SCAPE Microscopy for High-Speed 3D Tissue Imaging

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Solution Overview

Problem

Current microscopy techniques, such as MRI, ultrasound, and optical coherence tomography, face limitations in frame rate, resolution, and depth of penetration when characterizing tissue mechanical properties, particularly for cancerous tissues, which are essential for clinical utility.

Innovation Solution

The SCAPE microscopy system employs a scanning mechanism that projects excitation light at an oblique angle into a sample, forming a stationary intermediate image plane, allowing for high-resolution, high-frame-rate 3D imaging while perturbing the sample to quantify mechanical properties, using a novel image splitter to minimize light loss and optimize image capture.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of stationary object

If conventional microscopy techniques (MRI, ultrasound, optical coherence tomography) are used to characterize tissue mechanical properties, then depth of penetration is improved, but frame rate and resolution deteriorate

Engineering Contradiction:
Improvedepth of penetrationVSAvoidframe rate
Core Design Contradiction:
Length of stationary objectVSProductivity

Solution Approach 1:

The patent replaces mechanical scanning systems with optical field-based excitation. Instead of physically moving probes or scanners to achieve depth resolution, the invention uses swept confocally-aligned planar excitation with light sheets that can rapidly traverse the sample volume optically, achieving high frame rates while maintaining deep penetration capability through the optical properties of the light sheet geometry

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention transitions from conventional point-by-point or line-by-line scanning to volumetric planar excitation. By illuminating entire planes simultaneously with light sheets and using swept confocal alignment, the system achieves three-dimensional imaging at high speed, resolving the trade-off between depth penetration and frame rate through dimensional expansion of the excitation volume

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Length of stationary object

If conventional microscopy techniques are used, then depth of penetration is improved, but resolution deteriorates

Engineering Contradiction:
Improvedepth of penetrationVSAvoidresolution
Core Design Contradiction:
Length of stationary objectVSMeasurement precision

Solution Approach 1:

The patent replaces mechanical scanning with optical field-based excitation using swept confocally-aligned planar excitation. This substitution enables high-resolution imaging at depth by using light sheet geometry that maintains spatial coherence and confocal alignment throughout the excitation volume, avoiding the resolution degradation that occurs with conventional mechanical scanning methods at depth

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention applies localized high-intensity excitation only at the focal plane where the light sheet intersects the detection focal plane. This confocal alignment ensures that excitation and detection occur at the same spatial location with optimal resolution, while the swept configuration maintains this local quality throughout the entire depth range of the sample

Inventive Principle:
Principle #3Local quality

3Productivity

If swept confocally-aligned planar excitation is used to achieve high frame rates, then productivity is improved, but device complexity increases

Engineering Contradiction:
Improveframe rateVSAvoiddevice complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs a single swept confocal alignment mechanism that simultaneously performs excitation, detection, and depth scanning functions. The light sheet geometry and swept configuration enable the system to achieve volumetric imaging, confocal resolution, and high frame rates through a unified optical path, reducing overall device complexity compared to multiple separate systems

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention uses dynamic swept configuration where the light sheet and detection focal plane are swept through the sample volume in a coordinated manner. This dynamic alignment maintains confocal conditions throughout the sweep, enabling high frame rate volumetric imaging through temporal coordination of excitation and detection rather than static multi-component systems

Inventive Principle:
Principle #15Dynamics

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

SCAPE microscopy achieves high-quality 3D imaging at high frame rates with reasonable depth penetration, effectively quantifying tissue mechanical properties and providing real-time visualization of sample perturbations, overcoming the limitations of existing modalities.

Implementation Method 1

a first beam splitter positioned in the infinity space, wherein the first beam splitter is arranged to route light from the intermediate image plane having a first wavelength in a first direction and to route light from the intermediate image plane having a second wavelength in a second direction

Methodology Applied
Scientific EffectDichroic reflection: Dichroic Filter

Data Source

PatentUS11269169B2Three-dimensional imaging using swept, confocally aligned planar excitation and sample perturbation
Publication Date: 2022.03.08 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • US11269169B2 patent drawing
  • US11269169B2 patent drawing
  • US11269169B2 patent drawing

AI summary

In some embodiments, a SCAPE system routes light from a tilted intermediate image plane to an infinity space disposed behind a third objective. A first beam splitter positioned in the infinity space routes light from the intermediate image plane with different wavelengths in different directions. First and second light detector arrays capture first and second wavelength images, respectively, and optical components route light having the first and second wavelength towards the first and second light detectors, respectively. In some embodiments, a SCAPE system is used to capture a plurality of images while a sample is perturbed (e.g., vibrated, deformed, pushed, pulled, stretched, or squeezed) in order to visualize the impact of the perturbation on the sample.