Micro-PADI sources for applications in 2-D chemical imaging

在过去的几年中，随着高分辨率，小型（便携式）质谱仪的可用性，环境电离质谱法取得了一系列令人兴奋的发展。在这种技术中，普通样品表面的化学成分在其自然环境中可以用最少的样品制备直接分析。它已成功地应用于分析许多不同的材料，例如在制药和法医。其中一种主要的解吸-电离技术是解吸电喷雾电离（DESI），该技术于2004年由Cooks小组首次提出，已应用于环境条件下的大量样品。然而，环境电离的一些最令人兴奋的发展采用了各种大气压等离子体作为解吸和电离的介质。该项目的核心是等离子体辅助解吸电离（PADI）技术，该技术在包括生物样品在内的许多材料的分析中显示出巨大的前景，允许常规检测质量< 500 Da的物种。传统的PADI基于射频（13.56 MHz）等离子体针配置，产生冷的非平衡等离子体（气体温度约为300K）。它结构简单，在低电压下运行，并在针尖产生相对局部的等离子体羽流，宽度约为1毫米，长度可达几毫米，使其能够通过直接接触等离子体来远程激活表面。目前的PADI配置可能比电喷涂技术（DESI）有潜在的优势，因为它的设计允许在He原料中引入表面蚀刻或化学电离试剂。它也比DESI更容易使用，成本更低，对等离子体样品角度的精确要求更低，对样品的损害也很小（除了在最高功率下）。最重要的是，它产生的光谱更干净，信号强度通常比DESI高（通常是DESI的5-10倍）。尽管基于等离子体的环境解吸-电离技术取得了成功，但这些技术都没有提供足够的空间控制，以区分小于几百微米分辨率的化学特征。这显然限制了当前等离子体技术在二维表面化学成像应用中的应用，例如扫描探针显微镜。迄今为止，DESI是最成功的成像技术（空间分辨化学信息），因为它具有小的试剂束，据报道其空间分辨率低至40微米。然而，对于大面积的二维成像应用，DESI所需的相对大量的昂贵且有潜在危险的溶剂（1-10微升/分钟）使得二维方法不切实际。我们认为，生产适合高分辨率表面成像的小规模等离子体技术的解决方案是进一步开发最初为其他应用而设计的微等离子体源。这些是微空心阴极放电，开放式微通道放电和针状几何放电。通过精心设计，他们将产生小体积的等离子体，以实现低至10微米的解吸足迹的空间分辨率。最有希望的配置将进一步开发并集成到现有的质谱系统中。这项研究的一个关键特征是使用重复的纳秒持续时间，高压脉冲，为每个选择的源设计允许在环境空气中运行，包括静态和流动条件。本项目有5个主要研究任务。这些是，等离子体源设计和制造，源操作和测试，等离子体表征和诊断，解吸和电离研究以及通过扫描探针显微镜进行二维成像的发展。

In the last few years with the availability of high-resolution, small-scale (and portable) mass spectrometers, there has been a flurry of exciting developments in ambient ionisation mass spectrometry. In this technique the chemical composition of the surface of ordinary samples in their native environment can be analysed directly with minimal sample preparation. It has been applied successfully to the analysis many different materials, for instance in pharmaceuticals and forensics.One of the principle desorption-ionisation techniques is desorption electrospray ionization (DESI) first introduced by the group of Cooks in 2004, which has been applied to a plethora of samples in ambient conditions. However, some of the most exciting developments in ambient ionization employ a variety of atmospheric-pressure plasmas as the medium for desorption and ionisation. The plasma-based technique at the heart of this project is plasma-assisted desorption ionization (PADI) which is showing significant promise for the analysis of many materials including biological samples, allowing species of mass < 500 Da to be routinely detected. Conventional PADI is based on the RF (13.56 MHz) plasma needle configuration producing a cold non-equilibrium plasma (gas temperatures around 300K). It is simple in construction, runs at low voltages and produces a relatively localised plasma plume at the needle tip of about 1 mm in width and up to several mm's in length allowing it to remotely activate the surface through direct contact of the plasma. The current PADI configuration may have potential advantages over electro-spraying techniques (DESI), since its design allows for the introduction of surface etching or chemical ionisation reagents in the He feedstock. It is also easier to use than DESI, lower in cost, and with less precise requirements for plasma-sample angles and produces little damage to the sample (except at the highest powers). Most importantly, it produces cleaner spectra with generally higher signal intensities than DESI (5-10 times typically).Despite the success of the plasma-based ambient desorption-ionization techniques none of these techniques provide the sufficient spatial control necessary to distinguish chemical features with less than a few hundred microns resolution. This clearly limits current plasma techniques for 2-D surface chemical imaging applications, for instance in scanning-probe microscopy. To date, DESI is the most successful technique for imaging (spatially resolved chemical information) since it has small reagent beams with spatial resolutions reported to be down to 40 microns. However, for large area, 2D imaging applications the relatively large volume of costly and potentially hazardous solvent required by DESI (1-10 micro-L/min) makes the 2-D approach impractical. We believe the solution to producing small-scale plasma technology, suitable for high-resolution surface imaging, is to further develop micro-plasma sources originally designed for other applications. These are micro-hollow cathode discharges, open-ended micro-channel discharges and needle geometry discharges. Through careful design they will produce small volume plasmas necessary to achieve a spatial resolution of the desorption footprint down to 10 microns. The most promising configurations will be developed further and integrated into existing mass spectroscopic systems. One key feature of this research will be the use of repetitive nanosecond duration, high-voltage pulsing, for each of chosen source designs to allow operation in ambient air, both static and flowing conditions. The project has 5 main research tasks. These are, plasma source design and fabrication, source operation and testing, plasma characterisation and diagnosis, study of desorption and ionisation and the development of 2-D imaging through scanning probe microscopy.