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Applied Optics

Applied Optics


  • Editor: James C. Wyant
  • Vol. 46, Iss. 10 — Apr. 1, 2007
  • pp: 1890–1895

Oblique-incidence reflectivity difference microscope for label-free high-throughput detection of biochemical reactions in a microarray format

Xiangdong Zhu, James P. Landry, Yung-Shin Sun, Jeff P. Gregg, Kit S. Lam, and Xiaowen Guo  »View Author Affiliations

Applied Optics, Vol. 46, Issue 10, pp. 1890-1895 (2007)

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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 c m × 7.62 c m ) microscope slide.

© 2007 Optical Society of America

OCIS Codes
(240.0240) Optics at surfaces : Optics at surfaces
(310.0310) Thin films : Thin films

ToC Category:
Optics in molecular imaging and drug discovery

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

Virtual Issues
Vol. 2, Iss. 5 Virtual Journal for Biomedical Optics

Xiangdong Zhu, James P. Landry, Yung-Shin Sun, Jeff P. Gregg, Kit S. Lam, and Xiaowen Guo, "Oblique-incidence reflectivity difference microscope for label-free high-throughput detection of biochemical reactions in a microarray format," Appl. Opt. 46, 1890-1895 (2007)

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