Reduced Graphene Oxide Electrolyte‐Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti‐Drug Antibodies
Matteo Sensi, Rafael Furlan de Oliveira, Marcello Berto, Marina Palmieri, Emilio Ruini, Pietro Antonio Livio, Andrea Conti, Marcello Pinti, Carlo Salvarani, Andrea Cossarizza, Joan M. Cabot, J. Ricart, Stefano Casalini, Marı́a Begoña González-Garcı́a, Pablo Fanjul‐Bolado, Carlo Augusto Bortolotti, Paolo Samorı́, Fabio Biscarini
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. ADAs toward Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases, are focussed. An ambipolar electrolyte-gated transistor (EGT) immunosensor is reported based on a reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate and exhibit low voltage operations (≤ 0.3 V), a robust response within 15 min, and ultra-high sensitivity (10 am limit of detection). A multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution is proposed. It is demonstrated that it allows to selectively quantify ADAs also in the co-presence of its antagonist tumor necrosis factor alpha (TNF-α), the natural circulating target of IFX.