Silica nanoparticles coating in silicon nitride photonic label-free biosensing of s100 calcium-binding protein a6

Efficient functionalization of the silicon nitride waveguide with bioreceptors, e.g. antibodies, is key to increase antigen binding activity in photonic sensors based on silicon nitride (SiN) waveguides. A bioreceptor coating technique using silica nanoparticles (NPs) to enhance the density of functionalized antibodies, by increasing the surface areas for biomolecule binding, is proposed. The detection of S100 Calcium-Binding Protein A6 (S100A6), a proposed cholangiocarcinoma marker, has been demonstrated using the SiN resonator sensor with 400nm thick waveguide, fabricated by low-cost 500 nm technology. The NPs were synthesized by silica condensation. Antibodies were attached to the NPs by 1-ethyl-3-( 3-dimethyl aminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide ( NHS)-crosslinking. Then the NPs were coated on SiN sensor by N-terminal to N- terminal crosslinkers. It was found that the application of silica NPs coating showed increased sensor sensitivity at approximately 8.8 pm/(ng/ml) in optical resonant wavelength shift compared to 0.36 pm/(ng/ml) by our previous antibody coating technique using (3-Aminopropyl) triethoxysilane (APTES) silanization with EDC/NHS protein crosslink.