Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma.

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.