Solid-State Nanopore Sensors with Enhanced Sensitivity through Nucleic Acid Amplification

Abstract

Solid-state nanopores have wide applications in DNA sequencing, energy conversion and storage, seawater desalination, sensors, and reactors due to their high stability, controllable geometry, and a variety of pore-forming materials. Solid-state nanopore sensors can be used for qualitative and quantitative analyses of ions, small molecules, proteins, and nucleic acids. The combination of nucleic acid amplification and solid-state nanopores to achieve trace detection of analytes is gradually attracting attention. This review outlines nucleic acid amplification strategies for enhancing the sensitivity of solid-state nanopore sensors by summarizing the articles published in the past 10 years. The future development prospects and challenges of nucleic acid amplification in solid-state nanopore sensors are discussed. This review helps readers better understand the field of solid-state nanopore sensors. We believe that solid-state nanopore sensors will break through the bottleneck of traditional detection and become a powerful single-molecule detection platform.

Local Electric Potential-Driven Nanofluidic Ion Transport for Ultrasensitive Biochemical Sensing

“…Inspired by nature, artificial nanofluidic biosensors have been demonstrated as powerful tools for low-cost, rapid, ultrasensitive, and label-free detection of multiple biomolecule species including ions, small molecules, nucleic acids, proteins, cell types, and viruses. − They have done so by specific interactions of recognition probes and targets at the sensing interface followed by transduction of these interactions into a measurable ionic current signal driven by a certain voltage. − Specifically, the nanofluidic membrane surface is modified with target-specific probes capable of recognizing and capturing a target molecule, which results in the change of the membrane’s surface charge, − surface wettability, − and/or efficient size − of the nanofluidic channels. All these characters would affect the membrane resistance and, thus, increase or decrease ionic current signal of the biosensors. − However, probe–target interactions for some targets with few charges or low concentration have minimal effect on these factors, which result in unchanged system resistance and limited sensitivity.…”

Mathematical Approximation for Quantifying Noise Level in Silicon- and Nonsilicon-Based Chips for DNA Detection

“…Over the past decade, the exploration of nanopore membranes for DNA molecule sensing has experienced considerable growth in the scientific literature. , Three distinct types of nanopores currently exist, namely, biological pores; solid-state nanopores utilizing materials such as silicon, Al 2 O 3 , TiO 2 , and graphene chips; and hybrid nanopores combining solid-state and biological components, including nonsolid-state nanopores like graphene pores . It is noteworthy that solid-state nanopores while exhibiting certain advantages demonstrate relatively lower sensitivity in molecule detection compared to biological pores, primarily attributed to the thicker membrane leading to surface charge accumulation and reducing spatial resolution .…”

“…As previously mentioned, nanopore-based sensors demonstrate efficacy in detecting small molecules. 13 The nanopore's dimensions, typically ranging between 5 and 10 nm, play a pivotal role in this process. As ions traverse from one chamber to another and encounter an electrode with an opposing charge, the ammeter records a current directly proportional to the number of ions traversing the pore.…”

Solid-State Nanopore/Nanochannel Sensors with Enhanced Selectivity through Pore-in Modification

“…Enhancing sensitivity and specificity is the key to optimizing the performance of solid-state nanopore/nanochannel sensors . In a recent Perspective, we have outlined solid-state nanopore sensors with enhanced sensitivity through nucleic acid amplification …”