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Proceedings Paper

Molecular interferometric imaging study of molecular interactions
Author(s): Ming Zhao; Xuefeng Wang; David Nolte
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Paper Abstract

Molecular Interferometric Imaging (MI2) is a sensitive detection platform for direct optical detection of immobilized biomolecules. It is based on inline common-path interferometry combined with far-field optical imaging. The substrate is a simple thermal oxide on a silicon surface with a thickness at or near the quadrature condition that produces a π/2 phase shift between the normal-incident wave reflected from the top oxide surface and the bottom silicon surface. The presence of immobilized or bound biomolecules on the surface produces a relative phase shift that is converted to a far-field intensity shift and is imaged by a reflective microscope onto a CCD camera. Shearing interferometry is used to remove the spatial 1/f noise from the illumination to achieve shot-noise-limited detection of surface dipole density profiles. The lateral resolution of this technique is diffraction limited at 0.4 micron, and the best longitudinal resolution is 10 picometers. The minimum detectable mass at the metrology limit is 2 attogram, which is 8 antibody molecules of size 150 kDa. The corresponding scaling mass sensitivity is 5 fg/mm compared with 1 pg/mm for typical SPR sensitivity. We have applied MI2 to immunoassay applications, and real-time binding kinetics has been measured for antibody-antigen reactions. The simplicity of the substrate and optical read-out make MI2 a promising analytical assay tool for high-throughput screening and diagnostics.

Paper Details

Date Published: 22 February 2008
PDF: 8 pages
Proc. SPIE 6865, Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications V, 68650B (22 February 2008); doi: 10.1117/12.760783
Show Author Affiliations
Ming Zhao, Purdue Univ. (United States)
Xuefeng Wang, Purdue Univ. (United States)
David Nolte, Purdue Univ. (United States)

Published in SPIE Proceedings Vol. 6865:
Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications V
Alexander N. Cartwright; Dan V. Nicolau, Editor(s)

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