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Applied Optics

Applied Optics


  • Editor: James C. Wyant
  • Vol. 46, Iss. 24 — Aug. 20, 2007
  • pp: 6196–6209

Differential phase-contrast BioCD biosensor

Ming Zhao, Wonryeon Cho, Fred Regnier, and David Nolte  »View Author Affiliations

Applied Optics, Vol. 46, Issue 24, pp. 6196-6209 (2007)

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Common-path differential phase-contrast interferometry measures the spatial gradient of surface dipole density on a bio-optical compact disk (BioCD) and is sensitive to small changes in dipole density following molecular binding of target molecules out of solution. The recognition molecules are antibody IgG proteins that are deposited in periodic patterns on the BioCD using soft lithography or photolithography on the silanized silica surfaces of dielectric mirrors. Spatial carrier-wave sideband demodulation extracts the slowly varying protein envelope that modulates the protein carrier frequency. The experimental interferometric profilometry has surface height sensitivity down to 20 pm averaged over a lateral scale of 70 μm with a corresponding scaling mass sensitivity limit of 1.5 pg mm . Under the conditions of an IgG immunoassay with background changes caused during incubation, the scaling mass sensitivity is approximately 7 pg mm . A saturated reverse immunoassay performed with IgG at 100 ng ml showed false positive and false negative rates of 0.2%.

© 2007 Optical Society of America

OCIS Codes
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(260.3160) Physical optics : Interference

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: March 16, 2007
Manuscript Accepted: May 22, 2007
Published: August 20, 2007

Virtual Issues
Vol. 2, Iss. 9 Virtual Journal for Biomedical Optics

Ming Zhao, Wonryeon Cho, Fred Regnier, and David Nolte, "Differential phase-contrast BioCD biosensor," Appl. Opt. 46, 6196-6209 (2007)

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  1. G. Gauglitz, "Direct optical sensors: principles and selected applications," Anal. Bioanal. Chem. 381, 141-155 (2005). [CrossRef] [PubMed]
  2. R. Cush, J. M. Cronin, W. J. Stewart, C. H. Maule, J. Molloy, and N. J. Goddard, "The resonant mirror--a novel optical biosensor for direct sensing of biomolecular interactions 1. Principle of operation and associated instrumentation," Biosens. Bioelectron. 8, 347-353 (1993). [CrossRef]
  3. M. P. DeLisa, Z. Zhang, M. Shiloach, S. Pilevar, C. C. Davis, J. S. Sirkis, and W. E. Bentley, "Evanescent wave long period fiber Bragg grating as an immobilized antibody biosensor," Anal. Chem. 72, 2895-2900 (2000). [CrossRef] [PubMed]
  4. J. Homola, S. S. Yee, and G. Gauglitz, "Surface plasmon resonance sensors: review," Sens. Actuators B 54, 3-15 (1999). [CrossRef]
  5. V. S. Y. Lin, K. Motesharei, K. P. S. Dancil, M. J. Sailor, and M. R. Ghadiri, "A porous silicon-based optical interferometric biosensor," Science 278, 840-843 (1997). [CrossRef] [PubMed]
  6. C. Striebel, A. Brecht, and G. Gauglitz, "Characterization of biomembranes by spectral ellipsometry, surface-plasmon resonance, and interferometry with regard to biosensor application," Biosens. Bioelectron. 9, 139-146 (1994). [CrossRef] [PubMed]
  7. N. Ramachandran, D. N. Larson, P. R. H. Stark, E. Hainsworth, and J. LaBaer, "Emerging tools for real-time label-free detection of interactions on functional protein microarrays," FEBS J. 272, 5412-5425 (2005). [CrossRef] [PubMed]
  8. F. Prieto, B. Sepulveda, A. Calle, A. Llobera, C. Dominguez, and L. M. Lechuga, "Integrated Mach-Zehnder interferometer based on ARROW structures for biosensor applications," Sens. Actuators B 92, 151-158 (2003). [CrossRef]
  9. G. H. Cross, A. Reeves, S. Brand, M. J. Swann, L. L. Peel, N. J. Freeman, and J. R. Lu, "The metrics of surface adsorbed small molecules on the Young's fringe dual-slab waveguide interferometer," J. Phys. D 37, 74-80 (2004). [CrossRef]
  10. P. I. Nikitin, B. G. Gorshkov, E. P. Nikitin, and T. I. Ksenevich, "Picoscope, a new label-free biosensor," Sens. Actuators B 111, 500-504 (2005). [CrossRef]
  11. J. Dyson, "Common-path interferometer for testing purposes," J. Opt. Soc. Am. 47, 386-390 (1957). [CrossRef]
  12. J. Gluckstad and P. C. Mogensen, "Optimal phase contrast in common-path interferometry," Appl. Opt. 40, 268-282 (2001). [CrossRef]
  13. C. Chien, S. Jenn-Chyang, H. Yeu-Chuen, and Y. Chen-Kee, "Common-path optical heterodyne profilometer: a configuration," Appl. Opt. 37, 4137-4142 (1998). [CrossRef]
  14. C. M. Feng, Y. C. Huang, J. G. Chang, M. Chang, and C. Chou, "A true phase-sensitive optical heterodyne polarimeter on glucose concentration measurement," Opt. Commun. 141, 314-321 (1997). [CrossRef]
  15. R. Jenison, S. Yang, A. Haeberli, and B. Polisky, "Interference-based detection of nucleic acid targets on optically coated silicon," Nat. Biotechnol. 19, 62-65 (2001). [CrossRef] [PubMed]
  16. M. V. Sarunic, S. Weinberg, and J. A. Izatt, "Full-field swept-source phase microscopy," Opt. Lett. 31, 1462-1464 (2006). [CrossRef] [PubMed]
  17. M. M. Varma, H. D. Inerowicz, F. E. Regnier, and D. D. Nolte, "High-speed label-free detection by spinning-disk microinterferometry," Biosens. Bioelectron. 19, 1371-1376 (2004). [CrossRef] [PubMed]
  18. B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002). [CrossRef]
  19. C. W. See, M. V. Iravani, and H. K. Wickramasinghe, "Scanning differential phase-contrast optical microscope--application to surface studies," Appl. Opt. 24, 2373-2379 (1985). [CrossRef] [PubMed]
  20. A. J. Pidduck, D. J. Robbins, D. B. Gasson, C. Pickering, and J. L. Glasper, "In situ laser light scattering. II. Relationship to silicon surface topography," J. Electrochem. Soc. 136, 3088-3094 (1989). [CrossRef]
  21. M. Varma, D. D. Nolte, H. D. Inerowicz, and F. E. Regnier, "Multianalyte array microdiffraction interferometry," Proc. SPIE 4626, 69-77 (2002). [CrossRef]
  22. M. M. Varma, D. D. Nolte, H. D. Inerowicz, and F. E. Regnier, "Spinning-disk self-referencing interferometry of antigen-antibody recognition," Opt. Lett. 29, 950-952 (2004). [CrossRef] [PubMed]
  23. L. Peng, M. Varma, H. D. Inerowicz, F. E. Regnier, and D. D. Nolte, "Adaptive optical BioCD for biosensing," Appl. Phys. Lett. 86, 183902 (2005). [CrossRef]
  24. D. D. Nolte, T. Cubel, L. J. Pyrak-Nolte, and M. R. Melloch, "Adaptive beam combining and interferometry using photorefractive quantum wells," J. Opt. Soc. Am. B 18, 195-205 (2001). [CrossRef]
  25. D. D. Nolte, Photorefractive Effects and Materials (Kluwer Academic, 1995).
  26. C. W. See, R. K. Appel, and M. G. Somekh, "Scanning differential optical profilometer for simultaneous measurement of amplitude and phase variation," Appl. Phys. Lett. 53, 10-12 (1988). [CrossRef]
  27. M. R. Atkinson, A. E. Dixon, and S. Damaskinos, "Surface-profile reconstruction using reflection differential phase-contrast microscopy," Appl. Opt. 31, 6765-6771 (1992). [CrossRef] [PubMed]
  28. C. Chien, L. Chung-Wei, and P. Li-Cheng, "Polarized differential-phase laser scanning microscope," Appl. Opt. 40, 95-99 (2001). [CrossRef]
  29. D. D. Nolte and M. Zhao, "Scaling mass sensitivity of the BioCD at 0.25 pg/mm," Proc. SPIE 6380, 63800J (2006). [CrossRef]

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