Download Measurement and Standards for Chemical and Biochemical Analysis

Measurement and Standards for
Chemical and Biochemical Analysis
Hratch G. Semerjian
Director, CSTL
NRT
November 29, 2001
Washington, DC
Chemical Science and Technology Laboratory
NBS was established in 1901
“The necessity (for standards) had become
imperative as science and industry, ready to take
giant steps in the new century, looked for better
measurements and more uniformity, precision, and
control in the laboratory, factory, and plant.”
Measures for Progress – a History of NBS
Chemical Science and Technology Laboratory
CSTL Vision
A world class research laboratory recognized by the Nation as the primary
resource for chemical, biomolecular, and chemical engineering
measurements, data, models, and reference standards required to enhance
U.S. industrial competitiveness in the world market.
CSTL Mission
As the Nation’s Reference Laboratory, CSTL’s Mission is to provide the
chemical measurement infrastructure to:
• enhance U.S. industry's productivity and competitiveness;
• assure equity in trade; and
• improve public health, safety, and environmental quality.
Chemical Science and Technology Laboratory
Measurement Standards
Establish CSTL as the pinnacle of the national traceability and
international comparability structure for measurements in chemistry,
chemical engineering and biotechnology, and provide the fundamental
basis of the nation’s measurement system
Chemical and Process Information
Assure that U.S. industry has access to accurate and reliable data and
predictive models to determine the chemical and physical properties of
materials and processes
Measurement Science
Anticipate and address next generation measurement needs of the
nation, by performing cutting-edge research
Chemical Science and Technology Laboratory
CHEMICAL SCIENCE AND TECHNOLOGY
LABORATORY ORGANIZATION CHART
Hratch G. Semerjian, Director
William F. Koch, Deputy Director
Biotechnology
Process
Measurements
Surface &
Microanalysis
Science
Physical &
Chemical
Properties
Analytical
Chemistry
G. Gilliland, Chief
J. Whetstone, Chief
R. Cavanagh, Chief
M. Haynes, Chief
W. May, Chief
• Fluid Flow
• Fluid Science
• Process Sensing
• Thermometry
• Pressure and Vacuum
• Thermal and Reactive
Processes
• Atmospheric
Chemistry
• Microanalysis
Research
• Surface Dynamical
Processes
• Analytical
Microscopy
• DNA Technologies
• Bioprocess
Engineering
• Structural Biology
• Biomolecular
Materials
• BioInformatics
• Experimental
Kinetics &
Thermodynamics
• Chemical Reference
Data & Modeling
• Computational
Chemistry
• Experimental
Properties of Fluids
• Theory & Modeling
of Fluids
• Cryogenic Tech.
• Spectrochemical
Methods
• Organic Analytical
Methods
• Gas Metrology &
Classical Methods
• Molecular
Spectroscopy &
Microfluidic Methods
• Nuclear Methods
Chemical Science and Technology Laboratory
NIST Standards for Chemical Measurements
Chemical standards constitute 686 of ~1,400 NIST SRM types, and
more than 16,000 of nearly 32,000 NIST SRM Units Sold in FY01
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High Purity Neat Chemicals
Organic Calibration Solutions
Inorganic Calibration Solutions
Gas Mixture Standards
•
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Complex Matrix Standards
Advanced Materials
Biological Fluids/Tissues
Foods/Botanicals
Geologicals
Metal Alloys
Petroleum/Fossil Fuels
Sediments/Soils/Particulates
• Optical Filter Standards
• Conductivity Standards
• Ion Activity Standards
Chemical Science and Technology Laboratory
Industrial and Analytical Instruments and Services
Traditional partners … for dissemination of M&Ss
Standard Reference Data: compiled … evaluated … traceable
NIST Chemistry WebBook (on-line)
• Data for ~40,000 species
• New enthalpy of fusion database
• New fluid property models and capabilities
• User Profile: 80,000 hits per month
NIST Mass Spectral Library (CD)
• World’s most widely used MS library
• Evaluated spectra for 108,000 compounds
• Total of 138,000 spectra
• New automated methods of evaluation
• Extend applications to MS/MS
• Installed on >3000 instruments per year
Expert Analytical Systems:
• X-ray Spectrometry Simulation with DTSA
Additional database releases in FY 01:
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NIST/TRC Vapor Pressure DB
NIST/TRC Database - recommended values
Chemical Kinetics DB - online version
XPS DB - online version 3.0
FY 01 Outputs:
Items Directly Sold:
584
Distributor Sales:
3,972
Customers served: > 400,000
(includes web customers)
Chemical Science and Technology Laboratory
Analytical Database for OPCW
• Tool for directed verification of compliance
under the Chemical Warfare Convention
• Automatic Mass Spectral Deconvolution
and Identification Software for use by
OPCW for detecting CW and CW related
compounds in treaty inspections
• High quality data includes: infrared
spectra, retention data for GC, and mass
spectral data
• Database compares GC/MS experimental
data with spectral library, using
established and novel algorithms
NIST scientists provide training in the
use of SRDs and associated software
systems. One such system, coupled to a
GC/MS is designed specifically for field
detection and identification of chemical
warfare agents, and will be utilized for
verification of compliance to the CWC.
The United States is one of 143 signatory
parties to the Chemical Weapons Convention
(CWC), a global treaty that bans chemical
weapons. US companies engaged in
activities involving certain chemicals may be
required to submit reports to the Department
of Commerce and may be subject to
inspection by the Organization for the
Prohibition of Chemical Weapons (OPCW),
the international body that administers the
Chemical Weapons Convention.
SARIN
Chemical Science and Technology Laboratory
NIST Quantitative Infrared Database
SRD 79 – FTIR Database
• CD released Oct 1998 with
absorption coefficient data for
21 compounds
• FY 01 additional 19 on web
• Digital signature to ensure file
integrity
New Driver - GCC:
Supply spectra for ~ 50
global warming gases
Future Plans
• Interactive, web-based
FTIR calibration
NIST Quantitative Infrared Database (SRD 79)
−1
1.2e-3
−1
Absorption coefficient in base 10 (µmol/mol) m
Continuing Plan:
Supply spectra for ~ 100 of
EPA’s 189 HAPs
Resolution: 0.125 cm−1
Apodization: 3-Term Blackman-Harris
Methanol
1.0e-3
8.0e-4
6.0e-4
4.0e-4
2.0e-4
0.0e+0
1000
1500
2000
2500
3000
3500
4000
−1
Wavenumber (cm )
• Data at several resolutions
and apodization functions
• Traceable to NIST primary
gas standards
Chemical Science and Technology Laboratory
Environmental Technologies
Global Market for Environmental Technologies Estimated at $530 Billion
Standard Reference
Data
Standard Reference
Materials
FTIR
Database
Catalysts
REFPROP
Sediments,
and Dust
Acid Rain
Emissions Trading
Catalyst Poisoning
Source
Apportionment
Fossil Fuels
Gas
Mixtures
Standards for
Proficiency Testing
Chemical Science and Technology Laboratory
NIST/EPA Proficiency Testing of
Environmental Laboratories
CSTL, NVLAP, EPA, state and local
governments, and private sector
laboratories working together to
establish a proficiency testing system
for waste water and drinking water
testing
NIST / CSTL
Reference Materials
Accreditation
QA Oversight
Commercial and State Proficiency Testing
Providers (10-30)
PT Services
Approximately 6000 Environmental Laboratories
•• Issued
Issued NIST
NIST 150-19:
150-19: Chemical
Chemical
Calibration
Providers
Calibration - Providers of
of Proficiency
Proficiency
Testing
Testing
•• Received
Received 12
12 applications
applications for
for Testing
Testing
Providers
Providers
•• Producing
Producing primary
primary benchmark
benchmark materials
materials
where
where SRMs
SRMs are
are not
not available
available
–– to
to provide
provide infrastructure
infrastructure and
and
primary
standards
needed
primary standards needed to
to audit
audit
commercial
PT
samples
commercial PT samples
–– to
to assist
assist providers
providers in
in value
value
assigning
assigning their
their PT
PT materials
materials
Chemical Science and Technology Laboratory
Healthcare Measurements
Healthcare costs amount to ~ 14% of the GDP, an estimated $1.5 trillion
Diagnosis
Prevention
Folic Acid
Binding Protein
Treatment/Therapy
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Nutrition
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9
+
CSTL Maintains and Refines Definitive
Methods for 12 Health Status Markers
Calcium
Chloride
Cholesterol
Creatinine
Glucose
Lithium
Magnesium
Potassium
Sodium
Triglycerides
Urea
Uric Acid
Cancer, Blood Clotting
Kidney Function
Heart Disease
Kidney Function
Diabetes
Antipsychotic Treatment
Heart Disease
Electrolyte Balance
Electrolyte Balance
Heart Disease
Kidney Function
Gout
PSA
New Driver
EC IVD Directive
requires that all IVD
products sold in
Europe must show
“traceability to
standards of a higher
order”.
1
Chemical Science and Technology Laboratory
Healthcare Measurements
… supporting the national reference system for healthcare
NIST SRMs provide anchor for CAP evaluations:
• the peer group for grading and regulatory
purposes
• an accuracy-based assessment for
SRMs
medical utility for nine analytes
CAP
NIST Micronutrients QA Program:
• efficacy of nutrition in disease prevention
Program Participants
• 60 labs worldwide – fee supported
Continuous interactions with:
>60 Laboratories Worldwide
• CDC, NCCLS, AACC, NCI, AdvaMed
Expanded collaboration with:
Micronutrients QA
• NIH, FDA, CDC
Utilize core expertise to support an ever-changing range of needs Academia
Industry
Government
Areas of core expertise:
• Toxic inorganics – increased needs (Hg and Cd)
• Small organic markers – standards in place, measurement bias effects under study
jointly with Mayo clinic to determine impact on medical decision-making
• Protein-based markers – increased need
• Electrolytes – standards in place at currently acceptable levels
• DNA-based markers – increased need
Chemical Science and Technology Laboratory
Healthcare Measurements
New Drivers: EU IVD Directive and International Trade
Establish Reference Systems for New Clinical
Markers - Highest Priorities
Troponin-I
Glycated Hemoglobin
Homocysteine
Bilirubin
TSH
Speciated Iron
Human Serum Alb.
PSA
Cadmium & Mercury
Cortisol
Thyroxine
Folates
Myocardial Infarction
Diabetes Status
Risk of Heart Disease
Liver Function
Thyroid Function
Hemochromatosis, Anemia
Renal Failure
Prostate Cancer
Toxic Metal Poisoning
Endocrine Function
Thyroid Function
Neural Tube Defects
Glycated Hemoglobin
Hemoglobin
C2838H4416N768O794S16
glucose
C6H12O6
Needs Assessment:
IVD Workshop (Industry Driven),
November 2000
Follow-on Workshop, June 2002
Leading Global effort to address EU IVD Directive:
• ~100 well-defined chemical species on “A list”
• NIST to provide reference methods and SRMs for ~40%
• NMIs in EU, Japan and Australia to provide reference methods and CRMs for rest
• Mutual recognition of reference methods and CRM assigned values under discussion
• Work independently, and develop basis for recognition, OR
• Work jointly – HOWEVER issues of intellectual property are unresolved
Chemical Science and Technology Laboratory
Healthcare Measurements
NIST/ NCI Biomarker Validation Laboratory
EDRN Network: Supports development and implementation
of high-throughput biomarker analysis through technical
evaluations
NIST technical expertise: molecular cytogenetics,
genotyping, sequence analysis, mitochondrial DNA
sequencing, oxidative DNA damage and MALDI-TOF
high-throughput genotyping
“One of the major challenges is
finding ways to bring the physics
and engineering communities
together with biologists and
clinicians productively”.
George Whitesides excerpt from
Workshop Report
Validation Studies:
Active: Chromosomal Hotspots and Cancer Risk
Pending: High Throughput Analysis of Serum
Telomerase
Community Building:
NCI/NIST Workshop on Nanotechnology in Early
Detection of Cancer Workshop, held Aug 2001
Chemical Science and Technology Laboratory
Food and Nutrition … current activities
AOAC nine-sectored triangle
100% Fat
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in
Pr
ote
0%
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rb.
Ca
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5+
100% Carb.
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0%
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0% Fat
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9
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1100%
Protein
Needs Assessment: Interaction initiated
in 1997 as a result of US FDA study
regarding implementation of Nutritional
Labeling and Education Act
Populating the AOAC Food Triangle
Sector 1 Cholesterol and Fat-Soluble
Vitamins in Coconut Oil, SRM 1563
Sector 2 Baking Chocolate
Sector 3 Peanut Butter, proposed
Sector 4 Meat Homogenate, SRM 1546
Sector 5 Baby Food Composite, SRM 2383
Sector 6 Frozen Diet, SRM 1544, Infant
Formula, SRM 1846, Typical Diet,
SRM 1548a
Sector 7 Frozen Spinach, SRM 2385
Juncture, Fish Tissue, SRM 1946
Sectors 4,8,9
AOAC International requested 1-2
reference materials in each sector of the
nine-sectored triangle
Quality Assurance: Interlaboratory comparisons
Food SRMs facilitate:
• compliance with nutritional labeling laws
• traceability for food exports needed for
international trade
• the provision of accurate labeling
information
involve 20 laboratories from NFPA, plus other
collaborating labs
AOAC food triangle populated with appropriate standards to meet current needs –
shifting emphasis to new issues such as efficacy and purity of Nutraceuticals
Chemical Science and Technology Laboratory
Food and Nutrition
Nutraceuticals
New Market
• Total market of herbal supplements & functional foods estimated at $26B
• Market for Botanicals (herbal supplements) estimated at $3.5 B
Drivers:
• AOAC technical Division on Reference Materials identified nutraceuticals as their
highest priority need
• NIH concerned about efficacy (active ingredients) and contamination issues (such
as heavy metals and pesticides)
• FDA requested that NIST develop reference materials for seven herbal
supplements: St. John’s Wort, saw palmetto, Gingko Biloba, milk thistle,
echinacea, valerian, and feverfew
Timeline FY 02 - FY 04
• Obtain botanical raw materials and prepare candidate materials (2-3 per year)
• Develop and validate reference methodology
• Certify SRMs for active compounds, and contaminants
Chemical Science and Technology Laboratory
Food and Nutrition
Genetically Modified Organisms (GMOs)
Reference Methods and Standards for GMOs
Developing reference methods for detection of:
• genetic modification of foods
• proteins expressed by the genetic modification
Needs Assessment:
NIST sponsored workshop to be held in December 2001 with representation from the
EU, Asia-Pacific Rim, and all five subregions within the Americas (SIM), to discuss:
• Regulatory differences
• Existing measurement methods
• Gap analysis
• Plan of action
Current Activities with USDA/GIPSA – Biotech Grains
• Material (biocrops) transfer agreement complete
• Preliminary round-robin indicated the lowest level of “Round-Up Ready” trait that can be
detected by PCR
• Joint workshop/survey with GIPSA to fine-tune standards needs
• Develop candidate reference material with input from USDA, plant genomic testing labs, seed
producers, suppliers of reagents and other materials used in testing protocols
• Clone PCR products generated from trait materials into plasmid vectors for DNA sequencing
• Vectors will serve as positive controls for detecting specific traits in biotech grain
Chemical Science and Technology Laboratory
… current activities
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DNA Standards for Human Identity Testing
Standards for Alcohol and Drugs of Abuse Testing
Handgun and Explosives Residue Testing
Measurements & Standards for Chemical
Weapons Treaty Implementation
• Chemical and Biological Agent Detection
Chemical Science and Technology Laboratory
Forensics
Standards to Support Crime Scene Investigations
Alcohol and Drugs of Abuse Testing
• Long term commitment to develop and maintain SRMs for instrument
calibration and/or method validation associated with urine and hair testing,
and evaluation of products used to screen substances for illicit drug content
• Over last decade a series of human urine based SRMs were developed and
released
• Two new “drugs of abuse” in human hair SRMs will be developed and certified
for ten drugs of interest - to be released in 2002
• Investigating the measurement of chiral drugs in hair (example: chiral
separations required to distinguish illicit form of methamphetamine from the
legal form found in “over-the-counter” health products)
Organic Residue Analysis to investigate handgun and explosives crime
scenes
• Develop new measurement technology, and investigate standards issues for
the detection of handgun and explosives crime
Chemical Science and Technology Laboratory
Forensics
Standards for Human Identity Testing
NIST SRMs Provide Accuracy Base for
DNA Measurements
Release of SRM 2390: First DNA Profiling standard (1992)
R & D 100 Award
Release of SRM 2391: First PCR-based DNA
Profiling Standard (1995, renewal in 2000)
STR Database: Additional support provided with
Short Tandem Repeat DNA Internet Database
Release of SRM 2392: First Mitochondrial DNA
standard for: human mtDNA sequencing, forensic
ID, medical diagnosis, mutation detection (2000)
New Release in 2002: SRM 2395 ,Y-Chromosome Microsatellites
Complete: Methods evaluated, screened DNA extracts for potential inclusion in SRM
Plan: Sequence all Y-SRT loci, type all components for at least 20 Y-STR and 5Y-SNP loci
High throughput methods: MALDI-TOF sequencing of SNPs
Chemical Science and Technology Laboratory
Forensics
(with potential homeland security applications)
• MALDI – TOF (Matrix Assisted Laser Desorption Ionization – Time of Flight) Mass
Spectrometer for identification of bacterial agents – for implementation of Chemical
Weapons Convention
• Flow, particle analysis, vapor measurement for gas mask penetration
• Critical evaluation of field methods and protocols to be used in on-site inspections
– direct technical support for US Delegation to OPCW
• AMDIS (Automatic Mass Spectral Deconvolution and Identification Software) for
use by OPCW for detecting CW and CW related compounds in treaty inspections
• Insure high quality data for OPCW database including: infrared spectra, retention
data for GC, and mass spectral data
• Forensic analysis using isotopic signatures to ascertain origin
• Microarrays and microanalytical devices for detection of chemical and biological
agents
• MS database for identification of targeted chemical warfare agents
• Analysis of high explosive particles by SIMS
• Analysis of explosive residues to identify source
• DNA fingerprinting for identification of microorganisms
Chemical Science and Technology Laboratory
Selected Examples of NIST Capabilities to
Support Homeland Security
Detection: chemical, biochemical, radiological, nuclear and explosive
detection (CBRNE), forensic analysis and physical screening, lab-on-a-chip
technologies, X-ray security technology
Preparedness: cyber-security, protective equipment for emergency
responders, materials and ballistic testing, reduce building vulnerability to
CBR attacks
Prevention: biometric recognition technologies for human ID, sterilization of
biological agents in mail
Protection: building and fire research for physical infrastructure security,
protocols and tests to protect integrated buildings and services, IT
infrastructure security, detection of concealed weapons, detection of
explosive devices and other materials
Response and Recovery: forensic DNA analysis, support containment and
removal of CBRNE agents, IT security, support testing laboratories to
respond to increased demands, sterilization of biological agents in mail
Chemical Science and Technology Laboratory