Single‐Molecule Sensing with Nanopore Confinement: From Chemical Reactions to Biological Interactions

Abstract

The nanopore can generate an electrochemical confinement for single-molecule sensing that help understand the fundamental chemical principle in nanoscale dimensions. By observing the generated ionic current, individual bond-making and bond-breaking steps, single biomolecule dynamic conformational changes and electron transfer processes that occur within pore can be monitored with high temporal and current resolution. These single-molecule studies in nanopore confinement are revealing information about the fundamental chemical and biological processes that cannot be extracted from ensemble measurements. In this Concept article, we introduce and discuss the electrochemical confinement effects on single-molecule covalent reactions, conformational dynamics of individual molecules and host-guest interactions in protein nanopores. Then, we extend the concept of nanopore confinement effects to confine electrochemical redox reactions in solid-state nanopores for developing new sensing mechanisms.

Design of an electrochemiluminescence detection system through the regulation of charge density in a microchannel

“…The target recognition reactions adjusted the effective radius and the charge density along the channel structures which in turn altered the ionic transport inside them. [22][23][24][25][26][27][28][29][30] In early reports, articial channels were combined with ECL detection to design new ECL detection systems, where nanochannel structures acted as the gate and attached to the surface of the working electrode. The amount of electroactive material entering the nanochannels depended on the effective radius and the electrostatic interactions between the electroactive materials and the functionalized nanochannels.…”

Nanopore sensors for viral particle quantification: current progress and future prospects

“…One of the important factors that enable the application of nanopore sensors in the characterization and analysis of various molecules is their amenability to surface modification [ 80 ]. Introducing point-mutations onto the surface of nanopores enables controlling the interactions between the engineered nanopore surface with the target analyte [ 128 ], which enables the design and probe of the chemical interactions at the single-molecule level [ 129 ]. In general, a variety of surface modifications are applied to nanopores to increase their stability, change their diameter, minimize their clogging, manipulate their surface charges, reduce nonspecific interactions, increase the analytes’ residence time in the pore, enable interactions with target analytes, and reduce the current recording noise across nanopores [ 130 ].…”

“…Other surface modifications that have been used for modifying the surface of solid-state nanopores include biochemical modification using proteins, lipids, and nucleic acids, covalent modification methods such as plasma-induced graft polymerization, hydrosilylation, spin-coating, and direct crosslinking of functional groups such as spiropyrans or DNA to the pore wall’s surface [ 130 ]. Fluid lipid coatings have been shown to provide significant advantages in sensing proteins and macromolecules [ 129 ]. For example, they are shown to minimize or prevent nonspecific protein adsorption to the nanopore walls, which in turn eliminates clogging.…”

Toward Precision Measurement and Manipulation of Single‐Molecule Reactions by a Confined Space

“…In contrast to the Coulter counter, however, nanopore based approaches exhibit an additional unique feature, which is the unexpectedly significant, nanopore induced strong interaction with nanopore and the single molecule inside . Such properties can not only be used to stabilize the short‐lived intermediates of SMRs in nanopore, but also facilitate and drive thermodynamically unfavorable and/or kinetically sluggish SMRs in bulk systems …”