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Real-Time Monitoring of Insulin Using a Graphene Field-Effect Transistor Aptameric Nanosensor Zhuang Hao, Yibo Zhu, Xuejun Wang, Pavana Rotti, Christopher DiMarco, Scott Tyler, Xuezeng Zhao, John F. Engelhardt, James C. Hone, and Qiao Lin ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.7b07684 • Publication Date (Web): 03 Aug 2017 Downloaded from http://pubs.acs.org on August 8, 2017
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ACS Applied Materials & Interfaces
Real-Time Monitoring of Insulin Using a Graphene Field-Effect Transistor Aptameric Nanosensor Zhuang Hao,†,‡ Yibo Zhu,† Xuejun Wang,† Pavana G. Rotti,§,ǁ Christopher DiMarco,† Scott R. Tyler,§ Xuezeng Zhao,‡ John F. Engelhardt,§,ǁ James Hone,† and Qiao Lin*,† †
Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA ‡ Department of Mechanical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China § Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA ǁ Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA
ABSTRACT This paper presents an approach to the real-time, label-free, specific and sensitive monitoring of insulin using a graphene aptameric nanosensor. The nanosensor is configured as a field-effect transistor (FET), whose graphene-based conducting channel is functionalized with a guanine-rich IGA3 aptamer. The negatively charged aptamer folds into a compact and stable anti-parallel or parallel G-quadruplex conformation upon binding with insulin, resulting in a change in the carrier density, and hence the electrical conductance, of the graphene. The electrical conductance change is then measured to enable the real-time monitoring of insulin levels. Testing has shown that the nanosensor offers an estimated limit of detection (LOD) down to 35 pM and is functional in Krebs-Ringer Bicarbonate (KRB) buffer, a standard pancreatic islet perfusion medium. The results demonstrate the potential utility of this approach in label-free monitoring of insulin and in timely prediction of accurate insulin dosage in clinical diagnostics. Keywords: Affinity sensing, Aptamer, G-quadruplex, Graphene field-effect transistor (GFET), Insulin
1. INTRODUCTION Control of glucose level in blood is critical for patients suffering from both Type 1 and 2 Diabetes.1 Most of the therapeutic options for glucose control require the administration of insulin, an endocrine peptide hormone promoting absorption of blood sugar. While insulin can be injected or inhaled by patients, it remains challenging to choose a correct dose schedule, as the effective durations and strengths of different types of insulins vary significantly.2-3 Blood sugar levels are usually measured to assist in determining the dosage of insulin injection. This lacks accuracy because there is a lag from insulin introduction to effective glucose regulation.4 Therefore, the correct and timely use of insulin is strongly dependent on accurate predictions of insulin levels in the human body.
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Conventional antigen-antibody based methods to quantify insulin concentrations, such as the radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), are time-consuming and not amenable to real-time monitoring.5 Electrochemical or optical sensors have been developed to reduce the required detection time (
