Automated Assay Detection in Microfluidic Devices

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Solution Overview

Problem

Current microfluidic devices lack efficient methods for automated detection of assay-positive areas, particularly in identifying and quantifying analytes within microfluidic channels and sequestration pens, which hinders precise analysis and data interpretation.

Innovation Solution

An automated method that involves identifying assay areas based on the dimensions of microfluidic channels and sequestration pens, collecting digital images, calculating the rate of change of parameters such as light intensity, and comparing it to a threshold to determine assay positivity, along with a machine-readable storage device storing instructions for these processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If automated detection methods are implemented in microfluidic devices, then productivity and measurement precision are improved, but device complexity increases

Engineering Contradiction:
Improvedetection efficiencyVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The imaging device is configured to perform multiple functions: capturing images of microfluidic channels, identifying assay areas based on circuit element dimensions, and calculating rate of change parameters. This multi-functionality improves productivity without requiring separate dedicated devices for each task, thereby limiting the increase in device complexity.

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

Solution Approach 2:

The system automatically identifies assay areas based on the known dimensions of circuit elements (channels, sequestration pens) and autonomously calculates rate of change parameters from captured images. This self-service capability eliminates the need for manual area selection and parameter calculation, significantly improving productivity while the automation is integrated into the existing imaging system, limiting complexity increase.

Inventive Principle:
Principle #25Self-service

2Measurement precision

If manual identification of assay areas is used, then device complexity is reduced, but measurement precision and productivity deteriorate

Engineering Contradiction:
Improveassay area identification accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system is pre-programmed with the dimensions of circuit elements (channel width, sequestration pen dimensions) before the assay begins. During image analysis, these pre-stored dimensional parameters are automatically applied to identify assay areas, ensuring consistent and precise identification without manual intervention. This preliminary preparation enables high measurement precision while the automation is built into the software, limiting the perceived complexity increase.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system captures images, automatically identifies assay areas based on circuit element dimensions, calculates rate of change parameters, and compares results to thresholds to determine positivity. This closed-loop feedback process continuously refines measurements, improving precision. The feedback is handled by software algorithms integrated with the imaging device, which limits complexity increase compared to manual methods.

Inventive Principle:
Principle #23Feedback

3Productivity

If automated rate of change calculation is implemented, then productivity is improved, but use of energy increases

Engineering Contradiction:
Improvedata processing speedVSAvoidcomputational energy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The system calculates rate of change parameters only for the automatically identified assay areas within the microfluidic channels and sequestration pens, rather than processing entire images. This partial action approach focuses computational resources on relevant regions, improving productivity by quickly processing only necessary data while limiting energy consumption by avoiding unnecessary calculations in non-assay areas.

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentEP3230718B1Automated detection of assay-positive areas or of analyte quantities in microfluidic devices
Publication Date: 2022.03.02 BERKELEY LIGHTS INC
  • EP3230718B1 patent drawingFigure 1
  • EP3230718B1 patent drawingFigure 2A~2B
  • EP3230718B1 patent drawingFigure 2C~2D

AI summary

A method is provided for the automated detection of assay-positive assay areas in a microfluidic device comprising one or more circuit elements, the method comprising collecting a set of digital images of an automatically-identified assay area (570, 572), wherein the automatically-identified assay area is identified based, at least in part, on the dimensions of the one or more circuit elements (522), calculating a rate of change over the course of all or part of the assay based on the set of digital images of the automatically-identified assay area, comparing the rate of change to a threshold value, and determining that the automatically-identified assay region is assay-positive if the rate of change is greater than the threshold value.