Liquid Bridge Systems for Microfluidic Sample Combination

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Solution Overview

Problem

There is a need for improved methods and systems in microfluidics to effectively mix and combine multiple samples at a microscale, as existing technologies face challenges in accurately and efficiently handling small fluid volumes and laminar flow characteristics.

Innovation Solution

The use of liquid bridges, where sample droplets are formed and enveloped in an immiscible carrier fluid, allows for the creation of a sample array system that mixes multiple samples by determining the number of liquid bridges needed based on the number of wells in each sample array, using a formula (an×bn) to achieve desired sample combinations, and can be integrated with robotics, pumps, and thermocyclers for efficient sample analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microfluidic devices are used to handle small fluid volumes, then cost savings and reduced cycle times are achieved, but the ability to effectively mix and combine multiple samples is limited due to laminar flow characteristics

Engineering Contradiction:
ImprovethroughputVSAvoidmixing efficiency
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent divides the sample handling process into discrete droplets separated by immiscible carrier fluid. Each droplet acts as an independent sample container, allowing multiple samples to be handled simultaneously in parallel channels without cross-contamination. This segmentation enables effective mixing by bringing discrete droplets into controlled contact while maintaining the benefits of microfluidic laminar flow.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an immiscible carrier fluid as an intermediary substance between aqueous samples. This carrier fluid enables droplet formation, stable transport, and controlled interaction of multiple samples without direct mixing in the traditional sense. The carrier fluid acts as a mediator that allows samples to be combined through droplet coalescence while preventing unwanted cross-contamination during transport.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If the number of liquid bridges is increased to achieve more sample combinations, then the number of possible sample combinations increases, but the device complexity increases

Engineering Contradiction:
Improvenumber of sample combinationsVSAvoidnumber of liquid bridges
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent designs liquid bridges with multiple inlets and outlets that can handle different sample configurations. A single liquid bridge structure can perform multiple functions by varying the input droplets, eliminating the need for dedicated liquid bridges for each sample combination. This multi-functionality reduces the total number of liquid bridges needed while maintaining high adaptability for different experimental designs.

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

Solution Approach 2:

The patent implements a hierarchical structure where multiple sample arrays are combined through nested levels of mixing. First arrays are combined within individual liquid bridges to form intermediate combinations, which are then fed into subsequent liquid bridges for further combination. This nesting approach allows exponential increase in sample combinations while adding only linearly more liquid bridges to the system.

Inventive Principle:
Principle #7Nested doll (Nesting)

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 enables efficient mixing and combination of samples, preserving their integrity and allowing for the formation of predetermined sample combinations, enhancing the throughput and accuracy of microfluidic systems, particularly in applications like PCR reactions.

Implementation Method 1

The droplets formed in a liquid bridge are enveloped in an immiscible carrier fluid

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Implementation Method 2

Because liquid flow tends to be laminar, surface flux and surface tension start to dominate

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 3

surface forces that are responsible for capillary phenomena

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS9533304B2Forming sample combinations using liquid bridge systems
Publication Date: 2017.01.03 STOKES BIO LTD
  • US9533304B2 patent drawing
  • US9533304B2 patent drawing
  • US9533304B2 patent drawing

AI summary

The present invention generally relates to methods of constructing liquid bridges and methods of forming predetermined combinations of samples using liquid bridges.