Confocal microscopy and nonlinear optical (NLO) microscopy are powerful imaging techniques that are routinely used in many fields such as biological observation, chemical analysis and industrial inspection.
In confocal microscopy, a light source, such as a laser beam, is focused by an objective lens into a small focal volume within or on the surface of a specimen. Scattered and reflected light from the illuminated spot is then re-collected by the objective lens. A beam splitter is used to direct the light from the light source to the specimen and the returned light to a photodetection device. A spatial pinhole is used to eliminate out-of-focus light returned from specimens.
A similar procedure is used for NLO microscopy except that no pinhole is needed. Instead, the beam splitter is dichroic so that the excitation light will be filtered out and only allow the NLO signal to pass and be collected by the photodetector. NLO microscopy includes two-photon or multiphoton microscopy and second-harmonic-generation microscopy.
The advantages of confocal and NLO microscopy are the high contrast and high resolution capabilities, and the optical sectioning capacity.
However, standard confocal and NLO microscopes have large-sized optical systems. Therefore, specimens cannot be observed in vivo by the standard bulky confocal or NLO microscopes. Instead, specimens are removed from the living body (or other entity) and mounted onto slides for in vitro observation.
To realize in vivo, real time cross-sectional imaging, it is necessary to miniaturize the optical system of the confocal or NLO imaging system.
A first step of miniaturization can be realized by using optical fiber as the transmission medium. The fiber optical confocal scanning microscope is smaller than standard confocal microscopes, but remains too large for in vivo imaging. The fiber optical confocal scanning microscope utilizes the core of single mode fibers as the pinhole. However, a miniature scanning mechanism is also required to get real time in vivo images.
An example of a scanner based on successively illuminating the different fibers in an image guide comprising of a bundle of flexible fibers has been proposed by Le Gargasson et al. in U.S. Pat. No. 6,470,124. The scanning unit disclosed by Le Gargasson et al. produces successive angular deflections of the illuminated light from a source. A lens converts the angular deflections to lateral deflections, which correspond to different fibers' entry in the image guide. The microscope objectives focus the light from different fibers to different focal points. Though this method provides a fiber optic approach to imaging, the microscope objectives limit the miniaturization capabilities of this design, making it difficult to meet the desired dimension for endoscopic imaging. In addition, the distortion of images may be induced during scanning of the fibers; and the specular reflection at the face of the fiber bundle is also a problem in this design. Furthermore, the resolution is limited by the discrete characteristics of the cores in the fiber bundle.
Confocal and NLO imaging requires both lateral scanning and depth scanning of a specimen. Current confocal and NLO imaging relies on a movable carriage for depth scanning using manual manipulation of, for example, a probe, or mechanical translation of, for example, the end of a fiber. However, these approaches tend to have poor reliability in the mechanical translation, instability of light coupling, and provide difficulty in miniaturizing the scanning section to an acceptable dimension for endoscopic imaging.
Microelectromechanical systems (MEMS) have become attractive for miniaturizing optical scanning systems. In particular, MEMS mirrors are being utilized for their lateral scanning capabilities. However, the designs continue to be challenging when attempting to meet the stringent size requirements of endoscopic imaging. For example, the axial scanning requirement (depth scanning) continues to be the bottleneck for confocal and NLO microendoscopy.
Accordingly, research continues to be conducted to provide an optical image scanning apparatus that can be applied to microendoscopy.
Embodiments of the present invention provide MEMS-based optical image scanning. Light scanners are disclosed that can be suitable for endoscopic imaging applications. The endoscopic imaging applications can include confocal endoscopic imaging and nonlinear optical imaging. According to an aspect of the invention, light scanners are provided that can be miniaturized to sizes that can be inserted into the living body for real time endoscopic imaging.
The subject light scanners can be constructed using a MEMS mirror and/or MEMS lens in accordance with embodiments of the present invention. The MEMS lens refers to a microlens integrated into a MEMS lens holder. The MEMS mirror can be used to redirect a light beam and scan laterally, while the MEMS lens can be used to control the focal depth and scan axially.
The MEMS mirror and MEMS lens can have similar structures (differing in the mirror plate and lens portions) and can be actuated by electrothermal actuators that can achieve large scanning angles, large vertical displacement with minimal lateral shift, fast scanning, small size, and low operating voltage.
According to one embodiment, a one-dimensional (z direction) light scanner is provided that incorporates a MEMS lens. The MEMS lens can be actuated within a miniature head of a probe without the use of a movable stage.
According to another embodiment, a two-dimensional (x and y directions) light scanner is provided that incorporates a fixed objective lens and a MEMS mirror.
According to another embodiment, a three-dimensional (x, y, and z directions) light scanner is provided that incorporates a fixed objective lens and a MEMS mirror, where the z direction scan is obtained by the piston movement of the MEMS mirror.
According to yet another embodiment, a three-dimensional (x, y, and z directions) light scanner is provided that incorporates a MEMS mirror and a MEMS lens.
For a confocal imaging application according to one embodiment of the present invention, a probe is provided including a collimating lens, and a light scanner capable of receiving the collimated beam from the collimating lens and directing the beam onto an object. The probe is connected to a single fiber, which is used for both illuminating and detecting. The single fiber can be a single-mode fiber, which provides the pinhole that blocks out-of-focus light.
The light scanner can be a 1-D, 2-D, or 3-D light scanner in accordance with embodiments of the present invention. In one embodiment, a single GRIN lens can be used for collimating. In addition, for embodiments using the MEMS lens, such as for the 1-D and 3-D light scanners, the MEMS lens is used for focusing and depth scanning. For embodiments using the MEMS mirror, such as for the 2-D and 3-D light scanners, a single MEMS mirror is used for lateral scanning.
Embodiments of the present invention provide a MEMS-based scanning apparatus. In accordance with embodiments of the present invention, miniature light scanners for endoscopic confocal or NLO imaging based on MEMS mirrors and a MEMS lens are provided. Confocal microscopy and NLO microscopy are powerful imaging techniques now routinely used in many fields, such as biomedical imaging, chemical analysis and industrial inspection. Their major advantages are high contrast and high resolution capabilities, and the optical sectioning capacity. However, since standard confocal and NLO microscopes have large optical systems, the tissues cannot be observed in vivo by a standard bulky confocal or NLO microscope. Instead, tissues are removed from the living body and mounted onto microscope slides for in vitro observation.
To realize in vivo real-time confocal or NLO imaging, the optical scanning system is miniaturized. By using optical fibers as a transmission medium, a first step of miniaturization can be accomplished. However, to image non-stationary tissues, especially for medical in vivo imaging, it is necessary to further miniaturize optical scanners so that the scanning section could be inserted into the living body for real time endoscopic imaging.
According to certain embodiments of the present invention, MEMS mirror- and MEMS lens-based scanning apparatuses are provided for imaging applications. The MEMS mirror can be used to redirect an optical beam and scan the optical beam laterally. The MEMS lens can be used to control the focal depth and can be scanned along the optical axis (i.e. axially).
According to one aspect, since the MEMS mirror and MEMS lens have small size, the imaging probe can be miniaturized to apply to endoscopic imaging. Real-time imaging can also be achieved because of the fast scanning. Embodiments of the present invention can be used for confocal microscopy and nonlinear optical imaging.
According to an embodiment of the present invention, a confocal endoscope is provided with 3-D scanning capability. A single 2-D MEMS mirror is used to scan light laterally and a MEMS lens is used to scan the light axially. In addition, a single fiber can be used for both illuminating and detecting light. Implementations of the present invention can be used in a variety of applications including, but not limited to, confocal endoscopy for cancer detection, optical biopsy, minimally invasive imaging, image-guided surgery, surgical monitoring, and in vivo imaging.
Advantageously, 3-D scanning can be realized using a single MEMS mirror and MEMS lens without using an external galvanometer to determine depth. In addition to 3-D scanning, the subject scanners can achieve miniature size, fast speed, large scanning ranges, low voltage, and low cost.
In an embodiment, the MEMS components can utilize electrothermal actuation. In a specific embodiment, thermal bimorph beams are used to actuate the MEMS mirror and the MEMS lens.
The actuators can be designed to generate large piston motion of the microlens, for example, up to 800 μm, which results in a large tunable range of the focal plane (hundreds of microns to a few mm).
By using actuators in accordance with certain embodiments of the present invention, the platform (holder 12) can be maintained parallel to the substrate with a very small tilting angle (˜0.7°) in the full vertical scanning range. According to embodiments for confocal imaging applications using such a structure, errors caused by the tilting of the microlens, which leads to undesired and uncontrollable change of the focal plane, can be minimized.
In addition, the lateral shift of the platform (holder 12) is small (˜10 μm) in the full vertical scanning range. In particular, during the piston motion, the lateral position of the microlens can be consistent (i.e. any change in the lateral position is minimal). Thus, the focal point is nearly free of lateral shift during the axial scanning.
The 1-D confocal light scanner described with respect to
Referring to
In operation, light is redirected by the transverse scanning mirror (MEMS mirror 32) to the fixed lens 31, and then focused by the fixed objective lens 31 to a focal point.
According to certain implementations, the 2-D scanner as described with respect to
In a further embodiment, a z direction scan can be obtained by the piston movement of the MEMS mirror (32 or 42).
In addition to the 1-D and 2-D light scanners, embodiments of the present invention can provide a 3-D light scanner as shown in
The 3-D light scanner described with respect to
The light emitted from the laser source 70 is coupled into the single mode fiber 71a and transmitted to the light coupler 72. A portion of the light comes out of one terminal 71b of the coupler 72, is collimated by a. GRIN lens 75a of the light scanner 75 at the fiber end 71b, redirected by the 2-D scanning MEMS mirror 75b of the light scanner 75, and then focused by the tunable MEMS lens 75c of the light scanner 75 onto an object. Light returning from the object is collected by the MEMS lens 75c, redirected by the MEMS mirror 75b, and then focused by the lens 75a to the core of the end of the single mode fiber 71b. The core of the end surface of the fiber 71b has a conjugate relation with the focal point of the MEMS lens 75c. The single mode fiber is preferred because of its small fiber core, but embodiments are not limited thereto. The small core serves as the pinhole of the fiber optic confocal microscope to suppress out-of-focus returning light. A portion of the light is transmitted by the fiber 71c to the detector 73 through the coupler 72. The detector 73 then sends the detected signal to a signal processor 76.
This system can be modified in various ways. For example, according to one embodiment, a beam splitter can be used in place of the fiber coupler 72. In a further embodiment, polarization can be performed to screen out-of-focus light by the inclusion of a polarizing beam splitter, polarization-maintaining single fiber and quarter wave plate in place of the coupler 72 and single mode fibers (71a, 71b, 71c, 71d). According to another embodiment, an optical filter is placed in between the fiber 71c and the detector 73, and then the system can be used for two-photon microscopy or second-harmonic microscopy. According to yet another embodiment, an optical delay line is attached the end of the fiber 71d, and then the system can be used for optical coherence microscopy.
Though the light scanner 75 has been described as a 3-D light scanner, embodiments are not limited thereto. For example, the light scanner 75 can be a 1-D light scanner, a 2-D light scanner or a 3-D light scanner as described with respect to embodiments of the present invention.
In addition, according to an embodiment, the collimator for the light scanner 75 can be a GRIN lens, aspheric lens, or other collimating lens. In another embodiment, the beam from the tight source 10 can enter the light scanner 75 to be redirected by the MEMS mirror without being collimated.
According to certain embodiments, the light scanner 75 can be provided as a miniature probe to be inserted into an inner region of a body.
The subject MEMS mirrors and MEMS lenses used in light scanners according to embodiments of the present invention are capable of vertical displacement with minimal lateral shift. To accomplish this feature, embodiments of the present invention can utilize large-vertical-displacement lateral-shift-free bimorph actuators with large scanning angles and fast scanning speed.
The MEMS lens holder can have the same or similar design as the MEMS mirror shown in
The fabrication of the MEMS mirror and the MEMS lens can utilize a combination of surface micromachining and bulk micromachining.
Referring to
All patents, patent applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.
Any reference in this specification to “one embodiment,” “an embodiment,” “example embodiment,” etc., means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with any embodiment, it is submitted that it is within the purview of one skilled in the art to effect such feature, structure, or characteristic in connection with other ones of the embodiments. More particularly, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, the drawings and any appended claims. In addition to variations and modifications in the component parts and/or arrangements, alternative uses will also be apparent to those skilled in the art.
It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.
This application claims the benefit of U.S. Provisional Application Ser. No. 61/239,619 filed Sep. 3, 2009, which is hereby incorporated by reference in its entirety, including all figures, tables and drawings.
The subject invention was made with government support under Grant Nos. 0423557 and 0818473 awarded by the National Science Foundation. The government has certain rights in the invention.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US10/46775 | 8/26/2010 | WO | 00 | 1/10/2012 |
Number | Date | Country | |
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61239619 | Sep 2009 | US |