BEAMS Lab at MIT: Status report
Introduction
It has been almost nine years since the Biological Engineering Accelerator Mass Spectrometry (BEAMS) Lab at the Massachusetts Institute of Technology was established. The AMS instrument that is at the core of the laboratory is based on a 1 MV tandem accelerator and was designed as a dual-isotope instrument with a gas-fed ion source. Research goals of the laboratory are centered around the application of carbon and tritium AMS to life sciences research. The nature of the samples involved in this kind of research and the need of making sample processing easier, less expensive and with higher throughput has driven the development of novel ways of sample introduction into the ion source of the accelerator. The omnipresent aim of those developments has been to use the AMS instrument as an online detector, allowing the introduction of samples in their original matrices or subsequent to resolution through separation techniques such as liquid or gas chromatography.
Volatile samples are amenable to high resolution separation by gas chromatography and the gas chromatograph can be coupled with a gas-accepting AMS ion source relatively easily. We recently described one such configuration for analysis of 14C-labeled compounds which incorporates simultaneous mass spectrometric analysis to improve compound identification [1]. Non-volatile samples present a greater challenge. We continue to pursue technologies for coupling liquid chromatography with AMS analysis but focus in this paper on analysis of non-volatile carbon samples such as plasma, urine, HPLC (high performance liquid chromatography) fractions, tissues and cell cultures, and sub-cellular fractions. These types of samples are processed using a laser-induced combustion interface described previously [2], [3], with further improvements presented here. We also describe a method for increasing sensitivity in the analysis of large volume samples in which the radiocarbon concentration is relatively low.
The BEAMS Lab instrument was originally intended for dual-isotope operation [4]. For carbon, the design allows the possibility of simultaneously measuring one of the stable isotopes 12C or 13C in a Faraday cup before the accelerator, while the system is tuned for 14C on the beam line. This enables either determination of isotope ratios or use of the stable isotope current as a parameter to normalize 14C-only measurements for variation in cathode efficiency. Given the characteristics of the instrument and the inherent ion optical conditions, measuring 1H in the carbon Faraday cups requires a change of multiple operating parameters, including the injector magnet, relative to the settings for detecting tritium, making the measurement of hydrogen current in real time unrealistic. To overcome this problem a change in the optics and the control of the operation of the whole system was required and is reported here.
Section snippets
Laser-induced combustion interface upgrade; low 14C concentration samples protocol
Liquid-phase carbon samples such as HPLC eluents, urine, and plasma are processed by means of the laser-induced combustion interface that directs CO2 produced from the samples into the gas-fed ion source. The conversion to graphite normally used for radiocarbon measurements is not performed. One improvement to the interface involves the CuO support, which was initially in the form of a narrow trough for continuous operation. This had been changed to a multi-well format (circle of 16), with the
Modification of the instrument for simultaneous detection of hydrogen and tritium
As noted in the introduction the BEAMS Lab instrument was designed to be used for tritium AMS as well as radiocarbon AMS; however, no provision was made for measurement of mass-1 stable isotope current simultaneously – or nearly so – with tritium particle counting. A major difficulty for us to overcome was that ions with m/z 1 and m/z 3 take vastly different trajectories through the injector magnet at the same field. Because of geometrical constraints we did not even consider the possibility of
Control system upgrade
A completely new control system has replaced the original system that was based on Group3 technology. Hardware and custom software was provided by Pyramid Technical Consultants, Inc. [7]. The technical approach is based on distributed control modules for the various power supplies and diagnostic elements, such as pressure gauges, valves, etc. Each digital/analog input/output control module is located as close as possible to a controlled unit and linked fiber-optically in loops to a loop
Conclusions
The latest modifications to the laser-induced combustion interface as well as a new protocol for increasing usable sample volume reported here expand the range of non-volatile carbon samples that can be analyzed in their original matrixes. They also provide the groundwork for development of a laser-induced combustion interface based on industry standard well-plate formats. The modifications for measuring 1H near-simultaneously with tritium particle counting are not quite complete but are
Acknowledgements
This work was partially supported by GlaxoSmithKline, grants from the NIH, P30-ES02109 for the MIT Center for Environmental Health Sciences and R42-CA084688, and made possible by UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is
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