Molecular-Specific Sensing and Imaging of Biological Samples

在过去的三十年中，基于光学的传感和成像技术由于其安全的非电离性和检测组织结构异常的高灵敏度而受到了极大的关注。这些技术的对比来源主要是来自生物结构的光散射，在疾病的早期阶段往往无法发现健康组织和恶性组织之间的区别。这种限制是由于诱导的变化通常在早期疾病阶段在分子水平而不是结构水平开始。本研究计划旨在结合各种光-物质相互作用机制（如光的散射和吸收），为生物样品的结构和分子对比的同步传感/成像产生新的知识和技术，从而在早期阶段更准确地诊断疾病和病症。目标应用涵盖了广泛的生物样品，从生物分子到微生物到组织：生物分子的光热传感。我们将开发从流体生物样品（例如COVID-19病毒或大麻的四氢大麻酚/精神活性成分）中提取、浓缩和分离生物分子的知识和低成本技术，然后利用光的吸收来准确检测和量化生物分子的浓度。这些创新将使生物分子的低成本检测成为可能，但准确性由昂贵且耗时的实验室技术（例如，PCR）提供。蠕虫的高通量高含量显微镜。秀丽隐杆线虫是经常用于研究人类疾病（如帕金森病）潜在机制的模式生物。我们将开发人工智能引导的光流体解决方案，以高分辨率和前所未有的高速度连续成像秀丽隐杆线虫种群的结构和荧光表达。这些平台有望显著提高旨在揭示疾病机制或发现新药的生物学研究的效率。组织结构和化学的共登记断层扫描。我们将进行基础和应用研究，以实现组织的定量光热光学相干断层扫描。在3D和高分辨率下共同注册组织的结构和分子特征将能够早期检测疾病和病症（例如，识别容易破裂的心脏斑块）。该项目将在5年内培养22名本科生和7名研究生。他们将在物理、工程、生物和医学的界面上获得跨学科的技能，并与来自工业界、学术界和政府的合作者进行互动。受训者还将通过撰写论文和在会议上发表演讲，对研究成果的专业传播进行培训。

During the past three decades, optics-based sensing and imaging technologies have gained significant attention due to their safe non-ionizing nature and high sensitivity to detect tissue structural abnormalities. The source of contrast in these technologies is predominantly scattering of light from biological structures which frequently fails to detect the difference between healthy and malignant tissue at the early stages of diseases. This limitation is due to induced changes typically initiating at the molecular level rather than structural level at early disease stages. This proposed research program aims to employ a combination of various light-matter interactions mechanisms (e.g., scattering and absorption of light) to generate new knowledge and technologies for concurrent sensing/imaging of structure and molecular contrast of biological samples to enable more accurate diagnosis of diseases and conditions at early stages. Target applications covers a broad range of biological samples, spanning from biomolecules to microorganisms to tissue: Photothermal sensing of biomolecules. We will develop knowledge and low-cost technologies for the extraction, concentration, and isolation of biomolecules from fluidic biosamples (e.g., COVID-19 virus or THC/psychoactive element of cannabis) and then utilize absorption of light to accurately detect and quantify the concentration of the biomolecules. These innovations will enable low-cost detection of biomolecules at the points-of-need, but with accuracy offered by costly and time-consuming laboratory techniques (e.g., PCR). High-throughput high-content microscopy of worms. C. elegans worms are model organism frequently used for studying the underlying mechanisms of human diseases (e.g., Parkinson's disease). We will develop artificial-intelligence-guided optofluidic solutions for continuous imaging of both structure and fluorescent expression of C. elegans populations at high resolution and with an unprecedented high speed. These platforms are expected to significantly enhance the efficiency of biological studies aimed at revealing disease mechanisms or discovery of new drugs. Co-registered tomography of tissue structure and chemistry. We will perform fundamental and applied research to enable quantitative photothermal optical coherence tomography of tissue. Co-registered structural and molecular characterization of tissue in 3D and at high resolution will enable earlier detection of diseases and conditions (e.g., identification of rupture-prone cardiac plaques). This program will train 22 undergraduate students and 7 postgraduates over 5 years. They will gain interdisciplinary skills at the interface of physics, engineering, biology, and medicine and interact with our collaborators from industry, academia, and government. Trainees will also be trained on professional dissemination of research findings via writing papers and giving talks at conferences.