# The evolution of nanopore measurements: from biological out-of-plane pores to plastic in-plane pores

## TL;DR

This paper reviews the development of nanopore sensing technology, comparing biological and solid-state nanopores and their in-plane and out-of-plane configurations for detecting single molecules without labels.

## Contribution

The paper provides a comprehensive review of the evolution of nanopore configurations and materials for single-molecule detection.

## Key findings

- Biological nanopores are dominant due to their small size, while solid-state nanopores offer stability and versatility.
- In-plane nanopores fabricated in plastics via replication technologies represent a significant advancement.
- Signal-to-noise ratio is influenced by pore size relative to the target molecule and the material used.

## Abstract

Nanopore sensing provides an ideal strategy for the label-free detection of single molecules in a variety of application scenarios. Working under the principle of resistive pulse sensing (RPS), nanopores consist of constrictions with sub-100 nm dimensions to enable single-molecule resolution by matching pore size to target dimensions (scaling); the optimal signal-to-noise ratio (SNR) results when the electrically biased pore is comparable in size to the molecule to be analyzed. When single molecules are electrokinetically transported through such remarkably small pores, they temporarily disturb the flux of ions moving through them, generating unique signals. These signals vary based upon the molecules' shape, size, orientation, and other physicochemical properties. Nanopores are generally divided into two main categories owing to their fabrication approach and material: biological and solid state. While biological nanopores have been the dominant sensor format due to their exceptionally small size, solid-state nanopores can demonstrate high performance characteristics attributed to their rigidity, stability, and high versatility in shape, material, and configuration. This review will explore the state-of-the-art in biological and solid-state nanopores and their abilities to detect and identify single biomolecules in a label-free manner. We will also review two topographical configurations of nanopore sensors; in-plane and out-of-plane sensors. The evolution of nanopore sensing will be reviewed, starting with out-of-plane biological sensors and progressing to in-plane sensors fabricated in plastics via replication technologies.

A comprehensive review of in-plane and out-of-plane nanopore configurations for label-free single molecule detection is discussed herein. Also reviewed is a description of varied materials for both nanopore configurations and effects on target SNR.