Development of a Novel Multi-functional Single Cell Analyzer

新型多功能单细胞分析仪的研制

• 批准号: 8352874
• 负责人: YINFA MA
• 金额: $ 18.93万
• 依托单位: MISSOURI UNIVERSITY OF SCIENCE & TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8352874
• 关键词: A549; Address; Algorithms; Apoptosis; Area; Biochemistry; Biological; Biological Markers; Biological Sciences; Biomedical Research; Buffers; Carcinoma; Cell Line; Cell physiology; Cell surface; Cells; Cellular Morphology; Cellular Structures; Cellular biology; Characteristics; Chemistry; Collaborations; Complement; Computer software; Development; Distal; Electrical Engineering; Environment; Equipment; Evaluation; Faculty; Fiber; Fluorescence; Fostering; Foundations; Human; Image; Imaging Device; Immobilization; In Situ; In Vitro; Measurement; Measures; Microscope; Microscopic; Missouri; Modeling; Monitor; Morphology; Necrosis; Optics; Performance; Positioning Attribute; Process; Raman Spectrum Analysis; Research; Research Infrastructure; Resolution; Science; Signal Transduction; Silicon Dioxide; Solutions; Stimulus; Structure; Students; Surface; System; Techniques; Technology; Temperature; Testing; Time; Universities; base; cancer cell; cancer diagnosis; cancer therapy; cell analyzer; chemical standard; clinical practice; cytotoxicity; data acquisition; design; dosage; drug development; graphical user interface; image processing; innovation; instrument; instrumentation; member; multidisciplinary; nano; nanomaterials; nanoparticle; nanoprobe; nanosensors; nanosized; nanotoxicity; novel; novel strategies; optical fiber; professor; prototype; response; sensor; skills; stem cell differentiation; success; A549; Address; Algorithms; Apoptosis; Area; Biochemistry; Biological; Biological Markers; Biological Sciences; Biomedical Research; Buffers; Carcinoma; Cell Line; Cell physiology; Cell surface; Cells; Cellular Morphology; Cellular Structures; Cellular biology; Characteristics; Chemistry; Collaborations; Complement; Computer software; Development; Distal; Electrical Engineering; Environment; Equipment; Evaluation; Faculty; Fiber; Fluorescence; Fostering; Foundations; Human; Image; Imaging Device; Immobilization; In Situ; In Vitro; Measurement; Measures; Microscope; Microscopic; Missouri; Modeling; Monitor; Morphology; Necrosis; Optics; Performance; Positioning Attribute; Process; Raman Spectrum Analysis; Research; Research Infrastructure; Resolution; Science; Signal Transduction; Silicon Dioxide; Solutions; Stimulus; Structure; Students; Surface; System; Techniques; Technology; Temperature; Testing; Time; Universities; base; cancer cell; cancer diagnosis; cancer therapy; cell analyzer; chemical standard; clinical practice; cytotoxicity; data acquisition; design; dosage; drug development; graphical user interface; image processing; innovation; instrument; instrumentation; member; multidisciplinary; nano; nanomaterials; nanoparticle; nanoprobe; nanosensors; nanosized; nanotoxicity; novel; novel strategies; optical fiber; professor; prototype; response; sensor; skills; stem cell differentiation; success

DESCRIPTION (provided by applicant): In vitro quantitative measurements and analyses of various intracellular parameters is becoming an important aspect in cell research. Comprehensive understanding of a single cell in response to its biological environment and stimuli is becoming the foundation of many biomedical research fields, including drug development, nanotoxicity study, biomarker discovery, cancer diagnosis and treatment, and many other areas. However, there is no such instrument currently available to perform comprehensive, quantitative measurement of various key parameters inside a cell simultaneously. This project aims to develop a novel multi-functional single-cell analyzer that integrates the capability of in vitro measurements of a number of important intracellular parameters. The new cell analyzer will address a number of critical issues in biomedical research such as cell necrosis and apoptosis, stem cell differentiation, and cancer cell biology. Three specific aims are designed in this project, including: 1) Development of tapered-fiber microprobes and associated instrumentation for in situ measurement of intracellular pH, temperature, and Raman spectroscopy; 2) Integration of tapered-fiber microsensors with morphology and structure monitoring capabilities to construct the single-cell analyzer; and 3) Evaluation and demonstration of the multi-functional single-cell analyzer using cytotoxicity of nanomaterials as an application model. The proposed novel single-cell analyzer is uniquely enabled by a number of key innovations embedded in this project. Assembly-free micro- and nano-size sensor probes will be designed and fabricated on the distal end of optical fiber tapers that can be directly inserted into a livin cell for in situ, quantitative measurement of various important parameters with high resolution. The innovative integration of these microsensors with microscopic imaging tools will allow comprehensive, systematic studies of the cell responses to the bio-environment and stimuli. The use of cytotoxicity of nanoparticles as an example to evaluate and demonstrate the basic functions of the single-cell analyzer will also provide valuable information for further performance enhancement, system optimization, and expansion of applications. The proposed research will be conducted by a multidisciplinary team consisting of three professors at Missouri University of Science and Technology (Missouri S&T). All major equipment required for this project is available on Missouri S&T campus. The team members have complementing skills in biochemistry/bioanalysis, cytotoxicity of nanomaterials, optical micro/nano sensors and instrumentation, and analytical instrument design and implementation. The interdisciplinary project of life science, electrical engineering, and chemistry will foster strong collaborations among faculty and students in different fields, and strengthen the biomedical- related research and infrastructure at Missouri S&T. PUBLIC HEALTH RELEVANCE (provided by applicant): This proposed project will develop a novel multi-functional single-cell analyzer that integrates a number of key functions to satisfy th essential need for comprehensive study of cell biology and biomedical research. The new cell analyzer will address a number of critical issues in biomedical research such as cell necrosis and apoptosis, stem cell differentiation, and cancer cell biology. The functions of this proposed instrument include (1) single cell pH measurement; (2) single cell temperature measurement; (3) single cell Raman spectrum acquisition, and (4) single cell surface morphology monitoring. This represents our initial efforts to develop a comprehensive instrument platform for single-cell studies. We anticipate more functions (in both hardware and software) will be added to the instrument after the success of this project. The results of this study will directly benefit varios biomedical researches and clinical practices by providing a powerful technique for drug development, nanotoxicity study, biomarker discovery, cancer diagnosis and treatment, and many others.

描述（由申请人提供）：各种细胞内参数的体外定量测量和分析正在成为细胞研究中的重要方面。响应单个细胞的生物环境和刺激的全面了解已成为许多生物医学研究领域的基础，包括药物开发，纳米毒性研究，生物标志物发现，癌症诊断和治疗以及许多其他领域。但是，目前尚无此类工具可以同时对单元格内部的各种关键参数进行全面的定量测量。 该项目旨在开发一种新型的多功能单细胞分析仪，该分析仪整合了许多重要细胞内参数的体外测量能力。新的细胞分析仪将解决生物医学研究中的许多关键问题，例如细胞坏死和凋亡，干细胞分化和癌细胞生物学。该项目设计了三个特定的目标，包括：1）开发锥形纤维微探针和相关的仪器，用于原位测量细胞内pH，温度和拉曼光谱； 2）将锥形纤维微传感器与形态和结构监测能力集成以构建单细胞分析仪； 3）使用纳米材料的细胞毒性作为应用模型评估和演示多功能单细胞分析仪。 拟议的新型单细胞分析仪由嵌入该项目中的许多关键创新来实现。将在光纤锥度的远端设计和制造无装配的微型和纳米大小的传感器探针，这些探针可以直接插入livin细胞中以进行原位，定量测量具有高分辨率的各种重要参数。这些微传感器与微观成像工具的创新整合将允许对细胞对生物环境和刺激的细胞反应进行全面的系统研究。纳米颗粒的细胞毒性用作评估和证明单细胞分析仪的基本功能的示例，还将提供有价值的信息，以进一步增强性能，系统优化和应用程序的扩展。 拟议的研究将由一个多学科团队进行，由密苏里科学技术大学（密苏里S＆T）的三名教授组成。该项目所需的所有主要设备均可在密苏里州S＆T校园提供。团队成员在生物化学/生物分析，纳米材料的细胞毒性，光学微/纳米传感器和仪器以及分析仪器设计和实现方面具有互补的技能。生命科学，电气工程和化学的跨学科项目将促进不同领域的教职员工之间的强大合作，并加强密苏里州S＆T的生物医学相关研究和基础设施。 公共卫生相关性（由申请人提供）：该提议的项目将开发一种新型的多功能单细胞分析仪，该分析仪整合了许多关键功能，以满足对细胞生物学和生物医学研究的全面研究的必要需求。新的细胞分析仪将解决生物医学研究中的许多关键问题，例如细胞坏死和凋亡，干细胞分化和癌细胞生物学。该提出的仪器的功能包括（1）单细胞pH测量； （2）单细胞温度测量； （3）单细胞拉曼频谱采集和（4）单细胞表面形态监测。这代表了我们为开发单细胞研究的综合仪器平台的最初努力。我们预计该项目成功后，将添加更多功能（在硬件和软件中）。这项研究的结果将通过为药物开发，纳米毒性研究，生物标志物发现，癌症诊断和治疗等提供强大的技术，直接受益于Varios生物医学研究和临床实践。