Hilton G C, Martinis J M, Wollman D A, Irwin K D, Dulcie L L, Gerber D, Gillevet P M, Twerenbold D
National Institute of Standards and Technology, Boulder, Colorado 80303, USA.
Nature. 1998 Feb 12;391(6668):672-5. doi: 10.1038/35582.
Time-of-flight mass spectrometry-most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry-is an important class of techniques for the study of proteins and other biomolecules. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there has been limited success in achieving good mass resolution at higher masses. This is because the sensitivity of the microchannel plate (MCP) detectors used in most systems decreases rapidly with increasing particle mass, limiting the utility of MCP detectors for very large masses. It has recently been proposed that cryogenic particle detectors may provide a solution to these difficulties. Cryogenic detectors measure the thermal energy deposited by the particle impact, and thus have a sensitivity that is largely independent of particle mass. Recent experiments have demonstrated the sensitivity of cryogenic particle detectors to single biomolecules, a quantum efficiency several orders of magnitude larger than the MCP detectors, and sensitivity to masses as large as 750,000 daltons. Here we present results demonstrating an order of magnitude better energy resolution than previous measurements, allowing direct determination of particle charge state during acceleration. Although application of these detectors to practical mass spectrometry will require further development of the detectors and cryogenics, these detectors can be used to elucidate the performance-limiting processes that occur in such systems.
飞行时间质谱法——最显著的是基质辅助激光解吸电离飞行时间（MALDI - TOF）质谱法——是研究蛋白质和其他生物分子的一类重要技术。尽管这些技术在分析分子量高达约20,000道尔顿的物质时表现出色，但在更高分子量下实现良好的质量分辨率方面取得的成功有限。这是因为大多数系统中使用的微通道板（MCP）探测器的灵敏度会随着粒子质量的增加而迅速下降，限制了MCP探测器对非常大质量物质的应用。最近有人提出，低温粒子探测器可能为解决这些难题提供一种方案。低温探测器测量粒子撞击所沉积的热能，因此其灵敏度在很大程度上与粒子质量无关。最近的实验已经证明了低温粒子探测器对单个生物分子的灵敏度、比MCP探测器大几个数量级的量子效率以及对高达750,000道尔顿质量的灵敏度。在此，我们展示的结果表明能量分辨率比先前测量提高了一个数量级，从而能够在加速过程中直接确定粒子电荷状态。尽管将这些探测器应用于实际质谱分析还需要进一步开发探测器和低温技术，但这些探测器可用于阐明此类系统中出现的性能限制过程。
