Charge-Stripping Multiply-Charged Ions Mass Spectrometry
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Solution Overview
Problem
Current mass spectrometry techniques, such as MALDI-TOF-MS and ESI-TOF-MS, face challenges in resolving and detecting large peptides or proteins due to inadequate structural information and congested spectra, especially with PEGylated compounds, and existing charge stripping methods using radioactive sources are unstable and inefficient.
Innovation Solution
A field-free reaction region at atmospheric pressure is used for stable charge stripping, generating reagent ions without electric fields, and employing high-energy photons and neutral molecules with high electron affinity to reduce the charge states of analyte ions via gas-phase ion/ion reactions, ensuring minimal fragmentation and improved sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If MALDI-TOF-MS is used for polymer characterization, then singly-charged ions are generated, but resolving power and detection efficiency decrease with increasing mass to charge ratio
Solution Approach 1:
The invention changes the charge state parameter of the ions by using charge stripping reactions. Multiply charged ions generated by ESI are converted to singly charged or less highly charged ions through reactions with reagent ions in a field-free region, thereby changing the mass-to-charge ratio to improve resolution and detection efficiency without altering the molecular mass itself.
2Measurement precision
If ESI-TOF-MS is used for polymer analysis, then multiply charged ions are generated suitable for resolution, but peak envelopes overlap making spectra congested and uninterpretable
Solution Approach 1:
The invention changes the charge state parameter of the ions by using charge stripping reactions. Multiply charged ions generated by ESI are converted to singly charged or less highly charged ions through reactions with reagent ions in a field-free region, thereby changing the mass-to-charge ratio to improve resolution and detection efficiency without altering the molecular mass itself.
3Measurement precision
If radioactive sources are used to generate reagent ions for charge stripping, then charge states are reduced, but stability issues arise from natural decay of radioactivity
Solution Approach 1:
The invention replaces long-lived radioactive sources with a short-lived electrical discharge plasma source that generates reagent ions on-demand. The plasma is created by applying a high voltage pulse to a needle electrode in the presence of a buffer gas, producing a burst of reagent ions that immediately react with the analyte ions. This eliminates radioactive decay stability issues while providing sufficient reagent ions for charge stripping.
4Quantity of substance
If highly charged electrified sprayer is used in ESI, then multiply charged ions are generated, but it interferes with oppositely charged reagent ions and affects charge reduction reactions
Solution Approach 1:
The invention spatially segments the ion generation and charge stripping processes into distinct regions. The electrified sprayer generates multiply charged ions in the electrospray region, while a separate field-free region contains the plasma discharge and reagent ions. A drift region with buffer gas allows the multiply charged ions to travel from the sprayer to the reaction zone without significant interference from the highly charged sprayer, enabling efficient charge reduction reactions.
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 provides stable, reproducible, and sensitive charge stripping for structural characterization of polymers like PEGs and PEGylated compounds, enabling effective analysis of large molecules with reduced peak overlap and improved spectral clarity.
Implementation Method 1
employing high-energy photons and neutral molecules with high electron affinity to reduce the charge states of analyte ions via gas-phase ion/ion reactions
Implementation Method 2
A field-free reaction region at atmospheric pressure is used for stable charge stripping, generating reagent ions without electric fields
Implementation Method 3
employing high-energy photons and neutral molecules with high electron affinity to reduce the charge states of analyte ions via gas-phase ion/ion reactions
Data Source
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AI summary
A method of mass spectrometry or ion mobility spectrometry is disclosed wherein a sample is ionized by an electrified sprayer so as to produce multiply charged analyte ions of a first polarity in gas-phase. A reaction region is provided downstream of the electrified sprayer, wherein the reaction region is maintained substantially at atmospheric pressure and is maintained substantially free of electric-fields. A gas flow is provided from said electrified sprayer to said reaction region such that the gas flow carries the analyte ions from the electrified sprayer into the reaction region. Free electrons or reagent ions of a second polarity are generated in the reaction region, wherein the second polarity is opposite to said first polarity. The free electrons or reagent ions are then reacted with the analyte ions in the reaction region so as to reduce the charge state of the multiply charged analyte ions and thereby produce charge-reduced analyte ions.