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

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的一个重要方面。全面了解单个细胞对其生物环境和刺激的反应正在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、癌症诊断和治疗等许多领域。然而，目前还没有这样的仪器可以同时对细胞内的各种关键参数进行全面、定量的测量。 该项目旨在开发一种新型多功能单细胞分析仪，集成了许多重要细胞内参数的体外测量功能。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。该项目设计了三个具体目标，包括： 1) 开发锥形光纤微探针和相关仪器，用于细胞内 pH、温度和拉曼光谱的原位测量； 2）集成具有形态和结构监测功能的锥形光纤微传感器来构建单细胞分析仪； 3）以纳米材料细胞毒性为应用模型的多功能单细胞分析仪的评估和演示。 所提出的新型单细胞分析仪是由该项目中嵌入的许多关键创新所独特实现的。免组装的微米和纳米尺寸传感器探针将在光纤锥体的远端设计和制造，这些探针可以直接插入活细胞中，以高分辨率原位定量测量各种重要参数。这些微传感器与显微成像工具的创新集成将允许对细胞对生物环境和刺激的反应进行全面、系统的研究。以纳米粒子的细胞毒性为例来评估和演示单细胞分析仪的基本功能，也将为进一步的性能增强、系统优化和扩展应用提供有价值的信息。 拟议的研究将由密苏里科技大学（Missouri S&T）三名教授组成的多学科团队进行。该项目所需的所有主要设备均在密苏里科技园区提供。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、分析仪器的设计和实施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教师和学生之间的强有力合作，并加强密苏里科技大学的生物医学相关研究和基础设施。 公共健康相关性（由申请人提供）：本拟议项目将开发一种新型多功能单细胞分析仪，该分析仪集成了许多关键功能，以满足细胞生物学和生物医学研究综合研究的基本需求。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。该仪器的功能包括（1）单细胞pH测量； (2)单电池温度测量； (3)单细胞拉曼光谱采集，以及(4)单细胞表面形态监测。这代表了我们为单细胞研究开发综合仪器平台的初步努力。我们预计在该项目成功后，仪器将添加更多功能（硬件和软件）。这项研究的结果将直接惠及各种生物医学研究和临床实践，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。