Rapid, quantitative therapeutic screening for alzheimer's enzymes enabled by optimal signal transduction with transistors

作     者：Le, Son T. Morris, Michelle A. Cardone, Antonio Guros, Nicholas B. Klauda, Jeffery B. Sperling, Brent A. Richter, Curt A. Pant, Harish C. Balijepalli, Arvind 

作者机构：Alternative Computing Group Nanoscale Device Characterization Division National Institute of Standards and Technology GaithersburgMD20899 United States Theiss Research La JollaCA92037 United States Biophysics Group Microsystems and Nanotechnology Division National Institute of Standards and Technology GaithersburgMD20899 United States Information Systems Group Software and Systems Division National Institute of Standards and Technology GaithersburgMD20899 United States University of Maryland Institute for Advanced Computer Studies University of Maryland College ParkMD20742 United States Department of Chemical and Biomolecular Engineering University of Maryland College ParkMD20742 United States Chemical Process and Nuclear Measurements Group Chemical Sciences Division National Institute of Standards and Technology GaithersburgMD20899 United States National Institute of Neurological Disorders and Stroke National Institutes of Health BethesdaMD20892 United States 

出 版 物：《arXiv》 (arXiv)

年 卷 期：2019年

核心收录：

主　　题：Metals 

摘      要：We show that simple, commercially sourced n-channel silicon field-effect transistors (nFETs) operating under closed loop control exhibit an;«3-fold improvement in pH readout resolution to (7.2±0.3)×10-3at a bandwidth of 10 Hz when compared with the open loop operation commonly employed by integrated ion-sensitive field-effect transistors (ISFETs). We leveraged the improved nFET performance to measure the change in solution pH arising from the activity of a pathological form of the kinase Cdk5, an enzyme implicated in Alzheimer s disease, and showed quantitative agreement with previous measurements. The improved pH resolution was realized while the devices were operated in a remote sensing configuration with the pH sensing element off-chip and connected electrically to the FET gate terminal. We compared these results with those measured by using a custom-built dual-gate 2D field-effect transistor (dg2DFET) fabricated with 2D semi-conducting MoS2 channels and a moderate device gain, a=8. Under identical solution conditions the pH resolution of the nFETs was only 2-fold worse than the dg2DFETs pH resolution of (3.9±0.7)×10-3. Finally, using the nFETs, we demonstrated the effectiveness of a custom polypeptide, p5, as a therapeutic agent in restoring the function of Cdk5. We expect that the straight-forward modifications to commercially sourced nFETs demonstrated here will lower the barrier to widespread adoption of these remote-gate devices and enable sensitive bioanalytical measurements for high throughput screening in drug discovery and precision medicine applications. Copyright © 2019, The Authors. All rights reserved.