Label-Free Nucleic Acid Biosensing Using Nanomaterial-Based Localized Surface Plasmon Resonance Imaging: A Review

In the past couple of decades, the development of plasmonic nanosensors underwent rapid progress in the fields of fabrication, integration, and realized applications. Localized surface plasmon resonance imaging (LSPRi) promises the possibility of high-throughput biomolecule sensing integrated into miniaturized point-of-care devices. This paper aims to provide a critical review of the LSPRi-compatible sensor nanofabrication technologies and compare the most crucial characteristics of implemented LSPRi sensors, focusing on label-free nucleic acid detection. Besides the optimization of fabrication, a practical sensor needs meticulous design regarding the protocols used as well, and the challenging area of label-free DNA/RNA sensing thus provides a reasonable basis for benchmarking sensor capabilities. All previously reported LSPRi-compatible nucleic acid sensors are critically evaluated and compared based on their fabrication technologies (size and uniformity of the sensor area) and sensor performance (refractive index sensitivity, detection limit, and dynamic range). The most relevant factors to consider upon selection of a fabrication technology and the importance of proper DNA immobilization/hybridization conditions are also discussed in detail.