Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads

Abstract

We demonstrate a three-step assay on a silicon photonic microring resonator-based detection platform that enables the quantitation of the cardiac biomarker C-reactive protein (CRP) over a dynamic range spanning six orders of magnitude. Using antibody-modified microrings, we sequentially monitor primary CRP binding, secondary recognition of bound CRP by a biotinylated antibody, and tertiary signal amplification using streptavidin-functionalized beads. This detection methodology is applied to CRP quantitation in human serum and plasma samples.

Ultrasensitive detection of a protein by optical trapping in a photonic‐plasmonic microcavity

“…Protein detection with plasmon-coupled microcavity biosensor [5,6], optical sensors such as Raman spectroscopy [7][8][9][10][11], plasmon resonance [12] and emerging Whispering Gallery Mode (WGM) [13][14][15][16][17][18] sensors have been utilized for detecting biomolecules at mg-ng/ml sensitivity levels. WGM biosensing offers a particularly sensitive approach to quantify the mass loading of biomolecules on the resonator surface with ultimate sensitivity estimated on the single molecule level [19,20].…”

Optical Resonator Biosensors: Molecular Diagnostic and Nanoparticle Detection on an Integrated Platform

“…Adapted from ref. [34]. A three-step assay can greatly enhance sensitivity by amplifying the detection signal with a nanoparticle attached to a secondary antibody that specifically binds to analyte previously bound to a primary antibody immobilized on a silicon ring resonator.…”

“…[34] An antibody functionalized silicon microring sensors array was used to detect binding of CRP. The addition of biotinylated anti-CRP as a second marker was used to identify CRP specifically bound to the antibody-functionalized microring surface.…”

Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays

“…Labeling secondary probes with a particle commonly referred to as "mass-tagging" is a common method to enhance sensitivity. However, state-of-the-art mass tagging requires at least micron-size particles resulting in limitations due to diffusion and steric hindrance caused by the large size the particle [16]. SP-IRIS can detect Aunanoparticles as small as 20nm, which is only about twice the hydrodynamic diameter of an antibody, allowing this information to serve as an identifier of the biomolecule attached to the nanoparticle.…”