Hydrophobic Thread Electrospray for Direct Microsample Analysis

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Solution Overview

Problem

Current microsampling methods face challenges in analyzing small biological samples due to issues with sample homogeneity, stability, and the need for dilution, which increases analysis time and requires sensitive instruments not always available in resource-limited settings, especially for dried blood spots and lyophilization/vitrification techniques.

Innovation Solution

A hydrophobic thread is used to stabilize biological samples by ionizing compounds with a suitable voltage, allowing for direct analysis using mass spectrometry without the need for dilution or extensive sample preparation, enabling efficient collection, preservation, and analysis of microsamples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If dilution steps are used to convert small sample volume into a form that can be handled by traditional large volume analytical methods, then the sample can be analyzed using conventional instruments, but the analysis time increases and sample stability, storage and integrity are negatively impacted

Engineering Contradiction:
Improvesample analysis capabilityVSAvoidanalysis time
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical dilution and sample preparation steps with direct electrospray ionization of microsamples. The electrospray source directly ionizes compounds from the microsample without requiring dilution or extensive preparation, eliminating the time-consuming mechanical operations of pipetting, mixing, and transferring diluted samples.

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

Solution Approach 2:

The patent extracts and eliminates the unnecessary dilution steps from the analytical workflow. By using electrospray ionization that can directly handle microsamples, the method removes the intermediate dilution process that was previously required to make samples compatible with conventional LC-MS systems.

Inventive Principle:
Principle #2Taking out (Extraction)

2Ease of operation

If dilution steps are used to convert small sample volume into a form that can be handled by traditional large volume analytical methods, then the sample can be analyzed using conventional instruments, but sample stability, storage and integrity are negatively impacted

Engineering Contradiction:
Improvesample analysis capabilityVSAvoidsample integrity
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent replaces mechanical dilution steps with direct electrospray ionization, eliminating multiple handling operations that can compromise sample integrity. The direct ionization approach maintains sample stability by avoiding repeated pipetting, mixing, and storage of diluted samples.

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

Solution Approach 2:

The patent performs direct ionization of the microsample without preliminary dilution steps. The electrospray source is configured to directly ionize compounds from the undiluted microsample, eliminating the need for prior sample preparation that could affect integrity.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If dilution is performed on small liquid samples, then the sample volume is increased to a handleable form, but the accuracy of low-volume aliquots becomes low

Engineering Contradiction:
Improvesample volumeVSAvoidaccuracy of low-volume aliquots
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent replaces mechanical dilution with direct electrospray ionization of microsamples. The electrospray source directly ionizes compounds from the original microsample without requiring aliquoting or dilution steps that introduce measurement errors and reduce accuracy.

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

4Adaptability or versatility

If analysis of diluted sample is performed, then the sample can be analyzed using traditional instruments, but a more sensitive instrument is required which might not be readily available in resource-limited settings

Engineering Contradiction:
Improveinstrument compatibilityVSAvoidinstrument sensitivity requirement
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent replaces mechanical dilution with direct electrospray ionization, enabling conventional LC-MS instruments to achieve sensitive detection without requiring upgraded hardware. The direct ionization of microsamples produces sufficient ion signal for detection using standard instruments available in resource-limited settings.

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

5Ease of manufacture

If traditional DBS method is used for sample collection, then sample collection is achieved, but analyte homogeneity is significantly affected

Engineering Contradiction:
Improvesample collection capabilityVSAvoidanalyte homogeneity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent uses a porous support structure to hold the microsample during electrospray ionization. The porous material allows uniform distribution of the microsample and facilitates consistent ionization, improving analyte homogeneity while maintaining ease of sample collection.

Inventive Principle:
Principle #31Porous materials

6Productivity

If capillary microsampling is used for collection of small liquid samples, then toxicology studies are improved by reducing the number of animals required, but direct sample analysis is not possible requiring extensive sample preparations

Engineering Contradiction:
Improvetoxicology study efficiencyVSAvoidsample preparation requirements
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces mechanical dilution and preparation steps with direct electrospray ionization of capillary microsamples. The electrospray source directly ionizes compounds from the collected microsample without requiring extensive preparation, enabling immediate analysis and maintaining the productivity benefits of reduced animal usage.

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

Solution Approach 2:

The patent extracts and eliminates the extensive sample preparation steps that follow capillary microsampling. By using direct electrospray ionization, the method removes the intermediate preparation steps while preserving the advantage of small sample volumes that reduce animal requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

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 allows for the direct analysis of microsamples without dilution, maintaining sample integrity and stability, and providing ultra-sensitive analyte detection, even at low concentrations, with improved homogeneity and storage capabilities, making it suitable for resource-limited settings and field studies.

Implementation Method 1

a hydrophobic thread is contacted with a biological sample. The hydrophobic thread stabilizes the biological sample over prolonged periods of time

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

Compounds, including small molecules and/or biopolymers, can be ionized by applying a suitable voltage to the tread

Methodology Applied
Scientific EffectElectrospray ionization: Ionisation

Data Source

PatentUS12169197B2Thread spray ambient ionization
Publication Date: 2024.12.17 OHIO STATE INNOVATION FOUND
  • US12169197B2 patent drawing
  • US12169197B2 patent drawing
  • US12169197B2 patent drawing

AI summary

Disclosed herein are methods and apparatus useful for the collection, preservation, and analysis of biological fluids. In some embodiments, a hydrophobic thread is contacted with a biological sample. The hydrophobic thread stabilizes the biological sample over prolonged periods of time. Compounds, including small molecules and/or biopolymers, can be ionized by applying a suitable voltage to the tread. These ionized compounds can then be analyzed, for instance using mass spectrometry.