Lab on a Chip最新文献

{"title":"Zonal Patterning of Extracellular Matrix and Stromal Cell Populations Along a Perfusable Cellular Microchannel","authors":"Brea Chernokal, Bryan J Ferrick, Jason P Gleghorn","doi":"10.1039/d4lc00579a","DOIUrl":"https://doi.org/10.1039/d4lc00579a","url":null,"abstract":"The spatial organization of biophysical and biochemical cues in the extracellular matrix (ECM) in concert with reciprocal cell-cell signaling is vital to tissue patterning during development. However, elucidating the role an individual microenvironmental factor plays using existing textit{in vivo} models is difficult due to their inherent complexity. In this work, we have developed a microphysiological system to spatially pattern the biochemical, biophysical, and stromal cell composition of the ECM along an epithelialized 3D microchannel. This technique is adaptable to multiple hydrogel compositions and scalable to the number of zones patterned. We confirmed that the methodology to create distinct zones resulted in a continuous, annealed hydrogel with regional interfaces that did not hinder the transport of soluble molecules. Further, the interface between hydrogel regions did not disrupt microchannel structure, epithelial lumen formation, or media perfusion through an acellular or cellularized microchannel. Finally, we demonstrated spatially patterned tubulogenic sprouting of a continuous epithelial tube into the surrounding hydrogel confined to local regions with stromal cell populations, illustrating spatial control of cell-cell interactions and signaling gradients. This easy-to-use system has wide utility for modeling three-dimensional epithelial and endothelial tissue interactions with heterogeneous hydrogel compositions and/or stromal cell populations to investigate their mechanistic roles during development, homeostasis, or disease.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452416","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":"Integrated device for plasma separation and nucleic acid extraction from whole blood toward point-of-care detection of bloodborne pathogens","authors":"Abigail G. Ayers, Christia M. Victoriano, Samuel K. Sia","doi":"10.1039/d4lc00571f","DOIUrl":"https://doi.org/10.1039/d4lc00571f","url":null,"abstract":"Sample preparation presents a major challenge in point-of-care (POC) diagnostic assays, including ones requiring whole blood as the starting specimen. This study presents an integrated sample preparation device – which we call PRECISE – that performs both plasma separation and nucleic acid extraction, enabling streamlined sample preparation from whole blood requiring only a commercially available blood collection tool and a syringe, and no other external equipment or electricity. Plasma separation is performed using a dual-membrane filter (which filters out blood components while limiting membrane clogging) integrated into the cartridge, and nucleic acid extraction is performed by users moving magnets (to mix the samples, and along a guided track). The plasma filtration demonstrated recovery on par with lab-based centrifugation, and the extraction module showed performance similar to benchtop-based magnetic bead extraction. A sample-to-result demonstration on 50 μL of whole blood spiked with virions of hepatitis C virus (HCV), operating the PRECISE cartridge in 16 minutes followed by benchtop PCR, showed a limit of detection (∼6770 IU mL<small>⁻¹</small>) on the order of the minimal requirements of target product profile for POC HCV detection. Future work on the PRECISE cartridge, building on POC accessibility and fast sample preparation demonstrated in this work, may enable detection of bloodborne pathogens from whole-blood specimens collected at the POC.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448115","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":"Placental microphysiological systems: new advances on promising platforms that mimic the microenvironment of the human placenta","authors":"Inês M. Gonçalves, Muhammad Afzal, Nithil Kennedy, Ana Moita, Rui Lima, Serge Ostrovidov, Takeshi Hori, Yuji Nashimoto, Hirokazu Kaji","doi":"10.1039/d4lc00500g","DOIUrl":"https://doi.org/10.1039/d4lc00500g","url":null,"abstract":"One of the most complex human physiological processes to study is pregnancy. Standard animal models, as well as two-dimensional models, lack the complexity and biological relevance required to accurately study such a physiological process. Recent studies have focused on the development of three-dimensional models based on microfluidic systems, designated as placental microphysiological systems (PMPSs). PMPS devices provide a model of the placental barrier through culturing relevant cell types in specific arrangements and media to mimic the <em>in vivo</em> environment of the maternal–fetal circulation. Here, recent developments of PMPS models for embryo uterine implantation, preeclampsia evaluation, and toxicological screening are presented. Studies that use bioprinting techniques are also discussed. Lastly, recent developments in endometrium microphysiological systems are reviewed. All these presented models showed their superiority compared to standard models in recapitulating the biological environment seen <em>in vivo</em>. However, several limitations regarding the types of cells and materials used for these systems were also widely reported. Despite the need for further improvements, PMPS models contribute to a better understanding of the biological mechanisms surrounding pregnancy and the respective pathologies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443900","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 nanofluidic exchanger for harvesting saline gradients energy","authors":"Saranath Sripriya, Cyril Picard, Vincent Larrey, Frank Fournel, Elisabeth Charlaix","doi":"10.1039/d4lc00544a","DOIUrl":"https://doi.org/10.1039/d4lc00544a","url":null,"abstract":"The energy of saline gradients is a very promising source of non-intermittent renewable energy, the exploitation of which is hampered by the lack of viable technology. The most investigated harvesting methods rely on selective transport of ions or water molecules through semi-permeable or ion-selective membranes, which demonstrate limited power densities of the order of a few W/m2. While in the last decade single nanofluidic objects such as nanopores of nanotubes have opened up very promising prospects with power density capabilities in the kW or even MW/m2, scale-up efforts face serious issues, as concentration polarization phenomena result in a massive loss of performance. We propose here a concept of nanofluidic exchanger for power generation from saline gradients, focused on designing a nanoscale flow able to harvest the power at the output of the nanopores. We study analytically and numerically a simple exchanger made of a selective nanoslit fed by a nanofluidic assembly. One specific feature of such an exchanger relies on the non-linear ion fluxes through the nanoslit analytically expressed from the integration of the Poison-Nernt Planck equation. Such an elemental brick could be massively parallelized in stackable electricity-generating layers using standard technologies of the semi-conductors industry. We demonstrate here a scheme for rationalizing the choice of the exchanger parameters, taking into account the transport properties at all scales. The full numerical resolution of three-dimensional device shows that net power densities of 300 W/m2 and more can be achieved.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440003","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":"Real-time impedance-activated dielectrophoretic actuation for reconfigurable manipulation of single flowing particles","authors":"Alexis Lefevre, Cristian Brandi, Adele De Ninno, Filippo Ruggiero, Enrico Verona, Michael Gauthier, Paolo Bisegna, Aude Bolopion, Federica Caselli","doi":"10.1039/d4lc00622d","DOIUrl":"https://doi.org/10.1039/d4lc00622d","url":null,"abstract":"This work presents an innovative all-electrical platform for selective single-particle manipulation. The platform combines microfluidic impedance cytometry for label-free particle characterization and dielectrophoresis for contactless multi-way particle separation. The microfluidic chip has a straightforward coplanar electrode layout and no particle pre-focusing mechanism is required. An original online algorithm analyzes the impedance signals of each incoming particle and regulates in real-time the dielectrophoretic voltages according to a desired control logic. As proof-of-concept, three operation modes are demonstrated on a mixture of 8, 10, and 12 µm diameter beads: (i) particle position swapping across channel axis, irrespective of particle size, (ii) size-based particle separation, irrespective of particle position, and (iii) sorting of a selected sequence of particles. As a perspective, the versatility of impedance cytometry and dielectrophoresis and the possibility to configure alternative control logics hold promises for advanced particle and cell manipulation.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431705","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":"Compact lens-free imager using thin-film transistor for long-term quantitative monitoring of stem cell culture and cardiomyocyte production","authors":"Taishi Kakizuka, Tohru Natsume, Takeharu Nagai","doi":"10.1039/d4lc00528g","DOIUrl":"https://doi.org/10.1039/d4lc00528g","url":null,"abstract":"With advancements in human induced pluripotent stem cell (hiPSC) technology, there is an increasing demand for quality control techniques to manage the long-term process of target cell production effectively. While monitoring systems designed for use within incubators are promising for assessing culture quality, existing systems still face challenges in terms of compactness, throughput, and available metrics. To address these limitations, we have developed a compact and high-throughput lens-free imaging device named INSPCTOR. The device is as small as a standard culture plate, which allows for the installation of multiple units within an incubator. INSPCTOR utilises a large thin-film transistor image sensor, enabling simultaneous observation of six independent culture environments, each approximately 1 cm<small>²</small>. With this device, we successfully monitored the confluency of hiPSC cultures and identified the onset timing of epithelial-to-mesenchymal transition during mesodermal induction. Additionally, we quantified the beating frequency and conduction of hiPSC-derived cardiomyocytes by using high-speed imaging modes. This enabled us to identify the onset of spontaneous beating during differentiation and assess chronotropic responses in drug evaluations. Moreover, by tracking beating frequency over 10 days of cardiomyocyte maturation, we identified week-scale and daily-scale fluctuations, the latter of which correlated with cellular metabolic activity. The metrics derived from this device would enhance the reproducibility and quality of target cell production.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431706","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":"Acoustic enrichment of sperm for in vitro fertilization","authors":"Chunqiu Zhang, Ning Rong, Ziyi Lin, Pengqi Li, Jingyao Shi, Wei Zhou, Lili Niu, Fei Li, Rongxin Tang, Lei Li, Long Meng","doi":"10.1039/d4lc00604f","DOIUrl":"https://doi.org/10.1039/d4lc00604f","url":null,"abstract":"Assisted reproductive technology (ART) has emerged as a crucial method in modern medicine for tackling infertility. However, the success of fertilization depends on the quality and quantity of sperm, often necessitating invasive surgical intervention, which presents challenges for non-invasive in vitro fertilization. Acoustic microfluidics technology has found widespread application across various biological contexts. In this paper, we propose to introduce a novel approach using asymmetric acoustic streaming generated by a single interdigital transducer (IDT) to enhance sperm concentration and improve fertilization in vitro, particularly in cases of moderate oligozoospermia. The concentration of particles increased approximately 6-fold in the central region after acoustic enrichment. Moreover, sperm motility was significantly improved without additional DNA fragmentation, and all the oocytes remained viable after 5 min of acoustic enrichment. Notably, acoustic enrichment accelerated fertilization and embryo development, leading to a higher fertilization rate and faster cleavage speed. Specifically, within 36 hours, the multiple-cell embryo ratio was significantly increased compared to the control group. This finding further validates the feasibility and non-invasiveness of acoustic enrichment for sperm fertilization in vitro. This work provides a promising tool for in vitro fertilization, holding significant implications for assisted reproduction.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405505","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 low-cost assembly of modular microvessel-on-a-chip with benchtop xurography","authors":"Shashwat Agarwal, Marcos Cortes-Medina, Jacob C. Holter, Alex Avendano, Joseph W. Tinapple, Joseph M. Barlage, Miles M. Menyhert, Lotanna M. Onua, Jonathan W. Song","doi":"10.1039/d4lc00565a","DOIUrl":"https://doi.org/10.1039/d4lc00565a","url":null,"abstract":"Blood and lymphatic vessels in the body are central to molecular and cellular transport, tissue repair, and pathophysiology. Several approaches have been employed for engineering microfabricated blood and lymphatic vessels in vitro, yet these approaches invariably require specialized equipment, facilities, and research training beyond the capabilities of most biomedical laboratories. Here we present xurography as an inexpensive, accessible, and versatile rapid prototyping technique for engineering cylindrical and lumenized microvessels. Using a benchtop xurographer, or a cutting plotter, we fabricated modular multi-layer poly(dimethysiloxane) (PDMS) -based microphysiological systems (MPS) that house endothelial-lined microvessels approximately 260μm in diameter embedded within a user-defined 3-D extracellular matrix (ECM). We validated the vascularized MPS (or vessel-on-a-chip) by quantifying changes in blood vessel permeability due to the pro-angiogenic chemokine CXCL12. Moreover, we demonstrated the reconfigurable versatility of this approach by engineering three different vessel-ECM arrangements, which were obtained by minor adjustments to one or two steps of the fabrication process. Several of these arrangements, such as ones that incorporate close-ended vessel structures and spatially distinct ECM compartments along the same microvessel, cannot be readily achieved with other microfabrication strategies. Therefore, we anticipate that our low-cost and easy-to-implement fabrication approach will facilitate wider accessibility of MPS with tunable vascular architectures and ECM components while reducing the turnaround time required for iterative designs.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383747","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":"Real-time monitoring of a 3D blood-brain barrier model maturation and integrity with a sensorized microfluidic device","authors":"Maria Cristina Ceccarelli, Marie Celine Lefevre, Attilio Marino, Francesca Pignatelli, Katarzyna Krukiewicz, Matteo Battaglini, Gianni Ciofani","doi":"10.1039/d4lc00633j","DOIUrl":"https://doi.org/10.1039/d4lc00633j","url":null,"abstract":"A significant challenge in the treatment of central nervous system (CNS) disorders is represented by the presence of the blood-brain barrier (BBB), a highly selective membrane that regulates molecular transport and restricts the passage of pathogens and therapeutic compounds. Traditional in vivo models are constrained by high costs, lengthy experimental timelines, ethical concerns, and interspecies variations. To address these limitations, in vitro models, particularly microfluidic BBB-on-a-chip devices, have been developed. These advanced models aim to more accurately replicate human BBB conditions by incorporating human cells and physiological flow dynamics. In this framework, here we developed an innovative microfluidic system that integrates thin-film electrodes for non-invasive, real-time monitoring of BBB integrity using electrochemical impedance spectroscopy (EIS). EIS measurements showed frequency-dependent impedance changes, indicating BBB integrity and distinguishing well-formed from non-mature barriers. The data from EIS monitoring was confirmed by permeability assays performed with a fluorescence tracer. The model incorporates human endothelial cells in a vessel-like arrangement to mimic the vascular component and three-dimensional cell distribution of human astrocytes and microglia to simulate the parenchymal compartment. By modeling the BBB-on-a-chip with an equivalent circuit, a more accurate trans-endothelial electrical resistance (TEER) value was extracted. The device demonstrated successful BBB formation and maturation, confirmed through live/dead assays, immunofluorescence and permeability assays. Computational fluid dynamics (CFD) simulations confirmed that the device mimics in vivo shear stress conditions. Drug crossing assessment was performed with two chemotherapy drugs: doxorubicin, with a known poor BBB penetration, and temozolomide, conversely specific drug for CNS disorders and able to cross the BBB, to validate the model predictive capability for drug crossing behavior. The proposed sensorized microfluidic device represents a significant advancement in BBB modeling, offering a versatile platform for CNS drug development, disease modeling, and personalized medicine.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383958","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":"Integrated microfluidic platform for on-site qPCR analysis: food allergen detection from sample to result","authors":"Anne-Gaëlle Bourdat, Remco den Dulk, Bastien Serrano, Gervais Clarebout, Jean Porcherot, Armelle Keiser, Nicolas Sarrut, François Boizot, Xavier Mermet, Raymond Charles, Manuel Alessio, Patricia Laurent, Myriam Cubizolles","doi":"10.1039/d4lc00570h","DOIUrl":"https://doi.org/10.1039/d4lc00570h","url":null,"abstract":"Improving food safety is crucial in the contexte of “One Health” approach. To guarantee product quality and safety, food industry, having a very high turnover rate, needs short time-to-result analyses. Therefore, user-friendly systems at the point-of-need are necessary, presenting relevant analytical performances and fullfiling the current regulations. To answer these challenges, a microfluidic platform integrating sample preparation and subsequent multiplex qPCR detection has been developed for on-site testing. The system consists of a fully automated instrument driving a microfluidic cartridge dedicated to the detection of multiple allergens in complex food matrices. The first part of the microfluidic cartridge contains pumps, reservoirs, valves and a filter to achieve DNA extraction, concentration and purification. Multiplex qPCR detection is carried out in the second part of the cartridge including a negative control chamber and five chambers for target analyte detection. The in-house developed instrument contains all functions to autonomously drive the microfluidic cartridge: pneumatic control for fluid actuation, thermal control for qPCR amplification and an optical sytem using three fluorescent wavelengths for multiplex detection of the target analytes and controls. We demonstrate the simultaneous detection of four different allergens – gluten, sesame, soy and hazelnut – from various complex food matrices. The turn-around-time from sample to result is close to two hours and controls in place validate the obtained results. For gluten, a direct comparison with ELISA shows that the regulatory threshold of 20 ppm is comfortably fulfilled. Moreover, all results are in agreement with external laboratory analyses performed in parallel on the same samples. Our findings confirm that the system can be used safely on-site without risk for cross contamination between various samples to be analysed. In conclusion, our microfluidic platform offers a robust method for on-site allergen management.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377439","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}