Spatial biology fundamentally requires in-situ 3D visualization of biological processes with subcellular precision. However, conventional imaging techniques are limited in their native imaging depth, resolution, and ability to simultaneously image molecules tagged for different emission wavelengths. In this talk, we will demonstrate the advantages of using engineered point spread functions (ePSFs) in an integrated hardware/software solution to enable real-time quantitative spatial information recovery for applications from live-cell imaging to multiomics, including 3D counting, 3D imaging, and 4D particle tracking. Compared with conventional microscopy, our ePSF-based solutions allow for increased depth of field per frame with enhanced 3D precision, eliminating or reducing the need for axial scanning. Offering up to 10x depth extension and NIR to UV wavelength compatibility, the adaptability of the SPINDLE platform allows for optimization to target application requirements, including multi-color and multi-modal measurements, up to four-color imaging or counting, simultaneous imaging and tracking, and more. SPINDLE is easily adjusted to work with a wide range of scientific microscopes and can be readily switched between imaging modes, including bypass mode for brightfield imaging.