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

Girija Gaur, Shuren Hu, Raymond L. Mernaugh, Ivan I. Kravchenko, Scott T. Retterer, Sharon M. Weiss

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)394-401
Number of pages8
JournalSensors and Actuators, B: Chemical
Volume275
DOIs
StatePublished - Dec 1 2018

Funding

This work was supported in part by the Army Research Office ( W911NF-09-1-0101 , W911NF-15-1-0176 ) and the National Science Foundation ( ECCS1407777 ). Fabrication of the MRRs was conducted at the Center for Nanophase Materials Sciences (CNMS), which is a DOE Office of Science User Facility. The process of suspending the MRRs and scanning electron microscopy imaging of the suspended structures were carried out in the in Vanderbilt Institute for Nanoscale Science and Engineering.

FundersFunder number
National Science FoundationECCS1407777
Army Research OfficeW911NF-15-1-0176, W911NF-09-1-0101

    Keywords

    • Cancer
    • Label-free detection
    • Monoclonal antibody detection
    • Optical sensor
    • Ring resonator
    • Suspended resonator

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