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

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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.