|ΘΘ01) The present application relates to and claims priority from U.S. Provisional

Patent Application Serial No. 61/692.1 1? filed August 22, 012 and from U.S. Provisional Patent Application Serial No. 61/779,671 filed March 13, 2013, the disclosures of which are incorporated herein by reference in their entireties.

FIEL OF THE DISCLOSURE

|0002{ The present disclosure relates generally to a fabrication of a miniature microscope, and more particularly to exemplary system, method, and computer-accessible medium for fabrication of miniature endoscope using soft lithography, and for minimally- invasive imaging and image-guided therapy.

BACKGROUND IN FORM ATION

(0603] Spectrally encoded endoscopy {/'SEE") is a ni afcure endoscopy technology that can conduct high-defiiiition imaging through a sub~mm diameter probe. With SEE, broadband light is diffracted by a grating at the tip of the fiber, producing a dispersed spectrum on the saraple. Light returned from the sample is detected using a spectrometer; and each resolvable wavelength corresponds to reflectance from a different point on the sample. Previously, SEE procedures have been demonstrated using a 350 μηι diameter probe, which produced high-quality images in two- and three- dimensions. One of the technical challenges for fabricating SEE probes has been lo make a sub-rom transmission grating with a high diffraction efficienc and to precisely assemble the miniature grating with other optical components io th e probe.

[0004] Thus, there may be a need to improve the above-described fabrication of the

SEE probes, and to overcome at least some of the deficiencies of the conventional devices.

SUMMARY OF EXEMPLARY EMBODIMENTS

|60βδ] Thus, to address such exemplary need, system, method, and computer- accessible medium for fabrication of miniature endoscope using soft lithography according to exemplar)' embodiments of the present disclosure can be provided. According to one exemplary embodiment, method, system, and computer accessible medium can be provided for fabricating SEE probes using soft lithography, including a fabrication Of miniature diffraction gratings on the SEE imaging opii.cs.

[0006] in one exemplary embodiment, the miniature grating can be provided by first making a PDMS grating master pattern and then replicating the grating pattern on th miniature imaging lens. The smallest diameter of the grating fabricated by this method is only limited by the smallest size of the imaging lens, enabling the fabrication of yltramitiiatnre SEE probe, less than 0.1 mm in diameter. And the miniature gratings can be easily fabricated with UV curing epoxy, po!yurethanes, or other low-cost polymers making the final device inexpensive.

[0007] Thus, according to cert ain exempl ary embodiments of the present disclosure, exemplary method and system can be presented for providing a diffractive configuration in an optical arrangement can be provided. For example, an elastomeric material can be provided with at least one patterned surface. The elastomeric material can be connected with at least one portion of a waveguide arrangement using a pre-potymer adhesive composition, Further, the pre-polyraer adhesive composition can be caused to polymerize so as to form the diffractive configuration which at least approximately replicate a structure or at least one feature of an elastomeric mold.

[0008] For example, in one exemplary embodiment of the present disclosure, the diffractive configuration can be a grating. The elastomeric material can be removed from the optical arrangement. The optical arrangement can comprise at least one lens iu optical communication with the diffractive configuration. The elastomeric material can c mprise a hard elastomeric component and a soft back support. The elastomeric material can be provided by applying an elastomeric stamp to form the patterned surfaeeis). The pre-polymer adhesive composition can be caused to pol merize by applying at least one electro-magnetic radiation to the pre-polyraer adhesive composition to be polymerized. The electro- magnetic radiation can be provided via the waveguide arrangement. The pre-polymer adhesi e composition can have a refractive index of between 1.3 and 1.7. The diffractive

configuration can have a diameter or a cross-section that is smaller than 1mm. The grating can have (i) a grove density thai is larger than 1000 lines per mm. and/or {it) a grove aspect ratio that is larger than 1. The gratin can have diffraction efficiency that is larger than 70%. The diffractive configuration can have at least one lens element. The optical arrangement can include a GRIN lens. [0Θ09] These and other objects, features and advantages of the present disclosure will become apparent upon reading the following detailed, description of exemplary embodiments of the present disclosure, when taken in conjunction with the appended drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

|001 | Further objects, features and advantages of the disclosure will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments, results and/or features of the exemplary embodiments of the present disclosure, in which:

(0Θ11] FIG. 1 is a schematic diagram of an exemplary SEE probe according to an exemplary embodiment of .the present disclosure, fabricated by an. exemplary method according to an exemplary embodiment of the present disclosure;

j 0012 FIG. 2 is a flow diagram of an exemplary grating fabrication method according to an exemplary embodiment of the present disclosure;

f0013j FIG. 3 is a schematic diagram of an exemplary elastomerk stamp fabrication process according to an exemplary embodiment of the presen disclosure;

(ΘΘ14) FIG. 4 is a schematic diagram of an exemplary grating fabrication process according to an exemplary embodiment of the present disclosure;

[ΘΘ1.5) FIGS. 5A-5C are a set of exemplary microscopy photos of an exemplary SEE probe according to an exemplary embodiment ^" of the present disclosure;

|0016| FIG. (> is an exemplary photograph of the spectrally-encoded illumination by an exemplary SEE probe according to an exemplary embodiment of the present disclosure;

|¾01?| FIGS. 7A-7D are a set of exemplary SEE images of mouse embryos obtained with an exemplary SEE probe according to an exemplary embodiment of the present disclosure:

|θθ 18] FIG. 8 is a diagram of an exemplary method of fabricating a composite elastoraeric stamp according to an exemplary embodiment of the present disclosure;

|Θ019] FIG. 9 is a set of illustrations of an exemplary SEE probe that has more than one optical component at the distal end according to an exemplary embodiment of the present disclosure; [ΘΘ2Θ] FIGS. 1 A and 10B are illustration of exemplary methods of polyraer.iz.mg

UV-curable prepolymer according to an exemplary embodiment of the present disclosure;

[0021] FIG. 1 1 is an illustration of an exemplary method of polymerizing UV-curable prepolymer trader nitrogen-rich environment according to an exemplary eniboditnent of the present disclosure; and

[0022] FIG. 12 is an illustration of an exemplary elastoraeric stamp with multiple pillars with each pillar having a grating pattern according to an exemplary embodiment of the present disclosure.

[ΘΘ23] Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Similar features may thus be described by the same reference numerals, which indicate to the skilled reader thai exchanges of features between different embodiments can be done unless otherwise explicitly stated. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the particular

embodiments illustrated in the figures. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope and spirit of the present disclosure as defined by the appended claims,

^' DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[6024] A schematic of an exemplary embodiment of the SEE probe is shown in FIG.

1 according to an exemplary embodiment of the present disclosure. This exemplary SEE probe can include an optical fiber 100, a focusing lens 1 10, and a diffraction grating 120. As shown in FIG. i , a broadband light or a UV light 130 can be dispersed along a transverse aspect of the sample 140.

[ΘΘ25} in one exemplary embodiment of the present disclosure, the diffraction grating

120 can be fabricated based on the exemplary process according to an exemplary

embodiment of the present disclosure, as shown in FIG. 2. In this exemplary process, a master with a grating pattern can be fabricated (procedure 150). The grating master can be made by various methods, including, e.g., electron-beam lithography, photo-lithography, interference lithography, nanoetnbossing, nanoimprhit, or reactive ion etching. The

exemplary geometry of the grating master can be determined by a numerical simulation to provide high diffraction efficiency at the working spectrum. For example, for the working spectrum of 400-700 RIB, the grating can have the groove density of 1379 lines/mm and the groove depi ^' h o .I pm to provide a diffraction efficiency of 85% when the refractive index of the grating material is about 1 .47. The grating master can be an etched fused silica grating. Once the grating master is fabricated, an elastomeric stamp can be made (procedure 160), e.g., using the grating master. The final grating can be made by replica molding of the elastomeric stamp {procedure 170),

|0026) FIG. 3 shows an exemplary diagram of a process of fabricating the eSastorrieric stamp according to an exemplary embodiment of the present disclosure. For example, a prepolymer 210 can be applied on a grating master 200, The prepolymer 210 can be cured, thus, e.g., forming an elastomeric material 21 1 , and peeled Of to complete the elastomeric stamp with a grating pattern 220. The eiastoraene stamp can be made of, e.g.,

Polydimeihyisiloxane (POMS), An example of .POMS can be Sylgrad 1.84 by Dow Coming. Other elastomers, silicone based polymers, rubbers, or latex derivatives can also be used as stamps. The prepolymer 210 used as a stamp can be cured by heat, catalytic reaction with chemicals or moisture, and/or electromagnetic radiation.

[ΘΘ27] FIG. 4 shows an exemplary illustration of a process of fabri cating a miniature gratin at tire tip of the SEE probe optics, according to an exemplary embodiment of the present disclosure. For example, a prepolymer 400 can be placed at the tip of the focusin lens 1 10. The elastomeric stamp with the grating pattern 220 can come into contact with the prepolymer 400. The prepolymer can be polymerized 41 to complete the miniature grating 120. The elastomeric stamp 220 can be removed once the miniature grating is completed. The prepolymer 300 can be cured by heat, moisture, and/or electromagnetic radiation. The refractive index of the miniature grating 120 in conjunction with the grating geometry determines the diffraction efficiency. Therefore, the prepolymer 400 can. be carefully selected so that the refractive index of the miniature grating 120 can be close to the design refractive index that provides a high diffraction efficiency.

[0028] FIG 5 A depicts an exemplar highly magnified photograph of a tip of an exemplary SEE probe fabricated by tire method according to an exemplary embodiment of the present disclosure. The central elliptical region at th distal tip of the SEE probe is green because the grating formed at the probe's tip diffracted the illumination fight of the microscope system and preferentially directed the green light to the microscope camera at. this particular viewing angle. The area of th green region indicated the area where the miniature grating was well formed. Approximately 86% of the probe diameter along the long axis of the grating and 78% along the short axis showed the green diffraction pattern. A ^■ scanning electron microscope (SEM) image (see, e.g., FIG. 5B) of the SEE probe was acquired with a Zeiss Supra55 VP FESEM at 2 k ^' V at a working distance of 6 ram. Before SEM imaging, the exemplary SEE probe was placed on a silicon wafer and sputter coated with Pt/Pd at 60 mA for 15-45 seconds in order to improve the contrast of the image. The high-magnification. SEM image reveals the regular line pattem of the grating (see, e.g., FIG. 5C). The standard deviation of the groove pitch was measured to be about 1.2% of the mean grating pitch.

|o029| A diffraction performance of the exemplary miniature grating 120 shown in FiG . 1 was tested. I¼r exemplary SEE probe generated the spectrally-encoded illumination _. pattern 600, which appears as a linear rainbow (see FIG. 6). The diffraction efficiency of the +.1 st order, the intensity of the ÷lst order divided by the intensity of the input beam, was measured to be about 75% for the beam diameter of about 500 urn and the input wavelength of about 532 nm. This diffraction efficiency is lower than thai of the master grating, e.g., about 85%. The grating diameter was smaller than the probe diameter, and therefore a portion of light was not diffracted, which reduced the diffractio efficienc ^y . The difference of the refractive index between the master grating and the replicated grating might have also decreased the diffraction efficiency,

|t)()30| FIGS. 7A-7D show a set of exemplary SEE images of mouse embryos obtained with the exemplary SEE probe fabricated by the method according to an exemplary embodiment of the present disclosure. Mouse embryos were inside a polypropylene 50 ml tube, and the SEE imaging was conducted through an approximately 10 mm thick layer of 3.7% formaldehyde fixative solution. The SEE images (see, e.g., FIGS. 7A-7C) facilitate a clear visualisation of anatomic features of (he embryo, including the head, eye 700, tail 710 and paws with claws 720, which are similar to those shown in the photo of the same animal (see, e.g., FIG. 7D).

[0031] One of the advantages of the exemplary fabrication, meihod according to an exemplary embodiment of the present disclosure is that the exemplary SEE probes can be made at a low cost. An exemplary elastomeric stamp (e.g., ^' effective grating area - 13.5 mm by 12.5 mm) can be used to fabricate approximately 1 70 miniature gratings assuming that a 1 mm by 1 mm area of the stamp is needed for fabricating an approximately 500-pm-diameter grating. For example, multiple elastomeric stamps can be made without damaging the master. The low cost makes it possible to fabricate cheap and disposable SEE probes, which can facilitate the clinical use of this technology.

|fl0321 It is also advantageous that the exemplary fabrication method according to an exemplary embodiment of the present disclosure can form the miniature grating on the imaging optics as the last step. When the exemplary grating is not properly fanned during the fabrication process or is damaged during the use, the tip of the SEE probe can he easily

-polished, by a very small amount ( -20 urn) to remove the damaged grating. Following this exemplary corrective action, a new grating can then be fabricated on the same imaging optics, A procedure for handling and precisely aligning the miniature grating may not be needed, in the exemplary method according to an exemplary embodiment of the present disclosure, which makes the exemplary fabrication process easier than would a method requiring an alignment.

(ΘΘ33) Ano ther advantage of the exemplary fabrication method accordin g to an. exemplary embodimen t of the present di sclosure is that the exemplary SEE probe size can be decreased further. For example, an ultraroiniature GRIN lens -with a diameter of about SO pm has been recently being developed by GRINiech. The exemplary method according to an exemplary embodiment of the present disclosure can be used to make a grating at the tip of the 80-pm GRI lens, which can make it possible to consider an ultraminiature SEE probe with a diameter that is smaller than 100 p.m. For example, the small diameter of the ultraminiature SEE probe can facilitate imaging of the internal tissues thai are not currently accessible by the conventional endoscopic imaging devices.

[0034) The exemplary elastomer ic stamp can be made of two different materials, e.g., to improve the ^' resolution of the replica molding process. FIG. 8 shows an exemplary embodiment of the method according to an exemplary embodiment of the present disclosure that can be used to fabricate a composite elastomeric stamp, in this exemplary embodiment shown in FIG. 8, an elastomeric prepolymer 232 that can have high stiffness after curing may be placed on the grating master 200. An example of the elastomer with a high stiffness can be h-PDMS. Then, another elastomeric prepolymer 813 that can have lower stiffness than the first elastomeric material 212 may be poured on top of the first elastomeric material 212. The two elastomeric material can be cured and peeied off io complete the -final elastomeric stamp 220. [ΘΘ35] This exemplary embodiment can be advantageous in replicating a gratin pattern with a high aspect ratio. If the elastomeric stamp 220 is made of soft material., such as, e.g., Sylgrad 1 4, the replicated pattern can collapse and/or sag if the grating pattern has a high aspect ratio. This exemplary composite stamp 220 can combine the advantages of both a more rigid layer 212 (e.g., to achieve high-resolution-pattern transfer) and a more flexible support 213 (e.g., to facilitate a conformal contact with a surface withotu external pressure).

|0036) FIG. 9 shows a set of illustrations of the exemplary SEE probe according to an exemplary embodiment of the present disclosure, in this exemplary embodiment, the distal optics has more than one optical component. For example, light and/or other electromagnetic radiation from the liber 100 can be focused by a focusing lens 110, and light and/or other electro-magnetic radiation from the .sample can be collected by an additional fiber, e.g., a detection fiber 11 1. The focusing lens I I 0 and the detection fiber i .1 .1 can be assembled before the fabrication of the grating. Then the prepol mer 300 can be both the focusing lens 1 10 and detection fiber ϊ ί 1 and cured 310 to complete the miniature grating 120. The method described in this invention can be used for any imaging optics of a range of designs, regardl ess of the number and dimension of the optical components used.

|003?j According to another exemplary embodiment of the SEE probe of the present disclosure, the prepolymer can be -curable prepolymer. The UV-curable prepolymer can be cured by various approaches, including those as shown in in the exemplary illustration of FIG. 10. For example, as illustrated in FIG. 1 OA. the IJV light 1 0 can be provided and/or coupled to the fiber 100. In this exemplary embodiment, the area o f the prepolymer 300 that is polymerized can be confined to the size of, e.g., the probe diameter. However, when the coupling efficiency of the UV curing Sight 320 into the fiber 1 0 is low, the curing time can become long, in FIG. S OB, the UV light 320 is delivered from the back side of the elastomeric stamp 220. In this exemplary approach, the curing can be conducted quickly. However, if the prepolymer spreads to an area that is bigger than the probe diameter, the size of the miniature grating can be bigger than the probe diameter.

|ΘΘ38] In another exemplary embodiment of the SEE probe according to the present disclosure as shown in FIG. 1 1 , the curing can be conducted under nitrogen-rich

environment. For example, nitrogen 330 can be provided to the surrounding area of the prepolymer 300. The nitrogen can prevent the contact between the oxygen and the prepolymer 300, which can. improve the quality of the miniature grating. [0Θ39] in another exemplary embodiment according to the present disclosure, the elastomeric stamp 1220 can be made with multiple circular pillars, as shown in FIG. 1 . For example, each pillar 1221 can have the grating pattern at the top, and the diameter of each pillar is same to the imaging optics diameter. This exemplary stamp can ensure and/or facilitate that the epoxy does not spread behind, the diameter of the imaging optics and can make it easy to achieve a circular epoxy spread with a diameter same to the imaging optics diameter.

[ΘΘ40] The foregoin merely illustrates the principles of the invention. Various modifications and. alterations to the described embodiments will he apparent to those skilled in the art in view of the teachings herein, indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention can be used with any OCT system, OFDl system, SD-OCT system or other imaging systems, and for example with those described in International. Patent Application PCT/US2004/029148, filed September 8, 2004, U.S. Patent Application No. 1 1/266,779, filed November 2, 2005, and U.S. Patent

Application No. 10/501 ,276, filed July 9, 2004. the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled i the art will ^' be able to devise numerous systems, arrangements and methods which, although not explicitl shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. In addition, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly being incorporated herein in its entirety. All publications referenced herein above are incorporated herein by reference in their entireties..