Development of Nanomembrane Electronics and Machine-Learning Algorithms for Quantitative Screening of Dysphagia Therapeutics

项目摘要 吞咽困难是吞咽反射的神经和肌肉功能的损害， 导致虚弱和潜在的致命状况，如窒息，营养不良，脱水 或吞咽时发生肺炎。吞咽困难困扰着近1500万美国人， 50-60岁或以上的个体，吞咽困难的可能性高达20%。但无论 吞咽困难的原因，目前没有可用的治疗方法。限制 研究吞咽困难的临床前工具和方法是缺乏 治疗吞咽困难。视频透视吞咽研究（VFSS）已被 用于在临床研究以及药物动物模型研究中诊断吞咽困难 发展然而，VFSS方法在临床研究中依赖于 人类受试者，如摄取含钡食物（口服造影剂）和运动 X射线成像期间的固定。VFSS工具显示了动物研究中的严重问题 由于靶点不可控，导致图像质量差，药物不可靠 发展总的来说，现有的商业系统中没有一个能够提供便携式的、实时的、 持续监测人类或动物的吞咽。 在这里，该项目将开发一种新颖的纳米膜电子系统， 在皮肤上以非侵入性方式连续定量评估吞咽活动， 大鼠模型，这将有助于开发潜在的吞咽困难药物。具体来说，我们将开发 柔软、轻便、小型化的可穿戴电子设备，用于监测随时间变化的变化 吞咽肌肉功能通过无线，实时记录肌电图， 吞咽困难大鼠模型的吞咽肌肉。在这个项目中，我们的初步研究，在评估 吞咽困难治疗将集中在ALS相关的吞咽困难，因为有完善的 动物模型（转基因超氧化物歧化酶; SODG 93 A）在年轻时患有严重吞咽困难， 年龄SODG 93 A动物模型已被广泛用于筛选潜在的治疗药物 化合物，包括两种FDA批准的ALS药物：依达拉奉和利鲁唑。总体而言，如果 成功，新开发的纳米膜电子学将是一个游戏规则改变者， ALS相关吞咽困难以及其他疾病的候选药物的治疗评价- 相关的吞咽困难。该研究成果有望为有效的 治疗吞咽困难，这将最终降低死亡率，提高生活质量， 吞咽困难的病人。

Project Summary Dysphagia is an impairment of the swallow reflex's neurological and muscular functions that causes a debilitating and potentially deadly condition such as choking, malnutrition, dehydration or pneumonia during swallowing. Dysphagia afflicts almost 15 million Americans, particularly individuals 50-60 years or older with up to a 20% chance of dysphagia. However, regardless of the cause of dysphagia, currently there are no available therapeutic treatments. Limitation of preclinical tools and methods to study dysphagia is one of the biggest reasons for the lack of therapeutic treatment for dysphagia. Video-fluoroscopic swallowing study (VFSS) has been used to diagnose dysphagia in a clinical study as well as research with animal models for drug development. However, the VFSS method in clinical study relies on the active cooperation of a human subject, such as ingestion of food with barium (oral contrast agent) and movement immobilization during X-ray imaging. The VFSS tool shows the severe issue in an animal study due to uncontrollable target, which results in poor image quality and unreliable drug development. Overall, none of the existing commercial systems can offer a portable, real-time, continuous monitoring of swallowing with either humans or animals. Here, this project will develop a novel, nanomembrane electronic system that offers a continuous, quantitative assessment of swallowing activities in a non-invasive way on the skin of rat models, which will help to develop potential dysphagia drugs. Specifically, we will develop soft, ultrathin, lightweight, miniaturized wearable electronics to monitor time-dependent changes of swallowing muscle functions via wireless, real-time recording of electromyograms on swallowing muscles of a dysphagia rat model. In this project, our initial study in the evaluation of dysphagia therapeutics will focus on ALS-related dysphagia since there are well-established animal models (transgenic superoxide dismutase; SODG93A) with severe dysphagia at a young age. SODG93A animal models have been widely used to screen potential therapeutic compounds, including two FDA-approved ALS drugs: edaravone and riluzole. Collectively, if successful, the newly developed nanomembrane electronics will be a game-changer in the therapeutic evaluation of candidate drugs for ALS-related dysphagia as well as other diseases- related dysphagia. The research outcome is expected to provide a new drug for an effective treatment of dysphagia, which will eventually reduce mortality and improve the quality of life of dysphagia patients.