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Flow field analyses of a porous membrane-separated,double-layered microfluidic chip for cell co-culture

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Acta Mechanica Sinica 2020年第3期36卷 754-767页

作者： Shenbao Chen Jian Xue Jinrong Hu Qihan Ding Luwen Zhou Shiliang Feng Yuhong Cui Shouqin Lu Mian Long Center of Biomechanics and Bioengineering Key Laboratory of Microgravity(National Microgravity Laboratory)Beijing Key Laboratory of Engineered Construction and Mechanobiologyand CAS Center for Excellence in Complex System MechanicsInstitute of MechanicsChinese Academy of SciencesBeijing100190China School of Engineering Science University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Nonlinear Mechanics(LNM) Institute of MechanicsChinese Academy of SciencesBeijing 100190China Faculty of Mechanical Engineering and Mechanics Ningbo UniversityNingbo 315211ZhejiangChina Department of Mechanics Tianjin UniversityTianjin 300072China

Organs-on-chips composed of a porous membrane-separated,double-layered channels are used widely in elucidating the effects of cell co-culture and flow shear on biological *** the diversity of channel geometry and membrane permeability is applied,their quantitative correlation with flow features is still *** boundary methods(IBM)simulations and theoretical modelling were performed in this *** simulations showed that channel length,height and membrane permeability jointly regulated the flow features of flux,penetration velocity and wall shear stress(WSS).Increase of channel length,lower channel height or membrane permeability monotonically reduced the flow flux,velocity and WSS in upper channel before reaching a *** the flow flux in lower channel monotonically increased with the increase of each factor,the WSS surprisingly exhibited a biphasic pattern with first increase and then decrease with increase of lower channel ***,the transition threshold of maximum WSS was sensitive to the channel length and membrane *** modeling,integrating the transmembrane pressure difference and inlet flow flux with chip geometry and membrane permeability,was in good agreement with IBM *** analyses provided theoretical bases for optimizing flow-specified chip design and evaluating flow microenvironments of in vivo tissue.

关键词： Immersed boundary method Porous membrane Wall shear stress Penetration velocity microfluidic chip

2D profiling of tumor chemotactic and molecular phenotype at single cell resolution using a SERS-microfluidic chip

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Nano Research 2022年第5期15卷 4357-4365页

作者： Yizhi Zhang Lei Wu Kuo Yang Shenfei Zong Zhuyuan Wang Yiping Cui Advanced Photonics Center School of Electronic Science and EngineeringSoutheast UniversityNanjing 210096China Department of Biomedical Engineering Nanjing University of Aeronautics and AstronauticsNanjing 211106China

Emerging single-cell technologies create new opportunities for unraveling tumor ***,the development of high-content phenotyping platform is still at its ***,we develop a microfluidic chip for two-dimensional(2D)profiling of tumor chemotactic and molecular features at single cell *** cells were captured by the triangular micropillar arrays in the cell-loading channel,facilitating downstream single-cell *** 2D phenotyping,the chemotactic properties of tumor cells were visualized through cellular migratory behavior in microchannels,while their protein expression was profiled with multiplex surface enhanced Raman scattering(SERS)nanovectors,in which Raman reporter-embedded gold@silver core-shell nanoparticles(Au@Ag REPs)were modified with DNA aptamers targeting cellular surface *** a proof of concept,breast cancer cells with diverse phenotypes were tested on the chip,demonstrating the capability of this platform for simultaneous chemotactic and molecular *** chip is expected to provide a powerful tool for investigating tumor heterogeneity and promoting clinical precision medicine.

关键词： gold@silver nanoparticles surface enhanced Raman spectroscopy microfluidic chip single cell analysis two-dimensional(2D)phenotype profiling

microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells

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Cancer Drug Resistance 2020年第3期3卷 613-622页

作者： Karan Parekh Hamideh Sharifi Noghabi Jose Alejandro Lopez Paul Chi Hang Li Department of Molecular Biology&Biochemistry Simon Fraser UniversityBurnaby V5A 1S6Canada. Department of Chemistry Simon Fraser UniversityBurnaby V5A 1S6Canada. School of Environment&Science Griffith UniversityNathanQueensland 4111Australia.

Aims:Triple-negative breast cancer patients are commonly treated with combination ***,outcomes remain substandard with relapses being of a frequent *** the several mechanisms that result in treatment failure,multidrug resistance,which is mediated by ATP-binding cassette proteins,is the most *** of the substantial studies conducted on the heterogeneity of cancer types,only a few assays can distinguish the variability in multidrug resistance activity between individual *** aim to develop a single-cell assay to study ***:This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux ***:Selection of single cells,loading of drugs,and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic *** a result,measurements of the accumulation of chemotherapeutic drugs(e.g.,daunorubicin and paclitaxel)in single cells in the presence and absence of cyclosporine A were *** such as initial drug accumulation,signal saturation time,and fold-increase of drug with and without the presence cyclosporine A were also ***:The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine ***,this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.

关键词： MDA-MB-231 cell triple-negative breast cancer microfluidic chip lab-on-chip multidrug resistance single-cell analysis fluorescence measurement

Integrated Carbon Nanotubes Electrodes in microfluidic chip via MWPCVD

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Plasma Science and Technology 2010年第5期12卷 556-560页

作者：王升高王明洋余冬冬张文波邓晓清杜宇程莉莉汪建华 Provincial Key Laboratory of Plasma Chemistry and Advanced Materials Wuhan Institute of Technology School of Material Science and Engineering Wuhan Institute of Technology Key Laboratory for Green Chemical Process of Ministry of Education Wuhan Institute of Technology

An on-chip electrochemical detector for microfluidic chips was described, based on integrated carbon nanotube （CNT） electrodes directly onto the chip substrate through microwave plasma chemical vapor deposition （MWPCVD）. The attractive performance of the integrated CNT electrodes was demonstrated for the amperometric detection of sucrose, glucose and D-fructose. The integrated CNT electrodes showed stronger electrocatalytic activity than gold electrodes.

关键词： microfluidic chip integrated carbon naotube electrodes microwave plasmachemical deposition amperometrie detection

Droplet microfluidic chip for precise monitoring of dynamic solution changes

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Nanotechnology and Precision Engineering 2023年第3期6卷 55-63页

作者： Cong Ma Zehang Gao Jianlong Zhao Shilun Feng School of Information Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Institute of Microsystem and Information Technology Chinese Academy of SciencesShanghai 200050China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Department of Clinical Laboratory Third Affiliated Hospital of Guangzhou Medical UniversityGuangdong 510150China

In this work,an automated microfluidic chip that uses negative pressure to sample and analyze solutions with high temporal resolution was *** chip has a T-shaped channel for mixing the sample with a fluorescent indicator,a flow-focusing channel for generating droplets in oil,and a long storage channel for incubating and detecting the *** monitoring the fluorescence intensity of the droplets,the device could detect changes in solution accurately over *** chip can generate droplets at frequencies of up to 42 Hz with a mixing ratio of 1:1 and a temporal resolution of 3–6 *** had excellent linearity in detecting fluorescein solution in the concentration range 1–5μ*** droplet microfluidic chip provides several advantages over traditional methods,including high temporal resolution,stable droplet generation,and faster flow *** approach could be applied to monitoring calcium ions with a dynamic range from 102 to 107 nM and a detection limit of 10 nM.

关键词： microfluidic chip Droplet sampling Fluorescence detection Calcium ion dynamics Temporal resolution

Quantitative Determination of Urine Glucose： Combination of Laminar Flow in microfluidic chip with SERS Probe Technique

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Chemical Research in Chinese Universities 2018年第6期34卷 899-904页

作者： SUN Dan LIU Xiangyuan XU Shuping TIAN Yu XU Weiqing TAO Yanchun Key Laboratory of Supramolecular Structure and Materials Institute of Theoretical Chemistry Jilin Universiry Changehun 130012 P. R. China

A surface-enhanced Raman scattering（SERS） sensing approach for urine glucose was developed based on the laminar flow technology in a cross-type microfluidic chip with SERS probes, 4-mercaptophenylboronic acid （MPBA） functionalized Ag nanoparticles. MPBA as the glucose receptor can identify and bind up with glucose at a molar ratio of 2：1, which can cause the aggregation of SERS probes at a certain position of the chip channel and further enhance the SERS signal of MPBA significantly. Thus, the quantitative SERS detection of glucose was achieved indirectly. No sample pretreatment and separation were needed in this method since the SERS detection was achieved in the gradient diffusion and molecular recognition processes between urine glucose and SERS probe in the laminar flow, which simplified the sample treahnent procedures, saved detection time and made it feasible for clinic applications. This method shows a good linear relationship within human body＇s normal physiological range and has high sensitivity and selectivity： The lowest detection concentration can reach 1.0 mg/dL.

关键词： Surface-enhanced Raman scattefing(SERS) microfluidic chip 4-Mercaptophenylboronic acid Uurine glucose

Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by microfluidic chip

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Nano-Micro Letters 2018年第1期10卷 148-157页

作者： Ren Li Mingxing Zhou Jine Li Zihua Wang Weikai Zhang Chunyan Yue Yan Ma Hailin Peng Zewen Wei Zhiyuan Hu CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Academy for Advanced Interdisciplinary Studies Peking University University of Chinese Academy of Sciences Sino-Danish College University of Chinese Academy of Sciences Yangtze River Delta Academy of Nanotechnology and Industry Development Research

EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,which may be covered by the noises from majority of unmutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multimutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cellswere easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drugrelated mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations,but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.

关键词： EGFR mutation Single-cell analysis microfluidic chip Tyrosine kinase inhibitor

EXPERIMENTAL STUDY ON THE HOT EMBOSSING POLYMER microfluidic chip

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Chinese Journal of Mechanical Engineering 2008年第3期21卷 87-89页

作者： HE Yong FU Jianzhong CHEN Zichen College of Mechanical and Energy Engineering Zhejiang Unviersity Hangzhou 310027 China

Experiments are used to study the fabrication of polymer microfluidic chip with hot embossing method. The pattern fidelity with respect to the process parameters is analyzed. Experiment results show that the relationship between the imprint temperature and the microchannel width is approximately exponential. However, the depth of micro channel isn＇t sensitive to the imprint temperature. When the imprint pressure is larger than 1 MPa and the imprint time is longer than 2 min, the increasing of imprint pressure and holding time has little impact on the microchannel width. So over long holding time is not needed in hot embossing. Based on the experiment analysis, a series of optimization process parameters is obtained and a fine microfluidic chip is fabricated. The electrophoresis separation experiment are used to verify the microfluidic chip performance after bonding. The results show that 100bp-ladder DNA sample can be separated in less than 5 min successfully.

关键词： microfluidic chip Hot embossing Channel sizes Pattern fidelity

A lateral-immobilization zebrafish microfluidic chip-based system for in vivo real-time evaluation of antithrombotic agents

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Chinese Chemical Letters 2024年第3期35卷 312-315页

作者： Lijuan He Hongxia Du Yi Yang Zhihua Guan Jinjin Li Honglin Li Xudong Lin Lili Zhu Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument School of Biomedical EngineeringShenzhen Campus of Sun Yat-sen UniversityShenzhen 518000China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China

Thrombosis remains a major global health concern mainly characterized by high rates of morbidity and *** models serve as an indispensable tool to understand the underlying pathogenesis of thrombosis and assess the efficacy of novel antithrombotic ***,zebrafish has emerged as a valuable model organism for thrombosis ***,the traditional method of studying zebrafish thrombosis requires a laborious and time-consuming procedure,including anesthesia and manual immobilization of *** this study,based on hydrodynamic force,a lateral-immobilization zebrafish microfluidic chip(LIZMC)was designed to evaluate the cardiovascular system of multiple larvae within a single microscope field of ***,coupling with microscope imaging,real-time monitoring of the peripheral blood circulation in the tail of phenylhydrazine(PHZ)-induced zebrafish thrombosis was ***,the reliability of LIZMC for in vivo evaluation of antithrombotic agents in zebrafish was verified using ***,this novel LIZMC-based system can be used for in vivo zebrafish thrombosis studies and rapid screening of antithrombotic agents.

关键词： microfluidic chip Zebrafish Thrombosis In vivo evaluation Real-time monitor