Line excitation array detection microscopy

Patent metadata

Field	Value
Publication number	US-2021161385-A1
Application number	US-201917054266-A
Country	US
Kind code	A1
Filing date	May 10, 2019
Priority date	May 10, 2018
Publication date	Jun 3, 2021
Grant date	—

Abstract

Disclosed herein are systems and methods for line excitation array detection (LEAD) microscopy. The systems and methods include an excitation beam from an optical beam source and a subject of interest. Light is scanned across the subject of interest and optical signals are detected using a parallel optical detection means. A number of mechanical, acoustic and or optical components such as scanning mirrors, DMDs, OADs, electric motors may be used in separately or in conjunction to aid in the scanning of the excitation beam across the subject of interest

First claim

What is claimed is:

1 . A system for imaging of a subject of interest, comprising:
an optical beam source configured to provide an excitation beam; one or more beam scanners configured for line scanning of the excitation beam across the subject; and one or more linear arrays of optical detectors configured for parallel detection of the optical signals from the different segments of the subject in response to the excitation beam.

2 . The system of claim 1 , wherein the one or more beam scanners comprise one or more scanning mirrors coupled to the optical beam source.

3 . The system of claim 2 , wherein the one or more scanning mirrors perform the line scanning by movement using at least one of electric motors, galvanometers, piezoelectric actuators, magnetostrictive actuators, or MEMS.

4 . The system of claim 1 , wherein the one or more beam scanners comprise an acousto-optic deflector (AOD) coupled to the optical beam source.

5 . The system of claim 4 , wherein the AOD is comprised of a crystal in a longitudinal mode.

6 . The system of claim 4 , wherein the AOD operates in a chirped mode or a dwell mode.

7 . The system of claim 4 , wherein the AOD is configured to produce a scan rate of up to about 10 MHz.

8 . The system of claim 4 , wherein the AOD is comprised of a crystal in a shear mode.

9 . The system of claim 4 , wherein the AOD is comprised of TeO 2 , PbMoO 4 , Quartz, or Ge crystals.

10 . The system of claim 1 , wherein the one or more beam scanners comprise an electro-optic deflector (EOD) coupled to the optical beam source.

11 . The system of claim 1 , wherein the one or more beam scanners are configured for random access scanning.

12 . The system of any one of claims 1 - 11 , wherein the one or more linear arrays of optical detectors comprises a linear array of photomultiplier tubes (PMTs).

13 . The system of any one of claims 1 - 11 , wherein the one or more linear arrays of optical detectors comprise a silicon photomultiplier (SiPM) array, avalanche photodiode array, a linescan camera with an intensifier, or a linescan camera without an intensifier.

14 . The system of claim 1 , wherein each of the optical detectors collects light from a different respective segment of the excitation beam.

15 . The system of any one of claims 1 - 14 , further comprising a parallel data acquisition system coupled to the one or more linear arrays of optical detectors and an image reconstruction system coupled to one or more multi-channel data acquisition devices, configured to generate three-dimensional images of the subject based on the detected optical signals.

16 . The system of claim 15 , wherein the one or more multi-channel data acquisition devices includes a plurality of multi-channel data acquisition devices that operate in different computers that are synchronized to collect data from the one or more linear arrays optical detectors.

17 . The system of claim 1 , wherein the at least one of the one or more linear arrays of optical detectors is arranged at angle in between 10° to 170° to the scanning direction.

18 . The system of claim 1 , wherein the one or more linear arrays of optical detectors are configured for detecting one or more signals from a complete or partial excitation beam line as the beam scans and such that a full image frame is generated for each scan cycle.

19 . The system of claim 1 , wherein the one or more linear arrays of optical detectors are configured to measure fluorescence optical signals from the subject of interest, in response to excitation from the excitation beam.

20 . The system of claim 1 , configured for laser speckle contrast imaging, volumetric phosphorescence lifetime microscopy, or high-speed particle image velocimetry (PIV).

21 . The system of claim 1 , configured for flow cytometry wherein the subject is in motion through the system during the scanning.

22 . The system of claim 1 , wherein the subject comprises one or more cells or three-dimensional tissue constructs.

23 . The system of claim 1 , wherein the subject is a complete living organism.

24 . The system of claim 1 , wherein the subject is a non-biological object.

25 . The system of claim 1 , further comprising:
an optical feedback system configured to monitor location of the excitation beam during scanning, wherein the optical feedback system comprises an optical detector and slit configured to monitor location of a second order diffraction beam or calibration beam for calibrating location of the excitation beam.

26 . The system of claim 1 , wherein the system is configured for nonlinear microscopy.

27 . The system of claim 26 , wherein the system is configured for two-photon or multi-photon fluorescence or auto-fluorescence.

28 . The system of claim 26 , wherein the system is configured for second or third harmonic generation microscopies.

29 . The system of claim 26 or 27 , wherein the system is configured for imaging of a 3D tissue construct.

30 . The system of claim 1 , wherein the system is configured for imaging of at least part of the brain of the subject.

31 . The system of claim 1 , wherein the system is configured for in vivo imaging of at least part of the brain of the subject.

32 . The system of claim 1 , wherein the system is configured for imaging at least part of the heart of the subject and the imaging comprises imaging an active function of the heart of the subject.

33 . The system of claim 26 , wherein the system is configured to excite a plane that is from −80° to 80° at an angle to the optical axis and image through a single objective.

34 . The system of claim 26 , further comprising:
a simultaneous spatial and temporal focusing (SSTF) system for increasing axial resolution, wherein the SSFT system comprises a diffraction grating, a grism, or a digital micromirror device (DMD) configured as a grating.

35 . The system of claim 26 , further comprising an axial scanning system, the axial scanning system comprising at least one of:
a piezoelectric stage to which an objective is mounted, moving along the optical axis; a tunable lens before the objective; remote focusing in which an axially scanned mirror is imaged onto the subject; and a spatial light modulator configured as a reflective lens before the objective.

36 . The system of claim 1 , wherein the one or more linear arrays of optical detectors are combined with spectral filters and configured for multi-color imaging.

37 . The system of claim 1 , wherein the system is further configured to correct optical aberrations using customized objectives or an objective-device immersion system or adaptive optics or a prism below the microfluidic device, in the path of the excitation beam and collection signal or a tilted lens or tilted piece of glass in a conjugate imaging plane of the imaging path.

38 . The system of claim 1 , wherein the system is further configured to generate an excitation beam in the configuration of a Gaussian beam or Bessel beam or Airy beam.

39 . The system of claim 1 , wherein the system is further configured to shape the laser excitation beam entering the AOD apertu

Assignees

• Univ Texas

Inventors

• Ben-Yakar Adela
• Li Tianqi
• Martin Chris
• Zhao Peisen

Classifications

• G01N2015/1006

  for cytology · CPC title

• G01N15/1434

  Optical arrangements · CPC title

• G02B2207/114

  Two photon or multiphoton effect · CPC title

• G02B21/10

  affording dark-field illumination (G02B21/14 {and G02B21/125} take precedence) · CPC title

• G02B21/0076

  arrangements using fluorescence or luminescence · CPC title