Fully refractive adaptive optics fluorescence microscope using an optofluidic wavefront modulator.

Adaptive optics (AO) represents a powerful range of image correction technologies with proven benefits for many life-science microscopy methods. However, the complexity of adding a reflective wavefront modulator and in some cases a wavefront sensor into an already complicated microscope has made AO prohibitive for its widespread adaptation in microscopy systems. We present here the design and performance of a compact fluorescence microscope using a fully refractive optofluidic wavefront modulator, yielding imaging performance on par with that of conventional deformable mirrors, both in correction fidelity and articulation. We combine this device with a modal sensorless wavefront estimation algorithm that uses spatial frequency content of acquired images as a quality metric and thereby demonstrate a completely in-line adaptive optics microscope that can perform aberration correction up to 4th radial order of Zernike modes. This entirely new concept for adaptive optics microscopy may prove to extend the performance limits and widespread applicability of AO in life-science imaging.