Opportunities, Challenges, and Prospects in Electrochemical Biosensing of Circulating Tumor DNA and Its Specific Features

Abstract

Nowadays, analyzing circulating tumor DNA (ctDNA), a very small part of circulating free DNA (cfDNA) carried by blood, is considered to be an interesting alternative to conventional single-site tumor tissue biopsies, both to assess tumor burden and provide a more comprehensive snapshot of the time-related and spatial heterogeneity of cancer genetic/epigenetic scenery. The determination of ctDNA and/or mapping its characteristic features, including tumor-specific mutations, chromosomal aberrations, microsatellite alterations, and epigenetic changes, are minimally invasive, powerful and credible biomarkers for early diagnosis, follow-up, prediction of therapy response/resistance, relapse monitoring, and tracking the rise of new mutant subclones, leading to improved cancer outcomes This review provides an outline of advances published in the last five years in electrochemical biosensing of ctDNA and surrogate markers. It emphasizes those strategies that have been successfully applied to real clinical samples. It highlights the unique opportunities they offer to shift the focus of cancer patient management methods from actual decision making, based on clinic-pathological features, to biomarker-driven treatment strategies, based on genotypes and customized targeted therapies. Also highlighted are the unmet hurdles and future key points to guide these devices in the development of liquid biopsy cornerstone tools in routine clinical practice for the diagnosis, prognosis, and therapy response monitoring in cancer patients.

Current status of ctDNA in precision oncology for hepatocellular carcinoma

“…The device incorporates immobilized DNA as a molecular recognition element on the electrode surface. The introduction of nanostructured materials as an interfacial film enables improved recognition capability and increased signal output intensity [50,51]. A summary and comparison of all these technologies are shown in Table 2.…”

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives

“…Finally, other approaches are currently emerging to overcome sequencing technologies biases, such as plasmonic nanoparticles used in Surface-Enhanced Raman Scattering (SERS), mass spectrometry based assays and electrochemical biosensor technologies [ 7 , 21 , 22 , 23 ].…”

Nanotechnology Strategies for the Analysis of Circulating Tumor DNA: A Review

“…The high specificity of electrochemical biosensors relies on a special combination between capture probes and target DNA molecules. Currently, the reported capture probes in electrochemical biosensors involve ssDNA, DNA tetrahedron, and PNA [57]. The PNA probe has a higher specificity due to its increased thermal stability compared with that of the DNA probe [58][59][60][61].…”

“…Nanomaterials-based strategies for detection and analysis of circulating tumor DNA (ctDNA). This figure shows the beads, emulsion, amplification, magnetics (BEAMing) method, modified fromDressman et al, 2003 [27]; the polymerase chain reaction and surface-enhanced Raman spectroscopy (PCR-SERS) method, modified from Wee et al, 2016[42]; the suspension array method, modified from Chen et al, 2019[47]; Fe-Au nanoparticle-coupling strategy, modified from Hu et al, 2018[55]; the electrochemical DNA biosensor, modified from Campuzano et al, 2019[57]; and microfluidics method, modified from Ou et al, 2019[76].…”