title: Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma.
abstract: Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer's disease and its plasma concentration is in the pg mL(-1) range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL(-1). Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.
authors: Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Jinsik
authors: J
authors: Kim
authors: Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Myung-Sic
authors: MS
authors: Chae
authors: School of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 06974, Korea.
authors: Sung Min
authors: SM
authors: Lee
authors: Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Dahye
authors: D
authors: Jeong
authors: Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Byung Chul
authors: BC
authors: Lee
authors: Department of Electrical Engineering, Kwangwoon University, 447-1 Wolgye, Nowon, Seoul 01897, Korea.
authors: Jeong Hoon
authors: JH
authors: Lee
authors: Convergence Center for Dementia, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: YoungSoo
authors: Y
authors: Kim
authors: School of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 06974, Korea.
authors: Suk Tai
authors: ST
authors: Chang
authors: Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Kyo Seon
authors: KS
authors: Hwang
mesh_terms: D000544:Alzheimer Disease / Q000097:blood; D016229:Amyloid beta-Peptides; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D015374:Biosensing Techniques; D004195:Disease Models, Animal; D055664:Electrochemical Techniques / Q000295:instrumentation; D004867:Equipment Design; D006108:Graphite / Q000737:chemistry*; D057230:Limit of Detection; D008297:Male; D008422:Materials Testing; D051379:Mice; D008822:Mice, Transgenic; D055617:Micro-Electrical-Mechanical Systems; D010087:Oxides / Q000737:chemistry*; D010539:Permeability; D010949:Plasma / Q000737:chemistry*; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010087:Oxides; D006108:Graphite