Implantable Microarray Probe for Real-Time Glutamate and GABA Detection

用于实时谷氨酸和 GABA 检测的植入式微阵列探针

基本信息

批准号：
10761486
负责人：
Prabhu Arumugam
金额：
$ 90.4万
依托单位：
ALCORIX
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-18 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10761486
关键词：
Acceleration Affect Alzheimer&apos s Disease American Animal Model Animals Area BRAIN initiative Behavioral Biological Markers Biosensor Brain Brain Diseases Calibration Chemicals Chronic Communication Cortical Column Dementia Detection Development Disease Disease model Drug Delivery Systems Drug usage Electrodes Electrophysiology (science)Enzymes Epilepsy Equilibrium Event Feasibility Studies Formulation Glutamates Goals Healthcare Homeostasis Human Hybrids Hydrogels Implant In Situ In Vitro Inflammation Lead Louisiana Marketing Measurement Measures Mechanics Memory Mental disorders Methods Microdialysis Microelectrodes Microfluidics Modeling Monitor Motion National Institute of Neurological Disorders and Stroke Neuronal Plasticity Neurons Neurosciences Neurosciences Research Neurotoxins Neurotransmitters Parkinson Disease Pattern Penetration Performance Peroxides Pharmaceutical Preparations Phase Physiological Platinum Play Polymers Process Property Rattus Reagent Reproducibility Research Research Personnel Resistance Resolution Role Schizophrenia Silicon Small Business Technology Transfer Research Techniques Technology Temporal Lobe Epilepsy Testing Therapeutic Time Universities Validation Vibrissae Work addiction barrel cortex biomaterial compatibility cost density design detection sensitivity effective therapy flexibility functional improvement gamma-Aminobutyric Acid improved in vivo in vivo evaluation information processing manufacture miniaturize nervous system disorder neural neural implant neurochemistry neuronal circuitry neurotransmission novel process improvement prototype response sensor somatosensory spatiotemporal temporal measurement tool usability

项目摘要

Project Summary This STTR proposal will focus on developing and testing a novel, first-on-the-market implantable biosensor for in vivo, real-time sensing of gamma-aminobutyric acid (GABA) and glutamate (GLU) for animal studies. GABA and GLU are neurotransmitters (NTs) that are essential for information processing and plasticity, memory, and other functions. GLU is the major excitatory NT and GABA is the major inhibitory NT; a proper balance between them is vital for normal brain function. GLU-GABA dysregulation plays a critical role in several brain disorders, including epilepsy (a disease affecting 1.2% of Americans), dementia (which will affect 130M worldwide by 2050) and Parkinson’s (which affects 1.5M Americans today). A fundamental understanding of NT homeostasis including its temporal components and its role on behavioral events within and across brain areas would lead to a better understanding of human brain function and to new and more effective treatments. Existing NT sensing methods measure only one NT at a time, suffer from poor spatiotemporal resolution, are unable to measure NT dynamics at the circuit level, continuously in real time. Our goal is to develop an ultra-small, flexible (50µm) neural probe for chronic, direct and simultaneous amperometric detection of GLU&GABA, with sub-second temporal resolution and with no externally applied reagents. Phase I focused on manufacturing a prototype Si penetrating shank-type probe with 4 micropatterned sensors and one microfluidic on-demand in-situ calibrator (ODIC), optimizing the enzyme functionalization process, and performing a feasibility study on the measurement of physiologically-relevant changes in the levels of GLU&GABA in real time for freely moving rats for up to 2 weeks. The objectives of Phase II are an upgrade of the probe into a brain micromotion-resistant hybrid Si- flexible polymer probe of higher functionality (octrode + 2 ODIC micro-channels), improvements in selective functionalization, and validation of the probes in a rat model of temporal lobe epilepsy. The multifunctional ODICs will be applied to perform in-situ calibrations for chronic measurements and to investigate the circuit activity of 3 adjacent cortical layers in the whisker barrel cortex via chemical modulation. Upon completion, we expect to deliver a unique-on-the-market dual NT probe of excellent reliability and superior sensitivity, selectivity, and stability, with all performance parameters equal to or better than those offered by current technologies. To achieve this, Alcorix will partner with experts in amperometric NT sensing research from Louisiana Tech U. and experts in the manufacture of advanced neuroprobes from NeuroNexus, who will assist with hybrid Si-flexible polymer integration, in vitro and in vivo evaluation, and eventual market entry. The proposed research will also enable alternative uses such as point-of-use sensors for neurotoxins or disease bio-markers, and neural signal recording or neurostimulation in conjunction with specific locally-injected drugs. The 2023 world market for electrophysiological neuro-probes (Grand View Research) is about $266M, CAGR of 3.1%. If only 1% of that market can be captured by this technology it would be more than sufficient justification for the proposed work.

项目概要该 STTR 提案将重点开发和测试一种新颖的、市场上首个可植入生物传感器，用于体内实时感测 γ-氨基丁酸 (GABA) 和谷氨酸 (GLU)，用于动物研究。 GLU 和 GLU 是神经递质 (NT)，对于信息处理和可塑性、记忆力和认知能力至关重要。其他功能 GLU 是主要的兴奋性 NT 和 GABA 是主要的抑制性 NT 之间的适当平衡。它们对于正常的大脑功能至关重要，GLU-GABA 失调在多种大脑疾病中起着至关重要的作用，包括癫痫（一种影响 1.2% 美国人的疾病）、痴呆症（到 2050 年将影响全球 1.3 亿人）和帕金森病（目前影响着 150 万美国人）。包括其时间成分及其对大脑区域内和跨大脑区域的行为事件的作用将导致更好地了解人类大脑功能以及新的、更有效的现有 NT 传感治疗方法。方法一次只能测量一个 NT，时空分辨率较差，无法测量 NT 我们的目标是开发超小型、灵活（50μm）的电路级动态。用于亚秒级慢性、直接、同步电流检测 GLU 和 GABA 的神经探针第一阶段的重点是制造原型硅。具有 4 个微图案传感器和 1 个微流体按需原位校准器的穿透柄型探头 (ODIC)，优化酶功能化过程，并对测量进行可行性研究自由活动大鼠的 GLU 和 GABA 水平的实时生理相关变化最多 2 第二阶段的目标是将探针升级为抗大脑微运动的混合硅。更高功能的柔性聚合物探针（octrode + 2 ODIC 微通道），选择性改进多功能 ODIC 的功能化和探针在颞叶癫痫大鼠模型中的验证。将用于执行长期测量的现场校准并研究 3 的电路活动完成后，我们期望通过化学调节来实现胡须桶皮层中的相邻皮质层。提供市场上独特的双 NT 探头，具有卓越的可靠性和卓越的灵敏度、选择性和稳定性，所有性能参数等于或优于现有技术。为了实现这一目标，Alcorix 将与路易斯安那理工大学的电流 NT 传感研究专家合作， NeuroNexus 制造先进神经探针的专家将协助混合硅柔性聚合物整合、体外和体内评估以及最终的市场进入也将进行。实现替代用途，例如神经毒素或疾病生物标记物的使用点传感器以及神经信号与特定局部注射药物相结合的记录或神经刺激 2023 年的世界市场。电生理神经探针（Grand View Research）约为 2.66 亿美元，复合年增长率为 3.1%，仅占其中的 1%。如果这项技术能够占领市场，那么这将是拟议工作的充分理由。