Heated Capillary Thermal Dissociation for Mass Spectrometry

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Solution Overview

Problem

Conventional mass spectrometry systems face challenges in effectively fragmenting high molecular weight species, such as proteins and antibodies, which limits their ability to provide detailed structural information and efficient analysis.

Innovation Solution

The method involves thermally-induced dissociation of ions within the ionization/fragmentation region of the mass spectrometry system by increasing the temperature of ions to an elevated temperature, typically above 550°C, to break down high molecular weight species into smaller subunits, enhancing fragmentation efficiency and facilitating downstream analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional RF collisional cooling and radial focusing is used in the ion guide, then ions are effectively transported to the mass analyzer, but high molecular weight species are not effectively fragmented

Engineering Contradiction:
Improveion transport efficiencyVSAvoidfragmentation efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent introduces a heated capillary interface that raises the temperature of ions to elevated levels (typically 300-1000°C) during transfer, fundamentally changing the thermal parameter of the ion transport process. This temperature elevation enables effective fragmentation of high molecular weight species while maintaining ion transmission through the interface region.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The heated capillary acts as an intermediary component between the ion source and the mass analyzer. It provides a controlled thermal environment that facilitates fragmentation during the transfer process, serving as a mediator that reconciles the need for both ion transport and ion fragmentation that cannot be achieved in the conventional RF ion guide alone.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If thermal dissociation is applied to fragment high molecular weight ions, then fragmentation efficiency improves, but diffusional losses increase

Engineering Contradiction:
Improvefragmentation efficiencyVSAvoidion loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The heating is applied locally in the capillary interface region rather than throughout the entire ion path. This localized thermal treatment allows fragmentation to occur in a confined zone where ions can be efficiently re-focused and transmitted, minimizing diffusional losses in other regions of the system.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The heated capillary interface enables ions to rapidly pass through the fragmentation zone and be transmitted to the mass analyzer before significant diffusional losses can occur. The design allows ions to 'rush through' the thermal field quickly, minimizing exposure time and reducing losses.

Inventive Principle:
Principle #21Skipping (Rushing through)

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 significantly improves the fragmentation efficiency of high molecular weight species, allowing for enhanced structural information and analysis, with fragmentation efficiencies of at least 70% to 95%, and minimizes diffusional losses by maintaining a surface-free path for the fragment ions.

Implementation Method 1

increasing the temperature of ions to an elevated temperature, typically above 550°C, to break down high molecular weight species into smaller subunits

Methodology Applied
Scientific EffectThermal dissociation: Thermolysis

Data Source

PatentUS20220293406A1Apparatus and methods for thermal dissociation in a mass spectrometry system
Publication Date: 2022.09.15 DH TECH DEVMENT PTE
  • US20220293406A1 patent drawing
  • US20220293406A1 patent drawing
  • US20220293406A1 patent drawing

AI summary

Apparatus, systems and methods disclosed herein utilize an ion source region generally disposed between a sample introduction port and an ion guide of a mass spectrometry system to thermally fragment ions for transmission to and analysis by a downstream mass analyzer. In various aspects, the present disclosure provides methods of thermally fragmenting ions in an ion source region of a mass spectrometry system. Thermally fragmenting a plurality of ions can include increasing a temperature of the ions present in an ion source region. Thermally fragmenting a plurality of ions can include increasing the temperature of the ions in an ionization/fragmentation region associated with an ion source region defined by a substantially collision-free path. Implementations of the present disclosure are useful in mass spectrometry systems, including, for example, generating an enhanced fragmentation pattern.