Continuous Glucose Monitoring with Graphene-Based Disposable Wireless Sensors

描述（由申请人提供）：先进医疗电子公司（AME）和明尼苏达大学提议开发一种新的基于石墨烯的连续血糖监测仪，具有无源无线读出能力和可溶解/生物相容性金属化层，用于闭环血糖控制应用。糖尿病是美国第七大死亡原因，由于糖尿病引起的其他健康问题的增加，它很可能被低估为死亡原因。美国和国外的研究发现，改善血糖控制对糖尿病患者有益。一般来说，糖化血红蛋白血液检测结果每下降一个百分点，例如从8.0%降至7.0%，就可以将微血管并发症（眼睛、肾脏和神经疾病）的风险降低40%。在过去的几十年里，1型糖尿病（T1DM）治疗的发展已经取得了很大的进展，现在已经可以实现由闭环血糖监测系统和胰岛素递送机制组成的人工内分泌胰腺（AEP）系统。然而，在获得可靠、成本效益高、对患者友好的血糖监测系统方面仍然存在重大挑战。在这项工作中，我们描述了一种传感葡萄糖的全新方法，该方法有可能克服当前cgm的许多限制，特别是关于它们的大小，侵入性和对患者的不便。这种传感器是新颖的，因为它是基于石墨烯的一种鲜为人知的特性——量子电容效应。石墨烯是碳的二维同素异形体，具有许多独特和非凡的性质。石墨烯中的量子电容效应允许当石墨烯中的电子浓度变化时，适当配置的器件中的电容发生变化。这使得石墨烯可以作为一个非常敏感的可变电容器（变容器），其电容可以根据特定生物分子的存在进行调整，这取决于石墨烯表面的功能化方式。如果与电感器结合，该装置允许将葡萄糖浓度编码为无源谐振器电路的频移。这种传感方法有潜力克服传统gcm的众多限制，并提供独特的功能，非常适合用于闭环人工胰腺系统。在第一阶段，将通过制造对葡萄糖敏感的石墨烯表面的传感器来研究制造这种一次性传感器的可行性。将创建单独的变容管和电感设计，以便对可能的最终器件尺寸进行估计。还将研究使用生物相容性、可溶解金属（如镁）制造设备的可行性。无线读出电路也将被开发和测试。AME组建了一支优秀的团队来开发这种传感器和读出功能。在第二阶段，将生产原型传感器和读出电子设备，并在患者群体中进行测试。

DESCRIPTION (provided by applicant): Advanced Medical Electronics Corporation (AME) and the University of Minnesota propose to develop a new graphene based continuous glucose monitor with passive wireless readout capability and dissolvable / biocompatible metallization layers for use in close-loop glucose control applications. Diabetes is the seventh leading cause of death in America and is likely to be underreported as a cause of death due to increases in other health problems caused by diabetes. Studies in the United States and abroad have found that improved glycemic control benefits people with diabetes. In general, every percentage point drop in A1C blood test results, for example, from 8.0 to 7.0 percent, can reduce the risk of microvascular complications-eye, kidney, and nerve diseases-by 40 percent. Development of treatment for patients with type-1 diabetes mellitus (T1DM) has advanced considerably in the past several decades to the point where the realization of an artificial endocrine pancreas (AEP) system consisting of a closed-loop plasma glucose monitoring system combined with an insulin delivery mechanism is now within reach. However, significant challenges remain in obtaining reliable, cost-effect, patient-friendly glucose monitoring systems. In this work, we describe a fundamentally new method of sensing glucose that has the potential to overcome numerous limitations of current CGMs, particularly regarding their size, invasiveness and inconvenience to the patient. The sensor is novel, because it is based upon a little-appreciated property of graphene called the quantum capacitance effect. Graphene is a two-dimensional allotrope of carbon that has numerous unique and extraordinary properties. The quantum capacitance effect in graphene allows the capacitance in a suitably-configured device to change when the electron concentration in the graphene changes. This allows graphene to act as an extraordinarily sensitive variable capacitor (varactor) whose capacitance can be tuned in response to the presence of a particular biomolecule, depending upon how the graphene surface is functionalized. If combined with an inductor, this device allows the glucose concentration to be encoded as the frequency shift of a passive resonator circuit. This sensing method has the potential to overcome the numerous limitations of conventional GCMs, as well as provide unique capabilities that are ideally suited for use in closed-loop artificial pancreas systems. In phase I, the feasibility of creating a disposable version of this sensor will be investigated by fabricating sensors where the graphene surface has been modified to be sensitive to glucose. Separate varactor and inductor designs will be created in order develop an estimate of the final device sizes that are possible. The feasibility of creating devices using biocompatible, dissolvable metals, such as magnesium, will also be investigated. The circuitry for wireless readout will also be developed and tested. AME has assembled an excellent team to develop this sensor and readout capabilities. In phase II, production prototype sensors and readout electronics will be built and tested on a patient population.