OPTM 3D Imaging for Thin Biopsy Specimens

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Solution Overview

Problem

Current methods for diagnosing diseases using thin-needle core biopsies are inadequate due to the small size and fragility of specimens, which are too small for conventional handling and imaging, leading to challenges in determining the extent and invasiveness of diseases like cancer.

Innovation Solution

A system and method utilizing a microfluidic device for processing and imaging thin-needle core biopsy specimens, employing Optical Projection Tomography Microscopy (OPTM) to generate a continuous 3D image of the specimen, which includes chemical processing, optical inspection, and image stitching or blending for diagnostic imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If thinner needles are used for biopsy, then invasiveness is reduced, but the ability to reliably acquire tissue specimens deteriorates

Engineering Contradiction:
ImproveinvasivenessVSAvoidability to acquire tissue specimen
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the physical parameters of the needle by incorporating a cutting mechanism that activates upon tissue contact. The needle transitions from a simple puncture tool to an active cutting instrument through parameter changes in its operational mode, enabling thin needles to reliably acquire tissue specimens without increasing invasiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The needle system incorporates dynamic elements including a cutting blade that deploys after tissue penetration. The system transitions from a static thin needle to a dynamic cutting tool that adapts its functionality based on the biopsy process stage, maintaining thin profile during insertion while providing cutting capability during tissue acquisition.

Inventive Principle:
Principle #15Dynamics

2Measurement precision

If conventional optical microscopy is used for tissue imaging, then spatial resolution is sufficient, but tissue thickness is limited to less than 0.1 mm

Engineering Contradiction:
Improvespatial resolutionVSAvoidtissue thickness
Core Design Contradiction:
Measurement precisionVSLength of stationary object

Solution Approach 1:

The patent transitions from two-dimensional optical microscopy to three-dimensional optical projection tomography. By adding the depth dimension through rotational imaging and tomographic reconstruction, the system overcomes the thickness limitation while maintaining spatial resolution, enabling visualization of entire tissue specimens regardless of their thickness.

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

Solution Approach 2:

The patent introduces an optical clearing agent as an intermediary substance that reduces light scattering in thick tissues. This mediator improves light penetration and transmission through the tissue specimen, enabling optical imaging beyond the conventional 0.1 mm thickness limit while preserving spatial resolution.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If thin-needle core biopsy specimens are handled using conventional methods, then standard processing is possible, but specimen fragility and small size cause handling difficulties

Engineering Contradiction:
Improvestandard processing capabilityVSAvoidhandling ease
Core Design Contradiction:
Ease of manufactureVSEase of operation

Solution Approach 1:

The patent employs nested containment structures where the fragile tissue specimen is first captured in a needle, then transferred to a holding chamber, and finally embedded in support matrix. Each nested structure provides mechanical support and protection, enabling standard processing of specimens that would otherwise be too fragile to handle.

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent uses composite material structures combining the tissue specimen with support matrices and embedding media. This composite approach provides mechanical strength to the fragile specimen while preserving its biological integrity, enabling conventional handling and processing procedures.

Inventive Principle:
Principle #40Composite materials

4Device complexity

If 2D imaging is used for biopsy specimens, then imaging simplicity is maintained, but determination of disease extent and invasiveness is inadequate

Engineering Contradiction:
Improveimaging system simplicityVSAvoiddisease extent and invasiveness information
Core Design Contradiction:
Device complexityVSLoss of information

Solution Approach 1:

The patent transitions from 2D imaging to 3D optical projection tomography, adding the depth dimension through rotational acquisition and tomographic reconstruction. This dimensional enhancement recovers the disease extent and invasiveness information that is lost in 2D imaging, while the computational reconstruction processes maintain operational simplicity.

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

Enables accurate 3D imaging of thin-needle core biopsy specimens, providing clear localization of disease, extent, and invasiveness, reducing sampling errors and improving diagnostic precision for delicate organs like the pancreas and brain.

Implementation Method 1

an optical microscope is used in transmission

Methodology Applied
Scientific EffectLight transmission: Light

Implementation Method 2

tissue attenuates transmittance of white light, primarily due to scattering from refractive index differences

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 3

tissue attenuates transmittance of white light, primarily due to scattering from refractive index differences

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 4

The tissue is chemically fixed and stained with absorptive dyes... tissue attenuates transmittance of white light

Methodology Applied
Scientific EffectOptical clearing:

Data Source

PatentUS10557778B2Optical projection tomography microscopy (OPTM) for large specimen sizes
Publication Date: 2020.02.11 ROSEBIOPSY INC
  • US10557778B2 patent drawing
  • US10557778B2 patent drawing
  • US10557778B2 patent drawing

AI summary

An imaging and diagnostic system and method for focal scanning of a specimen using optical projection tomographic microscopy and computer generation of three-dimensional images is disclosed. One embodiment includes a light source and an imaging system having an adjustable focal position, which acquires a plurality of digital 2D projection images of biological tissue placed within a specimen tube that translates and rotates past an optical lens in a helical pattern. A computer captures the images and generates a 3D composite image. Also disclosed is a system and method for preparing a specimen for optical microscopy. One embodiment includes fixing, staining, and/or optically clearing biological tissue within a microfluidic specimen chamber prior to placement in a specimen tube.