Biodynamic Microscope Interferometric Imaging 3D Tissue

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Solution Overview

Problem

Current microscopes face limitations in observing fresh tumors and assessing therapeutic effects qualitatively, particularly in three-dimensional tissue imaging, which is crucial for selecting appropriate therapies and understanding drug responses in cancer treatment.

Innovation Solution

A microscope apparatus combining interferometric imaging capabilities with a short-coherence light source, Fourier transform lens, and pixel-array detector, allowing for high-resolution interferometric image data acquisition with coherence gating to control depth within the sample, enabling the observation of internal dynamics in living tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multi-photon microscopy is used for 3D tissue imaging, then imaging capability is achieved, but fluorescent dyes are required which complicates sample preparation

Engineering Contradiction:
Improve3D tissue imaging capabilityVSAvoidsample preparation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and removes the requirement for fluorescent dyes from the imaging process by using label-free interferometric microscopy. The system achieves 3D tissue imaging through optical path length measurements and phase information extraction without any exogenous labels, thereby simplifying sample preparation while maintaining imaging capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the fluorescent labeling mechanism with an interferometric optical measurement mechanism. Instead of using fluorescent dyes that require complex preparation, the system uses interference patterns and phase information from scattered light to achieve 3D imaging, substituting a chemical labeling approach with an optical physics-based approach

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

2Ease of operation

If conventional microscopy is used to observe tumors, then visual observation is possible, but therapeutic effect assessment is limited

Engineering Contradiction:
Improvevisual observation capabilityVSAvoidtherapeutic effect information
Core Design Contradiction:
Ease of operationVSLoss of information

Solution Approach 1:

The invention introduces interferometric measurement as an intermediary between conventional visual observation and therapeutic effect assessment. By measuring optical path length differences and phase information, the system extracts quantitative data about cellular dynamics and tissue properties that serve as intermediaries to assess therapeutic effects, bridging the gap between simple visualization and functional assessment

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the measurement parameters from simple intensity-based visual observation to phase-based interferometric measurements. By detecting changes in optical path length, phase shifts, and interference patterns, the system captures dynamic cellular processes and tissue property changes that provide information about therapeutic effects, transforming static visual observation into dynamic quantitative measurement

Inventive Principle:
Principle #35Parameter changes

3Length of stationary object

If deep tissue imaging is performed, then internal structures are accessible, but resolution decreases

Engineering Contradiction:
Improveimaging depthVSAvoidspatial resolution
Core Design Contradiction:
Length of stationary objectVSMeasurement precision

Solution Approach 1:

The invention transitions from two-dimensional intensity imaging to three-dimensional phase imaging by utilizing the phase dimension of light. Through interferometric measurement, the system extracts depth information and optical path length variations, enabling 3D reconstruction of tissue structures while maintaining high resolution at various depths through coherence gating and phase unwrapping algorithms

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

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 approach provides high-resolution imaging of intracellular motions in 3D tissues, facilitating the assessment of drug efficacy and personalized treatment selection, and can be used in cancer therapy and drug discovery by capturing dynamic cellular processes.

Implementation Method 1

the detector collects the reference beam and the signal beam to thereby acquire interferometric image data

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 2

light scattered by the sample forms a signal beam

Methodology Applied
Scientific EffectScattering: Scattering

Implementation Method 3

A Fourier transform lens and a pixel-array detector are positioned wherein light scattered by the sample forms a signal beam that is directed through the Fourier transform lens onto the pixel-array detector

Methodology Applied
Scientific EffectFourier transform:

Implementation Method 4

Fourier transform lens...directed through the Fourier transform lens onto the pixel-array detector

Methodology Applied
Scientific EffectFocusing: Focusing

Implementation Method 5

the depth within the sample at which the interferometric image data is acquired may be determined by coherence gating

Methodology Applied
Scientific EffectCoherence gating:

Data Source

PatentUS10642014B2Biodynamic microscopes and methods of use thereof
Publication Date: 2020.05.05 PURDUE RES FOUND
  • US10642014B2 patent drawing
  • US10642014B2 patent drawing
  • US10642014B2 patent drawing

AI summary

An apparatus for viewing a biological sample that functions as both a microscope and an interferometer. A short-coherence light source directs light onto the sample. A Fourier transform lens and a pixel-array detector are positioned to collect light scattered by the sample. An optic fiber assembly conveys a reference beam from the short-coherence light source. The detector collects the reference beam and the signal beam and uses coherence gating to acquire interferometric image data. In some embodiments the axis of the incident light striking the sample and the axis of collected scattered signal light form an angle of less than 180 degrees and advantageously an angle between 120 and 150 degrees. A method of converting a microscope into an interferometer is also disclosed.