TANDEM TIME-OF-FLIGHT FOR PROTEOMICS ANALYSIS

描述（由申请人提供）：我们建议设计，建造和开发一个 用于高通量蛋白质组学的紧凑型串联飞行时间质谱仪 基于我们实验室正在开发的几种技术的研究。在 特别地，第一质量分析器（MSI）将利用质量相关的 加速以聚焦具有不同动能的离子， 将第二质量分析器（MS2）的入口处的质量集中到焦点。 MS2将是一个端盖反射器，提供高阶（接近二次） 动能聚焦碰撞室将位于早期的 MS 1的飞行管，因为这是该仪器的一个基本特征， 没有减速或再加速场，无论是恒定的还是脉冲的， 在离子源和端盖反射器的入口之间。因此，在本发明中， 与质量选择的前体离子相关联的碎片离子，并通过 碰撞诱导解离（CID）或亚稳态分解，将是 记录在同一飞行时间。高能量带宽端盖反射器 不需要步进或扫描来记录整个产物离子质量 在每个飞行时间周期的范围内。此外，由于该反射器还 不需要在碰撞后重新加速， 在碰撞激活中利用全部离子动能（10 - 20 keV）。 该仪器将用于一些正在进行的研究项目 涉及肽和糖脂抗原，脂质A的结构， 芯片上的蛋白质阵列此外，一种新颖的平面端盖反射器设计 将开发与正交加速兼容的。这将是 用于现有的电子碰撞/正交加速仪器，以及 将进一步发展使用大气压MALDI作为电离 源头 这项技术有望带来高性能和串联能力 到一个简单，紧凑的仪器，可用于蛋白质组学研究。

DESCRIPTION (provided by applicant): We propose to design, build and develop a compact tandem time-of-flight mass spectrometer for high throughput proteomics research based upon several technologies being developed in our laboratory. In particular the first mass analyzer (MSI) will utilize mass-correlated acceleration to focus ions with different kinetic energies and independently of mass to a focus point that is the entrance to the second mass analyzer (MS2). MS2 will be an endcap reflectron, which provides high order (nearly quadratic) kinetic energy focusing. The collision chamber will be located early on in the flight tube of MS1 as it is an essential feature of this instrument that there are no decelerating or re-accelerating fields, either constant or pulsed, between the ion source and the entrance to the endcap reflectron. Thus, fragment ions associated with a mass-selected precursor ion, and produced by collision-induced dissociation (CID) or by metastable decomposition, will be recorded at the same flight time. The high energy bandwidth endcap reflectron does not require stepping or scanning to record the entire product ion mass range in each time-of-flight cycle. In addition, because this reflectron also does not require reacceleration of after collision, it will be possible to utilize the full ion kinetic energy (10-20 keV) in collisional activation. The instrument will be utilized in a number of ongoing research projects involving peptidic and glycolipid antigens, the structures of lipid A, and protein arrays on a chip. In addition, a novel planar endcap reflectron design will be developed that is compatible with orthogonal acceleration. This will be used on an existing electron impact/orthogonal acceleration instrument, and will be further developed using atmospheric pressure MALDI as the ionization source. This technology is expected to bring high performance and tandem capabilities to a simple, compact instrument that can be utilized in proteomics research.