Lab on a Chip最新文献

{"title":"Label-free differentiation of living <i>versus</i> dead single yeast cells using broadband electrical impedance spectroscopy.","authors":"Amirhossein Favakeh, Amir Mokhtare, Mohammad Javad Asadi, James C M Hwang, Alireza Abbaspourrad","doi":"10.1039/d5lc00043b","DOIUrl":"https://doi.org/10.1039/d5lc00043b","url":null,"abstract":"<p><p>The use of the intrinsic electrical properties of a single cell by broadband electrical impedance spectroscopy (EIS) as a label-free and non-invasive method to monitor cellular and intracellular features is an emerging field. Here, we present a novel EIS-based sheathless microfluidic platform with an integrated coplanar waveguide to probe the interior of a single cell. This platform allows for precise single-cell trapping by dielectrophoresis, hydrodynamic focusing, and sensing the electrical properties of the trapped single cell. We measured the impedance characteristics of a single <i>Schizosaccharomyces pombe</i> (fission) yeast cell by a single frequency sweep (30 kHz to 6GHz) in a stagnant sucrose solution using two-port scattering (<i>S</i>) parameters. The measurements revealed a clear distinction between the cytoplasm impedance of live <i>versus</i> dead cells at 3 GHz. This platform could provide real-time monitoring of cellular electrical responses to chemical and physical antagonists for diagnostic purposes.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522204","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":"Pulsatile-flow culture: a novel system for assessing vascular-cell dynamics.","authors":"Neda Salimi-Afjani, Robert Rieben, Dominik Obrist","doi":"10.1039/d4lc00949e","DOIUrl":"10.1039/d4lc00949e","url":null,"abstract":"<p><p>We describe a model system for vascular-cell culture where recirculating fluid flow in standard culture plates is generated by gravity using a combination of platform tilt and rotation (nutation). Placed inside a cell-culture incubator, variable nutation speeds provide pulsatile shear stresses to vascular cells within the physiological range. The effect of these stresses on cells is demonstrated here using standard laboratory techniques such as immunofluorescent staining, immunoblot, and supernatant analyses. This gravity-driven model framework is well-suited for assessing dynamic conditions for mono- and co-cultures. In addition, the modular design and the use of off-the-shelf components make the system economical and scalable.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522206","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 integratible acoustic micropump based on the resonance of on-substrate sharp-edge micropillar arrays.","authors":"Yu Zhang, Zeyi Wang, Yang Zhao, Qinran Wei, Haixiang Zheng, Dong Zhang, Xiasheng Guo","doi":"10.1039/d4lc00997e","DOIUrl":"https://doi.org/10.1039/d4lc00997e","url":null,"abstract":"<p><p>There is a growing demand for reliable, efficient, and easily integrated micropumps for microfluidics. Despite the demonstrated potential of acoustic wave-driven devices for on-chip pumping, current prototypes lack the practicality and integratability for deployment in microfluidic systems. This study presents an acoustic micropump based on the resonance of arrays of on-substrate sharp-edge micropillars prepared in a fluid-filled channel and driven by a piston ultrasonic transducer. At an operating frequency of 80.5 kHz and a driving voltage of 54 V_p-p, a flow rate of 16.2 μL min^-1 is achieved in a downstream straight channel with dimensions 12(<i>L</i>) × 0.6(<i>W</i>) × 0.2(<i>H</i>) mm³. The corresponding pumping pressure exceeds 1.3 kPa, more than an order of magnitude higher than its predecessors. In experimental demonstrations, two micropumps are employed as feeding units for an acoustofluidic particle separation device based on tilted-angle standing surface acoustic waves (TaSSAWs). The current micropump exhibits advantages of high pumping pressure, fast response time, and high reliability, making it a promising pumping unit for lab-on-a-chip systems.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522203","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":"Modelling of the multicellular tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) on a fit-for-purpose biochip for preclinical drug discovery.","authors":"Alina Deipenbrock, Ben Eric Wilmes, Thomas Sommermann, Nader Abdo, Kyra Moustakas, Martin Raasch, Knut Rennert, Nicole E Teusch","doi":"10.1039/d4lc01016g","DOIUrl":"https://doi.org/10.1039/d4lc01016g","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer. One major cause for a fast disease progression is the presence of a highly fibrotic tumor microenvironment (TME) mainly composed of cancer-associated fibroblasts (CAF), and various immune cells, especially tumor-associated macrophages (TAM). To conclusively evaluate drug efficacy, it is crucial to develop <i>in vitro</i> models that can recapitulate the cross talk between tumor cells and the surrounding stroma. Here, we constructed a fit-for-purpose biochip platform which allows the integration of PDAC spheroids (composed of PANC-1 cells and pancreatic stellate cells (PSC)). Additionally, the chip design enables dynamic administration of drugs or immune cells <i>via</i> a layer of human umbilical vein endothelial cells (HUVEC). As a proof-of-concept for drug administration, vorinostat, an FDA-approved histone deacetylase inhibitor for cutaneous T cell lymphoma (CTCL), subjected <i>via</i> continuous flow for 72 h, resulted in a significantly reduced viability of PDAC spheroids without affecting vascular integrity. Furthermore, dynamic perfusion with peripheral mononuclear blood cells (PBMC)-derived monocytes resulted in an immune cell migration through the endothelium into the spheroids. After 72 h of infiltration, monocytes differentiated into macrophages which polarized into the M2 phenotype. The polarization into M2 macrophages persisted for at least 168 h, verified by expression of the M2 marker CD163 which increased from 72 h to 168 h, while the M1 markers CD86 and HLA-DR were significantly downregulated. Overall, the described spheroid-on-chip model allows the evaluation of novel therapeutic strategies by mimicking and targeting the complex TME of PDAC.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522205","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":"Microfluidic loading of verteporfin into extracellular vesicles for neuroblastoma therapy.","authors":"Caterina Piunti, Sara Micheli, Sara Giancaterino, Pina Fusco, Cristiana Boi, Elisa Cimetta","doi":"10.1039/d4lc01103a","DOIUrl":"10.1039/d4lc01103a","url":null,"abstract":"<p><p>Despite contributing to cancer progression, extracellular vesicles (EVs) could serve as potential drug delivery systems in cancer treatment, having the ability to dissolve water-insoluble drugs and facilitate targeted delivery. However, the clinical translation of EVs is still in its infancy. While traditional methods for EV modifications will remain relevant, microfluidic approaches are expected to replace benchtop methods. Taking advantage of lab-on-chip devices, passive cargo loading through microfluidic mixing and incubation may be an important strategy to produce functional engineered EVs. This study focuses on developing a microfluidic device to generate EVs loaded with verteporfin (VP), a hydrophobic porphyrin with potential applications in neuroblastoma (NB) therapy, aiming to enhance its therapeutic effectiveness. The platform ensures perfect mixing and tunable incubation time for mesenchymal stem cell-derived EVs and VP, demonstrating a significantly higher loading efficiency than traditional methods, while operating under gentle conditions that preserve EV integrity and functionality, unlike other microfluidic techniques that involve harsh mechanical or chemical treatments. The VP-loaded EVs (VP-EVs) can then be easily recovered, making them available for subsequent analysis and use. MTT assay confirmed that VP-EVs are more efficient than free VP in reducing the viability of a NB cell line. Finally, immunofluorescence assay and western blot demonstrated a greater reduction in YAP expression after treatment with VP-EVs in an NB cell line when compared to free VP. Being both non-destructive and straightforward, this microfluidic loading technique facilitates its adaptability to a wide spectrum of therapeutic compounds. As a versatile tool, microfluidic technology will help to fully unlock the potential of EVs for speeding up precision medicine and disease treatment.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497497","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":"Sensor-integrated gut-on-a-chip for monitoring senescence-mediated changes in the intestinal barrier.","authors":"Konstanze Brandauer, Alexandra Lorenz, Silvia Schobesberger, Patrick Schuller, Martin Frauenlob, Sarah Spitz, Peter Ertl","doi":"10.1039/d4lc00896k","DOIUrl":"https://doi.org/10.1039/d4lc00896k","url":null,"abstract":"<p><p>The incidence of inflammatory bowel disease among the elderly has significantly risen in recent years, posing a growing socioeconomic burden to aging societies. Moreover, non-gastrointestinal diseases, also prevalent in this demographic, have been linked to intestinal barrier dysfunction, thus highlighting the importance of investigating aged-mediated changes within the human gut. While gastrointestinal pathology often involves an impaired gut barrier, the impact of aging on the human gastrointestinal barrier function remains unclear. To explore the effect of senescence, a key hallmark of aging, on gut barrier integrity, we established and evaluated an <i>in vitro</i> gut-on-a-chip model tailored to investigate barrier changes by the integration of an impedance sensor. Here, a microfluidic gut-on-a-chip system containing integrated membrane-based electrode microarrays is used to non-invasively monitor epithelial barrier formation and senescence-mediated changes in barrier integrity upon treating Caco-2 cells with 0.8 μg mL^-1 doxorubicin (DXR), a chemotherapeutic which induces cell cycle arrest. Results of our microfluidic human gut model reveal a DXR-mediated increase in impedance and cell hypertrophy as well as overexpression of p21, and CCL2, indicative of a senescent phenotype. Combined with the integrated electrodes, monitoring ∼57% of the cultivation area <i>in situ</i> and non-invasively, the developed chip-based senescent-gut model is ideally suited to study age-related malfunctions in barrier integrity.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497490","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":"Microfluidic cell unroofing for the <i>in situ</i> molecular analysis of organelles without membrane permeabilization.","authors":"Yuki Umeda, Shinya Yamahira, Koki Nakamura, Tomoko Takagi, Tomoko Suzuki, Kae Sato, Yusuke Hirabayashi, Akimitsu Okamoto, Satoshi Yamaguchi","doi":"10.1039/d5lc00102a","DOIUrl":"https://doi.org/10.1039/d5lc00102a","url":null,"abstract":"<p><p>Molecular networks of organelle membranes are involved in many cell processes. However, the nature of plasma membrane as a barrier to various analytical tools, including antibodies, makes it challenging to examine intact organelle membranes without affecting their structure and functions <i>via</i> membrane permeabilization. Therefore, in this study, we aimed to develop a microfluidic method to unroof cells and observe the intrinsic membrane molecules in organelles. In our method, single cells were precisely arrayed on the bottom surface of microchannels in a light-guided manner using a photoactivatable cell-anchoring material. At sufficiently short cell intervals, horizontal stresses generated by the laminar flow instantly fractured the upper cell membranes, without significantly affecting some organelles inside the fractured cells. Subsequently, nucleus and other organelles in unroofed cells were observed <i>via</i> confocal fluorescence and scanning electron microscopy. Furthermore, distribution of the mitochondrial membrane protein, translocase of outer mitochondrial membrane 20, on the mitochondrial membrane was successfully observed <i>via</i> immunostaining without permeabilization. Overall, the established cell unroofing method shows great potential to examine the localization, functions, and affinities of proteins on intact organelle membranes.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497494","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":"Study on the size and spatial configuration of liquid metal droplets in conductive hydrogels induced by surface acoustic waves.","authors":"Siyu Zhao, Zhaomiao Liu, Nan Zheng, Chenchen Zhang, Kai Zheng, Shuai Shi, Yan Pang","doi":"10.1039/d4lc00935e","DOIUrl":"https://doi.org/10.1039/d4lc00935e","url":null,"abstract":"<p><p>Conductive hydrogels based on liquid metal microdroplets are widely used as wearable electronic devices. Droplet uniformity affects sensor sensitivity for weak signals, such as heart rate and pulse rate. Surface acoustic waves at micrometer wavelengths allow precise control of a single droplet, and have the potential to make uniformly discrete liquid metal droplets and distribute them in hydrogels. But the control law of liquid metal droplet size and its spatial configuration by acoustic surface waves is not clear. The aim of this paper is to present an analysis of the acoustic regulation mechanism in the interfacial evolution of fluids with high interfacial tension coefficients, and to investigate the influence of microdroplet generation characteristics (size and spacing) on the conductive and mechanical properties of conductive hydrogels. The results showed that the combined action of acoustic radiation force, shear force and pressure difference force helped to overcome interfacial tension and speed up the interfacial necking process during the filling and squeezing stages. The use of acoustic surface waves serves to diminish the influence of droplet size on the two-phase flow rate. This provides an effective approach for achieving decoupled control of microdroplet size and spacing, alongside the formation of a homogenous array of liquid metal droplets. The acoustic surface wave effect makes the liquid metal microdroplets more uniform in size and spacing. As the liquid metal content relative to the hydrogel substrate solution increases, the liquid metal size decreases. The hydrogel's initial conductivity and conductivity after self-healing increase by 10% and 25%, respectively, which can realize the effective monitoring of ECG and EMG signals. This study helps to reveal the evolution mechanism of liquid-metal interfaces induced by acoustic surface waves, elucidate the effects of microdroplet size and spacing on the conductive and mechanical properties of hydrogels, and provide theoretical guidance for the high-precision preparation of wearable electronic devices.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497577","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: <i>In vitro</i> vascularized liver tumor model based on a microfluidic inverse opal scaffold for immune cell recruitment investigation.","authors":"Pingwei Xu, Junjie Chi, Xiaochen Wang, Meng Zhu, Kai Chen, Qihui Fan, Fangfu Ye, Changmin Shao","doi":"10.1039/d5lc90014j","DOIUrl":"https://doi.org/10.1039/d5lc90014j","url":null,"abstract":"<p><p>Correction for '<i>In vitro</i> vascularized liver tumor model based on a microfluidic inverse opal scaffold for immune cell recruitment investigation' by Pingwei Xu <i>et al.</i>, <i>Lab Chip</i>, 2024, <b>24</b>, 3470-3479, https://doi.org/10.1039/D4LC00341A.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497484","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":"Synthetic molecular communication through microfluidic oscillating droplets for intrabody physiological data transmission.","authors":"Fabrizio Pappalardo, Carla Panarello, Salvo Quattropani, Laura Galluccio, Antonino Licciardello, Roberta Ruffino, Giovanni Li-Destri, Alfio Lombardo, Giacomo Morabito, Nunzio Tuccitto","doi":"10.1039/d4lc00944d","DOIUrl":"https://doi.org/10.1039/d4lc00944d","url":null,"abstract":"<p><p>We explore the capabilities of a microfluidic-based synthetic molecular communication (SMC) system for the transmission of physiological data within the human body. The system employs oscillating water droplets as a means of transmitting information through pressure variations. The validity of this approach for binary communications is validated through a combination of simulations and experiments. A case study focused on monitoring gastroesophageal reflux disease (GERD) has been considered. The prototype platform demonstrated the capacity to transmit both synthetic raw esophageal pH values and severity classifications (<i>e.g.</i> acid reflux) through oscillating droplets. This finding underscores the promise of SMC for real-time physiological monitoring, paving the way for enhanced disease diagnosis and personalized treatment in medicine. Despite the need for miniaturization to facilitate <i>in vivo</i> use, this research establishes a robust foundation for the development of microfluidic SMC devices for medical diagnostics and physiological monitoring.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497672","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}