Smart Hydrogel Grating Immunosensors for Highly Selective and Sensitive Detection of Human-IgG

Abstract

A smart diffraction grating immunosensor based on antigen-responsive hydrogel with enhanced analyte-induced volume changes is developed for highly selective and sensitive detection of human immunoglobulin G (H-IgG). The hydrogel grating contains poly(N-isopropylacrylamide) (PNIPAM) backbones with dual-cross-linking based on the dynamic complexation between pendent goat-anti-human IgG (GAH-IgG) and pendent H-IgG, and the covalent bonding by 4-arm-polyethylene glycol-acrylamide. Upon recognizing free H-IgG in the environment, the pendent GAH-IgG in the hydrogel can form new GAH-IgG/H-IgG complexes with free H-IgG because the binding constant of GAH-IgG to the free H-IgG is much larger than that of GAH-IgG to the pendent H-IgG and thus result in the decomplexation of GAH-IgG/H-IgG complexes with the pendent H-IgG as well as the swelling of hydrogel. The thermo-responsive PNIPAM backbones enable enhancement of H-IgG-responsive volume change of the proposed hydrogel grating via temperature regulation. Moreover, the cross-linker 4-arm-polyethylene glycol-acrylamide provides excellent transparency for the PNIPAM backbones during the volume change, which ensures output of diffracted optical signals with high intensity. With the elaborately designed molecular structures, the hydrogel grating allows highly selective and sensitive detection of [H-IgG] with a detection limit as low as 1.3 × 10 −8 M. This work provides a simple and flexible strategy for developing diffraction grating immunosensors based on stimuli-responsive hydrogels for efficient detection of biomarkers.

Hydrogel-based holographic sensors and biosensors: past, present, and future

“…Another important aspect to consider is the recognition molecule's stability during the polymerization. For example, Wang and Spivak employ phosphate buffer saline (PBS) solutions as a solvent during polymerization when fabricating SRGs in the presence of aptamers [108] and IgGs [64,69], as these biomolecules easily denature in extreme pH or organic solvents..…”

“…Detection of antibodies has also been demonstrated by following a similar approach as in the case of thrombin [64,69]. In this case, the SRG incorporated vinylated monomers of human IgG and anti-human IgG, whose recognition acted as non-covalent crosslinking points in the hydrogel.…”

“…Whatever the chosen technique, the hydrogel should be moldable and easily detachable from PDMS. The direct replication of hydrogels on polyethylene terephthalate (PET) masters has also been reported, but no information about the fabrication and reutilization of the PET stamp was included in this study [69].…”

Processing of Holographic Hydrogels in Liquid Media: A Study by High-Performance Liquid Chromatography and Diffraction Efficiency

“…Biosensing with hydrogel-based surface relief diffraction gratings (SRG) has been reported for the detection of Thrombin [ 36 ] and Human Immunoglobulin-G [ 37 , 38 ]. In addition, we have recently reported the detection of C-reactive proteins in buffer and certified blood serum using a SRG fabricated with a hydrogel functionalized with phosphorylcholine units [ 39 ].…”

All Fiber-Optic Immunosensors Based on Elliptical Core Helical Intermediate-Period Fiber Grating with Low-Sensitivity to Environmental Disturbances

“…Other methods include immunochemical biosensor and quartz crystal microbalances, with the LOD reaching 49 ng/mL and 5 µg/mL, respectively [ 11 , 12 ]. Recently, a diffraction grating immunosensor was proposed for specific detection with the LOD of 1.3 × 10 − 8 M [ 13 ]. However, these methods are either time-consuming or complex processes.…”