TESTING APPLICATION OF THE FILTER DIAGONALIZATION METHOD TO FTMS

滤波器对角化方法在FTMS中的测试应用

• 批准号: 7955922
• 负责人: PETER B. O'CONNOR
• 金额: $ 0.19万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955922
• 关键词: Algorithms; Amaze; Back; Biology; Boston; Caliber; Charge; Computer Retrieval of Information on Scientific Projects Database; Computer software; Cyclotrons; Data; Data Analyses; Electrons; Frequencies; Funding; Grant; Housing; Institution; Ions; Isotopes; Length; Mass Spectrum Analysis; Medicine; Methods; Nipples; Noise; Ocular orbit; Pattern; Phase; Publishing; Quantum Mechanics; Research; Research Personnel; Resolution; Resources; Sampling; Shapes; Signal Transduction; Source; Substance P; System; Techniques; Testing; United States National Institutes of Health; Universities; base; cesium iodide; computerized data processing; density; instrument; open source; research study; simulation; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Filter Diagonalization Method (FDM) is a recently developed signal processing algorithm based on quantum mechanic's mathematical formalism of the harmonic inversion problem. FDM is shown to provide extremely high precision in finding resonance frequencies with 1ppm accuracy on small number of transient data points e.g. 10k. It was used in frequency shift chasing experiments for the purposes of determining intra-transient frequency shifts and using them for reference deconvolution and study of space charge effect. In this study we used an in-house C++ implementation of the FFT Square Window FDM, which will be available as open source software in an upcoming release of the Boston University Data Analysis (BUDA) system. Theoretical spectra were generated by using in-house simulation software with 1 mega-point length and 1 MHz sampling rate. Real spectra of Substance P were acquired on homebuilt ESI FTMS instrument (1 mega-point length with 1MHz acquisition rate). Frequency chasing experiments were performed on transient domains ranging from 1000 to 20000 data points starting with the 0 offset and shifting depending on the experiment from 1 to 200 data points into the transient. Kwin used ranges from 4-11 points. FDM shows amazing precision and high resolution on small number of data points. FDM is much slower and not as stable as FFT and for that reason cannot compete directly with FFT. However FDM proves to be a good tool for reconstructing frequency shift plots. On theoretical spectra it showed ability to trace frequency shifts of .005 Hz with signal:noise ratio of 2. A substance P spectrum was used in the frequency chasing experiment (figure 1). The isotopic beat pattern is faithfully reproduced in both abundance and frequency shifts. Space charge, even for such a simple spectrum, are approximately 400 ppm even though post FFT, it is possible to get 1ppm mass accuracy on this spectrum. This result indicates that the FFT effectively averages out these cyclic frequency shifts to achieve its results. FDM, therefore, is a new tool for study space charge. The frequency shift plots, if they are shown to be consistent, could be used in reference deconvolution. The application of FDM in extreme space charge conditions, such as those caused by the famous "nipple effect" has been carried out. The results were recently published in JASMS (2009, 20, 247-256). The spontaneous loss of coherence catastrophe (SLCC), colloquially known as the "nipple effect", describes a phenomenon in FT-ICR mass spectrometry, where the transient collapses and dies out quickly, forming a nipple-like shape. Although SLCC is a frequently observed, space-charge related effect in FT-ICR MS, it is also one that is poorly studied. In this study, the FDM is used to study the SLCC. Because FDM's resolution depends not on the length of the transient signal, but rather on the local peak density, it is capable of operating on very short transients. It is also reliable under noisy conditions, and reproduces complete information about a peak. All of these factors make it an ideal technique for studying rapid space charge induced frequency modulations in FT-ICR MS. It was found that frequency spikes correlated with amplitude minima before the SLCC, which agreed with the known observation that frequency increases at lower space-charge conditions. The fact that this correlation flipped over at the SLCC suggested that the isotope ion packets were temporarily coming back into phase (high space charge) at the amplitude minima. It was proposed that this may occur only when the magnetron orbit diameter is similar to that of the cyclotron orbit. This claim was supported by the electron promoted ion coherence (EPIC) experiments, which showed that the SLCC is observed only when there is a strong magnetron component. These findings reinforced the need for reduction of magnetron drift and space-charge induced frequency modulation when pursuing the higher mass accuracy and resolving power capabilities of the FT-ICR MS. Using the FDM based frequency shift analysis, we have also shown the ability to determine how axial oscillations perturb the cyclotron frequency. This is a far smaller effect than the isotopic beat pattern effect previously shown, so in order to do it, we had to use a peak without isotopes, and Cesium Iodide was able to provide a nice cluster peak for just this purpose.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 滤波器对角化方法（FDM）是最近开发的一种基于量子力学调和反演问题的数学形式主义的信号处理算法。 FDM 经证明能够以极高的精度在少量瞬态数据点（例如，数据点）上查找谐振频率，精度为 1ppm。 10k。 它用于频移追踪实验，目的是确定瞬态频移，并将其用于参考反卷积和空间电荷效应研究。 在本研究中，我们使用了 FFT 方窗 FDM 的内部 C++ 实现，该实现将在即将发布的波士顿大学数据分析 (BUDA) 系统中作为开源软件提供。理论光谱是通过使用内部模拟软件以 1 兆点长度和 1 MHz 采样率生成的。 P物质的真实光谱是在自制的ESI FTMS仪器上获得的（1兆点长度，1MHz采集速率）。频率追踪实验在 1000 到 20000 个数据点的瞬态域上进行，从 0 偏移开始，并根据实验从 1 到 200 个数据点移动到瞬态。 Kwin 使用的范围为 4-11 点。 FDM 在少量数据点上显示出惊人的精度和高分辨率。 FDM 比 FFT 慢得多且不稳定，因此无法与 FFT 直接竞争。然而，FDM 被证明是重建频移图的良好工具。在理论频谱上，它能够跟踪 0.005 Hz 的频移，信噪比为 2。 频率追踪实验中使用了物质 P 谱（图 1）。同位素拍频模式在丰度和频移方面均得到忠实再现。即使对于如此简单的光谱，空间电荷也约为 400 ppm，即使经过 FFT，也可以在此光谱上获得 1 ppm 的质量精度。该结果表明 FFT 有效地平均了这些循环频移以实现其结果。 因此，FDM 是研究空间电荷的新工具。如果频移图显示一致，则可以将其用于参考反卷积。 FDM在极端空间电荷条件下的应用已经开展，例如由著名的“乳头效应”引起的空间电荷条件。该结果最近发表在 JASMS (2009, 20, 247-256) 上。 自发相干性损失灾难 (SLCC)，俗称“乳头效应”，描述了 FT-ICR 质谱中的一种现象，即瞬态迅速崩溃并消失，形成乳头状形状。尽管 SLCC 是 FT-ICR MS 中经常观察到的一种与空间电荷相关的效应，但对其研究也很少。 在本研究中，FDM 用于研究 SLCC。由于 FDM 的分辨率不取决于瞬态信号的长度，而是取决于局部峰值密度，因此它能够在非常短的瞬态上运行。它在噪声条件下也很可靠，并再现有关峰值的完整信息。所有这些因素使其成为研究 FT-ICR MS 中快速空间电荷感应频率调制的理想技术。结果发现，频率尖峰与 SLCC 之前的振幅最小值相关，这与已知的观察结果一致，即频率在较低空间电荷条件下增加。事实上，这种相关性在 SLCC 处翻转，表明同位素离子包在振幅最小值时暂时恢复到同相（高空间电荷）。有人提出，只有当磁控管轨道直径与回旋加速器轨道直径相似时，这种情况才可能发生。这一说法得到了电子促进离子相干 (EPIC) 实验的支持，该实验表明，只有在存在强磁控管组件时才能观察到 SLCC。这些发现强调了在追求 FT-ICR MS 更高的质量精度和分辨能力时减少磁控管漂移和空间电荷感应频率调制的必要性。 使用基于 FDM 的频移分析，我们还展示了确定轴向振荡如何扰乱回旋加速器频率的能力。 这比之前显示的同位素拍频模式效应要小得多，因此为了做到这一点，我们必须使用没有同位素的峰，而碘化铯能够为此目的提供一个很好的簇峰。