Lab on a Chip最新文献

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Associating the morphology of helper T cells with cytokine activity through imaging flow cytometry and deep learning. 通过成像流式细胞术和深度学习将辅助性T细胞的形态与细胞因子活性联系起来。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00113k
Natsumi Tiffany Ishii, Ikuo Hieda, Yaqi Zhao, Tatsuhiko Akiyama, Yingdong Luo, Kazuma Kita, Yuma Oka, Masatoshi Yanagida, Tianben Ding, Keisuke Goda
{"title":"Associating the morphology of helper T cells with cytokine activity through imaging flow cytometry and deep learning.","authors":"Natsumi Tiffany Ishii, Ikuo Hieda, Yaqi Zhao, Tatsuhiko Akiyama, Yingdong Luo, Kazuma Kita, Yuma Oka, Masatoshi Yanagida, Tianben Ding, Keisuke Goda","doi":"10.1039/d6lc00113k","DOIUrl":"10.1039/d6lc00113k","url":null,"abstract":"<p><p>The immune system protects the body from foreign substances, such as viruses and bacteria. Among its key orchestrators are helper T cells, which coordinate immune responses by activating other immune cells to eliminate these threats. Helper T cell activation has been widely studied, often by stimulating cells <i>in vitro</i> and measuring changes in receptor expression. However, systematic assessment of activation at scale remains challenging because it requires both large single-cell imaging datasets and advanced computational methods to analyse complex morphological features. Here, using imaging flow cytometry and deep learning, we show that morphological information is crucial for identifying high-activity T cells. We also demonstrate that receptor clustering may associate with high cytokine activity. These findings provide a new perspective for assessing treatment options for patients with immune-related diseases.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4763-4774"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628969","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 MEMS-based point-of-care platelet counting system. 基于mems的即时血小板计数系统。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00195e
Luke A Beardslee, E Kendall Williams, Durga Gajula, Audrey Wang, Wilbur A Lam
{"title":"A MEMS-based point-of-care platelet counting system.","authors":"Luke A Beardslee, E Kendall Williams, Durga Gajula, Audrey Wang, Wilbur A Lam","doi":"10.1039/d6lc00195e","DOIUrl":"10.1039/d6lc00195e","url":null,"abstract":"<p><p>Thrombocytopenia is a major issue in pediatric patients undergoing therapy for hematological malignancies. A point-of-care test to measure platelet count will help alleviate the burden for these patients and their families by allowing them to test for thrombocytopenia at home instead of through frequent lab tests or by going to the emergency room if there is concern for easy bleeding. We present the development and initial testing of a silicon microelectromechanical systems (MEMS) based point-of-care diagnostic sensor to assess blood platelet concentrations. The transduction principle of the sensor is based on the forces that platelets exert in forming blood clots. The test uses a single drop of blood and can be realized as a small form factor system containing the developed sensor. We present the design, fabrication, electronic system integration and preliminary results towards the development of this point-of-care sensor for platelet count.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4739-4749"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617549","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
On-demand microfluidic encapsulation of Caenorhabditis elegans in hydrogel for long-term observation via AI detection. 按需微流体将秀丽隐杆线虫包封在水凝胶中,通过AI检测进行长期观察。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00148c
Sinthuran Jegatheeswaran, Teo Mesrkhani, Wei Liu, Mohammad Kashif, June H Tan, Basel A Khader, Elodie Lugez, Andrew G Fraser, Dae Kun Hwang
{"title":"On-demand microfluidic encapsulation of <i>Caenorhabditis elegans</i> in hydrogel for long-term observation <i>via</i> AI detection.","authors":"Sinthuran Jegatheeswaran, Teo Mesrkhani, Wei Liu, Mohammad Kashif, June H Tan, Basel A Khader, Elodie Lugez, Andrew G Fraser, Dae Kun Hwang","doi":"10.1039/d6lc00148c","DOIUrl":"10.1039/d6lc00148c","url":null,"abstract":"<p><p>Biocompatible hydrogel encapsulation of model organisms, such as <i>Caenorhabditis elegans</i>, is highly desirable over chemical or mechanical immobilization methods that can harm health and hinder long term imaging studies. This study introduces an automated, gentle method for continuous immobilization within hydrogel blocks, achieved through flow lithography and machine learning-assisted vision detection. To optimize this automated worm immobilization, we investigated operating parameters, such as flow rate, solution composition, and worm loading concentration. With 90% precision in AI worm detection, we achieved 86% encapsulation efficiency at low to moderate worm-loading concentrations (1-7 worms per μL). Higher loading concentrations of 10-15 worms per μL reduced the encapsulation efficiency to 71%. Worm loading concentration, composition, and flow-rate ratios of the two input solutions-the worm-suspended aqueous solution (WSAS) and the polyethylene glycol diacrylate (PEGDA) solution (PEGS)-significantly affected worm throughput, worm dehydration during encapsulation, and the viability of encapsulated worms. The WSAS-to-PEGS flow-rate ratio was set at 0.5, with a minimum WSAS flow rate of 1 μL min<sup>-1</sup> required to avoid backflow. The PEGDA concentration in PEGS was kept below 50% to avoid worm dehydration. By varying the concentrations of hydrogel precursor, PEGDA, we enabled both partial and complete immobilization suitable for short term and long-term studies, respectively. Results show the encapsulated worm's viability over 3 days, highlighting this method's potential for long-term studies without compromising worm health or movement.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4750-4762"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617556","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
Castable 3D monolithic microfluidic devices. 可浇注的三维单片微流控装置。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d5lc00950b
Bram Servais, David R Nisbet, David J Collins
{"title":"Castable 3D monolithic microfluidic devices.","authors":"Bram Servais, David R Nisbet, David J Collins","doi":"10.1039/d5lc00950b","DOIUrl":"10.1039/d5lc00950b","url":null,"abstract":"<p><p>Microfluidic devices remain difficult to translate into commercial products, particularly for three-dimensional (3D) applications. While soft lithography offers high-resolution features and biocompatibility, its workflows and planar geometries are limited. Conversely, industry-standard injection moulding enables scalability, but lacks flexibility and incurs high upfront costs. Here, we present an innovative hybrid microfabrication methodology combining stereolithographic 3D printed moulds with flexible wire templating and polydimethylsiloxane (PDMS) casting to create monolithic 3D microfluidic devices. Leveraging injection moulding design principles, this enables the rapid and repeatable fabrication of microfluidic devices with embedded internal channels, variable-height membranes, and curved geometries. Our methodology is validated using a variety of devices, including flexible membranes, plug-based flow distributors for 96-well plates, and high-aspect-ratio bioreactors with integrated electrodes. The resulting devices were leak-proof, reusable, and compatible with standard cell culture systems. This scalable, low-cost methodology retains the advantages of PDMS while allowing for 3D design freedom for both internal channels and external features, making it ideal for emerging applications such as organ-on-chip, bioprinting, diagnostics, and soft robotics.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4689-4704"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576376","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
Differential modulation of exhausted Th1 cell migration by immune checkpoint blockade: insights from 3D microfluidic and in vivo PDX platforms. 免疫检查点阻断对耗尽Th1细胞迁移的差异调节:来自3D微流体和体内PDX平台的见解。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00574h
Utku Horzum, Hamdullah Yanik, Ece Tavukcuoglu, Ekim Zihni Taskiran, Suleyman Can Ozturk, Kerim Bora Yilmaz, Gunes Esendagli
{"title":"Differential modulation of exhausted Th1 cell migration by immune checkpoint blockade: insights from 3D microfluidic and <i>in vivo</i> PDX platforms.","authors":"Utku Horzum, Hamdullah Yanik, Ece Tavukcuoglu, Ekim Zihni Taskiran, Suleyman Can Ozturk, Kerim Bora Yilmaz, Gunes Esendagli","doi":"10.1039/d6lc00574h","DOIUrl":"10.1039/d6lc00574h","url":null,"abstract":"<p><p>Effective anti-tumor immunity is critically dependent on the functional capacity and robust infiltration of type-1 helper T (Th1) cells into the tumor microenvironment (TME). However, persistent antigenic stimulation leads to T cell exhaustion, determining the efficacy of immunotherapy approaches such as immune checkpoint inhibitors (ICIs). A key barrier to successful immunotherapy therapy remains the impaired motility and infiltration of exhausted T cells. To address this, we investigated the dual impact of anti-PD-1 and anti-CTLA-4 blockade on the migratory efficacy of <i>ex vivo</i> generated exhausted Th1 (Th1-Ex) cells. Recognizing the limitations of 2D culture, we utilized a 3D microfluidic (lab-on-a-chip) platform to simulate the TME's complex physical and chemical constraints, alongside <i>in vivo</i> patient-derived xenograft (PDX) models. While ICI treatment did not alter static adhesion, it distinctly modulated focal adhesion dynamics. Critically, in the highly relevant 3D microfluidic environment, ICI-treated Th1-Ex cells exhibited significantly enhanced motility and directional persistence compared to untreated cells. Mechanistically, anti-PD-1/CTLA-4 treatment activated signalling pathways associated with both amoeboid and mesenchymal-like migration, but functional inhibition identified RAC1-dependent mesenchymal-like migration as the predominant contributor to the enhanced migratory response. These results were strongly corroborated <i>in vivo</i>, where the anti-PD-1/CTLA-4 combination conferred remarkable and selective tumor and lymph node infiltration capacity to the adoptively transferred Th1-Ex cells. Collectively, our findings highlight a dual role for ICIs on restoring Th1 cell functionality and actively promoting tumor-directed migration by altering adhesion-migration pathways, offering novel mechanistic insights for optimizing immunotherapies in solid tumors.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4788-4801"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672726","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
Perfused brain slice-on-chip platforms: a systematic review of long-term organotypic hippocampal tissue culture. 灌注脑切片芯片平台:长期器官型海马组织培养的系统回顾。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00266h
Tando Maduna, Anna Pancho, Yasin Ilgaz, Marsela Hakani, Atocha Guedán-Duran, Alan Morin, Julia Elisa Sepulveda-Diaz, Assunta Virtuoso, Ciro De Luca, Giovanni Cirillo, Michele Papa, Fivos Panetsos, José Pérez-Rigueiro, Andreas Vlachos
{"title":"Perfused brain slice-on-chip platforms: a systematic review of long-term organotypic hippocampal tissue culture.","authors":"Tando Maduna, Anna Pancho, Yasin Ilgaz, Marsela Hakani, Atocha Guedán-Duran, Alan Morin, Julia Elisa Sepulveda-Diaz, Assunta Virtuoso, Ciro De Luca, Giovanni Cirillo, Michele Papa, Fivos Panetsos, José Pérez-Rigueiro, Andreas Vlachos","doi":"10.1039/d6lc00266h","DOIUrl":"10.1039/d6lc00266h","url":null,"abstract":"<p><p>Organ-on-chip (OoC) platforms are increasingly used to replicate structural, functional and molecular features of native tissue within controlled microenvironments. While most current brain-on-chip (BoC) systems rely on 2D cultures or 3D stem cell-derived constructs, the integration of intact brain tissue slices-particularly organotypic explants of the central nervous system-offers distinct advantages by preserving native cytoarchitecture, synaptic connectivity, and regional specificity. This systematic review aimed to identify and critically assess OoC platforms that incorporate <i>ex vivo</i> brain tissue slices maintained under dynamic perfusion for extended periods (≥10 days <i>in vitro</i>). A structured PubMed search conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines identified 2796 records, of which 7 studies met the predefined inclusion criteria. All included studies employed organotypic brain slices derived from early postnatal rodents and integrated them into perfused microfluidic systems. Most platforms combined air-liquid interface culture with low-volume perfusion to support prolonged tissue viability and partial functional maintenance, including electrophysiological activity, preserved structural integrity, and molecular homeostasis. Notably, none of the identified studies reported the successful long-term cultivation of adult rodent or human brain tissue in a comparable perfused OoC configuration, underscoring a major limitation of current approaches. Moreover, assessment of tissue viability and function was heterogeneous and frequently relied on descriptive or insufficiently sensitive readouts, limiting cross-platform comparisons and translational relevance. Future development of BoC technologies should prioritize improved microenvironmental control, the integration of suitable biomaterials, and embedded monitoring strategies capable of assessing metabolic state and circuit-level function. Addressing these challenges will be essential for advancing OoC platforms towards physiologically meaningful and translationally relevant applications in neuroscience.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4624-4638"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704640","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
3-Dimensional flexible device for measuring concentric contractile force of in vitro ring-shaped smooth muscle tissue. 一种测量体外环形平滑肌组织同心收缩力的三维柔性装置。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00432f
DongWoo Lee, Byeongwook Jo, Minghao Nie, Shoji Takeuchi
{"title":"3-Dimensional flexible device for measuring concentric contractile force of <i>in vitro</i> ring-shaped smooth muscle tissue.","authors":"DongWoo Lee, Byeongwook Jo, Minghao Nie, Shoji Takeuchi","doi":"10.1039/d6lc00432f","DOIUrl":"10.1039/d6lc00432f","url":null,"abstract":"<p><p>Real-time quantification of concentric contractile force in engineered ring-shaped smooth muscle tissue remains challenging because conventional optical readouts provide indirect deformation-based measurements, whereas force-based systems often distort the circular tissue geometry. Here, we present a 3-dimensional flexible device for measuring the contractile force of <i>in vitro</i> ring-shaped smooth muscle tissue by electrical readouts while preserving its circular configuration. The device consists of a circular array of FEM-optimized n-shaped flexible pillars that convert tissue-derived contraction into n-shaped pillar bending and an electrical resistance change. To improve electrical robustness during bending, an air-sprayed SEBS polymer interlayer was introduced before Au deposition, reducing deformation-induced cracking and enabling continuous electrical response. The selected 300 μm pillar design showed a force-displacement relationship consistent with FEM prediction, and the calibrated Δ<i>V</i>-force relationship exhibited an approximately linear response up to ∼200 μN. Ring-shaped human aortic smooth muscle tissues formed by collagen-based self-assembly showed spontaneous compaction and expression of α-SMA and calponin. During 15 h of spontaneous compaction, the device detected a progressive increase in single-pillar force, reaching 125.3 ± 44.2 μN at 15 h. The device also detected high-K<sup>+</sup>/Ca<sup>2+</sup>-evoked active contraction, with a peak single-pillar force of ∼70 μN. These results demonstrate a calibrated electrical force-readout approach for ring-shaped smooth muscle tissue contractility and establish a device-level basis for future force-based evaluation of pharmacological responses and disease-associated contractile differences.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4775-4787"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663026","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
From flow to form: structuring and patterning hydrogels using microfluidic approaches. 从流动到形成:结构和图案水凝胶使用微流体方法。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00386a
Ella E Bouker, Lauren G Brown, Emilie Newsham Novak, Ariel Lin, Jamison M Whitten, Asha R Viswanathan, Laura A Milton, M Yunos Alizai, Siwan Park, Jungseub Lee, Liam A Knudsen, Sophie R Cook, Yi-Chin Toh, Jean Berthier, Amanda J Haack, Noo Li Jeon, Erwin Berthier, Ashleigh B Theberge
{"title":"From flow to form: structuring and patterning hydrogels using microfluidic approaches.","authors":"Ella E Bouker, Lauren G Brown, Emilie Newsham Novak, Ariel Lin, Jamison M Whitten, Asha R Viswanathan, Laura A Milton, M Yunos Alizai, Siwan Park, Jungseub Lee, Liam A Knudsen, Sophie R Cook, Yi-Chin Toh, Jean Berthier, Amanda J Haack, Noo Li Jeon, Erwin Berthier, Ashleigh B Theberge","doi":"10.1039/d6lc00386a","DOIUrl":"10.1039/d6lc00386a","url":null,"abstract":"<p><p>Three-dimensional (3D) cell culture can leverage the precise arrangement of materials, known as patterning, to generate physiologically relevant tissue-like structures. Hydrogels are widely used in 3D cell culture due to their ability to mimic the properties of biological extracellular matrix networks. In this tutorial review, we discuss the use of microfluidic systems to control fluid movement and placement within fabricated microchannels to pattern hydrogel precursors in 3D through the use of capillary flow. Such systems offer unique advantages in their ability to create complex biomimetic structures, organs-on-a-chip, and microphysiological systems with high spatial resolution and relatively small volumes of hydrogel material. We first discuss the fundamental principles behind capillary pinning and aspiration-mediated patterning. We then review literature describing the development and applications of three different types of microfluidic systems - closed, semi-open, and open - and describe how different patterning techniques are applied to each system. We also discuss modular microfluidic systems, in which multiple classes of microfluidic systems are combined together for complex and biomimetic modeling of biological systems. In each section, we provide synthesis and critical analysis of established and novel techniques to draw connections across diverse papers in literature. Finally, we offer our perspectives on the advantages of microfluidic systems for hydrogel patterning and the future of the field. Taken together, microfluidic flow-based patterning is an exciting tool for microphysiological systems and other 3D cell culture models that are poised to transform our understanding of basic biological mechanisms and provide new opportunities for studying diverse phenomena in physiologically relevant tissue models.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4602-4623"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785457","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
EPGD co-delivery of doxorubicin and gemcitabine enhances activity in EpCAM-high tumour models with lower renal injury-associated readouts in a microfluidic co-culture platform. 在微流体共培养平台中,阿霉素和吉西他滨共同递送EPGD增强epcam高肿瘤模型的活性,降低肾损伤相关读数。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-08-25 DOI: 10.1039/d6lc00007j
Qinrui Lu, Guohua Wu, Mengjiao Xia, Wenyin Zhang, Di Wu, Zipeng Yao, Jiashu Wang, Ao Xie, Wenqi Hu, Chenwei Sun, Youlong Yang, Lin Wu, Haijie Hu, Qijun Du, Shuqi Wang
{"title":"EPGD co-delivery of doxorubicin and gemcitabine enhances activity in EpCAM-high tumour models with lower renal injury-associated readouts in a microfluidic co-culture platform.","authors":"Qinrui Lu, Guohua Wu, Mengjiao Xia, Wenyin Zhang, Di Wu, Zipeng Yao, Jiashu Wang, Ao Xie, Wenqi Hu, Chenwei Sun, Youlong Yang, Lin Wu, Haijie Hu, Qijun Du, Shuqi Wang","doi":"10.1039/d6lc00007j","DOIUrl":"10.1039/d6lc00007j","url":null,"abstract":"<p><p>Cytotoxic chemotherapy remains indispensable for many epithelial malignancies, yet gemcitabine (GEM) and doxorubicin (DOX) are constrained by a narrow therapeutic index and clinically significant toxicity. Here, we developed an epithelial cell adhesion molecule (EpCAM)-targeted DNA aptamer (EP)-based construct for co-delivery of GEM and DOX and evaluated its antitumour activity together with renal injury-associated readouts <i>in vitro</i>. A GEM-integrating EP construct (EPG) was generated by substituting seven cytidines with GEM residues, followed by DOX loading through intercalation into GC-rich regions to form EPGD. Mass spectrometry confirmed the expected molecular species, and DOX association with EP/EPG was supported by fluorescence quenching. ELONA-based analyses further showed that EPG retained EpCAM binding with a modest increase in apparent <i>K</i><sub>d</sub> relative to EP, while competitive ELONA supported preserved, competitively inhibitable EpCAM engagement under the tested conditions. In an evaporation-driven microfluidic self-perfusion chip, EPGD induced greater tumour cytotoxicity and more pronounced γ-H<sub>2</sub>AX formation than free drugs or single-drug aptamer formulations at matched nominal drug concentrations. In patient-derived intrahepatic cholangiocarcinoma organoids, EPGD reduced viability in a concentration-dependent manner. In a dual-compartment microfluidic chip operated under shared perfusion, HK-2 proximal tubular cells cultured on a kidney-derived decellularised extracellular matrix showed higher viability together with lower kidney injury molecule-1 (KIM-1) secretion and lactate dehydrogenase (LDH) release after EPGD treatment than after free GEM and DOX. Together, these findings indicate that EPGD integrates CI-supported GEM/DOX synergism demonstrated in A549 cells with preferential activity in EpCAM-high tumour models and is associated with lower renal injury-associated readouts in this <i>in vitro</i> microfluidic platform.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4724-4738"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596652","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
Recruitment and local granulopoiesis of human hematopoietic stem/progenitor cells in a skin-on-a-chip 芯片皮肤中人造血干细胞/祖细胞的募集和局部颗粒生成
IF 6.1 2区 工程技术
Lab on a Chip Pub Date : 2026-08-24 DOI: 10.1039/d6lc00422a
Evan P Cirves,Stormy K Wallace,Bella S Chiaramonte,Madison Judy,Venktesh S Shirure,Bhupinder Shergill,Steven George
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