Automated Sample Fixation via Event-Triggered Fluidics

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Solution Overview

Problem

Current methods for preparing biological samples for electron microscopy lack a comprehensive and consistent way to automatically, reproducibly, and conveniently process samples observed through light microscopy, leading to inefficiencies and variability in sample preparation.

Innovation Solution

A device that combines light microscope imaging with image analysis and real-time feedback control of a fluidics system to detect specific biological events, triggering immediate and reproducible fixation or treatment of the sample, such as quick freezing, to prepare it for electron microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual sample preparation procedures are used for electron microscopy, then flexibility in handling different samples is maintained, but reproducibility and consistency of sample preparation deteriorate

Engineering Contradiction:
Improvereproducibility of sample preparationVSAvoidcomplexity of automated system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system uses a camera to capture images of the biological sample, an image analysis module to analyze the captured images and determine when a detectable event has occurred, and a fluidics activation module to automatically trigger treatment based on this detection. This closed-loop feedback system ensures reproducible and consistent sample preparation by objectively detecting biological events and automatically initiating fixation or treatment procedures, eliminating manual variability while maintaining adaptability to different sample types.

Inventive Principle:
Principle #23Feedback

2Reliability

If automated image analysis and fluidics activation are implemented, then reproducibility of sample preparation is improved, but device complexity increases

Engineering Contradiction:
Improveconsistency of sample preparationVSAvoidcomplexity of integrated system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent integrates three distinct functional modules into a single coordinated system: a microscope with camera for image capture, an image analysis module for event detection, and a fluidics activation module for sample treatment. By merging these modules into one integrated platform, the system achieves consistent and reproducible sample preparation while managing complexity through modular design, where each component performs a specific function but works seamlessly with the others.

Inventive Principle:
Principle #5Merging (Combining)

3Productivity

If real-time detection and automatic fixation are used, then throughput of sample preparation is enhanced, but measurement precision requirements increase

Engineering Contradiction:
Improvethroughput of sample preparationVSAvoidprecision of event detection
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system replaces manual observation and manual initiation of fixation procedures with an automated optical detection and fluidics control system. The camera captures images, the image analysis module automatically analyzes these images to detect biological events with high precision, and the fluidics activation module immediately triggers fixation or treatment. This substitution of manual mechanical operations with automated optical and fluidic systems enables high-throughput processing while maintaining precise event detection through digital image analysis.

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

Data Source

PatentEP2738540B1Signal based sample preparation
Publication Date: 2017.11.22 FEI CO
  • EP2738540B1 patent drawingFigure 1
  • EP2738540B1 patent drawingFigure 2
  • EP2738540B1 patent drawingFigure 3

AI summary

Described is a system and method for detecting whether a biological event has occurred in a cellular sample, and then activating a fluidics system to fix the cell at the point in time with the event occurred. In one example, a sample preparation system includes a camera linked to a confocal microscope that is interrogating a cellular sample. Once a detectable event, such as a binding event, has occurred, the sample preparation system releases a fixative to fix the cell at the point in time when the event was detected.