Faculty of Engineering and Natural Sciences
Applications of Optical Resonance to Biological Sensing&Imaging
M. Selim Ünlü
Boston University, Department of Electrical and Computer Engineering, Department of Physics
Optical resonance is one of the key properties of light enabling important devices such as interference filters and lasers. We present application of optical resonance and micro-resonators to biological sensing and imaging techniques. The importance of optical resonance has long been recognized and the interference due to multiple reflections had in fact been analyzed theoretically by George Airy nearly two centuries ago. Optical resonator has become a household name since Fabry and Perot and has been used for numerous sensing applications to improve sensitivity. Over the past 20 years we have been involved in the development of optoelectronic devices whose performance is enhanced by placing the active device structure inside a resonant microcavity .
A novel application of resonance to fluorescence microscopy promises nanometer resolution in biological imaging. We have developed a new technique – spectral self-interference fluorescent microscopy (SSFM) – that transforms the variation in emission intensity for different path lengths used in fluorescence interferometry to a variation in the intensity for different wavelengths in emission, encoding the high-resolution information in the emission spectrum . Using monolayers of proteins as well as single and double stranded DNA we have demonstrated sub nanometer axial height determination for thin layers of fluorophores. Using SSFM, we have estimated the shape of coiled single-stranded DNA, the average tilt of double-stranded DNA of different lengths, and the amount of hybridization . The data provide important proofs of concept for the capabilities of novel optical surface analytical methods of the molecular disposition of DNA on surfaces. The determination of DNA conformations on surfaces and hybridization behavior provide information required to move DNA interfacial applications forward and thus impact emerging clinical and biotechnological fields.
We have recently developed a new label-free microarray technique – Resonant Cavity Imaging Biosensor (RCIB) – that detects binding on a surface and promises high-sensitivity as well as simultaneous imaging of very large arrays. The resonant cavity is formed between two facing planar Bragg reflectors which have been developed for Si resonant cavity enhanced photodetectors . The wavelength illumination is swept in time using a wavelength tunable laser source. When the wavelength satisfies the resonant condition of the cavity for a particular location, the cavity builds up local energy that couples through and is recorded by a camera pixel corresponding to that location, or alternatively a photodiode in a photodiode array.
We have also demonstrated application of vertically coupled glass microring resonators to biomolecular sensing. Using balanced photodetection, very high signal to noise ratios, and thus high sensitivity to refractive index changes (limit of detection of 1.8 × 10−5 refractive index units), are achieved. Experimental data obtained separately for a bulk change of refractive index of the medium and for avidin-biotin binding on the ring surface demonstrated repeatability and close-to-complete surface regeneration after binding.
 M. S. Ünlü, and S. C. Strite, "Resonant Cavity Enhanced Photonic Devices," J. Appl. Phys., Vol. 78, No. 2, , pp.607 – 639, (1995)
 A. K. Swan, L. Moiseev, C. R. Cantor, B. J. Davis, S. B. Ippolito, W. C. Karl, B. B. Goldberg, and M. S. Ünlü, "Towards nanoscale optical resolution in fluorescence microscopy," IEEE J. Select. Topics Quantum Electron., Vol. 9, No. 2, pp. 294-300, (2003)
 L. Moiseev, M. S. Ünlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, "DNA Conformation on Surfaces Measured by Fluorescence Self-Interference," Proceedings of the National Academy of Science, Vol. 103, pp. 2623-2628, (2006)
 D. Bergstein, M. F. Ruane, and M. S. Ünlü, "Silicon Substrates with Buried Distributed Bragg Reflectors for Biosensing," Int’l.Semiconductor Dev.Res. Symp. 2005, 7-9 December 2005.
 M. K. Emsley, O. I. Dosunmu, and M. S. Ünlü, "Silicon Substrates with Buried Distributed Bragg Reflectors for Resonant Cavity-Enhanced Optoelectronics," IEEE J. Select. Topics Quantum Electron., Vol. 8, pp. 948-955, (2002)
 A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. F. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical Sensing of Biomolecules Using Microring Resonators," IEEE J. Select. Topics Quantum Electron., Vol. 12, No. 1, pp. 148-155, (2006)
M. Selim Ünlü was born in Sinop, Turkey, in 1964. He received the B.S. degree in electrical engineering from Middle East Technical University, Ankara, Turkey, in 1986 and the M.S.E.E. and Ph.D. degrees in electrical engineering from the University of Illinois, Urbana-Champaign, in 1988 and 1992, respectively. His dissertation topic dealt with resonant cavity enhanced (RCE) photodetectors and optoelectronic switches.
In 1992, he joined Boston University, as an Assistant Professor, and he is currently a Professor in the Department of Electrical and Computer Engineering. From January to July 2000, he worked as a Visiting Professor at University of Ulm, Germany. His career interest is in research and development of photonic materials, devices and systems focusing on the design, processing, characterization, and modeling of semiconductor optoelectronic devices, especially photodetectors. His current specific interests and expertise include high-speed RCE photodetectors, time and spatially resolved optical characterization of semiconductor materials, near-field and picosecond spectroscopy, near-field imaging of laser diodes, photonic bandgap and guided-wave devices, solid immersion lens microscopy, thermal imaging, biosensor fabrication and development of waveguide evanescent bio-imaging techniques, and hyperpolarized noble gas MRI. He has authored and coauthored more than 150 technical articles and several book chapters and magazine articles; edited one book; holds one U.S. patent; and has several patents pending.
Dr. Ünlü served as the Chair of IEEE Laser and Electro-Optics Society, Boston Chapter, winning the LEOS Chapter-of-the-Year Award, during 1994-1995. He served as the Vice President of SPIE New England Chapter from 1998 to 1999. He was awarded National Science Foundation Research Initiation Award in 1993, United Nations TOKTEN award in 1995 and 1996, and both the National Science Foundation CAREER and Office of Naval Research Young Investigator Awards in 1996. During 1999-2001, he served as the chair of the IEEE/LEOS technical subcommittee on photodetectors and imaging, and he is currently an Associate Editor for IEEE JOURNAL OF QUANTUM ELECTRONICS.
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