INTEGRAL BIOSENSORS FOR NEUROCHEMICAL MONITORING DURING

功能性电刺激（FES）普遍关注的是伴随长期电刺激的细胞外微环境的变化，这种变化可能导致可逆和不可逆的组织损伤和神经功能障碍。我们建议制造和评估一系列新的电化学生物传感器，用于监测急性和慢性神经刺激期间的化学微环境。这些生物传感器在第一阶段进行了演示，采用电化学检测将分析物特异性酶结合在含水氧化铱电极基质中的反应产物。它们已被直接制造到目前用于神经刺激的电极阵列元件上，其中IrOx用作去极化，低阻抗涂层。这些新工具将在神经假体研究中有价值，用于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FES阵列的永久补充。第二阶段将需要开发更广泛的改进的、长寿命的、无干扰的安培和电位IrOx生物传感器，用于体内操作（脑脊液、脑组织、肌肉），设计刺激和电化学测量仪器，以及在兔皮质神经和肌肉刺激过程中局部细胞外化学的体内研究。拟议的商业应用：FES电极和与生物传感器反馈控制相关的电子设备，用于视觉、听力、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周围神经假体。相关产品包括电化学转导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.).