Wide-field MEMS-based endoscope

Abstract

An optical arrangement for use in an endoscope is provided. The endoscope includes a single mode fiber for providing illumination, a collimator connected to the single mode fiber for producing a low numerical aperture beam, a scanner for reflecting the beam produced by the collimator, and a multimode fiber for collecting return light. Structural components for creating a compact arrangement may include an outer tube, a flexible tube, and an end tube. An optical system using the optical arrangement may further include an optical train having a plurality of dichroic mirrors, and a plurality of photomultiplier tube detectors.

Description

WIDE-FIELD MEMS-BASED ENDOSCOPECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of the filing date of U.S. Provisional Application No.63 / 532, 268, filed August 11, 2023, entitled “Wide-Field MEMS-Based Endoscope.” The entirety of U.S. Provisional Application No. 63 / 532,268 is hereby incorporated by reference into the present disclosure.STATEMENT OF GOVERNMENT INTEREST

[0002] This invention was made with government support under EB020644 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE DISCLOSURE

[0003] The disclosure relates generally to techniques for imaging tissue using an optical instrument and, more particularly, to techniques allowing scanning of an epithelium in hollow organs for early cancer detection.BACKGROUND

[0004] The brief description of related technology provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this brief description of related technology section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.

[0005] The incidence of cancer worldwide is growing steadily, and mortality is expected to double over the next two decades. More effective methods for early cancer detection are needed to effectively address this growing health care problem. Over 80% of all human cancers originate from the epithelium of hollow organs, including colorectal cancer (CRC). These organs have large mucosal surface areas at risk. During cancer transformation, molecular targets are expressed well before structural changes become grossly apparent.

[0006] Imaging of the epithelium of hollow organs is key to early detection. Endoscopic methods can readily gain access to this thin layer of highly metabolically active tissue to accurately localize pre-malignant lesions. Imaging agents, such as probes that are fluorescently labeled, allow real time visualization of cancer targets expressed in vivo.However, early detection with imaging is challenging because many epithelial-derived cancers are driven by multiple gene mutations. For example, in CRC, over 95% of all cases arise from either the serrated pathway (BRAF) or the adenoma-carcinoma sequence (APC / p53 / KRAS). Peptide sequence Prdxl is highly specific for pre-malignant lesions that arise from the serrated pathway, while cMet and EGFR are expressed early in the adenomacarcinoma sequence.

[0007] Fluorescence endoscopes are large and bulky in dimension, limited in resolution by number of pixels / fibers, and lack spectral flexibility for multiplexed imaging. Epithelial- derived cancers can be easily missed with conventional white light endoscopy because white light illumination has limited effectiveness to identify lesions that are flat and subtle in appearance. Improvements in multiplexed imaging methods are needed to detect multiple targets concurrently using wide-field endoscopy to address genetic heterogeneity of epithelial-derived cancers.SUMMARY

[0008] To address the foregoing, the present application describes an integrated imaging technology to detect cancer specific targets expressed by the epithelium in hollow organs for early cancer detection. More specifically, the present application is directed to a flexible fiber, wide-field endoscope using a scalable optical design.

[0009] In accordance with a first exemplary aspect of the disclosure, an optical arrangement for use in an endoscope includes a single mode fiber providing illumination, a collimator positioned at an exit end of the single mode fiber for producing a low numerical aperture beam, a scanner for reflecting the collimated beam onto a scan region, and a multimode fiber positioned to collect return light from the scan region and reflected into the multimode fiber by the scanner. An outer tube surrounds the single mode fiber, the collimator, and the multimode fiber at a distal tip. A flexible tube is connected to the outer tube, and an end tube is between the outer tube and the flexible tube to prevent unwanted vibrations.

[0010] In accordance with a second exemplary aspect of the disclosure, an optical system includes a single mode fiber providing illumination, a collimator positioned at an exit end of the single mode fiber for producing a low numerical aperture beam, a scanner for reflecting the collimated beam onto a scan region, and a multimode fiber positioned to collect return light from the scan region and reflected into the multimode fiber by the scanner. The opticalsystem includes an optical train having a plurality of dichroic mirrors, each of the dichroic mirrors deflecting fluorescence in distinct spectral bands. The optical system further includes a plurality of photomultiplier tube detectors, each photomultiplier tube detector receiving the fluorescence deflected by one of the dichroic mirrors.

[0011] In some forms, the distal tip of the optical arrangement may be less than or equal to 2.6 mm in diameter. The distal tip of the optical arrangement may be less than or equal to 12 mm in length. A medical endoscope within which the single mode fiber, collimator, scanner, and multimode fiber is configured to travel may be provided.

[0012] In some forms, a plurality of multimode fibers may collect the return light. In some forms, the single mode fiber and the plurality of multimode fibers may be arranged in a linear pattern where the multimode fibers are positioned to collect return light at different scan angles ranging between zero degrees and 45 degrees. In other forms, the multimode fibers may be arranged around the single mode fiber in one of a square pattern, a triangle pattern, and circular pattern, wherein the multimode fibers are positioned to collect return light at different scan angles.

[0013] In still further forms, the optical arrangement may further include a holder upon which the scanner is mounted, and the holder may be fabricated from M3 crystal using a 3D printer. The scanner may be formed on a silicon device layer of a silicon-on-insulator wafer. The outer tube may be made from stainless steel.

[0014] In some forms, the optical arrangement may have a longitudinal axis along which the collimated beam is produced. The scanner may be disposed at an angle less than 90 degrees relative to the longitudinal axis.

[0015] In some forms, the scanner may include a reflector coupled to two inner torsional springs arranged in-line along a length of the reflector.

[0016] In other forms, the scanner may include a reflector coupled to four outer torsional springs arranged with two outer torsional springs on a first side of the reflector and two outer torsional springs on a second side of the reflector.

[0017] In some forms, the single mode fiber may be configured to provide laser excitation at three wavelengths. The wavelengths may be 488 nm, 660 nm, and 785 nm. The optical trainmay include three dichroic mirrors, each dichroic mirror configured for a distinct spectral band.

[0018] In other forms, a convex lens may be provided to increase a scan angle. A working distance between the scanner and the collimator may be less than or equal to 30 mm. The field-of-view of the optical system may be greater than 4.2 mm in diameter at a working distance of 30 mm.

[0019] In still other forms, the scanner may be a MEMS mirror with a monolithic integrated design. The MEMS mirror may be configured to produce large angular deflections to achieve an image field-of-view greater than 60 degrees.BRIEF DESCRIPTION OF THE DRAWINGS

[0020] For a more complete understanding of the disclosure, reference should be made to the following detailed description and accompanying drawing figures, in which like reference numerals identify like elements in the figures. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0021] FIG. 1A illustrates schematically a first optical pathway of an optical arrangement using a MEMS mirror.

[0022] FIG. IB illustrates schematically a second optical pathway of the optical arrangement of FIG. 1A.

[0023] FIG. 2A illustrates schematically an optical system for the collection of fluorescence using the optical arrangement of FIGS. 1A and IB.

[0024] FIG. 2B shows graphically, for the optical arrangement depicted in FIG. 2A, the excitation wavelengths that excite FITC, Cy5, and IRDye800 result in spectra having minimal overlap.

[0025] FIG. 3A illustrates an optical arrangement in accordance with an example, the optical arrangement including lenses, a scanner, and optical fibers (SMF, MMF) that can be efficiently packaged.

[0026] FIG. 3B illustrates a packaging scheme for the optical arrangement of FIG. 3A having distal tip dimensions of 2.6 mm in diameter and 12 mm in length.

[0027] FIG. 3C illustrates a packaging scheme for the optical arrangement of FIG. 3A that allows for forward passage through a standard working channel of a medical endoscope.

[0028] FIG. 4A illustrates the scan mirror of the optical arrangement of FIG. 3A deflecting the excitation beams in a Lissajous pattern for x = 488 at a working distance of 20 mm.

[0029] FIG. 4B illustrates the scan mirror of the optical arrangement of FIG. 3A deflecting the excitation beams in a Lissajous pattern for x = 660 at a working distance of 20 mm.

[0030] FIG. 4C illustrates the scan mirror of the optical arrangement of FIG. 3A deflecting the excitation beams in a Lissajous pattern for x = 785 at a working distance of 20 mm.

[0031] FIG. 4D illustrates the scan mirror of the optical arrangement of FIG. 3A deflecting concurrent excitation beams in a Lissajous pattern for x = 488, 660, and 785 at a working distance of 20 mm.

[0032] FIG. 5A illustrates the illuminating functionality of an optical arrangement in accordance with an example, whereby illumination is delivered via a single mode fiber (SMF) collimated with an achromatic doublet and plano-convex lens and a miniature scanner deflects the beam at angles 0X>± 45°.

[0033] FIG. 5B illustrates the collecting functionality of the optical arrangement described in FIG. 5A, where fluorescence is de-scanned and collected by a row of multimode fibers (MMFs).

[0034] FIG. 5C illustrates a first configuration of the multimode fibers (MMFs) described in FIG. 5B whereby the fibers are arranged in a linear pattern for a scan angle of 0°.

[0035] FIG. 5D illustrates a second configuration of the multimode fibers (MMFs) described in in FIG. 5B whereby the fibers are arranged in a linear pattern for a scan angle of 45°.

[0036] FIG. 5E provides a graphical illustration of the image resolution of the optical arrangement described in FIGS. 5A-5D.

[0037] FIG. 6A illustrates a top perspective view of a scanner of an example having a simulated active scan mirror tilt motion along the X-axis at eigenmode EM7=13992 Hz.

[0038] FIG. 6B illustrates a side view of the scanner of FIG. 6A in the position illustrated in FIG. 6A.

[0039] FIG. 6C illustrates a top perspective view of the scanner of FIGS. 6A and 6B having a simulated active scan mirror tilt motion along the Y-axis at eigenmode EM7=4667.9 Hz.

[0040] FIG. 6D illustrates a side view of the scanner of FIGS. 6A-C in the position illustrated in FIG. 6C.

[0041] FIG. 6E illustrates mechanical stress for the two inner torsional springs arranged inline along the reflector length of the scanner of FIGS. 6A-6D.

[0042] FIG. 6F illustrates mechanical stress for four outer torsional springs of the scanner of FIGS. 6A-6D.

[0043] FIG. 6G illustrates dimensions of the inner torsional springs of the scanner of FIGS. 6A-6D.

[0044] FIG. 6H illustrates dimensions of the outer torsional springs of the scanner of FIGS. 6A-6D.

[0045] FIG. 7A illustrates a front view of the scanner of FIG. 6A.

[0046] FIG. 7B illustrates a photograph of the scanner of FIGS. 6A and 7 A.

[0047] FIG. 7C illustrates the frequency response of the scan mirror using a down-sweep (high-to-low frequencies) and up-sweep (low-to-high frequencies) along the X-axis.

[0048] FIG. 7D illustrates the frequency response of the scan mirror using a down-sweep (high-to-low frequencies) and up-sweep (low-to-high frequencies) along the Y-axis.

[0049] FIG. 8 A illustrates an -4 mm diameter adenoma located adjacent to normal mucosa in the prolapsed rectum of a live CPC;Apc mouse.

[0050] FIG. 8B illustrates a fluorescence image of the adenoma of FIG. 7A at a working distance of 10 mm using excitation 7=488.

[0051] FIG. 8C illustrates a fluorescence image of the adenoma of FIG. 7A at a working distance of 10 mm using excitation 7=660.

[0052] FIG. 8D illustrates a fluorescence image of the adenoma of FIG. 7A at a working distance of 10 mm using excitation 7=785.

[0053] FIG. 8E illustrates a merged fluorescence image of the adenoma of FIG. 7 A for 7ex = 488, 660, and 785 at a working distance of 10 mm.

[0054] FIG. 9 depicts an example block diagram illustrating various components used in implementing an exemplary embodiment of the optical arrangement, in accordance with an example.

[0055] Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and / or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments. It will further be appreciated that certain actions and / or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above except where different specific meanings have otherwise been set forth herein.DETAILED DESCRIPTION

[0056] Generally speaking, pursuant to these various embodiments, techniques for the design, fabrication, and performance of a wide-field MEMS-based endoscope is provided. The working principle is based on scanning of a collimated laser beam over a tissue surface. The return intensity (reflectance / fluorescence) is displayed as a function of position to reconstruct the image. At long working distances, higher resolution can be achieved because this parameter is determined by the size of the focused beam rather than the pixel size of the detector. Advantages over traditional endoscopy include smaller instrument dimensions, long depth-of-field, variable field-of-view (FOV), and multi- spectral fluorescence imaging. In addition, full color (RGB) imaging can be achieved. The endoscope can be used inside the human body to perform rapid surveillance of large surface areas found in the digestive tract, including esophagus, stomach, and colon, to detect pre-malignant lesions that are flat and visibly indistinct. Disease heterogeneity is addressed by detecting 3 molecular targetsconcurrently. The outer diameter of the endoscope can be scaled to a desired size, such as 2.5 mm.

[0057] FIG. 1A depicts an optical arrangement 102 including a MEMS mirror 100 (also referred to as scanner 100) in accordance with an example. The MEMS mirror 100 is a miniature, integrated monolithic, electrostatic 2D MEMS mirror having a compact chip size. The MEMS mirror 100 can produce large angular deflections to achieve an image field-of- view (FOV) of greater than 60 degrees. The optical arrangement 102 uses parametric excitation at near resonance frequencies to produce large optical deflection angles in the X- and Y-axes. Variable zoom is achieved by changing the scan angle of the MEMS mirror 100, thus there is no need for optical zoom. The MEMS mirror 100 can be fabricated by performing silicon micro -machining of front and backside features using deep reactive-ion etching (DRIE) process. Mirror speed and range-of-motion are characterized prior to installation into assembly fixtures (not pictured) for the optical arrangement 102. Mirror electrode and dynamic amplification geometry is optimized around the mirror surface by a combination of analytical and finite element analysis methods.

[0058] As shown in FIG. 1A, the optical arrangement 102 delivers laser excitation via a single-mode optical illumination fiber 104 to a collimator 106 including an aspheric lens 107 and an achromatic lens 108. The collimator 106 produces a low numerical aperture (NA) beam and allows for increased distance between the illumination fiber 104 and the scanner 100 to facilitate instrument packaging. A low numerical aperture (NA) beam is defined by near-collimated light whereby the optics is designed to accept and emit light at small angles. As an example, any numerical aperture below .25 would be considered low. The beam reflects off the scanner 100 through a concave lens 109 designed to increase the scan angle. As shown in FIG. IB, a first pair of right angle triangular prisms Pi and a second pair of right angle triangular prisms P2 allow fluorescence collection along a first multimode fiber 110a and a second multimode fiber 110b.

[0059] FIG. 2A illustrates another model of the optical arrangement 102. The optical arrangement 102 includes the single mode optical illumination fiber 104, the collimator 106 (including an aspheric lens 107 and an achromatic lens 108), the scanner 100, the concave lens 109, the first and second pairs of right angle triangular prisms Pi and P2, and the first and second multimode optical fibers 110a and 110b. The optical arrangement 102 further includes a longitudinal axis L along which a collimated beam is produced, and the scanner100 is disposed at an angle of less than 90 degrees relative to the longitudinal axis L. The optical arrangement 102 may have a diameter less than 2.6 mm in order to pass through the instrument channel of a standard medical endoscope (as shown, for example, as endoscope 130 in FIG. 3C). Laser excitation at three wavelengths can be delivered via the single mode illumination fiber 104, which may be flexible, to provide multi- spectral reflectance images that can be combined as a conventional white light (RGB) image. Multiplexed detection of fluorescence images can also be generated to reveal molecular properties of tissue. Imaging can then be performed to detect a panel of cancer biomarkers that are overexpressed in diseased tissues. This capability is useful because, as discussed above, many human diseases, such as cancer, are genetically heterogeneous.

[0060] In the example of FIG. 2A, the optical arrangement 102 provides fluorescence excitation at, for example, Xex= 488, 660, and 785 nm. The illumination beams are delivered through the single-mode optical illumination fiber 104, focused the aspheric lens 107 and the achromatic lens 108, and scanned by the MEMS mirror 100. Fluorescence is collected by the large core multimode optical fibers 110a and 110b and is delivered through an optical train 112 consisting of three dichroic mirrors (DMi (114a), DM2 (114b), and DM3 (114c)). Fluorescence in each distinct spectral band is deflected to their respective photomultiplier tube (PMT) detector (116a, 116b, and 116c). This set of laser excitation wavelengths is designed for use with FITC, Cy5, and IRDye800 because minimal overlap occurs between these spectral bands, as shown in FIG. 2C. While particular fluorescence wavelengths are collected in the illustrated example, in other examples fewer or greater number of fluorescence wavelengths may be collected. In some examples, the fluorescence wavelengths are captured by PMTs using dichroic mirrors tuned to different center wavelengths, where some those dichroics may have partially overlapping reflection spectra or where some of those dichroics have substantially non-overlapping reflection spectra, like that shown in FIG. 2B.

[0061] FIG. 3A shows how the optical arrangement 102 can be packaged efficiently. A side-view geometry allows for the optical arrangement 102 to deliver the excitation beams incident to a mucosal surface with only minimal maneuvering of a distal tip 128 of a medical endoscope. As previously discussed, the optical arrangement 102 includes a single mode optical illumination fiber 104, a collimator 106 including an aspheric lens 107 and an achromatic lens 108, a scanner 100, and multimode optical fibers 110a and 110b. As shownin FIG. 3 A, an outer tube 118 is used to center and align the single mode optical illumination fiber 104, the aspheric lens 107 and achromatic lens 108 of the collimator 106, and the multimode optical fiber 110 near the scanner 100 in the distal tip 128. The outer tube may be made from, for example, stainless steel. A more precise alignment of the center-to-center distance between the aspheric and achromatic lenses can improve collimation of the excitation beams and hence image resolution over the range of working distances. The scanner 100 is mounted onto a holder 120 that connects wires (not pictured) to provide power and deliver data. The holder 120 may be fabricated from M3 crystal, an acrylic based resin with high strength and stiffness, using a 3D printer with 16 m resolution. The scanner is aligned with concave lens 109. A fiber ferrule 122 is used to center the single mode optical illumination fiber 104 relative to the scanner 100. Prisms Pl and P2 are used to increase the effective area for fluorescence collection and delivery into the multimode optical fibers 110a and 110b. Additional sets of prisms can be introduced to increase the effective fluorescence capture area. A flexible tube 124 (e.g., made from polymer) is connected to the outer tube 118 a distance away from the scanner 100, and an end tube 126 is inserted between the outer tube 118 and the flexible tube 124 to mechanically isolate the scanner 100 from unwanted vibrations.

[0062] As shown in FIGS. 3B and 3C, the dimensions of the optical arrangement 102 may be such that the optical arrangement 102 can pass through a standard working channel of a medical endoscope 130 for broad clinical use. For example, as shown in FIG. 3B, the optical arrangement 102 may have a distal tip 128 measuring 2.6 mm in diameter D and 12 mm in length. This compact size allows the optical arrangement 102 to pass through a medical endoscope 130 having a 2.7 mm diameter working channel as shown in FIG. 3C. Other dimensions of the optical arrangement 102 are also within the scope of the present disclosure. For example, the optical arrangement 102 may have a diameter less than approximately 2.5 mm, less than approximately 3.0 mm, and less than approximately 3.5 mm. The optical arrangement 102 may have a distal tip 128 with a length that is less than approximately 10 mm, less than approximately 15 mm, and less than approximately 20 mm.

[0063] FIGS. 4A-4C illustrate photographs of the scanner 100 deflecting excitation beams excitation beams in a Lissajous pattern for x = 488 nm (as shown in FIG. 4A), 660 nm (as shown in FIG. 4B), and 785 nm (as shown in FIG. 4C) at a working distance of 20 mm. Concurrent excitation of these three wavelengths is shown in the merged image of FIG. 4D.

[0064] In FIG. 5A, the scanner 100 deflects the illumination beam at angles 0X>± 45°. Illumination is delivered via the single mode optical illumination fiber 104 (shown in FIG. 3A) and is collimated to produce a low numerical aperture (NA) beam. In FIG. 5B, fluorescence is de-scanned. As shown in FIGS. 5C and 5D, three multimode optical fibers 110 (110a, 110b, 110c, 1 lOd, 1 lOe, 1 lOf) are placed on either side of the single mode optical illumination fiber 104 in a linear pattern to maximize light collection in this geometry over scan angles that range between 0 degrees (shown in FIG. C) and 45 degrees (shown in FIG. D). Although the arrangement of the multimode optical fibers 110 in FIGS. 5C and 5D is linear, in other arrangements, the multimode optical fibers 110 may be arranged around the single mode optical illumination fiber 104 in a square pattern with the SMF at the center, in a circular pattern with the SMF at the center, or in another configuration entirely. Further, although three multimode optical fibers 110 are shown in FIGS. 5C and 5D, certain optical arrangements 102 may have more than three multimode optical fibers 110 while other optical arrangements 102 may have less than three multimode optical fibers 110. Further still, while symmetrical arrangements are shown, in other examples, arrangements may be implemented where the collection fibers are not symmetrical around the source fiber.

[0065] As shown in FIG. 5E, resolution of less than 250 pm is achieved at working distances of up to 30 mm using the optical arrangement 102 described with respect to FIGS. 5A-5D. The image resolution is defined by half-width of Gaussian beam. The working distance of up to 30 mm is a typical distance used in clinical imaging, and provides a large field-of-view (FOV) to rapidly visualize the mucosa surface of hollow organs. Specifically, the FOV is greater than 4.2 mm in diameter at a working distance of 30 mm. Large core multimode optical fibers 110 transmit a broad optical spectrum for multiplexed detection. Image resolution is determined by the dimensions of the focused beam, unlike in other fluorescence endoscopes where either the number of fibers in a bundle or pixels in the detector limits resolution. A side-view geometry provides maximum visualization of the mucosal surface in hollow organs when a 2.6 mm instrument is inserted through the working channel of a medical endoscope and rotation is performed using the external steering mechanisms.

[0066] As shown in FIGS. 6A-6H, according to one example, a compact 2D scan mirror 100 is designed with dimensions to fit in a distal rigid tip 128 of a wide-field accessory with 2.6 mm diameter and 12 mm length. A reflector 136 with dimensions of 1.30x0.45 mm2ismounted on a 2.02x2.5 mm2gimbal 138 to minimize cross-talk between the X and Y axes. Two inner torsional springs 140a and 140b are arranged in-line along the reflector length L. Four outer torsional springs 142a, 142b, 142c, and 142d are arranged with two of the four outer torsional springs 142a and 142b on a first side 141 of the of the reflector 136 and two of the four outer torsional springs 142c and 142d on a second side 143 of the reflector 136. The pair of inner torsional springs 140a and 140b allow the gimbal 138 that supports the reflector 136 to deflect at angles larger than that of the comb-drives actuating in the Y-axis. This design maintains a substantial overlap of comb fingers and accommodates large actuation torques throughout mirror operation even at large angles. The inner torsional springs 140a and 140b and outer torsional springs 142a, 142b, 142c, and 142d are designed to generate the desired resonance frequencies for wide angle scanning while avoiding unwanted, higher- order resonance modes. The inner torsional springs 140a and 140b and outer torsional springs 142a, 142b, 142c, and 142d can be optimized to increase the deflection angles of the scan mirror. The optical design allows for angles up to ±19.99° and ±13.98° in the X and Y axes, respectively, without loss of excitation power. Optical scan angles can reach ±32.75° and ±33.40° in the X and Y-axes, respectively.

[0067] The electrostatically actuated scan mirror 100 is designed and fabricated using MEMS processes. The device surface, including the reflector 136, is coated with a -70 nm layer of aluminum using a blanket evaporation process to enhance reflectivity in the visible and NIR spectral regimes.

[0068] In one use of the scanner 100, the scanner 100 was mounted on a custom fabricated holder to characterize performance at ambient temperature and pressure. The frequency response in the X and Y axes was measured using a position sensing detector (PSD, On- Track Photonics, #PSM 2-10). Scan angles at resonance frequencies were measured by driving each axis separately. The frequency response was evaluated using a down-sweep (high-to-low) and up- sweep (low-to-high) in the drive signal to determine the best direction to achieve resonance. These results were used to select the best set of parameters to produce a large range of angular deflections with minimal parasitic vibrations. The maximum scan angles in the X and Y axes were measured using a laser profilometer (KEYENCE, #LJ- V7020). Square wave signals were generated using a data acquisition board (DAQ, National Instrument, #PCI-6115) at 1 MSa / s, and delivered to a 20V / V voltage amplifier (TEGAM,#2350). The frequencies required to achieve optimal Lissajous scanning in the XY plane at 10 frames per sec (fps) were identified using custom MATLAB software (MathWorks).

[0069] Finite element analysis was performed using COMSOL software. Eigenmodes EM7 = 13992 Hz and EM2 = 4667.9 Hz, respectively, were identified for maximum X and Y axes tilt motions as shown in FIGS. 6 A - 6D. The resonance frequency in the X-axis was determined by the two inner torsional springs 140a and 140b as shown in FIG. 6E. Regions of increased stress are shown in pseudo-color. The resonance frequency in the Y-axis was determined by the four outer torsional springs 142a, 142b, 142c, and 142d as shown in FIG. 6F.

[0070] The shape, arrangement, and dimensions of one of the two inner torsional springs 140a and 140b are shown in FIG. 6G. The relevant dimensions include inner torsional spring lengths II of 5 pm, 12 of 16 pm, 13 of 52 pm, and 14 of 370 pm, as well as inner torsional spring radii including IR1 of 10.72, IR2 of 010.71, and IR3 of 02.40. The shape, arrangement, and dimensions of one of the four outer torsional springs 142a, 142b, 142c, and 142d is shown in FIG. 6H. The relevant dimensions include outer torsional spring lengths 01 of 337.5 pm, 02 of 12 pm, 03 of 5 pm, 04 of 25 pm, 05 of 171.25 pm, 06 of 187.5 pm, 07 of 8 pm, 08 of 15 pm, and 09 of 370 pm, as well as an outer torsional spring radii including OR of 043.40.

[0071] A CAD drawing is shown of the front-view of the scanner 100 in FIG. 7A. A photo of the fabricated device is shown in FIG. 7B. The frequency response in the X and Y axes was generated using a down-sweep (high-to-low frequencies) and up-sweep (low-to-high frequencies) as shown in FIGS. 7C and 7D, respectively. A time interval of -1 sec was employed in between frequency transitions to provide stable scan mirror motions at each drive frequency and to maximize the scan angles at resonance. Optical scan angles of ±27.4° and ±22.8° were measured in the X and Y axes, respectively, as shown in FIGS. 7C and 7D. The drive frequencies measured 2co agreed with the simulation results for co. Maximum mechanical scan angles of ±7.62° and ±9.44° were achieved in the X and Y axes using a square wave drive signal at 27.6 and 9.04 kHz, respectively, with 50% duty cycle at 60 Vpp during down- sweep of frequencies.

[0072] As shown in FIGS. 8A-E, in an example, multiplexed fluorescence images were collected in vivo from CPC; Ape mice that have been genetically engineered to spontaneouslydevelop colonic adenomas, like the one shown in FIG. 8A. Fluorescently-labeled peptides, including KCC*-FITC, QRH*-Cy5, and KSP*-IRDye800 were topically administered to a region of prolapsed rectum. The fluorophores were chosen with absorption spectra that match the laser excitation wavelengths at Xex= 488, 660, and 785 nm with minimal overlap of fluorescence emission spectra. The peptide ligands bind specifically to Prdxl, EGFR, and ErbB2, respectively. These molecular targets are overexpressed in pre-malignant (adenoma) but not normal mucosa. Fluorescence images collected at WD = 10 mm showed strong intensity from the adenoma (arrow) by comparison with adjacent normal mucosa as shown in FIGS. 8B-D. Target-to-background (T / B) ratios of 2.6, 3.1, and 3.9, respectively, were measured. The merged image shows fluorescence from all 3 excitation wavelengths concurrently as shown in FIG 8E.

[0073] FIG. 9 illustrates a system 400 illustrating the various components used in implementing an example embodiment of the optical arrangement discussed herein. A device 402 may have a controller 404 operatively connected to the database 414 via a link 422 connected to an input / output (RO) circuit 412. It should be noted that, while not shown, additional databases may be linked to the controller 404 in a known manner. The controller 404 includes a program memory 406, the processor 408 (may be called a microcontroller or a microprocessor), a random-access memory (RAM) 410, and the input / output (RO) circuit 412, all of which are interconnected via an address / data bus 420. It should be appreciated that although only one microprocessor 408 is shown, the controller 404 may include multiple microprocessors 408. Similarly, the memory of the controller 404 may include multiple RAMs 410 and multiple program memories 406. Although the RO circuit 412 is shown as a single block, it should be appreciated that the RO circuit 412 may include a number of different types of RO circuits. The RAM(s) 410 and the program memories 406 may be implemented as semiconductor memories, magnetically readable memories, and / or optically readable memories, for example.

[0074] The program memory 406 and / or the RAM 410 may store various applications (i.e., machine readable instructions) for execution by the microprocessor 408. For example, an operating system 430 may generally control the operation of the device 402 (including the optical arrangement 102) and provide a user interface to the testing apparatus to implement the processes described herein. The program memory 406 and / or the RAM 410 may also store a variety of subroutines 432 for accessing specific functions of the device 402. Theprogram memory 406 and / or the RAM 410 may further store data related to the configuration and / or operation of the device 402, and / or related to the operation of one or more subroutines. For example, the data may be data gathered by the optical arrangement 102, data determined and / or calculated by the processor 408, etc. In addition to the controller 404, the device 402 may include other hardware resources. The device 402 may also be coupled to various types of input / output hardware such as a visual display 426 and input device(s) 428 (e.g., keypad, keyboard, etc.) to fine tune actuation of the torsional and translation scanning. In an embodiment, the display 426 is touch-sensitive, and may cooperate with a software keyboard routine as one of the software routines 432 to accept user input. In some examples, the optical arrangement 102 may communicate with connected devices through a wired or wireless network interface 434 connected to a communication network 436.

[0075] Throughout this specification, plural instances may implement components, operations, or structures described as a single instance. Although individual operations of one or more methods are illustrated and described as separate operations, one or more of the individual operations may be performed concurrently, and nothing requires that the operations be performed in the order illustrated. Structures and functionality presented as separate components in example configurations may be implemented as a combined structure or component. Similarly, structures and functionality presented as a single component may be implemented as separate components. These and other variations, modifications, additions, and improvements fall within the scope of the subject matter herein.

[0076] Additionally, certain embodiments are described herein as including logic or a number of routines, subroutines, applications, or instructions. These may constitute either software (e.g., code embodied on a non-transitory, machine-readable medium) or hardware. In hardware, the routines, etc., are tangible units capable of performing certain operations and may be configured or arranged in a certain manner. In example embodiments, one or more computer systems (e.g., a standalone, client or server computer system) or one or more hardware modules of a computer system (e.g., a processor or a group of processors) may be configured by software (e.g., an application or application portion) as a hardware module that operates to perform certain operations as described herein.

[0077] In various embodiments, a hardware module may be implemented mechanically or electronically. For example, a hardware module may comprise dedicated circuitry or logic that is permanently configured (e.g., as a special-purpose processor, such as a fieldprogrammable gate array (FPGA) or an application- specific integrated circuit (ASIC)) to perform certain operations. A hardware module may also comprise programmable logic or circuitry (e.g., as encompassed within a general-purpose processor or other programmable processor) that is temporarily configured by software to perform certain operations. It will be appreciated that the decision to implement a hardware module mechanically, in dedicated and permanently configured circuitry, or in temporarily configured circuitry (e.g., configured by software) may be driven by cost and time considerations.

[0078] Accordingly, the term “hardware module” should be understood to encompass a tangible entity, be that an entity that is physically constructed, permanently configured (e.g., hardwired), or temporarily configured (e.g., programmed) to operate in a certain manner or to perform certain operations described herein. Considering embodiments in which hardware modules are temporarily configured (e.g., programmed), each of the hardware modules need not be configured or instantiated at any one instance in time. For example, where the hardware modules comprise a general-purpose processor configured using software, the general-purpose processor may be configured as respective different hardware modules at different times. Software may accordingly configure a processor, for example, to constitute a particular hardware module at one instance of time and to constitute a different hardware module at a different instance of time.

[0079] Hardware modules can provide information to, and receive information from, other hardware modules. Accordingly, the described hardware modules may be regarded as being communicatively coupled. Where multiple of such hardware modules exist contemporaneously, communications may be achieved through signal transmission (e.g., over appropriate circuits and buses) that connect the hardware modules. In embodiments in which multiple hardware modules are configured or instantiated at different times, communications between such hardware modules may be achieved, for example, through the storage and retrieval of information in memory structures to which the multiple hardware modules have access. For example, one hardware module may perform an operation and store the output of that operation in a memory device to which it is communicatively coupled. A further hardware module may then, at a later time, access the memory device to retrieve and process the stored output. Hardware modules may also initiate communications with input or output devices, and can operate on a resource (e.g., a collection of information).

[0080] The various operations of example methods described herein may be performed, at least partially, by one or more processors that are temporarily configured (e.g., by software) or permanently configured to perform the relevant operations. Whether temporarily or permanently configured, such processors may constitute processor-implemented modules that operate to perform one or more operations or functions. The modules referred to herein may, in some example embodiments, comprise processor-implemented modules.

[0081] Similarly, the methods or routines described herein may be at least partially processor- implemented. For example, at least some of the operations of a method may be performed by one or more processors or processor- implemented hardware modules. The performance of certain of the operations may be distributed among the one or more processors, not only residing within a single machine, but deployed across a number of machines. In some example embodiments, the processor or processors may be located in a single location (e.g., within a home environment, an office environment or as a server farm), while in other embodiments the processors may be distributed across a number of locations.

[0082] The performance of certain of the operations may be distributed among the one or more processors, not only residing within a single machine, but deployed across a number of machines. In some example embodiments, the one or more processors or processor- implemented modules may be located in a single geographic location (e.g., within a home environment, an office environment, or a server farm). In other example embodiments, the one or more processors or processor-implemented modules may be distributed across a number of geographic locations.

[0083] Unless specifically stated otherwise, discussions herein using words such as “processing,” “computing,” “calculating,” “determining,” “presenting,” “displaying,” or the like may refer to actions or processes of a machine (e.g., a computer) that manipulates or transforms data represented as physical (e.g., electronic, magnetic, or optical) quantities within one or more memories (e.g., volatile memory, non-volatile memory, or a combination thereof), registers, or other machine components that receive, store, transmit, or display information.

[0084] As used herein any reference to “one embodiment” or “an embodiment” means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearances of the phrase “in oneembodiment” in various places in the specification are not necessarily all referring to the same embodiment.

[0085] Some embodiments may be described using the expression “coupled” and “connected” along with their derivatives. For example, some embodiments may be described using the term “coupled” to indicate that two or more elements are in direct physical or electrical contact. The term “coupled,” however, may also mean that two or more elements are not in direct contact with each other, but yet still co-operate or interact with each other. The embodiments are not limited in this context.

[0086] Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the scope of the invention, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept.

[0087] While the present invention has been described with reference to specific examples, which are intended to be illustrative only and not to be limiting of the invention, it will be apparent to those of ordinary skill in the art that changes, additions and / or deletions may be made to the disclosed embodiments without departing from the spirit and scope of the invention.

[0088] The foregoing description is given for clearness of understanding only, and no unnecessary limitations should be understood therefrom, as modifications within the scope of the invention may be apparent to those having ordinary skill in the art.

Claims

What is Claimed:

1. An optical arrangement for use in an endoscope, the optical arrangement comprising: a single mode fiber for providing illumination; a collimator positioned at an exit end of the single mode fiber for producing a low numerical aperture collimated beam; a scanner for reflecting the collimated beam onto a scan region; a multimode fiber positioned to collect return light from the scan region and reflected into the multimode fiber by the scanner; an outer tube surrounding the single mode fiber, the collimator, and the multimode fiber at a distal tip; a flexible tube connected to the outer tube; and an end tube between the outer tube and the flexible tube to prevent unwanted vibrations.

2. The optical arrangement of claim 1 , wherein the distal tip of the optical arrangement is less than or equal to 2.6 mm in diameter.

3. The optical arrangement of claim 1 or claim 2, wherein the distal tip of the optical arrangement is less than or equal to 12 mm in length.

4. The optical arrangement of any one of claims 1 to 3 comprising a plurality of multimode fibers for collecting return light, the single mode fiber and the plurality of multimode fibers arranged in a linear pattern where the multimode fibers are positioned to collect return light at different scan angles ranging between zero degrees and 45 degrees.

5. The optical arrangement of any one of claims 1 to 3, comprising a plurality of multimode fibers for collecting return light, the multimode fibers arranged around the single mode fiber in one of a square pattern, a triangle pattern, and circular pattern, wherein the multimode fibers are positioned to collect return light at different scan angles.

6. The optical arrangement of any one of claims 1 to 5, further comprising a holder upon which the scanner is mounted, the holder being fabricated from M3 crystal using a 3D printer.

7. The optical arrangement of any one of claims 1 to 6, wherein the scanner is formed on a silicon device layer of a silicon-on-insulator wafer.

8. The optical arrangement of any one of claims 1 to 7, wherein the outer tube is made from stainless steel.

9. The optical arrangement of any one of claims 1 to 8, where in the scanner includes a reflector coupled to two inner torsional springs arranged in-line along a length of the reflector.

10. The optical arrangement of any one of claims 1 to 9, wherein the scanner includes a reflector coupled to four outer torsional springs arranged with two outer torsional springs on a first side of the reflector and two outer torsional springs on a second side of the reflector.

11. The optical arrangement of any one of claims 1 to 10, wherein the optical arrangement has a longitudinal axis along which the collimated beam is produced, and wherein the scanner is disposed at an angle less than 90 degrees relative to the longitudinal axis.

12. An optical system for wide-field scanning, the optical system comprising: a single mode fiber providing illumination; a collimator positioned at an exit end of the single mode fiber for producing a low numerical aperture collimated beam; a scanner for reflecting the collimated beam onto a scan region; a multimode fiber positioned to collect return light from the scan region and reflected into the multimode fiber by the scanner; an optical train having a plurality of dichroic mirrors, each of the dichroic mirrors deflecting fluorescence in distinct spectral bands; and a plurality of photomultiplier tube detectors, each photomultiplier tube detector receiving the fluorescence deflected by one of the dichroic mirrors.

13. The optical system of claim 12, wherein the single mode fiber is configured to provide laser excitation at three wavelengths.

14. The optical system of claim 13, wherein the wavelengths are 488 nm, 660 nm, and 785 nm.

15. The optical system of any one of claims 12 to 14, wherein the optical train includes three dichroic mirrors, each dichroic mirror configured for a distinct spectral band.

16. The optical system of any one of claims 12 to 15, further comprising a convex lens configured to increase a scan angle.

17. The optical system of any one of claims 12 to 16, further comprising a medical endoscope within which an optical arrangement including the single mode fiber, collimator, scanner, and multimode fiber is configured to travel.

18. The optical system of any one of claims 12 to 17, where a working distance between the scanner and the collimator is less than or equal to 30 mm.

19. The optical system of claim 18, wherein the field-of-view of the optical system is greater than 4.2 mm in diameter at a working distance of 30 mm.

20. The optical system of any one of claims 12 to 19, wherein the scanner is a MEMS mirror with a monolithic integrated design.

21. The optical system of claim 20, wherein the MEMS mirror is configured to produce large angular deflections to achieve an image field-of-view greater than 60 degrees.

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