Sensitive Detection of Single-Nucleotide Polymorphisms by Solid Nanopores Integrated With DNA Probed Nanoparticles.

Single-nucleotide polymorphisms (SNPs) are the abundant forms of genetic variations, which are closely associated with serious genetic and inherited diseases, even cancers. Here, a novel SNP detection assay has been developed for single-nucleotide discrimination by nanopore sensing platform with DNA probed Au nanoparticles as transport carriers. The SNP of p53 gene mutation in gastric cancer has been successfully detected in the femtomolar concentration by nanopore sensing. The robust biosensing strategy offers a way for solid nanopore sensors integrated with varied nanoparticles to achieve single-nucleotide distinction with high sensitivity and spatial resolution, which promises tremendous potential applications of nanopore sensing for early diagnosis and disease prevention in the near future.

Hybridization chain reaction (HCR) for amplifying nanopore signals.

Circulating tumor DNA (ctDNA) in the blood is an important biomarker for noninvasive diagnosis, assessment, prediction and treatment of cancer. However, sensing performance of solid nanopore is limited by the fast kinetics of small DNA targets and unmatched dimensions. Here, we combines hybridization chain reaction (HCR) with nanopore detection to translate the presence of a small DNA target to characteristic nanopore signals of a long nicked DNA polymer. The amplification of nanopore signals obtained by HCR not only overcomes the functional limitation of solid nanopore, but also significantly elevates both selectivity and signal-to-noise ratio, which allows to detect ctDNA at a detection limit of 2.8 fM (S/N = 3) and the single-base resolution. Furthermore, the proposed method can apply in detection of ctDNA of KRAS G12DM in serum sample.

Progress in Solid-state Nanopore-based Analysis Technology / 分析化学

Nanopore technique is a low-cost tool for single-molecule level analysis without the need of label or amplification. The solid nanopores have been widely used in many fields such as chemistry and life sciences due to their advantages such as high stability, good tolerability, controllable size, and easy for modification. The solid nanopores commonly used in recent years are fabricated using two types of materials: membrane and tube. The membrane materials include silicon nitride, two-dimensional materials, aluminium oxide, and polymer membranes. The tube materials mainly include glass capillary and carbon nanotube. This review summarizes and prospects the research progress of different solid nanopores.

Application of Single Solid State Nanopore / Nanochannel Based on Polymer Membrane and Glass Nanopipette in Analytical Chemistry / 分析化学

Nanopore / nanochannel sensing technique drawing more attention in analytical chemistry due to its unique advantages and the fabricated electrochemical sensors and electrochemical responsive gates have been widely used for more target detection, including single molecule protein and DNA sequencing. Nanopore /nanochannel that used for fabricating electrochemical detection system is mainly divided into biological nanopore and solid state nanopore, and among them, solid state nanopore / nanochannel has a wide range of application due to its inherent properties, such as easy for modification, good mechanical property and stability. Resistive pulse sensing and current-voltage curves (ion current rectification) are two main methods of nanopore / nanochannel sensing technique used for target analysis, so in this review, we introduced the fundamentals and applications of nanopore sensing technique based on the above two methods. In addition, we concluded the application and development of single state nanopore / nanochannel in recent years, and also gave a brief look at the future challenges and prospects in the development of this field.