Abstract

We describe a recently developed oblique-incidence reflectivity difference (OI-RD) microscope, a form of polarization-modulated imaging ellipsometer, for label-free-high-throughput detection of biomolecular reactions on DNA and protein microarrays. We present examples of application of this technique to end-point and real-time investigations of DNA-DNA hybridization, antibody-antigen capture, and protein-small-molecule binding reactions. Compared to a conventional imaging ellipsometer based on the polarizer-compensator-sample-analyzer scheme and under the off-null condition, a polarization-modulated OI-RD microscope is inherently more sensitive by at least 1 order of magnitude to thickness changes on a solid surface. Compared with imaging surface plasmon resonance microscopes based on reflectance change on falling or rising slopes of the surface plasmon resonance, the OI-RD microscope (1) has a comparable sensitivity, (2) is applicable to conventional microscope glass slides, and (3) easily covers a field of view as large as the entire surface of a 1 in.×3 in. (2.54 cm×7.62 cm) microscope slide.

© 2007 Optical Society of America

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History
Original Manuscript: June 29, 2006
Manuscript Accepted: September 15, 2006
Revised Manuscript: September 1, 2006
Published: March 13, 2007

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Author Affiliations

Xiaowen Guo

Clinical Diagnostics Group

Xiangdong Zhu, James P. Landry, Yung-Shin Sun, Jeff P. Gregg, Kit S. Lam

University of California

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