Identification of Phenol 2,2-methylene Bis, 6 [1,1-D] As Breath Biomarker of Hepatocellular Carcinoma (HCC) Patients and Its Electrochemical Sensing: E-nose Biosensor for HCC

Background: According to WHO, Hepatocellular cancer (HCC) was the second leading cause of death in 2019 and is gradually increasing. The lipid peroxidation mechanism in cancer cells causes the emission of VOCs in the breath. Volatile organic compounds (VOCs) in breath are becoming favorable biomarkers, especially for cancers, for their sample retrieval and specific association with early metabolic changes. Since both diagnosis and prognosis of the disease depend on the quantity and kind of circulatory biomarkers to be detected, sensitive and selective biosensors with the possibility for portability are constantly in demand.

Results: In this study, breath samples of HCC patients were screened for identification of VOCs via GCMS and later verified by applying unsupervised machine learning models. Phenol 2,2 methylene bis [6-(1,1-dimethyl ethyl)-4-methyl] (MBMBP) was found to be significant VOC in the breath of HCC patients, with a minimum concentration of 2100 ppm. Thiol-modified AuNPs were synthesized, as we reported earlier, and immobilized on the working electrode surface to electrochemically sense MBMBP in purified form and later from clinical breath samples. During the electrochemical experiment of AuNPs with MPMBP, the analyte gets electro-oxidized, whereas the Au (III) ions get reduced to the phenoxy radical's species. The electrochemical analysis of MBMBP detection using hexane thiol AuNPs showed a LOD of 0.005 molL . The thiolated AuNPs-based biosensor for HCC diagnosis via VOC detection confirmed MPMBP in lab standards and raw clinical breath samples of HCC patients.

Significance: This study reveals that GCE modified with hexanethiol AuNPs for the adsorption of significant breath biomarker, is a potential platform for the development of e-nose sensor for the detection of HCC at early stage.