Microfluidic Chip Pillar Array for Kinetic Immunoassay

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Solution Overview

Problem

Current immunoassay technologies interrupt the binding reaction to measure kinetics, leading to variability and inaccuracy due to factors like mixing quality, temperature, and washing procedures, especially for fast reactions and low concentrations.

Innovation Solution

A microfluidic chip with an array of pillars is used to continuously measure reaction kinetics by flowing beads through a laminar wash buffer, allowing real-time monitoring of binding reactions and removing non-specific interactions, enabling accurate kinetic analysis of antigen-antibody interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the binding reaction is interrupted to measure kinetics, then the measurement can be performed, but the measurement precision deteriorates due to variability in mixing quality, temperature, and washing procedures

Engineering Contradiction:
Improvekinetics measurement accuracyVSAvoidmeasurement variability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies continuous flow through the microfluidic chip to continuously monitor binding kinetics in real-time, eliminating the need to interrupt the reaction. This continuous monitoring approach removes the variability introduced by repeated interruption and recovery cycles, providing reliable kinetic measurements without the constraints of discrete time points

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent replaces manual washing procedures with an automated microfluidic washing system that uses controlled fluid flow. The washing buffer is delivered through precise fluidic control, eliminating the variability associated with manual washing operations and ensuring consistent measurement conditions

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

2Measurement precision

If the reaction is incubated for several hours to reach equilibrium, then the measurement becomes more stable, but the time required increases significantly

Engineering Contradiction:
Improveequilibrium stabilityVSAvoidincubation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The microfluidic system enables continuous real-time monitoring of binding kinetics from the start of the reaction, allowing equilibrium to be reached and detected without prolonged incubation. The continuous flow provides immediate feedback on reaction progress, enabling rapid determination of kinetic parameters and reducing the time required to reach stable measurements

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system continuously monitors binding events in real-time and provides feedback on reaction progress. This feedback mechanism allows the system to detect when equilibrium is reached and to adjust measurement parameters accordingly, eliminating the need for extended incubation periods while maintaining measurement stability

Inventive Principle:
Principle #23Feedback

3Measurement precision

If wash procedures are performed to remove excess label, then the label measurement accuracy improves, but the measurement time increases

Engineering Contradiction:
Improvelabel measurement accuracyVSAvoidwashing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The microfluidic system performs washing operations continuously and rapidly as part of the flow-through process. The washing buffer is delivered through controlled fluidic flow that simultaneously removes excess label while maintaining measurement capability, eliminating the need for separate, time-consuming washing steps

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent uses hydraulic flow control to precisely manage the washing process. The microfluidic channels deliver washing buffer at controlled rates, enabling rapid and efficient label removal without requiring prolonged washing times. The fluidic system provides precise control over wash duration and intensity, optimizing both accuracy and speed

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 method provides accurate and efficient real-time measurement of binding kinetics, reducing variability and enabling precise determination of antigen concentrations and kinetic rate constants, even at low concentrations, within a short time frame.

Implementation Method 1

flowing beads through a laminar wash buffer

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 2

a fluorescent label may bind to the antigen

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12030053B1Multi-step kinetic immunoassay systems and methods
Publication Date: 2024.07.09 PANAZEE INC
  • US12030053B1 patent drawing
  • US12030053B1 patent drawing
  • US12030053B1 patent drawing

AI summary

A microfluidic chip with an array of pillars for directing flow of beads is used to measure reaction kinetics. A stream may be continuously drawn from the reaction volume into the microfluidic chip. The bead is attached to a primary antibody. The reaction volume has an antigen. The primary antibody binds to the antigen. A secondary antibody with a label binds to the antigen, creating a sandwich of bead, antigen, and label. The binding reactions occur over time in the microfluidic chip. The beads may be imaged after traversing a laminar wash buffer, and the signal intensity is measured. Each bead provides a kinetic monitoring of the immunoassay over the reaction time at which the bead is removed from the reaction media. Methods and systems are described in this disclosure.