Micro- to Nanoscale Neurochemical Sensors

家长助学金项目摘要 目前测量细胞外空间神经化学物质的方法受到较差化学物质的限制， 空间和时间分辨率。因此，研究人员无法研究大脑的化学成分。 动态的，特别是在神经电路和广泛的信号分子阵列的水平上。 要了解与内在编码信息相关的时标上的细胞信号，真正 需要变革性传感器来提供高度多路传输的变化读数 细胞外神经化学浓度与亚秒响应时间。这样做的目的是 建议是设计、开发、测试和优化神经化学传感器，以接近这些关键的 属性。分子识别将通过与场效应相连的DNA序列(适配子)发生 用于通过电导电子传输可逆结合事件的晶体管(FET)传感器阵列 改变。首先将采用微型场效应管，然后是开发和实施 多路复用型纳米线FET。在硅微探针上光刻制造的FET，以及 它们被功能化的适配子将在体外、体外和植入后进行性能验证。 体内评价。通过开展拟议的研究，我们将整合和扩展独特的 我们团队成员在神经化学传感方面取得重大进展的不同能力 这些技术将使人们能够前所未有地深入了解信息是如何在细胞信令中编码的。 其影响将是为了了解健康大脑与复合体相关的功能 精神和神经退行性疾病的行为和相应的功能障碍 最终确定这些疾病的新治疗靶点。

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.