Preliminary design study for a benchtop, cryogen-free FTICR mass spectrometer

台式无制冷剂 FTICR 质谱仪的初步设计研究

• 批准号: EP/N021630/1
• 负责人: Peter O'Connor
• 金额: $ 13.94万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN021630%2F1
• 关键词: Preliminary; design; study; benchtop; cryogen

This preliminary design study is intended to investigate the feasibility and cost of developing a high-field FTICR mass spectrometer which can fit on a benchtop because of use of a cryogen-free superconducting magnet. This preliminary design study will likely follow on with a full proposal to develop this instrument but is intended to 'de-risk' a full design/construction project by separating out the design feasibility studies. In this manner, the low-cost design project can be done, followed by a full and detailed review of the main project at a later funding panel. This current preliminary design proposal will focus on two parts of the overall project, A) the magnet and B) the mass spectrometer that goes into said magnet. In part A, we will collaborate with our industrial partner, Bruker Corporation, to design the magnet (see attached letter of support from Dr. Frank Laukien, CEO of Bruker Corp). Bruker already has a preliminary magnet design, but it is not clear at this time that it will have the performance specificatioins that we need to achieve; this part of the project aims to coordinate our design needs with their design capabilities. The magnet required must made to be as small as possible, which we estimate to be about the size of a desktop laser printer. The magnet will be 7-Tesla or higher (and with high homogeneity), will have to be active-shielded to avoid problems with stray magnetic fields, will be cooled solely by a commercial cryocooler (to be determined), will need to be quench-stable, and will need to have an integrated, automated charging power supply. For this design, we should be able to calculate the cooldown time and the 'Mean-time-to-quench (MTTQ)' which is how long it will take for the magnet to quench after the power is lost, and the magnet stabilization time. If the MTTQ is a few minutes or hours, then the design is both feasible and likely to be stable, particularly if coupled with an uninteruptible power supply, but if it's a few seconds to milliseconds, then the system will be too unstable to be useful. And finally, we will aim to estimate the cost of the magnet in 7 T, 12 T, 15 T, and 21 T variants and in 110 - 150 mm bore diameter variations.In part B, we will design the instrument to go into this magnet, with the goal of minimizing instrument size while still maintaining performance in terms of resolving power, mass accuracy, and sensitivity. This requires a 1e-10 mbar vacuum in the ICR cell, so that a differential pumping system with at least 4, and maybe 6 differential stages of pumping are needed from atmospheric pressure, and there are several design tactics we can use to optimize this instrument. The Electrospray ionization source, pumping system, vacuum chambers, ion optics, and ICR cell will all be designed in 3D CAD software. Pumping speeds will be calculated and base pressures in the ICR cell will be estimated. Ion transfer efficiency can also be estimated using ion-modeling software such as SIMION. Part B will be primarily done in-house, with some consultation with Bruker as needed to make sure that our instrument designs are compatible with their electronics and software.Overall, if successful, we will generate a robust, compact design for a new mass spectrometer which will out-perform any other instrument in the field - of a similar size. This instrument will be applicable to the study of biomolecules involved in disease, pharmaceuticals, food-safety and environmental tracer studies, and pretty much any other kind of molecule available.

本初步设计研究的目的是调查的可行性和成本的开发高场FTICR质谱仪，可以安装在一个工作台上，因为使用无制冷剂超导磁体。该初步设计研究可能会随后提出开发该仪器的完整建议，但其目的是通过分离设计可行性研究来“降低”整个设计/施工项目的风险。通过这种方式，可以完成低成本设计项目，然后在稍后的筹资小组中对主要项目进行全面详细的审查。目前的初步设计方案将集中在整个项目的两个部分，A）磁体和B）进入所述磁体的质谱仪。在A部分，我们将与我们的工业合作伙伴布鲁克公司合作设计磁铁（请参阅随附的布鲁克公司首席执行官Frank Laukien博士的支持信）。布鲁克已经有了初步的磁体设计，但目前尚不清楚它是否具有我们需要实现的性能规格;该项目的这一部分旨在协调我们的设计需求与他们的设计能力。所需的磁铁必须尽可能小，我们估计大约是桌面激光打印机的大小。磁体将为7特斯拉或更高（并且具有高均匀性），必须进行主动屏蔽以避免杂散磁场的问题，将仅由商用制冷机（待定）冷却，需要淬火稳定，并且需要具有集成的自动充电电源。对于这种设计，我们应该能够计算冷却时间和“平均失超时间（MTTQ）”，这是失去电源后磁体失超所需的时间，以及磁体稳定时间。如果MTTQ是几分钟或几小时，那么该设计既可行又可能稳定，特别是如果加上不可中断的电源，但如果它是几秒到几毫秒，那么系统将太不稳定而无法使用。最后，我们将估算7 T、12 T、15 T和21 T磁体以及110 - 150 mm孔径磁体的成本。在B部分，我们将设计用于该磁体的仪器，目标是最小化仪器尺寸，同时保持分辨率、质量精度和灵敏度方面的性能。这需要ICR室中的1 e-10 mbar真空，使得需要具有至少4个、可能6个来自大气压的差分级泵送的差分级泵送系统，并且存在我们可以使用来优化该仪器的几种设计策略。电喷雾电离源、泵系统、真空室、离子光学器件和ICR室都将在3D CAD软件中设计。将计算泵送速度，并估计ICR室中的基础压力。离子转移效率也可以使用离子建模软件如SIMION来估计。B部分将主要在内部完成，并根据需要与布鲁克公司进行一些咨询，以确保我们的仪器设计与他们的电子和软件兼容。总体而言，如果成功，我们将为新的质谱仪设计一个坚固、紧凑的设计，该设计将优于该领域中任何其他类似尺寸的仪器。该仪器将适用于疾病、药物、食品安全和环境示踪剂研究中涉及的生物分子的研究，以及几乎任何其他类型的可用分子。

项目成果

Does deamidation affect inhibitory mechanisms towards amyloid protein aggregation?

• DOI: 10.1039/d0cc03548c
• 发表时间: 2020-09-04
• 期刊: CHEMICAL COMMUNICATIONS
• 影响因子: 4.9
• 作者: Lam, Yuko P. Y.;Chiu, Cookson K. C.;O'Connor, Peter B.
• 通讯作者: O'Connor, Peter B.

Bottom-Up Two-Dimensional Electron-Capture Dissociation Mass Spectrometry of Calmodulin

• DOI: 10.1007/s13361-017-1812-y
• 发表时间: 2018-01-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Floris, Federico;van Agthoven, Maria A.;O'Connor, Peter B.
• 通讯作者: O'Connor, Peter B.

New activation mechanism for half-sandwich organometallic anticancer complexes.

• DOI: 10.1039/c7sc05058e
• 发表时间: 2018-03-28
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Banerjee S;Soldevila-Barreda JJ;Wolny JA;Wootton CA;Habtemariam A;Romero-Canelón I;Chen F;Clarkson GJ;Prokes I;Song L;O'Connor PB;Schünemann V;Sadler PJ
• 通讯作者: Sadler PJ

Application of Tandem Two-Dimensional Mass Spectrometry for Top-Down Deep Sequencing of Calmodulin.

• DOI: 10.1007/s13361-018-1978-y
• 发表时间: 2018-08
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Floris F;Chiron L;Lynch AM;Barrow MP;Delsuc MA;O'Connor PB
• 通讯作者: O'Connor PB

Top-Down Deep Sequencing of Ubiquitin Using Two-Dimensional Mass Spectrometry

• DOI: 10.1021/acs.analchem.8b00500
• 发表时间: 2018-06-19
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Floris, Federico;Chiron, Lionel;O'Connor, Peter B.
• 通讯作者: O'Connor, Peter B.