High‐Performance Nucleic Acid Sensors for Liquid Biopsy Applications

Abstract

Circulating tumour nucleic acids (ctNAs) are released from tumours cells and can be detected in blood samples, providing a way to track tumors without requiring a tissue sample. This “liquid biopsy” approach has the potential to replace invasive, painful, and costly tissue biopsies in cancer diagnosis and management. However, a very sensitive and specific approach is required to detect relatively low amounts of mutant sequences linked to cancer because they are masked by the high levels of wild‐type sequences. This review discusses high‐performance nucleic acid biosensors for ctNA analysis in patient samples. We compare sequencing‐ and amplification‐based methods to next‐generation sensors for ctDNA and ctRNA (including microRNA) profiling, such as electrochemical methods, surface plasmon resonance, Raman spectroscopy, and microfluidics and dielectrophoresis‐based assays. We present an overview of the analytical sensitivity and accuracy of these methods as well as the biological and technical challenges they present.

RNA BioMolecular Electronics: towards new tools for biophysics and biomedicine

“…It can be used to discriminate tumor cells easily among billion healthy cells. 112 Blood samples, or other body fluids, can contain circulating free tumor nucleic acids (ctNA) such as circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA) that can be used as cancer biomarkers. 112 The amount of circulating tumor DNA in blood can range from 0.01% up to 1%, 112 an extremely low level compared to wildtype cell-free DNA.…”

“…This, combined with a low frequency of mutations relative to wild-type sequences, makes ctDNA detection in blood or other body fluids challenging. 112 Detecting RNA may be relatively easier because transcription allows RNA to be amplified naturally and produces more RNA for detection. Moreover, RNA provides information about the particular cellular state.…”

Graphene-Based Strategies in Liquid Biopsy and in Viral Diseases Diagnosis

“…The ctNA levels, compared to other circulating free biomarkers (such as CTCs), are detectable early in the bloodstream; therefore, they can be used for the initial tumor detection and the disease monitoring [ 80 ]. To date, several ctNA detection approaches based on fluorescence, SERS spectroscopy, radiochemical, enzymatic approach, chemiluminescence have been investigated [ 46 , 81 , 82 ]. Unfortunately, the detection of these biomarkers is challenging due to their small size and low concentrations in body fluids [ 80 ].…”

The Translational Potential of Electrochemical DNA-Based Liquid Biopsy

“…Smart and very sensitive (fM and aM) electrochemical strategies have been proposed for the determination of NAs (Bettazzi and Palchetti, 2018;Tavallaie et al, 2018;Das and Kelley, 2019;Soda et al, 2019). However, to the best of our knowledge, so far no examples of electrochemical DNA-based platforms have been proposed for the analysis of ctNAs in untreated human blood samples, just after venipuncture.…”