US 12,251,219 B2
Systems, methods, and apparatus for differential phase contrast microscopy by transobjective differential epi-detection of forward scattered light
Charles P. Lin, Arlington, MA (US); and Hari Prasad Paudel, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by The General Hospital Corporation, Boston, MA (US)
Filed on May 17, 2023, as Appl. No. 18/319,163.
Application 18/319,163 is a continuation of application No. 16/773,438, filed on Jan. 27, 2020, granted, now 11,690,540.
Claims priority of provisional application 62/892,621, filed on Aug. 28, 2019.
Claims priority of provisional application 62/796,703, filed on Jan. 25, 2019.
Prior Publication US 2023/0284939 A1, Sep. 14, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61B 5/145 (2006.01); A61B 5/00 (2006.01); A61B 5/1455 (2006.01); G01N 15/01 (2024.01); G01N 15/10 (2024.01); G01N 15/14 (2024.01); G01N 15/1434 (2024.01); G02B 21/00 (2006.01); G02B 21/08 (2006.01); G02B 21/14 (2006.01); G02B 21/36 (2006.01); G02B 26/12 (2006.01)
CPC A61B 5/14535 (2013.01) [A61B 5/0068 (2013.01); A61B 5/1455 (2013.01); G01N 15/1436 (2013.01); G01N 15/1468 (2013.01); G02B 21/002 (2013.01); G02B 21/0048 (2013.01); G02B 21/0056 (2013.01); G02B 21/0068 (2013.01); G02B 21/008 (2013.01); G02B 21/086 (2013.01); G02B 21/14 (2013.01); G02B 21/365 (2013.01); G02B 26/12 (2013.01); A61B 2562/0233 (2013.01); G01N 15/01 (2024.01); G01N 2015/1006 (2013.01); G01N 2015/144 (2013.01)] 24 Claims
OG exemplary drawing
 
1. A system for differential phase contrast microscopy by transobjective differential epi-detection of forward scattered light, comprising:
a scanning microscope comprising:
a light source;
an optical train defining an optical path of the scanning microscope having an optical axis comprising:
a scanner optically coupled to the light source and configured to scan a beam from the light source across a surface of a sample, and
a microscope objective optically coupled to the scanner; and
a detector mechanically coupled to the scanning microscope along the optical path within a first distance of a pupil plane of the optical train, the detector comprising:
a substrate defining a central aperture having a center configured to coincide with the optical axis of the optical path;
a first photodiode mechanically coupled to the substrate at a first radial distance from the center; and
a second photodiode mechanically coupled to the substrate at the first radial distance from the center and on an opposite side of the central aperture from the first photodiode,
wherein the first distance is less than or equal to twice the first radial distance, and
wherein the detector is integrated within the microscope objective; and at least one hardware processor that is programmed to:
cause the light source to emit a beam of light toward the sample via the optical train;
cause the scanner to scan the beam of light across the sample;
receive, from the detector, a plurality of output signals, each of the plurality of output signals indicative of a structure of the sample at a location at which the beam was focused;
generate an image based on the plurality of output signals; and
cause the image to be presented using a display.