Gold Nanoparticle-Based Nucleic Acid Detection Techniques

Gold nanoparticles (AuNPs) offer a versatile platform for the detection of specific nucleic acid sequences by combining their unique optical properties with high‐density oligonucleotide functionalisation. The underlying principle relies on controlled assembly or disassembly of AuNPs upon hybridisation events, which can be monitored by colourimetric shifts, fluorescence changes or surface‐enhanced Raman scattering. Advances in conjugation chemistries—such as classical thiol–gold bonding and novel poly(T/U) tag approaches—have streamlined the preparation of stable spherical nucleic acids (SNAs) carrying DNA or RNA probes. Rapid microwave‐assisted protocols now enable one‐step attachment of both short and long nucleic acid strands, expanding applications to CRISPR/Cas9 guide RNA assays, viral fragment detection and rolling‐circle amplification products. These nanoprobes have found utility in point‐of‐care diagnostics, genotyping, mutation analysis and multiplexed pathogen screening. Ongoing research addresses critical factors such as colloidal stability under varying pH or ionic strength, non‐specific adsorption by buffer components or proteins, and signal amplification through plasmonic or enzymatic reporters, thereby improving sensitivity, specificity and robustness for in‐field and clinical use.

Research from Nature Portfolio

Fast microwave‐assisted synthesis of DNA/RNA–AuNP conjugates has demonstrated that both thiolated and non‐thiolated oligonucleotides can be immobilised within minutes under heating‐dry conditions. This method yields SNAs capable of binding long RNA fragments—including CRISPR/Cas9 single guide RNAs and SARS-CoV-2 sequences—and supports downstream biosensing and delivery applications with enhanced simplicity and universality. Complementing this, studies on poly-adenine-anchored DNA describe how polyA–AuNP conjugates achieve high oligonucleotide loading and upright probe conformation for improved hybridisation. Systematic fluorescence assays reveal the temperature, ionic strength and solvent conditions that govern DNA dissociation, guiding assay design for stable, tunable plasmonic biosensors.

Gold Nanoparticle-Based Nucleic Acid Detection Techniques publication trend

The graph below shows the total number of articles in gold nanoparticle-based nucleic acid detection techniques across all publications each year (not limited to Nature Index journals).

Technical terms

Localised surface plasmon resonance (LSPR): Collective oscillation of conduction electrons in AuNPs that produces a strong, size‐ and environment‐dependent optical absorbance peak.

Spherical nucleic acid (SNA): A nanoparticle core densely functionalised with radially oriented oligonucleotides, enhancing cellular uptake and hybridisation kinetics.

Surface‐enhanced Raman spectroscopy (SERS): Amplification of Raman scattering signals by molecules near plasmonic nanostructures, enabling ultrasensitive detection.

Thiol–gold bond: A covalent linkage formed between sulphur atoms in thiolated oligonucleotides and gold surfaces, providing stable probe attachment.

Aptamer: A short, single‐stranded nucleic acid selected for high affinity and specificity to a target molecule, used as a recognition element in biosensors.

References

1. Fast microwave heating-based one-step synthesis of DNA and RNA modified gold nanoparticles. Nature Communications (2022).
2. Quantitative investigation of the poly-adenine DNA dissociation from the surface of gold nanoparticles. Scientific Reports (2015).
3. Development of gold nanoparticles biosensor for ultrasensitive diagnosis of foot and mouth disease virus. Journal of Nanobiotechnology (2018).
4. Good's buffers have various affinities to gold nanoparticles regulating fluorescent and colorimetric DNA sensing. Chemical Science (2020).
5. Nanoparticles based DNA conjugates for detection of pathogenic microorganisms. International Nano Letters (2016).