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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 滤波对角化方法是最近发展起来的一种信号处理算法，它是基于量子力学的谐波求逆问题的数学形式。结果表明，对于少量的瞬时数据点，如10K，FDM法能以1ppm的精度找到极高精度的共振频率。它被用于频移跟踪实验，目的是确定瞬变内频移，并将其用于参考反卷积和研究空间电荷效应。 在这项研究中，我们使用了内部C++实现的FFT Square Window FDM，它将作为开放源码软件在即将发布的波士顿大学数据分析(BUDA)系统中提供。理论光谱由1兆点长和1 MHz采样率的内部模拟软件生成。用自制的ESI FTMS仪器(1兆点长，1 MHz采集速率)采集P物质的真实光谱。频率跟踪实验是在1,000到20000个数据点的瞬变域上进行的，从0偏移开始，根据实验从1到200个数据点移位到瞬变点。Kwin使用的分数从4到11分不等。 有限差分方法在少量数据点上显示出惊人的精度和高分辨率。FDM码的速度比FFT慢得多，也不像FFT那样稳定，因此不能与FFT直接竞争。然而，事实证明，频分复用是一种很好的重建频移图的工具。在理论光谱上，它能够在信噪比为2的情况下跟踪0.005赫兹的频移。 在频率追逐实验中使用了P物质光谱(图1)。同位素节拍模式在丰度和频移上都得到了忠实的再现。即使对于这样一个简单的光谱，空间电荷大约是400ppm，即使在FFT之后，也有可能在这个光谱上获得1ppm的质量精度。这一结果表明，FFT有效地平均了这些循环频移以实现其结果。 因此，有限差分法是研究空间电荷的一种新工具。如果频移曲线被证明是一致的，则可以用于参考反褶积。在极端空间电荷条件下，如著名的“乳头效应”引起的情况下，有限差分方法已经得到了应用。这项研究结果最近发表在《美国医学杂志》(2009，20,247-256)上。 自发相干损失灾变(SLCC)，俗称“乳头效应”，描述了FT-ICR质谱学中的一种现象，即瞬变的崩塌和迅速消失，形成乳头状形状。尽管SLCC是FT-ICR MS中经常观察到的与空间电荷相关的效应，但它也是一个很少被研究的效应。 在本研究中，我们使用有限差分法来研究SLCC。由于FDM法的分辨率不取决于瞬变信号的长度，而取决于局部峰值密度，因此它能够在非常短的瞬变时间内工作。它在嘈杂的条件下也是可靠的，并重现关于峰值的完整信息。所有这些因素使其成为研究FT-ICR MS中快速空间电荷诱导频率调制的理想技术。研究发现，频率尖峰与SLCC之前的幅度极小值相关，这与已知的低空间电荷条件下频率增加的观察结果相一致。事实上，这种关联在SLCC上颠倒了过来，这表明同位素离子包暂时在幅度最小的时候回到了相(高空间电荷)。有人提出，只有当磁控轨道的直径与回旋轨道的直径相似时，才可能发生这种情况。电子促进的离子相干性(EPIC)实验证实了这一观点，该实验表明，只有当存在强磁控分量时，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率时，需要减少磁控漂移和空间电荷诱导的频率调制。 使用基于频分复用的频移分析，我们还展示了确定轴向振荡如何扰乱回旋频率的能力。这是一个比之前显示的同位素节拍模式效应小得多的影响，所以为了做到这一点，我们必须使用不含同位素的峰，而碘化铯能够提供一个很好的簇峰来达到这个目的。