Automated Tissue Milling for Precise Slide Microdissection

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Solution Overview

Problem

Current tissue dissection methods, such as manual dissection and laser microdissection, lack precision, are labor-intensive, and fail to provide adequate traceability and documentation, limiting their effectiveness in molecular or genomic analysis of biological specimens.

Innovation Solution

A tissue dissection instrument with automated workflow that includes image acquisition, annotation transfer, precise dissection, and automated sample collection, utilizing a base, stage, fill station, and head assembly for efficient and repeatable microdissection of slide-mounted biological specimens, with features like color recognition for tip and vial verification, and integration with downstream extraction processes.

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 tip system that mechanically mills tissue sections. The milling tip rotates at controlled speeds (e.g., 500-5000 rpm) to precisely dissect tissue according to digital annotations, eliminating the imprecision of manual blade work while maintaining operational simplicity through automation.

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

Solution Approach 2:

The system performs self-service through automated annotation transfer from reference slides to serial sections, automatic milling parameter adjustment, and automated sample collection. The instrument independently handles the dissection workflow without requiring manual intervention at each step, improving precision while reducing operational complexity.

Inventive Principle:
Principle #25Self-service

2Manufacturing precision

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

Engineering Contradiction:
Improvedissection precisionVSAvoidlabor efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent substitutes expensive laser-based ablation with a mechanically-driven milling tip system. The milling tip physically mills tissue sections with precision comparable to laser methods but without the high equipment cost and labor intensity. The mechanical milling allows for automated operation and easier integration with standard laboratory workflows.

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

Solution Approach 2:

The system uses disposable milling tips rather than expensive, maintenance-intensive laser systems. Each milling tip is a low-cost, single-use component that eliminates the need for expensive laser equipment, specialized photoactivation films, and complex calibration procedures, thereby improving productivity and reducing operational complexity.

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

3Reliability

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

Engineering Contradiction:
Improveprocess traceabilityVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system implements feedback through digital annotation transfer that tracks the dissection process from reference slide to serial sections. Each dissection step is documented with metadata including area coordinates, tissue characteristics, and collection information. This automated feedback loop ensures complete traceability without requiring complex manual documentation procedures.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs preliminary action by pre-annotating reference slides and automatically transferring these annotations to serial sections before dissection begins. This pre-planning step establishes the complete dissection pathway and collection protocol in advance, ensuring traceability is built into the process from the start rather than requiring complex post-processing documentation.

Inventive Principle:
Principle #10Preliminary action

4Manufacturing precision

If automated workflow is implemented, then precision and repeatability are improved, but device complexity increases

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

Solution Approach 1:

The system achieves universality by integrating multiple functions into a single platform: digital pathology imaging, annotation creation and transfer, automated milling dissection, and sample collection. This multi-functionality allows the instrument to perform the entire dissection workflow with consistent precision without requiring separate specialized devices, thereby managing complexity through integration rather than proliferation of components.

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

Data Source

PatentUS11971333B2Automated tissue dissection instrument and methods of using the same
Publication Date: 2024.04.30 VENTANA MEDICAL SYSTEMS INC
  • US11971333B2 patent drawing
  • US11971333B2 patent drawing
  • US11971333B2 patent drawing

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.