Development of Multiplexed ToF-SIMS Instrumentation

飞行时间二次离子质谱仪(ToF-SIMS)是一种功能强大、应用广泛的表面化学分析方法。这项技术包括用高能初级离子束轰击样品，并检测被抛出的分子次级离子的化学成分。曼彻斯特大学的研究小组在TOF-SIMS技术的开发和分析应用方面已经获得了30多年的国际领先声誉。近年来，新型初级离子束，如C60和大质量气体团簇(如Ar2000)的发展，扩大了可探测的化学范围，使深度和3D分子分析超越了表面区。这大大加快了该技术在学术和工业实验室中的采用，用于测量生物细胞和先进材料和设备等复杂分子系统，并在医疗诊断和制造方面取得了进展。传统上，ToF-SIMS测量依赖于多个实验周期的信号平均(SA)来最大化信噪比和由此产生的灵敏度。每个周期包括一个短的(纳秒)初级离子脉冲，然后测量次级离子从样品喷射到探测器的飞行时间(最长0.2毫秒)，以确定它们的质量电荷比(m/z)。M/z比反过来提供了有关被检测离子的化学信息，从而提供了样品的化学信息。在这种配置中，系统等待每个周期中的所有二次离子到达探测器，然后才开始下一个周期-数据本质上是稀疏的。由于最大m/z离子飞行时间的限制，导致较差的占空比，导致初级离子利用率低(&lt；0.1%)和实验测量时间过长。在产生样品表面的逐个像素的化学图像时，要使用很多(~100万)个实验循环来获得所需的灵敏度，通常需要几个小时的实验时间。将分析扩展到次表层区域(深度剖析或三维成像)需要的时间要长许多倍，或者涉及不同的方法，从而只分析一小部分样品，并丢失潜在的重要信息。在这里，我们提出了一种多路复用方法，其中多个二次离子包被同时测量。这允许更有效地(高达50%)使用主波束来产生信号，并确保总和质谱图更快地会聚到灵敏而准确的测量。这代表了ToF-SIMS的一个全新范式。开发必要的硬件(离子光学和电子学)、计算机控制和数据处理软件是一项冒险的任务，我们为此组建了一个多学科的学术和工业团队，处于独特的地位来迎接这一挑战。结果将大大改善信噪比，从而在更短的实验中获得更高的灵敏度。这将增加TOF-SIMS技术的吞吐量和分析能力，并扩大可以分析的复杂样品的范围。分析能力提高的好处将影响到许多使用这项技术的行业，包括先进制造业和医疗保健。

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a powerful and widely used method for surface chemical analysis. The technique involves bombarding a sample with a high energy primary ion beam and detecting the chemistry of the molecular secondary ions that are ejected. The research group at the University of Manchester has over 30 years acquired an internationally-leading reputation for the development and analytical application of the ToF-SIMS technique. In recent years the development of novel primary ion beams such as C60 and massive gas clusters (e.g. Ar2000) has extended the range of chemistry that can be detected and allowed in-depth and 3D molecular analysis beyond the surface region. This has greatly accelerated the uptake of the technique in academic and industrial labs, to measure complex molecular systems such as biological cells and advanced materials and devices, and to make advances in healthcare diagnostics and manufacturing. Conventionally, ToF-SIMS measurements rely on signal averaging (SA) over multiple experimental cycles to maximise the signal-to-noise ratio and resulting sensitivity. Each cycle consists of a short (nanosecond) primary ion pulse, followed by the measurement of the flight time (up to 0.2 milliseconds) of secondary ions, ejected from the sample, to a detector to determine their mass-to-charge (m/z) ratio. The m/z ratio in turn provides information about the chemistry of the detected ions and therefore of the sample. In this configuration the system waits for all secondary ions in each cycle to reach the detector before beginning the next cycle - the data is inherently sparse. The resulting poor duty cycle limited by the flight time of the largest m/z ion leads to inefficient (<0.1%) primary ion usage and long experimental measurements. In producing a pixel-by-pixel chemical image of the sample surface very many (~1 million) experimental cycles are used to gain the required sensitivity, often taking several hours of experiment time. Extending the analysis to the sub-surface region (depth-profiling or 3D imaging) requires many times longer or involves a different methodology whereby only a small fraction of the sample is analysed and potentially important information is lost. Here we present a multiplexing methodology in which multiple secondary ion packets are measured simultaneously. This allows much more efficient (up to 50%) usage of the primary beam for signal generation and ensures that the summed mass spectra more rapidly converge to a sensitive and accurate measurement. This represents a completely new paradigm for ToF-SIMS. The development of the necessary hardware (ion optics and electronics), computer control and data processing software is an adventurous task for which we have put together a multidisciplinary academic and industrial team, uniquely positioned to meet this challenge. The result will be greatly improved signal-to-noise and therefore greater sensitivity in shorter experiments. This will increase the throughput and analytical power of the ToF-SIMS technique and extend the range of complex samples that can be analysed. Benefits of improved analytical power will impact on many sectors using this technology including advanced manufacturing and healthcare.