Early Detection of Hepatocellular Carcinoma (HCC) through Biosensor

Abstract

A type of cancer known as hepatocellular carcinoma (HCC) is most frequently found in people with cirrhosis brought on by alcohol use, chronic hepatitis B or C virus infections, or nonalcoholic steatohepatitis (NASH). The early and noninvasive diagnosis of liver disease, i.e., hepatocellular carcinoma (HCC) and cirrhosis, are crucial for shortening the mortality rate. Current techniques and biomarkers for HCC, such as Ultrasound scan (USS), MRI, CT scans, and alpha-fetoprotein (AFP), generate excessive false negatives, necessitating the development of noninvasive methods with high sensitivity. To detect potential targets for the early diagnosis of liver diseases, volatile organic compounds (VOCs), a significant component of human breath, are being studied. Metabolically produced VOCs in breath samples were identified through the Gas chromatography and mass spectrometry approach. The significance of detected VOCs was then analyzed by utilizing an in-house R software-based diverse array of machine learning (ML) models. The exhaled breath samples at a ratio of 35:35:30 was collected from HCC, cirrhotic patients, and healthy individuals. The average age of all participants was 57.2±10.2 years. Based on the above results of GCMS, ML models and statistical analysis, electrochemical sensor will be designed for specific detection of HCC and cirrhosis. Utilizing monolayer thiolate gold nanoparticles such as hexanethiol, dodecane thiol and decanethiol capped AuNPs, the electrochemical detection of VOCs was carried out. Hexane thiol AuNPs were chosen as a sensor for studying the electrochemical detection of VOCs as analytes based on the best electrochemical results that could be demonstrated. The differential pulse voltammetry (DPV) biosensing platform based on hexane thiol capped AuNPs demonstrated high sensitivity with a LOD of 0.2 mmol L-1 and 0.0005 mol L 1 for cirrhotic and HCC, respectively. The amounts of limonene and phenol 2,2 methylene, bis [6,1,1-D] measured by GC-MS were 800ppm (cirrhotic) and 2100ppm (HCC), respectively. Electrochemical sensor measurements of VOCs concentrations were nearly identical, providing confidence for the quantitative detection by using synthesized hexane thiol capped AuNPs biosensing platform. For the biosensing application, analog device AD5940 and impedance analyzer were used to monitor the impedance (Z) and resistance (R) of a chemiresistive sensor response to VOCs. The results showed that Z increased with the increase of the D-limonene, whereas in the case of phenol 2,2 methylene bis 6 [1,1-D] first increased than decreased with the increase of concentration.