U-Shaped Separation Device with Hydrophilic Apertures for Low-Volume Samples

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Solution Overview

Problem

Current methods for chromatographic and liquid-liquid separation face challenges with low volume samples due to large sorption surfaces and dead volumes, leading to reduced sample yield and analysis bias, particularly in submicrolitre volumes, where existing devices are not suitable for handling small-volume liquid-liquid systems effectively.

Innovation Solution

A device with a V- or U-shaped chamber having apertures of 1 to 100 micrometers, which are hydrophilized or hydrophobized, allowing selective separation of immiscible liquids using pressure forces, eliminating the need for frits or membranes and enabling parallel processing of low-volume samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a porous barrier (frit, filter, or membrane) is used to retain sorbent in chromatographic columns, then the sorbent is prevented from outflowing with the elution liquid, but the barrier creates large dead volume and sorption surface that irreversibly bind and reduce sample yield

Engineering Contradiction:
Improvesorbent retentionVSAvoidsample yield
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The invention extracts and removes the porous barrier (frit, filter, or membrane) from the chromatographic column system. Instead of using a barrier to retain sorbent, the column is designed without any bottom barrier, allowing the sorbent to be retained by centrifugal force or gravity alone. This eliminates the dead volume and sorption surface of the barrier, preventing irreversible sample binding and improving sample yield.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the mechanical barrier system (porous frit/filter/membrane) with a force-based retention system. Centrifugal force generated by rotating the column at controlled speeds retains the sorbent in place without requiring a physical barrier. This substitution eliminates the harmful effects of barriers while maintaining sorbent retention functionality.

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

2Quantity of substance

If conventional chromatographic columns with barriers are used, then separation can be performed, but the dead volume outweighs the sample volume in submicrolitre samples, making separation ineffective

Engineering Contradiction:
Improvesample volumeVSAvoiddead volume
Core Design Contradiction:
Quantity of substanceVSVolume of stationary object

Solution Approach 1:

The invention extracts and removes the barrier structure that creates dead volume. By eliminating the porous frit, filter, or membrane at the column bottom, the dead volume is reduced to minimal levels. This allows the actual sample volume (even at submicrolitre levels) to exceed the dead volume, making separation effective for trace and low-volume samples.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the operational parameters by introducing centrifugal force as the driving mechanism. By rotating the column at controlled speeds, the system achieves separation without requiring large volumes to overcome barrier dead volume. The centrifugal force parameter allows efficient separation of very small sample volumes that would be lost in conventional columns.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If large sorption surface barriers are used to prevent sorbent outflow, then separation is achieved, but a substantial portion of the sample is bound by adsorption on the barrier surface

Engineering Contradiction:
Improveseparation functionVSAvoidsample recovery
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The invention extracts and removes the barrier structure that provides the large sorption surface. By eliminating the porous frit, filter, or membrane, the adsorption sites that would bind and retain sample components are removed. This prevents substantial sample loss through adsorption while maintaining separation functionality through the barrier-free column design.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the barrier-based retention system with a centrifugal force-based system. Instead of relying on the barrier surface to retain sorbent, centrifugal force generated by column rotation retains the sorbent particles. This substitution eliminates the adsorption problem associated with barrier surfaces while maintaining effective separation.

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

4Quantity of substance

If manual liquid-liquid separation techniques are used, then phase separation is achieved, but parallel processing of multiple low volume samples is precluded

Engineering Contradiction:
Improvesample volumeVSAvoidparallel processing capability
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The invention segments the separation system into multiple independent column units that can be processed simultaneously. Each column operates as an independent separation unit, allowing multiple low-volume samples to be separated in parallel. The centrifugal extraction device can accommodate multiple columns, enabling high-throughput processing of numerous samples without requiring manual sequential operations.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention replaces manual liquid-liquid separation operations with an automated centrifugal extraction system. The centrifugal device automatically performs phase separation by rotating the columns, eliminating the need for manual pipetting and separation steps. This automation enables parallel processing of multiple samples simultaneously, dramatically increasing productivity while maintaining compatibility with low-volume samples.

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

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 device enhances sample yield by minimizing dead volume and irreversible binding, allowing efficient separation of nanoliter volumes and enabling parallel processing of multiple samples, while simplifying production and avoiding interference with the separation process.

Implementation Method 1

at least the surface of each aperture is hydrophilized or hydrophobized

Methodology Applied
Scientific EffectHydrophile: Hydrophile

Implementation Method 2

The aperture in the first (upper) chamber is located at the tip or at the lowest point of the V- or U-shaped bottom... The surface of the aperture is the surface of the passage through the wall of the first chamber

Methodology Applied
Scientific EffectWetting: Wetting

Implementation Method 3

The centrifugal force is commonly applied in chromatographic separation by spin microcolumns... suitable for use in swing rotor centrifugation, or for applying overpressure or vacuum (negative pressure) as a pressure force to stimulate sample flow

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 4

application of pressure forces, which include the application of overpressure, vacuum (negative pressure) or centrifugal force

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Data Source

PatentUS20230113229A1Device and method for separation of components of a sample
Publication Date: 2023.04.13 USTAV HEMATOLOGIE A KREVNI TRANSFUZE
  • US20230113229A1 patent drawing
  • US20230113229A1 patent drawing
  • US20230113229A1 patent drawing

AI summary

A device and method for separation of components of a sample, in particular for pressure separation of immiscible or liquid systems with limited miscibility having at least one first chamber with a U- or V-shaped bottom wherein at least one aperture with a diameter within the range of 1 to 100 μm, preferably 1 to 40 μm, is provided in the first chamber and at least the surface of each aperture is hydrophilized or hydrophobized is disclosed. The device further has a second chamber surrounding the outside of the bottom of the first chamber. The invention also provides a method for separating components of a sample using this device and additionally enables parallel arrangement for plurality of separating conditions and serial arrangement for plurality of separated samples at the same time.