Accelerator Mass Spectrometry Measurements Research Articles

Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development

The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of (14)C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the (14)C label), stable across samples storage conditions for at least 1 year, linear over four orders of magnitude with an analytical range from 0.1 Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was excellent (between 1 and 3%), while precision expressed as coefficient of variation was between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of (14)C, respectively (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with (14)C corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a sensitive, accurate and precise method of measuring drug compounds in biological matrices.

Development of laboratory standards for AMS measurement of 237Np

Abstract A new method for the preparation of 237 Np/ 238 U laboratory standards for accelerator mass spectrometry (AMS) measurement was developed at China Institute of Atomic Energy (CIAE). 237 Np was generated by β-decay (6.75 days) of 237 U produced via fast neutron induced 238 U(n,2n) 237 U reaction. The 58 Co(n,2n) 59 Co and 93 Nb(n,2n) 92m Nb reactions were used to monitor the integral incident neutron flux. The cross-section of 238 U(n,2n) 237 U was determined by measuring the emission rate of 208.0 keV γ-rays from 237 U decay with a calibrated HPGe γ-ray spectrometer at CIAE. In order to correct for the self-attenuation of 208.0 keV γ-ray in the U sample, a 177 Lu–U method was introduced. The new correction method provided effective and high quality measurements of the cross-section for the 238 U(n,2n) 237 U reaction; and the 237 Np/ 238 U ratio. A series of AMS standards for 237 Np/ 238 U (10 −9 –10 −13 ) can be obtained by successive dilution of the original standard sample.

Zagrada—The New Zagreb Radiocarbon Database

After introducing the liquid scintillation counting (LSC) method and graphite target preparation for accelerator mass spectrometry (AMS) measurements in the Zagreb Radiocarbon Laboratory, the existing database software designed only for gas proportional counting (GPC) (using a DOS operating system) could not satisfy the requirements for parallel conduction of several techniques. This has been enabled recently by the development of the new relational database ZAGRADA, which—using SQL scripts and constraints defined by primary and foreign keys—enforces high data integrity and provides better performances in data filtering and sorting. The structural scheme of this database conceptually comprises 4 basic modules with data on the samples, chemical pretreatment and preparation, measurements and data on the final results. A user-friendly graphical user interface has been designed to perform various actions and data manipulation to the database. The implementation of a new database for 14C samples has significant contribution to scientific research performed in the Radiocarbon and Tritium Laboratory and to quality assurance and quality control, and will enable better and easier communication with customers.

Radiocarbon AMS Data Analysis: From Measured Isotopic Ratios to 14C Concentrations

Radiocarbon accelerator mass spectrometry (AMS) measurements are always carried out relative to internationally accepted standards with known 14C activities. The determination of accurate 14C concentrations relies on the fact that standards and unknown samples must be measured under the same conditions. When this is not the case, data reduction is either performed by splitting the collected data set into subsets with consistent measurement conditions or by applying correction factors.This paper introduces a mathematical framework that exploits the intrinsic variability of an AMS system by combining arbitrary measurement parameters into a normalization function. This novel approach allows the en-masse reduction of large data sets by providing individual normalization factors for each data point. Both general features and practicalities necessary for its efficient application are discussed.

Temporal and Spatial Variations in Freshwater14C Reservoir Effects: Lake Mývatn, Northern Iceland

Lake Mývatn is an interior highland lake in northern Iceland that forms a unique ecosystem of international scientific importance and is surrounded by a landscape rich in archaeological and paleoenvironmental sites. A significant freshwater reservoir effect (FRE) has been identified in carbon from the lake at some Viking (about AD 870–1000) archaeological sites in the wider region (Mývatnssveit). Previous accelerator mass spectrometry (AMS) measurements indicated this FRE was about 1500–190014C yr. Here, we present the results of a study using stable isotope and14C measurements to quantify the Mývatn FRE for both the Viking and modern periods. This work has identified a temporally variable FRE that is greatly in excess of previous assessments. New, paired samples of contemporaneous bone from terrestrial herbivores and omnivores (including humans) from Viking sites demonstrate at least some omnivore diets incorporated sufficient freshwater resources to result in a herbivore-omnivore age offset of up to 40014C yr. Modern samples of benthic detritus, aquatic plants, zooplankton, invertebrates, and freshwater fish indicate an FRE in excess of 500014C yr in some species. Likely geothermal mechanisms for this large FRE are discussed, along with implications for both chronological reconstruction and integrated investigation of stable and radioactive isotopes.

The Fifth International Radiocarbon Intercomparison (VIRI): An Assessment of Laboratory Performance in Stage 3

Proficiency testing is a widely used, international procedure common within the analytical chemistry community. A proficiency trial (which VIRI is) often follows a standard protocol, including analysis that is typically based on z-scores, with one key quantity, σp. From a laboratory intercomparison (sometimes called a proficiency trial), we hope to gain an assessment of accuracy (in this case, from dendro-dated samples), laboratory precision (from any duplicate samples), and generally, an overall measure of performance, including measurement variability and hence realistic estimates of uncertainty. In addition, given our stated aim of creating an archive of reference materials, we also gain a determination of consensus values for new reference materials.VIRI samples have been chosen to deliver these objectives and the sample ages included in the different stages, by design, spanned modern to background. With regard to pretreatment, some samples required intensive pretreatment (e.g. bone), while others required none (e.g. cellulose and humic acid). Sample size was not optimized, and indeed some samples were provided solely for accelerator mass spectrometry (AMS) measurement. In this sense, VIRI presented a more challenging exercise than previous intercomparisons, since by its design in stages, one can explore improvements (or deteriorations) over time in laboratory performance. At each stage, more than 50 laboratories have participated, with an increasing demographic shift towards more AMS and fewer radiometric laboratories.

Studies on the Preparation of Small 14C Samples with an RGA and 13C-Enriched Material

The minimum size of radiocarbon samples for which reliable results can be obtained in an accelerator mass spectrometry (AMS) measurement is in many cases limited by carbon contamination introduced during sample preparation (i.e. all physical and chemical steps to which samples were subjected, starting from sampling). Efforts to reduce the sample size limit down to a few μg carbon require comprehensive systematic investigations to assess the amount of contamination and the process yields. We are introducing additional methods to speed up this process and to obtain more reliable results. A residual gas analyzer (RGA) is used to study combustion and graphitization reactions. We could optimize the reaction process at small CO2 pressures and identify detrimental side reactions. Knowing the composition of the residual gas in a graphitization process allows a reliable judgment on the completeness of the reaction. Further, we use isotopically enriched 13C (≥98% 13C) as a test material to determine contamination levels. This offers significant advantages: 1) The measurement of 12C/13C in CO2 is possible on-line with the RGA, which significantly reduces turnaround times compared to AMS measurements; 2) Both the reaction yield and the amount of contamination can be determined from a single test sample.The first applications of isotopically enriched 13C and the RGA have revealed that our prototype setup has room for improvements via better hardware; however, significant improvements of our sample processing procedures were achieved, eventually arriving at an overall contamination level of 0.12 to 0.15 μg C during sample preparation (i.e. freeze-drying, combustion, and graphitization) of μg-sized samples in aqueous solution, with above 50% yield.

Optimization of the Graphitization Process at Age-1

The reaction conditions for the graphitization of CO2 with hydrogen were optimized for a fast production of high-quality carbon samples for accelerator mass spectrometry (AMS) measurement. The iron catalyst in use is first oxidized by heating with air to remove possible carbon and other impurities and then after evacuation reduced back to iron with hydrogen in several flushing steps to remove any iron oxide. The optimum conditions for a fast graphitization reaction were experimentally determined by changing the reaction temperatures and the H2/CO2 ratio. The resulting graphite samples were measured by AMS to find the smallest isotopic changes (δ13C) at a minimum of molecular fragment formation (13CH current). The improvements are based on thermodynamic data and are explained with Baur-Glaessner diagrams.

Refining Background Corrections for Radiocarbon Dating of Bone Collagen at Orau

During the laboratory pretreatment of samples for radiocarbon dating, small amounts of carbon may be added to a sample. Contamination can be incorporated at any stage: during chemical pretreatment, combustion to CO2, graphitization, or accelerator mass spectrometry (AMS) measurement. Such carbon contamination is often modern in age, and so can have an especially severe effect on samples older than ∼25 ka BP. During the extraction of collagen from bone using the ultrafiltration protocol at the Oxford Radiocarbon Accelerator Unit (ORAU), small amounts of young carbon are added to the sample. Currently, this contamination is poorly characterized when less than 10 mg of collagen is extracted from a bone. Demand to date small collagen samples with 14C concentrations that approach the detection limit of AMS measurement has increased recently with the growing interest in, for example, directly dating Neanderthal remains and Upper Paleolithic bone artifacts. This paper aims to reduce the minimum collagen sample size required to produce a reliable date from 10 to 5 mg by re-examining the combustion background and subsequently the pretreatment background for bone. The average of 136 measurements of directly combusted nylon suggests that 0.0007 ± 0.001 mg of modern carbon is added to each sample, although the distribution is positively skewed. Regression analysis of the measurements of 52 collagen samples extracted from a bone of background age results in a background of just less than 50,000 BP for bone treated at ORAU.

Developing Ultra Small-Scale Radiocarbon Sample Measurement at the University of Tokyo

We have developed accelerator mass spectrometry (AMS) measurement techniques for ultra small-size samples ranging from 0.01 to 0.10 mg C with a new type of MC-SNICS ion source system. We can generate 4 times higher ion beam current intensity for ultra-small samples by optimization of graphite position in the target holder with the new ionizer geometry. CO2 gas graphitized in the newly developed vacuum line is pressed to a depth of 1.5 mm from the front of the target holder. This is much deeper than the previous position at 0.35 mm depth. We measured 12C4+ beam currents generated by small standards and ion beam currents (15–30 μA) from the targets in optimized position, lasting 20 min for 0.01 mg C and 65 min for 0.10 mg C. We observed that the measured 14C/12C ratios are unaffected by the difference of ion beam currents ranging from 5 to 30 μA, enabling measurement of ultra-small samples with high precision. Examination of the background samples revealed 1.1 μg of modern and 1 μg of dead carbon contaminations during target graphite preparation. We make corrections for the contamination from both the modern and background components. Reduction of the contamination is necessary for conducting more accurate measurement.

Experiences of Production and Homogeneity Analysis of an AMS 14C Sucrose Standard for High-Activity Measurements

Accurate accelerator mass spectrometry (AMS) measurements rely on standards with well-known isotopic ratios. For radiocarbon measurements, a number of standards with different properties are commercially available, of which the IAEA-C6 sucrose standard with a 14C value of 150.61 pMC is the most active. When analyzing biological samples resulting from studies using 14C-labeled substances, the activity content can be up to 100 times this value. Thus, there is a need for a standard material with higher activity content than IAEA-C6 for making accurate AMS measurements on this type of sample. This paper describes the attempts of producing a standard with an activity content of about 10 times modern carbon. The material chosen has to be chemically inert, preferably non-toxic, commercially available in 14C-labeled form, and the activity must be homogeneously distributed within the material. Two different standard materials were considered: urea and sucrose. Sucrose was chosen for the new standard, since it is non-toxic, inexpensive, and organic and on combustion, forms only carbon dioxide (CO2) and water (H2O). In this paper, we discuss our experience in the production and homogeneity analysis of this material, from the crystallization of the sucrose solution to the graphitization of the samples. When using an online combustion method and a septa-sealed vial reduction method, the AMS measurements indicated that the activity was not homogeneously distributed throughout the material. Contrary to this, measurements of the sucrose solution prior to recrystallization indicated that the activity was more homogeneously distributed before than after the recrystallization. In order to determine whether the inhomogeneity depended on the graphitization method (i.e. the combustion or the reduction method) or on the material itself, 3 different graphitization methods and 2 different methods of recrystallization were tested.

Simple Pretreatment Method Development for Iron and Calcium Carbonate Samples

Since iron artifacts generally contain trace amounts of carbon, an iron sample needs to be relatively large, as compared to other materials, and a specially designed combustion system is required. An elemental analyzer (EA) was used for the combustion of iron without any special chemical treatment. CO2 gas with 1 mg of carbon was obtained from the combustion of an iron artifact by using an EA and reduced to graphite for accelerator mass spectrometry (AMS) measurement. In this work, AMS dating results done at the Korea Institute of Geoscience and Mineral Resources (KIGAM) for several ancient iron artifacts are presented and compared with independently estimated ages. This method was found to be useful for the pretreatment of iron artifacts that contained >0.1% carbon. A simple pretreatment method using an EA was also applied to calcium carbonate (CaCO3) samples. Samples were preheated overnight at 100–300 °C, without any special chemical treatment. This removed modern CO2 contamination and the background level decreased to a comparable value measured in samples treated with phosphoric acid under vacuum.

14C sample preparation for AMS microdosing studies at Lund University using online combustion and septa-sealed vials

The Department of Physics at Lund University is participating in a European Union project called EUMAPP (European Union Microdose AMS Partnership Programme), in which sample preparation and accelerator mass spectrometry (AMS) measurements of biological samples from microdosing studies have been made. This paper describes a simplified method of converting biological samples to solid graphite for C-14 analysis with AMS. The method is based on online combustion of the samples, and reduction of CO2 in septa-sealed vials. The septa-sealed vials and disposable materials are used to eliminate sample cross-contamination. Measurements of ANU and Ox I standards show deviations of 2% and 3%, respectively, relative to reference values. This level of accuracy is sufficient for biological samples from microdosing studies. Since the method has very few handling steps from sample to graphite, the risk of failure during the sample preparation process is minimized, making the method easy to use in routine preparation of samples. (C) 2009 Elsevier B.V. All rights reserved. (Less)

Direct measurements of small 14C samples after oxidation in quartz tubes

Small 14C samples gain importance in environmental research and for dating purposes. However, throughput of such samples is limited by the preparation of graphite targets for accelerator mass spectrometry (AMS) measurements. In our approach, oxidation of samples with copper oxide in quartz tubes was applied to form CO 2 which was measured directly with the gas ion source of the small AMS facility MICADAS. The presented method was designed to meet the requirements for fast and easy handling of small samples (<100 μg carbon). As combustion byproducts are likely to interfere with ionisation processes in the gas ion source, we additionally investigated the effects of several gases on C − currents.

Effective Determination of the Long-lived Nuclide 41Ca in Nuclear Reactor Bioshield Concretes: Comparison of Liquid Scintillation Counting and Accelerator Mass Spectrometry

The routine application of liquid scintillation counting to (41)Ca determination has been hindered by the absence of traceable calibration standards of known (41)Ca activity concentrations. The introduction of the new IRMM (41)Ca mass-spectrometric standards with sufficiently high (41)Ca activities for radiometric detection has partly overcome this although accurate measurement of stable Ca concentrations coupled with precise half-life data are still required to correct the certified (41)Ca:(40)Ca ratios to (41)Ca activity concentrations. In this study, (41)Ca efficiency versus quench curves have been produced using the IRMM standard, and their accuracy validated by comparison with theoretical calculations of (41)Ca efficiencies. Further verification of the technique was achieved through the analysis of (41)Ca in a reactor bioshield core that had been previously investigated for other radionuclide variations. Calcium-41 activity concentrations of up to 25 Bq/g were detected. Accelerator mass spectrometry (AMS) measurements of the same suite of samples showed a very good agreement, providing validation of the procedure. Calcium-41 activity concentrations declined exponentially with distance from the core of the nuclear reactor and correlated well with the predicted neutron flux.

Radiocarbon Dating History: Early Days, Questions, and Problems Met

W F Libby's new dating method from the 1940s, based on experience in physics and chemistry, opened possibilities to check and revise chronologies built on other principles than radioactive decay. Libby's method initially implied collaboration with archaeologists to demonstrate that it worked but also with physicists to improve the technique to measure low β–activities. Chemists, geophysicists, botanists, physiologists, statisticians, and other researchers have contributed to a prosperous interdisciplinary development. Some pitfalls were not recognized from the beginning, although issues such as contamination problems were foreseen by Libby. Pretreatment of samples was discussed very early by de Vries and collaborators, among others. This subject has not yet been abandoned. Closely related to pretreatment is the choice of fraction to be dated and chemicals to be used, especially for accelerator mass spectrometry (AMS) measurements. Calibration against tree rings and comparison with dates obtained using other methods as well as intercomparison projects are partly history but still very actual. The impact by man and climate is also studied since the early days of the method. Also, the carbon cycle has been of great interest. The tools for measurements and statistical analysis have been improved during these first 3 or 4 decades, allowing interpretations not possible earlier. δ13C determinations are mostly very important and useful, but sometimes they have been misleading in discussions of the origin of carbon, especially for human tissues—the metabolism was not yet fully understood. The history and development of the method can only be illustrated by selected examples in a survey like this.

Accelerator mass spectrometry 14C determination in CO2 produced from laser decomposition of aragonite

The determination of (14)C in aragonite (CaCO(3)) decomposed thermally to CO(2) using an yttrium-aluminum-garnet doped neodymium laser is reported. Laser decomposition accelerator mass spectrometry (LD-AMS) measurements reproduce AMS determinations of (14)C from the conventional reaction of aragonite with concentrated phosphoric acid. The lack of significant differences between these sets of measurements indicates that LD-AMS radiocarbon dating can overcome the significant fractionation that has been observed during stable isotope (C and O) laser decomposition analysis of different carbonate minerals. The laser regularly converted nearly 30% of material removed into CO(2) despite it being optimized for ablation, where laser energy breaks material apart rather than chemically altering it. These results illustrate promise for using laser decomposition on the front-end of AMS systems that directly measure CO(2) gas. The feasibility of such measurements depends on (1) the improvement of material removal and/or CO(2) generation efficiency of the laser decomposition system and (2) the ionization efficiency of AMS systems measuring continuously flowing CO(2).

The 14C AMS facility at LABEC, Florence

The main facility of the new INFN laboratory in Florence (LABEC, LAboratorio di tecniche nucleari per i BEni Culturali) is a 3MV Tandetron accelerator, manufactured by High Voltage Engineering Europe, used for both Accelerator Mass Spectrometry and Ion Beam Analysis (IBA) measurements. The AMS beam line is equipped with a 59-sample sputter ion source and a sequential injector – on the low energy side – and a spectrometer composed of a 115° analysing magnet and a 65° electrostatic analyser – on the high energy side.A sample preparation laboratory has been installed for radiocarbon measurements. Combustion of pre-treated organic samples is performed using an elemental analyser; four parallel graphitisation reactors are available for CO2 reduction.In this paper, the performance of the whole system is presented: 14C values of chemistry blanks correspond to radiocarbon ages in the order of 50,000 years BP; measurements of 14C concentration in different standard reference materials demonstrate good accuracy.

How Clean is Ultrafiltration Cleaning of Bone Collagen?

As part of our bone dating development, we have tested the ultrafiltration of bone gelatin using 2 different filters—Vivaspin 20™ (VS20), a polyethersulfone, and Vivaspin 15R™ (VS15R), a cellulose, both with a 30,000 molecular weight cutoff—and bone collagen from dated samples ranging in age from 1.5 to &gt;50 kyr BP. A direct accelerator mass spectrometry (AMS) measurement yielded radiocarbon concentrations of ∼0.5 pMC (∼42 kyr) for the polyethersulfone, ∼14.4–17.5 pMC (∼15.6–14 kyr) for the cellulose, and ∼107.4 pMC for the glycerin. The filters were cleaned before use similar to the Oxford protocol (Bronk Ramsey et al. 2004), and a series of freeze-dried archaeological bone gelatin samples and a modern pig-skin gelatin were passed through VS20 and VS15R filters (Vivascience™). We recovered both the eluent (&lt;30-kD fraction) and the liquid that stayed above the filter (&gt;30 kD) in order to obtain a carbon mass and isotope balance. While the &gt;30-kD collagen fraction that is usually selected for AMS analysis does not appear to be significantly contaminated, measurements show significant age differences between the eluent &lt;30 kD and the unfiltered bone collagen, indicating that, despite cleaning, both glycerin and filter still give off contaminants in the eluent. Ultrafiltration with young collagen from pig skin generally confirms these results for the &lt;30-kD fraction but also shows the possibility of small contaminations in the &gt;30-kD fraction. Until a contamination with filter carbon of the &gt;30-kD collagen fraction can be excluded, we would recommend caution in the use of ultrafiltration for cleaning bone collagen with VS20 or VS15R ultrafilters.

AMS 14C Sample Preparation at the KCCAMS/UCI Facility: Status Report and Performance of Small Samples

We present an overview of accelerator mass spectrometry (AMS) radiocarbon sample preparation and measurements, describing the technical upgrades that now allow us to routinely obtain 0.2–0.3% precision for 1-mg carbon samples. A precision of ∼1% on samples with 100 μg of carbon can also be achieved. We have also developed graphitization techniques and AMS procedures for ultra-small samples (down to 0.002 mg of carbon). Detailed time series are presented for large and small aliquots of standards such as NIST OX-I and OX-II; FIRI-C and -D; IAEA-C6, -C7 and -C8; and 14C-free samples.