Fiducial Marker Calibration for Tissue Thickness Measurement

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Solution Overview

Problem

Existing methods for tissue thickness measurement are not compatible with both dried and hydrated tissues due to changes in tissue dimensions, making it difficult to accurately measure tissue thickness in experimental procedures.

Innovation Solution

A method involving fiducial markers with predetermined heights on a calibration material, where optical metrics are determined to create a calibration model, allowing for the measurement of tissue thickness in both dried and hydrated states by correlating optical metrics with physical dimensions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If existing methods for tissue thickness measurement are used on dried tissues, then measurement can be performed, but the methods are not compatible with hydrated tissues due to dimensional changes

Engineering Contradiction:

Improvecompatibility with both dried and hydrated tissuesVSAvoidtissue thickness measurement accuracy

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent introduces fiducial markers as intermediary objects with known, stable dimensions that serve as reference standards. These markers are imaged alongside the tissue sample, and their known dimensions are used to calculate a scaling factor that accounts for dimensional changes in the tissue. This intermediary reference system enables accurate thickness measurement of hydrated tissues by providing a stable basis for comparison, resolving the incompatibility between measurement methods and hydrated tissue states.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the measurement parameter from direct tissue dimension measurement to relative measurement based on fiducial marker dimensions. By imaging both the fiducial markers and tissue at the same magnification and using the known marker dimensions to determine the scaling factor, the system adapts to dimensional changes in tissue (whether dried or hydrated) while maintaining measurement accuracy through the invariant marker reference.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If calibration models are created using fiducial markers with predetermined heights, then accurate thickness measurement in both dried and hydrated states is enabled, but the system complexity increases

Engineering Contradiction:

Improvetissue thickness measurement accuracyVSAvoidcalibration system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent implements preliminary action by pre-fabricating calibration materials with fiducial markers at predetermined heights before actual tissue measurement. These calibration standards are created in advance using various fabrication methods (photopatterning, micromilling, etching, injection molding, hot embossing, or 3D printing), establishing a known reference framework that simplifies subsequent tissue measurements rather than increasing complexity during the measurement process itself.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses fiducial markers as simplified copies or proxies for tissue structures. Instead of directly measuring complex tissue dimensions that change with hydration, the system measures the dimensions of simple, invariant fiducial markers and uses those measurements to infer tissue thickness through calculated scaling factors. This copying approach reduces measurement complexity while maintaining accuracy.

Inventive Principle:

Principle #26Copying

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 and efficient measurement of tissue thickness in both states, reducing computational costs and facilitating experimentation on a broader range of sample types.

Implementation Method 1

receiving an image of a plurality of fiducial markers, where the plurality of fiducial markers has at least one predetermined height relative to a substrate; determining at least one optical metric associated with the plurality of fiducial markers within the image

Methodology Applied

Scientific EffectOptical focusing and imaging: Lens

Implementation Method 2

determining a calibration model based on the at least one predetermined height and the at least one optical metric

Methodology Applied

Scientific EffectOptical metric correlation:

Data Source

PatentUS20240210161A1Systems and methods of measuring sample thickness

Publication Date: 2024.06.27 10X GENOMICS INC

AI summary

A method includes receiving an image of a plurality of fiducial markers, where the plurality of fiducial markers has at least one predetermined height relative to a substrate. The method also includes determining at least one optical metric associated with the plurality of fiducial markers within the image, and determining a calibration model based on the at least one predetermined height and the at least one optical metric.