Single molecule sensing with solid-state nanopores: novel materials, methods, and applications

Abstract

This tutorial review will introduce and explore the fundamental aspects of nanopore (bio)sensing, fabrication, modification, and the emerging technologies and applications that both intrigue and inspire those working in and around the field. Although nanopores can be classified into two categories, solid-state and biological, they are essentially two sides of the same coin. For instance, both garner popularity due to their ability to confine analytes of interest to a nanoscale volume. Due to the vast diversity of nanopore platforms and applications, no single review can cover the entire landscape of published work in the field. Therefore, in this article focus will be placed on recent advancements and developments taking place in the field of solid-state nanopores. It should be stated that the intention of this tutorial review is not to cite all articles relating to solid-state nanopores, but rather to highlight recent, select developments that will hopefully benefit the new and seasoned scientist alike. Initially we begin with the fundamentals of solid-state nanopore sensing. Then the spotlight is shone on the sophisticated fabrication methods that have their origins in the semiconductor industry. One inherent advantage of solid-state nanopores is in the ease of functionalizing the surface with a range of molecules carrying functional groups. Therefore, an entire section is devoted to highlighting various chemical and bio-molecular modifications and explores how these permit the development of novel sensors with specific targets and functions. The review is completed with a discussion on novel detection strategies using nanopores. Although the most popular mode of nanopore sensing is based upon what has come to be known as ionic-current blockade sensing, there is a vast, growing literature based around exploring alternative detection techniques to further expand on the versatility of the sensors. Such techniques include optical, electronic, and force based methods. It is perhaps fair to say that these new frontiers have caused further excitement within the sensing community.

Rapid Ultrasensitive Single Particle Surface-Enhanced Raman Spectroscopy Using Metallic Nanopores

“…the cell membrane where they are used for ion transport. They can also be synthetically produced using either biological building blocks and/or solid-state semiconductor processing materials 5 . The general underlying theme is that the nanopore is embedded in an ultra-thin membrane with a similar thickness to that of the lateral dimensions of the nanopore.…”

“…The predominant method used for the detection of a translocation event (i.e. passing of analytes through the nanopore) relies on electrical means using what is typically termed ionic current blockade sensing 5 (ESI Figure 1). …”

Effects of rotational symmetry breaking in polymer-coated nanopores

“…1 Artificial solid-state nanopores enable the detection of single molecules via changes in ionic currents through 2,3 or across 4 them. Nanopores can also be used as molecular filtration devices, with applications from separating biomolecules to water purification.…”

SSB Binding to Single-Stranded DNA Probed Using Solid-State Nanopore Sensors

“…This is performed using solid state nanopore sensors which encompass a thin, mechanically stable membrane made from materials such as silicon nitride (SiN x ) and features a nanometre sized pore (typical diameter ~ 5 25 nm). 7,8 Built into a fluidic cell, the membrane separates the cell into two compartments, with one electrode in each. Fluid and ion transport can only occur through the nanopore.…”