WO2025199128A1 - Dual off-axis parabolic mirrors-based capsule - Google Patents

Abstract

Disclosed herein are apparatus and systems of optical devices and methods of using the same. The optical device may include: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; an excitation optical waveguide configured to deliver light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and an emission detector configured to receive light from the sample.

Description

DUAL OFF-AXIS PARABOLIC MIRRORS-BASED CAPSULE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is based on and claims priority from U.S. Patent Application Ser. No. 63/566,784, filed on March 18, 2024, the entire disclosure of which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under award number 5R01EB034107-02 from the National Institutes of Health. The government has certain rights in the invention.

BACKGROUND

[0003] New endoscopic screening methods detect a high incidence of esophageal precancer, but only a small percent of pre-cancer progress to cancer. Multi-modal optical coherence tomography (OCT) tethered capsules have been developed using dual-clad fiber (DCF) which suffers from high fiber-generated autofluorescence, or a two-fiber design with poor co-axial beam alignment. To identify high-risk tissue in real-time for assessment of BE progression biomarkers, higher sensitivity is needed. A method to enhance risk progression identification is needed.

SUMMARY

[0004] Disclosed herein are apparatus, systems, and methods for an optical device. In some embodiments, the optical device may include: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; an excitation optical waveguide configured to deliver light from an excitation source to illuminate a sample using the first off- axis parabolic mirror and the second off-axis parabolic mirror; and an emission detector configured to receive light from the sample.

[0005] In other embodiments, a capsule-based optical device, including: a capsule including: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; a tether comprising an excitation optical waveguide configured to deliver light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and an emission detector coupled to the tether and configured to receive light from the sample.

[0006] In still other embodiments, a method of operating a capsule-based optical device, including: providing a capsule, the capsule including: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; delivering, using a tether comprising an excitation optical waveguide, light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and receiving, using an emission detector coupled to the tether, light from the sample.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Some embodiments of the disclosure are described herein with reference to the accompanying figures. The description and figures make apparent to a person having ordinary skill in the art how some embodiments of the disclosure may be practiced. The figures are for the purpose of illustrative discussion and no attempt is made to show structural details of an embodiment in more detail than is necessary for a fundamental understanding of the teachings of the disclosure, nor do they illustrate the invention to scale. Where dimensions are given in the text or figures, these dimensions are merely exemplary and do not limit the scope of the disclosed invention.

[0008] FIG. 1 A illustrated an embodiment of the DOAP capsule optics. A fiber tether includes a single mode fiber and multimode fiber. The light path of the single mode fiber (light traveling towards the sample as well as light returning from the sample) is shown in blue.

Autoflourescence is shown in yellow; the autofluorescence from the sample is directed to and collected by the multimode fiber.

[0009] FIG. IB illustrates an embodiment of the DOAP capsule optics. OCT light (light traveling towards the sample as well as light returning from the sample to the OCT platform) is shown in red, autofluorescence excitation is shown in blue, and autofluorescence emission is shown in yellow; the orange line between the WDM (wavelength division multiplexing) unit and the capsule represents combined autofluorescence excitation and OCT light.

[0010] FIG. 2A shows simulated performance comparison of the double off-axis parabolic (DOAP) capsule optics and a traditional Dual Clad Fiber (DCF) with ball lens approach. The optical collection is the fraction of emitted rays that get recollected in the detector after backscattering off the tissue. This approach ignores the fluorescence conversion efficiency.

[0011] FIG. 2B shows OCT resolution, defined as the full width half maximum (FWHM) spot size is improved in the DOAP design thanks to the well corrected focusing profile of the parabolic mirrors.

[0012] FIG. 3 shows an illustrated embodiment of capsule optics using a dual clad fiber and a ball lens. Light (traveling towards the sample as well as light returning from the sample) is shown in blue, and autofluorescence is shown in yellow; the gray circle represents a ball lens.

[0013] FIG. 4 illustrates an optical ray trace for DOAP autofluorescence modality. Excitation light is traced in blue and emission light is traced in green.

[0014] FIG. 5 shows a scaled-up benchtop set up of a DOAP optical configuration.

[0015] FIG. 6A shows a prototype of a DOAP optical configuration.

[0016] FIG. 6B shows a close up view of one DOAP in the prototype of a DOAP optical configuration.

[0017] FIG. 6C shows a close up view of one DOAP in the prototype of a DOAP optical configuration, focusing on the through-hole of one of the OAPs.

[0018] FIG. 7A shows a fluorescence channel (AFR) in the green wavelength. The red line shows the cut through shown in FIG. 7B. [0019] FIG. 7B shows an intensity profile of the cut through of FIG. 7A shown in red, as collected by a DOAP device.

[0020] FIG. 7C shows an OCT channel.

[0021] FIG. 7D shows an intensity profile of the cut through of FIG. 7C, as collected by a DOAP device.

DETAILED DESCRIPTION

[0022] In accordance with some embodiments of the disclosed subject matter, mechanisms (which can include, for example, systems, and methods) for an optical device are provided.

[0023] Endoscopies are frequently used to screen for esophageal cancer and have a high incidence of detecting pre-cancer. However, better methods are needed to differentiate pre-cancer that is at a high risk of progressing to cancer. One approach is to combine OCT imaging with autofluorescence imaging. Combining these two modalities allows the collection of more information in one procedure. While OCT provides high-resolution structural information, autofluorescence supplements this structural detail with information regarding the state of the imaged tissue, in particular whether the tissue is cancerous, the chemical/molecular structure composition of the tissue, amount of oxygenated/deoxygenated blood, and redox state of the cells. This can inform on abnormal phenotypes that are related to early cancer detection, risk of progression to cancer, and invasive cancer.

[0024] The optical devices described herein combines OCT and fluorescence focusing into a capsule platform. This novel configuration will allow clinicians to see deeper into tissue and accurately resolve distinct biological fluorescence signals to identify various conditions in the tissue including potential cancerous tissue.

[0025] Capsule

[0026] In one aspect, the device includes a capsule 102 which can house optical elements. See FIGS. 1A-1B. In some embodiments, the capsule 102 is a cylindrical (e.g., pill shaped) device measuring 8-11 mm in diameter and 18-25 mm in length. The outer cylinder is an optically clear, biocompatible plastic capped with two custom plastic caps that house the optics and motor. In some embodiments, the capsule 102 is swallowable (e.g., an adequate size and shape for a subject, such as a human, to swallow the capsule). In some embodiments, the biocompatible plastic is selected from polycarbonate or polymethyl methacrylate (PMMA). Two optical figures and four electrical wires used to control the motor within the capsule 102 exit the capsule via a tether 104, which is attached to an outside system for control and planning. See FIG. lAfor an example schematic.

[0027] The capsule 102 may be defined as having a proximal and distal end. The proximal end is defined as being close to the tether, and the distal end is defined as further from the tether.

[0028] Optics system

[0029] FIG. 2A and FIG. 2B show that using DOAP has higher OCT collection efficiency, and a finer/higher OCT resolution over a greater range of depths than dual-clad fibers (DCF), which are typically coupled to a ball lens. FIG. 3 shows an example diagram of a DCF/ball lens system. Thus, we designed a capsule device using a DOAP optical setup, which utilizes a through-hole configuration to ensure co-axial beam alignment. This configuration (1) allows for independent focusing to maintain OCT depth-of-focus and improves AFI collection, and (2) severely attenuates or virtually eliminating autofluorescence and scattering light generated by excitation and coupling into the cladding. We conducted simulations as noted above and based on this built a large-scale model.

[0030] In some embodiments, devices described herein include first and second off-axis parabolic (OAP) mirrors aligned coaxially, referred to as 106 and 108 respectively (FIGS. 1A- 1B), where the OAPs 106 and 108 are sized to fit within a capsule. OAP1 106 may be positioned at the proximal end of the capsule, and OAP2 108 may be positioned at the distal end of the capsule. Therefore, OAP1 106 may be referred to as the proximal OAP, and OAP2 108 may be referred to as the distal OAP. OAP mirrors have a parabolic surface profile, which ensures that a light source at the focal plane will be well collimated in the space between the mirrors.

[0031] The focus of OAP1 106 is located at the multimode fiber 114 end face. The focus of OAP2 108 is located 1-2 mm outside of the capsule wall. Therefore, the focal length of OAPs 1 and 2 is approximately 5-7mm. OAP1 106 may be coated with a broadband coating for optimal reflection in the visible wavelength range such as silver. OAP2 108 requires a wider reflection band, from the near UV all the way to the OCT wavelength of 1310 nm. In some embodiments, the OAP2 108 is coated with bare aluminum.

[0032] In general, using a pair of parabolic mirrors as shown in FIGS. 1A-1B allows the light to be transmitted between the two ends of the capsule in a collimated form, which facilitates rotation of one mirror (e.g., OAP2 as in FIGS. 1 A-1B) relative to the other. Given that the light is collimated, small lateral displacements and wide axial displacements in the mirrors relative to each other do not have a significant impact to the quality of the focused spot at the focal point, making this configuration tolerant to manufacturing errors. Using off-axis parabolic mirrors allows parallel light to focus at a point off to the side of the mirror and hence off to the side of the capsule, which allows the light beams to be directed to the sample. Typically, the sample is a luminal structure such as in the GI tract (e.g., the esophagus or intestines) although other structures are also possible. The focal points at each end of the capsule do not need to be the same and mirrors with different focal points can be selected at each end to accommodate the particular needs such as focusing at the proper distance outside the capsule (e.g., for OAP2 108) or at a location that is suitable for collecting autofluorescence signal (e.g., for OAP1 106). The focus for OAP1 106 is coincident with the face of the multimode fiber. The focal distance for OAP2 108 may change to optimize collection for different imaging conditions.

[0033] The first GAP mirror 106 has a through-hole in the center 110. The through-hole 110 may have an opening with a diameter in a range of 0.5-2 mm. The size of the through-hole 110 may be chosen to be as small as possible, while still being larger enough to fit the collimator optic within the through hole. In some embodiments, the through-hole 110 has a diameter of 1 mm.

[0034] The fiber tether 104 may be inserted into the proximal end of the capsule. In some embodiments, the fiber tether is a two-fiber tether. The two-fiber feature may include a single mode fiber (SMF) 112 and a multimode fiber (MMF) 114. The single-mode fiber may be an excitation fiber, and may be placed within the through-hole 110. The terms “single-mode fiber” and “excitation fiber” are used interchangeably herein.

[0035] The single mode fiber 112 may be placed within the through-hole 110. The excitation fiber 112 may be capped with a collimating optical element 116. The collimating optical element 116 may be a ball lens of a gradient refractive index (GRIN). If the collimating optical element 116 is a ball lens, the surface of the lens may be anti -reflection coated for 1310 nm. If the collimating optical element 116 is a GRIN lens, it is important to angle polish the faces for back reflection mitigation.

[0036] In some embodiments, excitation fiber 112 is an optical fiber, or an optical waveguide. The terms fiber and waveguide are used interchangeably throughout the specification and claims. The excitation fiber 112 may be used to deliver light to the tissue at a small NA, which can be useful for OCT and autofluorescence excitation systems and the collection fiber is conjugate to the focal plane of OAP2 108 at a more substantial NA, which provides higher autofluorescence collection than other capsule designs. In addition, the excitation fiber 112 can be a dual clad fiber (DCF) which will allow for another small numerical aperture (NA) beam to come from the first cladding of the DCF. This can offer more flexibility for the delivery of autofluorescence excitation light.

[0037] The use of a through-hole to emit both OCT and autofluorescence illumination light and collect reflected OCT light reduces the amount of autofluorescence that is returned to the OCT platform, while the autofluorescence light is reflected from the remaining portion of the lens and directed to the fluorescence emission detector. This difference in light collection pathways impacts the NA of the light from each channel (i.e., OCT vs. autofluorescence). For the autofluorescence collection channel, the NA tends to be higher and may range between 0.20- 0.40. In some embodiments, the NA = 0.36. For the OCT channel, the NA tends to be lower and may range between 0.02-0.20. In some embodiments, the NA = 0.05. In some embodiments, the approximate maximum fluorescence collection efficiency is 1.3% for 550 nm. In this configuration, the OAPs support relatively low numerical apertures for OCT light (1310 nm) and relatively high NAs for fluorescence collection.

[0038] The second OAP mirror 108 (OAP2) is placed apart from OAP1 106 such that OAP1 108 and OAP2 106 share a mechanical axis. OAP1 106 and OAP2 108 may be positioned such that OAP2 108 is above the OAP1 106, with regards to the vertical axis of the capsule (although the exact orientation in space is arbitrary since the capsule may be placed in a variety of positions during use). OAP1 106 and OAP2 108 may be positioned as close together as possible without interference. OAP1 106 and OAP2 108 may be positioned such that they are between 5 mm to 15 mm apart. In some embodiments, the distance between OAP1 106 and OAP2 108 is 5 mm.

[0039] The multimode fiber 114 may be a collection fiber. The terms “multimode fiber” and “collection fiber” are used interchangeably herein. A collection fiber 114 is placed at the focal plane of OAP1 106. A turning mirror 118 may be placed near the focal plane of OAP1 106 and tilted at an angle such that the light can be reflected off OAP1 108 and into the collection fiber 114, which can then be placed parallel to the excitation fiber 112 (see FIG. 1A, and FIG. 4). In some embodiments, he light from the focal plane of OAP1 106 may be directed towards the proximal end of the capsule.

[0040] The excitation fiber 112, collection fiber 114, OAP1 106, and optional turning mirror 118 are all static within the confined space (e.g., the capsule), while the second OAP mirror 108 will be placed on a rotating platform 120, which is attached to a motor 122. The motor 122 may rotate the rotating platform 120 and OAP2 108 at a rate between 0-100 Hz and is configured to image in a range of up to 360 degrees relative to the long axis of the capsule (as indicated by the circular arrow in FIGS. 1A-1B).

[0041] FIG. 4 shows exemplary ray-tracing for the device optics, showing how the excitation light (blue) is delivered to the sample (vertical lines on the right-hand side of the diagram) and how the emitted light (blue line for OCT light and green lines for autofluorescence) is directed to the detectors (which are not shown in this image).

[0042] The device may further include an OCT platform 124 (see FIG. IB). In some embodiments, an off-the-shelf OCT engine can be used. In some embodiments, the OCT platform is a 1310 nm SS-OCT system from Excelitas or Axsun.

[0043] The device may further include an excitation laser 126 that delivers light to the excitation fiber 112 (see FIG. IB). One advantage of our DOAP system is that any wavelength of laser may be used as a fluorescence excitation source without generating autofluorescent background noise in the DCF cladding 126. Many other capsules utilize components (like DCF) that limit the wavelength of excitation source that can be used. In some applications, fluorescence excitation lases as low as 405 nm, or 375 nm. Additionally, the capsule can perform reflectance measurements across the full visible spectrum (400-700 nm). In some embodiments, only single mode lasers can be used. LEDs cannot be coupled well to single mode fibers. [0044] The device may further include fluorescence emission detector 128 (see FIG. IB). Emission detector 128 may be a photodiode such as an avalanche photodiode (APD).

Additionally or alternatively, a photomultiplier tube (PMT) may be used as an emission detector. Spectrometers may be used for reflectance measurements. In either case, a fluorescence excitation filter must be used to protect the detector from leaked excitation light.

[0045] A scaled-up, benchtop version of the design has been created and has been used to perform validation testing (see FIG. 5). FIGS. 6A-6C show a to-scale prototype capsule. FIG. 6A provides a view such that OAP1 and OAP2 are in view. FIGS. 6A-6B show different views of OAP1. FIGS. 6B-6C show the through-hole in OAP1.

[0046] FIGS. 7A-7D show preliminary results of the resolution of the DOAP device of a fluorescence channel (AF/R) at a single wavelength (operating in reflectance mode) and the axial and lateral resolution of the OCT channel. FIG. 7A shows a green AF/R channel, and FIG. 7B shows the observed intensity of the red line shown in FIG. 7A. FIG. 7C shows an OCT channel, and FIG. 7D shows the observed intensity of a cut through of FIG. 7C. The DOAP is able to resolve the green AF/R channel and OCT channel with a high degree of accuracy.

[0047] Applications

[0048] In some embodiments, the devices described herein may be used for esophageal endoscopy. Further applications include prediction of precursor lesion progression to cancer, including Barrett’s esophagus and Barrett’s esophagus dysplasia, oral, oropharyngeal, laryngeal, and airway squamous dysplasia and cancer, gastric metaplasia, dysplasia, and cancer, small intestinal dysplasia and cancer, cervical intraepithelial lesions, colorectal adenomatous dysplasia, anorectal dysplasia.

[0049] Each of the following references is incorporated by reference in its entirety.

[0050] 1. Hvid-Jensen, F., et al. “Incidence of adenocarcinoma among patients with

Barrett’s esophagus.” New England Journal of Medicine 365.15 (2011): 1375-1383.

[0051] 2. Yelin, D., et al. “Double-clad fiber for endoscopy.” Optics letters 29.20 (2004):

2408-2419. [0052] 3. Thrapp, A., et al. “Detecting Barrett’s esophagus using a methylene blue fluorescent slurry and a multi-modal optical coherence tomography and fluorescence capsule.” SPIE Proceedings Volume PC12820, Endoscopic Microscopy XIX: PC1282006 (2024).

[0053] U.S. Patent Application No. 11/622,854.

[0054] While the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. A number of references to patent and non-patent documents are made throughout the publication, each of which is herein incorporated by reference in its entirety.

Claims

CLAIMS What is claimed is:

1. An optical device comprising: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; an excitation optical waveguide configured to deliver light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and an emission detector configured to receive light from the sample.

2. The device of claim 1, further comprising a capsule, wherein the first off-axis parabolic mirror, the second off-axis parabolic mirror, and the rotation platform are disposed within the capsule.

3. The device of any one of the preceding claims, wherein the first off-axis parabolic mirror comprises a through hole, and wherein the excitation optical waveguide is disposed within the through hole.

4. The device of claim 3, wherein the through hole comprises a diameter of between 0.5-2 mm.

5. The device of any one of the preceding claims, wherein the excitation optical waveguide comprises a dual clad fiber.

6. The device of any one of the preceding claims, further comprising a collimator optically coupled to the excitation optical waveguide such that light emitted from the excitation optical waveguide is collimated.

7. The device of any one of the preceding claims, wherein the emission detector and the excitation light source comprise an optical coherence tomography (OCT) system.

8. The device of any one of the preceding claims, wherein the excitation light source comprises an excitation laser optically coupled to the excitation optical waveguide.

9. The device of any one of the preceding claims, wherein the first off-axis parabolic mirror and the second off-axis parabolic mirror are positioned between 5 mm and 15 mm apart, and wherein light travels in a collimated pattern between the first off-axis parabolic mirror and the second off-axis parabolic mirror.

10. The device of any one of the preceding claims, wherein the rotating platform is configured to rotate at a rate of between 0.5 - 100 Hz.

11. The device of any one of the preceding claims, wherein the excitation source comprises a fluorescence excitation source optically coupled to the excitation optical waveguide.

12. The device of claim 11, wherein light from the fluorescence excitation source is directed through the first off-axis parabolic mirror and off the second off-axis parabolic mirror toward a sample.

13. The device of claim 12, wherein autofluorescence light emitted from the sample is directed off the second off-axis parabolic mirror toward the first off-axis parabolic mirror and toward the emission detector, wherein the emission detector comprises a fluorescence emission detector.

14. A capsule-based optical device, comprising: a capsule comprising: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; a tether comprising an excitation optical waveguide configured to deliver light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and an emission detector coupled to the tether and configured to receive light from the sample.

15. The capsule-based device of claim 14, wherein the capsule further comprises a cylindrical capsule body, wherein the first off-axis parabolic mirror, the second off-axis parabolic mirror, and the rotation platform are disposed within the cylindrical capsule body.

16. The capsule-based device of any one of claims 14 or 15, wherein the first off-axis parabolic mirror comprises a through hole, and wherein the excitation optical waveguide is disposed within the through hole.

17. The capsule-based device of claim 16, wherein the through hole comprises a diameter of between 0.5-2 mm.

18. The capsule-based device of any one of claims 14-17, wherein the excitation optical waveguide comprises a dual clad fiber.

19. The capsule-based device of any one of claims 14-18, further comprising a collimator optically coupled to the excitation optical waveguide such that light emitted from the excitation optical waveguide is collimated.

20. The capsule-based device of any one of claims 14-19, wherein the emission detector and the excitation light source comprise an optical coherence tomography (OCT) system.

21. The capsule-based device of any one of claims 14-20, wherein the excitation light source comprises an excitation laser optically coupled to the excitation optical waveguide.

22. The capsule-based device of any one of claims 14-21, wherein the first off-axis parabolic mirror and the second off-axis parabolic mirror are positioned between 5 mm and 15 mm apart, and wherein light travels in a collimated pattern between the first off-axis parabolic mirror and the second off-axis parabolic mirror.

23. The capsule-base device of any one of claims 14-22, wherein the rotating platform is configured to rotate at a rate of between 0.5 - 100 Hz.

24. The capsule-based device of any one of claims 14-23, wherein the excitation source comprises a fluorescence excitation source optically coupled to the excitation optical waveguide.

25. The capsule-based device of claim 24, wherein light from the fluorescence excitation source is directed through the first off-axis parabolic mirror and off the second off-axis parabolic mirror toward a sample.

26. The capsule-based device of claim 25, wherein autofluorescence light emitted from the sample is directed off the second off-axis parabolic mirror toward the first off-axis parabolic mirror and toward the emission detector, wherein the emission detector comprises a fluorescence emission detector.

27. A method of operating a capsule-based optical device, comprising: providing a capsule, the capsule comprising: a first off-axis parabolic mirror and a second off-axis parabolic mirror, configured such that the first off-axis parabolic mirror and the second off-axis parabolic mirror are optically coupled and share a mechanical axis, wherein the second off-axis parabolic mirror is configured on a rotating platform; delivering, using a tether comprising an excitation optical waveguide, light from an excitation source to illuminate a sample using the first off-axis parabolic mirror and the second off-axis parabolic mirror; and receiving, using an emission detector coupled to the tether, light from the sample.

28. The method of claim 27, wherein the capsule further comprises a cylindrical capsule body, wherein the first off-axis parabolic mirror, the second off-axis parabolic mirror, and the rotation platform are disposed within the cylindrical capsule body.

29. The method of any one of claims 27 or 28, wherein the first off-axis parabolic mirror comprises a through hole, and wherein the excitation optical waveguide is disposed within the through hole, and wherein delivering light further comprises: delivering light from the excitation optical waveguide via the through hole.

30. The method of claim 29, wherein the through hole comprises a diameter of between 0.5-2 mm.

31. The method of any one of claims 27-30, wherein the excitation optical waveguide comprises a dual clad fiber.

32. The method of any one of claims 27-31, wherein the capsule further comprises a collimator optically coupled to the excitation optical waveguide, and wherein delivering light further comprises: delivering light from the excitation optical waveguide in a collimated beam.

33. The method of any one of claims 27-32, wherein the emission detector and the excitation light source comprise an optical coherence tomography (OCT) system.

34. The method of any one of claims 27-33, wherein the excitation light source comprises an excitation laser optically coupled to the excitation optical waveguide.

35. The method of any one of claims 27-34, wherein the first off-axis parabolic mirror and the second off-axis parabolic mirror are positioned between 5 mm and 15 mm apart, and wherein delivering light further comprises: delivering light from the excitation optical waveguide in a collimated pattern between the first off-axis parabolic mirror and the second off-axis parabolic mirror.

36. The method of any one of claims 27-35, wherein the rotating platform is configured to rotate at a rate of between 0.5 - 100 Hz.

37. The method of any one of claims 27-36, wherein the excitation source comprises a fluorescence excitation source optically coupled to the excitation optical waveguide.

38. The method of claim 37, wherein delivering light further comprises: delivering light from the fluorescence excitation source through the first off-axis parabolic mirror and off the second off-axis parabolic mirror toward a sample.

39. The method of claim 38, wherein the emission detector comprises a fluorescence emission detector, and wherein receiving light further comprises: receiving autofluorescence light emitted from the sample which is directed off the second off-axis parabolic mirror toward the first off-axis parabolic mirror and toward the fluorescence emission detector.