Biosensing, Ultrashort Laser Therapeutics and Nanobiophotonics
This research program aims to employ advanced biophotonic and nanobiophotonic technologies to develop and implement novel test protocols, guidance documents, and standard test methodologies for evaluating safety and efficacy of emerging optical therapeutic devices including: medical laser systems concerning critical spectral (ultraviolet-to-infrared), temporal (cw-to-femtosecond), and spatial characteristics; medical fiber-optics; and integrated therapeutic sensing and imaging systems. The program includes three key research areas related to critical regulatory and public health needs: multifunctional biosensing; ultrashort laser therapeutics; and nanobiophotonics.
Fig. 1. A confocal laser method (CLM) invented for IOL power testing (a) [1-2]; a full-angle scanning light scattering profiler (SLSP) to quantitatively evaluate light scattering from IOL implants (b) ; a FO-FTIR spectroscopy platform (c) for label-free and remote sensing of medical device contaminations such as bacteria (c) , endotoxin in ophthalmic viscosurgical devices (d) , and intrinsic biomarkers in optical therapeutics (e) ; an OCT system for evaluating safety and efficacy of optical nerve stimulation (f).
1. Multifunctional Biosensing
Test methodologies for evaluating critical optical characteristics of novel intraocular lens (IOL) devices.
Employing advanced sensing and imaging approaches, we developed and implemented innovative test methods for pre- and post-market evaluation of critical characteristics of IOL implants such as: confocal laser method (CLM) for dioptric power measurements, Fig. 1a [1,2]; optical coherence tomography (OCT) method for geometrical/power testing ; and full-angle scanning light scattering profiler (SLSP) for evaluating light scattering and glare glare Fig. 1b .
Advanced sensing methods for label-free, remote and real-time detection of medical device contaminations.
We developed and implemented novel contamination detection and decontamination methodologies using: fiber-optic Fourier transform infrared (FO-FTIR) spectroscopy for label-free and remote sensing of device contaminations by endotoxins, bacteria, biofilms, and pathogens, Fig. 1(c)-(e) [4-6]; hyperspectral imaging for contamination monitoring; and near-IR ultrashort (nano-to-femtosecond) laser platform for remote and chemical-free decontamination.
Multifunctional sensing and imaging test methods.
Using advanced high-resolution OCT and confocal microscopy platforms, we developed novel multifunctional methods for safety and efficacy evaluation of emerging optical therapeutic technologies and devices, concerning: therapeutic lasers, fiber-optic technologies and new therapeutic sensing and monitoring systems in the areas of ophthalmology, optical nerve stimulation, Fig. 1(f), and optical therapeutics Fig. 1(f), .
2. Ultrashort Laser Therapeutics
We investigated unique therapeutic ultrashort (pico- and femtosecond) laser-tissue interactions associated with new safety and efficacy concerns such as femtosecond laser (FSL) stimulated nonlinear optical effects (NOEs). We evaluated potential FSL generated hazardous effects in order to improve the safety and efficacy of this rapidly expanding technology and to aid the review of FSL devices, and provide guidance to the industry.
Develop novel standard test methods to quantify the impact of critical tissue optical properties and laser parameters on therapeutic FSL induced UV-VIS harmonics, supercontinuum and self-focusing effects with new safety concerns.
We developed innovative test methods for evaluating the impact of critical tissue properties (transmission, thickness ) and laser parameters (polarization, pulse width, rep-rate, energy, beam size; Fig. 2a [7-8]) on the NOE efficacy.
The primary objective of this key research area is to develop and investigate innovative approaches in nanobiophotonics for noninvasive ultrahigh-resolution nanoscopy (Fig. 2b, ), biosensing and characterizing critical optical properties of novel nanobiomaterials as well as cellular, intracellular and tissue samples beyond the diffraction barrier in the subwavelength nanoscale range . This research aims also to develop alternative test methodologies for safety and performance evaluation of laser-based medical therapeutic devices employing laser stimulated plasmonic nanoparticles.
Fig. 2. Principle setup and typical experimental 3D and 2D plots of second- and third-harmonics generated by FSL in corneal tissue (a) ; and a confocal nanoscopy invented for ultrahigh-resolution imaging beyond the diffraction limit in the nanoscale range (b) .
Ilko K. Ilev, PhD
Moinuddin Hassan, PhD
Do-Hyun Kim, PhD
Xin Tan, PhD
Alex Beylin, PhD
William Calhoun, PhD
Malvina Eydelman, MD
Victoria Hitchings, PhD
Mehmet Kosoglu, PhD
Neil R. Ogden
Joshua Pfefer, PhD
Bennett Walker, PhD
Uniformed Services University of the Health Sciences
Johns Hopkins University
National Institute of Health
George Washington University
University of Maryland
Harvard Medical School
Selected peer-reviewed publications
- Hassan et al., Noninvasive and label-free sensing of endotoxin contamination in ophthalmic viscosurgical devices using a fiber-optic Fourier-transform infrared spectroscopy based method, IEEE Journal of Selected Topics in Quantum Electronics, 2017.
- Kosoglu et al, Developing test methodology to identify intrinsic biomarker in biological model using Fourier transform infrared (FTIR) spectroscopy, IEEE Journal of Selected Topics in Quantum Electronics, 2017.
- Ilev, Confocal fiber-optic laser device and method for intraocular lens power measurements, Patent No. 7,719,668 (May 18, 2010)
- Ilev et al, Confocal laser method and device for power measurement of toric intraocular lens�, U.S. PCT Patent Application No. PCT/US2016/015031, January 27, 2016.
- Walker et al., Confocal laser method for quantitative evaluation of critical optical properties of toric intraocular lenses, Journal of Cataract and Refractive Surgery, 2016.
- Walker et al., A novel full-angle scanning light scattering profiler to quantitatively evaluate forward and backward light scattering from intraocular lenses, Review of Scientific Instruments, 2015.
- Hassan et al., Detecting bacteria contamination on medical device surfaces using an integrated fiber-optic mid-infrared spectroscopy sensing method, Sensors and Actuators B, 2016.
- Calhoun et al., Evaluation of broadband spectral transmission characteristics of fresh and gamma-irradiated corneal tissues, Cornea, 2015.
- Calhoun and Ilev, Evaluation of broadband spectral transmission characteristics of fresh and gamma-irradiated corneal tissues, Lasers in Medical Science, 2015.
- Ilev et al., Ultrahigh-resolution fiber-optic confocal microscope and method of use, Patent No. 8,456,738 (June 4, 2013).
- Ilev et al., Introduction to the IEEE JSTQE Special Issue on Nanobiophotonics, IEEE Journal of Selected Topics of Quantum Electronics, 2014.