Electrochemiluminescence biosensors for detection of cancer biomarkers in biofluids: Principles, opportunities, and challenges

This review discusses electrochemiluminescence, ECL, bioassays and biosensors for cancer biomarkers detection with high analytical sensitivity and requirements for early-stage disease diagnosis. Electrochemiluminescence or electrogenerated chemiluminescence has the advantages of high sensitivity, the ability to resolve several targets based on different redox potentials or emission wavelengths, and exquisite control over the light emission in space and time, making it a powerful approach for detecting early-stage cancer biomarkers. Simple and cost-effective ECL systems enable accurate, selective, and sensitive detection of cancer biomarkers in a variety of body fluids. Coupling ECL components with nanomaterials can yield limits of detection that enable the disease to be detected before clinical symptoms appear and enable multiplexed assays that improve true-positive and true-negative rates, thereby increasing their clinical utility. Recent trends in the use of micro- and nanoparticles are discussed, with a focus on sensor platforms based on antibodies, microRNA, enzymes, and "synthetic antibodies" or molecularly imprinted polymers (MIPs). Various approaches are covered label-free and labeled detection (competitive, sandwich, and displacement assay formats) as well as luminescence detection strategies (signal-on, signal-off, and signal-switch modes). Novel ECL sensor platforms such as bipolar electrodes, paper-based electrodes, and microfluidic chips and their emerging applications for single cell, single biomarker, and multiplex biomarker detection are described. In addition, the operating principles of ECL, commercial applications, advantages, limitations, and ways to improve the strategies and performance of ECL technology are considered.