High resolution compact optical imaging system

Abstract

An exemplary embodiment of the present disclosure provides an imaging system, comprising an elongated member, an illumination system, one or more lenses, an image sensor, and a processing unit. The illumination system can be disposed on a portion of the elongated member and configured to illuminate an area to be imaged. The one or more lenses can be disposed within a distal end of the elongated member and configured to receive light from the area to be imaged. The image sensor can be disposed within a portion of the elongated member and configured to receive the light from the one or more lenses. The processing unit can be configured to receive a signal from the image sensor and generate an image indicative of the area to be imaged.

Description

HIGH RESOLUTION COMPACT OPTICAL IMAGING SYSTEMCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 572,502. filed on 1 April 2024, which is incorporated herein by reference in its entirety as if fully set forth below.GOVERNMENT LICENSE RIGHTS

[0002] This invention was made with government support under GM147437 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE DISCLOSURE

[0003] The various embodiments of the present disclosure relate generally to endoscopic imaging systems, specifically to quantitative oblique back-illumination microscopy (qOBM) endoscopic imaging systems.BACKGROUND

[0004] Endoscopic imaging systems are critical tools in modem medical diagnostics and minimally invasive surgeries. Traditional endoscopes utilize fiber bundles to transmit light from the imaging site to an external camera. While effective, these systems have several limitations. For example, conventional endoscopic imaging systems can be bulky. The use of fiber bundles necessitates a larger form factor, making the endoscope less maneuverable and more challenging to use in confined spaces. Conventional systems also suffer from resolution limitations. Fiber bundles inherently limit the resolution of the imaging system due to the discrete nature of the fibers and the potential for light loss and distortion as light travels through the bundle. These conventional systems are also fragile, as fiber bundles are delicate and prone to damage, which can degrade image quality and necessitate frequent repairs or replacements.

[0005] Accordingly, there is a need for advanced endoscopic imaging systems that overcome the limitations of traditional fiber bundle-based systems. Such a system would desirably offer a smaller form factor that allows for greater maneuverability and application in a wider range of medical procedure, higher resolution imaging to provide more detailed and accurate visualizations of the internal anatomy, and increased durability to reduce maintenance costs and improve the reliability of the imaging system.BRIEF SUMMARY

[0006] An exemplary embodiment of the present disclosure an imaging system for imaging tissues, comprising an elongated member, a light source, one or more micro lenses, an electronic image sensor, and a processing unit. The light source can be disposed on a portion of the elongated member and configured to illuminate a tissue to be imaged. The one or more microlenses can be disposed on a distal end of the elongated member and configured to receive light passing through at least a portion of the tissue. The electronic image sensor can be disposed within a portion of the elongated member and configured to receive the light from the one or more microlenses and generate one or more images of tissue, each of the one or more images having a resolution of 100 nm to 10 microns. The processing unit can be configured to receive a signal from the image sensor indicative of the one or more images and generate a phase image (including, but not limited to, a quantitative phase image) of the tissue, each pixel of the phase image indicative of refractive index properties of the tissue corresponding to the respective pixel.

[0007] In any of the embodiments disclosed herein, the one or more microlenses can have a numerical aperture of 0.2- 1.2.

[0008] In any of the embodiments disclosed herein, the one or more microlenses can comprise one or more gradient index lenses.

[0009] In any of the embodiments disclosed herein, the system can further comprise one or more rod lenses disposed within the elongated member between the one or more gradient index lenses and the image sensor, and the one or more rod lenses can be configured to alter a distance between a distal tip of the elongated member and the image sensor.

[0010] In any of the embodiments disclosed herein, the one or more microlenses can have a diameter of 0.5-30 mm.

[0011] In any of the embodiments disclosed herein, the one or more images can have a field of view of 50-5000 microns.

[0012] In any of the embodiments disclosed herein, the light source can comprise one or more selected from the group consisting of a light emitting diode, a laser, a diode, a super luminescent diode, a light bulb, and an optical fiber.

[0013] In any of the embodiments disclosed herein, the image sensor can comprise a CMOS sensor.

[0014] In any of the embodiments disclosed herein, the processing unit can comprise hardware and / or software for controlling the imaging system.

[0015] In any of the embodiments disclosed herein, the processing unit can be configured to receive one or more control parameters selected from the group consisting of: illumination intensity of the light source, illumination switching speed of the light source, camera readout speed of the image sensor, camera gain of the image sensor, camera exposure of the image sensor, camera bit depth of the image sensor, and image data format.

[0016] In any of the embodiments disclosed herein, the light source can comprise a first light emitting diode (LED) on a first side of a distal end of the elongated member and a second LED on a second side of the distal end of the elongated member, and the first and second LEDs cam be configured to emit light into the tissue to generate oblique back illumination.

[0017] In any of the embodiments disclosed herein, the light source can comprise a light emitting diode (LED) and an optical fiber, at least a portion of the optical fiber can extend along a length of a portion of the elongated member, and the optical fiber can be configured to receive light at a first end from the LED and direct the light out of a second end to the area to be imaged.

[0018] In any of the embodiments disclosed herein, the optical fiber can be a single mode optical fiber.

[0019] In any of the embodiments disclosed herein, the optical fiber can be a multi-mode optical fiber.

[0020] In any of the embodiments disclosed herein, the light source can comprise a light emitting diode (LED) and a rigid light guide (such as a waveguide), at least a portion of the light guide can extend along a length of a portion of the elongated member, and the light guide can be configured to receive light at a first end from the LED and direct the light out of a second end to the area to be imaged.

[0021] In any of the embodiments disclosed herein, the system can further comprise an actuator configured to alter a distance between a distal end of the elongated member and the image sensor.

[0022] In any of the embodiments disclosed herein, the system can further comprise a prism configured to alter an imaging direction by 90 degrees.

[0023] In any of the embodiments disclosed herein, the elongated member can be configured to be inserted into the body of a subject, and the tissue can be inside the body of the subject.

[0024] In any of the embodiments disclosed herein, the imaging system can be in the form of an endoscope.

[0025] In any of the embodiments disclosed herein, the light source can be configured to emit light having a wavelength of between 200-1750 nm.

[0026] In any of the embodiments disclosed herein, each of the one or more images can be taken at a same field of view.

[0027] In any of the embodiments disclosed herein, each of the one or more images can be taken with a distinct illumination pattern from the light source.

[0028] In any of the embodiments disclosed herein, the light source can be configured to illuminate the tissue at a plurality of directions.

[0029] In any of the embodiments disclosed herein, the one or more images can comprise no more than four images.

[0030] In any of the embodiments disclosed herein, the sensor can be one of a monochrome or a color sensor.

[0031] Another embodiment of the present disclosure provides a method of imaging a tissue. The method can comprise: providing an imaging system; illuminating, with a light source of the imaging system, the tissue; capturing, with an image sensor of the imaging system, one or more images of the tissue, each of the one or more images having a resolution of 100 nm to 10 microns; and generating, with a processing unit of the imaging system, a phase image based at least in part on the one or more images of the tissue.

[0032] In any of the embodiments disclosed herein, the method can further comprise: altering a distance between a distal end of the elongated member of the imaging system and the image sensor; and capturing, with the image sensor, one or more additional images of the tissue. The phase image can be a 3D phase image (including, but not limited to, a 3D quantitative phase image) based at least in part on the one or more images and the one or more additional images.

[0033] In any of the embodiments disclosed herein, the method can further comprise inserting the distal end of the elongated member into a subject proximate the tissue.

[0034] In any of the embodiments disclosed herein, illuminating the tissue can comprise illuminating the tissue with a first light source, and capturing the one or more images can comprise capturing a first image.

[0035] In any of the embodiments disclosed herein, illuminating the tissue can comprise illuminating the tissue with a second light source, and capturing the one or more images comprises capturing a second image.

[0036] In any of the embodiments disclosed herein, illuminating the tissue with the second light source can comprise illuminating the tissue at a first wavelength to cause at least a portionof the tissue to fluoresce, and the second image can be based on fluorescent light emitted from the at least a portion of the tissue.

[0037] In any of the embodiments disclosed herein, the method can further comprise filtering light reflected from the tissue at the first wavelength prior to capturing the second image.

[0038] These and other aspects of the present disclosure are described in the Detailed Description below and the accompanying drawings. Other aspects and features of embodiments will become apparent to those of ordinary skill in the art upon reviewing the following description of specific, exemplary embodiments in concert with the drawings. While features of the present disclosure may be discussed relative to certain embodiments and figures, all embodiments of the present disclosure can include one or more of the features discussed herein. Further, while one or more embodiments may be discussed as having certain advantageous features, one or more of such features may also be used with the various embodiments discussed herein. In similar fashion, while exemplary embodiments may be discussed below as device, system, or method embodiments, it is to be understood that such exemplary embodiments can be implemented in various devices, systems, and methods of the present disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The following detailed description of specific embodiments of the disclosure will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the disclosure, specific embodiments are shown in the drawings. It should be understood, however, that the disclosure is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

[0040] FIG. 1 provides a schematic of an imaging system, in accordance with some embodiments of the present disclosure.

[0041] FIG. 2 provides a schematic of a imaging system, in accordance with some embodiments of the present disclosure.

[0042] FIG. 3 provides a schematic of a portion of an imaging system, in accordance with some embodiments of the present disclosure.

[0043] FIG. 4 provides a schematic of a portion of an imaging system, in accordance with some embodiments of the present disclosure.

[0044] FIG. 5 provides a schematic of a portion of an imaging system, in accordance with some embodiments of the present disclosure.

[0045] FIG. 6 provides a schematic of a portion of an imaging system, in accordance with some embodiments of the present disclosure.DETAILED DESCRIPTION

[0046] Although preferred exemplary embodiments of the disclosure are explained in detail, it is to be understood that other exemplary embodiments are contemplated. Accordingly, it is not intended that the disclosure is limited in its scope to the details of construction and arrangement of components set forth in the following description or illustrated in the drawings. The disclosure is capable of other exemplary embodiments and of being practiced or carried out in various ways. Also, in describing the preferred exemplary embodiments, specific terminology will be resorted to for the sake of clarity.

[0047] To facilitate an understanding of the principles and features of the present disclosure, various illustrative embodiments are explained below. The components, steps, and materials described hereinafter as making up various elements of the embodiments disclosed herein are intended to be illustrative and not restrictive. Many suitable components, steps, and materials that would perform the same or similar functions as the components, steps, and materials described herein are intended to be embraced within the scope of the disclosure. Such other components, steps, and materials not described herein can include, but are not limited to, similar components or steps that are developed after development of the embodiments disclosed herein.

[0048] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0049] Also, in describing the preferred exemplary embodiments, terminology will be resorted to for the sake of clarity. It is intended that each term contemplates its broadest meaning as understood by those skilled in the art and includes all technical equivalents which operate in a similar manner to accomplish a similar purpose.

[0050] Ranges can be expressed herein as from “about” or “approximately” one particular value and / or to “about” or “approximately” another particular value. When such a range is expressed, another exemplary embodiment includes from the one particular value and / or to the other particular value.

[0051] Similarly, as used herein, “substantially free” of something, or “substantially pure”, and like characterizations, can include both being “at least substantially free” of something, or “at least substantially pure”, and being “completely free” of something, or “completely pure”.

[0052] By “comprising” or “containing” or “including” is meant that at least the named compound, member, particle, or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, method steps, even if the other such compounds, material, particles, method steps have the same function as what is named.

[0053] Mention of one or more method steps does not preclude the presence of additional method steps or intervening method steps between those steps expressly identified. Similarly, it is also to be understood that the mention of one or more components in a device or system does not preclude the presence of additional components or intervening components between those components expressly identified.

[0054] The materials described as making up the various members of the invention are intended to be illustrative and not restrictive. Many suitable materials that would perform the same or a similar function as the materials described herein are intended to be embraced within the scope of the invention. Such other materials not described herein can include, but are not limited to, for example, materials that are developed after the time of the development of the invention.

[0055] Reference will now be made in detail to exemplary embodiments of the disclosed technology, examples of which are illustrated in the accompanying drawings and disclosed herein. Wherever convenient, the same references numbers will be used throughout the drawings to refer to the same or like parts.

[0056] Embodiments of the present disclosure are directed to a quantitative oblique back- illumination microscopy (qOBM) endoscopic imaging system. This innovative system eliminates the need for fiber bundles by integrating advanced imaging technology directly onto the tip of the endoscope. The chip-on-tip design can significantly reduces the form factor, making the endoscope more compact and maneuverable. Additionally, the qOBM technology drastically increases the resolution of the imaging system, providing clearer and more detailed images. This advancement represents a significant improvement over conventional endoscopic systems, offering enhanced performance and broader applicability in medical diagnostics and surgical procedures.

[0057] Some embodiments of the present disclosure combine a high numerical-aperture imaging objective, such as a Gradient-Index (GRIN) lens, and an imaging sensor based on the chip-on-tip technology to realize a high resolution, compact size optical imaging device. This device can use illuminations delivered through optical setups, such as optical fibers, to maintainthe compactness, and can work in an epi-illumination mode on fresh, thick biological samples. Possible compatible imaging modalities include phase imaging, fluorescence, reflectance imaging and others. Possible applications include endoscopy, gastroscopy, colonoscopy, colposcopy, laparoscopy, optical assay, portable imaging in constrained environment, and others.

[0058] As shown in FIG. 1, an exemplary embodiment of the present disclosure provides a imaging system comprising a microlens 105, an electronic image sensor 110, and a light source 115A 115B. the light source 115A 115B can be configured to illuminate a tissue to be imaged (e.g., the tissue of a subject in vivo) to generate oblique back illumination in the tissue. The light source can be many light sources known in the art, including, but not limited to, light emitting diodes, lasers, diodes, super luminescent diodes, light bulbs, optical fibers, the like, and combinations thereof. The light source can emit light having wavelengths ranging from 200-1750 nm. The oblique back illuminated light from the tissue can then pass through the microlens and to the electronic image sensor. The electronic image sensor can then generate an image based on the received light. The image can then be processed by a processing unit to generate a phase image (or quantitative phase image) of the tissue, in which each pixel of the phase image indicative of refractive index properties of the tissue corresponding to the respective pixel. Techniques for this qOBM image generation are disclosed in PCT Patent Publication No. W02019191061, entitled “Cell Imaging Systems and Methods,” which is incorporated herein by reference in its entirety as if fully set forth below.

[0059] A used herein, the term “electronic image sensor” includes semiconductor-based devices that convert light into electrical signals for the purpose of capturing images. This includes, but is not limited to, Complementary Metal-Oxide-Semiconductor (CMOS) sensors and other semiconductor-based image sensors. The electronic image sensor can be integrated directly onto the tip of an endoscope, enabling the chip-on-tip design. The term “electronic image sensor,” however, explicitly excludes any image sensor that receives light transmitted through a long fiber bundle running the length of the endoscope. Instead, the electronic image sensor must directly capture light from the imaging site without relying on such fiber optic transmission methods.

[0060] An improvement provided by embodiments of the present disclosure over conventional devices that relied on a fiber bundle for image generation is that the electronic image sensors utilized herein can provide an improved image resolution. Indeed, electronic sensors of thepresent disclosure can provide image resolutions from 100 nm to about 10 microns — a three fold improvement over conventional fiber bundle-based devices.

[0061] The processing unit can be many processors known in the art and can include a combination of hardware and software (e.g., digital signal processing (DSP) chips) to process images from the image sensor to generate the phase image of the tissue.

[0062] In some embodiments, the system can further comprise a controller to control one or more parameters of the imaging system. The controller can be many controllers known in the art and can comprise a combination of hardware and software. The parameters can include, but are not limited to, illumination intensity of the light source, illumination switching speed of the light source, camera readout speed of the image sensor, camera gain of the image sensor, camera exposure of the image sensor, camera bit depth of the image sensor, and image data format. In some embodiments, the controller is integrated with the processing unit, (i.e., the processing unit can comprise the controller). The controller and processing unit can be electrically coupled to the imaging system (e.g., sensor, light sources, etc.) via one or more wires 121 126.

[0063] The imaging system can comprise one or more microlenses. In some embodiments, the microlenses can have a diameter of from about 0.5 mm to about 10 mm. In some embodiments, the microlenses can have a numerical aperture between about 0.2 and about 1.2. In some embodiments, the one or more microlenses can comprise a gradient index lens (GRIN lens).

[0064] As shown in FIG. 2, in some embodiments, the imaging system can be provided in the form of an endoscope. As used herein, the term “endoscope” is broadly defined to include any medical imaging device designed for insertion into the body to visualize internal organs, tissues, or cavities. This definition encompasses traditional endoscopes, laparoscopes, and similar devices used in medical imaging applications. The term “endoscope” includes flexible and rigid instruments that may be used for diagnostic, therapeutic, or surgical procedures, providing real-time imaging and visualization capabilities.

[0065] Accordingly, one or more components of the imaging system can be provided in an elongated member 230 forming in inner or outer shell of the endoscope. As shown in FIG. 2, the imaging system can comprise a microlens system 205 and an electronic image sensor 210 disposed in the elongated member 230. The microlens system 205can be disposed proximate the distal end of the elongated member 230. One of more LED light sources 215A 215B can also be disposed proximate a distal end of the elongated member 230 to direct light to the tissue to be imaged. The LED light sources 215A 215B can be coupled to the processing unit 220 viaone or more wires 221 A 22 IB. Light from the tissue can pass through the micro lens system 205 where it is captured by the image sensor 210 to generate an image. The image can then be transmitted to the processing unit 220 via a wire 226 where the image is processed to generate a phase image.

[0066] FIG. 3 provides an alternative configuration for a imaging system, in accordance with some embodiments of the present disclosure. As shown in FIG. 3, the system can comprise a microlens system 305 and an electronic image sensor 310 disposed in an elongated member 320. The light source comprises first and second LEDs 315A 315B. The LEDs 315A 315B are coupled to respective optical fibers 316A 316B, which have distal ends disposed proximate the distal end of the elongated member 320. Thus, the LEDs 315A 315B can be controlled to emit light which travels down the optical fibers 316A 316B where the light is then directed to the tissue to be imaged. The optical fibers utilized in the present disclosure can be many optical fibers known in the art, including, but not limited to, single mode fibers, multimode fibers, and the like.

[0067] FIG. 4 provide yet another alternative configuration for an imaging system, in accordance with some embodiments of the present disclosure. As shown in FIG. 4, the system can comprise a microlens system 405 and an electronic image sensor 410 disposed in an elongated member 420. The light source comprises first and second LEDs 415A 415B. The LEDs 415A 415B are coupled to respective optical fibers 416A 416B, which have distal ends disposed proximate the distal end of the elongated member 420. Thus, the LEDs 415A 415B can be controlled to emit light which travels down the optical fibers 416A 416B where the light is then directed to the tissue to be imaged. The system can further comprise one or more rod lenses 425A 425B disposed between the microlens system 405 and the electronic image sensor 410 . The one or more rod lenses 425A 425B can, thus, alter a distance between a distal tip of the elongated member 420 and the image sensor 410.

[0068] FIG. 5 provides yet another alternative configuration for an imaging system, in accordance with some embodiments of the present disclosure. As shown in FIG. 5, the system can comprise a microlens system 505 and an electronic image sensor 510. Though not shown in FIG. 5, the microlens system 505 and the image sensor 510 can be disposed in an elongated member. The light source comprises first and second LEDs 515A 515B. The LEDs 515A 515B are coupled to respective optical fibers 516A 516B, which have distal ends disposed proximate the distal end of the elongated member. Thus, the LEDs 515A 515B can be controlled to emit light which travels down the optical fibers 516A 516B where the light is then directed to thetissue to be imaged. The system can further comprise an actuator 520 configured to alter a distance between a distal end of the elongated member proximate the microlens system 505 and the image sensor 510. The actuator 520 can be used to provide for three dimensional imaging of the tissue. For example, one or more images can be taken at a first actuator position and then one or more additional images can be taken at one or more additional actuator positions. Each of these images can then be processed by the processing unit to generate three- dimensional phase images of the tissue.

[0069] FIG. 6 provides yet another alternative configuration for an imaging system, in accordance with some embodiments of the present disclosure. As shown in FIG. 6, the system can comprise a microlens system 605 and an electronic image sensor 610. Though not shown in FIG. 6, the microlens system 605 and the image sensor 610 can be disposed in an elongated member. The system can further comprise an LED light source 615 to illuminate a tissue to be imaged. The system can further comprise a prism 620 disposed at a distal end of the imaging system. The prism 620 can be configured to alter an imaging direction by 90 degrees, as shown in FIG. 6.

[0070] As those skilled in the art would appreciate, one or more features of the configurations shown in FIGs. 3-6 can be combined to form various imaging systems, in accordance with some embodiments of the present disclosure.

[0071] In some embodiments of the present disclosure, multiple images can be taken by the electronic image sensor, which are then used by the processing unit to generate phase images. For example, in some embodiments, multiple images can be taken with multiple illumination patterns. For example, a first light source on a first side of the imaging system can illuminate the tissue, and a first image can be taken during illumination by the first light source. Then, a second light source on a second side / location of the imaging system can illuminate the tissue (from a different angle), and a second image can be taken during illumination by the second light source. This process can be repeated any number of times utilizing any number of light sources and take any number of images (e.g., 1-4 images, or more). The processing unit can receive each of these images and generate a phase image based on the received image.

[0072] Similarly, one or more light sources can be utilized to illuminate the tissue at multiple wavelengths of light, and one or more images can be taken during illumination at each respective wavelength. These images can then be processed by the processing unit to generate the phase images.

[0073] In some embodiments where multiple wavelengths of light are used, one of the wavelengths can be at an excitation wavelength to cause at least a portion of the tissue to fluoresce (including auto fluorescence). Such embodiments can be used for multimodal imaging of both phase and fluorescence. For example, an excitation wavelength of light, e.g., 250 nm, can be emitted from the light source, causing a portion of the tissue to emit fluorescent light. That fluorescent light can then be captured through the microlens to the image sensor to generate an image. In these embodiments, the system can further comprise a filter configured to filter the excitation light wavelength so that only the fluorescent light is captured by the sensor.

[0074] In embodiments where multiple images are captured by the sensor to generate the phase image, each of the images can be captured at the same field of view (e.g., the imaging system and tissue can remain stationary during the image capture process). In some embodiments, the field of view can have width, length, and or diameter of about 50-5000 microns.

[0075] It is to be understood that the embodiments and claims disclosed herein are not limited in their application to the details of construction and arrangement of the components set forth in the description and illustrated in the drawings. Rather, the description and the drawings provide examples of the embodiments envisioned. The embodiments and claims disclosed herein are further capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purposes of description and should not be regarded as limiting the claims.

[0076] Accordingly, those skilled in the art will appreciate that the conception upon which the application and claims are based may be readily utilized as a basis for the design of other structures, methods, and systems for carrying out the several purposes of the embodiments and claims presented in this application. It is important, therefore, that the claims be regarded as including such equivalent constructions.

[0077] Furthermore, the purpose of the foregoing Abstract is to enable the United States Patent and Trademark Office and the public generally, and especially including the practitioners in the art who are not familiar with patent and legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The Abstract is neither intended to define the claims of the application, nor is it intended to be limiting to the scope of the claims in any way.

Claims

CLAIMSWhat is claimed is:

1. An imaging system for imaging tissues, comprising: an elongated member; an illumination light source disposed on a portion of the elongated member and configured to illuminate a tissue to be imaged; one or more microlenses disposed on a distal end of the elongated member and configured to receive light passing through at least a portion of the tissue; an electronic image sensor disposed within a portion of the elongated member and configured to receive the light from the one or more microlenses and generate one or more images of tissue, each of the one or more images having a resolution of 100 nm to 10 microns; and a processing unit configured to receive a signal from the image sensor indicative of the one or more images and generate a phase image of the tissue, each pixel of the phase image indicative of refractive index properties of the tissue corresponding to the respective pixel.

2. The imaging system of claim 1, wherein the one or more microlenses have a numerical aperture of 0.2- 1.2.

3. The imaging system of claim 1, wherein the one or more microlenses comprises one or more gradient index lenses.

4. The imaging system of claim 3, further comprising one or more rod lenses disposed within the elongated member between the one or more gradient index lenses and the image sensor, the one or more rod lenses configured to alter a distance between a distal tip of the elongated member and the image sensor.

5. The imaging system of claim 1, wherein the one or more micro lenses have a diameter of 0.5-30 mm.

6. The imaging system of claim 1, wherein the one or more images have a field of view of 50-5000 microns.

7. The imaging system of claim 1 , wherein the light source comprises one or more selected from the group consisting of a light emitting diode, a laser, a diode, a super luminescent diode, a light bulb, and an optical fiber.

8. The imaging system of claim 1, wherein the image sensor comprises a CMOS sensor.

9. The imaging system of claim 1 , wherein the processing unit comprises hardware and / or software for controlling the imaging system.

10. The imaging system of claim 1, wherein the processing unit is configured to receive one or more control parameters selected from the group consisting of: illumination intensity of the light source, illumination switching speed of the light source, camera readout speed of the image sensor, camera gain of the image sensor, camera exposure of the image sensor, camera bit depth of the image sensor, and image data format.

11. The imaging system of claim 1 , wherein the light source comprises a first light emitting diode (LED) on a first side of a distal end of the elongated member and a second LED on a second side of the distal end of the elongated member, the first and second LEDs configured to emit light into the tissue to generate oblique back illumination.

12. The imaging system of claim 1, wherein the illumination light source comprises a light emitting diode (LED) and an optical fiber, wherein at least a portion of the optical fiber extends along a length of a portion of the elongated member, wherein the optical fiber is configured to receive light at a first end from the LED and direct the light out of a second end to illuminate the area to be imaged.

13. The imaging system of claim 12, wherein the optical fiber is a single mode optical fiber.

14. The imaging system of claim 12, wherein the optical fiber is a multi-mode optical fiber.

15. The imaging system of claim 1, wherein the illumination light source comprises a light emitting diode (LED) and a rigid light guide, wherein at least a portion of the rigid light guide extends along a length of a portion of the elongated member, wherein the rigid light guide is configured to receive light at a first end from the LED and direct the light out of a second end to illuminate the area to be imaged16. The imaging system of claim 1, further comprising an actuator configured to alter a distance between a distal end of the elongated member and the image sensor.

17. The imaging system of claim 1 , further comprising prism configured to alter an imaging direction by 90 degrees.

18. The imaging system of claim 1, wherein the elongated member is configured to be inserted into the body of a subject, wherein the tissue is inside the body of the subject.

19. The imaging system of claim 1, wherein the imaging system is in the form of an endoscope.

20. The imaging system of claim 1, wherein the light source is configured to emit light having a wavelength of between 200-1750 nm.

21. The imaging system of claim 1, wherein each of the one or more images are taken at a same field of view.

22. The imaging system of claim 21 , wherein each of the one or more images is taken with a distinct illumination pattern from the light source.

23. The imaging system of claim 1, wherein the light source is configured to illuminate the tissue at a plurality of directions.

24. The imaging system of claim 1 , wherein the one or more images comprise no more than four images.

25. The imaging system of claim 1, wherein the sensor is one of a monochrome or a color sensor.

26. A method of imaging a tissue, the method comprising: providing the imaging system of any of claims 1-25; illuminating, with the light source, the tissue; capturing, with the image sensor, the one or more images of the tissue, each of the one or more images having a resolution of 100 nm to 10 microns; and generating, with the processing unit, the phase image based at least in part on the one or more images of the tissue.

27. The method of claim 26, the method further comprising: altering a distance between the distal end of the elongated member and the image sensor; and capturing, with the image sensor, one or more additional images of the tissue, wherein the phase image is a 3D phase image based at least in part on the one or more images and the one or more additional images.

28. The method of claim 26, further comprising inserting the distal end of the elongated member into a subject proximate the tissue.

29. The method of claim 26, wherein illuminating the tissue comprises illuminating the tissue with a first light source, and wherein capturing the one or more images comprises capturing a first image.

30. The method of claim 29, wherein illuminating the tissue comprises illuminating the tissue with a second light source, and wherein capturing the one or more images comprises capturing a second image.

31. The method of claim 30, wherein illuminating the tissue with the second light source comprises illuminating the tissue at a first wavelength to cause at least a portion of the tissueto fluoresce, and wherein the second image is based on fluorescent light emitted from the at least a portion of the tissue.

32. The method of claim 31, further comprising filtering light at the first wavelength prior to capturing the second image.

33. An imaging system, comprising: an elongated member; an illumination system disposed on a portion of the elongated member and configured to illuminate an area to be imaged; one or more lenses disposed on a distal end of the elongated member and configured to receive light from the area to be imaged; an image sensor disposed within a portion of the elongated member and configured to receive the light from the one or more lenses; and a processing unit configured to receive a signal from the image sensor and generate an image indicative of the area to be imaged.

34. The imaging system of claim 33, wherein the one or more lenses comprises a microobjective lens.

35. The imaging system of claim 33, wherein the one or more lenses comprises one or more gradient index lenses.

36. The imaging system of claim 33, wherein the one or more lenses comprises one or more rod lenses disposed within the elongated member, the one or more rod lenses configured to alter a distance between a distal tip of the elongated member and the image sensor. The imaging system of claim 1 , wherein the illumination system comprises one or more selected from the group consisting of a light emitting diode, a laser, a diode, a light bulb, and an optical fiber.

37. The imaging system of claim 33, wherein the image sensor comprises a CMOS sensor.

38. The imaging system of claim 33, wherein the image sensor is a chip-on-tip sensor.

39. The imaging system of claim 33, wherein the processing unit comprises hardware and / or software for controlling the imaging system.

40. The imaging system of claim 33, wherein the processing unit is configured to receive one or more control parameters selected from the group consisting of: illumination intensity, illumination switching speed, camera readout speed, camera gain, camera exposure, camera bit depth, and image data format.

41. The imaging system of claim 33, wherein the illumination system comprises a first light emitting diode (LED) on a first side of a distal end of the elongated member and a second LEDon a second side of the distal end of the elongated member, the first and second LEDs configured to emit light in a direction parallel to the elongated member.

42. The imaging system of claim 33, wherein the illumination system comprises a light emitting diode (LED) and an optical fiber, wherein at least a portion of the optical fiber extends along a length of a portion of the elongated member, wherein the optical fiber is configured to receive light at a first end from the LED and direct the light our of a second end to the area to be imaged.

43. The imaging system of claim 33, further comprising an actuator configured to alter a distance between a distal end of the elongated member and the image sensor.

44. The imaging system of claim 33, wherein the one or more lenses comprises a prism configured to alter an imaging direction by 90 degrees.

45. The imaging system of claim 33, wherein the elongated member is configured to be inserted into the body of a subject, wherein the area to be imaged is inside the body of the subject.

46. The imaging system of claim 33, wherein the imaging system is in the form of an endoscope.

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