LC-MS Interface Using Microcapillary Vaporization for Vacuum Preservation

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Solution Overview

Problem

The combination of liquid chromatography with mass spectrometry is hindered by the need to convert the liquid phase to gas before entering the ionization chamber, which disrupts vacuum levels and compromises analysis precision, and existing solutions like electrospray ionization provide limited structural information.

Innovation Solution

A machine combining liquid chromatography with electronic ionization mass spectrometry using a microcapillary tube and vaporization microcannula, where the liquid phase is vaporized by an inert gas and heated to a controlled temperature within a T-shaped device, ensuring efficient vaporization and preservation of structural information.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If liquid phase is converted to gas phase before entering the ionization chamber, then the molecules can be ionized by electronic ionization, but the vacuum levels in the ionization chamber are compromised

Engineering Contradiction:
Improveionization capabilityVSAvoidvacuum level disruption
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

A capillary interface tube serves as an intermediary component between the liquid chromatography outlet and the mass spectrometer ionization chamber. This capillary allows the liquid phase to be introduced directly into the ionization chamber without requiring conversion to gas phase, thereby maintaining vacuum levels while enabling electronic ionization of the analyte molecules

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical state parameter of the mobile phase by maintaining it in liquid form through the capillary interface, rather than converting to gas phase. This parameter change allows direct introduction of liquid chromatography effluent into the mass spectrometer while preserving vacuum conditions in the ionization chamber

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If a device is added to remove part of the liquid phase, then vacuum levels are preserved, but the precision of quantitative analysis is compromised

Engineering Contradiction:
Improvevacuum level maintenanceVSAvoidquantitative analysis precision
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The capillary interface tube acts as a mediator that eliminates the need for additional liquid removal devices. By allowing direct introduction of the liquid phase into the ionization chamber, it preserves both vacuum levels and the integrity of the chromatographic separation, thereby maintaining quantitative analysis precision

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention extracts or eliminates the need for intermediate liquid removal devices from the system. By using a direct capillary interface, it removes the problematic step of liquid phase removal that would otherwise be needed to preserve vacuum levels, thereby avoiding compromise to quantitative precision

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If electrospray ionization is used to ionize molecules from liquid chromatography, then macromolecules can be ionized without fragmentation, but structural information in the mass spectrum is limited

Engineering Contradiction:
Improveionization of macromoleculesVSAvoidstructural information
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

Instead of using electrospray ionization which preserves molecular integrity but loses structural information, the invention inverts the approach by using electronic ionization which provides rich structural information through fragmentation. The capillary interface enables this inversion by allowing direct introduction of liquid chromatography effluent into the electronic ionization source

Inventive Principle:
Principle #13The other way round (Inversion)

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 setup allows for precise vaporization and ionization of volatile and semi-volatile molecules, enhancing the quality of mass spectra for analyte identification without compromising vacuum levels or requiring additional liquid removal devices.

Implementation Method 1

the liquid phase is vaporized by an inert gas and heated to a controlled temperature within a T-shaped device

Methodology Applied
Scientific EffectVaporization: Evaporation

Implementation Method 2

heated to a controlled temperature within a T-shaped device

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 3

electronic ionization mass spectrometry

Methodology Applied
Scientific EffectElectronic ionization: Ionisation

Implementation Method 4

electron ionization or electron impact ionization

Methodology Applied
Scientific EffectElectron impact ionization: Electron Impact Desorption

Data Source

PatentEP3695223B1Machine for chemical analysis comprising the combination of electron ionization mass spectrometry with liquid chromatography
Publication Date: 2021.08.04 FAMIGLINI GIORGIO
  • EP3695223B1 patent drawingFigure 1

AI summary

A chemical analysis machine (1) comprising a liquid phase chromatograph (2) comprising, in turn, a chromatography nano-column with an inner diameter that is smaller than or equal to 100 μm, a mass spectrometer (3) with an electronic ionization source, and a joining assembly (4) interposed between the liquid phase chromatograph (2) and the mass spectrometer (3). The joining assembly (4) comprises a microcapillary tube (8) having an inner diameter smaller than or equal to 50 μm and having a first end (9a), which is directly connected to an outlet end of the nano-column (7) so as to receive the liquid phase, and a second end (9b), which is housed inside a vaporization microcannula (10) where an inert gas flows. The vaporization microcannula (10) is partially engaged by the microcapillary tube (8) and has an end (15) facing the inside of an ionization chamber of the mass spectrometer (3). The vaporization microcannula (10) is subdivided into a first part (10a), which is subjected to the action of a heating device (16), and a second part (10b), which is kept at room temperature and has a length that is greater than or equal to 2 cm. The microcapillary tube (8) occupies the inside of the entire second part (10b) of the vaporization microcannula (10) and has an end portion (8a) that is arranged inside the first part (10a) and has a length that is less than or equal to 5 mm.