Detection of a multi-disease biomarker in Saliva with Graphene Field Effect Transistors

Carbonic anhydrases (CAs) are a family of enzymes that catalyze the reversible reaction of CO₂ and water into bicarbonate and protons. Several studies have pointed to the importance of the CAs with their up/down regulations as an indicator for various diseases. Of particular importance is the human isozyme CA1, has been suggested as a biomarker for identification of several diseases including cancers, pancreatitis, diabetes, and Sjogren’s syndrome. However, the lack of a rapid, cheap, accurate, and easy-to-use quantification technique has prevented widespread utilization of CA1 for practical clinical applications. In this work, we realized a label-free electronic biosensor for detection of CA1 utilizing highly sensitive graphene field effect transistors (G-FETs) as a transducer and specific RNA aptamers as a probe. These aptameric G-FET biosensors showed the binding affinity (KD) of ~2.3 ng/ml (70 pM), which is four orders lower than that reported using a gel shift assay. This lower value of K_D enabled us to achieve a detection range (10 pg/ml - 100 ng/ml) which is well in line with the clinically relevant range. These highly sensitive devices allowed us to further prove their clinical relevance by successfully detecting the presence of CA1 in human saliva sample.