Reduced Graphene Oxide Electrolyte-Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti-Drug Antibodies.

Abstract

The advent of immunotherapies with biological drugs has revolutionized the treatment of cancers and auto-immune diseases. However, in some patients the production of anti-drug antibodies (ADAs) hampers the drug efficacy. The concentration of ADAs is typically in the range of 1-10 pM, hence their immunodetection is challenging. We focus here on ADAs towards Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases. We report an ambipolar electrolyte-gated transistor (EGT) immunosensor based on reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate, exhibit low voltage operations (≤ 0.3V), a robust response within 15min, and ultra-high sensitivity (10 aM limit of detection). We propose a multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution. We demonstrate that it allows us to selectively quantify ADAs also in the co-presence of its antagonist tumour necrosis factor alpha (TNF-α), the natural circulating target of IFX. This article is protected by copyright. All rights reserved.