Label-free brain injury biomarker detection based on highly sensitive large area organic thin film transistor with hybrid coupling layer

We describe a sensitive, large-area thin film transistor (TFT) sensor platform for real time detection of low-concentration protein analytes in solution. The sensing area is 7 mm by 7 mm. p-channel (pentacene) and n-channel (a naphthalenetetracarboxylic diimide, NTCDI) organic molecules were each used as semiconductors in conjunction with a newly designed receptor-antibody- functionalized top dielectric layer. This layer, incorporating both a fluorinated polymer and vapor-deposited hydrocarbon, provided maximum capacitive coupling and minimal interference from the aqueous analyte solution, and allowed convenient solvent processing of the antibody coupling layer. Additionally, a new antibody immobilization method was introduced, which led to high immobilization yield and surface coverage. Using glial fibrillary acidic protein (GFAP) as a model protein analyte, this sensor platform demonstrated significant selectivity and recognition of target protein even in much more concentrated non-target protein backgrounds. The dose-response relationship yielded a Langmuir isotherm from which a reasonable affinity constant was calculated for the protein and antibody. A zeta potential measurement provided further evidence of the surface potential change being detected by the TFTs. We explicitly verified for the first time that the response is in fact predominantly from perturbations of TFT channel current. To the best of our knowledge, this is the most sensitive organic TFT (OTFT) protein sensor yet reported, and also the first demonstration of the expected opposite current responses by p- and n-channel semiconductors to the same protein.