Real-Time Microscopy Triggered Fixation for Electron Sample Prep

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Solution Overview

Problem

There is currently no comprehensive and consistent method for automatically, reproducibly, and conveniently processing biological samples observed through light microscopy for electron microscopy, leading to inefficiencies in sample preparation and analysis.

Innovation Solution

A device and method that utilize image analysis from a microscope to detect specific biological events, triggering a fluidics activation system to treat the sample, such as fixation or cryofixation, ensuring reproducible sample preparation for electron microscopy by capturing images and analyzing them in real-time to initiate appropriate treatments based on predefined criteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual sample preparation procedures are used for electron microscopy, then flexibility in processing different samples is maintained, but reproducibility and automation are compromised

Engineering Contradiction:
Improvereproducibility of sample preparationVSAvoidautomation of sample preparation
Core Design Contradiction:
ReliabilityVSExtent of automation

Solution Approach 1:

The system employs image analysis to detect biological events in real-time and provides feedback to automatically trigger sample preparation procedures. The microscope captures images, the image analysis module processes them to detect events, and upon detection, the system automatically initiates the appropriate preparation protocol, ensuring reproducible results through automated feedback control

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system enables samples to serve themselves by automatically detecting their own biological events and triggering the necessary preparation procedures without manual intervention. The sample's inherent biological signals are detected and used to automatically initiate processing, making the system self-regulating and highly reproducible

Inventive Principle:
Principle #25Self-service

2Productivity

If comprehensive manual processing procedures are implemented, then sample preparation completeness is improved, but time consumption and operational complexity increase

Engineering Contradiction:
Improvethroughput of sample preparationVSAvoidtime for sample preparation
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The system performs preliminary actions by continuously monitoring samples and pre-positioning preparation protocols ready to execute. When a biological event is detected, the predetermined preparation sequence is immediately activated, eliminating delays associated with manual decision-making and procedure initiation

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces manual mechanical operations with an automated control system that uses image analysis and computer-controlled fluidics. The mechanical sample preparation steps are substituted with an automated system that detects biological events through imaging and automatically executes preparation procedures, dramatically increasing throughput while reducing time

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

3Ease of operation

If real-time image analysis is implemented to detect biological events, then automation and reproducibility are improved, but system complexity increases

Engineering Contradiction:
Improveease of sample preparationVSAvoidcomplexity of sample preparation system
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The system achieves ease of operation through multi-functionality, where a single integrated platform performs imaging, event detection, and automated sample preparation. This universal system eliminates the need for separate manual operations for each preparation step, making the complex automated process easy to operate through a unified interface

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

Solution Approach 2:

The patent merges multiple functions (microscopy, image analysis, event detection, and sample preparation control) into a single integrated system. By combining these previously separate operations into one coordinated platform, the system reduces operational complexity despite the advanced capabilities, making automated reproducible preparation accessible

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentUS10078037B2Signal based sample preparation
Publication Date: 2018.09.18 FEI CO
  • US10078037B2 patent drawing
  • US10078037B2 patent drawing
  • US10078037B2 patent drawing

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.