INTEGRAL BIOSENSORS FOR NEUROCHEMICAL MONITORING DURING

功能性电刺激（FES）中的一个普遍关注的问题是伴随长期电刺激的细胞外微环境的变化，其可引起可逆和不可逆的组织损伤以及神经功能障碍。我们建议制作和评估一种新的系列电化学生物传感器，用于监测急性和慢性神经刺激过程中的化学微环境。这些生物传感器，在第一阶段证明采用电化学检测的反应产物的分析物特异性酶纳入含水氧化铱电极矩阵。它们已经被直接制造到目前用于神经刺激的电极阵列的元件上，其中IrOx被用作去极化的低阻抗涂层。这些新的工具将是有价值的神经假体研究，以确定发生的化学失衡。最终，他们将提供人工神经刺激的反馈控制手段，作为长期植入的FES阵列的永久性补充。第二阶段将需要开发更广泛的改进，长寿命，无干扰的电流和电位IrOx生物传感器的操作在体内（脑脊液，braln组织，肌肉），刺激和电化学测量仪器的设计，并在兔皮层神经和肌肉刺激过程中的局部细胞外化学的体内研究。拟定商业应用：FES电极和具有生物传感器反馈控制的相关电子器件，用于视觉、听觉、震颤和感觉的皮质内假体;用于电排尿的骶根假体;以及用于运动控制和感觉的外周神经假体。相关产品包括电化学转换酶联免疫测定试剂盒和血液成分（葡萄糖、胆红素、尿酸、胆固醇等）的直接传感器。

A general concern in functional electrical stimulation (FES) is the changes in the extracellular microenvironment that accompany long-term electrical stimulation that can give rise to reversible and irreversible tissue damage and to neural dysfunction. We propose to fabricate and evaluate a novel series of electrochemical biosensors for monitoring the chemical microenvironment during acute and chronic neural stimulation. These biosensors, demonstrated in Phase I employ electrochemical detection of the reaction products of analyte-specific enzymes incorporated in a hydrous iridium oxide electrode matrix. They have been fabricated directly onto elements of electrode arrays currenfly employed in neural stimulation in which IrOx is used as a depolarizing, low impedance coating. These new tools will be valuable in neural prosthesis research for determining chemical imbalances which occur. Ultimately they will provide means of feedback control of artificial neural stimulation as long-lived, permanent additions to chronically implanted FES arrays. Phase II will entail developing a wider range of improved, long-lived, interference-free amperometric and potentiometric IrOx biosensors for operation in vivo (cerebrospinal fluid, braln tissue, muscle), design of stimulation and electrochemical measuring instrumentation, and in vivo studies of local extracellular chemistry during neural and muscular stimulation in the rabbit cortex. PROPOSED COMMERCIAL APPLICATION: FES electrodes and associated electronics with biosensor feedback control for intracortical prostheses for vision, hearing, tremor and sensation; sacral root prostheses for electromicturition; and peripheral nerve prostheses for motor control and sensation. Related products include electrochemically transduced enzyme-linked immunoassay kits and direct sensors for blood constituents (glucose, bilirubin, uric acid, cholesterol, etc.).