Biomarkers of liver fibrosis detecting with electrochemical immunosensor on clinical serum

Chronic hepatic disease causes high morbidity and mortality worldwide, which can lead to liver fibrosis and the subsequent development of cirrhosis and even hepatocellular carcinoma. For chronic liver injuries of many etiologies, including viral hepatitis, alcohol abuse, metabolic diseases, autoimmune diseases, and cholestatic liver diseases, they could produce fibrosis as a result of deregulation of the normal healing process with massive accumulation of extracellular matrix (ECM). Therefore, the early diagnosis of liver fibrosis is vital for therapeutic decisions and prognostic evaluations. Among the various diagnostic approaches, needle biopsy is considered as the ‘gold standard’. However, it was invasive, confounded by high sampling heterogeneity and carried a finite risk of complications. Especially, it is not suit for frequent evaluations of this chronic disease.

In the research, an electrochemical immunosensor was established to detect representative biomarkers of liver fibrosis, such as hyaluronate acid (HA) and transforming growth factor beta 1 (TGF1). Through a self-assembled monolayer of polyethylene glycol (PEG), anti-bodies against HA and TGF1 were successfully immobilized on interdigitated electrodes. It produced a robust and sensitive membrane by improving the uniformity, density, and distribution of the antibodies for the biomarkers. Based on impedance sensing, HA and TGF1 were sensitively detected in the ranges of 1-1000 ng/ml. The detection limits of HA and TGF1 reached 0.586 ng/ml and 0.570 ng/ml, respectively. In addition, for the detection of clinical serum samples, the results were in excellent agreement with the tests of HA, type III pre-collagen (PCIII), IV collagen (IV-C), and laminin (LN) that conducted by radio immunoassay for liver fibrosis. It indicated that the approach provided a valuable, universal, and label-free strategy in evaluating liver fibrosis and other chronic diseases for point-of-care diagnostics. Compared to the common immunoassays, electrochemical sensing had attracted more interests due to their inherent advantages, including high sensitivity, time-saving, and eases of operating. It exhibited great potential in point-of-care diagnostics for early detection of various diseases. Through sensitively detecting the serum biomarkers, the electrochemical immunosensor may be useful in detecting the presence of or severe, and probably moderate, fibrosis. The precise diagnostic for a disease is essential for successful treatment and recovery of patients. Therefore, the combination of different biomarkers, serum levels of HA, TGF-β1, would aid clinicians in diagnosing fibrosis during the early stages, eliminating the need for liver biopsy and allowing early treatment, thereby preventing fibrosis progression.