Micro- to Nanoscale Neurochemical Sensors

微米级到纳米级神经化学传感器

基本信息

批准号：
10001487
负责人：
ANNE MILASINCIC ANDREWS
金额：
$ 114.06万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001487
关键词：
Action Potentials Affinity Amino Acids Ammonium Animals Behavior Behavior Disorders Binding Biological Biosensor Brain Brain Chemistry Brain Diseases Brain Mapping Cations Chemicals Chemistry Code Collaborations Complement Complex DNA DNA Sequence Data Deoxyribonucleotides Detection Development Devices Disease Electrodes Enzymes Event Exhibits Exocytosis Extracellular Space Functional disorder Funding Glucose Goals Hyperacusis Implant In Vitro Individual Ions Link Lipids Measurement Measures Mental disorders Methods Microelectrodes Molecular Conformation Monitor Neural Pathways Neurodegenerative Disorders Neurohormones Neuromodulator Neurons Neurotransmitters Pattern Peptides Performance Prevention Property Reaction Time Research Research Personnel Serotonin Signal Transduction Signaling Molecule Silicon Speed Steroids Structure Surface Synapses System Technology Testing Time Transistors Translating Validation Work aptamer base cost design electric field expectation extracellular functional group in vivo in vivo evaluation innovation insight member molecular recognition nanoscale nanowire nerve supply neural circuit neural information processing neurochemistry neuronal circuitry neurosteroids new therapeutic target next generation novel novel strategies novel therapeutics programs protein expression receptor response sensor sensor technology small molecule temporal measurement

项目摘要

Micro- to Nanoscale Neurochemical Sensors Abstract 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 coded 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.

微米级到纳米级神经化学传感器抽象的目前测量细胞外空间神经化学物质的方法受到化学物质质量差的限制，空间和时间分辨率。因此研究人员无法研究大脑化学成分动态地，特别是在神经回路水平和广泛的信号分子阵列上。为了理解与内在编码信息相关的时间尺度上的细胞信号传导，真正需要变革性的传感器来提供高度多路复用的变化读数细胞外神经化学浓度的响应时间为亚秒级。此举的目的提案是设计、开发、测试和优化接近这些关键的神经化学传感器属性。分子识别将通过与场效应连接的 DNA 序列（适体）进行晶体管 (FET) 传感器阵列，用于通过电导进行可逆结合事件的电子转导变化。首先将采用微型 FET，然后进行开发和实施多路复用纳米线 FET。在硅微探针上光刻制造 FET，以及其功能化的适体将在体外、离体和植入时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和我们团队成员的不同能力在神经化学传感方面取得了关键进展这些技术将使我们能够前所未有地深入了解细胞信号传导中信息的编码方式。其影响将有助于理解健康大脑与复杂的大脑功能相关的功能。行为以及精神和神经退行性疾病中相应的功能障碍最终确定这些疾病的新治疗靶点。