Microcolumn with Reduced Diameter Bed for Analyte Extraction

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Solution Overview

Problem

Existing microcolumns for analyte extraction from liquid samples, particularly biological fluids, face challenges in improving process throughput, reducing environmental impact, minimizing media bed volume, ensuring transportability and storage stability, maintaining uniform flow, and compatibility with automated equipment while preventing leaching of interfering compounds.

Innovation Solution

The design incorporates a microcolumn with a full diameter and reduced diameter region, featuring an air gap layer, microparticulate extraction media with small particle sizes, and compression layers to enhance analyte extraction efficiency and sensitivity, while minimizing dead volumes and elution liquid volumes, and is compatible with existing automated systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If the media bed volume is minimized to reduce elution liquid volume and enhance sensitivity, then the extraction efficiency improves, but the flow uniformity becomes difficult to maintain and channeling may occur

Engineering Contradiction:
Improvemedia bed volumeVSAvoidflow uniformity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent applies local quality by creating a reduced-diameter region at the bottom of the column with a different diameter than the upper portion. This localized structural change allows the media bed to be compressed into a smaller volume while maintaining proper flow distribution through the specially designed transition zone and air gap layer, preventing channeling despite the minimized bed volume.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The air gap layer serves as an intermediary element between the compression layer and the extraction media. This air gap acts as a buffer that helps distribute flow uniformly across the media bed while allowing the bed to be compacted into a reduced-diameter region, thus maintaining flow uniformity despite the minimized media volume.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If the particle size of extraction media is reduced to increase extraction efficiency, then the analyte removal percentage improves, but the pressure drop across the bed increases and flow uniformity decreases

Engineering Contradiction:
Improveextraction efficiencyVSAvoidpressure drop
Core Design Contradiction:
ProductivityVSStress or pressure

Solution Approach 1:

The patent uses local quality by confining the fine particle size media to a reduced-diameter region rather than using fine particles throughout the entire column. This localized approach allows high extraction efficiency in the active extraction zone while the larger diameter upper portion and transition zone help manage pressure drop and maintain overall flow uniformity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The column is segmented into different diameter regions - a full diameter upper portion and a reduced diameter lower portion containing the extraction media. This segmentation allows the use of fine particles for high extraction efficiency in the reduced-diameter region while the overall column structure manages pressure effects.

Inventive Principle:
Principle #1Segmentation

3Quantity of substance

If a reduced diameter region is introduced to minimize dead volume and improve sensitivity, then the elution volume decreases, but the device complexity increases

Engineering Contradiction:
Improveelution volumeVSAvoidcolumn structure
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The column structure is segmented into a full diameter upper region and a reduced diameter lower region. This segmentation minimizes dead volume in the elution path while maintaining a relatively simple overall structure that can be manufactured using standard techniques, balancing complexity reduction with performance improvement.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a dimensional change by varying the column diameter along its length rather than maintaining a uniform diameter. This dimensional variation allows the creation of a reduced-diameter region that minimizes dead volume and elution volume while the transition zones manage the structural complexity.

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

4Productivity

If the ratio of full diameter region area to reduced diameter region area is increased to improve extraction capacity, then the analyte extraction efficiency improves, but the device complexity and manufacturing difficulty increase

Engineering Contradiction:
Improveextraction capacityVSAvoidmanufacturing difficulty
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent applies local quality by creating a reduced-diameter region with specific area ratios optimized for extraction capacity. The transition zones between different diameter regions are designed to manage flow uniformly, allowing high extraction capacity while maintaining manufacturability through standardized transition designs that can be produced using conventional manufacturing techniques.

Inventive Principle:
Principle #3Local quality

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 configuration significantly improves analyte extraction efficiency, reduces elution volumes, enhances sensitivity, and ensures compatibility with automated equipment, making the process more cost-effective and environmentally friendly.

Implementation Method 1

an air gap layer is located between layer (i') and layer (ii')

Methodology Applied
Scientific EffectPressure equalization: Pressure Gradient

Implementation Method 2

particulate silica has been used as the solid media in a column

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

media has been sandwiched between frits in a in a column

Methodology Applied
Scientific EffectCompression: Compression

Data Source

PatentEP3146331B1Sample extraction apparatus with micro elution bed design
Publication Date: 2021.02.17 TECAN SP INC
  • EP3146331B1 patent drawingFigure 1A~1B
  • EP3146331B1 patent drawingFigure 2A~3
  • EP3146331B1 patent drawingFigure 4

AI summary

An apparatus for extracting an analyte from a liquid sample having a container with an entrance, an exit, and a passage therebetween for passage of a liquid sample containing an analyte, the container having a full diameter bed region and a reduced diameter bed region. The container includes a layered construction extending across the passage, having from top to bottom: (i) an upper flow distributor/support layer, (ii) an upper compression layer, (iii) an extraction layer of microparticulate extraction medium adjacent to the layer (ii), and (iv) a lower compression layer located adjacent to the extraction layer (iii). At least some of the layers are located in the full diameter bed region, and some of the layers are located in the reduced diameter bed region.