Gold nanoparticles (GNPs) have been widely utilized to develop various biosensors for molecular diagnosis, as they can be easily functionalized and exhibit unique optical properties explained by plasmonic effects. These unique optical properties of GNPs allow the expression of an intense color under light that can be tuned by altering their size, shape, composition, and coupling with other plasmonic nanoparticles. Additionally, they can also enhance other optical signals, such as fluorescence and Raman scattering, making them suitable for biosensor development. In this review, we provide a detailed discussion of the currently developed biosensors based on the aforementioned unique optical features of GNPs. Mainly, we focus on four different plasmonic biosensing methods, including localized surface plasmon resonance (LSPR), surface-enhanced Raman spectroscopy (SERS), fluorescence enhancement, and quenching caused by plasmon and colorimetry changes based on the coupling of GNPs. We believe that the topics discussed here are useful and able to provide a guideline in the development of novel GNP-based biosensors in the future.

Flexible electrochemical biosensors are studied hugely because of tremendous advantages including the fast response, high sensitivity, inherent miniaturization, convenient operation, and portability which are suitable for wearable biosensors.

Controlling the selective one‐to‐one conjugation of RNA with nanoparticles is vital for future applications of RNA nanotechnology. Here, the monofunctionalization of a gold nanoparticle (AuNP) with a single copy of RNA is developed for ultrasensitive microRNA‐155 quantification using electrochemical surface‐enhanced Raman spectroscopy (EC‐SERS). A single AuNP is conjugated with one copy of the packaging RNA (pRNA) three‐way junction (RNA 3WJ). pRNA 3WJ containing one strand of the 3WJ is connected to a Sephadex G100 aptamer and a biotin group at each arm (SEPapt/3WJ/Bio) which is then immobilized to the Sephadex G100 resin. The resulting complex is connected to streptavidin‐coated AuNP (STV/AuNP). Next, the STV/AuNP–Bio/3WJa is purified and reassembled with another 3WJ to form a single‐labeled 3WJ/AuNP. Later, the monoconjugate is immobilized onto the AuNP‐electrodeposited indium tin oxide coated substrate for detecting microRNA‐155 based on EC‐SERS. Application of an optimum potential of +0.2 V results in extraordinary amplification (≈7 times) of methylene blue (reporter) SERS signal compared to the normal SERS signal. As a result, a highly sensitive detection of 60 × 10⁻¹⁸ m microRNA‐155 in 1 h in serum based on monoconjugated AuNP/RNA is achieved. Thus, the monofunctionalization of RNA onto nanoparticle can provide a new methodology for biosensor construction and diverse RNA nanotechnology development.