Label-free detection of Herceptin® using suspended silicon microring resonators

Abstract

Highly sensitive detection of heat denatured Herceptin® (trastuzumab), an important monoclonal antibody used in breast cancer therapeutics, is demonstrated using transverse magnetic (TM) mode suspended microring resonators (MRRs). The suspended MRRs are surface functionalized with a single chain fragment variable (scFv) recombinant antibody molecule (designated 2B4) that enables selective capture of denatured Herceptin molecules. Interaction between guided modes in suspended MRRs and Herceptin molecules captured on the surfaces of the suspended MRRs enable straightforward optical detection and quantification of the bound Herceptin molecules. Clinically relevant Herceptin detection at a concentration of 100 nM is demonstrated and negligible signal was obtained from the sensor when exposed to Avastin® (bevacizumab), a negative control human therapeutic monoclonal antibody. Importantly, at least a 2-fold enhanced detection sensitivity is obtained by suspending the microring (MRR) over the underlying substrate, effectively increasing the sensing surface area. Experimental results are supported by three-dimensional finite-difference time-domain simulations and optical mode analysis. The use of a label-free silicon photonic platform for high sensitivity molecular detection is compatible with high-throughput, low-cost diagnostics employing on-chip sensor arrays.