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In situ probing of cell-cell communications with surface- enhanced Raman scattering （SERS） nanoprobes and microfluidic networks for screening of immunotherapeutic drugs

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Nano Research 2017年第2期10卷 584-594页

作者： Lei Wu Zhuyuan Wang Yizhi Zhang Jiayuan Fei Hui Chen Shenfei Zong Yiping Cui Advanced Photonics Center School of Electronic Science and Engineering Southeast University Sipailou 2# Nanjing 210096 China

Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell-ceil communications. Here, we combined surface-enhanced Raman scattering （SERS） nanoprobes with microfluidic networks to monitor in situ the cancer-immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core--shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional （3D） barcode immunoassay with high sensitivity （1 ng/mL）. Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer-immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel druKs.

关键词： cell-cell communication microfluidic chip surface-enhanced Raman scattering (SERS) barcode immunoassay drug discovery

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Determination of ammonium on an integrated microchip with LED-induced fluorescence detection

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Journal of Environmental Sciences 2012年第3期24卷 564-570页

作者： Shuhua Xue Katsumi Uchiyama Hai-fang Li Department of Chemistry Tsinghua UniversityBeijing 100084China College of Chemistry and Chemical Engineering Fuzhou UniversityFuzhou 350108China Department of Applied Chemistry Graduate School of Urban Environmental SciencesTokyo Metropolitan UniversityMinamiohsawaHachiojiTokyo 192-0364Japan

A simply fabricated microfluidic device integrated with a fluorescence detection system has been developed for on-line determination of ammonium in aqueous samples. A 365-nm light-emitting diode （LED） as an excitation source and a minor band pass filter were mounted into a polydimethylsiloxane （PDMS）-based microchip for the purpose of miniaturization of the entire analytical system. The ammonium sample reacted with o-phthaldialdehyde （OPA） on-chip with sodium sulfite as reducing reagent to produce a fluorescent isoindole derivative, which can emit fluorescence signal at about 425 nm when excited at 365 nm. Effects of pH, flow rate of solutions, concentrations of OPA-reagent, phosphate and sulfite salt were investigated. The calibration curve of ammonium in the range of 0.018- 1.8 μg/mL showed a good linear relationship with R2 = 0.9985, and the detection limit was （S /N = 3） 3.6 × 10 4 μg/mL. The relative standard deviation was 2.8% （n = 11） by calculating at 0.18 μg/mL ammonium for repeated detection. The system was applied to determine the ammonium concentration in rain and river waters, even extent to other analytes fluorescence detection by the presented device.

关键词： microfluidic chip light emitting diode o-phthaldialdehyde fluorescence ammonium

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Development of a Miniature Permanent Magnetic Circuit for Nuclear Magnetic Resonance chip

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Chinese Journal of Mechanical Engineering 2013年第4期26卷 689-694页

作者： LU Rongsheng YI Hong WU Weiping NI Zhonghua Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments Southeast University

The existing researches of miniature magnetic circuits focus on the single-sided permanent magnetic circuits and the Halbach permanent magnetic circuits. In the single-sided permanent magnetic circuits, the magnetic flux density is always very low in the work region. In the Halbach permanent magnetic circuits, there are always great difficulties in the manufacturing and assembly process. The static magnetic flux density required for nuclear magnetic resonance(NMR) chip is analyzed based on the signal noise ratio(SNR) calculation model, and then a miniature C-shaped permanent magnetic circuit is designed as the required magnetic flux density. Based on Kirchhoff’s law and magnetic flux refraction principle, the concept of a single shimming ring is proposed to improve the performance of the designed magnetic circuit. Using the finite element method, a comparative calculation is conducted. The calculation results demonstrate that the magnetic circuit improved with a single shimming has higher magnetic flux density and better magnetic field homogeneity than the one improved with no shimming ring or double shimming rings. The proposed magnetic circuit is manufactured and its experimental test platform is also built. The magnetic flux density measured in the work region is 0.7 T, which is well coincided with the theoretical design. The spatial variation of the magnetic field is within the range of the instrument error. At last, the temperature dependence of the magnetic flux density produced by the proposed magnetic circuit is investigated through both theoretical analysis and experimental study, and a linear functional model is obtained. The proposed research is crucial for solving the problem in the application of NMR-chip under different environmental temperatures.

关键词： nuclear magnetic resonance microfluidic chip permanent magnet magnetic flux density

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Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

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Chinese Physics B 2024年第5期33卷 749-756页

作者：姚静如李国强姚喜耀周连杰叶志凯刘艳平郑栋天唐婷宋克纳陈果刘雳宇 Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials College of PhysicsChongqing UniversityChongqing 401331China Chongqing Key Laboratory for Resource Utilization of Heavy Metal Wastewater Aquatic Ecosystems in the Three Gorges Reservoir Region of Chongqing Observation and Research StationChongqing University of Arts and SciencesYongchuan 402160China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China Department of Biomedical Engineering Chongqing University of Posts and TelecommunicationsChongqing 400065China College of Medical Technology and Engineering Henan University of Science and TechnologyHenan 471023China

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and ***,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell ***,the further development of microfluidic technology has provided solutions for the study of such *** utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,*** combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP *** results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences ***,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration ***,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is *** findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is *** RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.

关键词： microfluidic chip random collagen fiber microenvironment(RFM) oriented collagen fiber microenvironment(OFM) cancer cell migration

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Recent progress on microfluidic biosensors for rapid detection of pathogenic bacteria

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Chinese Chemical Letters 2022年第4期33卷 1743-1751页

作者： Gaowa Xing Weifei Zhang Nan Li Qiaosheng Pu Jin-Ming Lin College of Chemistry and Chemical Engineering Lanzhou UniversityLanzhou 730000China Beijing Key Laboratory of Microanalytical Methods and Instrumentation Department of ChemistryTsinghua UniversityBeijing 100084China Division of Chemical Metrology and Analytical Science National Institute of MetrologyBeijing 100029China

Rapid on-site detection of pathogenic bacteria with high sensitivity and specificity is becoming an urgent need in public health assurance, medical diagnostics, environmental monitoring, and food safety fields. Despite being reliable and widely used, the existing methods of bacteria detection are cumbersome and time-consuming, which is not conducive to field detection. microfluidic lab-on-a-chip technology has provided a detective tool for various analytes, due to its miniaturization, portability and low reagent consumption. Within this progress report, advances in the bacteria detection using microfluidic biosensors were discussed. Typical methods for pathogenic bacteria capture, separation and detection were introduced respectively in the first part. Then key applications of microfluidic biosensor-based rapid bacteria detection were presented. Finally, we made a conclusion and discussed possible research prospects in aspects of microfluidic biosensors for rapid detection of pathogenic bacteria.

关键词： microfluidic chip Biosensors Pathogenic bacteria Rapid detection

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Effect of external electric field on the terahertz transmission characteristics of electrolyte solutions

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Chinese Physics B 2021年第11期30卷 180-184页

作者： Jia-Hui Wang Guo-Yang Wang Xin Liu Si-Yu Shao Hai-Yun Huang Chen-Xin Ding Bo Su Cun-Lin Zhang Beijing Advanced Innovation Centre for Imaging Theory and Technology Beijing 100048China Beijing Key Laboratory for Terahertz Spectroscopy and Imaging Beijing 100048China Key Laboratory of Terahertz Optoelectronics Ministry of EducationBeijing 100048China Department of Physics Capital Normal UniversityBeijing 100048China

We fabricated a microfluidic chip with simple structure and good sealing performance,and studied the influence of the electric field on THz absorption intensity of liquid samples treated at different times by using THz time domain spectroscopy *** tested liquids were deionised water and CuSO_(4),CuC_(l2),NaHCO_(3),Na_(2)CO_(3) and NaCl *** transmission intensity of the THz wave increases as the standing time of the electrolyte solution in the electric field *** applied electric field alters the dipole moment of water molecules in the electrolyte solution,which affects the vibration and rotation of the whole water molecules,breaks the hydrogen bonds in the water,increases the number of single water molecules and leads to the enhancement of the THz transmission spectrum.

关键词： terahertz microfluidic chip electrolyte solution electric field transmission intensity

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A pneumatic micromixer facilitating fluid mixing at a wide range flow rate for the preparation of quantum dots

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Science China Chemistry 2013年第6期56卷 799-805页

作者： WANG Xin MA XiuFeng AN LanLan KONG XiangWei XU ZhangRun WANG JianHua Research Center for Analytical Sciences Northeastern University School of Chemistry and Material Science Liaoning Shihua University Department of Mechanical Engineering and Automation Northeastern University

A novel fluid micromixer based on pneumatic perturbation and passive structures was developed. This micromixer facilitates integration and is applicable to fluid mixing over a wide range of flow rates. The microfluidic mixing device consists of an S-shaped structure with two mixing chambers and two barriers, and two pneumatic chambers designed over the S-shaped channel. The performance of the micromixer for fluids with wide variation of flow rates was significantly improved owing to the integration of the pneumatic mixing components with the passive mixing structures. The mixing mechanism of the passive mixing structures was explored by numerical simulation, and the influencing factors on the mixing efficiency were investigated. The results showed that when using a gas pressure of 0.26 MPa and a 100 pm-thick polydimethylsiloxane （PDMS） pneumatic diaphragm, the mixing of fluids with flow rates ranging from 1 to 650 ~tL/min was achieved with a pumping frequency of 50 Hz. Fast synthesis of CdS quantum dots was realized using this device. Smaller particles were obtained, and the size distribu- tion was greatly improved compared with those obtained using conventional methods.

关键词： microfluidic chip pneumatic micromixer quantum dots CdS

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microfluidics for cell-cell interactions： A review

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Frontiers of Chemical Science and Engineering 2016年第1期10卷 90-98页

作者： Rui Li Xuefei Lv Xingjian Zhang Omer Saeed Yulin Deng School of Life Science Beijing Institute of Technology Beijing 100081 China

Micro fluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fuidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special coculture models that are highly concerned in a different spatial and temporal way.

关键词： microfluidic chip co-culture cell-cell interactions review

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Poly（dimethylsiloxane） Microchips with Two Sharpened Stretching Tips and Its Application to Protein Separation Using Dynamic Coating

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Chinese Journal of Chemistry 2007年第2期25卷 190-195页

作者：刘春叶许旭高红军陈杰瑢 School of Life Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 China Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China

An integrated poly（dirnethylsiloxane）（PDMS） microchip with two sharpened stretching tips for convenient sample injecting, running buffer refreshing and channel cleaning has been presented. The sample was directly introduced into the separation channel through the stretching inlet tip without complicated power switching supplies and injection cross channel. The operation of running buffer refreshing or channel cleaning was simplified by vacuuming one end of the tip and placing the other tip into the solution vial. Therefore, this fabrication method can be easily applied to most analytical laboratories economically without soft lithography and plasma bonding equipments. The attractive performance of the novel PDMS microchips has been demonstrated by using laser-induced fluorescence detection for separation of proteins. The addition of 0.04% Brij 35 in 0.04 mol/L phosphate buffer （pH 7.0） can reduce the adhesion of proteins in multienzyme tablet and make separation more easily. The electroosmotic flow （EOF） exhibits pH-independence in the range of 3-1 1 in dynamic modified microchannel.

关键词： poly(dimethylsiloxane) microfluidic chip sampling dynamic coating protein

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Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis

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Regenerative Biomaterials 2021年第6期8卷 199-208页

作者： Lingzhi Jing Suna Fan Xiang Yao Yaopeng Zhang State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineCollege of Materials Science and EngineeringDonghua UniversityShanghai 201620P.R.China Jinan Jinquan Bio-Technology Co.Ltd Jinan 250101P.R.China

Bone tissue with strong adaptability is often in a complex dynamical microenvironment in vivo,which is associated with the pathogenesis and treatment of orthopedic ***,it is of great significance to investigate the effects of corresponding compound stimulation on cell ***,a fluid shear stress(FSS)plus ultrasound stimulation platform suitable for cell studies based on a microfluidic chip was constructed and bone marrow mesenchymal stem cell(BMSC)was chosen as a model *** proliferation and osteogenesis of BMSCs under the compound stimulation of FSS plus ultrasound in growth medium without any soluble induction factors were firstly *** FSS stimulation and static culture conditions were also *** illustrated that suitable single FSS stimulation(about 0.06 dyn/cm^(2))could significantly enhance cell proliferation and osteogenesis simultaneously when compared to the static control,while greater FSS mitigated or even restricted these enhancing ***,ultrasound stimulation combined with this suitable FSS stimulation further accelerated cell proliferation as the intensity of ultrasound *** for the osteogenesis under compound stimulation,it was relatively restricted under lower ultrasound intensity(about 0.075W/cm^(2)),while promoted when the intensity became higher(about 1.75W/cm^(2)).This study suggests that both the cell proliferation and osteogenesis are very responsive to the magnitudes of FSS and ultrasound stimulations and can be both significantly enhanced by proper combination ***,these findings will provide valuable references for the construction of effective cell bioreactors and also the treatment of orthopedic diseases.

关键词： compound stimulation microfluidic chip stem cell cell proliferation cell differentiation

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