Molecular interferometric imaging study of molecular interactions

Ming Zhao, Xuefeng Wang, David Nolte

Research output: Chapter in Book/Report/Conference proceedingConference contribution


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.

Original languageEnglish (US)
Title of host publicationNanoscale Imaging, Sensing, and Actuation for Biomedical Applications V
StatePublished - Apr 21 2008
EventNanoscale Imaging, Sensing, and Actuation for Biomedical Applications V - San Jose, CA, United States
Duration: Jan 21 2008Jan 23 2008

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
ISSN (Print)1605-7422


OtherNanoscale Imaging, Sensing, and Actuation for Biomedical Applications V
Country/TerritoryUnited States
CitySan Jose, CA


  • Antibody
  • BioCD
  • Common-path interferometry
  • Immunoassay
  • Interference microscopy
  • Molecular recognition
  • Protein microarray
  • Shot-noise limited detection

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging


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