Dual-Electrode Mass Spectrometry Probe for In-Situ Desalting

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Solution Overview

Problem

Mass spectrometers face challenges in analyzing samples with high ionic strength media due to adduct formation between cations and anions, which leads to convoluted data, reduced sensitivity, and suppressed analyte signals, especially in high salt conditions, where existing methods like polymeric gels or chemical modifiers have minimal effect.

Innovation Solution

Dual-electrode mass spectrometry probes create an electrophoretic field to rapidly desalt spray solutions by displacing interfering solution-phase ions, using a hollow conductive conduit and an electrode to polarize the liquid sample, allowing for the separation of ions away from the analytical region, thereby improving the analytical performance of peptides, proteins, and pharmaceuticals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If polymeric gels or liquid chromatography are used to remove salts, then adduct formation is reduced, but the device complexity and analysis time increase significantly

Engineering Contradiction:
Improveadduct formationVSAvoiddevice complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts and removes interfering solution-phase ions (such as Na+, K+, Ca2+, and their corresponding anions) from the spray solution using electrophoretic forces generated by the dual-electrode probe. This extraction of harmful ions occurs in-situ within the probe structure, eliminating the need for separate desalting devices like polymeric gels or liquid chromatography systems, thereby reducing device complexity while effectively preventing adduct formation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an electrophoretic field as an intermediary mechanism between the high salt concentration sample and the mass spectrometer detector. The dual-electrode probe creates this field to mediate the separation and removal of ions that would otherwise form adducts with analytes, providing a cleaner signal without requiring complex pre-treatment devices.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If polymeric gels or liquid chromatography are used to remove salts, then adduct formation is reduced, but the analysis time increases significantly

Engineering Contradiction:
Improveadduct formationVSAvoidanalysis time
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent performs preliminary desalting action directly within the probe structure before the sample enters the mass spectrometer. The electrophoretic field is established in advance to remove interfering ions from the spray solution, so that when analysis begins, the ions are already separated. This eliminates the need for time-consuming post-sample-preparation steps associated with polymeric gels or liquid chromatography.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent rushes through the desalting process by applying strong electrophoretic forces that rapidly migrate interfering ions away from the analytical region in seconds. This rapid ion removal skips the lengthy separation processes required by traditional methods, enabling fast analysis while still effectively preventing adduct formation.

Inventive Principle:
Principle #21Skipping (Rushing through)

3Object-affected harmful factors

If chemical modifiers such as acids or bases are added to reduce adduct formation, then some adducts are reduced, but under high salt conditions the effect is minimal and the data becomes convoluted

Engineering Contradiction:
Improveadduct formationVSAvoiddata quality
Core Design Contradiction:
Object-affected harmful factorsVSLoss of information

Solution Approach 1:

The patent replaces chemical modification approaches with a physical electrophoretic separation mechanism. Instead of adding acids or bases to chemically alter ion behavior, the dual-electrode probe uses electrical forces to physically separate and remove interfering ions from the spray solution. This mechanical/physical approach works effectively even under high salt conditions where chemical modifiers fail, and does not introduce additional chemical complexity that would convolute the data.

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

4Device complexity

If traditional single-electrode probes are used, then the structure is simpler, but ions cause multiple signals and suppressed analyte signals

Engineering Contradiction:
Improvedevice complexityVSAvoidsignal quality
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent segments the electrode system into two separate electrodes within the probe structure: a front electrode and a rear electrode. This segmentation allows independent control of electrical potentials to create an electrophoretic field that separates interfering ions from the spray region. The segmented electrode design adds minimal structural complexity compared to a single electrode while dramatically improving signal quality by preventing adduct formation and ion suppression.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent adds a spatial dimension to ion separation by positioning electrodes at different locations (front and rear) along the probe axis. This dimensional arrangement creates an electrophoretic field that acts in the axial direction, migrating ions away from the spray region along the length of the probe. This dimensional approach to ion management improves measurement precision without requiring complex lateral or radial separation mechanisms.

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

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 method effectively removes ions that cause adduct formation, resulting in improved signal-to-noise ratios and reduced cationic adducts, allowing for accurate analysis of therapeutic pharmaceuticals, peptides, and proteins, even in high salt conditions, with the desalting effect persisting for long periods.

Implementation Method 1

Aspects of the invention make use of electrophoretic forces to displace interfering solution-phase ions prior to chemical analysis, i.e., move solution-phase ions to a region of the solution remote from the sprayer

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

The hollow conduit polarizes the liquid sample as the liquid sample flows through the hollow conduit and into the hollow body. This generates a charge body of solution which is connected via the external hollow conduit to one pole of the power supply

Methodology Applied
Scientific EffectElectrical conduction: Conduction (electrical)

Implementation Method 3

When the appropriate electrical potentials (e.g., DC potentials) are applied to the electrode, the ions migrate to the rear of the capillary, away from the tip of the hollow body

Methodology Applied
Scientific EffectIon migration in electric field: Electrophoresis

Data Source

PatentUS11854781B2Electrophoretic mass spectrometry probes and systems and uses thereof
Publication Date: 2023.12.26 AMGEN INC
  • US11854781B2 patent drawing
  • US11854781B2 patent drawing
  • US11854781B2 patent drawing

AI summary

The invention generally relates to electrophoretic mass spectrometry probes and systems and methods of uses thereof. In certain aspects, the invention provides a mass spectrometry probe having a hollow body with a distal tip, an electrically conductive hollow conduit, and an electrode. The electrically conductive hollow conduit may be operably coupled to a reservoir and a power source, and the electrically conductive hollow conduit may be configured to transport a liquid sample into the hollow body and polarize the liquid sample as it flows through the electrically conductive hollow conduit and into in the hollow body. The electrode and the electrically conductive hollow conduit are disposed within the hollow body (e.g., at different heights within the hollow body).