Graphene FET Sensors for Alzheimer’s Disease Protein Biomarker Clusterin Detection

Frontiers in Molecular Biosciences

Giuliano Siligardi¹  Samar Damiati²  Jerome Charmet³  Theodore Bungon⁴  Benjamin O’Driscoll⁴  Shakil A. Awan⁴  Toby Whitley⁴  Paul Davey⁴  Carrie Haslam⁴ 

[1] Diamond Light Source, Rutherford Appleton Laboratory, Oxfordshire, United Kingdom;Division of Nanobiotechnology, Department of Protein Science, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden;Institute of Digital Healthcare, WMG, University of Warwick, Coventry, United Kingdom;Wolfson Nanomaterials and Devices Laboratory, School of Engineering, Computing and Mathematics, Faculty of Science and Engineering, University of Plymouth, Plymouth, United Kingdom;

关键词: graphene;    field-effect transistors;    biosensor;    Clusterin protein;    Alzheimer’s disease;    SRCD absorbance spectroscopy;   

DOI  :  10.3389/fmolb.2021.651232

来源: DOAJ

【 摘 要 】

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 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). Comparison 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.

【 授权许可】

Unknown