Piecing together the puzzle: nanopore technology in detection and quantification of cancer biomarkers

Abstract

Cancer is the result of a multistep process, including various genetic and epigenetic alterations, such as structural variants, transcriptional factors, telomere length, DNA methylation, histone-DNA modification, and aberrant expression of miRNAs. These changes cause gene defects in one of two ways: (1) gain in function which shows enhanced expression or activation of oncogenes, or (2) loss of function which shows repression or inactivation of tumor-suppressor genes. However, most conventional methods for screening and diagnosing cancers require highly trained experts, intensive labor, large counter space (footprint) and extensive capital costs. Consequently, current approaches for cancer detection are still considered highly novel and are not yet practically applicable for clinical usage. Nanopore-based technology has grown rapidly in recent years, which have seen the wide application of biosensing research to a number of life sciences. In this review paper, we present a comprehensive outline of various genetic and epigenetic causal factors of cancer at the molecular level, as well as the use of nanopore technology in the detection and study of those specific factors. With the ability to detect both genetic and epigenetic alterations, nanopore technology would offer a cost-efficient, labor-free and highly practical approach to diagnosing pre-cancerous stages and early-staged tumors in both clinical and laboratory settings.

Increased dwell time and occurrence of dsDNA translocation events through solid state nanopores by LiCl concentration gradients

“…Nanopore technology has the potential for detecting and characterizing biomolecules including DNA , RNA and proteins , viruses , and polysaccharides . As biomolecules pass through the nanopore, they cause ionic current blockages, which can be analyzed to characterize physical and chemical properties of the biomolecule . Although both biological and solid‐state nanopores are effective in biomolecular detection, solid‐state nanopores have the added benefit of increased durability and size tuning …”

Nanopore Technology and Its Applications in Gene Sequencing

“…In the human genome, DNA methylation is an epigenetic modification, including 5-methylcytosine (5-mC), N4-methylcytosine (4-mC), and N6-methyladenine (6-mA) [84]. In mammalian cells, CpG methylation can directly or indirectly suppress gene expression [85]. Moreover, the degree of abnormal methylation (high or low methylation) is associated with some cancers.…”

Nanopore-Based Single-Biomolecule Interfaces: From Information to Knowledge

“…Therefore, each ionic current response contains small ionic fluctuations, which offer continuous snapshots of the confined single molecule. After statistical time-domain analyses of duration, current amplitude, and occurrence of characteristic ionic current events as well as the frequency domain decomposition, differences in the features of single molecules, such as chemical properties, conformational changes, and charge distributions, could be detected. ,,,− Therefore, nanopore-based single-molecule analysis possesses features such as high temporal resolution, high throughput, in situ detection, and label-free operation, which meets the requirements for measuring the dynamic and stochastic behaviors of single molecules within biological environments. − , …”