STTR Phase I: Optimization of a device for peripheral nerve recordings to diagnose neuropathy

这项小型企业技术转移研究（STTR）第一阶段项目的更广泛影响/商业潜力是优化和验证一种用于周围神经病变（PN）早期检测和诊断的新型医疗设备。PN是神经纤维的损伤，通常始于皮肤和肢体远端，并随着疾病的进展向更深的组织层转移，估计有3000万人受到影响。目前还没有诊断工具或治愈方法，但早期发现提供了减缓疾病进展的可能性。该项目的目标是推进一种小型，具有成本效益，便携式微针装置测量神经电导的发展，这是直接确定神经功能和确定周围神经健康最准确评估的唯一方法。该设备解决了在临床环境中使用的非侵入性，无痛，早发性神经病变诊断设备的需求。拟议的STTR第一期项目将开发一种新型医疗设备，使用一系列改良的微针电极来测量皮肤和底层组织的小神经纤维中的神经传导。该项目的目标包括：1)通过整个针阵列重复记录神经传导，并使用数学算法平均信号来解释神经信号，以评估神经病变状态；2)确定电刺激检测神经传导的必要性；3)优化信号放大以获得适当的信噪比；4)确定最佳针头规格；5)开发记录信号的无线通信及信号处理和传输软件。信噪比的优化、信号放大、针的规格和电刺激需求的确定将利用健康动物模型进行。利用经过验证的周围神经病变动物模型，将设备测量值与神经传导速度（用于诊断晚期PN）和PN的标准（间接）评估进行比较，包括触觉异常性痛的定量评估（Von Frey试验）、行为分析（丙酮喷雾试验、热/冷板试验）和组织活检。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer Research (STTR) Phase I project is to optimize and validate a novel medical device for early detection and diagnosis of peripheral neuropathy (PN). PN is damage of nerve fibers, typically starting in the skin and distal limbs and migrating to deeper tissue layers as the disease progresses, and affecting an estimated 30 million people. Currently no diagnostic tool nor cure exists, but early detection affords the possibility of slowing disease progression. The goal of this project is to advance the development of a small, cost-effective, portable microneedle device measuring nerve conductance, the only method to directly determine nerve function and determine the most accurate assessment of peripheral nerve health. This device addresses the need for a non-invasive, painless, early onset neuropathy diagnostic device for use in a clinical setting. The proposed STTR Phase I project will develop a novel medical device using an array of modified microneedle electrodes to measure nerve conductance in small nerve fibers of skin and underlying tissues. The project goals include: 1) reproducibly recording nerve conductance across an entire needle array and averaging signals using mathematical algorithms to interpret nerve signals for an assessment of neuropathic state; 2) determining the necessity of electrical stimulation for detecting nerve conductance; 3) optimizing signal amplification for an appropriate signal-to-noise ratio; 4) determining optimal needle specifications; and 5) developing wireless communication of the recorded signal and software for signal processing and transmission. Optimization of signal:noise ratio, signal amplification, needle specification and determination of the need for electrical stimulation will be done utilizing healthy animal models. Utilizing validated animal models of peripheral neuropathy, device measurements will be compared to nerve conductance velocity (to diagnose advanced PN) and standard (indirect) assessments of PN, including quantitative assessment of tactile allodynia (Von Frey test), behavioral assays (acetone spray test, hot/cold plate assay), and tissue biopsies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.