Bungon, Theodore , Haslam, Carrie J., Damiati, Samar , O'driscoll, Benjamin, Whitley, Toby , Davey, Paul , Siligardi, Giuliano , Charmet, Jérôme and Awan, Shakil A. (2021) Graphene FET sensors for Alzheimer's Disease protein biomarker clusterin detection. Frontiers in Molecular Biosciences, 8 . 651232. doi:10.3389/fmolb.2021.651232 ISSN 2296-889X.

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Abstract

We report on the fabrication and characterisation of graphene field-effect transistor (GFET) biosensors for the detection of Clusterin, a prominent protein biomarker of Alzheimer’s disease (AD). The GFET sensors were fabricated on Si/SiO2 substrate using photolithographic patterning and metal lift-off techniques with evaporated chromium and sputtered gold contacts. Raman Spectroscopy was performed on the devices to determine the quality of the graphene. The GFETs were annealed to improve their performance before the channels were functionalized by immobilising the graphene surface with linker molecules and anti-Clusterin antibodies. Concentration of linker molecules was also independently verified by absorption spectroscopy using the highly collimated micro-beam light of Diamond B23 beamline. The detection was achieved through the binding reaction between the antibody and varying concentrations of Clusterin antigen from 1 pg/mL to 100 pg/mL, as well as specificity tests using human chorionic gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFETs were characterized using direct current (DC) 4-probe electrical resistance (4-PER) measurements, which demonstrated a limit of detection of the biosensors to be ~ 300 fg/mL (4 fM). Comparions with back-gated Dirac voltage shifts with varying concentration of Clusterin show 4-PER measurements to be more accurate, at present, and point to a requirement for further optimisation of the fabrication processes for our next generation of GFET sensors. Thus, we have successfully fabricated a promising set of GFET biosensors for the detection of Clusterin protein biomarker. The developed GFET biosensors are entirely generic and also have the potential to be applied to a variety of other disease detection applications such as Parkinson’s, cancer and cardiovascular.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RC Internal medicine T Technology > TA Engineering (General). Civil engineering (General) T Technology > TK Electrical engineering. Electronics Nuclear engineering
Divisions:	Faculty of Science, Engineering and Medicine > Engineering > WMG (Formerly the Warwick Manufacturing Group)
Library of Congress Subject Headings (LCSH):	Graphene, Field-effect transistors -- Materials, Biosensors , Alzheimer's disease, Clusterin
Journal or Publication Title:	Frontiers in Molecular Biosciences
Publisher:	Frontiers Media
ISSN:	2296-889X
Official Date:	26 March 2021
Dates:	Date Event 26 March 2021 Published 4 March 2021 Available 8 January 2021 Accepted
Volume:	8
Article Number:	651232
DOI:	10.3389/fmolb.2021.651232
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	5 March 2021
Date of first compliant Open Access:	8 March 2021
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID GD105227-104 University of Plymouth http://viaf.org/viaf/132672310 GD110025-104 University of Plymouth http://viaf.org/viaf/132672310 DLS-SM24459-1 Diamond Light Source http://dx.doi.org/10.13039/100011889 EP/M006301/1 [EPSRC] Engineering and Physical Sciences Research Council http://dx.doi.org/10.13039/501100000266

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