Label-free imaging of biological chromophores using photothermal signatures

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Optics-based imaging technologies have gained significant attention during the past three decades due to their safe non-ionizing nature and high resolving power. The source of contrast in these technologies is predominantly light scattering from tissue inhomogeneity. However, light scattering is insensitive to early disease-induced abnormalities as these changes typically initiate at the molecular level. Obtaining diagnostic contrast from light absorption is a label-free solution for improving the molecular sensitivity. The proposed research program intends to incorporate this idea to introduce new technologies as well as to enhance the current state-of-the-art in optics-based molecular-contrast imaging. ****In research theme 1, we will develop a modified photo-thermal optical coherence tomography (PT-OCT) system for visualizing and studying chromophores using their photo-thermal signatures. The amplitude and phase spectrums of photo-thermal responses will be used to study the physical properties of chromophores/absorbers. Moreover, radar matched-filter detection method will be introduced to the PT-OCT field. Here the photo-thermal beam will be intensity modulated in a codded manner and the corresponding OCT phase signal will be studied with cross-correlation matched-filtering. This approach is expected to improve PT-OCT resolution by allowing for deconvolution of individual responses from overlapping chromophores/absorbers. The outcomes of this research theme are useful not only to Canadian public as a disease diagnostic imaging device, but also to Canadian researchers as a label-free imaging tool for characterizing molecular species and studying their activities. The developed knowledge and techniques have the potential to be used in early disease diagnosis, quantification of blood oxygenation and glucose levels, and drug discovery. ****In research theme 2, taking PI's previous research as a starting point, we will develop a thermo-photonic long-wavelength infrared (LWIR) dental caries detection system. Use of LWIR detection band in dental samples is novel and also beneficial from the thermal-wave science point of view. Single-frequency and codded intensity modulation (i.e. lock-in and matched-filter detection) will be incorporated in the system to reveal early tooth demineralization. The outcomes of this research theme are useful to Canadian public as an early dental caries detection technology. The Government of Canada is also expected to benefit from this early detection technology by lowering the cost of dental care in the long run. Another potential application of the LWIR thermo-photonic system is non-destructive evaluation of manufacturing flaws and defects in materials. ****Five graduate students and five undergraduate students will be trained within 5 years, gaining a spectrum of technical and soft skills required for their future employment.**