Novel Graphene-based Label-free Biosensor Array for Smart Health and Drug Discovery

目标是利用石墨烯和氮化硼的独特材料特性开发生物植入式传感器，这将为实时检测血液和组织中各种离子的浓度提供更高的灵敏度，从而能够在临床表现之前预测疾病状态的发生。项目活动将把研究与高中、本科生和研究生的教育和培训结合起来，少数民族有大量参与。本研究的总体目标是开发基于石墨烯的柔性离子敏感场效应晶体管（ISFET）传感器，用于测量心肌细胞和神经胶质细胞中的K+、Ca2+和Na+离子浓度和相关离子通量，并开发一种新的方法来测定原代细胞培养中细胞膜离子转运。上述离子的检测具有重要的临床意义，因为它们是心肌缺血和癫痫发作的重要生物标志物。提出的石墨烯ISFET传感器阵列将使对神经胶质细胞和心肌细胞中K+、Ca2+和Na+膜运输的关键理解成为可能。利用氮化硼和石墨烯的新特性开发ISFET的方法解决了几个关键问题，包括：(i)基于膜片钳和微电极阵列技术的复杂性、低通量和细胞侵入性问题，以及（ii）商用si基ISFET的低灵敏度和降解问题。实验计划包括直接在石墨烯上培养细胞，并对心肌细胞和神经胶质细胞中的离子通量进行连续、实时和无标记的测量。所获得的测量结果有望提供培养中原代细胞的电生理特性，特别是其电特性的调节和药物诱导变化。成功完成将导致有用的ISFET传感器在体内检测心肌缺血和癫痫发作的发展。作为教育和推广活动的一部分，每年至少有一名本科生和一名高中生参与该项目，重点是招收少数民族学生。pi还将把研究成果整合到研究生课程中，并通过参加会议和研究网站传播这些成果。

PI: Koley, Goutam Proposal Number: 1606882 The goal is to develop bio-implantable sensors utilizing the unique material properties of graphene and boron nitride, which would offer much higher sensitivity for detecting concentration of various ions in blood and tissue in real time, enabling prediction of the onset of disease states before their clinical manifestation. The project activities would integrate research with education and training of high school, undergraduate and graduate students, with significant minority participation. The overall goal of the proposed research is to develop novel graphene-based flexible ion-sensitive field effect transistor (ISFET) sensors for the measurement of K+, Ca2+ and Na+ ion concentrations and correlated ion fluxes in cardiomyocytes and glial cells, with the overall objective of developing a new approach for assaying cell membrane ion transport in primary cell culture. The detection of the aforementioned ions is clinically significant as they serve as important bio-markers for onset of myocardial ischemia and epilepsy. The proposed graphene ISFET sensor array will enable critical understanding of K+, Ca2+ and Na+ membrane transport in glial cells and cardiomyocytes. The approach of ISFET development utilizing the novel properties of boron nitride and graphene addresses several critical issues including: (i) the complicacy, low throughput and cell invasiveness issues of patch clamp and microelectrode array based techniques, and (ii) the low sensitivity and degradation of commercially available Si-based ISFETs. The experimental plan includes growing cells directly on graphene and performing continuous, real-time and label-free measurements of ion fluxes in cardiomyocytes and glial cells. The measurements acquired are expected to provide electrophysiological properties of primary cells in culture, especially regulatory and drug-induced changes in their electrical properties. Successful completion would result in the development of useful ISFET sensors for in vivo detection of the onset of myocardial ischemia and epilepsy. As part of the educational and outreach activities, the PIs would each involve at least one undergraduate and one high school student to work on this project every year focusing strongly on recruiting minority students. The PIs would also integrate research results in a graduate course, and disseminate them through conference participation as well as research websites.