Biosensors Based on Bivalent and Multivalent Recognition by Nucleic Acid Scaffolds

Abstract

Several biological macromolecules adopt bivalent or multivalent interactions to perform various cellular processes. In this regard, the development of molecular constructs presenting multiple ligands in a specific manner is becoming crucial for the understanding of multivalent interactions and for the detection of target macromolecules. Nucleic acids are attractive molecules to achieve this goal because they are capable of forming various, structurally well-defined 2D or 3D nanostructures and can bear multiple ligands on their structures with precisely controlled ligand–ligand distances. Thanks to the features of nucleic acids, researchers have proposed a wide range of bivalent and multivalent binding agents that strongly bind to target biomolecules; consequently, these findings have uncovered new biosensing strategies for biomolecule detection. To date, various bivalent and multivalent interactions of nucleic acid architectures have been applied to the design of biosensors with enhanced sensitivity and target accuracy. In this review, we describe not only basic biosensor designs but also recently designed biosensors operating through the bivalent and multivalent recognition of nucleic acid scaffolds. Based on these designs, strategies to transduce bi- or multivalent interaction signals into readable signals are discussed in detail, and the future prospects and challenges of the field of multivalence-based biosensors are explored.

A High-Avidity, Thermostable, and Low-Cost Synthetic Capture for Ultrasensitive Detection and Quantification of Viral Antigens and Aerosols

“…Conversely, the 2–6 binding domain design of LCB1-BSA ensures consistent 1–6 binding site availability, creating high-density regions that optimize multivalent binding and analyte distribution (Figure C). While other techniques have utilized chemical functionalization of the LFA membrane and capture to induce the correct orientation of aptamer or antibody captures, LCB1-BSA can be seamlessly integrated without any procedural modifications because the intermolecular forces governing its immobilization are the same for antibodies. − Just so, we believe our results here have a great degree of transferability to a full-strip LFA.…”

Bivalent System of Deoxyribozymes for Efficient RNA Cleavage

“…Many biomolecular components use multivalent interactions to overcome weak monovalent, non-covalent interactions and to strengthen their biomolecular interactions, allowing the occurrence of desired biological processes [14]. Antibodies use two antigen recognition parts for immune response; viruses utilize multivalent interactions to attach themselves to host cells (Figure 1).…”