TY - JOUR
T1 - Single-frame 3D fluorescence microscopy with ultraminiature lensless FlatScope
AU - Adams, Jesse K.
AU - Boominathan, Vivek
AU - Avants, Benjamin W.
AU - Vercosa, Daniel G.
AU - Ye, Fan
AU - Baraniuk, Richard G.
AU - Robinson, Jacob T.
AU - Veeraraghavan, Ashok
N1 - Funding Information:
We thank A. C. Sankaranarayanan for valuable discussions and for providing feedback on this manuscript. Funding: This work was supported in part by the NSF (grants CCF-1502875, CCF-1527501, and IIS-1652633) and the Defense Advanced Research Projects Agency (grant N66001-17-C-4012). Author contributions: A.V., J.T.R., and R.G.B. developed the concept and supervised the research. J.K.A. fabricated prototypes and designed and built experimental hardware setup. V.B. developed T2S model, computational algorithms, and simulation platform. B.W.A. designed and built software for hardware interface. D.G.V. prepared samples and aided in related experimental investigations. F.Y. aided in design and fabrication of components for prototypes. J.K.A. and V.B. performed the experiments. All authors contributed to the writing of the manuscript. Competing interests: A.V., R.G.B., J.T.R., V.B., J.K.A., and B.W.A. are inventors on a patent application related to this work (application no. PCT/US2017/044448, filed on 28 July 2017). The other authors declare that they have no competing interests. Data and materials availability: Our team is committed to reproducible research. With that in mind, we will release detailed procedures and protocols that we followed in the fabrication of our prototypes. We will also release standard data sets of images and volumes (including all the data presented in the paper) along with the code for image and volume reconstructions. This will be released publicly on a website that will be updated with newer data sets as they are acquired.
Publisher Copyright:
Copyright © 2017 The Authors.
PY - 2017
Y1 - 2017
N2 - Modern biology increasingly relies on fluorescence microscopy, which is driving demand for smaller, lighter, and cheaper microscopes. However, traditional microscope architectures suffer from a fundamental trade-off: As lenses become smaller, they must either collect less light or image a smaller field of view. To break this fundamental trade-off between device size and performance, we present a new concept for three-dimensional (3D) fluorescence imaging that replaces lenses with an optimized amplitude mask placed a few hundred micrometers above the sensor and an efficient algorithm that can convert a single frame of captured sensor data into high-resolution 3D images. The result is FlatScope: perhaps the world’s tiniest and lightest microscope. FlatScope is a lensless microscope that is scarcely larger than an image sensor (roughly 0.2 g in weight and less than 1 mm thick) and yet able to produce micrometer-resolution, high–frame rate, 3D fluorescence movies covering a total volume of several cubic millimeters. The ability of FlatScope to reconstruct full 3D images from a single frame of captured sensor data allows us to image 3D volumes roughly 40,000 times faster than a laser scanning confocal microscope while providing comparable resolution. We envision that this new flat fluorescence microscopy paradigm will lead to implantable endoscopes that minimize tissue damage, arrays of imagers that cover large areas, and bendable, flexible microscopes that conform to complex topographies.
AB - Modern biology increasingly relies on fluorescence microscopy, which is driving demand for smaller, lighter, and cheaper microscopes. However, traditional microscope architectures suffer from a fundamental trade-off: As lenses become smaller, they must either collect less light or image a smaller field of view. To break this fundamental trade-off between device size and performance, we present a new concept for three-dimensional (3D) fluorescence imaging that replaces lenses with an optimized amplitude mask placed a few hundred micrometers above the sensor and an efficient algorithm that can convert a single frame of captured sensor data into high-resolution 3D images. The result is FlatScope: perhaps the world’s tiniest and lightest microscope. FlatScope is a lensless microscope that is scarcely larger than an image sensor (roughly 0.2 g in weight and less than 1 mm thick) and yet able to produce micrometer-resolution, high–frame rate, 3D fluorescence movies covering a total volume of several cubic millimeters. The ability of FlatScope to reconstruct full 3D images from a single frame of captured sensor data allows us to image 3D volumes roughly 40,000 times faster than a laser scanning confocal microscope while providing comparable resolution. We envision that this new flat fluorescence microscopy paradigm will lead to implantable endoscopes that minimize tissue damage, arrays of imagers that cover large areas, and bendable, flexible microscopes that conform to complex topographies.
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U2 - 10.1126/sciadv.1701548
DO - 10.1126/sciadv.1701548
M3 - Article
C2 - 29226243
AN - SCOPUS:85041930367
SN - 2375-2548
VL - 3
JO - Science advances
JF - Science advances
IS - 12
M1 - e1701548
ER -