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11
Chemical Science and Technology Laboratory:
Division Reviews
BIOTECHNOLOGY DIVISION
Technical Merit
The purpose of the Biotechnology Division is to maintain a research laboratory as the primary
resource for the biotechnology measurements, models, data, and reference standards required to produce
biochemical products, enhance competitiveness in the world market, and allow the government to apply
advances in biotechnology to the benefit of society. The Biotechnology Division has four groups: DNA
Technologies, Bioprocess Engineering, Biomolecular Materials, and Structural Biology. The emerging
Bioinformatics Group, mentioned in last year's assessment, remains as part of the Structural Biology
Group. This year the division is under new leadership; the Bioprocess Engineering Group leader has
been replaced and is now division chief.
The DNA Technologies Group is pioneering a number of important methods. These include the
development of SRMs for human identification and a critical database on short tandem repeats (STRs).
The group also houses the NISTINational Cancer Institute (NCI) Biomarker Validation Laboratory
(BVL), part of NCI's Early Detection Research Network (EDRN). Other programs include the geno-
typing of single nucleotide polymorphisms and the establishment of methods for detecting and quanti-
fying DNA damage and repair in cancer detection and treatment. This research is state of the art and
continues to push the technology into new, productive, and high-impact areas.
The Bioprocess Engineering Group focuses on developing measurement methods, databases, and
generic technologies related to the biomolecular field in manufacturing. The group is active in bio-
catalysts, biospectroscopy, biothermodynamics, and DNA separation and measurements. The group's
work is of high quality and is clearly described in a well-designed Web site (www.CSTL.nist.gov/
NOTE: Chapter 4, "Chemical Science and Technology Laboratory," which presents the laboratory-level review, includes a
chart showing the laboratory's organizational structure (Figure 4.1) and a table indicating its sources of funding (Table 4.1~.
143
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44
AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
biotech/bioprocess/projects.html). The Biomolecular Materials Group focuses on studies of biological
molecules and their potential uses in biotechnology. One emphasis is the study of thin films leading to
determinations of the surface effects or character of biomolecules at surfaces. A closely related interest
concerns the construction of biomolecular polymeric structures that act as scaffolds for tissue engineer-
ing. A particularly promising project involves single-molecule measurement using pores of nanometer
scale. Each of these studies is making fundamental advances in the understanding and control of
biomolecular materials engineering.
The Structural Biology Group participates in the Center for Advanced Research in Biotechnology
(CARB), a joint NIST/University of Maryland research center located on the Shady Grove campus of
the university about 4 miles from NIST. Scientists at CARE develop and apply measurement methods,
databases, and state-of-the-art modeling methods to advance the understanding of protein structure/
function relationships. The individual programs are outstanding, and the group contributes a number of
important resources such as the Protein Data Bank (PDB) to the world scientific community.
Program Relevance and Effectiveness
The Biotechnology Division faces unique challenges and vast opportunities resulting from the
breadth of topics in the biological sciences, the rapidly changing nature of technology supporting new
discoveries in life sciences, and the continuing emergence of new biotechnologies. To meet these
challenges, it will be necessary to have a critical mass of personnel and equipment to address the
appropriate issues in metrology and standards for each opportunity. A division 10 times the size of the
current Biotechnology Division could not respond to all of the possibilities. Thus, the division must
continually evaluate and reevaluate its portfolio of projects to ensure that they closely reflect and
anticipate commercial needs. The recent adjustments in personnel within the division reflect this sense
of reprioritization.
In some cases, both critical mass and appropriate range of expertise can be obtained only by cross-
divisional or cross-laboratory projects. Also, collaboration with external entities is clearly one method
to leverage NIST resources; CARE is a good example. For CSTL, the challenge is to ensure that biology
is incorporated appropriately into all divisions while fostering and enhancing within the Biotechnology
Division a strong core of integrative biology (across molecular and physiologic scales) that is both
current and quantitative in orientation.
Overall, CSTL and the division have responded well to these challenges, although continuous
reevaluation of the project portfolio remains a critical part of any strategy to respond to changing
customer needs. The division can conduct three basic types of projects: (1) those responsive to current,
identifiable needs; (2) those for the development of internal expertise in emerging areas in which
evaluation and standardization of methodology are likely to be important; and (3) those for the develop-
ment of new measurement technologies that, in themselves, will foster new biotechnologies. Examples
of the first category are the Protein Data Bank, a real gem for NIST, and the effort to develop method-
ology for the sampling and detection of genetically modified foods (a critical commercial need). Ex-
amples of projects of the second category (for internal expertise) are those on proteomics and RNA-
protein interactions. In particular with the Proteomics project, issues of standardization and validation
are almost certain to emerge. An example of the third type of project is the cross-divisional effort, Single
Molecule Manipulation and Measurement (SM3) initiative, which has a high probability of establishing
new measurement methodology. The panel believes that all projects in the division's portfolio should be
justified in one of these three categories. Within each category, the division must be willing to prioritize
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
145
project value and eliminate less valuable although technically sound projects. To minimize the elimina-
tion of technically sound projects, the division may need to seek out more extradivisiona1 partnerships to
satisfy critical mass on some projects (e.g., partner with CSTL's Analytical Chemistry Division on
analysis of genetically modified organism [GMO] foods). Overall, the division has made defensible
choices in the project portfolio, adjustment of personnel, and partnering in cross-divisional or cross-
laboratory projects and external collaborations.
The division continues to maintain high external visibility and programmatic relevance. It functions
with the fairly high level of external funding that it has received to sunnort its programs. Such funding
1 ·,. , · ·, · ,1 , · , · 1 · 1 1 r
has positive aspects, since it requires the group to maintain a high degree ot customer responsiveness.
The division has an ambitious portfolio of research projects that fall into the categories of health and
medical products, forensics and homeland security, and food and nutritional products. Several projects
serve as useful examples of responses to current, identifiable needs (category 1 projects) and highlight
the breadth of program relevance. In the Human Identity/Forensic Science project, the division is
developing new methods for DNA profiling, ranging from developing well-characterized DNA stan-
dards for restriction fragment-length polymorphisms to performing research for rapid determination of
DNA profiles by polymerase chain reaction (PCR) amplification and automated detection of fragments.
These new methods have proven important for the identification of victims of the World Trade Center
disaster of September 11, 2001, since the high degree of DNA fragmentation due to the severe environ-
mental conditions meant that only about 50 percent of the specimens yielded results under standard
DNA testing methods. An important project in the area of DNA diagnostics for the detection of human
disease is the NIST component of the NCI Early Detection Research Network. This NIST project serves
to refine recently discovered cancer biomarkers and to format new research tests for field trials in EDRN
clinical laboratories. The rigorous validation of biomarkers for diagnostics is a critical issue that fits well
with the development of measurement methodologies. These projects will offer high-impact improve-
ments to human health.
In 2002 the panel was concerned that the Proteomics Group might be spreading itself too thin and
thereby limiting its ability to mount the kind of program needed in proteomics. However, the panel is
now comfortable with the strategy of a small proteomics effort to develop the internal competency to
assess developments in the field that will determine future NIST directions.
A program that focuses development of new measurement technologies is the program on advanced
mass spectrometry measurements of DNA damage. For example, the cellular accumulation of two major
oxidative stress-induced DNA lesions in cells of Cocaine Syndrome patients after exposure to ionizing
radiation has been identified. As a disease with implications for understanding the human aging process,
these studies are undertaken as a collaborative effort with scientists at the National Institute of Aging.
The program researchers and management should continue to carefully assess priorities and resource
distribution to ensure that key programs are adequately supported. The group should also develop a plan
that prioritizes its efforts in a way that is consistent with ongoing commitments and its current expertise
base.
The DNA separations and analysis projects are responsive to current, identifiable needs. These
projects focus on GMO testing (a critical issue for agriculture and global trade), identification of
pathogens (important for medicine and homeland security), and the development of DNA standards for
use in industries involved in DNA vaccines and gene therapy. Much of the work in the biocatalysts and
biothermodynamics projects has focused on understanding the chorismate biosynthetic pathway (en-
zymes, thermodynamics, and so on). This pathway is important in agriculture and in the biomanu-
facturing of aromatic amino acids and related compounds, and it has served as a model system for
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AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
studying metabolism. The biospectroscopy projects address primarily categories 1 and 2. The develop-
ment and production of fluorescent reference materials in the biospectroscopy project also address
current, identifiable needs.
Much of the other work in the division involves the development of internal expertise in emerging
areas in which evaluation and standardization of methodology are likely to be important, such as broader
application of fluorescence. Although it is appropriate for NIST to take the lead in GMO testing, this
work is supported by only two people, who are also involved in several other projects. To increase the
critical mass on this project, the Bioprocess Engineering Group should enhance its level of collabora-
tions with both internal and external groups. The chorismate pathway project has been very successful;
however, the panel recommends a reconsideration of this work and its contribution to the mission of the
.. . .
alvlslon.
The issue of changing the group name to something other than Bioprocess Engineering came up
several times during the panel review. The reason for concern seems to be that "Bioprocess Engineer-
ing" does not accurately reflect the scope of the group and may be misleading to internal and external
collaborators. One suggestion provided to the panel was "Biophysical Measurements," but this name
seems too broad. Another, narrower suggestion was "Bioprocess Measurements," which may be too
narrow. The panel recommends that the group continue to think about names that reflect its scope and
purpose.
Finally, the panel was encouraged by the efforts within the Bioprocess Engineering Group in the
area of homeland security. These efforts include a substantial program funded by the Air Force. The
group is also preparing a white paper on opportunities in this area for the Biotechnology Division as a
whole.
The Structural Biology Group continues to realize its potential as a high-quality program with
international impact. The CARB center addresses projects in X-ray crystallography, biomolecular
nuclear magnetic resonance (NMR) spectroscopy, protein folding, computational chemistry and model-
ing, and mechanistic enzymology. This work can be characterized as being in categories 2 and 3; it is
outstanding. A stimulating research environment exists within CARB, and it maintains the mission-
oriented flavor critical to NIST programs. The value and uniqueness of CARB appear to be fully
appreciated by NIST senior management, which views it as a paradigm for future NIST/academic
_ _ ~ ~
ventures.
Last year the panel expressed concern that NIST staffing levels at CARB were too low, and several
decisions have been made in the past year to increase the NIST presence at CARB. The low staffing-
level trend is being reversed by relocating the Protein Data Bank workforce to CARB, where natural
scientific synergies exist. The NIST campus will continue to provide hardware support. The PDB, a
category 1 program, is the premier world resource for data on protein structure and function and as such
showcases NIST's role in biotechnology. The PDB Web site records approximately 6 million hits a
month, providing an impressive metric of its value to the scientific community. As part of its move to
increase the NIST presence at CARB, CSTL merged its Bioinformatics and Structural Biology Groups
at CARB.
Overall, the programs at CARB continue to be highly relevant, and the moves to bolster the NIST
presence are important. However, the success of the CARB experiment should not obscure the need for
a continued strategic plan. CSTL should develop a long-term plan that clearly describes what its future
vision of NIST's role at CARB is and how it will respond to new growth initiatives for CARB from the
University of Maryland. A clear plan of commitments will be an important component in attracting a
first-rate director for CARB.
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
Division Resources
147
With respect to division resources, the issues of critical mass and portfolio review merit attention,
given the breadth and depth of current interest in biotechnology. The division cannot do everything.
Considering the wealth of opportunities in this field, the panel believes that the division's staff should be
growing and is concerned that in fact it seems to have decreased slightly. On the other hand, the panel
is encouraged that some restructuring between groups was done to staff new projects more efficiently.
The facilities and equipment in the division are excellent and adequate to fulfill its mission.
The DNA Technologies Group lost two full-time employees, who were transferred to the Bioprocess
Engineering Group in a move to align expertise (the restructuring mentioned above). The DNA Tech-
nologies Group boasts a number of state-of-the-art resources. The high-speed matrix-assisted laser
desorption ionization (MALDI) time-of-flight mass spectrometers with automated sample preparation,
capillary electrophoresis (CE), and gas chromatography/mass spectrometry (GC/MS) facilities are ex-
cellent.
The Structural Biology Group has maintained constant staffing over the past year. The group is well
outfitted for cutting-edge research, given that the X-ray diffraction and ultrahigh-field NMR facilities
are outstanding. The PDB resources are impressive.
The Biomolecular Materials Group lost one full-time employee in the past year. The group's
relatively small size restricts its ability to take on new projects and continues a long-term trend in loss of
faculty. The facilities and equipment available for the work of this group are excellent.
PROCESS MEASUREMENTS DIVISION
Technical Merit
The Process Measurements Division of CSTL provides a central, national source for reference
materials, calibration of measurement equipment, and data on materials properties. A core responsibility
of the division is the improvement and dissemination of national measurement standards for tempera-
ture, fluid flow, air speed, pressure and vacuum, humidity, liquid density, and volumetric measure-
ments.
To facilitate communicating the panel' s findings concerning the Process Measurements Division, a
summary is first provided, followed by details of the visits to each of the division's groups.
The technical quality and merit of the Process Measurements Division can be illustrated by the
following achievements during FY 2003:
· Achievement of the ability to concentrate an analyte ~10,000x in a microfluid environment. The
panel is impressed with the clever use of thermal and electric-field gradients used to achieve this
competence;
· Involvement of the division with two NIST Competence projects, which in the panel's view
speaks to the quest for excellence and for advancing the state of the art in measurement science;
· Development of a new piston calibrator for jet fuel flow sensors and pioneering of a unique
design for a diverter valve needed to reduce the uncertainty of large water flow calibrations;
· Capturing the distinction of being first in the world to advocate the use of the backscattering
configuration for Raman spectroscopy to eliminate polarization effects as sources of intensity differ-
ences for samples measured by different laboratories, and development of an advanced mathematical
model to simulate such scattering by ternary and quaternary III-V compounds;
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AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
· Completion of a study of the intrinsic stability of sensors without their electronics, which indi-
cated that the electronics may be limiting the uncertainty and therefore will require improvements to
match the stability of MEMS pressure sensors;
· Development of plans to explore standardization needs in the area of dynamic pressure measure-
ment; and
· Adoption of ISO/IEC 17025 standards for all calibration projects.
The panel continues to be impressed by the concentration of measurement knowledge and expertise
in this division and by the quality of its work. Delving more deeply, the panel was especially impressed
with the ongoing projects discussed in the following subsections.
Molecular Electronics
Molecular Electronics a competence project funded at approximately $1.3 million per year for 5
years (it is in its third year) appears to be a model for its breadth, integration of talent at NIST (six
groups in three divisions and two laboratories), and collaboration with Hewlett Packard and IBM. This
project's alternative approach to electronics technology is based on single-electron devices having
molecular-sized components, and it uses nonlinear processes that are analogous to silicon-based diodes
and transistors. Because the processes originate from synthesized molecules, the dimensionality is much
smaller and is more dense than that of traditional devices. The CSTL effort is focused on testing a
variety of methods that will provide early input into the feasibility of this approach. One such method is
two-photon photoemission, which accesses unoccupied electronic levels and tracks electron relaxation
effects. In this impressive project, short pulses (~10 femtoseconds) of variable wavelength from titanium-
sapphire lasers are used to analyze molecular structure using the two-photon photoemission technique.
Fluid Science
The division's determination and dissemination of fluid properties respond directly to industry
needs for thermal-based mass flow measurement systems, which are limited in performance by the
accuracy to which fluid properties are known. Technologies and competencies developed in the fluid
science project have been applied by the division's thermometry researchers. Acoustic technology
developed in the Fluid Science Group has been applied by the Thermometry Group to primary acoustic
thermometry. Improvements to the ITS-90 temperature scale have resulted. This method has been
applied up to 575 K, and the goal of 800 K appears obtainable.
This fluid science project is also striving for development of a primary pressure standard based on
measurements of the dielectric properties of helium. the goal is to achieve a 1() to 2() ppb uncertainty
with the cross-capacitor He-dielectric measurement approach. So far, 100 ppb has been demonstrated. A
novel, cross-capacitor made from a single edge-grown sapphire crystal has been developed and shows
promise; however, a state-of-the-art capacitance bridge is required to meet the ultimate goal. Vendors
are being sought to provide the needed tool. The panel raises a question that must be considered: If a key
measurement tool needed for the primary standard is not currently available, does this introduce an extra
limitation into the utility of a primary standard? The panel also questions how this approach compares
to the resonant silicon pressure sensing approach being pursued by others.
The project continues its ongoing effort to map the thermophysical properties of gases used in
semiconductor processing, which is challenging because some of these gases are highly reactive or
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
149
corrosive. This acoustic resonator R&D area seems well connected with the semiconductor industry and
academia and might benefit from closer interactions with the Fluid Flow Group.
Work accomplished by the fluid property measurements project includes the use of an oscillating
gas column around a heated honeycomb in combination with an acoustic resonator to measure fluid
properties with greater accuracy Art and k to 0.3 percent, p and cp to 0.1 percent, and c to 0.01 percent).
The Raman Spectra Calibration Library has made significant advances in the calibration of Raman
spectra by creating Raman intensity standards, promoting the use of backscattering and advanced
modeling of the scattering from spatially inhomogeneous samples.
Thermal and Reactive Processes
Optical absorption measurements of synthetic soot produced from the controlled combustion of
heptanes are being studied, with the goal of developing SRMs of known composition and with known
characteristics. These SRMs will allow users (especially transportation, energy, and environmental
industries) to calibrate their instruments, determine uncertainties in their measurements, and develop
appropriate models. The Process Measurements Division has a unique technical competency in this
area. It would be interesting to see a correlation between the absorption characteristics of soot in the air
caused by air pollution and the synthetic soot standards developed as reference materials.
The group developed an SRM for Raman spectroscopy. Raman spectroscopy is becoming widely
used in a number of industries, so the need has increased for a simple, reliable calibration technique for
this measurement method. The development of a standardized glass (SRM 2241) is a practical approach
for providing an easily transferred, stable, intensity calibration source that can be activated by laser light
at 785 nm, a common laser wavelength. SRMs used for Raman spectroscopy at other wavelengths will
be developed and made available in the future. The panel is pleased with this activity.
Fluid Flow
The Process Measurements Division has continued to improve fluid flow rate measurement capa-
bilities and to reduce uncertainties. The completion of the small PVTt (pressure, volume, temperature,
time) system gas flow standard represents a significant milestone, replacing traditional proven piston
and cylinder and bell technologies with a fully automated calibrator that had been documented to reduce
uncertainty by a factor of 10. This represents a level of accuracy that is best in the world for gas flow
rate. A larger PVTt system is under development and approaching completion.
The division has also developed an improved liquid flow rate calibration technique that is expected
to have a significant impact throughout the liquid flow rate calibration community. The division has
pioneered a uniquely designed prototype diverter valve that provides for self-cancellation of an error
source that has plagued gravimetric flow rate calibrator systems for decades. The panel views this
accomplishment as a creative solution to reducing the uncertainty of this calibration.
The Process Measurements Division continues to lead the international community through CIPM
and Sistema Interamericano Metrology (SIM) working groups. The division is conducting projects for
DOD aimed at improving flow rate measurement accuracies for both liquid and gas flow by an order of
magnitude. A newly constructed liquid fuel piston calibrator with a flow range of 0.01 to 3 gal/min and
accuracy of 0.025 percent is now being tested for a DOD customer.
The division is pursuing development of a low-gas-flow measurement assurance program utilizing
a new breed of highly stable commercial flow sensor nozzles and laminar flow elements (annular,
Re < 500, L/D 2 ~2000~. Round-robin testing and participation with outside testing organizations are
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AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
exemplary. The division also continued the effort to complete the Exhaust Gas Flow Laboratory, which
cost between $3 million and $4 million to build. Once completed, this facility will allow the develop-
ment of important collaborations with the automotive industry.
Process Sensing
With respect to work on microheater sensors, conductometric SnO2 or TiO2 film sensors of ~500 A
in thickness and ~ 100 x 100 Em in size have been able to sense 20 to 200 ppb of satin and can also detect
mustard gas and GA-tabun with a response time of ~50 s. A new, monolithic pre-concentrator may
increase sensitivity by 10 times. In addition, carbon nanotube growth on MEMS micro-ho/plates has
been demonstrated, clearing the way for the evaluation of their performance as gas sensors. Sensitivity,
selectivity, speed, and stability issues must still be addressed to improve performance. As with other
micro-ho/plate microsensors based on doped SnO2, TiO2, or differential calorimetry which promise
the possibility of attractive performance parameters such as low power, low cost, and compactness-
achieving stable operation over thousands of hours still represents a major challenge and should be
considered carefully. This project is relevant to homeland security and chemical warfare agent defense
technologies.
Plasma Process Metrology
In 2002 the Plasma Process Metrology project developed a method for two-dimensional mapping of
the gas temperature of plasmas using the planar, laser-induced fluorescence method. Results have been
shown for a CF4 plasma operating at several different pressures. This is a nice application for a high-
level, advanced metrology method. This measurement method could potentially be used to explore the
thermal effects of particles in plasmas which, along with heat transfer studies, will likely be of interest
to the semiconductor industry.
In response to last year's concerns of the panel, the Plasma Process Metrology team has developed
a new, inductively coupled, 300-mm plasma process reactor. This system closely resembles the process
tools used by chip manufacturers and is a significant advance beyond the tool previously used, which is
referred to as the GEC tool.
Microfluidics
The Microfluidics project developed an ingenious approach to both concentrate (210,000:1) and
separate analyte in liquid/ionic microfluidic streams. This procedure is based on achieving a unique
balance of forces on ionic analyses (fluorescent dyes, amino acids, proteins, DNA, and colloidal par-
ticles) in overlapping and opposed electric field and temperature gradients (temperature gradient focus-
ing). Concentration of analyses at ratios greater than 10,000 to 1 were demonstrated and considered by
the panel to be a significant achievement.
Pressure and Vacuum
The panel discussed with the group leader the merits of developing alternate approaches for support-
ing calibration service customers. One approach discussed would be to replace such traditional calibra-
tion services with "NIST traceable programs." Such a program might apply processes similar to those
used for NIST-traceable reference materials, laboratory intercomparisons, and measurement assurance
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
151
programs. Among its benefits would be the sort of traceability and proficiency test data required by the
customer to meet the requirements of ISO/IEC 17025 standards. The program would benefit the cus-
tomer by transferring the world-class accuracies of NIST to commercial and military primary calibration
laboratories and by providing continuous assurance of accuracy. NIST would benefit by having flexibil-
ity in the scheduling of workloads for better utilization of laboratory resources and a more stable income
stream.
The panel was told that the cultural change associated with the application of ISO/IEC 17025
standards throughout the Process Measurements Division has been beneficial, and that improvements in
the quality of calibration services are expected. An objective evaluation of the impact, if any, of the new
quality program on the technical merit of divisional programs would be appropriate after full implemen-
tation at the end of 2004. The adoption of ISO/IEC 17025 standards is also applauded by the panel.
Thermometry
The panel noted that the Thermometry Group continues to exert technical influence on the interna-
tional temperature measurement community, as demonstrated by its developing the program for and
peer reviewing articles for the 8th International Temperature Symposium that took place in 2002 in
Chicago. The Thermometry Group presented eight papers. The group also completed work on Key
Comparison 3 (K3) of the international Consultative Committee on Temperature. NIST was the pilot
laboratory for the most comprehensive intercomparisons ever conducted. A temperature range covering
-189 °Cto+660°C was done.
This past year, the Johnson Noise Thermometer prototype was completed, and a noise-to-power
accuracy ratio of better than 0.1 percent was documented over the range considered. The ability to
recalibrate such sensors in situ for example, for space station applications is viewed by the panel as
very significant.
Completion of construction of the acoustic thermometer was followed by validation testing, includ-
ing the measurement of the temperature of the gallium melting point, which showed excellent agreement
with earlier work. Excellent results at indium and tin freezing points give confidence that the division
will finally be able to resolve problems in the temperature scale.
Program Relevance and Effectiveness
The Process Measurements Division continues to be responsive and forward thinking in supporting
certain industries (e.g., semiconductor and automotive). It was not clear to the panel whether other
important segments of U.S. industry (e.g., process, gas, biomedical) were getting the same attention or
would perceive the division's programs as relevant to their needs. Overall, this panel was again im-
pressed by the effectiveness and progress toward automation in many of the division's projects.
A fair amount of effort at CSTL seems to be focused on the semiconductor industry. How does this
compare to the effort it invests in the other 5 out of the 12 CSTL program areas that the division is
supporting? The division has continued efforts to develop and maintain close contact with manufactur-
ers and other customers, including integrated circuit manufacturers, in response to comments made in
the FY 2002 assessment.
The division's determined effort to bring all calibration programs into compliance with the ISO/IEC
17025 standards is expected to highlight the relevance of NIST programs, especially in the eyes of its
calibration service customers. It would be especially beneficial for NIST to publish its ISO-compliant
quality manual and other relevant quality documents on the Web. Commercial and government calibra-
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AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
tion and testing laboratories could use such documents for a variety of purposes, not the least of which
would be as guides and templates for their own documents.
The division provides considerable consultative and advisory services for its calibration customers
and researchers. The availability of NIST experts for telephone consultations is a valuable service to
U.S. industry and the U.S. government. Providing such assistance is said to consume as much as 25
percent of division researchers' time. NIST seminars and workshops provide another valuable dissemi-
nation vehicle for technologists and researchers to interact with NIST experts in their field.
The results of NIST programs and technical information were made available to the public during
the past year through a variety of means, including free, Web-based processes, computer media, publi-
cations, talks, participation in committees, and workshops. The division's output included 93 publica-
tions, 90 presentations, 1 CRADA, 9 patents or patent applications, 1 SRM, 187 calibrations or tests,
participation in 96 committees, 1 editorship, and 5 workshops/meetings.
Division Resources
Division facilities continue to show improvement. Construction of the new metrology building is
progressing, and the panel looks forward to the day when many divisional areas are able to take
advantage of this environment that will be among the best in the world.
Calibration charges to customers currently cover only about 70 percent of CSTL' s costs. The panel
encourages CSTL to recover its full costs through a combination of cost reduction and price increases.
This may result in performing fewer calibrations and transferring more calibration work to secondary
standard laboratories, such as CCESI, Flow Dynamics, and Aldan, but would leave more time for
research on measurement and calibration automation. The resources of the division are adequate, espe-
cially in view of the impending readiness of the new metrology building.
Responsiveness to Panel Recommendations
The division's response to the panel's suggestions in the FY 2002 report to boost Web-based data
dissemination was that "data for gases used in semiconductor manufacturing are freely disseminated."
This response is not viewed as being especially proactive. There was no mention of adding one property
column (viscosity), nor of attempts to relate the division's Web site to other CSTL Web activities.
The panel did not see that resources and structure for increasing the rate of Web-based data dissemi-
nation were implemented as recommended.
Additional Comments
The Process Measurements Division has developed and demonstrated the capabilities of micro-
hotplate and microcalorimetry sensors in terms of their high sensitivity, and it could earn high regard in
the sensors community if it were able to clarify the fundamental expectations and limitations of the
stability of nanoscale and thin-film sensor technology. The panel also suggests that rather than abandon-
ing the established custom of charging for the use of NIST's property data, some minimum access in
terms of downloaded megabytes or computer milliseconds over a subscription period could be allotted
to each new e-mail address in order to familiarize potential customers and researchers with the hidden
wealth of information.
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
SURFACE AND MICROANALYSIS SCIENCE DIVISION
Technical Merit
The Surface and Microanalysis Science Division performs research to accomplish the following:
153
· Determine the chemistry and physics of surfaces, interfaces, particles, and bulk materials and
determine their interactions with a broad spectrum of analytical probes, including electrons, photons,
ions, atoms, and molecules;
· Determine the chemical and isotopic compositions, morphology, crystallography, and electronic
structure at scales ranging from millimeters to nanometers;
· Determine the energetics, kinetics, mechanisms, and effects of processes occurring on solid
surfaces and interfaces as well as within materials and devices;
· Study the total chemical measurement process as well as source apportionment in atmospheric
chemistry using advanced isotope metrology and chemometrics; and
· Develop and certify key Standard Reference Materials and Standard Reference Data.
The overall quality and dedication of the division's staff are extremely high. Since last year's
review, the Surface and Microanalysis Science Division has further modified its organizational structure
in order to focus its projects on its primary mission. It has reduced the number of groups from four to
three, having redistributed the staff assigned to the Atmospheric Chemistry Group to other groups. This
change is an excellent example of the division's responsiveness to recommendations of the review panel
in the FY 2002 report. The reorganization appears to be an effective step toward concentrating the staff
talents on core competencies. The transition is proceeding as important legacy projects are brought to a
proper conclusion, and assimilation into the new group structure should be completed this year. The
three remaining groups are the Microanalysis Research Group, the Surface and Interface Research
Group, and the Analytical Microscopy Group.
The division's technical programs continue to be world-class, with many clearly being at the leading
edge of research. During the past year, the division organized six major workshops on a national level
and organized a number of sessions at other types of conferences as well. The division has participated
in important site visits to approximately a dozen major companies and is involved with a number of
important CRADAs. Furthermore, it has active collaborations with several external companies, both
domestic and international. Multiple collaborations with other NIST laboratories and external support-
ing organizations attest to the high value of its scientific work. The division has also presented numerous
important technical papers and talks at both domestic and international technical conferences. This
output attests to the intent of the division to share appropriate results with the professional community
in order to further the general aims of the scientific community. All of this speaks very well for the
division and its current activities.
The research work performed by the Microanalysis Research Group has long been noted as being
world-class and leading edge. Many of the standard techniques used worldwide in microanalysis are
almost fully based on this valuable NIST program. Recently, this group has shown its determination to
retain its research leadership by continually developing new approaches to what has been standard
methodology. An example is the use of the NIST microcalorimeter in Boulder to obtain high-resolution
X-ray spectroscopic data and apply them to the problems of electron probe microanalysis. This major
development in instrumentation is currently being commercialized in the United States and Europe by
two instrument manufacturers. Although it is unfortunate that intellectual property issues in NIST kept
this technology from being widely distributed for some time, that problem has apparently been solved,
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The panel continues to look for improvement in Web access to the products produced by the
division. Coordinated access to the data in the Chemistry WebBook and the TRC database, and indeed
a single Web point of entry for access to all chemical data at NIST, are goals acknowledged by the
division. With the growing trend away from hard-copy distribution to Web-based distribution of data,
there is a need to ensure permanent accessibility by the user community. Because the Physical and
Chemical Properties Division generates more than 95 percent of the sales of Standard Reference Data-
bases, the division should take the lead in developing and implementing a strategic plan for NIST to
ensure archiving and permanence of the Web-based data distribution systems.
Because of ongoing resource pressures, the panel strongly recommends that the division address the
issue of cost recovery for databases in general, possibly through a subscription mode for full access to
the data via the Web or through a workable per-retrieval charging mechanism. Current division plans are
to develop a proposal by the end of FY 2003 to provide access to the TRC tables via the Web on a fee
basis.
Finally, the panel encourages increased use of remote interaction and collaboration tools, such as
Web-based audio- and videoconferencing and application sharing. These tools are now available at
relatively low cost and have the potential to enhance interactions among researchers in different groups.
Some additional investments in hardware and software infrastructure may be necessary for taking full
advantage of these tools. Although this is a broader NIST issue, the Physical and Chemical Properties
Division is the only NIST division divided between Gaithersburg and Boulder, and it thus stands to gain
significant benefits from such tools.
ANALYTICAL CHEMISTRY DIVISION
Technical Merit
The Analytical Chemistry Division (ACD) carries out the following activities:
· Research concerning the qualitative and quantitative determination of chemical composition;
· Development and maintenance of state-of-the-art chemical analysis capabilities;
· Dissemination of tools for measurement traceability and quality assurance (such as reference
materials, reference data, and other services); and
· Demonstration of the international comparability of U.S. standards for chemical measurement.
The division serves as the nation's reference laboratory for chemical measurements and standards to
enhance U.S. industry's productivity and competitiveness, ensure equity in trade, and provide quality
assurance for chemical measurements used for assessing and improving public health, safety, and the
environment. The division maintains world-class metrology based on core competencies in analytical
mass spectrometry, analytical separation science, atomic and molecular spectroscopy, chemical sensing
technology, classical and electroanalytical methods, gas metrology, nuclear analytical methods, and
microanalytical technologies.
These core competencies reside in five groups: Spectrochemical Methods, Organic Analytical Meth-
ods, Gas Metrology and Classical Methods, Molecular Spectroscopy and Microfluidic Methods, and
Nuclear Methods. The skills and knowledge derived from laboratory-based research concerning the
phenomena that underpin the measurement of chemical species in a broad spectrum of matrices are
continuously applied to the development and critical evaluation of measurement methods of known
accuracy and uncertainty. The five primary research groups collaborate in a number of high-priority
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program areas, including reference methods and standards for clinical diagnostics; measurement stan-
dards for forensics and homeland security; measurement methods and standards for nutrients, contami-
nants, and adulterants in foods; environmental measurements and standards; methods and standards for
advanced materials characterization; methods and standards for commodities characterization; and mi-
croanalytical technologies (lab-on-a-chip).
The technical merit of the work within ACD has been acknowledged in a number of ways. During
this past year, research in the division resulted in 147 peer-reviewed publications, up from an average of
123 per year over the previous 4 years. In addition, two members of the division staff maintained an
editorial board membership and an editorship, respectively, with prestigious international journals. The
Department of Commerce Bronze Medal for work in visualization methodologies for the communica-
tion of complex statistical information was awarded to a division scientist. Finally, the position of the
division within the national and international metrology communities is demonstrated by staff participa-
tion in 136 scientific committee assignments an increase from an average of 116 per year over the
previous 4 years. Discussions of current division work illustrating technical merit are presented by
group in the following sections.
Spectrochemical Methods
Research activities of the Spectrochemical Methods Group continue to set an extremely high stan-
dard, and the panel compliments this group for its diligent performance in accordance with the mission
of NIST. The various programs associated with mass spectrometry, X-ray fluorescence, optical spec-
trometry, and sample preparation are proceeding well, and they underscore the productive role that this
group plays in creating, developing, and maintaining the SRMs that constitute 71 percent of such
products produced by the division. The group has also adapted well to the demands created by new
projects aligned to homeland security and the World Trade Center investigation. Furthermore, it contin-
ues to show its leadership, relative to other worldwide activities, in all its areas of involvement.
The Spectrochemical Methods Group has a long history of providing research and standards to
support environmental measurements regulated by the Clean Water Act of 1972, the Safe Drinking
Water Act of 1974, and the Clean Air Act of 1970. A new inductively coupled plasma mass spectrom-
etry method for high-precision comparisons of multielement standards was designed and applied this
year to support the quality assurance and proficiency testing programs conducted for the Department of
Energy and the Environmental Protection Agency (EPA). This method is capable of yielding 0.2 percent
uncertainty for multielement solution standards, and it was applied in the determination of five elements
in 13 different mixtures analyzed in support of the EPA-proficiency testing program.
Projects associated with the existence of mercury in the environment continue to deal with one of
the most important regulatory concerns, and the group made measurements and certified standards
across a range of projects using the recently developed method based on cold-vapor isotope-dilution
inductively coupled plasma mass spectrometry. Mercury was determined in a wide variety of SRMs:
urine, inorganic sediment, crude oils, pine needles, bovine blood, mussel tissue, fish tissue, and coal.
In the area of air quality, the Spectrochemical Methods Group has been working with the National
Institute of Occupational Safety and Health to develop a new series of SRMs: Silica on Filters. Respi-
rable crystalline silica is an occupational hazard whose presence in the workplace is strictly regulated by
the Occupational Safety and Health Administration. It is poorly measured by standard industrial tech-
niques (X-ray diffraction, infrared, ultraviolet/visible). Thus, both the demonstration of a safe work-
place and effective enforcement of regulations have been frustrated. The new SRMs have been prepared
by depositing SRM 1878a, which is certified 100.00 percent + 0.21 percent crystalline alpha-quartz, on
polyvinyl chloride filters.
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The Organic Analytical Methods Group is responsible for the publication of 44 papers in peer-
reviewed journals, 5 NIST special publications, and 62 presentations at national or international scien-
tific meetings, and it issued 10 SRMs. These accomplishments represent an impressive annual record,
all the while maintaining high technical quality. This group is quite effective in providing advanced
metrology work in its key activity areas and is highly regarded, as attested to by awards received and
publications.
Major group activities included measurements and standards in these areas: clinical/health, the
environment, food and nutrition, forensics and homeland security, and international comparison studies.
STRS activities included development in the five main areas of support based on the major group
activity categories. SRM development was completed in each of the major areas: the environment,
clinical/health, food and nutrition, and forensics. The clinical/health activity placed an emphasis on in
vitro diagnostics with its completion of several SRMs.
Recent research activities in organic mass spectrometry have focused on the development and
critical evaluation of new approaches to the quantitative determination of biomolecules (e.g., proteins)
in biological matrices. The recent acquisition of a liquid chromatography capability with tandem mass
spectrometry (LC/MS/MS) system and a matrix-assisted laser desorption ionization time-of-flight
(MALDI-TOF) mass spectrometer has significantly increased the group's capacity for the determination
of trace-level analyses of health, nutritional, forensic, and environmental importance, as well as for
structural studies of natural products. Recent efforts have been directed toward the development and
critical evaluation of reference methods for trooping I (a new marker of myocardial infarction), thyroxin
and triiodothreonine (thyroid function), cortisol (a marker for endocrine function), speciated iron (ane-
mia and hemochromatosis), homocysteine (a risk factor for myocardial infarction), folio acid (an essen-
tial nutrient that reduces the risks of heart disease and neural tube defects), and prostate-specific antigen
for prostate cancer. A particularly timely project currently under way is the development of an ephedrine
SRM for both tablet and drink-additive matrices.
The group currently maintains the National Biomonitoring Specimen Bank at two locations, the
NIST Gaithersburg campus and the Hollings Marine Laboratory in Charleston, South Carolina. At
present, the primary specimen banking activities involve tissues collected from marine mammals
throughout the United States, including Alaska, and seabird eggs collected from seabird colonies in
Alaska. There are now 2,087 marine mammal tissue specimens banked in the National Biomonitoring
Specimen Bank, representing 737 individual animals and 34 species, and 188 seabird eggs from 3
species. These banked specimens represent a resource that has the potential for addressing future issues
of marine environmental quality and ecosystem changes through retrospective analyses.
. .. . .
Gas Metrology and Classical Methods
The Gas Metrology and Classical Methods Group is composed of a staff of 17. During the past year,
12 gas mixture standards, 7 conductivity solution standards, 1 anion solution standard, 3 pH materials,
and a sodium oxalate reductometric standard were completed. In addition, 42 gas mixture standards
were recertified for various clients. The group also worked with five specialty gas companies to develop
35 batches of NIST-Traceable Reference Materials. The more than 1,000 individual gas cylinders
comprised by these 35 NTRM batches will be used to produce approximately 100,000 NIST-traceable
gas standards for end users worldwide. This work, completed over the preceding calendar year, repre-
sents excellent productivity and quality for a technical group of this size.
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In work of the Classical Methods team, pH is being ascertained with an uncertainty of 0.0015 to
0.002 pH units using a NIST Harned Cell. This current work has improved NIST primary pH metrology
and seeks to relate pH measurement across national laboratories worldwide. Other work includes the
development of an absolute conductivity cell for pure water.
Improved analytical tools for real-time measurement of trace-level vapors in the atmosphere are
critical for the evaluation of new technologies for reducing hazardous industrial emissions. Toward this
end, the group is critically evaluating the capabilities of Fourier Transform microwave spectroscopy for
real-time sensing applications. The high spectral resolution and high sensitivity of Fourier transform
microwave spectroscopy suggest that the technique can provide unambiguous identification of vapor-
phase analyses. The original goal of this project was to address the needs of the automobile industry to
identify and quantify trace levels of oxygenates in exhaust emissions. Success in this work will also
affect many other critical applications, including the detection of chemical warfare agents.
Molecular Spectroscopy and Microfluidic Methods
The Molecular Spectroscopy and Microfluidic Methods Group conducts research on the metrology
of molecular spectroscopy; develops standards for the calibration, validation, and performance of instru-
ments for measuring molecular spectra; and conducts research on microfluidic devices, methods, and
applications for chemical analysis, including studies of materials and material properties affecting the
flow of liquids in microchannels and the use of microchannel and other electrophoretic methods for
forensic and toxicological applications and standards. The group is also responsible for the development
and certification of optical transmittance and wavelength standards in the ultraviolet (UV), visible
(VIS), and near-infrared (JR) spectral regions; Raman intensity correction standards; and fluorescence
wavelength and intensity standards. Finally, the group works with users and manufacturers of analytical
instruments to assess and measure the performance of analytical methods and to determine and address
existing and future needs for analytical instrument standards ranging from device calibration and instru-
ment performance through specifications for remote device control and data interchange.
This group continues to demonstrate energy, innovation, and exceptional collaborative efforts with
other sections and groups at NIST and with institutions and agencies outside NIST. The microfluidics
team is particularly active in collaborative efforts and continues to recruit young, promising talent. The
program relevance associated with this group's work is exemplified by its certification or recertification
of nearly 70 solid absorbance filter SRMs and 202 optical filter sets. Continuing measurements were
made on a number of other filter sets. In addition, nearly 250 units of SRM 2034 (holmium oxide
UV-VIS wavelength standard) were certified and delivered to the Standard Reference Materials Program.
These products are used across a wide spectrum of industry and fulfill an essential requirement.
This year the microfluidics projects resulted in 11 publications, 4 patent applications, and 10 talks
and posters. Funding for this area has come from the microscale analytical laboratory's competence
award, an ATP intramural grant, a Single Molecule Manipulation and Measurement competence award,
and STRS. This program area maintains collaborations with the Process Measurements Division, the
Biotechnology Division, the Optical Technology Division, and the Semiconductor Electronics Division.
The group continues to attract National Research Council postdoctoral research associates, adding one
more this year to bring the group total to four.
In the new competence area of Single Molecule Manipulation and Measurement, several solid
accomplishments were achieved. Microchips were developed for the handling of water in fluorocarbon
emulsions using optical tweezers; also, protocols were developed for wet chemical bonding of PDMS
(polydimethylsiloxane) to PDMS and PDMS to glass. Other protocols developed included those for the
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production of ultrathin laminated chips with integral capillary ports for high-pressure, low-dead-volume
applications, and for a filled loop injector for two-phase fluid systems. The group continued to study the
parameters that affect flow in plastic microchannel devices. This past year, major progress was made in
applying UV-laser ablation for fabricating microdevices, for studying parameters important to the
postmachining properties of microdevices, and for carrying out both physical and chemical modifica-
tions to the surfaces of microdevices. There seems little doubt that these studies will have a profound
impact on the understanding of microfluidic design in micromachined systems in the future.
Nuclear Methods
Research in the Nuclear Methods Group focuses on the science that supports the identification and
quantification of chemical species by nuclear analytical techniques. Current laboratory research activi-
ties involve a range of nuclear analytical techniques, including instrumental and radiochemical neutron
activation analysis (INAA and RNAA), prompt gamma activation analysis (PGAA), and neutron depth
profiling (NDP). In addition, the group is developing further analytical applications of neutron focusing
technology. The measurement capabilities within this group provide an excellent complement to those
in the Spectrochemical Methods Group, as nuclear analytical methods depend on characteristics of the
nucleus of the atom rather than on those of the electron shells, and therefore are insensitive to the
chemical state of the analyte (i.e., matrix effects). In addition, the nuclear methods are generally nonde-
structive and do not require sample dissolution, thus providing an independent assay. NDP and focused
beam PGAA provide unique capabilities for the NIST facility in terms of location, sensitive analysis,
and elemental mapping.
To develop SRMs for microanalysis, the group has applied new INAA procedures to study the
homogeneity of SRMs at small sample sizes. Many analytical techniques used in industry and academia
rely on the analysis of very small samples (e.g., 1 log), typically in the solid (undissolved) form.
Unfortunately, most SRMs are certified with minimum sample sizes of 100 to 500 ma, and they are
therefore unsuitable for use as control materials for these techniques unless additional information is
made available. Taking advantage of the sensitivity and nondestructive properties of INAA, the use of
this technique for homogeneity studies of small samples has been evaluated and implemented for the
determination of sampling characteristics for a number of environmental SRMs. The small analytical
uncertainty associated with the INAA measurements allows extraction of the variability due to material
inhomogeneity from the observed total variability within a given set of measurements.
A good deal of this past year's effort has coincidentally involved materials of interest in advanced
energy systems. A method has been developed and an apparatus built to produce titanium (and other
metal) SRMs of known hydrogen concentration on the scale of a few kilograms. After preparation, the
hydrogen concentration is verified by cold-neutron PGAA and gravimetry. This apparatus has also been
used to prepare standards for the neutron-tomographic nondestructive analysis of turbine blades at
McClellan Air Force Base.
Current experiments of interest at the NDP instrument include the measurement of lithium concen-
tration and distribution in thin films being studied for battery applications, studies of boron mobility in
tungsten with the Army Research Laboratory, studies of shallow-doped boron content in silicon in
conjunction with Advanced Micro Devices, the study of lithium distribution in lithium niobate, and the
measurement of nitrogen in layers such as TiN and GaN. As a recent example, NDP has been used to
measure nitrogen distributions in GaN/GaAs bilayers with Corning. This material is a base material for
the construction of devices such as blue, light-emitting lasers. The nitrogen concentration is a crucial
parameter for establishing the device characteristics. Nitrogen concentrations of MnN/ScN have been
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determined in conjunction with scientists from the NIST Center for Neutron Research and Ohio Univer-
sity. MnN is a metallic antiferromagnetic material that can be used with ferromagnetic semiconductors
to make spintronic devices for data storage systems.
In addition to the collaborations highlighted above, staff in the Nuclear Methods Group have also
worked on a number of high-priority projects with more than 20 other "outside clients" as part of their
responsibility for supporting the NIST Center for Neutron Research National Users' Facility. Many of
the current PGAA collaborations involve determining hydrogen in a wide variety of materials for
different applications. For example, the group is currently collaborating with Jefferson Laboratory to
monitor the hydrogen content of niobium that was used in the construction of the accelerator for the
Spallation Neutron Source at Oak Ridge National Laboratory. PGAA has also been used to determine
the hydrogen content of carbon nanotubes (a potential hydrogen storage material) and to study hydrogen
uptake by solid proton conductors of formula BaPr~_xYxO3 for fuel cell applications. Other measure-
ments made at the PGAA facility this year include H. S. Ca, and K in Nations, which have potential use
as membranes in electrochemical separations and in fuel cells.
Program Relevance and Effectiveness
The issue of identity and differentiation is an important one for the Analytical Chemistry Division.
Among the ever-expanding number and complexity of sensors and measurement devices throughout the
nation, one unique capability of this division is not duplicated anywhere in the United States. This is the
critical function of developing SRMs and concurrent technologies that provide exacting performance
for highly repeatable, accurate, and reproducible measurements. The objective of the division is not
preeminence in research to develop new measurement technologies, but rather the perfection of these
technologies using specialized analytical metrology expertise. The expertise of the division should be
applied to improve newer technologies into accurate, traceable, and reproducible measurements. These
functions clearly differentiate the essential value of the Analytical Chemistry Division over other
national laboratories, industrial research, and university skill sets.
Increased requirements for quality of systems documentation for trade and effective decision mak-
ing regarding the health and safety of the U.S. population have increased the need for demonstrating
traceability to NIST measurements and standards and establishing a more formal means for document-
ing measurement comparability with standards laboratories of other nations and/or regions. SRMs are
certified reference materials issued under the National Institute of Standards and Technology trademark
that are well characterized using state-of-the-art measurement methods and/or technologies for chemical
composition and/or physical properties. Traditionally, SRMs have been the primary tools that NIST
provides to the user community for achieving chemical measurement quality assurance and traceability
to national standards.
The division provides traceability of chemical measurements used in programs of national and
international importance through SRMs, NIST-Traceable Reference Materials (NTRMs), measurement
quality assurance programs in critical areas, and comparisons of NIST chemical measurement capabili-
ties and standards with those of other National Metrology Institutes. Examples demonstrating program
relevance and effectiveness follow.
The NTRM program was created to partially address the problem of increasing requirements for
reference materials with a well-defined linkage to national standards. An NTRM is a commercially
produced reference material with a well-defined traceability linkage to existing NIST standards for
chemical measurements. This traceability linkage is established via criteria and protocols defined by
NIST and tailored to meet the needs of the metrology community to be served. The NTRM concept was
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implemented initially in the gas standards area to allow NIST to respond to increasing demands for high-
quality reference materials needed to implement the emissions-trading provisions of the Clean Air Act
of 1970 (while facing the fact that human and financial resources have not been increasing at NIST). The
program has been highly successful. Since its inception, 12 specialty gas companies have worked with
NIST to certify more than 9,000 NTRM cylinders of gas mixtures that have been used to produce more
than 500,000 NIST-traceable gas standards. A recent study conducted by RTI International estimates
that the net benefits of the NTRM program projected through 2007 will be between $50 million and $63
million, with a social rate of return of about 225 percent.
International agreements and decisions concerning trade and our social well-being are increasingly
calling upon mutual recognition of measurements and tests between nations. The absence of such
mutual recognition is considered to be a technical barrier to trade, environmental, and health-related
decision making. In recent years, mutual recognition agreements have been established related to testing
and calibration services and with respect to the bodies accrediting such activities. The Analytical
Chemistry Division has taken a leadership role on the International Committee of Weights and Measures-
Consultative Committee on the Quantity of Material (CCQM) and the Chemical Metrology Working
Group of the Inter-American System for Metrology (SIM) in order to ensure the effective, fair, and
metrologically sound implementation of this mutual recognition agreement. Division staff members are
leading various activities within CCQM and chairing the Organic Analysis Working Group. During the
past 5 years, 53 comparison studies have been conducted under the auspices of the CCQM. The
Analytical Chemistry Division has participated in 46 of these, serving as pilot laboratory in 18. An
additional 36 studies are planned to be conducted over the next 3 years, and NIST has committed to pilot
9 of them.
Providing chemical measurement quality assurance services in support of other federal and state
government agency programs (on a cost-reimbursable basis) continues to be an important part of the
division's measurement service delivery portfolio. During the past year, the Analytical Chemistry
Division was involved in 25 projects with 11 federal and state government agencies. The division also
had technical interactions that involved laboratory research and measurement activities with more than
20 professional organizations and societies, including the American Industry/Government Emissions
Research (AIGER) consortium, American Association for Clinical Chemistry, American Society for
Testing and Materials, Certified Reference Materials Manufacturers Association, National Food Proces-
sors Association, National Council on Clinical Chemistry, and the National Environmental Laboratory
Accreditation Council. Specific details concerning many of these interactions are provided below.
Other high-priority efforts are directed at the detection of various poison agents in food, water, or air
that might be used less for mass destruction and more for mass terror. Thus, the ongoing efforts to
benchmark the detection of trace elements and the characterization of "natural" levels of elements in the
environment, body fluids, and in our foods take on increased relevance. The division has added new
certified values for Cd and Hg in the blood SRM 966 at concentrations of a few tens of parts per trillion
and has completed analyses for a suite of toxic elements in the urine SRM 2670a at levels as low as 5
parts per trillion.
NIST works with other government agencies, professional organizations, the private sector, and the
international community through the recently formed Joint Committee on Traceability in Laboratory
Medicine to prioritize measurement and standards needs.
In addition to the clinical measurement reliability and cost issues that have driven measurement and
standards for the clinical diagnostic markers project over the past 20 years, a very significant commerce
and competitiveness issue has recently emerged the European Directive 98/79/EC on in vitro diagnos-
tic (IVD) medical devices. By December 2003, manufacturers must declare that any new IVD product to
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be sold within the European Union complies with all the "essential requirements" of this directive. One
of these requirements is that IVD products be traceable to "standards of the highest order" for ex-
ample, nationally and/or internationally recognized reference methods and/or certified reference materi-
als. At present, IVD devices are used in clinical laboratories to measure more than 300 different
chemical or biochemical species. Reference methods and/or materials exist for about 30 of these.
Approximately 60 percent of the IVD products currently on the European market are imported from the
United States. Excluding home diagnostics, the overall worldwide IVD market is an approximately $20
billion market.
Over the next decade, driven by the availability of new sensor-based measurement technologies,
more and more clinical testing will be done outside the traditional clinical laboratory. The annual U.S.
market alone for this new form of clinical measurements, called point-of-care testing (POCT), is cur-
rently a billion-dollar market, growing at an annual rate of 10 percent. POCT is expected to be used
extensively in the home as part of a self-care trend, which is currently experiencing a 70 percent growth
rate. Published studies have concluded that POCT provides at least the same level of diagnostic value as
centralized testing, but at half the cost. The standards infrastructure that has supported clinical chemistry
for the past two decades must adapt to support POCT. Collaborative efforts need to be established
among national standards laboratories, IVD manufacturers, and others in the medical professional
community to develop appropriate technologies and nonbiohazardous standards to facilitate the provi-
sion of data for medical decision making that are accurate and traceable to national/international stan-
dards. NIST leadership in developing traceable POCT standards will help ensure continued U.S. domi-
nance of the worldwide IVD market and foster more affordable health care both at home and abroad.
The main directive to the Gas Metrology team is to produce universally available large-volume
traceable mixtures. The primary standards are actually prepared at the NIST facilities in Gaithersburg.
The requirements for new standards are determined based on inputs from the U.S. EPA, automobile
manufacturers, specialty gas manufacturers, the AIGER consortium, and others. The team seeks to
respond to regulatory and industry needs while maintaining world-class excellence in gas metrology. In
response to AIGER's request, low-level NO (nitrogen monoxide) in nitrogen mixtures was provided.
Specialized techniques were developed to condition aluminum cylinders to make them capable of
holding such a mixture at stable conditions for extended periods. The team continues to interact with
industry and regulatory groups, such as the California Air Resource Board and the EPA, in efforts to
provide accurate standards for stack gas and automobile emissions measurements. The team is looking
for industrial partners to work with in producing low-volume standards, which do not require SRM
status. It seeks to be responsive to customer needs while managing the effort with limited resources.
The Gas Metrology and Classical Methods Group has continued its collaboration with the EPA and
the remote-sensing community in the development of a quantitative database of IR spectra for the
calibration of IR-based technology used for real-time monitoring of airborne chemical contaminants
along plant boundaries and within plant facilities. The spectra are being prepared using NIST primary
gas standards. These standards have been critically evaluated at NIST and intercompared internation-
ally. The use of SRD-79 to establish the traceability of open-path IR measurements will be required in
the update of EPA method TO-16. SRD-79 currently has data for 40 compounds.
The group also continues to support U.S. industry through the development and dissemination of
high-priority reference materials on the basis of input from organizations such as the AIGER consortium
and ASTM. Over the past 2 years, two new low-concentration nitric oxide gas SRMs have been
developed. These SRMs are needed by the automotive industry in the development of new cars and to
meet new regulations in California. These standards are also required by industry to meet new regula-
tions covering stack gas emissions. These gas SRMs, one at 0.5 ppm (SRM 2737) and one at 1.0 ppm
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(SRM 2738), will be available for sale late in FY 2003. They are the result of an active collaboration
between NIST and the AIGER consortium, which donated the candidate gas mixtures for the SRM. This
work also involved collaboration with the Scott Specialty Gases Company to develop the technology
used in passivating the cylinders.
Interactive activities of the Molecular Spectrometry and Microfluidic Methods Group during the
past year included measurements for the SIM intercomparison of holmium oxide solutions for the
completed UVIVIS wavelength standards. Report preparation is under way. The report of the similar
North American Metrology Organization study was published in Analytical Chemistry, and the results
were used to establish new uncertainty values for the wavelength assignments of SRM 2034, Holmium
Oxide Solution. To this end, it has been proposed that the spectrum of holmium oxide may be useful as
an "intrinsic" standard a standard whose purity can be assessed inherently and whose wavelength
"peak" values at given spectral slit widths can be certified independently and published as standard
reference data. Therefore, a given artifact, independent of source, can be accurately assessed and, if
found suitable, can be utilized as a standard. To substantiate this concept, it is necessary to assess the
extent of the international agreement on the wavelength assignments for holmium oxide solutions.
Accordingly, this group has begun a holmium oxide wavelength intercomparison with several NMIs
around the world. If this concept proves correct, the wavelength values as a function of spectral slit
width will be published as a Standard Reference Database.
The Molecular Spectroscopy and Microfluidic Methods Group continues to provide statistics and
data representation studies for the FBI, the NIST Office of Law Enforcement Standards, and other
agencies investigating the use of DNA methods of forensic analysis. In close collaboration with the
CSTL Biotechnology Division, significant progress has been made on three projects: the Armed Forces
DNA Identification Laboratory-sponsored study of DNA extractability from archival media was com-
pleted and the final report published; data entry and validation for the OLES-sponsored Mixed Stain
Study #3 interlaboratory challenge exercise has been completed; and database and quality assurance
procedures have been (and are being) developed for the Biotechnology Division's Y-STR databank,
sponsored by the National Institute of Justice.
Division Resources
The Analytical Chemistry Division had approximately 90 scientists, technicians, and administra-
tive/clerical support staff as of January 2003. The division has an annual budget of about $15 million, of
which about $6 million supports programs for other federal and state government agencies and/or U.S.
industry on a cost-reimbursable basis.
Most of the funding sources have been relatively constant over the FY 1998-2003 period, with the
STRS base funding increasing at a reasonable rate. The greatest variability over the past few years has
been in the working capital fund derived from the SRM program.
Over the past 4 years, there has been a steady decrease in personnel, specifically in the permanent
and term professional categories. Unlike in previous years, a formal reduction in force (RIP) was
undertaken this year based on budgetary concerns; the positions of four permanent professionals and
one technician were eliminated. RIFs in scientific personnel have a particularly profound effect in this
division, which has a very high service load with regard to the SRM program and international activities.
It should be stated that part of the budget pressure experienced by this division is a direct conse-
quence of needing to place priorities on the purchases of modern instrumentation that had long been
delayed. For example, as pointed out in last year's assessment report, the lack of an inductively coupled
plasma mass spectrometry system having collision cell capabilities was a glaring shortcoming. This and
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CHEMICAL SCIENCE AND TECHNOLOGY LABORATORY: DIVISION REVIEWS
173
other purchases were made this year, at the partial expense of personnel. While these purchases are key
to the performance of the division, the situation of having to choose between personnel and the tools
necessary to carry out the mission of the division is disturbing. The successful operation of the division
should be of concern at all levels of NIST, as the potential impact on U.S. industry is enormous.
Given the financial difficulties of the past year, and particularly considering the RIF, the mood of
the staff present at the skip-session (with no management present) was better than expected. Clearly
there was a feeling of having to continue to do more with less. The staff members are extremely positive
as suggested in their comments regarding the opportunities and the working environment at NIST, but
they do express concern about the growing difficulty in replacing equipment or maintaining the scien-
tific leadership position that they have come to expect. International cooperation was felt by staff to be
beneficial; however, some commented that competition with other NMIs is not all positive: "Our
interaction has been more of form or politically oriented than scientific results-oriented." It was felt by
staff members that the division, while highly touted in CSTL and NIST reports, did not receive in-kind
recognition internally through financial support of the programs. In short, they felt that the division as a
whole was not valued, as exhibited through underrepresentation in exploratory research funding and
from its being the sole division experiencing a RIF during the year. Interestingly, they did understand
that division-level decisions regarding personnel and instrumentation purchases were not independent
of one another. There was also concern expressed about a shortage of staff to maintain the SRM
programs that generate significant revenue for NIST. Many comments were made relative to the leader-
ship and communication skills of group leaders. As in previous years, communication relative to the
budgeting process was noted as a shortcoming. On the other hand, the methods of setting priorities did
seem to be well elucidated by the division leadership. In general, though, the vast majority of the staff in
attendance at the skip-level session indicated that NIST and the Analytical Chemistry Division are very
good places to work.
The panel is concerned over the potential loss of expertise in some technical areas: in glass mixing,
cutting, and polishing with the high precision required for SRMs and in precision machining for SRM
quality fixtures. It is the panel's understanding that glasswork is contracted to former NIST employees,
now retired, with some 70-plus combined years of NIST glasswork experience relative to SRMs. There
is not a sufficient effort to replace this expertise with younger trainees. Secondly, the precise machine
shops must operate in a nonsubsidized manner, placing pressure on the future existence of this function
and expertise within NIST. With the world-class skill levels required in the manufacturing of quality
SRMs, neglect of these functions could seriously jeopardize future SRM quality or costs of production.
These important support services are considered to be of vital interest to CSTL as a whole.
Recommendations
Given the critical positioning of the Analytical Chemistry Division as the primary laboratory for the
development and certification of an appreciable fraction of the NIST SRM portfolio, it is imperative that
the division maintain the highest quality of personnel and instrumentation available in the United States.
As demonstrated through the division's international activities, its participation and capabilities are
crucial to the competitiveness of U.S. industries. The program directed at in vitro diagnostics is an
excellent example. The RIF this year reflects strains on the organization in terms of making decisions
between keeping highly skilled employees and maintaining state-of-the-art capabilities in supporting
instrumentation. Clearly, given the charter of the division, this either/or situation cannot be tolerated, as
both productivity and quality will suffer. The laboratory is encouraged to evaluate the real costs of SRM
development and recertification, keeping in mind that both of these activities are de facto more expen-
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74
AN ASSESSMENT OF THE NIST MEASUREMENT AND STANDARDS LABORATORIES: FY 2003
sive in terms of personnel and instrumentation costs than is reflected in the current SRM pricing and cost
reimbursement. As an example of pricing disparities, a comparison of the cost of a NIST aluminum
alloy SRM and a commercial aluminum Certified Reference Material (CRM) product reveals that the
SRM costs approximately one-half the price of the commercial CRM. Clearly, this does not reflect the
quality of SRMs and the supporting infrastructure required to maintain world leadership in standard
materials. It is further suggested that unlike the situation with the current structure of the working fund,
such projects have a nominal surcharge that is assessed specifically for instrument purchases that can in
fact be accessed at the front end of projects (if needed).
The division should begin to plan for major personnel changes in the Nuclear Methods Group.
While there is no apparent immediate need in this area, it is clear from the demographics of that group
that the vast majority of its scientists might take retirement over a limited time frame. Plans should be
made for training potential replacement scientists as well as for developing new leadership within the
group. Given the highly specialized nature of this group, there is not expected to be a large, young, talent
pool, so the challenge will be great.
The direction of standards development and basic research naturally evolves over time. In many
respects, the success of the microfluidics effort in the Molecular Spectroscopy and Microfluidic Meth-
ods Group has resulted in the creation of a very strong subgroup that is reasonably distinct from the
remainder of the program. In fact, this subgroup addresses a long-standing shortcoming in the area of
microanalytics. Clearly, the impact of micro-total analysis systems as its own subdiscipline within
analytical chemistry is felt in many industrial sectors and is worthy of more serious attention by NIST in
general, and not only through aspects of microfluidics. Perhaps a realignment of the groups in terms of
elemental/inorganic analysis, organic analysis, molecular spectrometry, gas metrology and classical
methods, and a new microanalytics group, may make sense. A microanalytics group would in many
respects contain aspects of the other groups, but such a change would allow a focus specifically on
analytical systems (i.e., a systems approach) and reference materials as they pertain to the ever-broaden-
ing scope of micro-total analysis systems.
The participation of division staff in international comparison activities is seen as a vital function.
At present, staff limitations could eventually begin to place limits on the necessary activities. In addition
to the time required to perform comparisons, report generation and travel also place demands on time
and other resources. Finally, efforts are also required in the mentoring of staff of other NMIs not having
the skill sets of the division scientists. To recoup these costs requires some specific mechanism other
than the standard operating budget, which does not account for these activities in terms of personnel
time and other direct costs.
The activities related to homeland security are progressing well. Other opportunities may exist, in
collaboration with the Transportation and Security Administration (TSA) possibly in the areas of
methodology standardization, performance assessment, and reference material development. It may be
that TSA is performing such services in-house, but these activities would certainly be appropriate for
and well performed by the Analytical Chemistry Division. Such opportunities should be investigated.
Representative terms from entire chapter:
nist measurement
