Graphene Nanomaterial for Biosensors - A Boon for Early Cancer Detection: A Systematic Review

Abstract

Background: Cancer remains the second leading cause of death globally, with approximately 10 million deaths in 2020 according to the World Health Organization [1]. Early detection significantly improves survival rates, with 5-year survival rates exceeding 90% for many cancers when detected at early stages [2]. Conventional diagnostic methods including enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and immunohistochemistry often lack the sensitivity required for detecting low-abundance biomarkers in early-stage cancer [3,4]. Graphene-based nanomaterials have emerged as revolutionary platforms for biosensor development due to their exceptional electrical conductivity (up to 6000 S/cm), large specific surface area (2630 m²/g), and superior electron transfer properties [5,6].

Objectives: To systematically review and synthesize evidence on graphene, graphene oxide (GO), and reduced graphene oxide (rGO)-based biosensors for early cancer detection, evaluating their analytical performance, clinical validation status, and translational potential for point-of-care applications.

Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and IEEE Xplore databases from inception to September 2024. Studies investigating graphene-based biosensors for detecting cancer biomarkers were included. Search terms combined "graphene," "biosensor," and "cancer detection" with appropriate Boolean operators. Two independent reviewers performed screening, data extraction, and quality assessment. Data on biosensor types, target biomarkers, cancer types, limit of detection (LOD), sensitivity, specificity, and clinical validation were extracted and synthesized.

Results: A total of 87 studies met inclusion criteria, encompassing electrochemical (n=52, 59.8%), optical (n=21, 24.1%), field-effect transistor-based (n=10, 11.5%), and other biosensor platforms (n=4, 4.6%). Graphene-based biosensors demonstrated LOD values ranging from 0.1 fg/mL to 100 ng/mL for various cancer biomarkers, representing 10- to 1000-fold improvement over conventional ELISA methods. Breast cancer (n=28), lung cancer (n=19), prostate cancer (n=15), and colorectal cancer (n=12) were most frequently investigated. Protein biomarkers including carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP) were detected with LODs as low as 1 fg/mL. MicroRNA detection achieved LODs of 0.1 fM, and circulating tumor cell detection sensitivity reached 1-5 cells/mL. Clinical validation using patient samples was reported in only 23% (n=20) of studies, with sample sizes ranging from 10 to 156 patients.

Conclusions: Graphene-based biosensors demonstrate exceptional analytical performance with ultra-high sensitivity and low detection limits superior to conventional methods. Electrochemical platforms show the most promise for clinical translation due to simplicity, cost-effectiveness, and miniaturization potential. However, significant challenges remain including lack of standardization, limited large-scale clinical validation, regulatory approval pathways, and manufacturing reproducibility. Future research priorities should focus on prospective multicenter clinical trials, point-of-care device development, multiplexed detection systems, and establishing standardization protocols for clinical implementation.