Practical Application of Thermal Ionization Mass Spectrometry for the Determination of Plutonium for the LANL Bioassay Program

(LA-UR-00-1697)

Sandra E. Wagner*, Stephanie Boone, John W. Chamberlin, Clarence J. Duffy, Deward W. Efurd, Kimberley M. Israel, Nancy L. Koski, Diana L. Kottmann, Dawn Lewis,

Peter C. Lindahl, Fred R. Roensch, Robert E. Steiner

Los Alamos National Laboratory, P.O. Box 1663, MS J514, Los Alamos, NM, USA 87545

Presented at the Fifth International

Conference on Methods and Applications of Radioanalytical Chemistry (MARC V)

Kailua-Kona, HI, USA, April 9-14, 2000

This paper discusses the practical application of thermal ionization mass spectrometry for the determination of ultra low-level plutonium in urine for the Los Alamos National Laboratory Bioassay Program. Utilization of thermal ionization mass spectrometry as a routine analytical service provided to the Los Alamos National Laboratory internal dosimetry group has evolved significantly since its implementation just over three years ago. Converting this unique research tool designed to support nuclear weapons testing to a quasi-production mode for the routine analysis of ~300 urine samples/year has required resolution of numerous practical issues. These issues include clean-room sample preparation, adequate tracer recovery, customer specified turn-around times, throughput, water and urine blank values, statistical data reduction, and quality control and performance evaluation sample requirements. Ongoing improvements identified include software development and electronics upgrades to allow automation of the system for reduced labor costs and increased efficiency.

INTRODUCTION

Routine bioassay monitoring for Department of Energy workers who may incur intakes of radioactive materials resulting in a committed effective dose equivalent of 100 mrem (0.1 mSv) is mandated by United States law [1]. To provide the level of measurement sensitivity necessary to meet this monitoring requirement, Los Alamos National Laboratory (LANL) developed an ultra-sensitive analytical procedure through the application of thermal ionization mass spectrometry (TIMS) for determination of plutonium-239/240 in urine samples [2].

Since the days of the Manhattan Engineering District Project, plutonium-worker monitoring was accomplished through radiochemical alpha spectroscopy (RAS), which besides being less sensitive, cannot distinguish between the isotopes of plutonium-239/240. However, RAS remains the technique for the determination of plutonium-238 and -239 in routine monitoring, and TIMS is used as an adjunct for baseline and front-line plutonium workers providing more sensitive determinations of plutonium-239, and the 239/240 ratio.

For over 40 years, TIMS was a well-established research tool used for analysis of one-of-a-kind samples. Since the addition of the TIMS procedure to the LANL Bioassay Program in January 1997, numerous technical and management challenges have been encountered during the transition from a specialized research tool to a production analytical technique. Chemical separation procedures used in the determination of RAS levels of plutonium were not suitable for the more sensitive TIMS analyses. Numerous opportunities for quality improvement have occurred in the three years of routine TIMS operations to support the LANL Bioassay Program. These lessons could only be learned once TIMS was implemented, as the first series of problems had to be solved before the next set of challenges were identified.

PLUTONIUM PROCESS CHEMISTRY

RAS Analysis

All LANL Bioassay Program samples are analyzed for plutonium by RAS first, and then if requested, by TIMS. The RAS portion of the process starts with determination of sample parameters (temperature, weight, and specific gravity). Plutonium-242 tracer is added to the sample prior to processing. Calcium nitrate, phosphoric acid and ammonium hydroxide are added to the urine to precipitate the plutonium from solution. The sample is centrifuged, and the supernatant liquid is decanted and discarded, leaving the precipitated plutonium solids. The solids are dissolved in nitric acid and heated. The solution is then transferred into a Class-100 clean-room. The nitric acid solution is passed through an anion exchange column, and the plutonium is eluted from the column with hydrochloric acid followed by a hydroiodic acid solution. The solution is evaporated to dryness. The sample is redissolved in a sodium bisulfate-sodium sulfate solution and electroplated onto a stainless steel planchette. The planchette is alpha counted for plutonium-238 and-239.

TIMS Chemistry

All chemistry done to support the preparation of the TIMS samples is conducted in a Class-100 clean-room environment. The stainless steel planchette from alpha-spectroscopy analysis is washed with a hydrofluoric/nitric acid solution to remove the plutonium. The plutonium solution is passed through an anion exchange column and the plutonium is eluted from the column with a hydrochloric/hydroiodic acid solution. The sample is evaporated to dryness and re-dissolved in a hydrochloric acid/hydrogen peroxide solution. The sample is loaded onto a second anion exchange column and the plutonium is eluted with hydrobromic acid. The plutonium solution is evaporated to dryness in a pre-cleaned quartz test tube.

TIMS Analysis

The solid material is dissolved in a buffered hydrochloric acid-ammonium hydroxide solution. The plutonium is co-electroplated with platinum onto a rhenium filament. The platinum-plutonium layer is overplated with platinum. The filament is inserted into the ion source of the mass spectrometer, and a current is passed through the filament causing the plutonium atoms to ionize. The ions are accelerated through a magnetic field, resulting in separation of the ions by mass, with heavier ions having more momentum. The amount of plutonium-239 in the original sample is calculated by comparing the number of those ions to ions resulting from a known amount of plutonium-242 tracer. TIMS analytical operations are conducted in a Class-100 clean-room environment.

CONTRACTUAL PERFORMANCE REQUIREMENTS

During the three years of TIMS implementation, the data generators and the end-user of the data—the LANL Dosimetry Program—have developed and refined specific technical, performance, cost and quality data requirements. All LANL bioassay analytical work is done in accordance with a detailed Project Management Plan that includes an Analytical Service Agreement, Data Acceptance Criteria, Quality Assurance Project Plan, and detailed analytical procedures [3]. These documents contain the specific requirements for the products and services to be provided to ensure that quality assured and sufficient data are reported to the end-user. The LANL Analytical Bioassay Program is also conducted in compliance with the requirements of the DOE Laboratory Accreditation Program (DOELAP) [4].

Internal tracer recovery

Tracer recovery in radiochemical analysis methods is an important factor in achieving lower detection levels for the determination of plutonium. A plutonium-242 spike is added as an internal tracer to each urine sample, blank and quality control (QC) sample. Tracer recoveries, as established by the end-user of the data and determined by RAS, must fall between 40% and 110 % for RAS, and between 15% and 110% for TIMS. The percent tracer recovery results are tracked on a monthly basis as part of the overall bioassay quality assurance (QA) program. Samples that do not meet the tracer recovery requirements are re-collected from the individual being monitored, and re-analyzed (re-runs).

The tracer recovery performance has improved dramatically over the past three years. In the first year of production TIMS analysis, the number of re-runs was not tracked or evaluated. However, complaints from individuals being monitored indicated that numerous requests for resubmission of samples were occurring. In CY1998, re-runs were carefully tracked, and reached an all-time high of 30% when a work-suspension was enacted on the RAS portion of the plutonium bioassay program. The corrective actions resulting from the work-suspension included a technician certification program that required a dedicated technician for complete analysis of a sample set, allowing personal accountability for the quality of each sample set. The certification program requires 3 consecutive, successful practice sets that have at least 8 of 10 samples with acceptable tracer recovery through RAS. To maintain certification, a technician must produce 2 of 3 consecutive sample sets with at least 8 of 10 samples with acceptable tracer recovery. Since implementation of the corrective actions, re-runs for unacceptable tracer recovery for RAS are ~5%. Although RAS analysis has to be redone if the tracer recovery is less than 40%, TIMS analysis may proceed if it is greater than 15%. The number of TIMS samples lost through failure to meet this metric is <1%.

Turn-around times

The Bioassay Program has two categories for target turn-around-times for analysis and reporting results: priority and routine. Samples designated for TIMS analysis are initially analyzed by RAS to determine the plutonium-238 and -239 values, to screen for elevated levels of plutonium, and to determine the tracer recovery. Urine samples designated for priority plutonium analysis require RAS results to be reported within 8 working days and TIMS results within 10 days. Urine samples designated for routine plutonium analysis require RAS results to be reported within 25 working days and TIMS results within 35 days. Establishing realistic target turn-around-times for sample analysis has required iterative integration between the generators and the end-users of the data. The need for obtaining analytical data in a timely fashion must be balanced with the historical routine performance of the RAS and TIMS operations of sample receipt, login, preparation, analysis and data reporting.

Achievement of TIMS turn-around times is totally dependent on the RAS portion of the program. In CY1998 TIMS met turn-around times 79%; in 1999 25%; and to date in 2000 90%. The work-suspension in late CY1998 created a significant backlog in RAS that impacted TIMS turn-around times in CY1999 accordingly. In response to exposure accidents, sample analyses have been completed through both RAS and TIMS in five days with dedicated staff working 10-hour days solely on those samples.

Throughput

Production capability of the existing TIMS chemistry operation is 12 samples/week, which is adequate to meet current in-house sample load. Increasing chemistry staff can easily accommodate additional sample load. Analysis by TIMS with one instrument can handle up to 24 samples/week. Samples analyzed in the three years of operation have averaged about 300/year for routine turn-around, and 20-50 for priority, well below capacity.

The TIMS facility houses three identical NBS 12-90 TIMS units, one of which is dedicated to bioassay analyses. The DOELAP requires back-up capability, and the availability of the other two instruments allows full back-up to support the Bioassay Program. Currently, a significant electronics upgrade is being performed on all of the TIMS units. Additionally, one unit is being modified and the necessary software developed to fully automate the analysis of bioassay plutonium samples by TIMS. Full automation will allow the technician to simply load the samples into the turret, and let the computer run the analysis with no operator attention. Automation will reduce labor costs for sample analysis by ~40%, and will increase throughput efficiency by 50%. Additionally, consistency between samples and background levels should be improved by minimizing variation introduced by human operators. A second TIMS system will be automated in the future to provide full back-up capability.

Performance Evaluation (PE) Samples

The internal QA program requires the incorporation and analysis of QC samples including blanks and single blind QC samples at a 5% level in the sample batches. These QC samples are incorporated into the analysis batch during login and are processed concurrently with the sample batch. Duplicate samples are not analyzed due to volume limitations. The LANL Bioassay Program has established operational control limits for acceptability of tracer recovery for RAS and TIMS, +/- the Minimum Detectable Activity (MDA) for the blank, and +/- 25% for the bias on single-blind QC samples spiked at >10X the MDA. The percent bias performance of plutonium-239 blind QC samples, spiked at > 10X MDA, and analyzed by TIMS from September 1998 through February 2000 is shown in Figure 1.

Early data show a distinct positive bias, partially resulting from a slight body burden of plutonium in the individual donating urine for preparation of the QC samples, which was not observed at RAS analysis levels. This situation was remedied by establishing a controlled system to identify urine donors, certify their urine as clean, i.e., plutonium-free, through TIMS, and maintain an approved donor pool of about 15 people. The QC program requires 5-10 liters of “certified” urine per week for use as RAS/TIMS blanks and for the preparation of internal plutonium control samples.

Figure 2 compares the recent RAS and TIMS plutonium-239 QC sample percent bias results that were outside the acceptance criteria, along with the plutonium-242 tracer recoveries. All tracer recoveries are well above the required TIMS 15%, and in the typical range for other samples that are within control. There appears to be no correlation between tracer recoveries and percent bias. The percent bias between the RAS plutonium-239 and TIMS plutonium-239 QC samples tracks very closely, which indicates that there is no loss or contamination in the TIMS chemistry, or the TIMS analysis. Potential areas for further process improvement include modifications in the preparation of QC samples and RAS process chemistry.

The LANL Bioassay Program analytical chemistry laboratories participate in the Oak Ridge National Laboratory (ORNL) In-vitro Bioassay Inter-comparison Study (natural urine); the National Institute for Standards and Technology (NIST) Radiochemistry Inter-comparison Program (synthetic urine); and DOELAP (synthetic urine). Currently, there is no program that is capable of providing routine PE samples at the aCi level for evaluation of TIMS at 10-20X MDA. The ORNL program currently provides routine PE samples at the lowest levels available at the fCi level, which is ~60X MDA for plutonium-239 by TIMS. LANL plans to participate in a second inter-comparison study designed to evaluate and validate the capabilities of TIMS in the determination of ultra-low-levels of plutonium in synthetic urine at the aCi level. This study is being coordinated by NIST and Duke Engineering and Services and is planned for CY 2000.

In CY1997, ORNL began providing PE samples for the TIMS program. Results for plutonium-239 in urine by TIMS have always met the –25% to +50% ANSI N13.30 [5] acceptance criteria used by ORNL, as well as the more restrictive internal LANL values of +/-25% relative bias are shown in Figure 3. There does not appear to be any correlation between the levels of spike in the samples and the performance of TIMS, as the spike levels range from 9 fCi/Kg up to 1,500 fCi/Kg. Each set includes more than one spike level. Precision and bias seem to be more dependent over time with changes in the RAS processing and changes in analysts. The ORNL PE samples have proven to be an invaluable tool in assessing the performance of TIMS, and identifying areas of opportunity for improvement within the program.

STATISTICAL DATA TREATMENT FOR TIMS

Initially, data treatment used a running average of a set of data points instead of considering each data point individually. In FY98, the software was modified to store each counting event and track it against time and temperature, significantly changing the statistical approach to the analysis of low-level TIMS data.

Basic principles

Count-rates for isotope masses of interest are measured and the ratio of the isotope of interest to a known reference isotope is determined. Ratio determination is complicated because the count rate is not constant, and the single ion counting channel does not allow the isotope of interest and the reference isotope to be measured concurrently. Further complications include background and isobar signal contributions that do not originate from the isotopes of interest, and system noise that generates occasional counts.

Once noise, background, and isobar signal contributions are subtracted from the data, curve shapes of the count rate, as a function of time (and temperature) will be identical. That is, , where is the count-rate for isotope i, is the count-rate for the reference isotope as a function of time t and temperature T, and is the desired ratio between isotope i and the reference isotope. Noise is removed based on Chauvenet's criterion. Background subtractions are made based on an average of the half-mass measured on both sides of the peak of interest. The isobar is identified and removed by taking advantage of the fact that the isobar count rate follows a different curve than that of the reference isotope.

Isobar correction

The background corrected count-rate data for the isotope i is fitted to a function of the form . The desired isotope ratio between the isotope i and the reference isotope is given by . The count-rate function for isotope i is given by , which corresponds to the desired condition noted earlier stating that the isotope and reference have the same time-temperature function shaped curves. The count rate curve for the isobar is given by , such that the isobar decays to zero at infinite time. This model generally describes the data quite well. Figure 4 shows the background, isobar, and isotope counts components.

Further work

The present method of data reduction is only applicable to data where the background and isobar contributions are small relative to the uncertainty in the count-rate of the reference isotope. This limitation is being addressed in an ongoing effort by applying the background and isobar model to the reference data and by fitting all the data simultaneously.

The functional form of the isobar model is also being refined. There is evidence that there is a component of the isobar that is not proportional to the reference curve, which is not presently accounted for. Much of the blank appears to be a residual isobar that cannot be subtracted at the present time, but could likely be reduced with an improved isobar model.

Minimum detectable activity

Chemical yield appears to be the most important factor in determining MDAs. Since the MDA is based on the variability of blank data, low chemical yield¾which results in low count rates¾leads to higher MDAs due to lower precision and more variable blank measurements. Figure 5 shows plutonium-239 process blanks as a function of date and matrix.

For the first year water blanks were used. For the past year both water and urine blanks were used, and currently all blanks are TIMS certified, clean urine. Urine blanks yield significantly lower blanks, apparently due to better chemical yield.

LESSONS LEARNED

Sophisticated process chemistry

Although only a fraction of the urine samples analyzed for plutonium eventually go through TIMS, it is essential that the chemistry used is sufficiently clean to meet the sensitivity requirements for TIMS, such that any sample analyzed by RAS can be further processed for TIMS if required. The chemistry used must be sufficiently robust and efficient to be applied to ~2,000 samples a year for alpha-spectroscopy, of which 300-400 go on for TIMS analysis.

Techniques commonly used for RAS analysis were not suitable for the more sensitive TIMS analysis. Practices that are perfectly acceptable for RAS can cause detectable sample contamination when used to process TIMS samples. All operating procedures had to be re-evaluated to ensure compatibility with the more sensitive measurement technique. Processing of samples has to be conducted in Class-100 clean-rooms to support the sensitivity of TIMS. Although conducted in a clean-room facility, the rooms, equipment and reagents used by the bioassay program have to be "blanked" prior to use, to ensure that there are no programs in the area that could negatively affect the bioassay results.

Culture change

Transition to a routine production environment required implementation of a much more rigorous formality of operations than was originally used during the research and development phase of the TIMS program. It took two years of operation to fully develop operating procedures and protocols acceptable to the chemists, TIMS analysts, and QA staff. Once the analytical procedures were in place, a significant culture change was required to accept and implement the rigor and consistency imposed by the QA program.

Attention to detail

The RAS chemistry developed for TIMS is much more sensitive to analyst technique and attention to detail. A tracking system was developed to monitor the performance of analysts. As the formality of operations has increased, the program has become more rigorous and demanding, and while personnel turnover is minimal, periodic re-training and process refreshers are essential to maintain proficiency.

Equipment

Most equipment is used only once to minimize the potential for cross-contamination. However, some equipment is simply too expensive to be single-use, e.g. the 2 liter Teflon^® bottles that are used to precipitate the plutonium from urine. Early on, the bottles were carefully cleaned and re-used at random. The processing of high-level QC samples (some over 10,000 times above TIMS limits of detection) resulted in contamination of samples at levels above the TIMS limits of detection and may have caused false positive results to be reported during the first year TIMS analyses were performed. This contamination was not identified until sufficient TIMS data were available. To solve the contamination problem, levels of plutonium in the QC samples were reduced, and a strict protocol for Teflon^® bottle re-use was implemented. The containers used for QC samples are segregated and re-used only for other QC samples, and not used for customer samples. Additionally, the Teflon^® bottles are not re-used in incident response situations where elevated-levels of plutonium in urine are suspected.

Throughput

A culture change was also required to move from success on one set of samples to success for every set of samples on a continuing daily basis. The primary reason for sample loss is tracer recovery¾generally a result of error in technique, inattention to detail, and occasionally matrix problems. Physical sample losses, e.g., spilling, dropping, mix-ups, etc., are rare.

Samples from the routine program are rigorously scheduled, with negotiated sample loads and turn-around times. In incident response situations, an additional sample load of priority samples with faster turn-around times severely impacts the routine program. Parallel systems were developed to provide sufficient resources to maintain the routine program, while meeting deadlines for priority samples.

CONCLUSIONS

Transition of an in-house research tool to a production analytical process has provided a fertile area for application of formality of operations and project management practices. Continuous improvements in efficiency and the quality of product include: increasing the plutonium ionization efficiency to increase sensitivity and lower blanks; improving the stability of the TIMS instruments through electronics upgrades and automation: developing more sophisticated data reduction and background correction routines; and maintaining a rigorous QC program to monitor ongoing TIMS analytical quality.

REFERENCES

1. United States of America, Code of Federal Regulations, 10 CFR 835.402(b).

2. W.C. Inkret, et al, International Journal of Mass Spectrometry, 178 (1998) 113-120.

3. Los Alamos National Laboratory Analytical Bioassay Project Management Plan, LA-UR-99-4817, February 2000.

4. The U.S. Department of Energy Laboratory Accreditation Program for Radiobioassay, DOE-STD-1112-98, December 1998.

5. American National Standard, Health Physics Society, Performance Criteria for

Radiobioassay, HPS N13.30-1996.

FIGURES

Figure 1: Results of Pu-239 TIMS Blind QC samples spiked at >10X MDA, September 1998 through February 20000.

Figure 2: RAS and TIMS Pu-239 QC results that exceed +/- 25% relative bias, September 1999 through February 2000.

Figure 3: TIMS analysis of ORNL PE samples spiked with Pu-239, January 1997 through December 1999.

Figure 4: Components of the fit to the 239-plutonium counts.

Figure 5: Plutonium-239 process blanks as a function of date and sample matrix