Laser Ablation-ICPTOF for fast multi-element imaging of biomedical samples

了解细胞、器官和组织中元素的空间分布有助于了解 疾病、诊断和治疗。激光烧蚀电感耦合等离子体质谱(LA-ICPMS) 是一种基于实验室的元素成像技术，它正越来越多地应用于生物医学应用 具有与其他基本成像技术相当或更低的检测极限，并且潜在地更容易获得 和可操作性。达特茅斯微量元素分析核心(TEAC)是一个久负盛名的 支持全美研究人员的共享资源由经验丰富的研究人员组成 元素成像和电感耦合等离子体质谱仪，并与行业合作伙伴建立了良好的联系。2021年，TEAC的资金来自 NIGMS(R24 GM141194-01)建立生物医学国家元素影像资源(BNEIR)以 加快并简化生物医学研究人员获取仪器、专业知识的途径，并促进 基本成像用户社区。为了真正使BNIER成为世界级的元素成像设备，我们 建议将目前的TEAC LA-ICP-MS仪器升级为更快的激光消融系统，具有 超快洗涤电池(ImageBIO266，Elemental Science Laser，Bozeman，MT)和飞行时间电感耦合等离子体质谱仪 (ICPTOF)。ImageBIO266是专门为用激光对生物标本成像而新设计的 频率高达1000赫兹，而不是我们目前的20赫兹，这意味着它可以扫描(图像)高达 比我们目前的系统快50倍。这种新系统的快速洗出样品池(TV3)提供了 脉冲宽度为1-3毫秒的激光脉冲到电感耦合等离子体质谱仪，从而向背景提供异常信号 比率。然而，只有ICPTOF系统具有足够快的数据采集速度，可以在50%到50%的范围内收集每个像素的数据。 1000赫兹激光发射速率和短脉冲宽度。在过去的五年里，这些快速激光消融-ICPTOF 系统已经成为快速元素成像的最先进技术。IcpTOF S2(瑞士TOFWERK) 是一种高灵敏度飞行时间电感耦合等离子体质谱仪模型，专为生物医学等应用而设计 元素成像。IcpTOF S2每30微秒收集一次所有可能的基本数据，而传统 四极ICPMS(Q-ICPMS)系统的速度要慢得多(毫秒)，特别是当多种元素 收好了。相比之下，连接到icpTOF S2的ImageBIO266可以更快地成像10-50倍并且默认情况下， 收集所有可测量的元素。ImageBIO266的最高分辨率(最小激光光斑尺寸)为1微米 而以这种细胞级别的分辨率收集数据只有在时间上使用icpTOF才是可行的 S2。因此，更高分辨率、更快的激光发射频率和更快的冲刷样品池的全部潜力 ImageBIO266只能由icpTOF S2充分利用。这种尖端的仪器将在 NIGMS资助的元素成像资源的成功，并将立即使我们的NIH资助的用户受益， 包括IDEA州的地区性INBRE计划，在其数据的质量和空间分辨率方面并增加了 样本吞吐量。

Knowledge of the spatial distribution of elements within cells, organs and tissue can help inform mechanisms of disease, diagnosis, and treatment. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a laboratory-based elemental imaging technique that it is increasingly being applied to biomedical applications with comparable or lower detection limits than other elemental imaging techniques and, potentially, easier access and operability. The Dartmouth Trace Element Analysis Core (TEAC) is an established and highly regarded shared resource that supports researchers throughout the US, is staffed by experienced researchers in elemental imaging and ICP-MS and has excellent links to industry partners. In 2021 the TEAC was funded by NIGMS (R24 GM141194-01) to establish the Biomedical National Elemental Imaging Resource (BNEIR) to accelerate and simplify access for biomedical researchers to instrumentation, expertise, and to foster a dynamic community for elemental imaging users. To truly make BNIER a world class elemental Imaging facility we proposed to upgrade the current TEAC LA-ICP-MS instrumentation to a faster laser ablation system with an ultrafast washout cell (imageBIO266, Elemental Scientific Lasers, Bozeman, MT) and a time-of-flight ICP-MS (ICPTOF). The imageBIO266 is newly designed specifically for imaging biological specimens with a laser frequency of up to 1000 Hz as opposed to the 20Hz of our current laser, meaning that it can scan (image) up to 50 times faster than our current system. The fast wash out sample cell (TV3) of this new system delivers the laser pulse to the ICP-MS with pulse widths of 1 -3 msec and thus provides exceptional signal to background ratios. However, only ICPTOF systems have fast enough data acquisition to collect per pixel data at the 50 – 1000HZ laser firing rates and short pulse widths. Within the last five years these fast laser ablation-ICPTOF systems have become the state for the art for fast elemental imaging. The icpTOF S2 (TOFWERK, Switzerland) is a high sensitivity time-of-flight ICP-MS model designed specifically for applications such as biomedical elemental imaging. The icpTOF S2 collects all possible elemental data every 30 µsec, whereas conventional quadrupole ICP-MS (Q-ICP-MS) systems are much slower (msec), especially when multiple elements are collected. By contrast, the ImageBIO266 coupled to an icpTOF S2 can image 10 – 50X faster and by default, collects all measurable elements. The highest resolution (smallest laser spot size) of the ImageBIO266 is 1 µm and collecting data at this cellular-level resolution would only be practical from a time standpoint with an icpTOF S2. Hence, the full potential of higher resolution, faster laser firing frequency, and faster washout sample cell of the imageBIO266 can only be fully utilized by icpTOF S2. This cutting-edge instrumentation will be pivotal in the success of our NIGMS-funded elemental imaging resource and will immediately benefit our NIH-funded users, including regional INBRE programs in IDeA states, in the quality and spatial resolution of their data and increased sample throughput.