Phase-contrast BioCD: High-speed immunoassays at sub-picogram detection levels

Ming Zhao, Leilei Peng, W. Cho, F. Regnier, D. D. Nolte

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

11 Scopus citations


We previously introduced the biological compact disk (BioCD) as a sensitive detection platform to detect patterned biomolecules immobilized on the surface of a spinning disk. Spinning-disk interferometry allows high speed detection (10 microseconds per spot) of optical path length changes down to sub-nanometer scales with high repeatability. The key to performing stable interferometry on a mechanically spinning disk is self-referencing: locking the phase of the signal and reference beams to quadrature (π/2 phase difference) independent of mechanical vibrations or relative motion. Two quadrature classes of BioCD have been reported previously: the micro-diffraction class (MD-Class) and the adaptive optical class (AO-Class) {Peng, 2004 #565; Varma, 2004 #440}. In this paper, we introduce a third class of BioCD, the Phase-Contrast-Class (PC-Class) BioCD. Protein is immobilized using photolithography on a disk in a 1024 spoke pattern. The edge of the printed protein pattern diffracts a focused laser beam that is detected in the Fourier plane with a split detector. The signal from the split detector is differenced, which plays a role in the electronic domain similar to that of a phase plate in optical phase contrast imaging. The PC-Class BioCD is simple in both theory and implementation, requiring no microstructure fabrication and no complex detection. Its potential in high speed label-free biosensing is demonstrated by a two-analyte immunoassay that shows good rejection of nonspecific binding and low antibody cross-reactivity. Immunoassays were performed against IgG immunoglobulins with detection of bound analyte on pictogram level. To show the potential of scaling up to hundreds or thousands of analytes per disk, an experiment was also performed with small drops of protein solution.

Original languageEnglish (US)
Title of host publicationNanobiophotonics and Biomedical Applications III
StatePublished - 2006
EventNanobiophotonics and Biomedical Applications III - San Jose, CA, United States
Duration: Jan 23 2006Jan 24 2006

Publication series

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


OtherNanobiophotonics and Biomedical Applications III
Country/TerritoryUnited States
CitySan Jose, CA


  • Antibody
  • BioCD
  • Edge diffraction
  • Fourier optics
  • Immunoassay
  • Microarray
  • Molecular recognition
  • Phase contrast imaging
  • Phase-locked quadrature
  • Protein chip
  • Self-referencing interferometry
  • Spinning-disk interferometry

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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