IP Library Granted Patent US 12,301,990
Granted Patent B2
US 12,301,990 · App. 17/444,603 · Granted May 13, 2025

Deep learning model for auto-focusing microscope systems

Inventors: Denis Sharoukhov (Brooklyn, NY); Tonislav Ivanov (Brooklyn, NY); Jonathan Lee (New York, NY)
Assignee: Nanotronics Imaging, Inc.
H04N23/675G06T7/0012G06T2207/10056
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Quick Facts
Patent No.
US 12,301,990
App. No.
17/444,603
Granted
May 13, 2025
Kind
B2
Abstract

A computing system receives, from an image sensor, at least two images of a specimen positioned on a specimen stage of a microscope system. The computing system provides the at least two images to an autofocus model for detecting at least one distances to a focal plane of the specimen. The computing system identifies, via the autofocus model, the at least one distance to the focal plane of the specimen. Based on the identifying, the computing system automatically adjusts a position of the specimen stage with respect to an objective lens of the microscope system.

Claims (52)

1. A microscope system comprising:

an optical system for imaging a specimen, the optical system comprising an objective lens and a specimen stage configured to support the specimen during imaging; and

a focus detection system for automatically focusing the optical system, the focus detection system comprising a computing system that includes a processor and a memory, the memory has programming code stored thereon, which, when executed by the processor, causes the computing system to perform operations, comprising:

receiving, by the computing system from the optical system, only two images of the specimen positioned on the specimen stage, wherein the two images comprise a first image taken above or below a focal plane of the specimen and a second image taken above or below the focal plane;

providing, by the computing system, the two images, as input, to a convolutional neural network to detect at least one distance to the focal plane of the specimen;

identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen by analyzing both the first image and the second image; and

based on the identifying, automatically adjusting, by the computing system, a position of the specimen stage with respect to the objective lens of the microscope system.

2. The microscope system of claim 1 , wherein receiving, by the computing system from the optical system, the two images of the specimen positioned on the specimen stage of the microscope system comprises:

receiving the first image at a first z-position; and

receiving the second image of the two images at a second z-position.

3. The microscope system of claim 2 , wherein an x-position and a y-position of the specimen stage remains constant while the first z-position differs from the second z-position.

4. The microscope system of claim 1 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

generating a range of distances to the focal plane, wherein the range of distances comprises an actual distance to the focal plane.

5. The microscope system of claim 1 , wherein the focal plane is one of multiple focal planes.

6. The microscope system of claim 5 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

identifying at least one first distance to a first focal plane of the multiple focal planes of the specimen; and

identifying at least one second distance to a second focal plane of the multiple focal planes of the specimen.

7. The microscope system of claim 1 , wherein automatically adjusting, by the computing system, the position of the specimen stage with respect to the objective lens of the microscope system comprises:

causing a drive mechanism of the microscope system to adjust the distance between the specimen stage and the objective lens.

8. A method comprising:

receiving, by a computing system from an image sensor, only two images of a specimen positioned on a specimen stage of a microscope system, wherein the two images comprise a first image taken above or below a focal plane of the specimen and a second image taken above or below the focal plane;

providing, by the computing system, the two images, as input, to a convolutional neural network to detect at least one distance to the focal plane of the specimen;

identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen by analyzing both the first image and the second image; and

based on the identifying, automatically adjusting, by the computing system, a position of the specimen stage with respect to an objective lens of the microscope system.

9. The method of claim 8 , wherein receiving, by the computing system from the image sensor, the two images of the specimen positioned on the specimen stage of the microscope system comprises:

receiving the first image of the two images at a first z-position; and

receiving the second image of the two images at a second z-position.

10. The method of claim 9 , wherein an x-position and a y-position of the specimen stage remains constant while the first z-position differs from the second z-position.

11. The method of claim 8 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

generating a range of distances to the focal plane, wherein the range of distances comprises an actual distance to the focal plane.

12. The method of claim 8 , wherein the focal plane is one of multiple focal planes.

13. The method of claim 12 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

identifying at least one first distance to a first focal plane of the multiple focal planes of the specimen; and

identifying at least one second distance to a second focal plane of the multiple focal planes of the specimen.

14. The method of claim 8 , wherein automatically adjusting, by the computing system, the position of the specimen stage with respect to the objective lens of the microscope system comprises:

causing a drive mechanism of the microscope system to adjust the distance between the specimen stage and the objective lens.

15. A non-transitory computer readable medium comprising one or more sequences of instructions, which, when executed by a processor, causes a computing system to perform operations comprising:

receiving, by the computing system from an image sensor, only two images of a specimen positioned on a specimen stage of a microscope system, wherein the two images comprise a first image taken above or below a focal plane of the specimen and a second image taken above or below the focal plane;

providing, by the computing system, the two images, as input, to a convolutional neural network for detecting at least one distance to the focal plane of the specimen;

identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen by analyzing both the first image and the second image; and

based on the identifying, automatically adjusting, by the computing system, a position of the specimen stage with respect to an objective lens of the microscope system.

16. The non-transitory computer readable medium of claim 15 , wherein receiving, by the computing system from the image sensor, the two images of the specimen positioned on the specimen stage of the microscope system comprises:

receiving the first image of the two images at a first z-position; and

receiving the second image of the two images at a second z-position.

17. The non-transitory computer readable medium of claim 15 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

generating a range of distances to the focal plane, wherein the range of distances comprises an actual distance to the focal plane.

18. The non-transitory computer readable medium of claim 15 , wherein the focal plane is one of multiple focal planes.

19. The non-transitory computer readable medium of claim 18 , wherein identifying, via the convolutional neural network, the at least one distance to the focal plane of the specimen comprises:

identifying at least one first distance to a first focal plane of the multiple focal planes of the specimen; and

identifying at least one second distance to second focal plane of the multiple focal planes of the specimen.

20. The non-transitory computer readable medium of claim 15 , wherein automatically adjusting, by the computing system, the position of the specimen stage with respect to the objective lens of the microscope system comprises:

causing a drive mechanism of the microscope system to adjust the distance between the specimen stage and the objective lens.

Assignments (2)
SECURITY INTEREST Recorded Nov 30, 2023
From: NANOTRONICS IMAGING, INC.; NANOTRONICS HEALTH LLC; CUBEFABS INC.
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES IV, LP
Reel/Frame 065726/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 2, 2021
From: SHAROUKHOV, DENIS; IVANOV, TONISLAV; LEE, JONATHAN
To: NANOTRONICS IMAGING, INC.
Reel/Frame 057372/0823 →
Continuity (2)
Provisional Application 63062592 · Aug 7, 2020
Related Publication 20220046180A1 · Feb 10, 2022
References Cited (43)
US 5245173A · Yamana et al. · 1993 [cited by applicant]
US 5932872A · Price · 1999 [cited by examiner]
US 7576307B2 · Yazdanfar et al. · 2009 [cited by applicant]
US 10146041B1 · Putman et al. · 2018 [cited by applicant]
US 20050056767A1 · Kaplan et al. · 2005 [cited by applicant]
US 20080266440A1 · Yazdanfar et al. · 2008 [cited by applicant]
US 20080266652A1 · Yazdanfar · 2008 [cited by examiner]
US 20080291532A1 · Xu et al. · 2008 [cited by applicant]
US 20090074393A1 · Park et al. · 2009 [cited by applicant]
US 20090195688A1 · Henderson et al. · 2009 [cited by applicant]
US 20120106937A1 · Molin et al. · 2012 [cited by applicant]
US 20120236120A1 · Kramer · 2012 [cited by examiner]
US 20180292638A1 · Bredno et al. · 2018 [cited by applicant]
US 20180329194A1 · Small et al. · 2018 [cited by applicant]
US 20190339503A1 · Putman et al. · 2019 [cited by applicant]
US 20200160065A1 · Weinzaepfel · 2020 [cited by applicant]
US 20210011271A1 · Putman et al. · 2021 [cited by applicant]
US 20220028116A1 · Sieckmann et al. · 2022 [cited by applicant]
US 20230113528A1 · Putman et al. · 2023 [cited by applicant]
CN 106842534 · 2017 [cited by applicant]
DE 102018219867A1 · 2020 [cited by applicant]
JP H04330411A · 1992 [cited by applicant]
JP H0593845A · 1993 [cited by applicant]
JP H10502466A · 1998 [cited by applicant]
JP 2009069831A · 2009 [cited by applicant]
JP 2016527549A · 2016 [cited by applicant]
JP 202027659 · 2020 [cited by applicant]
KR 20140045331 · 2014 [cited by applicant]
KR 20150034757 · 2015 [cited by applicant]
WO 9601438A1 · 1996 [cited by applicant]
WO 0239059 · 2002 [cited by applicant]
WO 2019159627 · 2019 [cited by applicant]
Wei L, Roberts E. Neural network control of focal position during time-lapse microscopy of cells. Scientific reports. May 9, 2018;8(1): 1-0. (Year: 2018). [cited by examiner]
Dastidar TR, Ethirajan R. Whole slide imaging system using deep learning-based automated focusing. Biomedical Optics Express. Jan. 1, 2020;11(1):480-91. (Year: 2020). [cited by examiner]
Sun, Y., Zhu, L., Wang, G. and Zhao, F., 2017. MultiaInput Convolutional Neural Network for Flower Grading. Journal of Electrical and Computer Engineering, 2017(1), p. 9240407. (Year: 2017). [cited by examiner]
PCT International Application No. PCT/US21/44988, International Search Report and Written Opinion of the International Searching Authority, dated Nov. 9, 2021, 8 pages. [cited by applicant]
Office Action for Taiwan Patent Application No. 110129282, mailed Apr. 6, 2023, 4 pages. [cited by applicant]
Office Action for Japanese Patent Application No. 2023507491, mailed Dec. 22, 2023, 11 Pages. [cited by applicant]
Office Action of JP Patent Application No. 2023-5074991, dated Jul. 5, 2024, 7 pages. [cited by applicant]
Extended European Search Report for Application No. 21853698.5, dated Aug. 2, 2024, 11 pages. [cited by applicant]
Shajkofci A., et al., “DeepFocus: A Few-Shot Microscope Slide Auto-Focus Using a Sample Invariant CNN-Based Sharpness Function,” 2020 IEEE 17th International Symposium on Biomedical Imaging (ISBI), IEEE, Apr. 3, 2020, p… [cited by applicant]
Wang C., et al., “Intelligent Autofocus,” arXiv:2002.12389v1, Feb. 27, 2020, 12 pages. [cited by applicant]
Office Action for Korean Patent Application No. 10-2023-7000838, mailed Jan. 3, 2025, 8 pages. [cited by applicant]