# Addressing the Challenges of Solid-State Nanopores: Strategies for Performance Enhancement

## TL;DR

This paper reviews strategies to improve solid-state nanopore sequencing, a promising DNA sequencing technology, by addressing challenges like noise and clogging.

## Contribution

The paper systematically examines and categorizes strategies to enhance the performance of solid-state nanopores for sequencing applications.

## Key findings

- Ultrathin materials like graphene improve spatial resolution in nanopore sequencing.
- Surface functionalization techniques reduce pore clogging and increase specificity.
- Machine learning and material innovations help suppress electrical noise in sequencing signals.

## Abstract

Solid-state nanopore sequencing, a key third-generation sequencing technology, offers considerable potential for genomics and diagnostics due to its long read lengths, real-time detection, and amplification-free operation. The technology identifies DNA sequences by measuring characteristic changes in ionic current as single-stranded DNA translocates through a nanoscale pore. However, its practical development faces challenges including limited spatiotemporal resolution, pore clogging from nonspecific adsorption, and significant electrical noise. This review systematically examines strategies developed to address these limitations. We discuss the use of ultrathin two-dimensional materials such as graphene and molybdenum disulfide to improve spatial resolution, and methods to modulate DNA translocation through optimized solution conditions, pore geometry, surface charge engineering, and bio-solid hybrid pore designs. Furthermore, we detail noise suppression strategies targeting key sources like thermal noise, 1/f noise, and dielectric noise. These approaches encompass careful material selection, surface coatings, innovations in chip and amplifier design, and machine learning–based signal processing. The review also outlines surface functionalization techniques that reduce clogging and enhance analytical specificity. While challenges remain, continued convergence of materials science, nanofabrication, and data science is advancing solid-state nanopore technology toward reliable, high-precision sequencing platforms, promising to significantly impact personalized medicine and biological research.