Label-free imaging of biological chromophores using photothermal signatures

在过去的三十年里，基于光学的成像技术因其安全、非电离和高分辨率而受到极大的关注。在这些技术中，对比度的来源主要是来自组织不均匀的光散射。然而，光散射对早期疾病诱导的异常不敏感，因为这些变化通常始于分子水平。通过光吸收获得诊断对比度是一种提高分子灵敏度的无标记解决方案。建议的研究计划旨在结合这一想法来引入新技术，并提高基于光学的分子对比成像的最新水平。在研究主题1中，我们将开发一种改进的光热光学相干层析成像(PT-OCT)系统，用于利用发色团的光热特征来可视化和研究发色团。光热响应的幅度和相位谱将被用于研究生色团/吸收体的物理性质。此外，还将雷达匹配滤波检测方法引入PT-OCT领域。在这里，光热光束将以编码的方式进行强度调制，相应的OCT相位信号将用互相关匹配滤波进行研究。这种方法有望通过允许重叠的生色团/吸收体的单个响应的去卷积来提高PT-OCT的分辨率。这一研究主题的结果不仅对加拿大公众作为疾病诊断成像设备有用，而且对加拿大研究人员作为表征分子物种和研究其活动的无标签成像工具也很有用。所发展的知识和技术有可能用于疾病的早期诊断、血氧和血糖水平的量化以及药物开发。在研究主题2中，我们将以Pi以前的研究为起点，开发一种热光子长波红外(LWIR)龋齿检测系统。在牙齿样本中使用长波红外探测波段是新颖的，从热波科学的角度来看也是有益的。该系统将结合单频和编码强度调制(即锁定和匹配滤波检测)来揭示牙齿早期脱矿。本课题的研究成果对加拿大公众作为一种早期的龋齿检测技术具有一定的参考价值。从长远来看，加拿大政府也有望从这项早期检测技术中受益，因为它降低了牙齿护理的成本。LWIR热光子系统的另一个潜在应用是对制造缺陷和材料缺陷进行无损评估。*5名研究生和5名本科生将在5年内接受培训，获得他们未来就业所需的一系列技术和软技能。

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.**