MRI: Development of an Instrument for Single Cell Electrical Stimulation and Analysis

MRI：单细胞电刺激和分析仪器的开发

• 批准号: 1625544
• 负责人: Jiang Zhe
• 金额: $ 26.09万
• 依托单位: University of Akron
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1625544&HistoricalAwards=false
• 关键词: MRI; Development; Instrument; Single; Cell

Understanding how the smallest organism unit, a single cell, responds to electrical stimulations is vital for developing precision electrical stimulation treatments for tissue repair, inventing novel conductive biomaterials for tissue regeneration, and identifying new sensitive biomarkers for cancer therapy. Researchers at University of Akron through the Major Research Instrument (MRI) program are working on developing a new instrument to discover and interpret specific responses of single cells to defined electrical stimulations. By integrating the advances in microfluidics and bio-nanotechnology, the instrument will have the following unique capabilities and significances: a) precise delivery of controlled electrical stimulation to single cells, b) collection and analysis of multiple types of molecules secreted by cells, c) direct assessment of resultant single cell responses without the interfering signals from surrounding cells, tissues or substances, and d) "touch free" cell manipulation during the stimulation procedure, avoiding enzymatic, physical treatment of cells. With these unique capabilities, this instrument will advance basic understanding of how cells sense, function, proliferate, and communicate in response to electrical stimulations, which will undoubtedly have transformative impacts on tissue engineering, regenerative medicine, cancer biology, biomaterials and biomimetic devices. The instrument will serve as a major research facility that will build new research and training capacities for faculty members and students at University of Akron, especially for the university's newly created Biomimicry Research and Innovation Center and Integrated Bioscience Ph.D. Program, and benefit bioscience researchers from other research institutes, industry and government laboratories in Akron-Cleveland area. The design concept and the instrument will also provide excellent training opportunities for graduate, undergraduate and K-12 students via course development, University of Akron's "Increasing Diversity in Engineering Academics", and "Women in Engineering" programs. Deciphering and manipulation of specific responses of single cells to definable electrical stimulations is urgently needed to advance current cell research. However, to date a universal instrument is unavailable than can precisely deliver various electrical stimulation to individual cells, collect and analyze secreted molecules by cells. This NSF project aims to develop a new instrument that will enable cracking the bioelectrical code of single cells of any type, building new research capacities for single cell level manipulation and characterization. To achieve the desired functions and specifications, the instrument will consist of 1) a standing surface acoustic wave (SSAW) cell focuser in which single cells will be focused in the centerline of microchannels, 2) an array of microelectrodes in a serpentine microchannel to apply controlled electrical stimulations to single cells in a continuous flow, 3) an array of cell culture chambers to culture the stimulated cells, and form target molecule-microparticle aggregates, and 4) a resistive pulse sensor array to measure the aggregates and determine multiple type of molecule concentrations in cell secretome. Ultimately, the above four major parts will be integrated into a compact yet powerful new instrument for cell research. The new instrument will directly impact the advanced researches on 1) Cardiac repair and regeneration, 2) Neural tissue engineering, 3) Electrical stimulation assisted wound healing and 4) Conductive biomaterials for nerve regeneration.

了解最小的生物体单位，即单细胞如何响应电刺激，对于开发用于组织修复的精确电刺激治疗，发明用于组织再生的新型导电生物材料以及识别用于癌症治疗的新的敏感生物标志物至关重要。阿克伦大学的研究人员通过主要研究仪器（MRI）计划正在开发一种新的仪器，以发现和解释单细胞对特定电刺激的特定反应。通过整合微流体和生物纳米技术的进步，该仪器将具有以下独特的功能和意义：a）将受控的电刺激精确递送到单细胞，B）收集和分析由细胞分泌的多种类型的分子，c）在没有来自周围细胞、组织或物质的干扰信号的情况下直接评估所得的单细胞应答，和d）在刺激过程中的“无接触”细胞操作，避免了细胞的酶、物理处理。凭借这些独特的功能，该仪器将推进对细胞如何感知，功能，增殖和响应电刺激的通信的基本理解，这无疑将对组织工程，再生医学，癌症生物学，生物材料和仿生设备产生变革性影响。该仪器将作为一个主要的研究设施，为阿克伦大学的教师和学生建立新的研究和培训能力，特别是为该大学新成立的仿生研究和创新中心以及综合生物科学博士。计划，并使来自阿克伦-克利夫兰地区其他研究机构，工业和政府实验室的生物科学研究人员受益。 设计概念和仪器还将通过课程开发，阿克伦大学的“增加工程学术的多样性”和“工程中的女性”计划为研究生，本科生和K-12学生提供极好的培训机会。 解读和操纵单细胞对可定义的电刺激的特异性反应是推进当前细胞研究的迫切需要。然而，到目前为止，还没有一种通用的仪器可以精确地将各种电刺激传递到单个细胞，收集和分析细胞分泌的分子。NSF的这个项目旨在开发一种新的仪器，能够破解任何类型的单细胞的生物电密码，为单细胞水平的操作和表征建立新的研究能力。为了实现所需的功能和规格，该仪器将由1）驻波表面声波（SSAW）细胞聚焦器组成，其中单细胞将聚焦在微通道的中心线上，2）蛇形微通道中的微电极阵列，以向连续流中的单细胞施加受控的电刺激，3）细胞培养室阵列，以培养刺激的细胞，并形成目标分子-微粒聚集体;以及4）电阻脉冲传感器阵列，用于测量聚集体并确定细胞分泌组中多种类型的分子浓度。最终，上述四个主要部分将被集成到一个紧凑而强大的细胞研究新仪器中。新仪器将直接影响1）心脏修复和再生，2）神经组织工程，3）电刺激辅助伤口愈合和4）用于神经再生的导电生物材料的先进研究。