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

本初步设计研究旨在研究开发高场FTICR质谱仪的可行性和成本，该质谱仪由于使用无低温超导磁体而可以安装在工作台上。该初步设计研究可能会在开发该仪器的完整提案之后进行，但旨在通过分离设计可行性研究来“降低”完整设计/施工项目的风险。通过这种方式，可以完成低成本的设计项目，然后在以后的资助小组中对主要项目进行全面和详细的审查。目前的初步设计方案将集中在整个项目的两个部分，A)磁铁和B)进入磁铁的质谱仪。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（见附件中布鲁克公司首席执行官Frank Laukien博士的支持信）。布鲁克已经有了一个初步的磁铁设计，但目前还不清楚它是否会有我们需要达到的性能规格；这部分项目的目的是协调我们的设计需求和他们的设计能力。所需的磁铁必须做得尽可能小，我们估计大约是台式激光打印机的大小。磁体的强度将达到7特斯拉或更高（并且具有高均匀性），必须采用主动屏蔽以避免杂散磁场的问题，将完全由商用冷冻器冷却（待定），需要淬火稳定，并且需要集成的自动充电电源。对于这个设计，我们应该能够计算冷却时间和“平均淬灭时间（MTTQ）”，即磁铁在断电后淬灭所需的时间，以及磁铁稳定时间。如果MTTQ是几分钟或几小时，那么设计既可行又可能稳定，特别是如果加上不间断电源，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，我们的目标是估计磁铁在7 T、12 T、15 T和21 T型号以及110 - 150毫米口径变化下的成本。在B部分中，我们将设计仪器进入这个磁体，目标是最小化仪器尺寸，同时保持在分辨率、质量精度和灵敏度方面的性能。这需要在ICR单元中有1e- 10mbar的真空，因此需要一个至少有4个，也许6个大气压泵送的差压泵送系统，我们可以使用几种设计策略来优化该仪器。电喷雾电离源、泵送系统、真空室、离子光学和ICR电池都将在3D CAD软件中设计。将计算泵送速度，并估计ICR单元中的基压。离子传输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，根据需要与Bruker进行一些磋商，以确保我们的仪器设计与他们的电子设备和软件兼容。总的来说，如果成功的话，我们将为一种新的质谱仪产生一个坚固的、紧凑的设计，它将胜过该领域任何其他类似尺寸的仪器。该仪器将适用于疾病、药品、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分子。

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.