Automated Tissue Microdissection With Slide Annotation Alignment

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Solution Overview

Problem

Current tissue dissection methods, such as manual dissection and laser microdissection, lack precision, are labor-intensive, and expensive, and do not provide adequate traceability and documentation for molecular or genomic analysis of biological specimens.

Innovation Solution

An automated tissue dissection instrument that acquires and transposes annotated reference slide images onto serial samples, automates the filling and unloading of milling tips, and uses color recognition to verify tip and vial presence, allowing for precise, quantifiable, and serial microdissection with integrated annotation, alignment, tracking, and reporting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If manual dissection using a blade is used, then the process is simple and inexpensive, but precision and resolution are insufficient due to tissue heterogeneity

Engineering Contradiction:
Improvedissection precisionVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent replaces manual mechanical blade dissection with an automated milling instrument that uses a rotating mill to precisely dissect tissue sections. This substitution provides quantifiable precision through automated control while reducing the complexity of manual visual alignment and blade handling procedures.

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

Solution Approach 2:

The system incorporates automated image acquisition and analysis capabilities that allow the dissection process to self-correct and self-align based on digital pathology images. The automated mill positioning and tissue tracking features enable the system to perform without continuous manual intervention, improving precision while maintaining manageable complexity.

Inventive Principle:
Principle #25Self-service

2Manufacturing precision

If laser microdissection is used, then precision is improved, but the instrument becomes expensive and labor intensive

Engineering Contradiction:
Improvedissection precisionVSAvoidlabor intensity
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

The patent replaces laser-based ablation with a mechanical milling system that uses a rotating mill to physically remove tissue. This substitution maintains high precision through automated control while eliminating the need for specialized laser equipment and photoactivation films, reducing both cost and operational complexity.

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

Solution Approach 2:

The system uses disposable milling tips instead of expensive laser systems. These single-use mills provide consistent precision without requiring costly instrument maintenance or specialized training, significantly reducing labor intensity and operational expenses while maintaining high dissection precision.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Loss of information

If conventional dissection methods are used, then equipment cost is low, but traceability and documentation are inadequate for molecular analysis

Engineering Contradiction:
Improveprocess traceabilityVSAvoidsystem complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The system incorporates real-time image acquisition during the dissection process, allowing continuous monitoring and verification of tissue selection. This feedback mechanism ensures complete traceability by recording which specific tissue regions were dissected from which slides, providing documentation required for molecular and genomic analysis without requiring overly complex tracking systems.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent introduces a digital pathology image as an intermediary between the physical tissue and the dissection process. This digital representation serves as a map that guides the automated mill, providing complete documentation and traceability of the dissection process while keeping the overall system complexity manageable through software-based solutions.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Productivity

If automated filling and unloading of milling tips is implemented, then productivity and precision are improved, but device complexity increases

Engineering Contradiction:
Improvedissection throughputVSAvoidautomation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system divides the automation function into separate modular components: an automated tip holder for milling tips, a separate tip changing mechanism, and an integrated fill station. This segmentation allows each component to be optimized independently, improving overall productivity while keeping individual component complexities manageable and maintenance straightforward.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP3538863B1Automated tissue dissection instrument and methods of using the same
Publication Date: 2022.12.21 F HOFFMANN LA ROCHE & CO AG
  • EP3538863B1 patent drawingFigure 1
  • EP3538863B1 patent drawingFigure 2
  • EP3538863B1 patent drawingFigure 3

AI summary

A system, an instrument, a computer-implemented method, and a clinical workflow for mesodissection of biological specimens on tissue slides by incorporating annotations. An image of an annotated reference slide is acquired and transposed onto a plurality of serial samples on the tissue slides along with the corresponding annotations and metadata. The serial samples are milled based on the annotations, and the milled tissue is automatically collected along with a milling buffer solution inside milling tips, and then dispensed in designated collection vials. The instrument automates the filling of aqueous buffer inside the milling tips and the monitoring of the buffer solution and the sequential filling of the milling tips. The workflow provides an integrated interface that performs tissue annotation, alignment, dissection, tracking, and reporting on a single screen. The degree of precision, ease of use and repeatability will improve PCR and NGS test results, ultimately providing timely patient results.