US 12,253,469 B2
Systems and methods for improved light-sheet microscopy
Yehe Liu, Cleveland, OH (US); and Michael Jenkins, Cleveland, OH (US)
Assigned to CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
Appl. No. 17/626,328
Filed by Case Western Reserve University, Cleveland, OH (US)
PCT Filed Jul. 16, 2020, PCT No. PCT/US2020/042212
§ 371(c)(1), (2) Date Jan. 11, 2022,
PCT Pub. No. WO2021/011709, PCT Pub. Date Jan. 21, 2021.
Claims priority of provisional application 62/936,757, filed on Nov. 18, 2019.
Claims priority of provisional application 62/874,688, filed on Jul. 16, 2019.
Prior Publication US 2022/0269058 A1, Aug. 25, 2022
Int. Cl. G02B 21/36 (2006.01); G01N 21/64 (2006.01); G02B 7/08 (2021.01); G02B 21/08 (2006.01); G02B 21/16 (2006.01)
CPC G01N 21/6458 (2013.01) [G02B 7/08 (2013.01); G02B 21/082 (2013.01); G02B 21/16 (2013.01); G02B 21/36 (2013.01); G02B 21/361 (2013.01); G02B 21/367 (2013.01); G02B 21/368 (2013.01); G01N 2021/6439 (2013.01); G01N 2201/0221 (2013.01); G01N 2201/0621 (2013.01)] 24 Claims
OG exemplary drawing
 
1. A system that facilitates light-sheet microscopy comprising:
a light generation system consisting essentially of:
a multimode laser diode configured to output a light beam with a high order Hermite-Gaussian mode, wherein a Hermite polynomial of a Gaussian function of a beam profile of the light beam has a Hermite-Gaussian index equal to zero in one dimension and greater than zero in another dimension, wherein the one dimension with the index equal to zero has a higher output divergence than the other dimension;
a collimating lens configured to collimate the light beam;
a light focusing system comprising:
a focusing lens configured to focus the collimated light beam into a focal sheet within a focal plane of an imaging device by achieving a wide and flat beam profile at a center of the light beam corresponding to a field of view, wherein the focal sheet is a light sheet, wherein the focusing lens is configured to focus the light beam in the one dimension that the Hermite-Gaussian index equal to zero has a higher output divergence, wherein the focusing lens is a cylindrical lens or an acylindrical lens; and
a voice coil motor (VCM) attached to the focusing lens and configured to move the focusing lens along an axis of the light beam by vibrating at a rate of 10 Hz to 100 Hz, causing a change in a position of the light sheet within the focal plane of the imaging device; and
a fluid chamber configured to immerse a sample in a medium and configured to receive a focused and collimated light beam, the fluid chamber comprising:
a sample holder configured to secure the sample immersed in the medium in the fluid chamber; and
a positive cylindrical optical window attached directly to an outside of the fluid chamber, wherein the distance between the sample and the focusing lens is reduced by a factor of 1.25 compared to traditional light sheet microscopy.