TOF Mass Spectrometry Pulse Sequencing for High Duty Cycle
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Solution Overview
Problem
Conventional mass spectrometers face a challenge in increasing the duty cycle while maintaining sensitivity, as speeding up the selection of precursor ions leads to a linear drop in detected ion sensitivity.
Innovation Solution
A method involving a mass spectrometer with an ion separator and a time-of-flight (TOF) mass analyzer that pulses ions into a separation region, performs multiple separation cycles with varying pulse sequences, and combines mass spectral data from these cycles before decoding to enhance sensitivity and duty cycle.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the rate at which precursor species are selected is increased, then productivity is improved, but sensitivity deteriorates
Solution Approach 1:
The patent implements periodic action by using cyclic ion separator operation where ions are separated in discrete cycles and then pushed in batches to the TOF analyzer. The ion separator performs multiple separation cycles, accumulating ions of different precursor species in temporal sequence, then transfers them to the TOF analyzer in organized batches. This periodic operation allows the system to maintain high selection rates while ensuring sufficient ion accumulation for sensitive detection.
Solution Approach 2:
The patent applies preliminary action by performing ion separation and accumulation in the ion separator before transferring to the TOF analyzer. Ions are pre-separated by mass-to-charge ratio in the ion separator during multiple cycles, building up sufficient ion populations before the actual detection phase. This preliminary separation and accumulation ensures that when ions are pushed to the TOF analyzer, there are enough ions for sensitive measurement even though the selection rate is high.
2Productivity
If the number of precursor species transmitted per second is increased, then productivity is improved, but the number of ions per fragment ion scan decreases, worsening sensitivity
Solution Approach 1:
The patent applies segmentation by dividing the ion analysis process into distinct functional segments: the ion separator segment that performs mass-based separation in cyclic operations, and the TOF analyzer segment that performs detection. The ion separator segments ions by mass-to-charge ratio across multiple cycles, accumulating different precursor species in temporal sequence. This segmentation allows the system to handle many precursor species per second while maintaining sufficient ion numbers in each detection segment by organizing them into coherent batches.
Solution Approach 2:
The ion separator performs preliminary action by pre-separating and accumulating ions of different precursor species before they reach the TOF analyzer. During multiple separation cycles, the ion separator builds up ion populations for each mass-to-charge ratio in temporal sequence. This preliminary accumulation ensures that when ions are transferred to the TOF analyzer, there are sufficient numbers of ions for each precursor species despite the high transmission rate, because the ions have been pre-concentrated in organized batches.
3Device complexity
If conventional single-cycle decoding is used, then device complexity is low, but sensitivity deteriorates due to loss of low abundance ion data
Solution Approach 1:
The patent applies merging by combining mass spectral data from multiple ion separator cycles before performing decoding. Instead of decoding data from each cycle separately, the system accumulates and merges the spectral data across multiple cycles, creating a composite data set that contains information from all cycles. This merging process allows low abundance ions that may be below detection threshold in individual cycles to become detectable when their signals are combined across multiple cycles, thereby improving sensitivity without significantly increasing processing complexity.
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 increases the duty cycle and sensitivity by ensuring that ions with low abundance are detected as part of combined data, reducing the likelihood of misidentification and improving overall analysis efficiency.
Implementation Method 1
an ion separator for separating ions according to a physicochemical property
Implementation Method 2
a time of flight (TOF) mass analyser having an ion detector and a pusher that, when pulsed, pushes ions into a time of flight region to a detector
Data Source
AI summary
A method of mass spectrometry comprising: a) providing a mass spectrometer having a time of flight (TOP) mass analyser: b) performing a survey scan comprising separating a packet of precursor ion species and mass analysing ions so as to obtain first mass spectral data: c) determining a time window over which one of the precursor ion species. or fragment or product ions derived therefrom, were mass analysed: d) separating another packet of precursor ion species and mass analysing ions so as to obtain second mass spectral data. wherein the pusher of the TOP mass analyser is pulsed according to a plurality of consecutive pulse sequences during a plurality of respective pulse sequence time periods. wherein each pulse sequence consists of consecutive pushes that are arranged such that the duration between any pair of pushes in the pulse sequence is different to the duration between any other pair of pushes within the pulse sequence: f) selecting mass spectral data, from the second mass spectral data, that was obtained during a time period corresponding to said time window of the survey scan, so as to obtain selected data; g) repeating steps d) to f) at least one further time such that multiple sets of said selected data are obtained; combining said multiple sets of selected data and decoding the combined data to obtain mass spectral data representative of the mass to charge ratios of the ions detected by the TOP mass analyser.