Real-time chromatography data filter for scans with non-uniform data intervals

Abstract

To provide systems and methods for enabling improved filtering of chromatographic data.SOLUTION: Systems and methods taught herein enable improved filtering of chromatography data acquired during a series of scans with non-uniform data sampling intervals (also referred to herein as "scan durations") by use of a chromatography data filter that operates on a time base that is shorter than any of the data sampling intervals in the series of scans. By employing a filter with such a time base, the systems and methods taught herein improve the signal-to-noise ratio (S / N) of the resulting data and enhance the quality of chromatograms in mass spectrometry real-time signal processing, leading to clearer signals, reduced baseline noise, and smoother peaks in the chromatographic data.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 654,877, filed May 31, 2024, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] One way to improve sensitivity in liquid chromatography-mass spectrometry (LC-MS) scans is to reduce the noise level in the chromatogram. Because noise is inherently high frequency (compared to the chromatographic peaks), it can be removed from the chromatographic profile by frequency-dependent filtering. Summary of the Invention

[0003] In one aspect, a method is taught herein for processing data obtained from scans having non-uniform data sampling intervals to form a chromatogram. The method includes acquiring a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, with each scan of the plurality of scans occurring for a corresponding data sampling interval. The method further includes applying a chromatographic data filter to at least a portion of the plurality of data points. The filter includes a time base, the time base being shorter than any of the corresponding data sampling intervals. A non-transitory computer-readable storage medium including instructions for a computer to perform this method is also taught herein.

[0004] In one aspect, a method is taught herein for processing data obtained from scans having non-uniform data sampling intervals to form a chromatogram. The method includes acquiring a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, with each scan of the plurality of scans occurring for a corresponding data sampling interval. The method further includes measuring at least one corresponding data sampling interval. The method further includes dividing the at least one corresponding data sampling interval by an interpolation factor to determine a time base of a chromatographic data filter. The method further includes calculating filter coefficients for the chromatographic data filter based on the time base. The method further includes applying the chromatographic data filter to at least a portion of the plurality of data points. A non-transitory computer-readable storage medium including instructions for a computer to perform this method is also taught herein. [Brief explanation of the drawings]

[0005] The accompanying drawings illustrate various embodiments and are a part of this specification. The illustrated embodiments are merely examples and are not intended to limit the scope of the present disclosure. Throughout the drawings, the same or similar reference numbers refer to the same or similar elements. To easily identify the discussion of any particular element or act, the most significant digit in the reference number refers to the number of the figure in which that element is first introduced.

[0006] [Figure 1] 1A-1C illustrate the application of a conventional filter and a filter taught herein to experimental data obtained during the time a sample enters a mass spectrometer. [Figure 2] FIG. 1 illustrates an exemplary chromatographic data filter in a network format that converts raw chromatographic data into filtered chromatographic data. [Figure 3A] FIG. 1 illustrates two plots of raw data for different m / z ranges over the same time span from scans spaced with non-uniform data sampling intervals. [Figure 3B] FIG. 3B shows the raw data of FIG. 3A obtained with non-uniform data sampling intervals filtered using a conventional static filter. [Figure 3C] FIG. 3B illustrates the raw data of FIG. 3A acquired with non-uniform data sampling intervals filtered by a chromatographic data filter according to examples taught herein. [Figure 4] 10A-10C illustrate the time shift between raw and filtered peaks according to some embodiments of the chromatographic data filter taught herein. [Figure 5] FIG. 1 illustrates an exemplary method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram. [Figure 6] FIG. 10 illustrates an additional exemplary method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram. [Figure 7] FIG. 1 illustrates an exemplary computing device suitable for controlling a mass spectrometer and executing computer-readable instructions for implementing the methods described herein. DETAILED DESCRIPTION OF THE INVENTION

[0007] The systems and methods taught herein enable improved filtering of chromatographic data acquired during a series of scans with non-uniform data sampling intervals (sometimes referred to herein as "scan duration") through the use of a chromatographic data filter that operates on a time base shorter than any of the data sampling intervals in the series of scans. Traditionally, mass spectrometer data acquisition systems can use low-pass filters to reduce or remove high-frequency noise and enhance chromatographic signals. Traditional chromatographic data filters operate on a time base equal to the uniform data sampling interval. When such traditional chromatographic data filters are used to filter data acquired with varying (e.g., non-uniform) data sampling intervals, the filter response can introduce irregularities that make the resulting data unstable and unpredictable. The systems and methods taught herein use a chromatographic data filter that operates on a time base shorter than the shortest data sampling interval in a given series of scans. By using such short time-based filters, the systems and methods taught herein improve the signal-to-noise ratio (S / N) of the resulting data and enhance the quality of chromatograms in mass spectrometry real-time signal processing, resulting in clearer signals, reduced baseline noise and smoother peaks, and significantly improved stability in the chromatographic data compared to the same data processed using conventional static filters.

[0008] The filtering can be performed in real time during the acquisition of the chromatogram, based on initial parameters provided by the user, or based on determination of initial conditions during the initial acquisition of the chromatographic data.

[0009] FIG. 1 illustrates the application of a conventional filter and a filter taught herein to experimental data acquired during the time a sample elutes from an inlet system and enters a mass spectrometer. Examples of inlet systems compatible with the present system and method include a chromatographic column, a batch inlet system, a direct probe inlet, or an electrophoresis capillary inlet system. The introduction of a sample into a mass spectrometer is illustrated by an elution peak 114 having a peak width 112. During the peak width 112 of the elution peak 114, several scans can be performed, each requiring a specified time to execute. As used herein, a "data sampling interval" refers to the time between receiving data from adjacent scans of the same scan type within an experimental method. Traditionally, a series of scans 116 (e.g., MS1 scans) were performed with a non-varying periodic data interval 108 (i.e., data was acquired from scans at regular intervals) during the time the analytes in the elution peak 114 were eluting into the mass spectrometer. The data from the series of scans was filtered using a conventional static chromatographic filter with a constant time base 104 that matched the scan's periodic data interval 108.

[0010] As technology advances, new experimental methodologies and scheduling strategies have been introduced that allow for non-uniform (i.e., non-periodic, random, or aperiodic) data sampling intervals. A user can define a data acquisition method, for example, using a mass spectrometer's method editor. A particular method can include several scans, each with a corresponding scan type (e.g., scans can all be the same type or different types within the method), and a schedule (e.g., user-defined time frames). Scans of different types or of the same duration can take different amounts of time to complete, depending on the goal achieved by the scan. For example, some scans may cover a wider range of m / z values ​​and therefore take longer to complete than a targeted scan spanning a narrow m / z window. Other scans may use different automatic gain controls for target ions, resulting in different times for ion accumulation before the scan is completed. Furthermore, a mixture of different scan types can be performed on a single eluting peak 114, and each of these different scan types can have a different associated time for the scan to complete and provide output data. Furthermore, the schedules of different scans may overlap, and therefore the sampling rate for a particular scan type may be uneven or inconsistent between scans. The chromatographic data filter taught herein operates on a time base 106 that is shorter than the shortest data sampling interval in a sequence of scans to ensure that the data from each scan is properly sampled and properly incorporated into the filter.

[0011] In various examples, scans that generate chromatographic data that can be processed using the chromatographic data filters taught herein can include full-scan MS1 ​​data acquisition (either hybrid or quantitative), adaptive gain control (AGC), selected reaction monitoring (SRM), selected ion monitoring (SIM), tandem mass spectrometry such as MS2, MS3, and up to MSn, data-independent acquisition (DIA), product ion scan, neutral loss scan, data-dependent acquisition (DDA) including full scan, adaptive retention time (RT) method, or any combination of these scan types within a single method. In some examples, the chromatographic data filter applied to data acquired using one scan type can be different (e.g., user-specified) from the chromatographic data filter applied to data acquired using a different scan type. In some embodiments, the data acquired in the data sampling interval 110 can include, for example, peak intensities for one or more specific analytes or all of the measured analytes at a given value of m / z measured during the scan. These data can be obtained from multiple scans over time and assembled into a chromatogram (eg, abundance or intensity as measured by detector response over time).

[0012] For example, FIG. 1 illustrates a series of overlapping scans in time, including an automatic gain control (AGC) scan 118, a data-dependent (DD) scan 120, and a multiple-experiment scan 122. In an AGC scan, the mass spectrometer can adjust experimental conditions to increase or decrease the number of ions obtained in a given m / z range, for example, based on feedback from the detector. This can be achieved, for example, by applying different injection times based on signal intensity. Accordingly, the data sampling interval 110 between scans in a series of AGC scans 118 can be varied from a relatively long time between scans to a shorter time. Similarly, FIG. 1 illustrates a series of data-dependent scans, also referred to as DD scans 120. In data-dependent scans, a mixture of survey and target m / z scans can be performed, with different scans completed using different data sampling intervals 110, which can depend on signal intensity. Finally, FIG. 1 illustrates a series of multiple-experiment scans 122 in which a mixture of different scan types is used. In some cases, the scans in a multiple-experiment scan 122 can overlap in time. For example, one scan type can be interrupted to perform a different scan type from which data is obtained. The experiment then returns to the initial scan type for the remainder of the planned period. In some multi-experiment scans 122, scans may be added or terminated (removed) throughout the elution time according to a predefined window. Different scan types can all return data at different rates, either within a single scan type or as different scan experiments are completed.

[0013] In a sequence of scans with varying data sampling intervals 110, conventional filters utilizing a constant time base 104 that matches the static or initial periodic data interval 108 produce unreliable and unpredictable results. The chromatographic data filter taught herein can use a time base 106 that is shorter than the shortest data sampling interval 110 in the sequence of scans. For example, a graphical representation of the time base 106 shows that the filter samples data at a faster rate (i.e., closer time points due to the shorter time base) than the fastest scan acquisition or sampling rate (i.e., the closest data sampling interval 110 point) in either the AGC scan 118, the DD scan 120, or the multi-experiment scan 122. The chromatographic data filter advantageously reduces baseline noise, produces smoother peaks, improves reproducibility (e.g., avoids shifts or changes in peak shape during repeated scans), and improves signal clarity in these scans.

[0014] In some examples, the time base 106 operates by applying interpolation to ensure sufficient sampling for the filter. The time base 106 can be a small, fixed time interval, which increases the stability and performance of the filter. In other embodiments, the time base 106 can vary over the time of the elution peak 114. For example, in response to modifying the method in real time to introduce a new, faster scan type, the chromatographic data filter time base 106 can be shortened to remain below the minimum data sampling interval 110 in the modified experiment.

[0015] As described in more detail below with respect to FIG. 6 , the chromatographic data filter can be initialized with input parameters derived from a user, stored in memory, or derived in real time from analysis of raw data generated by the mass spectrometer. In some examples, the time base 106 is determined in real time by analyzing data from the mass spectrometer. For example, a computing device in communication with the mass spectrometer can receive two raw data points from two scans. The computing device can determine the time difference between the receipt of these two data points, which corresponds to the data sampling interval 110 of the first scan. The computing device can then divide the determined data sampling interval 110 by an interpolation factor (e.g., an integer) to determine the time base 106. The interpolation factor can be selected to balance competing factors. For example, a larger interpolation factor divides the data sampling interval 110 into smaller segments, increasing the smoothness of the resulting filter. At the same time, computational overhead increases. In various examples, the interpolation factor is in the range of 2 to 20, in the range of 2 to 10, or an integer equal to 5. In some examples, the interpolation factor is not an integer and can take a value such as 1.5. In some examples, the interpolation factor is in the range of 1.5 to 1000, in the range of 1.5 to 500, in the range of 1.5 to 100, or in the range of 1.5 to 50.

[0016] In some implementations, the time base 106 determined from an initial scan in a series of scans may be applied in a chromatographic data filter to all scans for a given elution peak 114. However, some sequences of multiple experiment scans 122 may incorporate the dynamic addition or termination of scans that may shorten the data sampling interval 110 to a level that becomes comparable to the existing time base 106 originally determined by measurements of the initial scans. In some examples, the computing system may monitor the data sampling interval 110 and take action to adjust future data sampling intervals 110 to be longer and / or adjust the time base 106 to be shorter so that the time base 106 is not greater than the dynamically updated data sampling interval 110 during a series of scans.

[0017] In some examples, an entire series of scans and associated data sampling intervals 110 are prescribed (e.g., in a method editor) before analytes begin eluting in the mass spectrometer. The prescribed scans may be stored, for example, in a list or database. As an alternative or in addition to real-time measurement of the data sampling intervals 110 as described above, a computing device configured to perform a chromatographic data filter may, in some examples, examine the prescribed scans to determine or predict the shortest data sampling interval 110 in the series of scans. The computing device may then determine the time base 106 for the chromatographic data filter by dividing the shortest data sampling interval 110 by an interpolation factor (e.g., an integer), as described above.

[0018] By increasing the sampling rate of the chromatographic data filter (i.e., increasing the interpolation coefficient or shortening the time base 106), additional data operations are performed per unit time. As the time base 106 shortens, peak shape can improve, while computational overhead can increase. Therefore, some implementations of chromatographic data filters can take into account available computational resources (i.e., processing power, available memory, and / or input / output speed) when determining an appropriate time base 106 for the filter. In some examples, a computing device can select the time base 106 to strike a balance between data quality and available computational resources.

[0019] There are several reasons why the chromatographic data filters taught herein, when applied to data obtained from scans with non-uniform data sampling intervals, may outperform conventional data filters operating on a fixed time basis 104.

[0020] Non-constant scan duration: In mass spectrometry, there are scans with non-constant scan durations. For example, in scans that include automatic gain control (AGC) or data-dependent (DD) scans, the scan time varies based on the signal intensity. Similarly, multiple scan events involving scan windows or overlapping scans in a method can result in varying scan durations. Classical IIR filters that rely on a constant time base may not handle these variations effectively.

[0021] Irregularities in filter response: Traditional filters assume a constant time interval between two sampled data points. If the time interval between samples is not consistent, irregularities can be introduced into the filter response. This can result in unstable or unpredictable behavior, resulting in suboptimal noise reduction and signal smoothing.

[0022] Limited adaptability: Traditional filters have limited adaptability to handle dynamic changes in data. In mass spectrometry, where signal characteristics can change significantly, filters may not adapt effectively to changing conditions, resulting in poor performance.

[0023] The chromatographic data filter taught herein addresses some of these issues by applying interpolation in sampling to inform the filter parameters of the chromatographic data filter. By doing so, the chromatographic data filter can utilize a fine time base even in the presence of non-constant or non-uniform scan durations. The use of a fine time base to perform interpolation improves the stability and performance of the filter, allowing it to effectively handle mass spectrometry scans with varying time intervals between data points while maintaining filter strength.

[0024] Examples of utilizing chromatographic data filters to filter raw data in real time are taught herein above (i.e., data from a scan in a series of scans is filtered while additional scans in the series are still being performed), however, it is also contemplated that the chromatographic data filters taught herein can be applied in a post-processing step to data already acquired after all scans in an experiment have been completed.

[0025] FIG. 2 illustrates a chromatographic data filter 202 taught herein in a network representation that converts raw chromatographic data into filtered chromatographic data. The chromatographic data filter can be defined or determined according to filter parameters, which can include, but are not limited to, filter coefficients and filter bandwidth. The chromatographic data filter 202 is an example of a second-order infinite impulse response (IIR) filter. The illustrated chromatographic data filter 202 acts as a type of low-pass filter that can effectively remove high-frequency baseline noise and smooth data jitter across chromatographic peaks. In some examples, the chromatographic data filter 202 can improve overall performance by at least a factor of two. The chromatographic data filter 202 can be a feedback or recursive filter. The transfer function of the chromatographic data filter 202 is given by Y n =b0×X n +b1×X n-1 +b2×X n-2 +a1×Y n +a2×Y n-1 where the filter coefficients b0...b i and a0...a i is f cutoff The cutoff frequency can be defined according to the relationship: = 0.5 × time base ÷ bandwidth. The bandwidth filter parameter can be a user-specified parameter or can be determined based on the peak width 112. In some examples, the bandwidth can be equal to the peak width ÷ 4.

[0026] The chromatographic data filters taught herein can use low-pass filters to remove high-frequency noise. These filters, which can be implemented with either analog components, digital components, or a combination of both analog and digital components, operate in both the time domain, corresponding to the mass-to-charge ratio of the acquired band, and the chromatographic time domain. Multidimensional filters thus remove high-frequency noise in the chromatographic peak profile that is not related to the actual analytical signal. Filters can be applied to ion signals in real time as the data is acquired. Signal-to-noise improvements can range from 2x to 5x. Furthermore, peak integration is more reliable, resulting in improved limits of quantitation, and assay linearity is unaffected.

[0027] In some examples, the chromatographic data filters taught herein can be implemented by instructions (e.g., stored on a non-transitory computer-readable medium) executed by a computing device in communication with or part of a chromatograph and mass spectrometer system. For example, the instructions can be executed by a digital signal processor (DSP) within the mass spectrometer system. The chromatographic data filters can be applied to the data (e.g., ion signals) in real time. Some parameters can be specified by a user, such as the expected baseline width of chromatographic peaks in an assay. The computing device, DSP, or other processor can calculate appropriate bandwidths based on the input peak widths and apply them to the data.

[0028] In some examples, the bandwidth parameter is set by a user or by a computing system based on an examination of the actual chromatographic data in the analysis (e.g., the actual raw data acquired in the same series of scans or in a previously acquired series of scans). If the bandwidth is set too low, high-frequency noise may reappear in the baseline and peak profile. In extreme cases, the filter may have little or no effect, and the filtered signal may look the same as if the filter were turned off. If the bandwidth parameter is set too high, the chromatographic peak profile may become significantly broader (i.e., the peaks may become shorter and thicker). Note that the peak areas are still correct even when the bandwidth parameter is set too high.

[0029] In some implementations, the actual peak width 112 can deviate significantly from the expected bandwidth setting (i.e., the bandwidth filter parameter determined from inspection of previous data or provided by the user) without adversely affecting the quality of the results. As noted above, a longer bandwidth can broaden the peak, reducing its height, while preserving the peak area. In some examples, the user can set the bandwidth to the highest value that does not cause significant peak broadening.

[0030] If some of the chromatographic peaks in an assay have significantly different peak shape characteristics (i.e., broadening, tailing, etc.), the system can adjust the bandwidth parameters using a time-framed procedure. If a chromatographic peak begins to tail significantly in later runs of the analysis, such as when a chromatographic column or other inlet system begins to deteriorate, the filter bandwidth may need to be updated or changed. In this case, the signal-to-noise ratio may be reduced, and automatic peak integration may miss parts of the peak or integrate irrelevant baseline noise. To avoid this effect, the systems and methods taught herein can monitor peak shape and automatically adjust the bandwidth parameters or notify the user that the bandwidth parameters should be updated if a change in peak shape is identified.

[0031] In some systems, a computing device connected to the mass spectrometer can obtain input from a user to define filter parameters for the chromatographic data filter, such as bandwidth. This can be done, for example, through a graphical user interface of the mass spectrometer. In some examples, the user can define different bandwidths to be used for different subsets of scans in a series of scans.

[0032] Although the chromatographic data filter 202 in FIG. 2 is illustrated in a network format as a convenient example, other forms of data filtering that use a time base shorter than the minimum data sampling interval are also contemplated within this disclosure.

[0033] Figure 3A illustrates two plots of raw data for different m / z ranges over the same time span from scans spaced with non-uniform data sampling intervals. The raw data contain significant jitter and fluctuations due to factors such as ion statistical noise caused by low ion signal.

[0034] FIG. 3B shows the raw data of FIG. 3A obtained with non-uniform data sampling intervals filtered using a conventional static filter. The resulting peaks are unstable and may contain artifacts such as shoulders 302. Because the constant time base 104 of a conventional static filter can be longer than the data sampling interval, multiple scans may occur within the filter's sampling period, or potentially no scans may occur within the sampling period. This situation can lead to erroneous amplification or reduction of the influence of past data points on the filter's performance, which may shift unpredictably as a function of the data point's proximity to the filter sampling time point. An example of this erroneous behavior can be seen in the inverted portion 304 of FIG. 3B, where the relative intensities of two peaks near 0.66 and 0.76 minutes in the raw data of FIG. 3A are erroneously inverted in FIG. 3B.

[0035] FIG. 3C shows the raw data of FIG. 3A acquired with non-uniform data sampling intervals, filtered by a chromatographic data filter according to examples taught herein. The chromatographic peaks in FIG. 3C are significantly smoother than those in FIG. 3A, demonstrating reduced baseline noise. Furthermore, the amplitude of high-frequency noise associated with individual ion events is reduced, preserving all regions relevant for detecting ion signals. The attenuation of high frequencies from the baseline and peak profile can improve the chromatographic signal-to-noise ratio by approximately 2-3 times over standard data acquisition conditions.

[0036] Smoother peak profiles aid in more consistent peak integration, which can improve precision and result in lower limits of quantitation (LOQ) in quantitative assays. Unlike conventional post-acquisition smoothing algorithms that smear peaks and include adjacent baseline noise, the chromatographic data filters taught herein preserve the shape of chromatographic peaks and do not induce artificial peak tailing.

[0037] The performance and stability of the chromatographic data filter taught herein was investigated by evaluating the relative standard deviation of peak areas across replicate scans. Full scans were acquired, and the %RSD of peak areas for n=6 scans was measured for three peaks of varying intensity. As shown in Table 1, the chromatographic data filter taught herein significantly improves the standard deviation of peak areas for data obtained using non-uniform data sampling intervals. [Table 1]

[0038] In some instances, applying chromatographic data filters can improve spectral stability. Multidimensional filtering can be performed on the profile data, which is then passed to the centroiding algorithm. As a result, the centroider has a more stable signal to work with from scan to scan. This advantage is readily apparent when the system is scanned over a wide mass range, where peak heights and widths are more stable. This allows for lower bandwidths with fast scans. Chromatographic distortion is reduced by simultaneously maximizing all masses associated with the elution of a component. In SRM analysis, where the scan window is typically less than one dalton, the benefit to the centroider may not be very significant. However, lower bandwidths relative to the number of scans per second can improve the reconstructed ion chromatogram in SRM analysis.

[0039] 4 is a diagram illustrating the time shift between a raw peak and a filtered peak according to some embodiments of a chromatographic data filter taught herein. A raw data peak 402 results in a uniform data filtered peak 404 (i.e., data filtered using a conventional data filter whose time base is equal to the static data sampling interval) and a non-uniform data filtered peak 406 (i.e., data filtered using a chromatographic data filter taught herein adapted to use a time base 106 that is shorter than the shortest dynamic (e.g., non-uniform or fluctuating) data sampling interval 110 in a series of scans). Because the time base 106 and adjusted bandwidth of the present data filter operate at an artificially higher sampling rate than the constant time base 104 of a conventional data filter, the chromatographic data filter taught herein can utilize a new set of filter coefficients that reduce the time difference of the non-uniform data filtered peak 406 compared to the time difference of the uniform data filtered peak 404.

[0040] Due to the recursive nature of some implementations of chromatographic data filters (e.g., infinite impulse response formats), an artificial time delay can be introduced into peaks once enough data points are acquired that they can be fed back into the chromatographic data filter (e.g., chromatographic data filter 202). In some instances, the time delay corresponds to approximately one or two data points. This delay can affect acquisition or processing algorithms that rely on precise timing or apex detection. Use of the chromatographic data filters taught herein reduces the time delay between raw and filtered data compared to conventional filters. In some embodiments, the chromatographic data filters can include compensation techniques to account for the delay. For example, the chromatographic data filters can adjust timing or incorporate predictive algorithms to align the filtered signal with the original, unfiltered signal. Such compensation can reduce or minimize any adverse effects on apex detection or peak analysis.

[0041] 5 illustrates an exemplary method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram. Although the exemplary routine operations illustrate a particular sequence of actions, this sequence may be modified without departing from the scope of the present disclosure. For example, some of the actions illustrated may be performed in parallel or in a different sequence without substantially affecting the functionality of the routine operations. In other examples, different components of an exemplary device or system implementing the routine operations may perform functions substantially simultaneously or in a particular sequence.

[0042] According to some examples, the method includes, at block 502, acquiring a plurality of data points corresponding to a plurality of scans while the sample is eluting from the inlet system, each scan in the plurality of scans being taken during a corresponding data sampling interval.

[0043] According to certain examples, the method includes, at block 504, applying a chromatographic data filter to the plurality of data points, the filter including a time base shorter than any of the corresponding data sampling intervals.

[0044] 6 illustrates an exemplary method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram. Although the exemplary routine operations illustrate a particular sequence of actions, this sequence may be modified without departing from the scope of the present disclosure. For example, some of the actions illustrated may be performed in parallel or in a different sequence without substantially affecting the functionality of the routine operations. In other examples, different components of an exemplary device or system implementing the routine operations may perform functions substantially simultaneously or in a particular sequence.

[0045] According to some examples, the method includes, at block 604, acquiring a plurality of data points corresponding to a plurality of scans while the sample is eluting from the inlet system, each scan in the plurality of scans being taken during a corresponding data sampling interval.

[0046] According to some examples, the method includes, at block 606, measuring a data sampling interval (scan duration) for the first scan.

[0047] According to some examples, the method includes, at block 608, dividing the data sampling interval by an interpolation factor to determine a time base for the chromatographic data filter.

[0048] According to some examples, the method includes, at block 610, calculating filter coefficients for a chromatographic data filter based on a time base.

[0049] According to some examples, the method includes, at block 612, applying a chromatographic data filter to at least a portion of the plurality of data points a number of times equal to the interpolation factor.

[0050] According to some examples, the method includes, at block 614, combining (eg, integrating) the results of the multiple filtering operations to generate output filtered data points.

[0051] In some examples, a computer program product embodied in a non-transitory computer-readable storage medium may be provided. In such examples, the non-transitory computer-readable storage medium may store computer-readable instructions in accordance with the principles described herein. The instructions, when executed by a processor of a computing device, may direct the processor and / or computing device to perform one or more operations, including one or more of the operations described herein. Such instructions may be stored and / or transmitted using any of a variety of known computer-readable media.

[0052] Non-transitory computer-readable media as referred to herein may include any non-transitory storage medium that participates in providing data (e.g., instructions) that can be read and / or executed by a computing device (e.g., by a processor of a computing device). For example, non-transitory computer-readable media may include, but are not limited to, any combination of non-volatile and / or volatile storage media. Exemplary non-volatile storage media include, but are not limited to, read-only memory, flash memory, solid-state drives, magnetic storage devices (e.g., hard disks, floppy disks, magnetic tape, etc.), ferroelectric random access memory ("RAM"), and optical disks (e.g., compact disks, digital video disks, Blu-ray disks, etc.). Exemplary volatile storage media include, but are not limited to, RAM (e.g., dynamic RAM).

[0053] 7 illustrates an exemplary computing device 700 that may be specifically configured to perform one or more of the operations, methods, and processes described herein. Any of the systems, computing devices, and / or other components described herein may be implemented by computing device 700.

[0054] As shown in Figure 7, computing device 700 may include a communication interface 706, a processor 708, a storage device 710, and input / output ("input / output" or "I / O") 712 communicatively coupled to each other via a communication infrastructure 720. While an exemplary computing device 700 is shown in Figure 7, the components illustrated in Figure 7 are not intended to be limiting. Computing device 700 may, in some examples, be operatively coupled to or incorporated into a mass spectrometer. In other embodiments, additional or alternative components may be used. The components of computing device 700 shown in Figure 7 will now be described in further detail.

[0055] Communications interface 706 may be configured to communicate with one or more computing devices. Examples of communications interface 706 include, but are not limited to, a wired network interface (such as a network interface card), a wireless network interface (such as a wireless network interface card), a modem, an audio / video connection, and any other suitable interface.

[0056] The processor 708 generally represents any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing the execution of one or more of the instructions, processes, and / or operations described herein. The processor 708 may perform operations by executing computer-executable instructions 722 (e.g., applications, software, code, and / or other executable data instances) stored on the storage device 710.

[0057] The storage device 710 may include one or more data storage media, devices, or configurations, and any type, form, and combination of data storage media and / or devices can be used. For example, the storage device 710 may include, without limitation, any combination of non-volatile and / or volatile media described herein. Electronic data, including the data described herein, may be stored temporarily and / or permanently within the storage device 710. For example, data representing computer-executable instructions 722 configured to instruct the processor 708 to perform any of the operations described herein may be stored within the storage device 710. In some examples, the data may be located in one or more databases residing within the storage device 710.

[0058] I / O module 712 may include one or more I / O modules configured to receive user input and provide user output. One or more I / O modules may be used to receive input for a single virtual experience. I / O module 712 may include any hardware, firmware, software, or combination thereof that supports input and output capabilities. For example, I / O module 712 may include hardware and / or software for capturing user input, including, but not limited to, a keyboard or keypad, a touchscreen component (e.g., a touchscreen display), a receiver (e.g., an RF or infrared receiver), a motion sensor, and / or one or more input buttons.

[0059] I / O module 712 may include one or more devices for presenting output to a user, including, but not limited to, a graphics engine, a display (e.g., a display screen), one or more output drivers (e.g., a display driver), one or more audio speakers, and one or more audio drivers. In a particular embodiment, I / O module 712 is configured to provide graphical data to a display for presentation to a user. The graphical data may represent one or more graphical user interfaces and / or any other graphical content as may be useful in a particular implementation.

[0060] The advantages and features of the present disclosure can be further explained by the following enumerated aspects:

[0061] Aspect 1: A method for processing data obtained from scans at non-uniform data sampling intervals to form a chromatogram, the method comprising: obtaining a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, each scan in the plurality of scans occurring during a corresponding data sampling interval; and applying a chromatographic data filter to at least a portion of the plurality of data points, the filter including a time base, the time base being shorter than any of the corresponding data sampling intervals.

[0062] Aspect 2: The method of aspect 1, further comprising: determining a first data sampling interval in a plurality of corresponding data sampling intervals; setting a time base equal to the first data sampling interval divided by an interpolation factor; and adjusting filter parameters of a chromatographic data filter using the time base.

[0063] Aspect 3: The method of aspect 1, further comprising: determining a shortest data sampling interval in the corresponding data sampling interval; setting a time base equal to the shortest data sampling interval divided by an interpolation factor; and adjusting filter parameters of the chromatographic data filter using the time base.

[0064] Aspect 4: The method of aspect 2 or 3, wherein the interpolation factor is 5.

[0065] Aspect 5: The method of any one of aspects 1 to 4, wherein at least two of the corresponding data sampling intervals are unequal.

[0066] Aspect 6: The method of aspects 2 or 3, wherein the interpolation coefficients are selected to balance data quality and available computational resources.

[0067] Embodiment 7: The method of any one of embodiments 1-6, further comprising adjusting the timing of the plurality of data points to match the filtered signal with the original unfiltered signal.

[0068] Embodiment 8: The method of any one of embodiments 1-7, further comprising: monitoring a peak shape generated from the filtered data points in the plurality of data points; and adjusting a filter bandwidth of the chromatographic data filter in response to identifying a change in the peak shape.

[0069] Embodiment 9: The method of any one of embodiments 1 to 8, further comprising monitoring a data sampling interval during sample elution and adjusting a time base of the chromatographic data filter such that the time base is not greater than the data sampling interval during multiple scans.

[0070] Aspect 10: A non-transitory computer-readable storage medium comprising instructions that, when processed by a computing device, configure the computing device to: acquire a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, wherein each scan in the plurality of scans is taken during a corresponding data sampling interval; and apply a chromatographic data filter to at least a portion of the plurality of data points, wherein the filter includes a time base, the time base being shorter than any of the corresponding data sampling intervals.

[0071] Aspect 11: A method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram, the method comprising: obtaining a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, each scan in the plurality of scans occurring during a corresponding data sampling interval; measuring at least one corresponding data sampling interval; dividing the at least one corresponding data sampling interval by an interpolation coefficient to determine a time base of a chromatographic data filter; calculating filter coefficients of the chromatographic data filter based on the time base; and applying the chromatographic data filter to at least a portion of the plurality of data points.

[0072] Embodiment 12: The method of embodiment 11, wherein the at least one corresponding data sampling interval is for a first scan in the plurality of scans.

[0073] Aspect 13: The method of aspect 11, wherein at least one corresponding data sampling interval is for the shortest scan in the plurality of scans.

[0074] Embodiment 14: The method of any one of embodiments 11-13, further comprising applying the chromatographic data filter to the data points a number of times equal to the interpolation coefficients.

[0075] Example 15: The method of example 14, further comprising combining results of the multiple filter applications to generate output filtered data points.

[0076] Embodiment 16: The method of any one of embodiments 11-15, further comprising: monitoring a peak shape generated from the filtered data points in the plurality of data points; and adjusting a filter bandwidth of the chromatographic data filter in response to identifying a change in the peak shape.

[0077] Embodiment 17: The method of any one of embodiments 11-16, further comprising adjusting the timing of the plurality of data points to match the filtered signal with the original unfiltered signal.

[0078] Embodiment 18: The method of any one of embodiments 11 to 17, further comprising monitoring the data sampling interval during sample elution and adjusting the time base of the chromatographic data filter such that the time base is not greater than the data sampling interval during multiple scans.

[0079] Aspect 19: A non-transitory computer-readable storage medium comprising instructions that, when processed by a computing device, configure the computing device to: acquire a plurality of data points corresponding to a plurality of scans during elution of a sample from an inlet system, wherein each scan in the plurality of scans occurs during a corresponding data sampling interval; acquire the data points; measure at least one corresponding data sampling interval; divide the at least one corresponding data sampling interval by an interpolation factor to determine a time base of a chromatographic data filter; calculate filter coefficients for the chromatographic data filter based on the time base; and apply the chromatographic data filter to at least a portion of the plurality of data points.

[0080] Aspect 20: The method of aspect 19, further comprising applying the chromatographic data filter to the data points a number of times equal to the interpolation coefficients.

[0081] In the foregoing specification, various exemplary embodiments have been described with reference to the accompanying drawings. However, it will be apparent that various modifications and changes may be made thereto, and additional embodiments may be implemented, without departing from the scope of the invention as set forth in the following claims. For example, certain features of one embodiment described herein may be combined with, or substituted for, features of other embodiments described herein. Accordingly, the specification and drawings should be considered in an illustrative, and not a restrictive, sense.

Claims

1. acquiring a plurality of data points corresponding to a plurality of scans while the sample is eluting from the inlet system, each scan in the plurality of scans occurring during a corresponding data sampling interval; applying a chromatographic data filter to at least a portion of the plurality of data points, the filter including a time base; 1. A method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram, comprising: the time base is shorter than any of the corresponding data sampling intervals; method.

2. determining a first data sampling interval in the plurality of corresponding data sampling intervals; setting the time base equal to the first data sampling interval divided by an interpolation factor; using the time base to adjust filter parameters of the chromatographic data filter; The method of claim 1 further comprising:

3. determining a shortest data sampling interval among the corresponding data sampling intervals; setting the time base equal to the shortest data sampling interval divided by an interpolation factor; using the time base to adjust filter parameters of the chromatographic data filter; The method of claim 1 further comprising:

4. The method of claim 2 wherein the interpolation factor is five.

5. The method of claim 2 , further comprising applying the chromatographic data filter to the data points a number of times equal to the interpolation coefficients.

6. The method of claim 5 , further comprising combining the results of applying the multiple filters to generate an output filtered data point.

7. The method of claim 2 , wherein the interpolation factors are selected to balance data quality and available computational resources.

8. The method of claim 1 , wherein at least two of the corresponding data sampling intervals are unequal.

9. adjusting the timing of the plurality of data points to match the filtered signal with the original unfiltered signal; The method of claim 1 further comprising:

10. monitoring peak shapes generated from filtered data points in the plurality of data points; adjusting a filter bandwidth of the chromatographic data filter in response to identifying a change in peak shape; The method of claim 1 further comprising:

11. monitoring data sampling intervals during said elution of said sample; adjusting the time base of the chromatographic data filter such that the time base is no greater than the data sampling interval during the plurality of scans; The method of claim 1 further comprising:

12. When processed by a computing device, the computing device is acquiring a plurality of data points corresponding to a plurality of scans while the sample is eluting from the inlet system, each scan in the plurality of scans occurring during a corresponding data sampling interval; applying a chromatographic data filter to at least a portion of the plurality of data points, the filter including a time base; 1. A non-transitory computer-readable storage medium comprising instructions configured to: the time base is shorter than any of the corresponding data sampling intervals; A non-transitory computer-readable storage medium.

13. 1. A method for processing data obtained from scans with non-uniform data sampling intervals to form a chromatogram, comprising: acquiring a plurality of data points corresponding to a plurality of scans while the sample is eluting from the inlet system, each scan in the plurality of scans occurring during a corresponding data sampling interval; measuring at least one corresponding data sampling interval; dividing the at least one corresponding data sampling interval by an interpolation factor to determine a time base of a chromatographic data filter; calculating filter coefficients for the chromatographic data filter based on the time base; applying the chromatographic data filter to at least a portion of the plurality of data points; A method comprising:

14. The method of claim 13 , wherein the at least one corresponding data sampling interval is for a first scan in the plurality of scans.

15. The method of claim 13 , wherein the at least one corresponding data sampling interval is for a shortest scan in the plurality of scans.

16. The method of claim 13 , further comprising applying the chromatographic data filter to the data points a number of times equal to the interpolation coefficients.

17. The method of claim 16 , further comprising combining the results of the multiple filter applications to generate an output filtered data point.

18. monitoring peak shapes generated from filtered data points in the plurality of data points; adjusting a filter bandwidth of the chromatographic data filter in response to identifying a change in peak shape; The method of claim 13 further comprising:

19. adjusting the timing of the plurality of data points to match the filtered signal with the original unfiltered signal; The method of claim 13 further comprising:

20. monitoring data sampling intervals during said elution of said sample; adjusting the time base of the chromatographic data filter such that the time base is no greater than the data sampling interval during the plurality of scans; The method of claim 13 further comprising:

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