This technology is a hybrid solid-liquid optical system that corrects spherical aberration in low-cost air objectives, enabling high-resolution light sheet imaging of large cleared and living biological samples.
Light sheet microscopy is the method of choice for volumetric imaging of cleared and living samples, but achieving subcellular resolution depends on specialized immersion objectives. These objectives cost tens of thousands of dollars and offer only millimeters of working distance, limiting imaging depth and flexibility across sample types and immersion media. Inexpensive air objectives provide the long working distances needed for large specimens, but refraction at the air-liquid boundary causes severe spherical aberration that degrades lateral and axial resolution. As a result, routine high-throughput, high-resolution imaging of large intact specimens remains out of reach for most laboratories.
This technology pairs a solid optical element with a refractive index-matched liquid to pre-compensate the aberrations that arise when an air objective images into an immersion medium. A curved off-the-shelf lens serves as the sample chamber window and is positioned so that light rays cross the air-liquid boundary nearly perpendicular, suppressing spherical aberration. Matching the refractive index of the lens material to the chamber liquid further raises the objective’s effective numerical aperture. The approach applies to both illumination and detection paths, is objective-agnostic, and integrates with existing light sheet platforms without specialized optics or adaptive correction hardware.
The corrective optics and imaging systems have been prototyped and validated with cleared tissue and large intact biological specimens, achieving submicron resolution with standard air objectives.
Patent pending
IR CU25135, CU25425, and CU26183
Licensing Contact: Kristin Neuman
