M. Selim Ünlü, Electrical and Computer Engineering, Biomedical Engineering, and Photonics Centre
"Digital Biodetection by Pixel-Diversity IRIS"
Interferometric Reflectance Imaging Sensor (IRIS) technology defies the conventional wisdom that calls for enhancing the signal through complex optical resonances. Instead, we exploit light interference from an optically transparent thin film—the same phenomenon that gives rainbow colors to a soap film when illuminated by white light. One of the most exciting applications of IRIS is nanoparticle counting or digital detection, that provides resolution and sensitivity beyond the reach of ensemble measurements. As a kinetic (real-time) assay with single-molecule readout, IRIS can measure analytes at attomolar concentrations. IRIS detection relies on interference of light reflected from the sensor surface being modified by the presence of particles producing a distinct signal that correlates to the polarizability (or size) of the particle. For smaller nanoparticles, discerning the optical signatures becomes particularly challenging with a single image capture. Thus, conventional IRIS utilizes z-scan acquisition (a stack of images taken from different focal positions) to capture the defocus signature unique to sub-diffraction limited scattering objects (nanoparticles on the surface). Recently, we demonstrated a new modality of digital detection, ‘pixel-diversity’ IRIS (PD-IRIS), that introduces a paradigm shift for encoding the necessary optical signature of target particles as it compresses the relevant optical information within a single image frame rather than an image stack. This is achieved by using camera sensors that simultaneously record multiple spectral or polarization channels. Therefore, a single image can record distinct spectral responses of target particles with respect to different excitation wavelengths (multi- spectral PD-IRIS) or the distinct scattering characteristics with respect to polarization (polarization PD-IRIS).
We will present experimental results on single image detection of spherical nanoparticles as well as gold nanorods. It is important to note that while polarization PD-IRIS is based on a straightforward mathematical formulation, spectral PD-IRIS is based on empirical observations due to chromatic aberrations that could vary for each instrument. Thus, we consider that Machine Learning Tools would be a powerful alternative method for nanoparticle detection in this case. With the practical implementation of single-molecule detection and counting, ‘digital detection – the new frontier in biomarker analysis’ will be accessible to all research laboratories.
M. Selim Ünlü received the B.S. degree from the Middle East Technical University, Ankara, Turkey, in 1986, and the M.S.E.E. (1988) and Ph.D. (1992) degrees from the University of Illinois at Urbana-Champaign, all in electrical engineering. Since 1992, he has been a professor at Boston University. He is currently a Distinguished Professor of Engineering appointed in electrical and computer engineering, biomedical engineering, physics, materials science and engineering, and graduate medical sciences. His research interests are in the areas of nanophotonics and biophotonics focusing development of biological detection and imaging techniques, particularly in high-throughput digital biosensors based on detection of individual biological nanoparticles, viruses, and single molecule counting. Dr. Ünlü has authored and co-authored >200 journal articles with >13,000 citations (h-index of 59) and holds 22 US/international patents. He was the recipient of the NSF CAREER and ONR Young Investigator Awards in 1996. He has been selected as a Photonics Society Distinguished Lecturer for 2005-2007 and Australian Research Council Nanotechnology Network (ARCNN) Distinguished Lecturer for 2007. He is a fellow of IEEE, Optica, and AIMBE. He was awarded the Science Award (2008) by the Turkish Scientific Foundation. In 2021, he was selected as Boston University Innovator of the Year. His past professional service includes serving as the Editor-in-Chief for IEEE Journal of Quantum Electronics and General Chair of IEEE Photonics Society Annual Meeting.