Abstract
Nanopore-based single-entity detection shows immense potential in sensing and sequencing technologies. Solid-state nanopores permit unprecedented detail while preserving mechanical robustness, reusability, adjustable pore size, and stability in different physical and chemical environments. The transmission electron microscope (TEM) has evolved into a powerful tool for fabricating and characterizing nanometer-sized pores within a solid-state ultrathin membrane. By detecting differences in the ionic current signals due to single-entity translocation through the nanopore, solid-state nanopores can enable gene sequencing and single molecule/nanoparticle detection with high sensitivity, improved acquisition speed, and low cost. Here we briefly discuss the recent progress in the modification and characterization of TEM-fabricated nanopores. Moreover, we highlight some key applications of these nanopores in nucleic acids, protein, and nanoparticle detection. Additionally, we discuss the future of computer simulations in DNA and protein sequencing strategies. We also attempt to identify the challenges and discuss the future development of nanopore-detection technology aiming to promote the next-generation sequencing technology.
Highlights
The capability to achieve single-entity detection has provided considerable progress in medicine and science (Raveendran et al, 2020a)
Nanopores have emerged as the leading single-entity analytical tool for label-free, high-throughput, and low-cost characterization of individual protein molecules, nucleic acids, and nanoparticles (NPs), with a nanometer-sized hole or channel embedded in an ultrathin membrane that separates two chambers containing electrolyte solutions
Many challenges associated with easy clogging in the pores, high translocation speed, and low signal-to-noise ratios (SNRs) are not completely resolved and shall necessitate further research (Wang et al, 2021). In this mini review, we focus on the latest progress in fabrication, characterization, modification, and SNR enhancing strategies of transmission electron microscope (TEM)-fabricated nanopores
Summary
The capability to achieve single-entity detection has provided considerable progress in medicine and science (Raveendran et al, 2020a). Among these solid-state nanopores, introducing nanopores in the thin membranes, such as graphene (Arjmandi-Tash et al, 2016), silicon nitride (SiNx) (Dimitrov et al, 2010), silicon dioxide (SiO2) (Luan et al, 2012), aluminum oxide (Al2O3), and molybdenum disulfide (MoS2) (Graf et al, 2019) has been proved to be advantageous because of their easy modification, controllable pore size, adjustable membrane thickness, and surface charge These unique characteristics could facilitate the enhancing of the spatiotemporal resolution of nanopore sensing and prevent biomolecular clogging in the pore. Many challenges associated with easy clogging in the pores, high translocation speed, and low signal-to-noise ratios (SNRs) are not completely resolved and shall necessitate further research (Wang et al, 2021) In this mini review, we focus on the latest progress in fabrication, characterization, modification, and SNR enhancing strategies of TEM-fabricated nanopores. Future research directions to overcome the challenges in nanopore-based single-entity detection are discussed
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