Development of advanced non-invasive dynamic photoacoustic and photothermal imaging technologies for biomedical and industrial diagnostics

拟议的研究项目构成了我在先进扩散波和光声技术中心（CADIPT）正在进行的研究计划的基本支持，该计划旨在开发和有针对性地应用新型先进光声（PA）、光热（PT）和光电扩散波（DW）CADIPT中首创的成像技术。在生物医学成像方面，拟议的研究集中在3种PA和PT模式：1）波长调制差分光声雷达（WM-DPAR）; 2）波长调制差分光热辐射测量（WM-DPTR）; 3）增强截断相关光热相干断层扫描（TC-PCT）。光-超声（US）WM-DPAR和光-热波WM-DPTR和TC-PCT能量转换性质以及这些模态的非常有效的信号基线抑制对于在非常早期阶段诊断疾病非常有希望，并且形成了设计所提出的研究目标的主要标准。WM-DPAR具有低成本的连续波（CW）激光波长调制，深度分辨率约为2-3 cm，可集成到商业超声成像仪中，为US图像增加光谱分子对比度增强。WM-DPTR工作在中红外光谱范围内的激光诱导黑体发射，具有比PA更简单的仪器，没有耦合液和便携性。TC-PCT是一种高轴向分辨率（25 um）PT 3D成像方法，也基于激光诱导中红外光子发射和~4 mm深度分辨率。上述模式的应用被提出在三个主要领域：1）用于早期冠状动脉疾病的微创临床兼容WM-DPAR导管开发（动脉粥样硬化）诊断; 2）用于路边监测受损驾驶员四氢大麻酚的非侵入性WM-DPTR大麻传感器（THC;大麻的精神活性成分）组织液（与血液密切相关）浓度;和3）基于血红蛋白时间瞬变的eTC-PCT成像的棕色脂肪代谢的实时非侵入性测量（梯度）在健康和肥胖/糖尿病小鼠中，进行高脂肪饮食。 还建议开发超高频外差锁定载波成像（UHF-HeLIC）成像，作为半导体整个表面区域的独特非接触式无损光电DW检查工具，特别是快速生长清洁能源光伏Si太阳能电池技术。UHF-He LIC的一个独特功能是它可以用全光学非接触测量（例如电流-电压特性）来取代需要成品电子器件的传统局部电气测试，从而在任何和所有器件制造阶段都可以进行快速的晶圆级检测，而无需电引线。成像将识别并帮助最大限度地减少光电表面和体陷阱，并评估表面钝化和湿法清洗在光伏器件中的有效性。

The proposed research projects constitute fundamental support of my ongoing research program at the Center for Advanced Diffusion-Wave and Photoacoustic Technologies (CADIPT) toward the development and targeted applications of new advanced photoacoustic (PA), photothermal (PT) and optoelectronic diffusion-wave (DW) imaging technologies pioneered in the CADIPT. In biomedical imaging the proposed research focuses on 3 PA and PT modalities: 1) Wavelength-Modulated Differential Photoacoustic Radar (WM-DPAR); 2) Wavelength-Modulated Differential Photothermal Radiometry (WM-DPTR); and 3) Enhanced Truncated-Correlation Photothermal Coherence Tomography (TC-PCT). The light-to-ultrasound (US) WM-DPAR and light-to-thermal-wave WM-DPTR and TC-PCT energy conversion nature and the very efficient signal baseline suppression of these modalities are very promising for diagnosis of diseases at very early stages and form the major criterion for designing the objectives of the proposed research. WM-DPAR features low-cost continuous wave (CW) laser-wavelength modulation, ~ 2-3 cm depth resolution, and can be integrated into commercial ultrasound imagers to add spectroscopic molecular contrast enhancement to the US image. WM-DPTR operates on laser induced blackbody emissions in the mid-infrared spectral range and features simpler instrumentation than PA, no coupling fluid and portability. TC-PCT is a high axial-resolution (25 um) PT 3D imaging method, also based on laser-induced mid-infrared photon emissions and ~4 mm depth resolution. Applications of the aforementioned modalities are proposed in three major areas: 1) Minimally- invasive clinically compatible WM-DPAR catheter development for early coronary artery disease (atherosclerosis) diagnosis; 2) A non-invasive WM-DPTR cannabis sensor for roadside monitoring of impaired driver tetrahydrocannabinol (THC; the psychoactive component of cannabis) interstitial fluid (strongly related to blood) concentration; and 3) Real-time noninvasive measurements of brown fat metabolism based on eTC-PCT imaging of hemoglobin time transients (gradients) in healthy and obese/diabetic mice, subjected to a high fat diet.. It is also proposed to develop Ultra-High Frequency Heterodyne Lock-In Carrierography (UHF-HeLIC) imaging as a unique non-contacting nondestructive optoelectronic DW inspection tool of entire surface areas of semiconductors, specifically rapid-growth clean energy ultrathin photovoltaic Si solar cell technologies. A unique feature of UHF-He LIC is that it can replace conventional localized electrical testing requiring finished electronic devices with all-optical noncontact measurements of e.g. current-voltage characteristics, allowing fast, wafer-level inspections at any and all device fabrication stages with no need for electrical leads. The imaging will identify and help minimize optoelectronic surface and bulk traps and assess the effectiveness of surface passivation and wet cleans in ultrathin PV devices.