Microfluidic Immunoassay Mixing via Bellows Pumps and Apertures

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Solution Overview

Problem

Current microfluidic device-based immunoassays face challenges in efficiently mixing small volumes for point-of-care diagnostics, particularly in fully closed systems, which is crucial for handling infectious samples without contamination risks and for adapting to a wide range of biomarkers.

Innovation Solution

The use of tandem bellows pumps with flow constricting apertures for micro-eductive mixing, which generates turbulent flow to efficiently mix small volumes without venting, ensuring a completely closed system and reducing incubation time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If capillary action is used for fluid transport in microfluidic devices, then the system can be simple and disposable, but mixing efficiency is poor and sensitivity is reduced

Engineering Contradiction:
Improvedevice simplicityVSAvoidassay sensitivity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent employs acoustic radiation pressure (a form of mechanical vibration) to drive fluid flow and mixing in the microfluidic device. Acoustic standing waves are generated to create acoustic radiation pressure that moves fluid through channels and mixes reagents, eliminating the need for complex mechanical pumps while achieving effective mixing in small volumes.

Inventive Principle:
Principle #18Mechanical vibration

2Quantity of substance

If small sample volumes are used for point-of-care testing, then patient care outcomes improve and sample volume decreases, but mixing efficiency deteriorates

Engineering Contradiction:
Improvesample volumeVSAvoidmixing efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

Acoustic radiation pressure is used to generate intense mixing in the small sample volumes. The acoustic standing waves create localized high-pressure regions that drive chaotic advection and enhance mixing efficiency even in the confined spaces of microfluidic channels containing only small volumes of sample and reagent.

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent uses acoustic pressure fields (a form of pneumatic action) to drive fluid movement and mixing. Acoustic radiation pressure creates pressure gradients that propel fluid through the microfluidic device and generate intense mixing without requiring mechanical contact or large sample volumes.

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Productivity

If acoustic radiation pressure is used for fluid mixing, then mixing efficiency improves and incubation time decreases, but device complexity increases

Engineering Contradiction:
Improvemixing efficiencyVSAvoiddevice structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The device uses acoustic radiation pressure generated by piezoelectric transducers to achieve intense mixing. The acoustic field creates standing waves that produce radiation pressure nodes and antinodes, driving fluid flow and mixing through acoustic streaming and chaotic advection, thereby achieving high mixing efficiency without mechanical moving parts.

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent replaces traditional mechanical mixing mechanisms (such as magnetic stirrers, pumps, or valves) with an acoustic field-based system. Piezoelectric transducers generate acoustic waves that create radiation pressure to drive fluid movement and mixing, eliminating the need for complex mechanical components while achieving effective mixing in small volumes.

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

4Reliability

If a closed system is used to prevent contamination, then reliability improves, but mixing capability deteriorates

Engineering Contradiction:
Improvecontamination preventionVSAvoidmixing capability
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

Acoustic radiation pressure is used to drive fluid flow and mixing within the closed microfluidic system. The acoustic field generates pressure gradients that move fluid through sealed channels, achieving effective mixing without requiring open systems or mechanical access points that could compromise the closed configuration and risk contamination.

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 approach enables efficient mixing of small volumes within microfluidic devices, facilitating robust and versatile point-of-care immunoassays that can handle various biomarkers, while maintaining a closed system to prevent contamination and improve diagnostic efficiency.

Implementation Method 1

acoustic radiation pressure to mix small volumes

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 2

acoustic radiation pressure to mix small volumes

Methodology Applied
Scientific EffectAcoustic streaming:

Implementation Method 3

piezoelectric transducers

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 4

generates turbulent flow to efficiently mix small volumes

Methodology Applied
Scientific EffectTurbulent flow: Turbulence

Implementation Method 5

Capillary action has proven useful in designing small disposable diagnostic devices

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentEP2041573B1Methods and devices for microfluidic point-of-care immunoassays
Publication Date: 2019.09.04 REVVITY HEALTH SCIENCES INC
  • EP2041573B1 patent drawingFigure 1
  • EP2041573B1 patent drawingFigure 2
  • EP2041573B1 patent drawingFigure 3

AI summary

Microf luidic methods and devices for heterogeneous binding and agglutination assays are disclosed, with improvements relating to mixing and to reagent and sample manipulation in systems designed for safe handling of clinical test samples. In operation, sample port (2), via microchannel (3), is used to introduce test sample into the reservoir of left bellows pump (4). Similarly, "waste" port (9), via microchannel (10), is used to introduce and discard reagent solutions into and out of the fluid chambers of right bellows pump (8). Ports (2) and (9) extend through the device cover (14) and are continuous with the fluid chambers of bellows pumps (4) and (8). Microchannels (3) and (10) may be modified to include valves (not shown). Active reciprocal flow of fluid between the right and left reservoirs is conducted through assay chamber (5) via focusing apertures (6) and (7).