Rapid and high-contrast photothermal microscopy with a novel tunable ZGP source

具有新型可调谐 ZGP 光源的快速高对比度光热显微镜

基本信息

批准号：
10600781
负责人：
Adam M Hanninen
金额：
$ 30.56万
依托单位：
TRESTLE OPTICS LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-05 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10600781
关键词：
Address Algae Back Bacteria Biological Assay Biology Biopsy Cell Line Cell Separation Cells Cellular biology Chemicals Comparative Study Complement Dark-Field Microscope Data Development Diagnostic Engineering Fingerprint Fourier Transform Germanium Goals Health Health Promotion Heating Histopathology Image Imaging Techniques Industrialization Label Lasers Light Light Microscope Lipids Malignant Neoplasms Mammary Gland Parenchyma Maps Medicine Methods Microbe Microfluidic Microchips Microfluidics Microscopic Microscopy Molecular Probes Molecular Profiling Morphology Natural Products Noise Nutraceutical Optics Pain Performance Phenotype Physiologic pulse Physiological Play Polyunsaturated Fatty Acids Population Predictive Value Process Production Productivity Protocols documentation Public Health Pump Qualifying Rapid screening Refractive Indices Research Research Personnel Resolution Role Sampling Science Signal Transduction Source Specialist Specimen Spectrum Analysis Speed System Techniques Technology Tissue Microarray Tissue imaging Tissues Visible Radiation Visualization Yeasts Zinc absorption biomedical imaging commercialization contrast imaging design detection limit detector experimental study fundamental research high standard imaging approach imaging modality improved infrared microscopy innovation lens light microscopy long chain fatty acid novel prevent prototype quantum screening submicron tool

Address Algae Back Bacteria Biological Assay Biology Biopsy Cell Line Cell Separation Cells Cellular biology Chemicals Comparative Study Complement Dark-Field Microscope Data Development Diagnostic Engineering Fingerprint Fourier Transform Germanium Goals Health Health Promotion Heating Histopathology Image Imaging Techniques Industrialization Label Lasers Light Light Microscope Lipids Malignant Neoplasms Mammary Gland Parenchyma Maps Medicine Methods Microbe Microfluidic Microchips Microfluidics Microscopic Microscopy Molecular Probes Molecular Profiling Morphology Natural Products Noise Nutraceutical Optics Pain Performance Phenotype Physiologic pulse Physiological Play Polyunsaturated Fatty Acids Population Predictive Value Process Production Productivity Protocols documentation Public Health Pump Qualifying Rapid screening Refractive Indices Research Research Personnel Resolution Role Sampling Science Signal Transduction Source Specialist Specimen Spectrum Analysis Speed System Techniques Technology Tissue Microarray Tissue imaging Tissues Visible Radiation Visualization Yeasts Zinc absorption biomedical imaging commercialization contrast imaging design detection limit detector experimental study fundamental research high standard imaging approach imaging modality improved infrared microscopy innovation lens light microscopy long chain fatty acid novel prevent prototype quantum screening submicron tool

展开

项目摘要

Abstract. Natural products offer excellent sources of health-promoting medicines yet challenges in efficiently and economically sourcing these value-add bio-compounds have prevented their greater availability and promotion to public health. We address this problem by developing a novel image-based screening technology that offers highly sensitive, phenotypic bioassays of metabolite concentrations on live single cells. This allows a greatly improved method for identification of better natural product producers, as well as quantitative information about the production per cell and production distribution across the population. This high-resolution, non- destructive, label-free cell screening and cell sorting system is based on vibrational photothermal microscopy which uses mid-infrared light to probe molecular vibrational absorptions at resolutions comparable to visible light microscopes. To demonstrate the utility of the approach we focus on the production of essential polyunsaturated fatty acids (PUFAs) in lipid droplets sourced from microalgae (thraustochytrids) – a natural producer of PUFAs. These long-chain fatty acids play a vital role in the physiological health of cells and tissues throughout the body are commercialized as a prominent nutraceutical. To develop enriched cell lines, we will engineer and prototype a multichannel microfluidic chip with an active piezoelectric actuator to selectively save cells identified through photothermal as being highly productive. Our goal is to provide an attractive method to non-destructively evaluate metabolite content in engineered microbes including bacteria and yeast, not just algae, and for a variety of high-value metabolites. To accomplish these goals, we have established a team of qualified experts including specialists in advanced microscopy, microfluidics design, and algae cultivation for industrial applications. Ultimately, the methods developed here will showcase a roadmap toward rare-cell discovery and active cell sorting based on chemical mapping allowed through the photothermal imaging contrast.

抽象的。天然产品提供了促进健康的药物的绝佳来源，但在有效，经济地采购这些增值生物化合物已经阻止了他们的更大的可用性和促进公共卫生。我们通过开发小说来解决这个问题基于图像的筛选技术，可提供高度敏感的表型生物测定活细胞上的代谢物浓度。这允许大大改进识别更好的天然产品生产者，以及有关每个细胞的生产和人群的生产分布。这种高分辨率，非 - 破坏性，无标签的细胞筛选和细胞分选系统基于振动光热显微镜使用中红外光在分辨率下探测分子振动滥用者与可见光显微镜相当。为了证明我们关注的方法的实用性脂质液滴中必需的多不饱和脂肪酸（PUFAS）的产生来自微藻（Thraustochytrids） - Pufas的天然生产者。这些长链脂肪酸发挥在整个体内细胞和组织的身体健康中的重要作用是商业化的作为重要的营养。为了发展富集的细胞系，我们将设计和原型A 具有活性压电执行器的多通道微流体芯片可选择性地保存单元格通过光热鉴定为高生产力。我们的目标是提供有吸引力的非破坏性评估工程微生物中代谢物含量的方法细菌和酵母，不仅是藻类，以及各种高价值代谢产物。完成这些目标，我们建立了一个合格的专家团队，包括高级专家用于工业应用的显微镜，微流体设计和藻类种植。最终，此处开发的方法将展示通向稀有细胞发现和活动单元格的路线图基于通过光热成像对比度允许的化学映射进行排序。