IP Library › Granted Patent US 12,442,766
Granted Patent B2
US 12,442,766 · App. 18/582,748 · Granted Oct 14, 2025

Bond-selective intensity diffraction tomography and uses thereof

Inventors: Ji-Xin Cheng (Newton, MA); Jian Zhao (Boston, MA); Lei Tian (Newton, MA); Alex Matlock (Brighton, MA)
Assignee: Trustees of Boston University
G01N21/636G01N2021/637G01N2021/655
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Quick Facts
Patent No.
US 12,442,766
App. No.
18/582,748
Granted
Oct 14, 2025
Kind
B2
Abstract

An example microscope includes a pump laser for providing a first illumination to a sample. A laser array provides a second illumination to the sample. The laser array may include a plurality of laser elements, each providing oblique illuminations to the sample. An illumination collecting source collects the first illumination and the second illumination from the sample. The illumination collecting source may capture transient 3D refractive index (RI) variations in the sample due to the first illumination and second illumination.

Claims (27)

1. An imaging system comprising:

an illumination source for providing oblique illuminations to a sample, the illumination source including a plurality of laser elements and a pump laser that are synchronized to produce the oblique illuminations, wherein the plurality of laser elements is arranged to form a ring of laser elements such that each laser element on the ring of laser elements is positioned to produce an oblique illumination on the sample; and

a camera for collecting scattered illuminations from the sample, the camera producing intensity images encoding a volume of the sample for each of the oblique illuminations, wherein the camera captures three-dimensional chemical-specific refractive index (RI) variations of the sample due to the oblique illuminations using the intensity images.

2. The imaging system of claim 1 , further comprising:

an objective lens that is disposed between the sample and the camera, wherein an angle of an oblique illumination produced by each of the plurality of laser elements corresponds to a numerical aperture of the objective lens.

3. The imaging system of claim 1 , wherein the pump laser is a mid-IR pump laser.

4. The method of claim 1 , wherein the illumination source triggers mid-infrared photothermal (MIP) effects in the sample.

5. The imaging system of claim 1 , wherein the first illumination comprises a mid-IR fingerprint region between 5 μm and ˜20 μm.

6. The imaging system of claim 1 , wherein each of the laser elements is a Continuous Wave (CW) diode laser.

7. The imaging system of claim 1 , wherein each of the laser elements comprises a central wavelength between 400 nm and 700 nm.

8. The imaging system of claim 1 , wherein each of the laser elements is modulated at a tunable repetition rate between 0 kHz and 10 kHz.

9. The imaging system of claim 1 , wherein each of the laser elements comprises a pulse duration between 0.6 μs and 1 μs.

10. The imaging system of claim 1 , wherein the pump laser illuminates the sample under an on-axis configuration.

11. The imaging system of claim 1 , wherein each of the laser elements is operated at a same repetition rate and pulse duration as the pump laser.

12. The imaging system of claim 1 , wherein the camera is a CMOS camera or CCD camera.

13. A method for microscopic imaging comprising:

providing, using an illumination source, oblique illuminations to a sample, the illumination source including a plurality of laser elements and a pump laser that are synchronized to produce the oblique illuminations, wherein the plurality of laser elements is arranged to form a ring of laser elements such that each laser element on the ring of laser elements is positioned to produce an oblique illumination on the sample; and

using a camera, collecting scattered illuminations from the sample and producing intensity images encoding a volume of the sample for each of the oblique illuminations, wherein the camera captures three-dimensional chemical-specific refractive index (RI) variations of the sample due to the oblique illuminations using the intensity images.

14. The method of claim 13 , wherein the pump laser comprises a mid-IR pump laser.

15. The method of claim 13 , wherein each of the laser elements is a Continuous Wave (CW) diode laser.

16. The method of claim 13 , wherein each of the laser elements comprises a central wavelength between 400 nm and 700 nm.

17. The method of claim 13 , wherein each of the laser elements is modulated at a tunable repetition rate between 0 kHz and 10 kHz.

18. The method of claim 13 , wherein each of the laser elements comprises a pulse duration between 0.6 μs and 1 μs.

19. The method of claim 13 , further comprising illuminating, using the pump laser, the sample under an on-axis configuration.

20. The method of claim 13 , wherein each of the laser elements is operated at a same repetition rate and pulse duration as the pump laser.

21. The method of claim 13 , wherein the camera is a CMOS camera or CCD camera.

22. The method of claim 13 , wherein an off-axis gold parabolic mirror focuses an oblique illumination produced by the pump laser to enhance an intensity at an area of interest on the sample.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 5, 2024
From: CHENG, JI-XIN; ZHAO, JIAN; TIAN, LEI; MATLOCK, ALEX
To: TRUSTEES OF BOSTON UNIVERSITY
Reel/Frame 067624/0930 →
Continuity (3)
Continuation 18100347 · Jan 23, 2023
Provisional Application 63389582 · Jul 15, 2022
Related Publication 20240272074A1 · Aug 15, 2024
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