Electronic Tongues as the Next Generation of Electrochemical Biosensors for Real-Time Analysis of Biomarkers in Biofluids

Electrochemical biosensors are translational and mobile analytical micro-systems that enable rapid and label-free analyses of redox biomarkers, bringing benchtop medical diagnostic methods to the point-of-care. However, the selectivity of these electrochemical biosensors towards the biomarkers-of-interest dramatically decreases in the presence of biofluids due to other redox molecules generating masking electrochemical signals, requiring pretreatment steps to filter the interfering molecules and limiting the biosensor’s real-time analysis capabilities. In this work, we demonstrate the unique use of film-modified multi-electrode arrays to rapidly probe redox biomarkers in biofluids without pretreatment steps in three modes of detection: (1) direct detection of a specific biomarker, (2) indirect detection by influencing the masking signals that interfere with the biomarker’s electrochemical signal, and (3) simultaneous detection of multiple biomarkers using intelligent machine learning algorithms (`Electronic Tongue`). Our main innovation lies in the use of electrodes that are modified by coating with bioelectronic films that control the electrochemical signal characteristics based on the physicochemical properties of redox molecules, and enables the electronic tongue to distinguish between overlapping and masking signals. Finally, we demonstrate the proof of concept detection in real-world scenarios: (1) amplification of antipsychotic clozapine electrochemical signal that enables improved detection in serum and will provide better schizophrenia treatment outcomes, (2) shifting the interfering signal generated by uric acid using carbon nanotubes encapsulated in a chitosan film improves the in situ detection of the neurotransmitter dopamine, and (3) utilizing electronic tongue to analyze profiles of neurotransmitters using machine learning algorithms enables their simultaneous differentiation in urine.