High-resolution extended-depth phase-engineered objectives to accelerate spatial 'omics R&D through computational optics

高分辨率扩展深度阶段工程物镜加速空间组学研究

• 批准号: 10761173
• 负责人: Scott Gaumer
• 金额: $ 38.72万
• 依托单位: DOUBLE HELIX OPTICS INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10761173
• 关键词: 3-Dimensional; Acceleration; Adopted; Algorithms; Back; Bioinformatics; Biological Assay; Cell Survival; Cells; Chromatin; Colorado; Comparative Study; Complex; Computational algorithm; Consumption; DNA; Data; Data Collection; Data Set; Data Storage and Retrieval; Development; Discrimination; Drops; Electromagnetics; Elements; Engineering; Evaluation; Family; Feedback; Gene Expression; Genomics; Goals; Hour; Image; Imaging Device; Industry Collaboration; Investigation; Knowledge; Label; Licensing; Light; Marketing; Masks; Measurement; Messenger RNA; Methodology; Methods; Microscope; Microspheres; Modeling; Optics; Performance; Phase; Phototoxicity; Positioning Attribute; Process; Proteins; Proteomics; RNA; Recovery; Research; Research Personnel; Resolution; Rights; Sampling; Scanning; Slice; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Speed; Structure; System; Techniques; Technology; Testing; Three-Dimensional Image; Three-Dimensional Imaging; Time; Transcript; Universities; Validation; Work; bioinformatics pipeline; biological systems; cell fixing; data reduction; density; design; empowerment; epigenomics; experience; experimental study; genomic locus; human disease; imaging approach; imaging system; improved; innovation; instrumentation; lens; novel; optical imaging; protein complex; ratiometric; reconstruction; research and development; response; restoration; spatiotemporal; transcriptomics

Summary This SBIR Phase I project is focused on the design, development, and testing of groundbreaking engineered point spread function (ePSF) objective lenses, and matched computational algorithms for spatial omics research and development, which will be suitable for fixed and live-cell applications and will enable breakthroughs in fast live-cell spatial omics R&D by increasing the depth of field, with high-NA, for 3D volumetric projection and 3D volume data capture. By exploiting Double Helix Optics’ (DHO) Light Engineering™ technology, we will design, develop, and validate engineered Point Spread Function (ePSF) microscope objective lenses that extend the depth of field 2 to 5 times. This project will transform experiments by increasing the speed of data capture, enabling increased sample labeling density, reducing the size of datasets, reducing the burden on downstream bioinformatics pipelines, and empowering the spatio-temporal study of omics processes in living cells with decreased phototoxicity. The ePSF objectives will be easily integrated into commercially available microscopes, enhancing any closed-box imaging system or lab-built optical microscope. Recent research has demonstrated the need for novel optical imaging approaches in spatial omics applications, including ratiometric imaging of protein complexes, counting of mRNA in gene expression, localization and quantification of genomic loci, and understanding of chromatin dynamics. Unfortunately, current techniques rely on high resolution widefield microscopes, designed to perform best at focus with limited depth of field, leading to missed information. Thus, current techniques turn to axial scanning to capture the entirety of sample information, resulting in longer sample acquisition times, additional photodamage, bloated datasets, increased data storage, and n-fold increases in computation needed in bioinformatics pipelines. The ability to capture more information about a biological system under investigation in a single image with extended depth of field will enhance spatial omics studies by providing researchers with more quality information in less time, with less data to process; hence, it will improve their understanding of biological system structure, function, and dynamics. This will aid in the advancement of spatial genomics, transcriptomics, proteomics, and epigenomics. The ePSF objectives proposed here will address bottlenecks in spatial omics assays by accelerating capture of quality data, replacing the need for complex and time-consuming multi-slice imaging. Advances in spatial imaging will help elucidate many outstanding questions in biological systems. Ultimately, the ePSF objectives will provide a commercially available high-throughput imaging tool that will generate high-quality data for use in spatial omics studies, thus contributing to our knowledge of human disease processes. Double Helix Optics, a leader in 3D imaging, with exclusive licensing rights to its Light Engineering technology from U of Colorado and Stanford University, is optimally positioned to successfully bring this product to market.

摘要 该SBIR第一阶段项目专注于开创性工程的设计、开发和测试 点扩展函数(EPSF)物镜和用于空间组学研究的匹配计算算法 和开发，这将适用于固定和活细胞应用，并将使FAST取得突破 活细胞空间组学研发通过增加景深，高NA，用于3D体积投影和3D 卷数据捕获。通过利用双螺旋光学公司的光工程™技术，我们将设计、 开发并验证工程化点扩散函数(EPSF)显微镜物镜 景深2至5倍。这个项目将通过提高数据捕获的速度来改变实验， 实现了更高的样本标记密度，减少了数据集的大小，减轻了下游负担 生物信息学管道，并支持活细胞组学过程的时空研究 降低了光毒性。EPSF物镜将很容易集成到市场上可以买到的显微镜中， 增强任何封闭式成像系统或实验室建造的光学显微镜。 最近的研究表明在空间组学应用中需要新的光学成像方法， 包括蛋白质复合体的比率成像、基因表达中的mRNA计数、定位和 基因组位置的量化，以及对染色质动力学的理解。不幸的是，目前的技术依赖于 在高分辨率广域显微镜上，设计为在有限景深的情况下在聚焦时表现最佳，导致 遗漏的信息。因此，当前技术转向轴向扫描以捕获全部样本信息， 导致更长的样本采集时间、额外的光损伤、膨胀的数据集、增加的数据存储， 生物信息学管道所需的计算量增加了n倍。 能够在单个图像中捕获有关正在研究的生物系统的更多信息 扩展景深将通过为研究人员提供更高质量的信息来加强空间组学研究 在更短的时间内，需要处理的数据更少；因此，它将提高他们对生物系统结构的理解， 功能和动力学。这将有助于空间基因组学、转录组学、蛋白质组学和 表观基因组学。这里提出的EPSF目标将通过以下方式解决空间组学分析中的瓶颈 加快了高质量数据的捕获，取代了复杂且耗时的多层成像。 空间成像的进展将有助于阐明生物系统中许多悬而未决的问题。归根结底， EPSF Goals将提供商业上可用的高通量成像工具，该工具将产生高质量的 用于空间组学研究的数据，从而有助于我们对人类疾病过程的了解。 3D成像领域的领先者Double Helix Optics拥有其Light Engineering技术的独家许可权 来自科罗拉多大学和斯坦福大学的，处于成功将该产品推向市场的最佳地位。