Near-infrared confocal microendoscopy is a promising technique for deep in vivo imaging of tissues and can generate high-resolution cross-sectional images at the micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical images of human colorectal mucosa. High-speed two-dimensional en face scanning was achieved through a microelectromechanical systems (MEMS) scanner while a micromotor was used for adjusting the axial focus. In vivo images of human patients are collected at 5 frames/sec with a field of view of 362×212 μm2 and a maximum imaging depth of 140 μm. During routine endoscopy, indocyanine green (ICG) was topically applied a nonspecific optical contrasting agent to regions of the human colon. The DAC microendoscope was then used to obtain microanatomic images of the mucosa by detecting near-infrared fluorescence from ICG. These results suggest that DAC microendoscopy may have utility for visualizing the anatomical and, perhaps, functional changes associated with colorectal pathology for the early detection of colorectal cancer.
KEYWORDS: Skin, Microscopes, Green fluorescent protein, In vivo imaging, Confocal microscopy, 3D image processing, Visualization, Mouse models, Molecular imaging, Luminescence
A fluorescence confocal microscope incorporating a 1.8-mm-diam gradient-index relay lens is developed for in vivo histological guidance during resection of brain tumors. The microscope utilizes a dual-axis confocal architecture to efficiently reject out-of-focus light for high-contrast optical sectioning. A biaxial microelectromechanical system (MEMS) scanning mirror is actuated at resonance along each axis to achieve a large field of view with low-voltage waveforms. The unstable Lissajous scan, which results from actuating the orthogonal axes of the MEMS mirror at highly disparate resonance frequencies, is optimized to fully sample 500×500 pixels at two frames per second. Optically sectioned fluorescence images of brain tissues are obtained in living mice to demonstrate the utility of this microscope for image-guided resections.
We report a miniature mechanical gyroscope that utilizes optical means to detect rotation-induced displacements in a
mechanical structure. It utilizes the Foucault pendulum principle used in some existing MEMS gyroscopes: a rotating
reference frame induces a Coriolis force that oscillates the structure about an axis orthogonal to the driving-mode axis.
The main difference with similar MEMS gyroscopes is that this rotation-induced oscillation is sensed using a pair of
high-finesse fiber Fabry-Perot displacement sensors instead of a capacitive device. The drive axis is also driven by
radiation pressure inside a set of auxiliary fiber Fabry-Perot cavities, making this device immune to electromagnetic
interference. Calculations predict that a rotation sensitivity on the order of 1°/h/Hz1/2 is achievable. We show that this
structure solves several problems associated with MEMS gyroscopes utilizing electrostatic sensing methods.
Here we describe a simple optical design for a MEMS-based dual-axes fiber optic confocal scanning microscope that has
been miniaturized for handheld imaging of tissues, and which is capable of being further scaled to smaller dimensions
for endoscope compatibility while preserving its field-of-view (FOV), working distance, and resolution. Based on the
principle of parallel beams that are focused by a single parabolic mirror to a common point, the design allows the use of
replicated optical components mounted and aligned within a rugged cylindrical housing that is designed for use as a
handheld tissue microscope. A MEMS scanner is used for high speed scanning in the X-Y plane below the tissue
surface. An additional design feature is a mechanism for controlling a variable working distance, thus producing a scan
in the Z direction and allowing capture of 3-D volumetric images of tissue. The design parameters that affect the
resolution, FOV, and working distance are analyzed using ASAPTM optical modeling software and verified by
experimental results. Other features of this design include use of a solid immersion lens (SIL), which enhances both
resolution and FOV, and also provides index matching between the optics and the tissue.
This paper presents a dual-axes confocal microscope based on a two-dimensional (2-D) MicroElectroMechanical system
(MEMS) scanner. Dual-axes confocal microscopy provides high resolution in both transverse and axial directions, and is
also well-suited for miniaturization and integration into endoscopes for in vivo imaging. The gimbaled MEMS scanner
is fabricated on a double silicon-on-insulator (SOI) wafer (a silicon wafer bonded on a SOI wafer) and is actuated by
self-aligned, vertical, electrostatic combdrives. The reflecting surface of the scanner is covered with a 10-nm aluminum
layer. Reflectance and fluorescence imaging is successfully demonstrated in a breadboard setup. Images with a
maximum field of view (FOV) of 340 μm x 420 μm are achieved at 8 frames per second. The transverse resolution is
3.9 μm and 6.7 μm for the horizontal and vertical dimensions, respectively.
In this paper we present scanning micromirrors, actuated by self-aligned, bidirectional, vertical electrostatic combdrives, for dual-axes confocal microscopy. The fabrication process, which is based on Deep Reactive Ion Etching (DRIE) of Silicon-on-insulator (SOI) wafers with two silicon device layers, requires only three lithography steps for one-dimensional scanners, while an additional two lithography steps must be performed to create two-dimensional scanners. Only front side processing is required and the two oxide layers of the double SOI wafers provide efficient and reliable etch stops. These features combined with the fact that the combs are self aligned, enable high-speed, high-resolution microscanners with stable and reliable operation as required for endoscopic implementations of confocal microscopes.
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