Feedback Control for Rare Cell Detection Assays

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Solution Overview

Problem

Conventional methods for rare cell detection, such as ICC and ISH, face challenges with high background noise and low signal efficiency due to non-specific binding and evaporation, which can lead to false positives and reduced detection rates, especially when combining ICC and ISH techniques.

Innovation Solution

An automated system with feedback control and temperature control elements is implemented to maintain optimal fluid concentration and flow, reducing background noise and enhancing signal detection by adjusting fluid delivery and temperature settings based on real-time sensor feedback.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ICC and ISH methods are used for rare cell detection, then detection capability is achieved, but background noise increases and signal efficiency decreases due to non-specific binding and evaporation

Engineering Contradiction:
Improverare cell detection accuracyVSAvoidbackground noise
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent implements a feedback control system using sensors to monitor fluid concentration and evaporation in real-time during ICC and ISH assays. The system automatically adjusts reagent delivery and incubation conditions based on sensor feedback, compensating for evaporation losses and maintaining optimal fluid concentrations. This reduces background noise caused by concentration variations and improves rare cell detection accuracy by ensuring consistent assay conditions throughout the process.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent dynamically adjusts critical assay parameters including fluid concentration, temperature, and incubation time based on real-time monitoring. By changing these parameters adaptively rather than using fixed protocols, the system optimizes signal-to-noise ratio during the assay, reducing non-specific binding background while maintaining specific signal detection efficiency for rare cells.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If manual ICC and ISH procedures are performed, then flexibility in assay optimization is maintained, but evaporation and non-specific binding increase leading to false positives

Engineering Contradiction:
Improveassay optimization flexibilityVSAvoiddetection accuracy
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The automated system incorporates real-time feedback control that monitors and adjusts assay conditions to maintain optimal parameters throughout the procedure. This ensures reliable, reproducible results by eliminating manual handling variability and preventing evaporation-related artifacts that cause false positives, while still allowing protocol customization for different assay requirements.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs self-adjustment of reagent volumes and incubation conditions based on sensor feedback, automatically compensating for evaporation and maintaining optimal assay conditions without continuous manual intervention. This self-regulating capability improves reliability by ensuring consistent execution of optimized protocols while preserving the ability to program different assay configurations.

Inventive Principle:
Principle #25Self-service

3Device complexity

If fluid delivery is not controlled during ICC/ISH assays, then procedure simplicity is maintained, but evaporation causes concentration changes leading to increased background noise

Engineering Contradiction:
Improveassay procedure complexityVSAvoidevaporation-induced background noise
Core Design Contradiction:
Device complexityVSObject-affected harmful factors

Solution Approach 1:

The system uses sensors to monitor fluid levels and concentration parameters in real-time, with automatic feedback control adjusting reagent delivery to compensate for evaporation. This maintains optimal concentrations throughout the assay without requiring complex manual monitoring or adjustment procedures, reducing background noise while keeping the operational interface simple for the user.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces manual fluid handling and monitoring with automated sensor-based detection and computer-controlled reagent delivery. This substitution eliminates the need for complex manual procedures while providing precise control over fluid concentrations, reducing evaporation-related background noise through automated compensation rather than user intervention.

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

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

The system significantly improves rare cell detection by minimizing background noise and enhancing signal amplification, leading to more accurate and reliable identification of rare cells through reduced evaporation and optimized assay conditions.

Implementation Method 1

Feedback control thus ensures a proper concentration of components and optimal flow volume over the duration of the assay, which both reduces background noise and enhances signal detection

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

In addition, in certain aspects, a temperature control element is provided that can be positioned over a membrane of a filtration apparatus to optimize the temperature on the membrane

Methodology Applied
Scientific EffectHeating: Heating

Data Source

PatentEP3172336B1Feedback control for improved rare cell detection
Publication Date: 2020.06.17 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • EP3172336B1 patent drawingFigure 1A~1B
  • EP3172336B1 patent drawingFigure 2
  • EP3172336B1 patent drawingFigure 3

AI summary

There is provided a system (10) and method (100) for improving ICC and/or ISH rare cell detection by lowering background noise and providing enhanced detection of rare cells (15). In an embodiment, background noise for an ICC and/or an ISH rare cell detection assay is reduced and rare cell signaling is enhanced via feedback control. To accomplish the feedback control, an electronic control circuit (24) can direct a fluid delivery apparatus (18) to add an adjustment amount to account for fluid loss in the system (10) when fluid loss is indicated.