Ion Source Expanding Beam for Biomolecule Fragmentation

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Solution Overview

Problem

Current mass spectrometers and ion mobility spectrometers lack an effective ion activation mechanism to unfold and fragment larger biomolecules at high pressures without causing electrical discharge, limiting their ability to analyze complex biological samples.

Innovation Solution

The implementation of an ion source with a reduced-pressure chamber and an ion transfer device that emits ions and neutral gas molecules as an expanding beam, allowing for increased collision energy through an electric field without voltage breakdown, enabling ion activation, unfolding, and fragmentation of biomolecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If high collision energy is applied to activate and fragment ions in high-pressure regions, then ion activation and fragmentation effectiveness is improved, but electrical discharge occurs

Engineering Contradiction:

Improvecollision energyVSAvoidelectrical discharge

Core Design Contradiction:

Use of energy by moving objectVSObject-affected harmful factors

Solution Approach 1:

The system divides the pressure environment into distinct regions: a high-pressure ionization chamber for ion generation, a medium-pressure activation region for controlled ion activation and fragmentation, and a low-pressure transmission region for ion delivery to the analyzer. This segmentation allows high collision energy to be applied in the medium-pressure region without causing electrical discharge in the high-pressure ionization chamber.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A pressure gradient interface acts as an intermediary between the high-pressure ionization chamber and the low-pressure analyzer region. This interface enables controlled transmission of ions while maintaining distinct pressure environments, allowing high collision energy activation without electrical discharge by isolating the activation region from the high-pressure zone.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If atmospheric pressure ionization is used to produce ions, then ionization efficiency is improved, but ion activation and fragmentation cannot be achieved without electrical discharge

Engineering Contradiction:

Improveionization efficiencyVSAvoidion activation capability

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The system separates the ionization function (performed at atmospheric pressure in the ionization chamber) from the activation and fragmentation function (performed at medium pressure in the activation region). This segmentation allows atmospheric pressure ionization to maintain high ionization efficiency while the downstream activation region provides ion activation and fragmentation capabilities without causing electrical discharge.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Ions are pre-formed in the atmospheric pressure ionization chamber with high ionization efficiency, then transmitted through the pressure gradient interface to the activation region where collision-induced fragmentation is applied. This preliminary ionization at atmospheric pressure enables subsequent activation without electrical discharge by decoupling the ionization and activation steps.

Inventive Principle:

Principle #10Preliminary action

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 approach allows for higher ion activation energies in high-pressure regions, effectively unfolding large biomolecules and improving desolvation and declustering, enabling more comprehensive structural analysis of biological samples without electrical discharge.

Implementation Method 1

The ion transfer device may be positioned to emit ions and neutral gas molecules from the outlet as an expanding beam comprising a low-gas density zone

Methodology Applied

Scientific EffectGas expansion:

Implementation Method 2

The outlet and the electrode may be configured to generate an electric field therebetween to accelerate ions emitted from the outlet to a collision energy that is effective to induce ion activation of ions in the reduced-pressure chamber without voltage breakdown

Methodology Applied

Scientific EffectElectrical acceleration: Electric Field

Implementation Method 3

subjecting the ions emitted into the reduced-pressure chamber to an electric field that accelerates the ions to a collision energy that is effective to induce ion activation of the ions without voltage breakdown

Methodology Applied

Scientific EffectCollision-induced dissociation:

Implementation Method 4

enabling ion activation, unfolding, and fragmentation of biomolecules

Methodology Applied

Scientific EffectCollision-induced unfolding:

Data Source

PatentUS20230126290A1Ion activation and fragmentation in sub-ambient pressure for ion mobility and mass spectrometry

Publication Date: 2023.04.27 AGILENT TECHNOLOGIES INC

AI summary

An ion source may include an ionization chamber to be maintained at atmospheric-pressure. The ion source may further include a reduced-pressure chamber to be maintained at sub-atmospheric pressure, and an ion transfer device comprising an inlet in the ionization chamber and an outlet in the reduced-pressure chamber. The ion transfer device may define an ion path from the inlet to the outlet. The ion transfer device may be positioned to emit ions and neutral gas molecules from the outlet as an expanding beam comprising a low-gas density zone enveloped by a high-gas density region that includes a gas density that is higher than the low-gas density zone. The ion source may be utilized, for example, for ion mobility spectrometry (IMS), mass spectrometry (MS), and hybrid IM-MS.