System, method and computer-accessible medium for providing wide-field superresolution microscopy

• US 8,097,864 B2
• Filed: 01/26/2010
• Issued: 01/17/2012
• Est. Priority Date: 01/26/2009
• Status: Expired due to Fees

• Current Assignee: Boston Beer Corporation (Boston Beer Co., Inc.), The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Tearney, Guillermo J., Bouma, Brett E., Yuan, Jing
• Primary Examiner(s): Kim, Kiho
• Application Number:
  US12/693,563
• Publication Number:
  US 20100207037A1
• Time in Patent Office: 721 Days
• Field of Search: 250/459.1, 250/458.1
• US Class Current: 250/459.1
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G02B 21/0032 Optical details of illumination, e.g. light-sources, pinholes, beam splitters, slits, fibers G02B21/0036 - G02B21/008; means for illumination of specimens in general G02B21/06
• CPC Class Codes: G02B 21/0072 details concerning resolution or correction, including general design of CSOM objectives
• CPC Class Codes: G02B 21/0076 arrangements using fluorescence or luminescence
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 27/48 Laser speckle optics

Abstract

Exemplary embodiments of apparatus, system, method and computer-accessible medium using which at least one first pulsed electro-magnetic radiation is generated. Such radiation depletes at least one excited state of at least one molecule. Further, it is possible to generate at least one second electro-magnetic radiation based on the first pulsed electro-magnetic radiation(s). For example, the second electro-magnetic radiation(s) can have a pattern with a plurality of spots.

Claims

1. An apparatus comprising:

at least one first arrangement configured to generate at least one first pulsed electro-magnetic radiation which excites at least one molecule; and

at least one second arrangement which is configured to generate at least one second electro-magnetic radiation based on the at least one first pulsed electro-magnetic radiation, wherein the at least one second electro-magnetic radiation has a speckle pattern with a plurality of spots, and which depletes at least one excited state of the at least one molecule.

2. The apparatus according to claim 1, wherein the pattern is changeable.

3. The apparatus according to claim 2, further comprising at least further arrangement configured to (i) receive further radiation from a sample based on the first and second radiation and generate at least image associated with a depth of the sample, and (ii) measure at least one of a variance, edges or a high spatial frequency content of the at least one image as it is changed over time.

4. The apparatus according to claim 1, wherein the at least one molecule is provided in a biological structure.

5. The apparatus according to claim 1, further comprising at least one third arrangement which is configured to forward the further and second radiations to a substantially the same location on or in a biological structure.

6. The apparatus according to claim 5, further comprising at least one fourth arrangement which is configured to receive at least one third electro-magnetic radiation from the biological structure, the at least one third electro-magnetic radiation has a wavelength which is different from a wavelength of the at least one first electro-magnetic radiation.

7. The apparatus according to claim 6, wherein the at least one fourth arrangement generates an image of at least one portion of the biological structure based on the at least one third electro-magnetic radiation.

8. The apparatus according to claim 7, wherein the at least one fourth arrangement includes an array of detectors or at least one charged coupled detector.

9. The apparatus according to claim 6, wherein the at least one fourth arrangement generates a plurality of different images of a plurality of portions of the biological structure having a plurality of distinct patterns based on the at least one third electro-magnetic radiation, and forms a final images from the plurality of the image.

10. The apparatus according to claim 9, wherein the at least one fourth arrangement is further configured to process and associate at least one image of the images with one or more predetermined functions.

11. The apparatus according to claim 10, wherein the at least one fourth arrangement is further configured to determine one or more center of the one or more predetermined functions.

12. The apparatus according to claim 10, wherein the at least one image is acquired associated with a plurality of the one or more of the centers.

13. The apparatus according to claim 10, wherein the at least fourth arrangement processes a plurality of the images based on a plurality of the centers to form a final image.

14. The apparatus according to claim 6, wherein the at least one third electro-magnetic radiation is a florescence radiation.

15. The apparatus according to claim 1, wherein the at least one second arrangement is controllable to change the pattern of the at least one second electro-magnetic radiation.

16. The apparatus according to claim 1, further comprising at least one fifth arrangement which controls the at least one second arrangement to change the pattern of the at least one second electro-magnetic radiation.

17. The apparatus according to claim 16, wherein the at least one fifth arrangement includes at least one of (i) a spatial light modulator, (ii) a digital light processor, (iii) a movable diffusing arrangement, or (iv) a digital mirror arrangement.

18. A method comprising:

using at least one hardware arrangement, generating at least one first pulsed electro-magnetic radiation which excites at least one molecule; and

generating at least one second electro-magnetic radiation based on the at least one first pulsed electro-magnetic radiation, wherein the at least one second electro-magnetic radiation has a speckle pattern with a plurality of spots, and which depletes at least one excited state of the at least one molecule.

19. A computer-accessible medium which has software thereon, wherein, when a computing arrangement retrieves and executes the software, the computing arrangement is configured to perform procedures comprising:

causing a generation of at least one first pulsed electro-magnetic radiation which excites at least one molecule; and

causing a generation of at least one second electro-magnetic radiation based on the at least one first pulsed electro-magnetic radiation, wherein the at least one second electro-magnetic radiation has a speckle pattern with a plurality of spots, and which depletes at least one excited state of the at least one molecule.