System and method for efficient detection of the phase and amplitude of a periodic modulation associated with self-interfering fluorescence

• US 9,784,681 B2
• Filed: 05/13/2014
• Issued: 10/10/2017
• Est. Priority Date: 05/13/2013
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: de Boer, Johannes F., De Groot, Mattijs
• Primary Examiner(s): Porta, David
• Assistant Examiner(s): Maupin, Hugh H
• Application Number:
  US14/890,530
• Publication Number:
  US 20160084763A1
• Time in Patent Office: 1,246 Days
• CPC Class Codes: G01J 3/0218 using optical fibers
• CPC Class Codes: G01J 3/433 Modulation spectrometry; Derivative spectrometry
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01J 3/453 by correlation of the amplitudes
• CPC Class Codes: G01J 3/4532 Devices of compact or symmetric construction G01J3/4531 takes precedence
• CPC Class Codes: G01J 3/4537 Devices with refractive scan
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

Systems and methods according to exemplary embodiments of the present disclosure can be provided that can efficiently detect the amplitude and phase of a spectral modulation. Such exemplary scheme can be combined with self-interference fluorescence to facilitate a highly sensitive depth localization of self-interfering radiation generated within a sample. The exemplary system and method can facilitate a scan-free depth sensitivity within the focal depth range for microscopy, endoscopy and nanoscopy.

Claims

1. An apparatus which is configured to obtain at least one electro-magnetic radiation from at least one portion of a sample, comprising:

at least one optical first arrangement which is configured to receive the at least one electro-magnetic radiation from the at least one portion, and generate at least one first radiation based on the at least one electro-magnetic radiation, wherein the at least one optical first optical arrangement receives, separates and recombines the at least one electro-magnetic radiation to be self-interfered to generate the first radiation;

at least one interference second arrangement which is configured to receive, separate and recombine the first radiation so as to self-interfere and generate at least one second radiation;

detector elements configured to detect the at least one second radiation; and

at least one computer third arrangement which is configured to determine information regarding the at least one portion based on the detected portions of the at least one second radiation.

2. The apparatus according to claim 1, wherein a path-length difference of the separated and recombined at least one electro-magnetic radiation is substantially the same as a path-length difference of the separated and recombined first radiation.

3. The apparatus according to claim 1, wherein the second arrangement generates a plurality of second radiations, and further comprising:

at least one combiner fourth arrangement which is configured to recombine at least two of the second radiations to generate a plurality of self-interfered third radiations wherein the detector elements are configured to detect the third radiations.

4. The apparatus according to claim 3, wherein the third arrangement is further configured to generate Fourier-transform data associated with the at least one particular radiation and the third radiations into transformed data, and wherein the transformed data is indicative of amplitude and phase of the self-interfered first radiation.

5. The apparatus according to claim 3, wherein the second and fourth arrangements are optical fiber arrangements.

6. The apparatus according to claim 1, wherein the information includes data regarding a position of a source of the at least one electro-magnetic radiation provided from the at least one portion of the sample.

7. The apparatus according to claim 1, wherein the at least one first arrangement is a catheter arrangement.

8. The apparatus according to claim 7, wherein the at least one first arrangement includes a phase-plate which introduces a path-length difference between portions of the separated and recombined electro-magnetic radiation so as to produce the self-interfered first radiation.

9. The apparatus according to claim 7, further comprising at least one radiation-providing arrangement which is configured to provide a particular radiation having characteristics to excite at least one fluorophore within the at least one portion so as to cause the at least one electro-magnetic radiation to be provided from the at least one portion.

10. The apparatus according to claim 1, wherein the at least one computer third arrangement determines the information regarding the at least one portion by generating the image of the at least one portion.

11. The apparatus according to claim 1, wherein the first and second arrangements are separate from one another.

12. The apparatus according to claim 1, wherein the detector elements include at least three detector elements which provide at least one of a phase or an amplitude of a spectral modulation of the at least one second radiation.

13. A method for obtaining at least one electro-magnetic radiation from at least one portion of a sample, comprising:

receiving the at least one electro-magnetic radiation from the at least one portion, and generating at least one first radiation based on the at least one electro-magnetic radiation, wherein the at least one electro-magnetic radiation is separated and recombined with at least one optical arrangement to be self-interfered to generate the first radiation;

receiving, separating and recombining the first radiation with at least one interference arrangement so as to further self-interfere and generate at least one second radiation; and

with detector elements, detecting portions the at least one second radiation;

using at least one computer arrangement, determining information regarding the at least one portion based on the detected portions of the at least one second radiation.

14. The method according to claim 13, wherein a path-length difference of the separated and recombined at least one electro-magnetic radiation is substantially the same as a path-length difference of the separated and recombined first radiation.

15. The method according to claim 13, further comprising:

generating a plurality of second radiations;

recombining at least two of the second radiations to generate a plurality of self-interfered third radiations; and

with the detector elements, detecting the third radiations.

16. The method according to claim 15, further comprising generating Fourier-transform data associated with the at least one particular radiation and the third radiations into transformed data, wherein the transformed data is indicative of amplitude and phase of the self-interfered first radiation.

17. The method according to claim 13, wherein the information includes data regarding a position of a source of the at least one electro-magnetic radiation provided from the at least one portion of the sample.

18. The method according to claim 13, further comprising providing a particular radiation having characteristics to excite at least one fluorophore within the at least one portion so as to cause the at least one electro-magnetic radiation to be provided from the at least one portion.

19. The method according to claims 13, wherein the determination of the information regarding the at least one portion includes generating the image of the at least one portion.

20. The method according to claim 13, wherein the optical and interference arrangements are separate from one another.

21. The method according to claim 13, wherein the detector elements include at least three detector elements, and further comprising providing at least one of a phase or an amplitude of a spectral modulation of the at least one second radiation using the at least three detector elements.