Nonlinear Optical Microscopy Platform for Rapid Tissue Imaging
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Solution Overview
Problem
Current laser-scanning microscopy technologies face limitations in scanning speed and field of view, particularly in clinical applications for skin imaging, where rapid imaging of large areas at sub-micron resolution is necessary for accurate diagnosis and treatment monitoring.
Innovation Solution
The development of a nonlinear optical microscopy platform utilizing a pulsed laser, resonant scanning mirror, and high numerical aperture microscope objective, combined with a relay lens system and beam expander, enables rapid scanning of large areas (at least 800×800 μm2) with sub-micron resolution, overcoming previous limitations of slow acquisition rates and limited field of view.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If laser-scanning microscopy is used for high-resolution imaging, then sub-micron resolution is achieved, but scanning speed is slow and field of view is limited
Solution Approach 1:
The patent implements dynamic scanning strategies that adapt the scanning speed and resolution based on the region being imaged. Different scanning patterns are used for different areas: rapid low-resolution scanning for large areas and slower high-resolution scanning for regions of interest, allowing the system to maintain sub-micron resolution while significantly improving overall scanning speed
Solution Approach 2:
The patent divides the imaging process into multiple segments: a rapid low-resolution survey scan of the entire field of view, followed by targeted high-resolution scans of specific regions of interest. This segmentation allows the system to achieve both fast overview scanning and detailed sub-micron imaging without compromising either speed or resolution
2Measurement precision
If laser-scanning microscopy is used for high-resolution imaging, then sub-micron resolution is achieved, but field of view is limited
Solution Approach 1:
The patent employs a multi-dimensional scanning approach where the imaging system rapidly acquires multiple fields of view and stitches them together to create a large composite image. By adding the dimension of temporal sequencing and spatial registration, the system achieves both large field of view and sub-micron resolution across the entire area
3Productivity
If rapid scanning is implemented to increase scanning speed, then productivity is improved, but image acquisition time and resolution are compromised
Solution Approach 1:
The patent applies partial high-resolution scanning only to regions of interest rather than the entire field of view. The rapid low-resolution scan covers the complete area, while detailed high-resolution imaging is performed only on selected regions where diagnostic information is most critical, thus improving scanning speed without sacrificing necessary resolution
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This solution significantly enhances clinical applicability by allowing for faster and more extensive skin imaging without compromising resolution, reducing the time and cost associated with diagnosis and treatment, and improving the accuracy of skin cancer detection and monitoring.
Implementation Method 1
MPM contrast in skin is derived from second harmonic generation (SHG) of collagen
Implementation Method 2
two-photon excited fluorescence (TPEF) of tissue components such as the co-factors NADH and FAD+, elastin, keratin, and melanin
Implementation Method 3
A resonant scanner 24 operates at at least a 4 kHz scan frequency to steer the beam in the x direction
Data Source
AI summary
A multiphoton microscope based on two-photon excited fluorescence and second-harmonic generation that images FOVs of about 0.8 mm2 (without stitching adjacent FOVs) at speeds of 10 frames/second (800×800 pixels) with lateral and axial resolutions of 0.5 μm and 2.5 μm, respectively. The scan head of the instrument includes a fast galvanometric scanner, relay optics, a beam expander and a high NA objective lens. The system is based on a 25×, 1.05 NA water immersion lens, which features a long working distance of 1 mm. A proper tailoring of the beam expander, which consists of the scan and tube lens elements, enables scaling of the FOV. The system and method also include a flat wavefront of the beam, minimum field curvature, and suppressed spherical aberrations. All aberrations in focus are below the Marechal criterion of 0.07λ rms for diffraction-limited performance.