Application of smart-responsive hydrogels in nucleic acid and nucleic acid-based target sensing: A review

In recent years, nucleic acid-related sensing and detection have become essential in clinical diagnostics, treatment and genotyping, especially in connection with the Human Genome Project and the COVID-19 pandemic. Many traditional nucleic acid-related sensing strategies have been employed in analytical chemistry, including fluorescence, colorimetric and chemiluminescence methods. However, their key limitation is the lack of understanding of the interaction during analysis, particularly at the 3D matrix level close to biological tissue. To address this issue, smart-responsive hydrogels are increasingly used in biosensing due to their hydrophilic and biocompatible properties. By combining smart-responsive hydrogels with traditional nucleic acid-related sensing, biological microenvironments can be mimicked, and targets can be easily accessed and diffused, making them ideal for nucleic acid sensing. This review focuses on utilizing smart-responsive hydrogels for nucleic acid-related sensing and detection, including nucleic acid detection, other nucleic acid-based analyte detection and nucleic acid-related sensing platforms applying nucleic acid as sensing tools in hydrogels. Additionally, the analytical mechanisms of smart-responsive hydrogels with the combination of various detection platforms such as optical and electrochemical techniques are described. The limitations of using smart-responsive hydrogels in nucleic acid-related sensing and proposed possible solutions are also discussed. Lastly, the future challenge of smart-responsive hydrogels in nucleic acid-related sensing is explored. Smart-responsive hydrogels can be used as biomimetic materials to simulate the extracellular matrix, achieve biosensing, and exhibit great potential in nucleic acid-related sensing. They serve as a valuable complement to traditional detection and analytical methods.