Ion Mobility TOF Mass Spectrometry for High-Duty Precursor Selection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional mass spectrometers face a challenge in achieving a high duty cycle when increasing the rate of precursor ion selection, leading to a linear drop in sensitivity for detected ions.
Innovation Solution
A method involving ion accumulation, separation, mass filtering, fragmentation or reaction, and synchronized release of ions into a TOF mass analyzer, allowing multiple fragment or product ion species to be analyzed simultaneously, with synchronization between ion accumulators and the TOF mass analyzer to enhance duty cycle.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the rate of precursor ion selection is increased to improve productivity, then more precursor species can be analyzed per unit time, but sensitivity drops linearly due to fewer ions in each fragment ion scan
Solution Approach 1:
The ion mobility separator performs separation of precursor ions before the QMS selects and transmits them for fragmentation. This preliminary separation allows the system to rapidly cycle through different precursor species while maintaining adequate ion counts for each, as ions are pre-sorted by mobility rather than being sequentially selected from a mixed population.
Solution Approach 2:
The system segments the ion population by mobility using the ion mobility separator, creating distinct mobility-based groups that can be rapidly cycled through the QMS. This segmentation allows multiple precursor species to be analyzed in succession without the sensitivity loss that occurs in conventional sequential scanning, where all ions must be collected before selection begins.
2Measurement precision
If conventional sequential selection of precursor ions is used to maintain measurement precision, then sensitivity is preserved, but productivity decreases due to linear drop in ions per scan
Solution Approach 1:
The ion mobility separator performs separation of precursor ions before the QMS selects and transmits them for fragmentation. This preliminary separation allows the system to rapidly cycle through different precursor species while maintaining adequate ion counts for each, as ions are pre-sorted by mobility rather than being sequentially selected from a mixed population.
Solution Approach 2:
The ion mobility separator operates continuously to separate precursor ions by mobility, providing a steady stream of sorted ions to the QMS. This continuous separation process eliminates the idle time and ion loss associated with conventional sequential scanning, where the system must wait for complete ion collection between selection cycles.
3Productivity
If multiple precursor ion species are transmitted simultaneously to improve productivity, then more ions can be analyzed in parallel, but mass filtering precision deteriorates due to inability to resolve individual species
Solution Approach 1:
The ion mobility separator performs separation of precursor ions before the QMS selects and transmits them for fragmentation. This preliminary separation allows the system to rapidly cycle through different precursor species while maintaining adequate ion counts for each, as ions are pre-sorted by mobility rather than being sequentially selected from a mixed population.
Solution Approach 2:
The system applies different selection criteria to different mobility-separated ion groups. The QMS is configured to transmit specific m/z ranges corresponding to particular precursor species that have been spatially separated by mobility, allowing precise mass filtering for each species while maintaining high overall throughput through parallel processing of multiple mobility groups.
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 achieves a high duty cycle by ensuring that precursor ions are fragmented and analyzed while others are delayed, rather than discarded, thereby improving the overall efficiency of the mass spectrometer.
Implementation Method 1
releasing the set of fragment or product ion species from the second ion accumulator into a TOF mass analyser
Implementation Method 2
wherein operation of the TOF mass analyser is synchronised with the release of ions from the second ion accumulator such that multiple different species of the set of fragment or product ion species are simultaneously pulsed into a time of flight region of the TOF mass analyser by a pusher electrode
Implementation Method 3
The ion separator may be an ion mobility separator configured to drive ions through a background gas arranged therein. The ions may be driven through the background gas by an electric field in order that they separate according to mobility.
Implementation Method 4
mass filtering the precursor ions that elute from the ion separator so as to transmit a selected precursor ion species
Data Source
AI summary
A method of mass spectrometry comprising: a) accumulating precursor ions in a first ion accumulator; b) performing a separation cycle comprising pulsing a packet of the precursor ions out of the first ion accumulator and into an ion separator, and separating the precursor ions such that precursor ions having different values of a first physicochemical property elute from the ion separator at different times; c) mass filtering the precursor ions that elute from the ion separator so as to transmit a selected precursor ion species; d) fragmenting or reacting the selected precursor ion species so as to generate a set of fragment or product ion species therefrom; e) accumulating the set of fragment or product ion species in a second ion accumulator; f) releasing the set of fragment or product ion species from the second ion accumulator into a TOP mass analyser, wherein operation of the TOP mass analyser is synchronised with the release of ions from the second ion accumulator such that multiple different species of the set of fragment or product ion species are simultaneously pulsed into a time of flight region of the TOP mass analyser by a pusher electrode; and g) repeating steps c) to f) at least once during said separation cycle, wherein said selected precursor ion species is different each time steps c) to f) are performed.