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In vivo lensless microscopy via a phase mask generating diffraction patterns with high-contrast contours

Jesse K. Adams, Dong Yan, Jimin Wu, Vivek Boominathan, Sibo Gao, Alex V. Rodriguez, Soonyoung Kim, Jennifer Carns, Rebecca Richards‐Kortum, Caleb Kemere, Ashok Veeraraghavan, Jacob T. Robinson

2022Nature Biomedical Engineering100 citationsDOIOpen Access PDF

Abstract

Abstract The simple and compact optics of lensless microscopes and the associated computational algorithms allow for large fields of view and the refocusing of the captured images. However, existing lensless techniques cannot accurately reconstruct the typical low-contrast images of optically dense biological tissue. Here we show that lensless imaging of tissue in vivo can be achieved via an optical phase mask designed to create a point spread function consisting of high-contrast contours with a broad spectrum of spatial frequencies. We built a prototype lensless microscope incorporating the ‘contour’ phase mask and used it to image calcium dynamics in the cortex of live mice (over a field of view of about 16 mm 2 ) and in freely moving Hydra vulgaris , as well as microvasculature in the oral mucosa of volunteers. The low cost, small form factor and computational refocusing capability of in vivo lensless microscopy may open it up to clinical uses, especially for imaging difficult-to-reach areas of the body.

Topics & Concepts

OpticsMicroscopyMicroscopePoint spread functionPhase contrast microscopyOptical microscopeBright-field microscopyContrast (vision)Computer sciencePhase (matter)Materials scienceComputer visionPhysicsScanning electron microscopeQuantum mechanicsDigital Holography and MicroscopyAdvanced Fluorescence Microscopy TechniquesRandom lasers and scattering media
In vivo lensless microscopy via a phase mask generating diffraction patterns with high-contrast contours | Litcius