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Optical Characterization and Nanophotonics Laboratory

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Interferometric Reflectance Imaging Sensor

Members: Sunmin Ahn, Jeffrey Robert Bintz, Pankil Mukund Butala, Clarissa Campanella, Jyothsna Chinnala, Tenzile Berkin Cilingiroglu, George Gaby Daaboul, David S. Freedman, Ryan Joseph Gelly, Carlos A. Lopez, Allison Marie Marn, Alexander Reddington, Derin Deniz Sevenler, Aidyn Shaikhov, Jacob Thomas Trueb, M. Selim Ünlü, Abdulkadir Yurt, Xirui Zhang, Isha Zinzuwadia

 

Alumni: Leslie Baggesen, Aaron Jacob Berliner, Vivek Naresh Bhatia, Amy E Canham, Austin Daniel Collins, Michael Samuel Friedman, Nikka B Ghalili, Alexander Symeon Giannakos, Joseph Thomas Greenspun, Shannon Kathleen Grover, Rostem Irani, Malin Jansson, Nickvash Kani, Craig David Laboda, Aaron J Larocque, Nicholas Mauriello Luzod, Christopher Michael Myers, Ali Nejat, Emre Ozkumur, Alp Ozturk, Chelsea Pereira, George Woodman Pratt, Karishma Sekhon, Philipp Stefan Spuhler, Gultekin Tasdirek, Rahul Srinivasa Vedula, Ayca Yalcin

 

Collaborators: Mario Cabodi

 

Development of the Interferometric Reflectance Imaging Sensor (IRIS), formerly known as the Spectral Reflectance Imaging Biosensor (SRIB), is the primary biosensing project being pursued in the Ünlü Group. IRIS has demonstrated the capability to monitor protein-protein (antigen/antibody), protein-DNA, and DNA-DNA interactions in a multiplexed, high-throughput microarray format without the use of labels. To prepare sensor surfaces, biological probes are immobilized on functionalized bi-layered Si/SiO2 substrates. Samples are illuminated at different wavelengths using a tunable laser and reflections from this surface are detected as intensity variations by a CCD camera. Layered substrates demonstrate characteristic spectral reflectance due to the interference of reflected light from the Si-SiO2 and SiO2-air interfaces. As binding of specific targets occurs at the microarray surface, changes in optical path length result in quantifiable shifts in this wavelength dependent reflectivity, and this information is used to calculate precise amounts of biomass accumulation. Potential applications for IRIS include microarray format immunoassays, single nucleotide polymorphism (SNP) detection, pathogen detection and bio-defense monitoring, kinetic analysis of biomolecular interactions, and general biomolecular interaction studies for research applications. The figure below gives a more detailed description of the working principle of IRIS with a schematic of the experimental setup. Below, are several of the more recent advancements in this technology:

IRIS Platform
Figure 1: (a) Basic working principle of the IRIS system. A tunable laser illuminates the surface and reflections from the surface are recorded by a CCD camera. Multiple reflections from the layered substrate form an interference pattern. This interference pattern is detectable on a CCD camera as intensity variations when the illumination wavelength is changed. Accumulation of biological material on the surface shifts the interference pattern which is detected by the corresponding pixels as a change in height. (b) Schematic of the IRIS system. Laser light is passed through a pair of rotating ground glass disks prior to illumination. Reflection is captured by a CCD camera using an imaging system that has variable zoom for optimizing the field of view to a variety of array sizes. The photodetector is used to track changes in the intensity of the laser.

LED-IRIS
Recently, a new embodiment of the IRIS was developed using narrow bandwidth LEDs as the illumination source. The working principle remains the same, but the use of these small and inexpensive LEDs allows for the simplification of the overall platform, eliminating the costly laser source and all moving components. The LED-IRIS has shown comparable sensitivity and detection capability as the Laser-IRIS and imaging SPR systems.

Solidworks illustration of LED-IRIS
Figure 2: Solidworks illustration of LED-IRIS

Reconstructed image from the LED-IRIS
Figure 3: Image of whole virus detection microarray taken by LED-IRIS

Single Particle Detection - IRIS
The most recent success in the IRIS project is the development of a high-magnification, single particle detection system. The single particle IRIS has demonstrated detection and size discrimination capability for polystyrene beads ranging from 70nm-150nm in diameter, as well as specific capture and identification of single H1N1 virus particles.

Single Particle IRIS Image
Figure 4: Image of specific capture of single virus particles using the single particle IRIS.

Compact LED-IRIS
Recently awarded the Boston University Office of Technology Development’s Ignition Award for healthcare, our group is also working on a compact and portable version of the LED-IRIS as a low-cost, field deployable solution for many research and clinical applications. The goal of this project is to develop a self-contained, compact, battery operated, and robust biosensor for global health field diagnostics where resources and skilled personnel are limited. Target diseases for this system are prevalent worldwide infectious diseases including malaria, dengue fever, and acute lower respiratory infections. Currently, development of a much simpler optical path and an embedded software system is being conducted as well implementation of a cell-phone to operate to the device so that eventual field testing can be performed.

Publications

A. Tuysuzoglu, "Robust Inversion and Detection Techniques for Improved Imaging Performance," Ph.D. Dissertation, May 2014

C. Yu, C. A. Lopez, H. Hu, Y. Xia, D. S. Freedman, A. Reddington, G. G. Daaboul, M. S. Ünlü, and C. A. Genco, "A high-throughput method to examine protein-nucleotide interactions identifies targets of the bacterial transcriptional regulatory protein Fur.," PLoS ONE, Vol. 9, No. 5, May 2014

A. Reddington, "Instrument Design and Optimization of Interferometric Reflectance Imaging Sensors for In Vitro Diagnostics," Ph.D. Dissertation, January 2014

A. Reddington, J. T. Trueb, D. S. Freedman, A. Tuysuzoglu, G. G. Daaboul, C. A. Lopez, W. C. Karl, J. H. Connor, H. E. Fawcett, and M. S. Ünlü, "An Interferometric Reflectance Imaging Sensor for Point of Care Viral Diagnostics," IEEE Transactions on Biomedical Engineering, Vol. 60, No. 12, December 2013, pp. 3276-3283

A. Reddington, M. R. Monroe, and M. S. Ünlü, "Integrated Imaging Instrument for Self-Calibrated Fluorescence Protein Microarrays," Review of Scientific Instruments, Vol. 84, No. 10, 4 October 2013

S. Ahn, D. D. Sevenler, and M. R. Monroe, "Biosensors - Innovations in nanobiosensing and biophotonics at Boston University," Boston University, August 2013

S. Ahn, D. S. Freedman, P. Massari, M. Cabodi, and M. S. Ünlü, "A Mass-Tagging Approach for Enhanced Sensitivity of Dynamic Cytokine Detection Using a Label-Free Biosensor," Langmuir, Vol. 29, No. 17, April 2013, pp. 5369-5376

M. Cretich, M. R. Monroe, A. Reddington, X. Zhang, G. G. Daaboul, F. Damin, L. Sola, M. S. Ünlü, and M. Chiari, "Interferometric silicon biochips for label and label-free DNA and protein microarrays.," Proteomics, Vol. 12, 2013, pp. 2963-2977

S. Ahn, C. Huang, E. Ozkumur, X. Zhang, J. Chinnala, A. Yalcin, S. Bandyopadhyay, S. Russek, M. S. Ünlü, C. DeLisi, and R. Irani, "TATA binding proteins can recognize nontraditional DNA sequences," Biophysical Journal, Vol. 103, October 2012, pp. 1510-1517

G. G. Daaboul, C. A. Lopez, A. Yurt, B. B. Goldberg, J. H. Connor, and M. S. Ünlü, "Optical Biosensors for Virus Detection and Characterization," IEEE Journal of Selected Topics in Quantum Electronics, Vol. 18, No. 4, July/August 2012, pp. 1422-1433

S. Ahn, P. S. Spuhler, M. Chiari, M. Cabodi, and M. S. Ünlü, "Quantification of surface etching by common buffers and implications on the accuracy of label-free biological assays ," Biosensors and Bioelectronics, Vol. 36, June 2012, pp. 222-229

A. Yurt, G. G. Daaboul, J. H. Connor, B. B. Goldberg, and M. S. Ünlü, "Single nanoparticle detectors for biological applications," Nanoscale, Vol. 4, No. 3, 2012, pp. 715 - 726

M. R. Monroe, A. Reddington, A. D. Collins, C. D. Laboda, M. Cretich, M. Chiari, F. F. Little, and M. S. Ünlü, "Multiplexed method to calibrate and quantitate fluorescence signal for allergen-specific IgE," Analytical Chemistry, November 2011

C. A. Lopez, G. G. Daaboul, S. Ahn, A. Reddington, M. R. Monroe, X. Zhang, R. Irani, C. Yu, C. A. Genco, M. Cretich, M. Chiari, B. B. Goldberg, J. H. Connor, and M. S. Ünlü, "Biomolecular Detection employing the Interferometric Reflectance Imaging Sensor (IRIS)," Journal of Visualized Experiments, Vol. 51, May 2011, pp. doi: 10.3791/2694.

M. S. Ünlü, "Pulse," EEWeb, No. 2, February 2011

C. A. Lopez, G. G. Daaboul, R. S. Vedula, E. Ozkumur, D. A. Bergstein, T. W. Geisbert, H. Fawcett, B. B. Goldberg, J. H. Connor, and M. S. Ünlü, "Label-free multiplexed virus detection using spectral reflectance imaging," Biosensors and Bioelectronics, 2011

R. S. Vedula, G. G. Daaboul, A. Reddington, E. Ozkumur, D. A. Bergstein, and M. S. Ünlü, "Self-Referencing Substrates for Optical Interferometric Biosensors," Journal of Modern Optics, Vol. 57, No. 16, 20 September 2010, pp. 1564–1569

M. Cretich, D. Breda, F. Damin, M. Borghi, L. Sola, M. S. Ünlü, S. E. Burastero, and M. Chiari, "Allergen microarrays on high-sensitivity silicon slides," Analytical and Bioanalytical Chemistry, No. DOI 10.1007/s00216-0, 22 August 2010

E. Ozkumur, C. A. Lopez, A. Yalcin, J. H. Connor, M. Chiari, and M. S. Ünlü, "Spectral Reflectance Imaging for a Multiplexed, High-Throughput, Label-Free, and Dynamic Biosensing Platform," IEEE Journal of Selected Topics in Quantum Electronics, Vol. 16, No. 3, May/June 2010, pp. 635-46

E. Ozkumur, S. Ahn, A. Yalcin, C. A. Lopez, E. Cevik, R. Irani, C. DeLisi, M. Chiari, and M. S. Ünlü, "Label-free microarray imaging for direct detection of DNA hybridization and single-nucleotide mismatches," Biosensors and Bioelectronics, Vol. 25, No. 7, 15 March 2010, pp. 1789-1795

E. Ozkumur, A. Yalcin, S. Ahn, B. B. Goldberg, M. Chiari, and M. S. Ünlü, "Spectral Reflectance Imaging Biosensor for high-throughput and label-free detection of biomolecular interactions," Proceedings of IEEE Photonics Society 2009 Annual Meeting, October 2009

E. Ozkumur, A. Yalcin, M. Cretich, F. Damin, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Ünlü, "Optical Phase to Biological Mass Conversion for Label-free Interferometric Sensing Methods," Proceedings of IEEE Photonics Society 2009 Annual Meeting, October 2009

E. Ozkumur, A. Yalcin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Ünlü, "Quantification of DNA and protein adsorption by optical phase shift ," Biosensors and Bioelectronics, Vol. 25, September 2009, pp. 167-172

E. Ozkumur, "Optical Interference Based Microarray Imaging for Label-Free Multi-Analyte Detection ," Ph.D. Dissertation, May 2009

E. Ozkumur, A. Yalcin, M. Cretich, M. S. Ünlü, and M. Chiari, "Label-free, dynamic and quantitative measurement of biomolecular interactions," 23rd International Symposium on MicroScale Bioseparations (MSB) 2009, February 2009

E. Ozkumur, A. Yalcin, F. Damin, B. B. Goldberg, M. Chiari, and M. S. Ünlü, "Label-free and dynamic measurement of biomolecular interactions for high-throughput diagnostics," Photonics West 2009 - BIOS, January 2009

E. Ozkumur, J. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. Gershoni, B. B. Goldberg, and M. S. Ünlü, "Label-free and dynamic detection of biomolecular interactions for high-throughput microarray applications," Proceedings of the National Academy of Science, Vol. 105, 10 June 2008, pp. 7988-7992

E. Ozkumur, J. Needham, D. A. Bergstein, B. B. Goldberg, and M. S. Ünlü, "Label-free real-time microarray imaging using spectral reflectivity information," Photonics West 2008 - BIOS, January 2008

E. Ozkumur, J. Needham, D. A. Bergstein, M. F. Ruane, B. B. Goldberg, and M. S. Ünlü, "Label-free and high-throughput screening of biomolecular interactions," Proceedings of CLEO/QELS 2008, 2008

E. Ozkumur, J. Needham, D. A. Bergstein, A. C. Wu, M. F. Ruane, B. B. Goldberg, and M. S. Ünlü, "Label-free microarray imaging using spectral reflectance information," 2007 BMES Annual Fall Meeting, September 2007


Collaborators

Marcella Chiari of the (CNR; "Italian National Research Council") Institute of Chemistry of Molecular Recognition


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