Lab on a Chip最新文献

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Enhancing cancer cell immunocapture on orientation-controlled nanoimprinted microcone arrays in microgap channels. 微间隙通道中定向控制纳米印迹微锥阵列增强癌细胞免疫捕获。
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-04 DOI: 10.1039/d5lc00143a
Yuhei Saito, Natsumi Shimmyo, Shuhei Aoyama, Rie Utoh, Minoru Seki, Masumi Yamada
{"title":"Enhancing cancer cell immunocapture on orientation-controlled nanoimprinted microcone arrays in microgap channels.","authors":"Yuhei Saito, Natsumi Shimmyo, Shuhei Aoyama, Rie Utoh, Minoru Seki, Masumi Yamada","doi":"10.1039/d5lc00143a","DOIUrl":"https://doi.org/10.1039/d5lc00143a","url":null,"abstract":"<p><p>Cancer detection through circulating tumor cell (CTC)-based liquid biopsy has been expected to be a new modality for less-invasive, next-generation diagnosis. However, due to limitations such as the complexity of the cell capture devices, as well as the cost and reproducibility of their fabrication and surface functionalization, these methods are not yet practical for clinical use. In this study, we propose a new strategy for affinity-based selective capture of cancer cells using a microfluidic system integrating nanoengineered polymeric structures. Polycarbonate (PC) sheets with closely assembled microcone arrays were prepared using thermal nanoimprint lithography (T-NIL). These structures are suitable for mass production and can strongly absorb antibodies without the need for chemical linkers. Microgap channels incorporating the microcones were formed by simply sandwiching the sheet between two plates, which were highly functional in capturing cancer cells from blood samples. In this study, we clarified the effect of the orientation angle of the microcone array in a closely packed hexagonal pattern to ensure high capture efficiency even under high flow-rate conditions. The feasibility of detecting cancer cells through post-capture processing was also demonstrated. The cell capture structures proposed in this study are simple and reproducible in their fabrication, highly productive, and practical, and may become a new tool for cell-based cancer diagnosis.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214402","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}
引用次数: 0
Patient-derived organotypic tumor spheroids, tumoroids, and organoids: advancing immunotherapy using state-of-the-art 3D tumor model systems 患者来源的器官型球形肿瘤、类肿瘤和类器官:利用最先进的3D肿瘤模型系统推进免疫治疗
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-04 DOI: 10.1039/D5LC00062A
David J. Bozym, David X. Zheng, Or-Yam Revach, Amir Aref and Russell W. Jenkins
{"title":"Patient-derived organotypic tumor spheroids, tumoroids, and organoids: advancing immunotherapy using state-of-the-art 3D tumor model systems","authors":"David J. Bozym, David X. Zheng, Or-Yam Revach, Amir Aref and Russell W. Jenkins","doi":"10.1039/D5LC00062A","DOIUrl":"10.1039/D5LC00062A","url":null,"abstract":"<p >Preclinical <em>ex vivo</em> models capable of probing patient-specific tumor–immune interactions are particularly attractive candidates for interrogating mechanisms of resistance, developing predictors of response as well as assessing next-generation immunotherapeutics. By maintaining features of a patient's own tumor microenvironment, such patient-derived <em>ex vivo</em> models are poised to meaningfully contribute to the functional assessment of individual tumors to provide a tailored approach to treatment. Among contemporary <em>ex vivo</em> models, patient-derived organotypic tumor spheroids (PDOTS) have emerged as a promising microfluidic-based platform that is well positioned to become a useful tool for precision medicine efforts. The advantages and limitations of PDOTS and related state-of-the-art patient-derived tumor models, as well as ongoing challenges facing the clinical implementation of patient-derived <em>ex vivo</em> tumor models, are reviewed.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3038-3059"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211177","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}
引用次数: 0
Controllable Pump-Free Electrokinetic-Driven Microdevice for Single-Cell Electrorotation 用于单细胞电旋的可控无泵电动驱动微装置
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-04 DOI: 10.1039/d5lc00202h
Jianming Shu, Xijiang Wang, Liang Huang
{"title":"Controllable Pump-Free Electrokinetic-Driven Microdevice for Single-Cell Electrorotation","authors":"Jianming Shu, Xijiang Wang, Liang Huang","doi":"10.1039/d5lc00202h","DOIUrl":"https://doi.org/10.1039/d5lc00202h","url":null,"abstract":"Single-cell electrorotation (ROT) has emerged as a fundamental technique for characterizing cellular electrical properties, yet conventional methodologies face significant limitations including laborious cell loading procedures, time-consuming measurements, low throughput, and confined effective operational regions. To address these challenges, we present an innovative pump-free single-cell electrorotation device that synergistically integrates electroosmotic flow (EOF) with ROT technologies. Our design employs time-division multiplexed electrical signal modulation to achieve real-time regulation of EOF velocity and directionality, effectively resolving cell positioning challenges while eliminating the need for complex pumping system. This approach not only reduces experimental cost but also significantly simplifies operational complexity. Furthermore, the implementation of thick-electrode architecture successfully mitigates electric field spatial attenuation, thereby expanding the effective ROT zone and enhancing measurement stability and precision. Comprehensive numerical simulations and experimental validations demonstrate the capability of microdevice for accurate determination of cellular parameters, (eg. membrane permittivity εmem and cytoplasmic conductivity σcyto). We envision that the pump-free single-cell ROT microdevice will provide a new platform for convenient and high-throughput cell electrical characterization.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211175","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}
引用次数: 0
Parallel dilution microfluidic device for enabling logarithmic concentration generation in molecular diagnostics† 平行稀释微流控装置,用于分子诊断中对数浓度的产生
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-04 DOI: 10.1039/D5LC00356C
Akira Miyajima, Fumiya Nishimura, Daigo Natsuhara, Yuka Kiba, Shunya Okamoto, Moeto Nagai, Tadashi Yamamuro, Masashi Kitamura and Takayuki Shibata
{"title":"Parallel dilution microfluidic device for enabling logarithmic concentration generation in molecular diagnostics†","authors":"Akira Miyajima, Fumiya Nishimura, Daigo Natsuhara, Yuka Kiba, Shunya Okamoto, Moeto Nagai, Tadashi Yamamuro, Masashi Kitamura and Takayuki Shibata","doi":"10.1039/D5LC00356C","DOIUrl":"10.1039/D5LC00356C","url":null,"abstract":"<p >In this study, we present a genetic diagnostic device with a four-stepwise logarithmic dilution capability for rapid and reliable detection of target nucleic acids in a single operation using the colorimetric loop-mediated isothermal amplification (LAMP) method. An innovative feature is the confluent point with differing microchannel heights ensuring the synchronized inflow of liquids while preventing backflow, even under large volumetric flow rate variations (10–10 000-fold). This enabled the independent generation of each dilution factor under constant pressure. Furthermore, an integrated asymmetric micromixer effectively mixed two liquids under laminar flow conditions, enabling simultaneous dispensing of the mixed solution at uniform concentrations into five microchambers for each dilution factor. Additionally, a permanent stop valve in the outlet of each microchamber prevented leakages, minimizing the waste of valuable samples and reagents. We demonstrate that diluted samples were accurately prepared at the intended logarithmic dilution factors in a single operation using purified cannabis seed DNA, achieving detection sensitivity similar to that of conventional turbidity-based LAMP assays. Moreover, we used crudely extracted cannabis resin DNA, which contains several gene amplification inhibitors, successfully detecting the target nucleic acids in a single test. Overall, this versatile device eliminates extensive manual sample preparation and has potential for on-site genetic testing in applications such as infectious disease detection, food safety, and illegal drug testing.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3242-3253"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00356c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211174","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}
引用次数: 0
Transient osmotic flows in a microfluidic channel: measurements of solute permeability and reflection coefficients of hydrogel membranes 微流体通道中的瞬时渗透流动:水凝胶膜溶质渗透率和反射系数的测量
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-03 DOI: 10.1039/d5lc00276a
Julien Renaudeau, Pierre Lidon, Jean-Baptiste Salmon
{"title":"Transient osmotic flows in a microfluidic channel: measurements of solute permeability and reflection coefficients of hydrogel membranes","authors":"Julien Renaudeau, Pierre Lidon, Jean-Baptiste Salmon","doi":"10.1039/d5lc00276a","DOIUrl":"https://doi.org/10.1039/d5lc00276a","url":null,"abstract":"We first highlight theoretically a microfluidic configuration that allows to measure two fundamental parameters describing mass transport through a membrane: the solute permeability coefficient L<small><sub>D</sub></small>, and the associated reflection coefficient σ. This configuration exploits the high confinement of microfluidic geometries to relate these two coefficients to the dynamics of a transient flow induced by forward osmosis through a membrane embedded in a chip. We then applied this methodology to hydrogel membranes photo-crosslinked in a microchannel with textit{in situ} measurements of osmotically-induced flows. These experiments enable us to estimateL<small><sub>D</sub></small> and σ and their dependence on the molecular weight of the solute under consideration, ultimately leading to a precise estimate of the molecular weight cut-off of these hydrogel membranes.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"359 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219134","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}
引用次数: 0
Ion concentration polarization focusing at a millimeter-scale microbead junction: towards higher volumetric throughput 毫米级微珠结的离子浓度偏振聚焦:迈向更高的体积吞吐量
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-06-03 DOI: 10.1039/d5lc00183h
Umesha Peramune, Zisun Ahmed, Robbyn Kimberly Anand
{"title":"Ion concentration polarization focusing at a millimeter-scale microbead junction: towards higher volumetric throughput","authors":"Umesha Peramune, Zisun Ahmed, Robbyn Kimberly Anand","doi":"10.1039/d5lc00183h","DOIUrl":"https://doi.org/10.1039/d5lc00183h","url":null,"abstract":"Ion concentration polarization focusing (ICPF) is an electrokinetic technique that has shown promise in achieving even billion-fold preconcentration factors. However, increasing the volumetric throughput of ICPF is challenging because disruptive processes that reduce preconcentration efficiency worsen as the channel cross-section extends beyond the microscale. We previously introduced an approach for mitigating the above challenges in a microfluidic regime. However, in that system, the flow rate was limited to less than 1.0 µL/min. Herein, we report a high throughput and scalable ICPF of charged analytes in a millimeter-scale channel. Using 3D-printed channels of 4.0 mm2 cross-section, we achieve preconcentration factors above 200 fold within 10 min at a flow rate of 30 µL/min. In this system, ICP is accomplished by ion permselective transport through a packed bed of commercially available cation exchange microbeads (30 µm and 200 µm). We investigate the scalability of the approach by comparing the ICPF performance of channels with four distinct cross-sectional areas. While ICPF occurs in all four cases, the degree of preconcentration drops below 100 fold (per 10 min) in channels with cross-sections beyond 4.0 mm2. This drop in efficiency is attributed to dispersion associated with Joule heating. Therefore, by improving the device design to dissipate heat more effectively, we anticipate that this approach can be scaled up further for applications that demand high volumetric throughput electrokinetic focusing.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"5 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211178","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}
引用次数: 0
High-throughput Monoclonal Antibody Screening from Immunized Rabbits via Droplet Microfluidics 用微流控液滴技术筛选免疫兔高通量单克隆抗体
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-05-31 DOI: 10.1039/d5lc00340g
Johnson Q Cui, Ruyuan Song, Weihong Song, Ouyang Li, Xin Yuan, Hongbo Zhou, Lu Zhang, Shuhuai Yao
{"title":"High-throughput Monoclonal Antibody Screening from Immunized Rabbits via Droplet Microfluidics","authors":"Johnson Q Cui, Ruyuan Song, Weihong Song, Ouyang Li, Xin Yuan, Hongbo Zhou, Lu Zhang, Shuhuai Yao","doi":"10.1039/d5lc00340g","DOIUrl":"https://doi.org/10.1039/d5lc00340g","url":null,"abstract":"The discovery of monoclonal antibodies (mAbs) is critical to advancing therapeutics, diagnostics, and biomedical research. While mouse-derived mAbs dominate current applications, their limitations—short serum half-life, human immunogenicity, and restricted recognition of human-specific antigens—highlight the need for alternative sources. Rabbit-derived mAbs have been gaining significant traction with their superior antigen-binding affinity, broader epitope diversity, and higher yield potential. However, the absence of well-defined surface markers on rabbit B cells has hindered efficient enrichment strategies, limiting the exploration of this valuable antibody repertoire. In this study, we present an integrated workflow that combines magnetic negative selection with high-throughput droplet microfluidics to overcome these barriers. By optimizing a pan B cell enrichment protocol using a tailored antibody cocktail, we achieved a notable boost in IgG secretion and B cell enrichment. Through two complementary droplet-encapsulated assays using particle aggregation for soluble antigens and reporter cells for membrane-bound antigens, we identified target cells capable of secreting high-affinity IgGs. Subsequent sequencing, in vitro antibody production and characterization confirmed the high affinity rate of the discovered antibodies, outperforming rates previously reported. The use of droplet microfluidics streamlines the analysis of rabbit IgG repertoires, providing a robust platform for rabbit single B cell antibody discovery with promising applications in precision medicines and diagnostics.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"53 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211179","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}
引用次数: 0
In situ electrochemical measurement of alkaline phosphatase activity in engineered gut models using a porous membrane electrode device. 利用多孔膜电极装置原位电化学测量工程肠模型中碱性磷酸酶活性。
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-05-30 DOI: 10.1039/d5lc00341e
Yoshinobu Utagawa, Takeo Miyake, Yasuhiko Shinoda, Masateru Yamazaki, Hiroya Abe, Hitoshi Shiku, Kosuke Ino
{"title":"<i>In situ</i> electrochemical measurement of alkaline phosphatase activity in engineered gut models using a porous membrane electrode device.","authors":"Yoshinobu Utagawa, Takeo Miyake, Yasuhiko Shinoda, Masateru Yamazaki, Hiroya Abe, Hitoshi Shiku, Kosuke Ino","doi":"10.1039/d5lc00341e","DOIUrl":"https://doi.org/10.1039/d5lc00341e","url":null,"abstract":"<p><p><i>In vitro</i> assays utilizing human cells have attracted attention as alternatives to animal testing for drug screening. Microphysiological systems (MPS) have been proposed as cell culture platforms that more closely mimic the <i>in vivo</i> microenvironment. Engineered gut models have been extensively studied using human colorectal adenocarcinoma cell lines (Caco-2 cells). Alkaline phosphatase (ALP) activity indicates Caco-2 cell differentiation and is a component of the chemical barrier that maintains intestinal barrier function. However, conventional absorbance-based methods for ALP measurement can harm cells owing to prolonged exposure to alkaline conditions (approximately 60 min). In this study, we developed an engineered gut model with a porous membrane electrode for <i>in situ</i> measurement of ALP activity. The electrochemical sensors, positioned directly beneath the cells on porous membrane electrodes, allowed for rapid short-term measurements. ALP activity was detected after a 3 min treatment through <i>in situ</i> electrochemical measurements, which indicated low cytotoxicity. Therefore, we measured ALP activity multiple times using the same device over 21 days. The proposed system offers potential for <i>in situ</i> measurement and real-time monitoring in <i>in vitro</i> organ models, including MPS devices.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179729","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}
引用次数: 0
A polystyrene-film-based device for engineered cardiac tissues enables accurate analysis of drug responses on contractile properties. 一种用于工程心脏组织的聚苯乙烯薄膜装置能够准确分析药物对收缩特性的反应。
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-05-30 DOI: 10.1039/d4lc00691g
Yuya Fujiwara, Masako Sasaki, Sohei Funaoka, Takuro Yoshikuni, Yuki Naka, Kazumi Ida, Taichi Aihara, Shunsuke Funakoshi, Kenichi Imahashi, Yoshinori Yoshida
{"title":"A polystyrene-film-based device for engineered cardiac tissues enables accurate analysis of drug responses on contractile properties.","authors":"Yuya Fujiwara, Masako Sasaki, Sohei Funaoka, Takuro Yoshikuni, Yuki Naka, Kazumi Ida, Taichi Aihara, Shunsuke Funakoshi, Kenichi Imahashi, Yoshinori Yoshida","doi":"10.1039/d4lc00691g","DOIUrl":"https://doi.org/10.1039/d4lc00691g","url":null,"abstract":"<p><p>Engineered heart tissues (EHTs) using human induced pluripotent stem cells provide a valuable <i>in vitro</i> platform for assessing pharmacological and toxicological effects on cardiac functions. EHT devices offer a feasible approach to readily evaluate drug responses on contractile properties, including contractile force and relaxation, by measuring the moving distance of pillars attached to EHTs. However, the absorption of small molecule compounds by polydimethylsiloxane (PDMS), the material commonly used to construct EHT devices, hinders the accurate evaluation of the pharmacodynamic properties of drug candidates on contractility. Here, we developed a low-absorption EHT device using polystyrene (PS) to address this issue. Moreover, we generated an original Python-based analysis program to avoid analytical bias when tracking pillar positions and analyzing the contractile waveform drawn from EHT movements. This analytical platform enables the detection of increased contractile force during EHT maturation and the negative inotropic effects of diltiazem and blebbistatin on EHT contractile functions. Moreover, EHTs with PS-based devices suppressed the absorption of a cardiotoxic drug, doxorubicin, thus allowing the detection of cardiotoxic effects even at low concentrations compared to EHTs grown on PDMS-based devices. Together, our EHT system represents a useful <i>in vitro</i> platform for accurate evaluations of drug responses by the human heart.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186085","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}
引用次数: 0
Development of on-chip cell domes using Ca-alginate hydrogel shells for non-adherent cell studies. 利用海藻酸钙水凝胶壳进行非贴壁细胞研究的芯片细胞圆顶的开发。
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2025-05-29 DOI: 10.1039/d5lc00204d
Shinji Sakai, Hiroyuki Fujiwara, Ryotaro Kazama, Riki Toita, Satoshi Fujita
{"title":"Development of on-chip cell domes using Ca-alginate hydrogel shells for non-adherent cell studies.","authors":"Shinji Sakai, Hiroyuki Fujiwara, Ryotaro Kazama, Riki Toita, Satoshi Fujita","doi":"10.1039/d5lc00204d","DOIUrl":"https://doi.org/10.1039/d5lc00204d","url":null,"abstract":"<p><p>Cell domes are hemispherical microstructures comprising hydrogel shells that enclose cells within their cavities. They are approximately 500 and 300 μm in radius and height, respectively. Multiple domes can be fabricated in an array on a single glass plate to facilitate optical observations and provide a localised and stable environment for non-adherent cell studies. However, current limitations, such as cytotoxicity, reduced cell viability and complex fabrication strategies, hinder their advancements. Thus, we address these limitations by proposing a cell dome system based on calcium ion (Ca<sup>2+</sup>)-crosslinked alginate hydrogel shells anchored to glass plates. The fabrication process was significantly streamlined and improved compared to previously reported enzyme-mediated methods, rendering it more accessible for biomedical applications. The resulting cell domes exhibited excellent adhesion stability to glass plates, maintaining an adhesion rate of >90% following 168 h of incubation under cell culture conditions. Enclosed K562 cells, which represent a non-adherent erythroleukemia cell line, exhibited consistent viability (>95%) and a 14-fold increase in cell proliferation over 72 h. The hydrogel shell enabled reagents, such as calcein-AM and ethidium homodimer-1, to enter the dome from the external environment. In addition, reagents could be transferred to the enclosed cells from within the dome by pre-depositing them onto the glass prior to dome preparation. Our proposed Ca-alginate cell dome broadens the application of cell domes as a scalable and versatile platform for high-throughput drug screening and cellular analysis, offering precise control over non-adherent cell studies.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172079","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}
引用次数: 0
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