Sol-Gel Concentrating Device for Capillary Electrophoresis Sensitivity

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Solution Overview

Problem

Capillary zone electrophoresis (CZE) has limited sensitivity due to short in-capillary path lengths, requiring higher analyte concentrations for detection, which can lead to sample manipulation issues and potential loss or contamination, especially when analyzing dilute samples.

Innovation Solution

A sol-gel concentrating device with a channel containing a polymerized alkylsilicate gel matrix and chromatographic sorbent particles is used, formed through a step-wise heating process to create a stable monolith within a capillary tube, enhancing analyte concentration and detection sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If capillary zone electrophoresis is used for analysis, then fast and efficient sample separation is achieved, but detection sensitivity is limited due to short in-capillary path lengths

Engineering Contradiction:
Improveseparation speedVSAvoiddetection sensitivity
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The system is divided into two functional segments: a concentrating device (pre-column) and a separation capillary. The concentrating device accumulates analytes from a large volume sample, then transfers the concentrated analytes to the separation capillary for fast electrophoretic separation. This segmentation allows the detection sensitivity to be improved by concentration while maintaining the fast separation capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention adds a spatial dimension to the analysis by incorporating a concentrating device that occupies additional volume outside the narrow capillary. This external concentration chamber provides a larger path length and volume for analyte accumulation, compensating for the limited in-capillary path length and enhancing detection sensitivity without compromising separation speed.

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

2Measurement precision

If higher analyte concentrations are used for detection, then detection sensitivity improves, but sample manipulation issues and potential loss or contamination occur

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample integrity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention extracts the concentration function from the main capillary electrophoresis system and places it in a separate concentrating device. This extraction allows concentration to be achieved in a controlled environment with minimal sample manipulation, reducing the risk of sample loss or contamination while still achieving the required detection sensitivity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The concentrating device acts as an intermediary between sample introduction and capillary electrophoresis separation. It provides a buffer zone where samples can be concentrated under controlled conditions before entering the separation capillary, minimizing direct manipulation of the sample in the narrow capillary and reducing associated risks of loss or contamination.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If a sol-gel concentrating device is used to concentrate analytes, then detection sensitivity improves, but the monolith may become destabilized during polymerization

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmonolith stability
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The polymerization process is initiated and allowed to proceed to a sufficient degree before ethanol evaporation begins. This preliminary polymerization action creates a stable gel network that can withstand the subsequent evaporation process without destabilization, ensuring both monolith integrity and effective analyte concentration.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The polymerization and evaporation processes are conducted in periodic stages rather than simultaneously. First, polymerization occurs under controlled conditions to establish structural stability, then evaporation proceeds in a subsequent stage. This periodic action sequence prevents monolith destabilization while achieving the desired concentration effect.

Inventive Principle:
Principle #19Periodic action

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

The sol-gel concentrating device significantly improves the detection sensitivity of CZE by concentrating analytes, allowing for the analysis of low-concentration samples with enhanced peak resolution and reproducibility, even at very low concentrations, without destabilizing the monolith.

Implementation Method 1

a) filling a tube with a composition comprising an alkylsilicate material, ethanol, and particles; b) heating the composition in a step-wise manner at temperatures from 35°C to 60°C to accelerate polymerization of the slurry

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

heating the composition from b) at a temperature from 60°C to 80 °C to evaporate the ethanol; and c) curing the heated composition from c) at a temperature from 90°C to 130 °C

Methodology Applied
Scientific EffectCondensation: Condensation

Implementation Method 3

heating the composition from b) at a temperature from 60°C to 80 °C to evaporate the ethanol

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 4

a sol-gel concentrating device comprising a channel that contains a column of a monolith of a polymerized alkylsilicate gel matrix containing chromatographic sorbent particles

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 5

Capillary electrophoresis (CE) is a process for separating molecules based on their size or charge. In capillary electrophoresis molecules are introduced into a fluid-filled capillary tube and subjected to an electric field

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentEP1893967B1Methods for improving the sensitivity of capillary zone electrophoresis
Publication Date: 2015.11.04 BECKMAN COULTER INC
  • EP1893967B1 patent drawingFigure 1
  • EP1893967B1 patent drawingFigure 2
  • EP1893967B1 patent drawingFigure 3

AI summary

The present invention relates to novel methods and apparatus for improving the sensitivity of capillary zone electrophoresis (CZE). The invention particularly concerns devices comprising a channel that contains an in-line sol-gel column to concentrate samples being subjected to capillary zone electrophoresis, and the use of such devices to enhance the sensitivity of capillary zone electrophoresis.