Single-Entity Detection With TEM-Fabricated Nanopores

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.

Plasmonic Photochemistry as a Tool to Prepare Metallic Nanopores with Controlled Diameter for Optimized Detection of Single Entities

“…It is important to stress that, although the preparation of a single nanopore with a diameter of a few nm has already been reported in the literature, [9,[56][57][58][59][60] the controllable preparation of a metallic (plasmonic) nanopore array with a diameter between tens of nm down to 5 nm is still very challenging. [61] The method proposed here enables a controlled diameter reduction of the nanopore (1 nm min −1 with Ag growth) both in single pore configuration and in arrays with arbitrary pores shapes and arrangements.…”

Nanoscale Luminescence Imaging/Detection of Single Particles: State-of-the-Art and Future Prospects

“…The coreactant pathway is then divided into two types: one is oxidative−reductive ECL, and the other is reductive−oxidation ECL. The coreactant ECL exhibits several superiorities as compared to the annihilation ECL: (1) generation of ECL can be achieved in aqueous media at low potentials; (2) a single step oxidation/reduction ECL process that can be used for luminophores which exhibit only one reversible oxidation or reduction; (3) ) was the first coreactant discovered for ECL studies. Later, Ru(bpy) 3 2+ was utilized with C 2 O 4 2− to construct a new system for ECL studies as shown in eqs 7−13 in Figure 1d.…”

“…For the particles, each of them has distinct surface chemistry, lattice defects, atomic arrangement, morphology, and chemical composition, which results in considerably different activities during chemical and electrochemical processes . Ensemble recordings only measure the average response of various particles, which denies access to the microscopic picture at a single entity level. , Therefore, single particle detection is an overarching measurement concept that is driven by a desire to understand heterogeneity (both spatially and among population), recording of faster processes, exploring the underlying mechanisms, optimizing the reactions performance/ yields/ outcomes, improvement of analytical detection, and addressing emerging questions from inherently interdisciplinary fields including catalysis and surface science, , cellular biology, drug delivery, and so on. , …”

“…2 Ensemble recordings only measure the average response of various particles, which denies access to the microscopic picture at a single entity level. 3,4 Therefore, single particle detection is an overarching measurement concept that is driven by a desire to understand heterogeneity (both spatially and among population), recording of faster processes, exploring the underlying mechanisms, optimizing the reactions performance/ yields/ outcomes, improvement of analytical detection, and addressing emerging questions from inherently interdisciplinary fields including catalysis and surface science, 5,6 cellular biology, 7 drug delivery, and so on. 8,9 Traditionally, reaction mechanisms, performance, kinetics, and chemical (photochemical, electrochemical, photoelectro-chemical) properties are optimized and measured at the bulk level, wherein chemical systems are composed of ensemble/ larger collection of particles.…”

Large-scale production of polyimide micropore-based flow cells for detecting nano-sized particles in fluids

“…In the past two decades, nanopores have been discovered as an effective and reliable tool for counting molecules. 44,45 Our goal was to nd alternate materials and processes to shorten production times while lowering costs and improving signal quality. We were able to fabricate micropores in a single step, which is the rst time a micropore has been opened in a PI membrane using a femtosecond laser.…”