Micro- to Nanoscale Neurochemical Sensors

家长资助计划摘要 目前测量细胞外空间中神经化学物质的方法受到化学性质差的限制， 空间和时间分辨率。因此，研究人员无法研究大脑化学物质 动态地，特别是在神经回路的水平上和跨越广泛的信号分子阵列。 为了理解细胞信号在与内在编码信息相关的时间尺度上的作用， 需要变革性的传感器，将提供高度多路复用的变化读数， 细胞外神经化学物质浓度与次秒级反应时间。的目的 一项提案是设计、开发、测试和优化神经化学传感器， 美德.先知-愿分子识别将通过与场效应连接的DNA序列（适体）发生 用于通过电导对可逆结合事件进行电子转导的晶体管（FET）传感器阵列 变化微尺度场效应管将首先采用，其次是开发和实施 多路复用纳米线场效应晶体管。在硅微探针上光刻制造的FET， 它们所官能化的适体将在体外、离体和植入中进行性能验证 体内评价。通过开展拟议的研究，我们将整合和扩展独特的， 我们团队成员的各种能力，使神经化学传感的关键进展 这些技术将使人们能够前所未有地深入了解信息是如何编码在细胞信号中的。 其影响将是了解健康大脑的功能与复杂的 行为，以及精神和神经退行性疾病的相应功能障碍， 最终为这些疾病找到新的治疗靶点。

Parent Grant Project Summary Current methods to measure neurochemicals in the extracellular space are limited by poor chemical, spatial, and temporal resolution. Researchers are therefore unable to investigate brain chemistries dynamically, particularly at the level of neural circuits and across broad arrays of signaling molecules. To understand cell signaling at the time scales pertinent to intrinsically encoded information, truly transformative sensors are needed that will provide highly multiplexed readouts of changes in extracellular neurochemical concentrations with sub-second response times. The objective of this proposal is to design, develop, test, and optimize neurochemical sensors that approach these critical attributes. Molecular recognition will occur via DNA sequences (aptamers) linked to field-effect transistor (FET) sensor arrays for electronic transduction of reversible binding events via conductance changes. Microscale FETs will be employed initially, followed by the development and implementation of multiplexed nanowire FETs. Lithographically fabricated FETs on silicon microprobes, and the aptamers they are functionalized with will be validated in vitro, ex vivo, and implanted for performance evaluation in vivo. By carrying out the proposed research, we will integrate and extend the unique and diverse capabilities of the members of our team to make critical advances in neurochemical sensing technologies that will enable unprecedented insight into how information is encoded in cell signaling. The impact will be towards understanding the function of the healthy brain in relation to complex behaviors, and corresponding dysfunction in psychiatric and neurodegenerative disorders to ultimately identify new therapeutic targets for these diseases.