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

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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.