The importance of nano-bio interfacial design in the sensing performance of nanoparticle-based affinity biosensors

Biosensors with good sensing performances with regards to high sensitivity, specificity, shorter response time, the ability to be multiplexed, excellent stability and reproducibility, are always in high demand. As modern biosensors are often fabricated using bioreceptors immobilized on nanoparticles to achieve efficient signal transduction or easier handling, the nanoparticle-bioreceptor (nano-bio) interface has a significant impact on the final sensing metrics. However, the role of nano-bio interfaces in sensing performance could be better understood, to facilitate the rational design of high performing nano-bio based devices. Herein, we aim to provide some basic rules and considerations to optimize nano-bio interfaces to achieve better detection performance when fabricating biosensors. The impact of the nano-bio interfaces on sensing characteristics is discussed from the perspective of bioreceptor-analyte interaction. Four interfacial parameters are included in this review: (1) the conformation of bioreceptors, (2) the coverage of the bioreceptors, (3) composition of mixed ligands, such as bioreceptors and other functional molecules and (4) spatial distribution of bioreceptors on nanoparticle surfaces. Methods to tailor these four interfacial factors are systematically investigated. In parallel, how these tailored nano-bio factors improve the sensing performances is emphasized with corresponding biosensor examples. The analytical methods for characterization of nano-bio interfaces are summarized, particularly at the single particle level. Additionally, the integration of artificial intelligence (AI) with nano-bio interfaces is discussed, highlighting how AI can improve nano-bio interfacial design. Finally, future perspectives on the role of nano-bio interfacial design in enhancing sensing capabilities are presented. This review aims to elucidate the relationship between nano-bio interfacial factors and sensing performances, as well as strategies for achieving precisely controlled nano-bio interfaces, which facilitates the rational design of high-performance biosensors.