Molecular Recognition Materials Synthesized Based on Small molecules, DNA, and Imprinted Polymers for Bioanalytical Applications

The development of sensitive, convenient, and cost-effective methods for detecting disease biomarkers is very important for meeting the growing demand for early clinical diagnosis. Additionally, the detection of disease biomarkers at ultralow concentrations is very important for disease prevention and treatment and posttreatment rehabilitation. However, current ultrasensitive detection strategies often require sophisticated instruments or complex sample pretreatments that may not be available in laboratories that have limited resources. Therefore, we focused on assembling various inorganic and organic building blocks to synthesize integrated multifunctional materials and improve the performance of analytical systems and methods.
Boronic acid (BA), which is a small synthetic molecule, was conjugated in nanopores of dendritic fibrous nanosilica (DFNS) through a high-efficiency click reaction and a temperature-responsive polymer intermediate. The developed boronate affinity materials provide more affinity sites for cis-diol enrichment, and the well-defined narrow pores of DFNS provide highly selective affinity binding toward low-molecular-weight cis-diols. Moreover, a BA derivative, 4-vinylphenylboronic acid (VPBA), was employed to develop a fluorescence technique for monitoring molecular imprinting in real time and gaining insights into molecular recognition mechanisms. Molecularly imprinted polymers (MIPs) were synthesized using Alizarin Red S (ARS) as the template and VPBA as the functional monomer. The fluorogenic VPBA–ARS complex enables molecular imprinting signaling. The resulting MIPs also exhibited specific binding toward ARS and served as a fluorescent probe for detecting Cu2+ ions without any tedious sample preparation.
Fluorescein-labeled single-stranded nucleic acid was directly adsorbed on polydopamine-functionalized DFNS to develop a “turn-on” fluorescence biosensor, which functions using an adsorption–quenching–recovery mechanism that enables the simple and highly efficient detection of nucleic acid biomarkers. A proof of concept was demonstrated using microRNA as a biomarker model.
Nucleic acid amplification and MIPs were employed to achieve the low-cost, simple, and reliable detection and quantification of protein biomarkers. MIPs were prepared using Pickering emulsion polymerization and DFNS as a stabilizer to produce surface-accessible binding sites for protein biomarkers. The MIP-induced protein recognition was amplified by the hybridization chain reaction and translated into an easily detectable fluorescence signal.