Micellar Gradient Focusing for Neutral Analyte Separation

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Solution Overview

Problem

Existing methods for separating and concentrating analytes in solutions are limited by their reliance on electrophoretic mobility, making it difficult to focus neutral or chiral species, and they have theoretical limits on concentration factors and flexibility in manipulation.

Innovation Solution

A method that combines affinity gradient focusing with micellar electrokinetic chromatography, using a pseudostationary phase to create a steady-state gradient in retention factor, allowing analytes to move at different velocities and focus based on affinity, enabling separation and concentration of neutral or charged analytes without electrophoretic mobility limitations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional focusing methods (IEF, EMF, TGF) are used to separate and concentrate analytes, then analytes can be focused at zero velocity points, but these methods only work with analytes that have non-zero electrophoretic mobility

Engineering Contradiction:
Improveapplicability to different analyte typesVSAvoidlimitation on analyte selection
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent introduces a pseudostationary phase (micellar phase) as an intermediary that mediates the separation process. This pseudostationary phase interacts with analytes through affinity-based mechanisms rather than direct electrophoretic interaction, enabling focusing of neutral and chiral species that cannot be separated by electrophoretic mobility alone. The pseudostationary phase acts as a mediator that provides alternative separation dimensions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If stacking methods are used to concentrate analytes, then analyte peaks become narrower and more concentrated, but there is no point of zero analyte velocity and concentration factor is theoretically limited

Engineering Contradiction:
Improveanalyte concentrationVSAvoidtheoretical concentration limit
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent merges the concepts of stacking and focusing into a unified approach. By combining the velocity gradient manipulation of stacking with the zero-velocity-point accumulation of focusing, the method achieves both peak narrowing and unlimited concentration factors. The micellar gradient focusing system creates conditions where analytes experience both velocity differentiation and zero-velocity accumulation points simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

3Adaptability or versatility

If EKC separations are used to separate analytes based on affinity for pseudostationary phase, then neutral and chiral species can be separated, but separations require constant velocity movement rather than focusing at zero velocity

Engineering Contradiction:
Improveability to separate neutral and chiral speciesVSAvoidmanipulation flexibility
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent introduces dynamic control capabilities to the EKC system. By applying voltage gradients and controlling bulk flow rates, the system can dynamically adjust the velocity of the pseudostationary phase and mobile phase. This dynamic control enables the system to transition between separation mode (constant velocity) and focusing mode (zero velocity points), providing operational flexibility for different analytical requirements.

Inventive Principle:
Principle #15Dynamics

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 achieves high concentration factors with no theoretical limits, allows manipulation of focused analytes for detection or further analysis, and can separate neutral species and identical electrophoretically mobile analytes, offering greater flexibility and selectivity compared to traditional techniques.

Implementation Method 1

a method and device which focuses and separates analytes using affinity gradient focusing

Methodology Applied
Scientific EffectAffinity gradient focusing:

Implementation Method 2

Micellar electrokinetic chromatography and related methods (hereinafter 'EKC') take advantage of an analyte's affinity for a pseudostationary phase to facilitate separations using capillary electrophoresis

Methodology Applied
Scientific EffectMicellar electrokinetic chromatography:

Implementation Method 3

The pseudostationary phase serves the same function—to provide selectivity—as a stationary phase in chromatography, but is not actually stationary, and can move with the buffer and/or with its own electrophoretic mobility

Methodology Applied
Scientific EffectElectrophoretic mobility: Electrophoresis

Implementation Method 4

focusing refers to methods for manipulating the velocity of an analyte and thereby causing the analyte to move towards a point at which its velocity is zero and where the analyte will therefore accumulate and increase in concentration

Methodology Applied
Scientific EffectVelocity gradient focusing:

Data Source

PatentUS7718046B2Micellar gradient focusing
Publication Date: 2010.05.18 GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SEC OF COMMERCE THE NAT INST OF STANDARDS & TEHCNOLOGY
  • US7718046B2 patent drawing
  • US7718046B2 patent drawing
  • US7718046B2 patent drawing

AI summary

A method and device are provided for affinity gradient focusing for directing at least one analyte in a solution containing a pseudostationary phase and located in a channel such as a capillary or a microchannel. The method includes establishing a steady-state spatial gradient in a retention factor of the pseudostationary phase for the at least one analyte. The analyte is caused to be moved within the channel whereby the concentration of the at least one analyte changes at one or more positions along the gradient. The pseudostationary phase is charged and the analyte is either neutral or charged or alternatively, the pseudostationary phase is neutral and the analyte is charged. The device may include a fluid channel, a pseudostationary phase having a retention factor gradient, an electrical current source and a pump system for establishing the bulk flow in the solution in the channel.