Development and validation of an immunosensor for monocyte chemotactic protein 1 using a silicon photonic microring resonator biosensing platform

Abstract

a) Objectives We report the development of an optical immunosensor for the detection of monocyte chemotactic protein 1 (MCP-1) in serum samples. MCP-1 is a cytokine that is an emerging biomarker for several diseases/disorders, including ischemic cardiomyopathy, fibromyalgia, and some cancers. b) Design and Methods The detection of MCP-1 was achieved by performing a sandwich immunoassay on a silicon photonic microring resonator sensor platform. The resonance wavelengths supported by microring sensors are responsive to local changes in the environment accompanying biomarker binding. This technology offers a modularly multiplexable approach to detecting analyte localization in an antibody-antigen complex at the sensor surface. c) Results The immunosensor allowed the rapid detection of MCP-1 in buffer and spiked human serum samples. An almost 2 order of magnitude linear range was observed, between 84.3 and 1582.1 pg/mL and the limits of blank and detection were determined to be 0.3 and 0.5 pg/mL, respectively. The platform's ability to analyze MCP-1 concentrations across a clinically-relevant concentration range was demonstrated. d) Conclusions A silicon photonic immunosensor technology was applied to the detection of clinically-relevant concentrations of MCP-1. The performance of the sensor was validated through a broad dynamic range and across a number of suggested clinical cut-off values. Importantly, the intrinsic scalability and rapidity of the technology makes it readily amenable to the simultaneous detection of multiplexed biomarker panels, which is particularly needed for the clinical realization of inflammatory diagnostics.

A Guide to Quantitative Biomarker Assay Development using Whispering Gallery Mode Biosensors

“…Figure 5 Examples of fluid delivery: Genalyte M1 cartridge assembly for a single chip array (A-B), Genalyte M24 cartridge assembly for 12 arrays with integrated fluidics (C), and an optical configuration to monitor a microsphere resonator in a polymeric chamber as described by the Vollmer group (D). Panels A and B are adapted with permission from Valera, Shia, & Bailey (2016). Panel D is adapted with permission from Baaske, Foreman, & Vollmer (2014).…”

“…Although alternative WGM sensors with different geometries and materials systems are viable platforms for detection, this protocol is written from the perspective of using arrays of chip-integrated silicon photonic microring resonators (Iqbal et al, 2010)-a platform that has been commercialized by Genalyte, Inc. Furthermore, this protocol focuses on enzymatically enhanced sandwich immunoassays (Kindt, Luchansky, Qavi, Lee, & Bailey, 2013;Valera, Shia, & Bailey, 2016), which have been found by our laboratory to provide the highest specificity and lowest limits of detection for protein detection in complex matrices; however, many of the general steps are based upon or closely related to earlier examples of label-enhanced (Luchansky & Figure 1 Operating principles for microring resonator sensors. (A) A scanning electron microscope (SEM) image shows a 30-μm active microring with an adjacent linear waveguide.…”

PCR-Free, Multiplexed Expression Profiling of microRNAs Using Silicon Photonic Microring Resonators

“…(8–13) The operational theory and measurement instrumentation behind the technology has been previously discussed in detail. (14–15) Briefly, a tunable wavelength laser centered around 1550 nm is coupled into linear waveguides via on chip grating couplers.…”

Improved Sensitivity of Microring Resonator-Loaded Mach–Zehnder Interferometer Biosensor

“…(4)(5)(6)(7)(8)(9)(10)(11) In addition, microring resonator (MRR)-based biosensors have also been intensively developed because of their compactness, high sensitivity, and low cost. (12)(13)(14)(15)(16)(17)(18)(19)(20) We have also proposed and developed a biosensor based on an MRR-loaded Mach-Zehnder interferometer (MRR-MZI) (21) that has a higher sensitivity than conventional MRR sensors. Although avidin at a concentration as low as 20 pM was detected as a change in light transmittance with the MRR-MZI sensor, a sufficient change in transmittance has not yet been obtained.…”