PEGylated Artificial Antibodies: Plasmonic Biosensors with Improved Selectivity

Abstract

Molecular imprinting, which involves the formation of artificial recognition elements or cavities with complementary shape and chemical functionality to the target species, is a powerful method to overcome a number of limitations associated with natural antibodies. An important but often overlooked consideration in the design of artificial biorecognition elements based on molecular imprinting is the nonspecific binding of interfering species to noncavity regions of the imprinted polymer. Here, we demonstrate a universal method, namely, PEGylation of the noncavity regions of the imprinted polymer, to minimize the nonspecific binding and significantly enhance the selectivity of the molecular imprinted polymer for the target biomolecules. The nonspecific binding, as quantified by the localized surface plasmon resonance shift of imprinted plasmonic nanorattles upon exposure to common interfering proteins, was found to be more than 10 times lower compared to the non-PEGylated counterparts. The method demonstrated here can be broadly applied to a wide variety of functional monomers employed for molecular imprinting. The significantly higher selectivity of PEGylated molecular imprints takes biosensors based on these artificial biorecognition elements closer to real-world applications.

Single Molecule Force Spectroscopy to Compare Natural versus Artificial Antibody–Antigen Interaction

“…We have previously demonstrated the feasibility of molecular imprinting on gold nanostructures, which serve as nanotransducers for plasmonic biosensors . In the case of artificial antibodies, the molecular imprinting process on gold nanorods (AuNRs) involves multiple steps as schematically illustrated in Figure A.…”

Aromatic Functionality of Target Proteins Influences Monomer Selection for Creating Artificial Antibodies on Plasmonic Biosensors

“…6,7 We recently demonstrated plasmonic biosensors based on artificial antibodies achieved through molecular imprinting on the nanotransducer surface. 8–10 Artificial antibodies to a kidney injury biomarker had no change in analyte recognition over a pH range of 4.5–8.5 and specific gravity up to 1.03. 9 Apart from significantly improving the stability and lowering the cost of the biosensors, use of artificial antibodies instead of the natural antibodies as biorecognition elements significantly shortens the bioassay development time as the synthetic imprinting approach can be rapidly applied to a broad class of biomolecules.…”

Thermo‐sensitive surface molecularly imprinted magnetic microspheres based on bio‐macromolecules and their specific recognition of bovine serum albumin

“…Nevertheless, experiments have shown that although the MCS functional monomer indeed increases the adsorption capacity of MIPs, it does not improve the specific adsorption capacity. Sulfobetaine methacrylate (SBMA) can increase the specific adsorption , and NIPAM can endow the imprinted material with temperature sensitivity. Therefore, a protein imprinted material with both responsiveness and specificity has been prepared from an environmentally responsive macromolecular chain structure and an anti‐protein adsorption structure, which attaches to the surface of the imprinted polymer.…”