Microfluidic Flow Cell Hydrodynamic Isolation

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Solution Overview

Problem

Current flow-based sample delivery technologies in microfluidic devices are inadequate for efficiently transitioning between samples and buffers, leading to long transition times, inaccurate kinetic rate measurements, and inefficient molecular diffusion, which limits the accuracy and sensitivity of molecular interaction analysis, especially for low-affinity interactions and high-throughput sampling.

Innovation Solution

A flow cell device utilizing hydrodynamic isolation with reagent inlet and evacuation ports to create a clean leading edge of the sample fluid, allowing for precise control over fluid volumes and locations, eliminating the need for mechanical valves and enabling efficient addressing of discrete fluid volumes onto specific detection substrates within a two-dimensional array.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If continuous flow-based sample delivery is used to deliver sample plugs through the detection flow cell, then sample molecules can be presented to the detection substrate for interaction analysis, but long transition times occur between samples and buffers leading to inaccurate kinetic rate measurements

Engineering Contradiction:
Improvekinetic rate measurement accuracyVSAvoidtransition time between samples
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The flow cell is segmented into multiple independent channels, each capable of handling sample delivery and buffer flow separately. This segmentation allows for precise control of sample plugs and rapid switching between samples without cross-contamination or long transition times, directly improving kinetic rate measurement accuracy while reducing transition time losses.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the flow cell are optimized for different functions: sample injection zones, interaction zones with detection substrates, and buffer flow zones. This local optimization enables efficient sample delivery and rapid buffer exchange in specific areas, improving measurement precision while minimizing overall transition time.

Inventive Principle:
Principle #3Local quality

2Reliability

If mechanical valves are used to control sample delivery and switching, then discrete sample volumes can be delivered, but the device complexity increases and reliability decreases due to moving parts

Engineering Contradiction:
Improvedevice reliabilityVSAvoidvalve system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Mechanical valves are replaced with a valveless flow control system that uses fluid dynamic principles and microfluidic channel design to achieve sample delivery and switching. This substitution eliminates moving parts, significantly improving device reliability while reducing mechanical complexity. The system uses pressure gradients and channel geometry to control fluid flow instead of mechanical components.

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

Solution Approach 2:

The system uses hydraulic principles and pressure-driven flow control to manage sample and buffer delivery through the microfluidic channels. By utilizing pressure gradients and fluid dynamics rather than mechanical valves, the system achieves reliable sample handling with reduced device complexity and improved overall reliability.

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Measurement precision

If large flow cell chambers are used to accommodate detection substrates, then detection capabilities are maintained, but inefficient molecular diffusion occurs and transition times increase

Engineering Contradiction:
Improvemolecular interaction detection accuracyVSAvoiddiffusion time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The flow cell design transitions from a traditional large three-dimensional chamber to a planar two-dimensional microfluidic structure with thin flow paths. This dimensional change maintains adequate detection substrate area while dramatically reducing the distance molecules must diffuse, thereby improving detection accuracy and reducing diffusion time.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

Hydraulic flow control in the microfluidic channels ensures laminar flow conditions and optimized fluid velocity, which enhances molecular diffusion efficiency across the detection substrate. The controlled flow regime maintains detection accuracy while minimizing transition and diffusion times.

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 precise and efficient delivery of small, discrete fluid volumes to detection surfaces, reducing mixing and transition times, improving the accuracy and sensitivity of molecular interaction analysis and facilitating high-throughput sampling by allowing independent addressing of multiple locations on an array.

Implementation Method 1

a laminar flow of a guide fluid is introduced into a flow cell through a fluid inlet

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 2

a reagent in the laminar flow of guide fluid is continuously withdrawn using a vacuum

Methodology Applied
Scientific EffectVacuum withdrawal: Suction

Implementation Method 3

the vacuum applied to the reagent in the laminar flow of guide fluid is stopped, such that the discrete volume reagent sample is introduced into the guide fluid flow to move along the flow cell and pass over the detection substrate

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Data Source

PatentEP2139599B1Hydrodynamic isolation method and apparatus
Publication Date: 2020.09.02 BRUKER DALTONIK GMBH
  • EP2139599B1 patent drawingFigure 1~4g
  • EP2139599B1 patent drawingFigure 5~6
  • EP2139599B1 patent drawingFigure 7~10

AI summary

The present invention is a flow cell (100) and method for use in microfluidic analyses that presents highly discrete and small volumes of fluid to isolated locations on a two- dimensional surface contained within an open fluidic chamber defined by the flow cell that has physical dimensions such that laminar style flow occurs for fluids flowing through the chamber. This process of location specific fluid addressing within the flow cell is facilitated by combining components of hydrodynamic focusing with site specific cell evacuation. The process does not require the use of physical barriers within the flow cell or mechanical valves to control the paths of fluid movement.