and its subsequent electrochemical detection in a single device. The design, fabrication, and electrochemical characterization of the ElectrochemCap are reported here, demonstrating its suitability for LAMP detection. Rapidly emerging technologies, such as 3D printing or xurography, are the basis of a prototype that has been validated for the detection of SARS-CoV-2 using reverse transcription LAMP (RT-LAMP), achieving results comparable to those obtained by gold-standard RT-qPCR. Moreover, we have explored the versatility of the ElectrochemCap presenting several additional designs (for containers with different volumes, shapes and materials, as well as multiplexed approaches), expanding its potential applications. Overall, the ElectrochemCap represents an affordable, versatile, and marketable innovation for integrated quantitative electrochemical detection, with enormous possibilities in bioelectroanalytical procedures and portable laboratory setups.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00395k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726278","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":"Monomeric and oligomeric amyloid-β cause distinct Alzheimer's disease pathophysiological characteristics in astrocytes in human glymphatics-on-chip models†","authors":"Aria R. Yslas, Rena Park, Nozomi Nishimura and Esak Lee","doi":"10.1039/D4LC00287C","DOIUrl":"10.1039/D4LC00287C","url":null,"abstract":"<p >Alzheimer's disease (AD) is marked by the aggregation of extracellular amyloid-β (Aβ) and astrocyte dysfunction. For Aβ oligomers or aggregates to be formed, there must be Aβ monomers present; however, the roles of monomeric Aβ (mAβ) and oligomeric Aβ (oAβ) in astrocyte pathogenesis are poorly understood. We cultured astrocytes in a brain-mimicking three-dimensional (3D) extracellular matrix and revealed that both mAβ and oAβ caused astrocytic atrophy and hyper-reactivity, but showed distinct Ca<small>²⁺</small> changes in astrocytes. This 3D culture evolved into a microfluidic glymphatics-on-chip model containing astrocytes and endothelial cells with the interstitial fluid (ISF). The glymphatics-on-chip model not only reproduced the astrocytic atrophy, hyper-reactivity, and Ca<small>²⁺</small> changes induced by mAβ and oAβ, but recapitulated that the components of the dystrophin-associated complex (DAC) and aquaporin-4 (AQP4) were properly maintained by the ISF, and dysregulated by mAβ and oAβ. Collectively, mAβ and oAβ cause distinct AD pathophysiological characteristics in the astrocytes.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00287c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631303","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":"Outstanding Reviewers for Lab on a Chip in 2023","authors":"","doi":"10.1039/D4LC90056A","DOIUrl":"10.1039/D4LC90056A","url":null,"abstract":"<p >We would like to take this opportunity to thank all of <em>Lab on a Chip</em>'s reviewers for helping to preserve quality and integrity in the chemical science literature. We would also like to highlight our Outstanding Reviewers for <em>Lab on a Chip</em> in 2023.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615306","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}