Microfluidic Flow Injection Layout for Rapid Sample Transition

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Solution Overview

Problem

Current microfluidic systems for biosensing face challenges with high dead volumes, which lead to dispersion and delayed sample transition, affecting the accuracy and reproducibility of biomolecular interaction analysis, particularly in SPR-based biosensors.

Innovation Solution

A fluidic configuration with counter flows that remove the dispersed sample region to waste before injecting non-dispersed sample into the flow cell, allowing rapid transition to 100% sample, thereby reducing dead volume and enhancing kinetic range and data quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional flow injection analysis fluidic systems are used, then robustness is improved, but dead volume increases leading to sample dispersion and delayed transition

Engineering Contradiction:
Improvesystem robustnessVSAvoiddead volume
Core Design Contradiction:
ReliabilityVSVolume of stationary object

Solution Approach 1:

The flow cell is segmented into distinct functional zones: a flow reversal region with inlet/outlet ports at opposite ends, and a sensing region positioned between them. This segmentation allows the system to separate the dispersion-prone flow reversal operations from the sensing operations, enabling robust flow control while minimizing dead volume impact on the sensing area.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system employs bidirectional flow reversal through the flow cell. Instead of unidirectional flow, the fluid direction can be inverted by switching between inlet and outlet ports, allowing the dispersed sample region to be flushed out in reverse direction while fresh sample enters, thereby reducing dead volume effects and improving sample transition speed.

Inventive Principle:
Principle #13The other way round (Inversion)

2Device complexity

If microfluidic channels are integrated into the fluidic card, then device complexity is reduced, but dead volume increases affecting measurement accuracy

Engineering Contradiction:
Improveintegration levelVSAvoidsample transition accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

Different regions of the flow cell are assigned different functional qualities: the flow reversal region handles high-flow-direction-changes and dispersion, while the sensing region maintains stable, laminar flow conditions optimal for measurement. This local differentiation allows integrated microfluidic channels to provide robust flow control without compromising measurement precision in the sensing zone.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The sensing region is extracted as a distinct functional zone within the flow cell, positioned between the inlet and outlet ports. This extraction allows the sensing area to be shielded from the dispersed sample regions that form during flow reversal operations, thereby maintaining measurement accuracy even with integrated microfluidic channels.

Inventive Principle:
Principle #2Taking out (Extraction)

3Speed

If sample flows directly to sensing region, then rise time is reduced, but dispersed sample region contacts sensing area reducing data quality

Engineering Contradiction:
Improvesample transition speedVSAvoiddata quality
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

Before sample enters the sensing region, the system performs preliminary flow reversal operations in the flow reversal region to establish proper flow direction and minimize dispersion. The inlet and outlet ports are positioned to allow sample to be pre-conditioned and directed away from dispersed regions before reaching the sensing area, ensuring high-quality data collection.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The flow cell structure acts as an intermediary between the microfluidic channels and the sensing region. It provides a controlled flow path that mediates the transition of sample from the channels to the sensing area, allowing dispersion to be minimized through strategic port positioning and flow direction control while maintaining rapid sample transition.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 significantly reduces dead volume, enabling rapid rise and fall times, improving the accuracy of kinetic model fitting and data quality by ensuring that the sample transitions quickly and accurately to the sensing area, thus extending the range of measurable interaction rates.

Implementation Method 1

The evanescent field created at the surface decays exponentially from the surface and falls to one third of its maximum intensity at approximately 300 nanometers (nm) from the surface. Hence the SPR technique is sensitive to surface refractive index changes.

Methodology Applied
Scientific EffectEvanescent field:

Implementation Method 2

A particularly effective evanescent field based technology, known as surface plasmon resonance (SPR), exploits the behavior of light upon reflection from a gold-coated optical substrate

Methodology Applied
Scientific EffectSurface plasmon resonance (SPR):

Implementation Method 3

A fluidic configuration with counter flows that remove the dispersed sample region to waste before injecting non-dispersed sample into the flow cell

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Data Source

PatentEP2179261B1Fluidic configuration for flow injection analysis system
Publication Date: 2021.09.15 MOLECULAR DEVICES LLC
  • EP2179261B1 patent drawingFigure 1~2
  • EP2179261B1 patent drawingFigure 3~6
  • EP2179261B1 patent drawingFigure 7~10

AI summary

A fluidic configuration, both structural and methodological, for the injection of sample greatly reduces dead volume allowing rapid transition to 100% sample in a flow cell. For a continuous flow injection analysis system the structure and method provide counter flows to remove in one direction the dispersed region of the sample to waste before injecting non-dispersed sample into the flow cell by reversing the effective flow direction. The injection point itself is directly adjacent to the flow cell where all channels are microfluidic channels. Therefore, only the flow cell volume needs to be displaced during injection of sample in order to achieve 100% transition to sample within the flow cell. This greatly accelerates the rise and fall times thereby extending the kinetic range of the real-time interaction analysis instrument. In addition such rapid transition to sample improves overall data quality thereby improving kinetic model fitting.