A Tissue Implantable Microbiosensor

描述（由申请人提供）：本申请的目的是开发，原型，验证，制造和商业化一种新的，通用的微生物传感器，设计用于非人类使用，基于功能化纳米颗粒。生产的微生物传感器将能够在体内监测广泛的非电活性、神经学相关分析物，包括但不限于葡萄糖、谷氨酸、乳酸、胆碱、组胺、d -丝氨酸和乙醇。该设计可以扩展到多个连接的毛细血管，为同时监测多种分析物提供一系列生物传感器，具有高时间和空间分辨率，对周围组织的损害最小。第一阶段的具体目标是通过原型设计和表征组织植入式酶功能化纳米颗粒微生物传感器来证明可行性，该传感器适用于体内大脑测量，并可扩展到多分析物微生物传感器阵列。这种被提议的微生物传感器将使研究人员能够瞄准大脑中较小的亚区域，这些区域可能会被目前可用的探针损坏。反过来，这将导致对功能的更好理解，并有助于量化药物反应。所提出的微生物传感器设计也可以适应于在单个空间区域内同时监测多种分析物。能够提高特异性和粒度水平的交钥匙工具将广泛用于研究神经系统疾病的病因、预防、诊断和治疗，这将导致新的发现。Pinnacle将领导这一应用程序，并与堪萨斯大学的三位顶尖科学家组成的跨学科联盟合作。吴教授在材料科学和纳米制造技术方面拥有丰富的经验，Mark Richter教授在蛋白质工程方面拥有丰富的经验，George Wilson教授则为该项目带来了30多年的生物传感器开发经验。Pinnacle的设施和设备以及堪萨斯大学的各个实验室将为成功完成该项目提供所需的资源。该应用的创新方面包括使用活性酶功能化纳米颗粒作为传感元件，以及这些纳米颗粒的受控电泳沉积。同样新颖的是一种设计，最大限度地利用氧气和过氧化氢检测效率。这将导致对被监测分析物具有高灵敏度的线性微生物传感器。在应用中提出了广泛的初步结果。这些结果是第一阶段工作的基础。

DESCRIPTION (provided by applicant): The aim of this application is to develop, prototype, validate, manufacture and commercialize a new, generalized microbiosensor designed for non-human use and based on functionalized nanoparticles. The microbiosensors produced will enable in vivo monitoring of a wide range of non-electroactive, neurologically relevant analytes, including, but not limited to, glucose, glutamate, lactate, choline, histamine, D-serine, and ethanol. The design can be extended to multiple conjoined capillaries to provide an array of biosensors for the simultaneous monitoring of multiple analytes, with high temporal and spatial resolution, which causes minimal damage to the surrounding tissue. The specific aim for Phase I is to demonstrate feasibility by prototyping and characterizing a tissue implantable enzyme functionalized nanoparticle microbiosensor that is suitable for in vivo brain measurements and extensible to multianalyte microbiosensor arrays. The proposed microbiosensor will allow researchers to target smaller subregions of the brain that would be damaged by currently available probes. This, in turn, will lead to a better understanding of function and assist in quantifying drug response. The proposed microbiosensor design can also be adapted to the simultaneous monitoring of multiple analytes within a single region of space. Turn-key tools that allow an enhanced level of specificity and granularity will be widely useful in research on the causes, prevention, diagnosis, and treatment of neurological disorders, and this will lead to new discoveries. Pinnacle will lead this application and work in conjunction with an interdisciplinary consortium of three leading scientists at the University of Kansas. Professor Judy Wu possesses extensive experience in materials science and nanofabrication techniques, Professor Mark Richter is skilled in protein engineering, and Professor George Wilson brings over 30 years of experience in biosensor development to the project. The facilities and equipment available at Pinnacle, and the various University of Kansas laboratories, will provide the resources required to successfully complete this project. Innovative aspects of this application include the use of active enzyme functionalized nanoparticles as the sensing element, and the controlled electrophoretic deposition of these nanoparticles. Also novel is a design that maximizes oxygen reuse and hydrogen peroxide detection efficiency. This will lead to linear microbiosensors with high sensitivity for the analyte being monitored. Extensive preliminary results are presented in the application. These results are the foundation for this Phase I effort. Overall, worldwide biosensor sales in FY2009 were $6.9 billion with 31 percent of the sales due to human glucose sensors. Pinnacle is an established manufacturer of biosensors and is well positioned to introduce this new class of biosensors to a broad pre-clinical market. PUBLIC HEALTH RELEVANCE: In the United States, over 1000 disorders of the brain and nervous system result in more hospitalizations than for any other disease group including heart disease and cancer. The quality of life, and economic, cost of brain and nervous system related disorders, is staggering. These disorders disrupt the lives of more than 50 million Americans each year and costs exceed $400 billion.