Microreactor Microfluidic Systems with Human Microsomes and Hepatocytes for use

Xona Microfluidics LLC美国公司神经元突触轴突培养舱Microfluidic Chamber，突触虽然是神经系统重要的功能单位,但针对突触的通用研究方法仍具有一定局限性,有待完善改进,为加深对突触发生、病变现象及机制的研究,MICOFORCE米力光CO本实验设计建立创新性研究方法,实现体外动态观察神经元突触结构的变化。

【设计思路】本实验引入新型培养装置Microfluidic Chamber和跨突触结构重组GFP荧光蛋白对mGRASP实现神经元突触体外动态观察。

Microfluidic Chamber有双侧培养空间,由微通道相通,仅能允许神经元轴突通过,同时根据流体动力学原理其双侧液体不会发生混合。

mGRASP全称为mammalian GFP reconstitution across synaptic partners,包括Pre 和Post两个蛋白,分别携带GFP蛋白的一部分,当二者距离约为20 nm左右时,能重组成GFP发出绿色荧光,反之则无荧光信号。

Pre和Post通过neurexin和neuroligin固定表达在突触前膜和突触后膜上,利用突触间隙约为20 nm且小于正常细胞间距的原理,用绿色荧光特异性标记突触,体外动态观察突触结构。

【实验内容】本实验在新型培养装置Microfluidic Chamber进行孕17天小鼠胎鼠皮层神经元原代培养,体外培养6~7 d,在两侧分别加入携带mGRASP Pre和Post基因的慢病毒感染神经元,基于Microfluidic Chamber 良好的液相分隔性,能做到两侧分别表达Pre和Post蛋白,而不会出现二者同一细胞中共表达的情况。

培养4周左右,表达Pre的神经元轴突穿过微通道与另一侧表达Post的神经元接触,形成突触后即可在突触间隙发出绿色荧光。

可在培养基中加入神经营养因子或药物,体外动态观察生理、病理刺激对突触结构的影响。

微生物燃料电池英语Microbial Fuel Cells (MFCs) are innovative bioelectrochemical systems that harness the metabolicactivity of microorganisms to convert organic or inorganic substrates directly into electrical energy. These systems are gaining attention for their potential applications in wastewater treatment, energy recovery from waste, and remote power generation.The core of an MFC consists of an anode and a cathode, separated by a proton exchange membrane or a cation exchange membrane. Microorganisms, typically bacteria, are present at the anode, where they oxidize the substrate, releasing electrons and protons. These electrons are then transferred through an external circuit to the cathode, where they are accepted by an electron acceptor, such as oxygen, which is reduced to water.One of the key advantages of MFCs is their ability to utilize a wide range of substrates, including domestic sewage, agricultural waste, and even industrial effluents. This not only makes them environmentally friendly but alsoeconomically viable, as they can convert waste into avaluable resource.However, there are challenges associated with MFCs. The efficiency of energy conversion is currently relatively low, and the design of the MFCs needs to be optimized to enhancetheir performance. Moreover, the selection and cultivation of microorganisms that can efficiently transfer electrons to the anode is a critical aspect of MFC research.Recent advancements in MFC technology have focused on improving the biofilm formation on the anode, enhancing the electron transfer rate, and developing novel materials for the construction of the anode and cathode. The integration of MFCs with other technologies, such as solar cells or wind turbines, is also being explored to create hybrid systemsthat can provide a more consistent power output.In conclusion, microbial fuel cells represent a promising and sustainable approach to energy production and waste management. With continued research and development, these systems could play a significant role in meeting the growing global demand for clean and renewable energy.。

微纳米流动和核磁共振技术英文回答：Microfluidics and nuclear magnetic resonance (NMR) are two important technologies that have revolutionized various fields of science and engineering.Microfluidics refers to the study and manipulation of fluids at the microscale level, typically in channels or chambers with dimensions ranging from micrometers to millimeters. It allows precise control and manipulation of small volumes of fluids, enabling a wide range of applications such as chemical analysis, drug delivery systems, and lab-on-a-chip devices. Microfluidic devices are often fabricated using techniques such as soft lithography, which involve the use of elastomeric materials to create microchannels and chambers.NMR, on the other hand, is a powerful analytical technique that utilizes the magnetic properties of atomicnuclei to study the structure and dynamics of molecules. It is based on the principle of nuclear spin, which is the intrinsic angular momentum possessed by atomic nuclei. By subjecting a sample to a strong magnetic field and applying radiofrequency pulses, NMR can provide information about the chemical composition, molecular structure, and molecular interactions of the sample. NMR has diverse applications in fields such as chemistry, biochemistry, medicine, and materials science.Microfluidics and NMR can be combined to create powerful analytical tools for studying various biological and chemical systems. For example, microfluidic devices can be used to precisely control the flow of samples and reagents, while NMR can provide detailed information about the composition and structure of the samples. This combination has been used in the development ofmicrofluidic NMR systems, which allow rapid and sensitive analysis of small sample volumes. These systems have been applied in areas such as metabolomics, drug discovery, and environmental monitoring.中文回答：微纳米流体力学和核磁共振技术是两种重要的技术，已经在科学和工程的各个领域引起了革命性的变化。

MITResearch in nano- and micro- scale technologies is in the departments of Material Sci. and Eng. And Computer Sci. or Chemical Eng.MIT’s major micro and nano centers are MTL(Microsystem Technology Laboratories) which provide microelectronics fabrication lab/research/index.html.MTL is home to several research centers, including:∙The Center for Integrated Circuits and Systems (CICS) serves to promote closer technical relation between MIT's Microsystems Technology Lab's (MTL) research and industry, initiate and fund new research in integrated circuits and systems, produce more students skilled in the same area, address important research issues relevant to industry, and solicit ideas for new research from industry.∙The Intelligent Transportation Research Center (ITRC) focuses on the key Intelligent Transportation Systems (ITS) technologies, including an integrated network of transportation information, automatic crash & incident detection, notification and response, advanced crashavoidance technology, advanced transportation monitoring and management, etc., in order toimprove the safety, security, efficiency, mobile access, and environment. There are two emphasis for research conduced in the center: the integration of component technology research andsystem design research, and the integration of technical possibilities and social needs.∙MEMS@MIT is a collection of faculty/staff/students working in the broad area of a Micro/nano systems and MEMS. This center was created to serve as a forum for collectingintellectually-synergistic but organizationally diverse groups of researchers at MIT. In addition, we have organized an industrial interaction mechanism to catalyze the transfer of knowledge to the larger MEMS community.The research:Chemical/Mechanical/Optical MEMS1. A MEMS Electrometer for Gas Sensing2. A Single-Gated CNT Field-Ionizer Array with Open Architecture3. A MEMS Quadrupole that Uses a Meso-scaled DRIE-patterned Spring Assembly System4. Digital Holographic Imaging of Micro-structured and Biological Objects5. Multi-Axis Electromagnetic Moving-Coil Microactuator6. Multiphase Transport Phenomena in Microfluidic Systems7. Microfluidic Synthesis and Surface Engineering of Colloidal Nanoparticles8. Microreactor Enabled Multistep Chemical Synthesis9. Integrated Microreactor System10. Crystallization in Microfluidic Systems11. Microreactors for Synthesis of Quantum Dots12. A Large Strain, Arrayable Piezoelectric Microcellular Actuator13. MEMS Pressure-sensor Arrays for Passive Underwater Navigation14. A Low Contact Resistance MEMS-Relay15. "Fast Three-Dimensional Electrokinetic Pumps for Microfluidics16. Carbon Nanotube - CMOS Chemical Sensor Integration17. An Energy Efficient Transceiver for Wireless Micro-Sensor Applications18. Combinatorial Sensing Arrays of Phthalocyanine-based Field-effect Transistors19. Nanoelectromechanical Switches and Memories20. Integrated Carbon Nanotube Sensors21. Organic Photovoltaics with External Antennas22. Integrated Optical-wavelength-dependent Switching and Tuning by Use of Titanium Nitride (TiN)MEMS Technology23. Four Dimensional Volume Holographic Imaging with Natural Illumination24. White Light QD-LEDs25. Organic Optoelectronic Devices Printed by the Molecular Jet Printe26. Design and Measurement of Thermo-optics on SiliconBioMEMS1. A Microfabricated Platform for Investigating Multicellular Organization in 3-D Microenvironments2. Microfluidic Hepatocyte Bioreactor3. Micromechanical Control of Cell-Cell Interaction4. A MEMS Drug Delivery Device for the Prevention of Hemorrhagic Shock5. Multiwell Cell Culture Plate Format with Integrated Microfluidic Perfusion System6. Characterization of Nanofilter Arrays for Biomolecule Separation7. Patterned Periodic Potential-energy Landscape for Fast Continuous-flow BiomoleculeSeparation8. Continuous-flow pI-based Sorting of Proteins and Peptides in a Microfluidic Chip Using DiffusionPotential9. Cell Stimulation, Lysis, and Separation in Microdevices10. Polymer-based Microbioreactors for High Throughput Bioprocessing11. Micro-fluidic Bioreactors for Studying Cell-Matrix Interactions12. A Nanoscanning Platform for Biological Assays13. Label-free Microelectronic PCR Quantification14. Vacuum-Packaged Suspended Microchannel Resonant Mass Sensor for BiomolecularDetection15. Microbial Growth in Parallel Integrated Bioreactor Arrays16. BioMEMS for Control of the Stem-cell Microenvironment17. Microfluidic/Dielectrophoretic Approaches to Selective Microorganism Concentration18. Microfabricated Approaches for Sorting Cells Using Complex Phenotypes19. A Continuous, Conductivity-Specific Micro-organism Separator20. Polymer Waveguides for Integrated BiosensorsEnabling Technology1. A Double-gated CNF Tip Array for Electron-impact Ionization and Field Ionization2. A Double-gated Silicon Tip, Electron-Impact Ionization Array3. A Single-Gated CNT Field-Ionizer Array with Open Architecture4. Aligning and Latching Nano-structured Membranes in 3D Micro-Structures5. Characterization and Modeling of Non-uniformities in DRIE6. Understanding Uniformity and Manufacturability in MEMS Embossing7. Atomic Force Microscopy with Inherent Disturbance Suppression for Nanostructure Imaging8. Vacuum-Sealing Technologies for Micro-chemical Reactors9. Direct Patterning of Organic Materials and Metals Using Micromachined Printheads10. MEMS Vacuum Pump11. Rapid and Shape-Controlled Growth of Aligned Carbon Nanotube Structures12. Prediction of Variation in Advanced Process Technology Nodes13. Parameterized Model Order Reduction of Nonlinear Circuits and MEMS14. Development of Specialized Basis Functions and Efficient Substrate Integration Techniques forElectromagnetic Analysis of Interconnect and RF Inductors15. A Quasi-convex Optimization Approach to Parameterized Model-order Reduction16. Amorphous Zinc-Oxide-Based Thin-film Transistors17. Magnetic Rings for Memory and Logic Devices18. Studies of Field Ionization Using PECVD-grown CNT Tips19. Growth of Carbon Nanotubes for Use in Origami Supercapacitors20. Self-Alignment of Folded, Thin-Membranes via Nanomagnet Attractive Forces21. Control System Design for the Nanostructured Origami™ 3D Nanofabrication Process22. Measuring Thermal and Thermoelectric Properties of Single Nanowires and Carbon Nanotubes23. Nanocomposites as Thermoelectric Materials24. CNT Assembly by Nanopelleting25. Templated Assembly by Selective Removal26. Building Three-dimensional Nanostructures via Membrane FoldingPower MEMS1. Hand-assembly of an Electrospray Thruster Electrode Using Microfabricated Clips2. A Fully Microfabricated Planar Array of Electrospray Ridge Emitters for Space PropulsionApplications3. Thermal Management in Devices for Portable Hydrogen Generation4. Autothermal Catalytic Micromembrane Devices for Portable High-Purity Hydrogen Generation5. Self-powered Wireless Monitoring System Using MEMS Piezoelectric Micro Power Generator6. An Integrated Multiwatt Permanent Magnet Turbine Generator7. Micro-scale Singlet Oxygen Generator for MEMS-based COIL Lasers8. A Thermophotovoltaic (TPV) MEMS Power Generator9. MEMS Vibration Harvesting for Wireless Sensors10. Fabrication and Structural Design of Ultra-thin MEMS Solid Oxide Fuel Cells11. Tomographic Interferometry for Detection of Nafion® Membrane Degradation in PEM Fuel Cells∙The Center for Integrated Photonic Systems (CIPS) mission is to create a meaningful vision of the future, a framework for understanding how technology, industry and business interact and evolve together in the future is required. Models provide us with a process for analyzing the many complex factors that shape this industry and the progress of related technologies.The materials processing center .Making matter meet human needsResearchThe Center brings together MIT faculty and research staff from diverse specialties to collaborate on interdisciplinary materials problems. Center research involves over 150 faculty, research staff, visiting scientists, and graduate and undergraduate students.MPC researchers cover the full range of advanced materials, processes, and technologies, including∙electronic materials∙batteries & fuel cells∙polymers∙advanced ceramics∙materials joining∙composites of all types∙photonics∙electrochemical processing ∙traditional metallurgy∙environmental degradation∙materials modeling- many scale ∙materials systems analysis∙nanostructured materials∙magnetic materials and processes ∙biomaterials∙materials economicsFaculty ProfilesA.I. AkinwandeFlat panel displays,Vacuum Microelectronics and its application to flat panel displays, RF power sources, and sensors. Wide bandgap semiconductors and applications to flat panel displays, UV emitters and RF power sourcesView current research abstracts (pdf)G. BarbastathisBiomedical design instrumentation; precision engineering robotics; volume holographic architectures for data storage, color-selective tomographic imaging, and super-resolving confocal microscopy; interferometric surface characterization; and adaptive micro-opto-mechanics. Optical MEMS.View current research abstracts (pdf)View group web siteM. BazantResearch focuses on transport phenomena in materials and engineering systems, especially diffusion coupled to fluid flow. My group is currently studying granular flow in pebble-bed nuclear reactors, nonlinear electrokinetic flows in microfludic devices, ion transport in thin-film lithium batteries, and advection-diffusion-limited aggregation.View current research abstracts (pdf)View group web siteS. BhatiaResearch focuses on applications of micro- and nanotechnology to tissue repair and regeneration. Emphasis on development of microfabrication tools to improve cellular therapies for liver disease, living cell arrays to study stem cell biology, and nanoparticles for cancer diagnosis and treatment.View current research abstracts (pdf)View group web siteD. BoningSemiconductor manufacturing. Modeling and control of chemical mechanical polishing. Variation modeling and reduction in fabrication processes, devices, and interconnects. Run by run and feedback control for quality and environment in semiconductor fabrication. Software systems for distributed and collaborative computer aided design and fabrication.View current research abstracts (pdf)View group web siteA.P. ChandrakasanDesign of digital integrated circuits and systems. Emphasis on the energy efficient implementation of distributed microsensor and signal processing systems. Protocols and Algorithms for Wireless Systems. Circuits techniques for deep sub-micron technologies.View current research abstracts (pdf)View group web siteG. ChenMicro- and nanoscale heat transfer and energy conversion with applications in thermoelectrics, photonics, and microelectronics; nano-mechanical devices and micro-electro-mechanical systems; radiation and electromagnetic metamaterials.View current research abstracts (pdf)View group web siteM. CulpepperResearch focuses on precision interfaces, precision manufacturing, design for manufacturing, applying precision principles as enabling technologies in multi-disciplinary product design: electronic test equipment, automotive systems, precision compliant mechanisms.View current research abstracts (pdf)View group web siteL. DanielResearch focuses on engineering design applications to drive research in simulation and optimization algorithms and software, design of microfabricated inductors.View current research abstracts (pdf)View group web siteP. DoyleUnderstanding the dynamics of single polymers and biomolecules under forces and fields; lab-on-chip separations, polymer rheology. DNA electrophoresis in microdevices. Superparamagnetic colloids. Brownian Dynamics simulations of complex molecules. Microheology of biopolymers.View current research abstracts (pdf)View group web siteA. EpsteinSmart engines, turbine heat transfer and aerodynamics, advanced diagnostic instrumentation, turbomachinery noise, environmental impact of aircraft.View current research abstracts (pdf)View group web siteD. FreemanBiological micromechanics, MEMS, light microscopy and computer microvision.View current research abstracts (pdf)牋牋牋牋牋牋牋牋牋牋牋?牋View group web siteM. GrayMicrofabricated devices for use in diagnostic medicine and biological research. Particle and fuid analysis of flowing media using absorbance and fluorescence techniques as a means for understanding cell or organism metabolism and phenotypic expression.View group web siteJ. HanBioMEMS, biomolecule analysis, micro/nanofluidics, micro-analysis systems.View current research abstracts (pdf)View group web siteJ. JacobsonDevelopment of processes for directly and continuously printing communication, computation, and displays onto arbitrary substrates. Electronic control of biomolecules.View group web siteK. JensenMicrofabrication and characterization of devices and systems for chemical synthesis and detection, hydrocarbon fuel conversion to electrical energy, bioprocessing and bioanalytics. Multiscale simulation of transport and reaction processes. Chemical vapor deposition of polymer, metal, and semiconductor thin films. Synthesis and characterization of quantum dot composite materials.View current research abstracts (pdf)View group web siteR. KarnikMicro- and nanofluidic systems. Application of transport phenomena in nanofluidics for flow control, separation, sensing. Microfluidic devices for studying chemical kinetics and nanoparticle synthesis.View group web siteS.G. KimSystems Design and Manufacturing, MEMS for optical beam steering, microphotonic packaging and active alignment, micro power generation, massive parallel positional assembly of nanostructures, and nano actuator array.View current research abstracts (pdf)View group web siteJ.H. LangAnalysis, design and control of electromechanical systems. Application to traditional electromagnetic actuators, micron scale actuators and sensors, and flexible structures.View current research abstracts (pdf)View group web siteC. LivermoreMicroElectroMechanical Systems (MEMS). Design and fabrication of high power microsystems. Nanoscale self-assembly and manufacturing.View current research abstracts (pdf)View group web siteS. ManalisApplication of micro- and nanofabrication technologies towards the development of novel methods for probing biological systems. Current projects focus on electrical and mechanical detection schemes for analyzing DNA, proteins, and cells.View current research abstracts (pdf)View group web siteD.J. PerreaultAnalysis, design, and control of cellular power converter architectures. DC/DC Converters fordual-voltage electrical systems. Electrical system transient investigation. Exploration of non-conventional electricity sources for motor vehicles.View group web siteM.A. SchmidtMicroElectroMechanical Systems (MEMS). Microfabrication technologies for integrated circuits, sensors, and actuators. Design of microsensor and microactuator systems.View current research abstracts (pdf)A. SlocumPrecision Engineering; Machine Design; Product Design.View current research abstracts (pdf)View group web siteC.V. ThompsonProcessing, structure, properties, performance, and reliability of thin films and structures for micro- and nano-devices and systems. Reliability and Interconnect.View current research abstracts (pdf)View group web siteT. ThorsenIntegrating microfluidic design and fabrication techniques, electronics and optics with biochemical applications. Optimizing channel dimensions, geometry, and layout to generate 3-D fluidic networks that are functional and scalable. Interface development to combine microfluidic technologies with pneumatic valves, MEMS-based detector systems, and software-based data acquisition and interpretation, creating devices for fundamental research and diagnostic applications.View current research abstracts (pdf)View group web siteH.L. TullerCharacterize and understand key electronic, microstructural, and optical properties of advanced ceramic materials. Fabrication andcharacterization of crystals, ceramics and glasses for electronic devices, lasers, electrochemical energy conversion, sensors and actuators.View current research abstracts (pdf)View group web siteJ. VoldmanBiological applications of microsystem technology. Engineering and use of microsystems for analysis and engineering of single cells. Physical and electrical cell manipulation. Design, modeling, microfabrication, and testing of microfluidic biological devices employing unconventional materials and fabrication processes. Electromechanics at the microscale.View current research abstracts (pdf)View group web siteE. N. WangDevelopment of MEMS/NEMS for: Biochemical sensing and detection; Thermal management of high power density and high performance systems; Diagnostics for biological systems and bio-functionality View group web siteB. WardlePower MEMS microyhydraulics, structural health monitoring, nanocomposites, damageresistance/tolerance of advanced composite materials, cost modeling in the structural design process, conversion of technology to value.View current research abstracts (pdf)View group web siteJ. WhiteTheoretical and practical aspects of numberical algorithms for problems in circuit, device, interconnect, packaging, and micromechanical system design; parallel numerical algorithms; interaction between numerical algorithms and computer architecture.View current research abstracts (pdf)View group web siteLaser-cooling brings large object near absolute zeroAnne Trafton, News OfficeApril 5, 2007Using a laser-cooling technique that could one day allow scientists to observe quantum behavior in large objects, MIT researchers have cooled a coin-sized object to within one degree of absolute zero.Fig.1Assistant professor Nergis Mavalvala, left, and Ph.D. student Thomas Corbitt are part of an international team that has devised a way to cool large objects to near absolute zero. Enlarge image (no JavaScript)Fig.Super-mirrorMIT researchers have developed a technique to cool this dime-sized mirror (small circle suspended in the center of large metal ring) to within one degree of absolute zero. Enlarge image (no JavaScript)Fig.2Assistant professor Nergis Mavalvala, right, and Ph.D. student Thomas Corbitt look over the laser system they use to cool a coin-sized mirror to within one degree of absolute zero. Enlarge image (no JavaScript)。

纳米生物学英文单词nanometer 纳米nanoparticle 纳米粒子nanomateria 纳米材料lnanobiology 纳米生物学nanotechnology 纳米技术nanocapsule 纳米胶囊nanocapsulation 纳米胶囊化nanocolloidal 纳米溶胶nanosphere 纳米球AFM atomic force microscope 原子力显微镜STM scanning tunneling microscope 扫描扫显微镜nanolabel 纳米标记nano-drug 纳米药物nano-medicine 纳米医药nano-carrier 纳米载体controlled-releaseing system 控制释放系统micro emulsion微乳biodegradable可降解的liposome 脂质体lipid vehicle 脂质小泡magnetic nano particle 磁性纳米微粒solid lipid nanoparticle 固体脂质纳米粒emulsification-evaporation technique 乳化蒸发法high pressure homogenization technique 高压均质法nano-precipitation 纳米沉淀envelop包封disperse 分散drug delivery system 药物递送系统drug incorparation 药物掺入nanostructure 纳米结构nanocrystal 纳米晶体nanosized 纳米尺寸diffusion 扩散diameter 直径polydispersity 多分散性surfactant 表面活性剂self-microemulsion drug delivery system自乳化药物递送系统micelle 胶束molecular cluster 分子簇amphilic 亲脂性的catanionic surfactant 阳离子表面活性剂anionic surfactant 阴离子表面活性剂amphoteric surfactant 两性表面活性剂amphipathic 两亲性disperse system 分散系统aggregate 凝聚reticuloendothelial system 网状内皮系统macrophage 巨噬细胞polylactic acid 聚乳酸poly(lectide-co-glycolide 乳酸、羟基乙酸共聚物poly(D, L-lactide-co-glycolide D，L-乳酸、羟基乙酸共聚物latex 乳液microencapsulattion 微囊包裹chitosan 壳聚糖poly ethylene glycol 聚乙二醇polyethyleneeinine 聚乙二氨oligonucleotide 寡核苷酸colloid 溶胶conjugate 偶连sustained release 持续释放long circulation 长循环gene delivery 基因递送drug-loaded 载药的spray-drying 喷雾干燥phagocytic 吞噬性uptake 吸收gene transfer 基因转导entry 进入lipid fusion 脂质融合cationic liposome 阳离子脂质体non-viral gene transfer system 非病毒基因递送系统polycation liposome 多聚阳离子脂质体glycosylated 糖基化modified 修饰targeting 靶向immunoliposome 免疫脂质体gelator 明胶organogel 有机凝胶cross-link 交联reverse aerogel 反相气凝胶sol-gel 溶胶-凝胶法gelatin 明胶magnetic microsphere 磁性微球magnetic nanoparticle 磁性纳米粒magnetic capsule 磁性微囊magnetic nanosphere 磁性毫微球magnetic liposome 磁性脂质体magnetic emulsion 磁性乳液magnetic starch microsphere 磁性淀粉微球magnetic albumin nanosphere磁性白蛋白毫微球biocompatibility 生物相溶性immunomagnetic microsphere免疫磁性微球immunomagnetic bead 免疫磁性微球superparamagnetic iron oxide 超顺磁性铁氧化物ferrocolloid 铁溶胶bioseperation 生物分离vector 载体graft 偶联bioavailability 生物利用度complexelectrochemical biosensor 电化学生物传感器optical biosenser 光学生物传感器thermal biosensor 热生物传感器piezoelectric biosensor 压电生物传感器intelligent microreactor 智能微反应器reversed micelle 反相胶束nano bioprobe 生物探针biochip 生物芯片microfluidic chip 微流芯片gene chip 基因芯片。

The modern methods of three dimensional microfabrication have lead to the development of extremely miniaturized chemical and biotechnological systems.These so called micro-reactors represent novel approaches in respect of production flexibility and chemical reactions not yet applied in chemical processing.This has stimulated world-wide research in this field so that the technical feasibility of such devices has been demonstrated in the laboratory scale.Microreactor technology has developed to such an extent that a wide variety of micro-reactor components,e.g.micropumps,mixers,reaction chambers,heat exchangers,separators and complete integrated microreaction systems with process control units have been fabrica-ted using the appropriate microfabrication process and materials that are suitable for specific applications.Keywords:Microreactors,microsystems,LIGA technique,chemistry,biotechnology.List of Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2341Worldwide Activities in the Field of Microreactors . . . . . . . . . .2342Definitions of Microreactors . . . . . . . . . . . . . . . . . . . . . . .2353Microreactor Components and Integrated Systems . . . . . . . . . .2383.1Micropumps and -valves . . . . . . . . . . . . . . . . . . . . . . . . .2383.2Micro Heat Exchangers . . . . . . . . . . . . . . . . . . . . . . . . . .2383.3Micromixers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2403.4Microseparators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2433.5Micro Reaction Units . . . . . . . . . . . . . . . . . . . . . . . . . . .2443.6Integrated Microeaction Systems . . . . . . . . . . . . . . . . . . . .2454Major Applications of Microreaction Systems . . . . . . . . . . . . .2454.1Microreactors for Chemical Production . . . . . . . . . . . . . . . . .2464.2Microreactors for Mass Screening . . . . . . . . . . . . . . . . . . . .2475Fabrication Techniques and Materials for Microreaction Systems . .2486Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2487References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .250Microreactors for C hemical Synthesis and Biotechnology – C urrent Developments and Future ApplicationsW.Ehrfeld · V .Hessel · H.LehrInstitut für Mikrotechnik Mainz GmbH,Carl-Zeiss-Str.18–20,D-55129 Mainz-Hechtsheim,GermanyTopics in Current Chemistry,V ol.194© Springer V erlag Berlin Heidelberg 1998234W.Ehrfeld · V.Hessel · H.Lehr List of AbbreviationsACHEMA Ausstellungstagung für Chemisches Apparatewesen,Frankfurt, GermanyAGIE AGIE,Losone,SuisseAIChE American Institute of Chemical EngineersBASF Badische Anilin und Soda Fabrik,Ludwigshafen,Germany DECHEMA Deutsche Gesellschaft für Chemisches Apparatewesen,Chemische Technik und Biotechnologie e.V.,Frankfurt,GermanyDMST Abteilung Mikrosystemtechnik (Department of Microsystem Technology),Technische Universität Ilmenau,Germany DUPONT DuPont de Nemours,Wilmington,USAIMM Institut für Mikrotechnik Mainz GmbH,GermanyISFET Ion Sensitive Field Effect TransistorKFK former Kernforschungszentrum Karlsruhe,present:Forschungs-zentrum Karlsruhe (FZK),GermanyLIGA Lithographie,Galvanoformung,AbformungµTAS Micro Total Analysis SystemsPNNL Pacific Northwest National Laboratory,USA1Worldwide Activities in the Field of MicroreactorsIn the last two decades powerful tools have been developed for the fabrication of microdevices [1–3].This led to the miniaturization of mechanical,optical, thermal and fluidic components.Recently,micromachine technologies are also being applied for synthetic and screening purposes in the field of microreactors [4–13].Main achievements of this vivid development have been made in Europe and the United States [8].In Europe research groups and industry are especially active in Great Britain,Denmark,France,Belgium and Germany [14].In the United States most of the developments have been made by institutes,e.g. Redwood Microsystems or the Pacific Northwest National Laboratory (PNNL),to mention only two.In the Far East,especially in Japan,founding programs for microsystem technology of large financial volume have been started [8].However, these activities are more related to fields different from microfluidic applications.Although some components of microreactors,e.g.micropumps [15] and miniaturized analytical systems [16,17] have been described much earlier,a systematic development and fabrication of components and integrated systems for chemical synthesis started only 3 or 4 years ago [18].While the development was mainly initiated by research institutes [18],considerable interest is mean-while found in the chemical and pharmaceutical industry [19].This is not only manifested by joined projects between institutes and industry,but,moreover,by first microreaction systems which are currently under commercial investigation in industry [19].A first national conference (with many international contribu-tions) which dealt with microreactors for chemical and biological applications was jointly organized by IMM and DECHEMA (the German equivalent of AIChE) already in 1995 [18].In 1996 a session of the Spring National Meeting ofMicroreactors for Chemical Synthesis and Biotechnology – Current Developments 235 the AIChE was related to microreaction systems [8].The first international con-ference about microreactors was held in 1997,again under the leadership of IMM and DECHEMA.Microreactors were selected as a separate topic on the ACHEMA (June 1997),the German exhibition of chemical technology.2Definitions of MicroreactorsThe term microreactor has actually been used a long time before microtechniques were applied for microfluidic purposes [20].Small fixed bed reactors with typical dimensions in the centimeter range were termed microreactors and used to pro-be reactions under process conditions similar to those in macroscopic reactors. These reactors were fabricated by conventional mechanical engineering techni-ques and are still a powerful tool in chemical engineering,e.g.in fluid catalytic cracking.Thus,from the very beginning,investigations of miniaturized reactors were believed to give important data for the control of large-scale processes [21].Miniaturization of chemical and biological systems started in the last decade with the development of a number of microanalytical systems.These devices combine sensors,actuators and microfluidic elements to create micro total analysis systems (µTAS).The subject has been treated in a series of conferences held every two years [16,17].Main goals were the fabrication of systems which needed reduced amounts of expensive chemicals due to miniaturization and integration of several subunits.Further interest concentrated on the favorable use of surface phenomena for an increase in sensitivity and gain in analysis time per sample due to parallelization or use of different process regimes.Only two among a huge number of these devices are mentioned here:the group of N.Rooij developed biological reactors which were applied in outer space [16].Miniaturi-zed micro electrophoresis chips were built by several groups,e.g.by Widmer, Manz and colleagues [22] and by Mathies [23,24].One main effect of chip miniaturization is the decrease of heat release,the so-called Joule effect,by enhanced heat flow which led to much shorter analysis times still at a high resolution due to higher voltages achievable [24].While a big scientific community has been established for analysis systems (such as m TAS),the interest in research on synthesis and screening systems is relatively new and only identified around three years ago [17].It is still a very vivid and open circle whose industrial part has significantly increased during the last two years [19].Nearly all chemical companies are at present more or less involved in this development.Microstructures which are used in this context will be termed microreactors in the following (a more precise definition is given below and in the next chap-ters).It should be emphasized that microreactors are not constrained to micros-copic sizes (nor to minuscule processing rates) as first outlined by Wegeng [8]. His precise definition of microreactors is repeated here:“Components and systems that exploit engineered structures,surface features or dimensions that are typically measured in terms of microns (one millionth of a meter) to hundreds or thousands of microns,and that may include microelectronic components as an integral part of the system”.236W.Ehrfeld · V.Hessel · H.Lehr The most remarkable point of this definition is the conclusion that,in con-trast to many analytical systems,not all lateral dimensions along the axis of flow have to be in the µm range,but only some of them as much as it is demanded by the application desired.Actually,in today’s microreactors a number of small microchannels are often connected to a common large feed stream (principle of manifolding or partitioning [7]).This combination of very small and large units requires a high technological flexibility which needs the application of both microfabrication and precision engineering techniques.The parallelization of microchannels leads to a high throughput which is needed in synthetical rather than in analytical applications [8,25].Parallelization is often accompanied by a shortening of the flow axis in order to keep the pressure drop as low as possible, if this is allowed by the kinetics of the process [8].Indeed,a micromixer array developed at IMM utilizes both effects and can be operated at a flow rate of up to 3l/h while still maintaining good mixing quality [26].However,reactions running at this high speed have to be necessarily fast,otherwise the length of the miniaturized part has to be increased with the consequence of reduced flow rates.Having this in mind,three categories of process regimes can be defined which correspond to different types of microreactors:1.In the regime of fast single reactions continuous flow systems with relativelyshort miniaturized paths will be used.2.In the regime of slow single reactions semi-batch systems including valveswill be adequate.3.In the regime of multiple parallel reactions,either fast or slow,semi-batchsystems similar to titer plates have to be developed which are connected to microdispensing systems and separation/analysis units (Fig.1).Microreactor components of types 1 and 3 have been developed in a number of cases [8].Those of type 2 have not been realized to our best knowledge.Howe-ver,future developments will certainly move into this field,since the majority of reactions,in particular those in liquid media,are of that type.Microreactors can not only be characterized by the types of reactions and process regimes they address.In addition,a task definition should be given which determines the complexity of the systems and,therefore,what kind of functions are provided (see Fig.1).The simplest subsystems are microreaction components which correspond to a single operation.Most often these are unit operations which e.g.perform mixing,heat exchange,reaction,separation and others.The majority of present microfluidic structures actually belong to this group [5].Since usually more than one (unit) operation is necessary to result in a net effect,individual microreactor components are mainly used to serve as demonstration units.Heat transfer coefficients and heat fluxes have been deter-mined for this purpose,e.g.by temperature measurements of hot and cold sol-vent streams passing through micro heat exchangers [5].The quality of mixing has been analyzed in micromixers by standard reactions which have originally been developed for the characterization of macroscopic vessels,e.g.neutraliza-tion reactions yielding a change of color [9,27]or,much more elaborated,con-current reactions which are affected by local changes of mixing quality [26].Microreactors for Chemical Synthesis and Biotechnology – Current Developments 237Phenomenological Definition of Microreactors1)Microreactors for fast single reactions Continuous flow systems with relativelyshort miniaturized paths2)Microreactors for long single reactions Semi-batch systems including valves3)Microreactors for multiple parallel Semi-batch systems similar to titer-platesreactions,either fast or long connected to microdispensing systemsand separation/analysis unitsFunctional definition of microreactors1)Microreaction components Single (unit) operation,e.g.mixing,heatexchange,reaction,separation2)Integrated microreaction systems Single reaction with several (unit)for single reactions operations ÆSystem with severalcomponents in fixed sheets3)Integrated microreaction automats Multiple reaction with several (unit)for multiple-step reactions operations ÆSystem with severalcomponents in flexible sheetsFig.1.Different types of microreactors:Functional definition of microreactors However,some of these microreaction components may be successfully applied for specific purposes,e.g.for the production of colloidal particles whose pre-cipitation process is sensitive to mixing or for the preparation of emulsions for cosmetic industry.In the majority of applications,more complex systems have to be constructed which will be termed integrated microreaction systems [8,29].Here,com-ponents are assembled to form a complete and complex unit so that macro-scopic channels are only found at the end and beginning of the whole system, while fluidic channels in the system show diameters in the m m-range.These devices can be regarded as microscopic analogues of typical laboratory equip-ment such as three-necked flasks connected to coolers,distillers and drop fun-nels.First integrated systems have been realized by PNNL,IMM and DuPont by a sandwich-type arrangement of microstructured sheets [7,8,28].Each of these integrated systems is especially designed for one single reaction so that the microstructured units are fixed.Although structural details may be varied by the exchange of sheets,the reactors are still confined to one purpose.Designs different from sheet architecture have also been realized,mainly for m TAS appli-cations.Fiehn proposed a fluidic ISFET microsystem (FIM) based on a planar integrated system [29].Also,alternatives with reversibly mounted components perpendicular to the substrate have been presented [30].Finally,van den Berg developed a so-called mixed circuit board (MCB) containing the fluid channels as well as the electronic circuitry in combination with the silicon-based fluidic components (modules) [31].Even more complex systems will be given by integrated microreaction systems for multiple-step reactions.They will be composed of flexible sheets which may be divided into classes each representing a homologous series of components.Thus,similar to the series of flasks with variable sizes of25,50,238W.Ehrfeld · V.Hessel · H.Lehr 100 and 250 ml,micromixer sheets with variable dimensions of lamella and lengths of mixing zone may be part of such systems.However,this demands a standardization for interconnection (similar to that for laboratory equipment).If microreactors,either as components or integrated systems,will run in parallel as an array,new solutions for feeding or dispensing systems have to be developed.This is also true for the process control of a large number of product streams which will be a challenge for realization.Tomorrow’s answers to these questions will determine which type of microreactor will be favored and will specify the major applications,either simulation of processes,synthetic pro-duction or mass screening.3Microreactor C omponents and Integrated SystemsIn order to introduce the basic microreactor components this chapter gives an overview of some important developments which have been achieved in the last five years,instead of presenting a comprehensive survey of the whole field of microreactor technology.Different components and their applications are discussed,also leading to a characterization of their efficiency for synthetic applications.3.1Micropumps and -valvesMicropumps and -valves were the first components to be explored on a large scale.They were fabricated with or without moving mechanical parts [8].Active pumps contain a diaphragm which is actuated by electrostatic,piezoelectric, electromagnetic or electro-thermopneumatic forces resulting in a constant volume displacement with each stroke.Although many of these pumps have been designed for purposes different from those discussed here,e.g.for medical applications,some of them may be applied as components in microreactors depending on their flow rate,cycle time and pressure accessible.Wegeng attributes electro-thermopneumatic actuators with the highest force output and the capability of extremely short cycle times (from 10–3to 10–5s) [8,32].Typical flow rates published for a number of micropumps are in the range of 10–500m l/min [33–39].Higher pump rates were reported for a bi-directional pump (about 800m l/min) [40,41].Still higher rates of14,000m l/min were found for a valveless diffusor-nozzle micropump [42]and an electro-hydrodynamic (EHD) micropump with 16,000m l/min [43].A microvalve delivered by Redwood Microsystems even withstands a backpressure of67 bar [8] (Fig.2).3.2Micro Heat ExchangersMicro heat exchangers were expected to give enhanced heat transfer in chemical reactions,e.g.in order to control undesired reactions.Wegeng and Ehrfeld attri-bute the main potential of miniaturized heat exchangers to the minimization oflocal temperature changes in case of exo- and endothermic reactions,thus yielding essentially isothermal conditions [8,25].While tube-like micro heat exchangers have been reported to be applied as components in integrated systems by IMM [44],planar sheet architectures have been favored in other cases[8,45].For the design of micro heat exchangers,it has to be considered that both heat and mass transport time-scales are strongly correlated with the characteristic dimensions of the exchanger according to diffusion theory [8,9]:Heat transport:t ~d 2/aMass transport:t ~d 2/D(t:time-scale,d:channel width,a :thermal diffusivity of fluid,D:mass diffusivity)Taking into account typical numbers for a and D,this underlines that the channel width should be considerably smaller than 1 mm (1000m m) in order to achieve short residence times.Actually,heat exchangers of such small dimens-ions are not completely new,because liquid cooled microchannel heat sinks for electronic applications allowing heat fluxes of 790 watts/cm 2were already known in 1981 [46].About 9 years later a 1 cm 3cross flow heat exchanger with a high aspect ratio and channel widths between 80 and 100m m was fabricated by KFK [10,47].The overall heat transport for this system was reported to be 20 kW.This concept of multiple,parallel channels of short length to obtain small pressure drops has also been realized by other workers,e.g.by PNNL and IMM.IMM has reported a counter-current flow heat exchanger with heat transfer coefficients of up to 2.4 kW/m 2K [45] (see Fig.3).Microreactors for Chemical Synthesis and Biotechnology – Current Developments239Fig.2.Mold insert in nickel for membrane micropump made by LIGA technique using multiple irradiationThis number is comparable to that of macroscopic heat exchangers with fins.PNNL designed similar structures and different ones with pins resul-ting in a heat transport of up to 100 W/cm 2and heat transfer coefficients of 10–35 kW/m 2K at low pressure drops of about 0,13–0,20 bar [8,48].The channel widths and depths were varied in a relatively huge range from 50 to 1000m m and the lengths were in the order of several centimeters.Not only single-phase flow experiments were performed,but also evaporative and condensing flow cases have been realized.The high performance of evaporative micro heat exchangers has also been demonstrated by other authors [49].3.3MicromixersDifferent types of static mixers have been reported which nearly all use the principle of multi lamination to achieve fast mixing via diffusion [5,8,9,27,28,44,45].The flow regime in microreactors is laminar in almost all cases due to small channel dimensions so that diffusion is the only mechanism which con-tributes to mixing,while convective segmentation mechanisms as found in the turbulent regime are absent.An intermediate region with Reynolds numbers between 2 and 100 exists where inertia forces assist segmentation [9].Apart from that,the subdivision of laminar sheets by means of geometric constraints 240W.Ehrfeld · V .Hessel · H.Lehr Fig.3.Miniaturized plate-type heat exchanger fabricated by LIGA technique and housing.Structural height:300µm,Materials:Nickel on copper,aluminum oxide and aluminum.The aluminum oxide and aluminum heat exchangers were realized by embossing with embossing tools.In the first case an embossing tool in nickel on copper was used which was realized by electroforming.In the second case the embossing tool in stainless steel was fabricated by die sinking with LIGA electrodes241 Microreactors for Chemical Synthesis and Biotechnology – Current Developments(=changes in the dimensions of the microchannels) is the only solution to achieve mixing in microreactors.This is to be compared with stirring and creation of turbulent flow which are the most prominent ways to achieve good mixing in macroreactors.Different concepts have been reported for microreac-tors,including the direct subdivision of the channel size by splitting [2] the main stream into a large number of substreams or other indirect means,e.g.multiple splitting,drilling or bending which are based on a separation-reunification mechanism [5,8,9,27,28,44,45] (see Fig.4).Drilling and bending mechanisms regenerate the original channel geometry before reunification so that a multiple repetition of the separation step can be performed.Thereby,the widths of the lamellae are halved in each consecutive step.In the case of direct subdivision the width of the lamella depends on that of the channel,although repeating steps may be included,too.It was pointed out by different authors that these mechanisms allow a mixing in a time interval considerably shorter than 1 s [4,8,9].This mixing time t is pro-portional to d2/D,d being the width of the channel and D the mass diffusivity[9].Thus,the reduction of the channel width strongly influences the quality ofFig.4.Concepts to achieve multilamination:Direct subdivision by splitting of a main stream and indirect methods by splitting,drilling or bending based on separation-reunification mechanisms242W.Ehrfeld · V.Hessel · H.Lehr mixing.Channel widths reported for microstructures made by silicon micro-machining and LIGA technology were in the range of20 to 50m m which allow complete mixing in a time-scale of approximately 100–300 ms.Although this time-scale seems to be rather short,one has to consider that for velocities of about 0.1 m/s (which is high,but still typical for reactions in microreactors) an according channel length results of10,000–30,000m m for complete mixing! This also defines the minimal length of the passage through a heat exchanger in case of exothermic reactions with heat release after mixing.These crude estimations determine the distance between mixer and heat exchanger (if not directly embedded) which should be smaller than about 1000–3000m m corresponding to 10% of the overall mixing length.This simple calculation exhibits two important issues of future development work:The channel dimensions have to be minimized to achieve a better mixing condition. Mixer and heat exchanger have to be part of an integrated system for effective mixing in the subsequent heat exchange step.A negative effect of the reduction of the channel widths is certainly a decrease of the overall flow.This may be overcome by a parallel arrangement of mixing units in arrays and high aspect ratios to increase the depth of the channels.These requirements are easily met applying LIGA technology as well as micro spark erosion techniques.Another aspect of the so-called vertical lamination of LIGA technology is the lower pressure drop compared to that of mixers based on horizontal lamination such as silicon microstructures made by wet etching technologies [9].The length oftypical silicon mixers ranges between 3000 and 10,000m m [9,27],while theFig.5.Single mixer and micromixer array in nickel on copper fabricated by LIGA technique and housing.Channel width:40µm,Materials:Nickel on copper,silver and titanium diboride. The silver and nickel-on-copper micromixers were realized by electroforming,the titanium diboride micromixer was fabricated by die sinking with LIGA electrodeslength of LIGA type mixers can be less than 300m m [45] resulting in a higher throughput (up to 3l/h compared to 10–600m l/h).Thus,the field of applications for LIGA mixers is at present completely different from that of silicon mixers. The latter were designed for m TAS applications,while the former meet the requirements of synthetic processes.Silicon-type mixers using the separation-reunification principle have been reported by PNNL [8],Danfoss [9]and DMST [27].Polymeric analogues made by LIGA technology have been reported by IMM [25] (see Fig.5).The quality of these mixers was characterized by ultrafast acid–base reac-tions which prove a certain degree of mixing by a change of colour indicating a change of pH [8,9].These experiments led to important information for the feasibility of the systems,but hardly resulted in any quantitative data.Since the concentration of acids and bases vary in each publication and are sometimes not reported in detail,the degree of mixing associated with the colour change is different for each system which limits the comparability of the results.Further-more,first experiments to disperse gas and liquids as well as immiscible liquids have been reported [27].A mixer based on the principle of direct subdivision was fabricated by IMM [5,45].This LIGA-type mixer is available as single units as well as mixer arraysFig.6.Test reaction and characterization of mixing in the micromixer arraywith 10 mixing units.The parallelization allows a flux of up to 3l/h.The LIGA-type mixer was recently characterized by a modified reaction which was originally applied for the analysis of mixing in batch macroreactors [26].Two concurrent reactions take place:An ultrafast acid-base reaction between an acid and sodium acetate and a fast redox reaction between iodide and iodate ions yielding iodine whose concentration can be determined by UV-vis spectro-scopy.In the case of perfect mixing the ultrafast reaction dominates the fast one so that no iodine can be observed.Instead,incomplete mixing leads to local concentration changes of the solutions to be mixed,so that the fast reaction takes place parallel to the ultrafast one.The concentration of the iodine can hence be used as a quantitative indicator of the degree of mixing.Experiments with the micromixer array prove good mixing quality over a huge range of flux (250–3000 ml/h).The mixing is better than in reference systems,namely stirred and non-stirred batch macrosystems and T-pieces with a turbulent and laminar flow regime as analogues for continuous flow macrosystems.The authors expect for single mixing units even better results,since the reaction is not only sensitive to local concentration changes,but also to changes which result from distribu-tion problems of the main stream to the single units which are only present in an array.(See Fig.6)3.4MicroseparatorsMicroseparation units make use of the enhancement of mass transport between different phases.PNNL workers reported a microchannel gas-liquid contactorFig.7.Demonstration unit of a membrane module with a dense,thin polymeric membrane and polymeric microstructured support。

综述生命科学仪器2020第18卷/10月刊微流控芯片-质谱联用接口的研究进展张荣楷谭聪睿徐伟*(北京理工大学生命学院北京100081)摘要：微流控芯片由于具有尺寸小、集成程度高、结构功能多样化和样品用量少等优势被广泛应用于化学、生命科学和医学等多个领域:质谱具有灵敏度高、检测速度快和便于定性定量分析等优点：微流控芯片与质谱的联用充分结合了二者各自的优势，通过简便的操作实现对微量样品的快速分析检测：接口的研究是二者联用的前提和关键.经过20余年的发展，微流控芯片与质谱的接口技术逐渐成熟，实现了高效稳定的离子化效果，保证了分析的效率和准确性。

本文总结了基于电喷雾和基质辅助激光解吸两种离子化方式中.微流控芯片与质谱接口的主要类型和相关应用并分析了目前存在的问题及未来发展方向。

关键词：微流控芯片；质谱；接口；电喷雾电离源；基质辅助激光解吸电离源中图分类号：0657文献标识码：A DOI:10.11967/2020181002Recent Advances of Microfluidic Chip-Mass Spectrometry InterfacesZhang Rongkai Tan Congrui Xu Wef(School of L ife Science,Beijing Institute of Technology,Beijing100081,China)Abstract:Microfluidic chips are widely used in many fields such as chemistry,life sciences and medical science due to their small size,high integration,diversified functions and little sample usage.Mass spectrometry has the advantages of high sensitivity,fast detection speed,and convenient qualitative and quantitative analysis.The combination of microfluidic chip and mass spectrometry fully combines their respective advantages and achieves the rapid analysis of trace samples through simple operation..The research on the interface is the key of microfluidic chip-mass spectrometry.After more than20years' development,the interface technology between the microfluidic chip-mass spectrometry has gradually matured,achieving an efficient and stable ionization effect,ensuring the efficiency and accuracy of the analysis.In this review,the main types and related applications of the interface based on ESI and MALDI between microfluidic chip-mass spectrometry,as well as the current problem and future development were discussed.Key Words:Microfluidic chip;Mass spectrometry;Interface;ESI;MALDI|CLC Number]0657[Document Code]A DOI::10.11967/20201810021、引言统基于流动注射分析、色谱和电泳的理论，通过减小通道内径、缩短通道长度以实现分离性能更微流控芯片，又称芯片实验室(lab on achip),是一种将生物、化学、医学分析过程的样品制备、反应、分离和检测等基本操作单元集成到微小尺寸芯片的技术。

Journal of China Pharmaceutical University 2023，54（6）：695 - 705学 报微流控芯片技术及质谱技术用于细菌耐药性检测及耐药机制研究张冬雪，乔亮*（复旦大学化学系，复旦大学生物医学研究院，上海 200433）摘 要 细菌耐药性严重影响全球公共卫生安全。

抗生素错用和滥用不仅没有达到治疗细菌感染性疾病的效果，反而会刺激细菌发生DNA损伤修复反应（SOS反应），加剧细菌耐药性的进化和耐药菌的传播。

本文聚焦于耐药菌，简明介绍细菌耐药性与SOS反应，系统概述了质谱技术、微流控技术及其联用技术在细菌检测及细菌耐药机制研究中的应用。

本文为细菌耐药性相关的药物靶点挖掘及新药开发提供理论参考，以期发展细菌耐药性快速检测新方法和抑菌新方法，推动临床细菌感染性疾病的诊断与治疗。

关键词细菌耐药；耐药机制；微流控技术；质谱检测；组学分析中图分类号O65；R318 文献标志码 A 文章编号1000 -5048（2023）06 -0695 -11doi：10.11665/j.issn.1000 -5048.2023060203引用本文张冬雪，乔亮.微流控芯片技术及质谱技术用于细菌耐药性检测及耐药机制研究［J］.中国药科大学学报，2023，54（6）：695–705.Cite this article as：ZHANG Dongxue，QIAO Liang. Microfluidic chip and mass spectrometry-based detection of bacterial antimicrobial resis⁃tance and study of antimicrobial resistance mechanism［J］.J China Pharm Univ，2023，54（6）：695–705.Microfluidic chip and mass spectrometry-based detection of bacterial antimi⁃crobial resistance and study of antimicrobial resistance mechanism ZHANG Dongxue, QIAO Liang*Department of Chemistry, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, ChinaAbstract Bacterial antimicrobial resistance (AMR) is a globally serious problem that threatens public health security.Misuse and abuse of antibiotics cannot achieve the effect of treating bacterial infectious diseases, but will trigger the SOS response of bacteria, exacerbating the evolution of bacterial AMR and the spread of resistant bacteria.This article focuses on antibiotic-resistant bacteria, briefly introduces the pathogenesis of bacterial AMR and SOS response, and systematically summarizes the determination and mechanism study of bacterial AMR based on microfluidics and mass spectrometry.This article provides theoretical basis for AMR-related drug target mining and new drug development, aiming to develop new methods for rapid detection of bacterial AMR and new methods for bacteria inhibition, and promote the diagnosis and treatment of clinical bacteria infectious diseases. Key words bacterial antimicrobial resistance; mechanism of antimicrobial resistance; microfluidics; mass spec⁃trometry detection; omics analysisThis study was supported by China Postdoctoral Science Foundation (No.2022M720806)细菌是最常见的病原微生物之一，是引起大部分感染性疾病的重要原因。

专利名称：Microfluidic system发明人：Klaus Witt,Monika Dittmann,Friedrich Bek申请号：US10178569申请日：20020624公开号：US07243670B2公开日：20070717专利内容由知识产权出版社提供专利附图：摘要：A microfluidic system, particularly a microfluidic chip, with at least oneoperational channel, in which a fluid and/or the constituents contained therein aremoveable in the direction of the operational channel by a driving force, particularly by using pressure, acoustic energy, or an electrical and/or a magnetic field. At least onemeasurement sensor used to measure a measurable value assigned to the fluid and derivable in the region of the fluid and at least one regulator is provided to regulate the driving force and/or a parameter that may be influenced by it, wherein the regulator is coupled with a measurement sensor and a device used to alter the driving force and/or the parameter that may be influenced by it. The microfluidic system further relates to a procedure to transport and guide a fluid and/or the constituents contained therein within a microfluidic system of the type described above. For this, the regulator regulates the driving force and/or the parameter that may be influenced by it by means of a measurement sensor to measure a parameter assigned to the fluid and derivable in the vicinity of the fluid and by means of a device used to alter the driving force and/or a parameter that may be influenced by it.申请人：Klaus Witt,Monika Dittmann,Friedrich Bek地址：Keltern DE,Marxzell DE,Pfinztal DE国籍：DE,DE,DE更多信息请下载全文后查看。

我研究微波遥感的英语作文Title: Exploring Microwave Remote Sensing。

Microwave remote sensing is a crucial tool in contemporary scientific research, offering a unique perspective on various aspects of the Earth's surface and atmosphere. In this essay, we will delve into the principles, applications, and advancements in microwave remote sensing.Firstly, it's essential to understand the underlying principles of microwave remote sensing. Microwave radiation, with wavelengths ranging from about one millimeter to one meter, interacts differently with different materials. This interaction provides valuable information about the properties of the target being observed. Unlike visiblelight or infrared radiation, microwave radiation can penetrate clouds, vegetation, and soil, allowing for observations regardless of weather conditions or time of day.Microwave remote sensing finds extensive applications in various fields such as meteorology, agriculture, hydrology, and environmental monitoring. One of its primary applications is in weather forecasting, where microwave sensors onboard satellites provide data on atmospheric temperature, humidity, and cloud cover. This information is crucial for predicting weather patterns and severe weather events.In agriculture, microwave remote sensing helps monitor soil moisture levels, crop growth, and detect anomalies such as drought stress or pest infestations. By analyzing microwave signals reflected or emitted from the Earth's surface, scientists can assess soil moisture content with high precision, aiding in irrigation management and crop yield optimization.Moreover, microwave sensors play a vital role in monitoring Earth's water resources. By measuring microwave radiation emitted by water bodies, scientists can estimate parameters like sea surface temperature, sea ice extent,and ocean salinity. This data is essential for understanding climate dynamics, ocean circulation patterns, and assessing the impact of climate change on marine ecosystems.Furthermore, microwave remote sensing is instrumental in studying Earth's cryosphere, including polar ice caps, glaciers, and permafrost. Microwave sensors onboard satellites provide valuable data on ice extent, thickness, and melting rates, contributing to our understanding of global sea-level rise and polar climate change.In recent years, significant advancements have been made in microwave remote sensing technology, leading to improved data resolution, accuracy, and coverage. New sensor designs, such as synthetic aperture radar (SAR), enable high-resolution imaging of Earth's surface with unparalleled detail. Additionally, advancements in data processing techniques, including machine learning algorithms, facilitate the extraction of meaningful information from vast amounts of remote sensing data.Looking ahead, the future of microwave remote sensing holds promise for further innovations and applications. Continued advancements in sensor technology, coupled with enhanced data processing capabilities, will enable scientists to address pressing environmental challenges with greater precision and efficiency.In conclusion, microwave remote sensing is a powerful tool for studying Earth's surface and atmosphere, offering valuable insights into various environmental processes and phenomena. From weather forecasting to agricultural monitoring and climate change research, microwave remote sensing plays a vital role in advancing our understanding of the planet's dynamic systems. With ongoing technological advancements, the potential for further discoveries and applications in this field is vast.。