Automated Staining System with Real-Time Optical Feedback

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Solution Overview

Problem

The existing manual staining processes for biological samples are time-consuming, prone to errors, and inefficient, particularly in multiplexing techniques where multiple stains are required, leading to excessive reagent consumption and limited shelf life issues.

Innovation Solution

An automated closed-loop system that includes a flow cell, illumination source, monitoring unit, and controller to optimize staining cycles by monitoring optical characteristics and adjusting reagent application based on real-time data, minimizing reagent volume and dwell time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If manual staining techniques are used, then flexibility in handling different stains is maintained, but the process becomes time-consuming and prone to errors

Engineering Contradiction:
ImproveFlexibility in handling different stainsVSAvoidStaining process speed
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The system uses automated feedback loops where the controller monitors staining progress in real-time and automatically adjusts reagent application timing and duration based on actual sample conditions, eliminating the need for manual timing adjustments while maintaining optimization for each specific stain type

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system incorporates real-time monitoring of staining progress with feedback to the controller, which automatically adjusts the staining cycle parameters based on the actual state of the sample, ensuring both speed and accuracy without manual intervention

Inventive Principle:
Principle #23Feedback

2Device complexity

If fixed staining times are used for all antibodies, then the process is simple to control, but weak stains are over-processed and strong stains are under-processed

Engineering Contradiction:
ImproveControl simplicityVSAvoidStaining intensity optimization
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The controller receives real-time feedback on staining intensity and automatically adjusts the duration and intensity of reagent application for each antibody, ensuring optimal staining for both weak and strong signals without requiring complex pre-programming for each stain type

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system dynamically adjusts staining parameters during the process based on real-time monitoring data, allowing the control algorithm to adapt to different antibody strengths and sample conditions while maintaining simple operator interface

Inventive Principle:
Principle #15Dynamics

3Reliability

If extended reagent dwell time is used, then staining completeness is improved, but reagent consumption increases and shelf life is reduced

Engineering Contradiction:
ImproveStaining completenessVSAvoidReagent consumption
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The system monitors staining progress in real-time and automatically terminates reagent application as soon as optimal staining is achieved, preventing over-exposure and reducing reagent consumption while ensuring complete staining for each specific sample

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The automated system self-regulates reagent application duration based on real-time feedback, eliminating the need for conservative extended dwell times and optimizing reagent usage for each individual staining cycle

Inventive Principle:
Principle #25Self-service

4Adaptability or versatility

If multiple serial stains are applied, then multiplexed analysis capability is improved, but total operation time increases significantly

Engineering Contradiction:
ImproveMultiplexed analysis capabilityVSAvoidTotal operation time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The system performs multiple staining cycles in continuous sequence without manual intervention between steps, maintaining automated reagent application and monitoring throughout the entire multiplexed staining process to minimize idle time

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The controller dynamically optimizes each staining cycle duration based on real-time feedback, allowing faster processing of each individual stain while maintaining quality, thereby reducing the cumulative time for multiple serial stains

Inventive Principle:
Principle #15Dynamics

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

This approach reduces manual intervention, optimizes reagent usage, and enhances the reliability and efficiency of the staining process, allowing for precise control of each step and minimizing sample degradation.

Implementation Method 1

a monitoring unit operatively coupled to the flow cell and configured for monitoring one or more optical characteristics of the biological sample

Methodology Applied
Scientific EffectOptical detection: Absorption Spectroscopy

Data Source

PatentEP2646796B1Closed loop monitoring of automated molecular pathology system
Publication Date: 2015.08.26 GENERAL ELECTRIC CO
  • EP2646796B1 patent drawingFigure 1
  • EP2646796B1 patent drawingFigure 2

AI summary

A closed loop automated method for staining of a biological sample is provided. The method comprises providing a biological sample, staining at least a portion of the biological sample by flowing in a reagent, monitoring one or more optical characteristics of the biological sample, and calculating a figure of merit based on at least one of the optical characteristics. An automated device for iterative staining of a biological sample is also provided.