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

Author:

Sensi Matteo1ORCID,de Oliveira Rafael Furlan23ORCID,Berto Marcello1ORCID,Palmieri Marina1,Ruini Emilio1,Livio Pietro Antonio2ORCID,Conti Andrea4ORCID,Pinti Marcello1,Salvarani Carlo5ORCID,Cossarizza Andrea6ORCID,Cabot Joan M.7ORCID,Ricart Jordi7,Casalini Stefano28ORCID,González‐García María Begoña9,Fanjul‐Bolado Pablo9,Bortolotti Carlo Augusto1ORCID,Samorì Paolo2ORCID,Biscarini Fabio110ORCID

Affiliation:

1. Department of Life Sciences University of Modena and Reggio Emilia via Campi 103 Modena 41125 Italy

2. Université de Strasbourg, CNRS, ISIS 8 allée Gaspard Monge Strasbourg 67000 France

3. Brazilian Nanotechnology National Laboratory (LNNano) Brazilian Center for Research in Energy and Materials (CNPEM) Campinas 13083‐970 Brazil

4. Dermatology Unit Surgical Medical and Dental Department of Morphological Sciences Related to Transplant Oncology and Regenerative Medicine University of Modena and Reggio Emilia via del Pozzo 71 Modena 41125 Italy

5. Rheumatology Unit University of Modena and Reggio Emilia Medical School Azienda Ospedaliero‐Universitaria Policlinico di Modena via del Pozzo 71 Modena 41125 Italy

6. Department of Medical and Surgical Sciences for Children and Adults University of Modena and Reggio Emilia Via Campi 287 Modena 41125 Italy

7. Leitat Technology Center Innovació 2 Barcelona 08225 Spain

8. Dipartimento di Scienze Chimiche University of Padova via Marzolo 1 Padova 35131 Italy

9. Metrohm DropSens S.L. Vivero Ciencias de la Salud C/Colegio Santo Domingo de Guzmán s/n Oviedo 33010 Spain

10. Center for Translational Neurophysiology Istituto Italiano di Tecnologia Via Fossato di Mortara 17–19 Ferrara 44121 Italy

Abstract

AbstractThe 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.

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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