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The Quarterly Magazine of NIST’s Material Measurement Laboratory

FALL 2016

MATERIAL MATTERS

Helping Ensure Accurate Clinical 

Measurements of HER2 Breast 

Cancer Gene
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TABLE OF CONTENTS

A Message from the MML Director 3

NIST and Frederick National Laboratory for Cancer Research Help Ensure Accurate Clinical Measurements 

of HER2 Breast Cancer Gene 4

NIST Releases New “Family” of Standardized Genomes 5

NIST Team Suggests Nanoscale Electronic Motion Sensor as DNA Sequencer 6 

Let’s Roll: Material for Polymer Solar Cells May Lend Itself to Large-Area Processing 7

Novel 3-in-1 “Rheo-Raman” Microscope Enables Interconnected Studies of Soft Materials 8

NIST Unveils Forensic Technique to Measure Mechanical Properties of Evidence 9

NIST Releases Expanded “Fractography” Guide for Analyzing, Understanding Material Failures 10

NIST-Made “Sun and Rain” Detail How Nanoparticles Can Escape from Plastic Coatings into the Environment 11

Perfluorinated Compounds Found in African Crocodiles, American Alligators 12

New NIST Reference Material Helps Ensure Accurate Measurement of Constituents in Tobacco Products 13

Outreach and Partnering 16

Awards 17

NIST Standard Story 18

Publications 19

CONTRIBUTORS

Editor | Torey Liepa

Contributors | Leah Kauffman | Anne Plant | Michael Newman | Mark Bello | Laura Ost

Cover Image | NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health

Contact MML | mmlinfo@nist.gov
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A MESSAGE FROM THE MML DIRECTOR

About five years ago, scientists from the Material Measurement Laboratory met with 

representatives from companies that make DNA sequencers and asked, “What can NIST 

do to help genome sequencing mature into a clinical tool?” 

Once limited to research applications, genome sequencing was rapidly becoming fast and 

inexpensive enough to be used as a diagnostic tool and to guide treatment decisions for 

patients. It was clear to everyone in the field that sequencing technology had the potential to 

enable an individual’s genetic profile to determine the best therapies for a disease—perhaps 

before it began to take a toll on a patient’s health. To make genome sequencing a valid and 

powerful clinical tool, however, the field needed to minimize errors in the way a genome is 

sequenced and analyzed.

To address quality control, industry members said they needed well-characterized genomes. 

They wanted a widely available sample of DNA that had been extracted, sequenced, and 

“read” using a combination of different methods to help sequencer developers and clinical 

and research laboratories check their processes, equipment, and data analysis. This would 

help ensure that treatment decisions—as well as determinations about where to invest 

dollars for the development of improved hardware and software, and clinical research—were 

based on reliable data.

NIST responded with a “genome in a bottle”: literally, little bottles of a highly characterized 

DNA (and the associated data) that are the world’s first human genome reference material. 

Recently, NIST released three additional human genome reference materials, which you can 

read about on page 5 of this issue of Material Matters. A new reference material for bacteria 

also joins the toolkit. 

Development of NIST’s human genome reference materials is overseen by scientists at 

the Joint Initiative for Metrology in Biology, a partnership of the Material Measurement 

Laboratory and Stanford University, working with representatives from sequencing 

manufacturers, government agencies, and academia in what is now known as the Genome 

in a Bottle consortium. The consortium member’s input will help NIST continue to enable 

new sequence techniques and clinical treatments, and is a textbook example of work that 

meets the NIST mission to assist a whole industry and contribute to the quality of life of 

all Americans.

Laurie Locascio, Ph.D.

Director

Material Measurement 

Laboratory

NIST
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NIST AND FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH HELP ENSURE 

ACCURATE CLINICAL MEASUREMENTS OF HER2 BREAST CANCER GENE

A new measurement standard developed 

by NIST has been used successfully by the 

Frederick National Laboratory for Cancer 

Research to check the performance 

of next-generation DNA-sequencing 

technologies for evaluating gene variations 

associated with an increased risk of breast 

cancer.

Scientists at the Molecular 

Characterization Laboratory (MCL) 

at the Frederick National Lab, which 

is sponsored by the National Cancer 

Institute, evaluated the usefulness of the 

NIST HER2 Standard Reference Material 

(SRM 2373) for ensuring the accuracy 

of measurements of HER2 gene copy 

numbers. Excessive copies of the HER2 

gene indicate heightened risk for an 

aggressive form of breast cancer.

The trial run “clearly demonstrated the 

value of SRM 2373” for both evaluating 

assay performance and “increasing 

confidence in reporting HER2 

amplification for clinical applications,” 

Frederick National Lab and NIST 

researchers report in a recent issue of the 

Journal of Molecular Diagnostics. 

“The gene is a biomarker for treatment 

selection. Diagnostic sequencing tests 

like HER2 assays make it possible to 

select the best treatment for individual 

patients based on the genetic makeup of 

their tumors,” said MCL Director Mickey 

Williams.

Normal cells have two copies of HER2, 

but about 20 to 25 percent of breast 

cancers have multiple copies of the gene, 

resulting in overproduction of the HER2-

encoded protein. This gene amplification 

stimulates tumors to be particularly fast 

growing in this subset of breast cancer 

patients—about 40,000 women in the 

United States annually.

Fortunately, these patients can be treated 

with a monoclonal antibody called 

trastuzumab (brand name Herceptin) that 

targets and inhibits the growth of tumor 

cells with higher-than-normal levels of 

the HER2 protein. The combination of 

more traditional chemotherapy drugs plus 

trastuzumab has been found to increase 

long-term survival rates significantly.

The treatment also can have adverse side 

effects, so it’s important to screen for 

those patients who would benefit from 

it by testing them. However, the two 

primary tests used prior to the ongoing 

transition to genomic screening—one 

relying on fluorescent probes and the 

other on tissue staining—have been prone 

to error. An estimated 20 percent of tests 

were estimated to yield inaccurate results, 

either false positives or false negatives.

In fact, NIST had originally set out to 

develop measurement tools to improve 

the accuracy of those diagnostic tests. 

But with the rapid emergence of nextgeneration genome sequencing, NIST 

chose, instead, to focus on developing 

measurement references that support the 

more sensitive and more specific detection 

capabilities of the new technologies.

SRM 2373 consists of DNA extracted 

from five breast-cancer cell lines, each with 

a different average number of copies of 

the HER2 genes, relative to a selected set 

of unvarying reference genes. Across the 

five-vial set, NIST-certified ratios of HER2 

copies to the reference genes range from 

just over one to about 18.

“The collaboration with the Frederick 

National Lab is very valuable for NIST 

to ensure that the reference materials we 

develop are relevant and timely to meet 

the needs of the clinical and research 

communities in the rapidly changing field 

of molecular diagnosis of cancer,” said 

NIST biochemist Kenneth Cole. 

Continued on page 14

Immunohistochemical detection of HER2 cancer biomarker with IgY antibody and quantum dots in 

breast cancer cells. Cell nuclei are stained blue, quantum dots responding to the HER2 protein light up 

in bright red at the cell membranes. Credit: NIST
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NIST RELEASES NEW “FAMILY” OF STANDARDIZED GENOMES

With the addition of four new reference 

materials (RMs) to a growing collection 

of “measuring sticks” for gene sequencing, 

NIST can now provide laboratories 

with even more capability to accurately 

“map” DNA for genetic testing, medical 

diagnoses and future customized 

drug therapies. The new tools feature 

sequenced genes from individuals in two 

genetically diverse groups, Asians and 

Ashkenazic Jews; a father-mother-child 

trio set from Ashkenazic Jews; and four 

microbes commonly used in research.

NIST issued the world’s first genome 

reference material (NIST RM 8398)—

detailing the genetic makeup for a woman 

with European ancestry—in May 2015. 

Together, all five RMs serve as a collection 

of well-characterized, whole genome 

standards that can tell a laboratory how 

well its DNA sequencing processes are 

working by measuring the performance 

of the equipment, chemistry and data 

analysis involved.

The latest reference materials are:

• NIST RM 8391—male of Eastern 

European Ashkenazic Jewish ancestry

• NIST RM 8392—male son, father 

and mother who are a family of 

Eastern European Ashkenazic Jewish 

ancestry (with the son’s genome 

being the same released as NIST RM 

8391)

• NIST RM 8393—male of East Asian 

(Chinese) ancestry

• NIST RM 8375—genomes for 

four bacterial species: Salmonella 

typhimurium LT2, Staphylococcus 

aureus, Pseudomonas aeruginosa and 

Clostridium sporogenes

The individual human RMs provide a 

baseline for comparing and contrasting 

genes from distinctly different lineages 

while the Ashkenazic trio set aids the 

analysis of genetic links between family 

members. The bacterial genomes come 

from species that challenge the technical 

performance of sequencing methods 

and have been determined by the Food 

and Drug Administration (FDA) to 

have significant relevance to the research 

of public health issues such as food 

contamination, antibiotic resistance and 

hospital-acquired infections.

The three individual and one family set 

of standardized human genomes were 

created by NIST and its partners in 

the Genome in a Bottle consortium, 

a group that includes members from 

the federal government, academia and 

industry. The consortium is managed 

by the Joint Initiative for Metrology in 

Biology (JIMB), a collaboration between 

NIST and Stanford University. Through its 

effort to develop, produce and distribute 

a suite of genome RMs, the consortium is 

providing medical and research laboratories 

worldwide with the tools they need to 

advance clinical applications of whole 

genome sequencing, and the FDA with the 

ability to conduct science-based regulatory 

oversight of the technology.

Reference materials are critical to properly 

evaluate the next-generation of gene 

sequencing and genetic testing methods 

that will increase the reliability and 

effectiveness of precision medicine (also 

known as “personalized medicine”), in 

which a person’s genetic profile is used to 

create treatments and therapies unique to 

that individual.

Continued on page 14

This electron micrograph shows an oral squamous cancer cell (white) being attacked by two 

cytotoxic T cells (red). The tumor-specific T cells were developed from the patient’s own immune 

system, a “personalized cancer vaccine” like those that may be developed in the future with the help 

of NIST’s standardized human genomes. Credit: R.E. Serda/National Cancer Institute and Duncan 

Comprehensive Cancer Center at Baylor College of Medicine
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NIST TEAM SUGGESTS NANOSCALE ELECTRONIC MOTION SENSOR AS DNA SEQUENCER 

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NIST researchers and collaborators 

have proposed a design for the first 

DNA sequencer based on an electronic 

nanosensor that can detect tiny motions 

as small as a single atom.

The proposed device—a type of capacitor, 

which stores electric charge—is a 

tiny ribbon of molybdenum disulfide 

suspended over a metal electrode and 

immersed in water. The ribbon is 15.5 

nanometers (nm, billionths of a meter) 

long and 4.5 nm wide. Single-stranded 

DNA, containing a chain of bases (bits 

of genetic code), is threaded through a 

hole 2.5 nm wide in the thin ribbon. 

The ribbon flexes only when a DNA base 

pairs up with and then separates from a 

complementary base affixed to the hole. 

The membrane motion is detected as an 

electrical signal.

As described in a new paper, the NIST 

team made numerical simulations 

and theoretical estimates to show the 

membrane would be 79 to 86 percent 

accurate in identifying DNA bases in a 

single measurement at speeds up to about 

70 million bases per second. Integrated 

circuits would detect and measure 

electrical signals and identify bases. The 

results suggest such a device could be a 

fast, accurate and cost-effective DNA 

sequencer, according to the paper. 

Conventional sequencing, developed in 

the 1970s, involves separating, copying, 

labeling and reassembling pieces of DNA 

to read the genetic information. Newer 

methods include automated sequencing 

of many DNA fragments at once—still 

costly—and novel “nanopore sequencing” 

concepts. For example, the same NIST 

group recently demonstrated the idea of 

sequencing DNA by passing it through a 

graphene nanopore, and measuring how 

graphene’s electronic properties respond 

to strain. 

The latest NIST proposal relies on a thin 

film of molybdenum disulfide—a stable, 

layered material that conducts electricity 

and is often used as a lubricant. Among 

other advantages, this material does not 

stick to DNA, which can be a problem 

with graphene. The NIST team suggests 

the method might even work without a 

nanopore—a simpler design—by passing 

DNA across the edge of the membrane.

“This approach potentially solves the 

issue with DNA sticking to graphene 

if inserted improperly, because this 

approach does not use graphene, period,” 

NIST theorist and lead author Alex 

Smolyanitsky said. “Another major 

difference is that instead of relying on the 

properties of graphene or any particular 

material used, we read motions electrically 

in an easier way by forming a capacitor. 

This makes any electrically conductive 

membrane suitable for the application.”

Nanomaterials expert Boris Yakobson 

of Rice University, a co-author on the 

paper, suggested the capacitor idea. 

Computational support was provided 

by the University of Groningen in the 

Netherlands.

DNA has four bases. For the simulations, 

cytosine (C), which naturally pairs up 

with guanine (G), is attached to the inside 

of the pore. When a piece of DNA passes 

through the pore, any G in the strand 

temporarily attaches to the embedded C, 

pulling on the nanoribbon and signaling 

the electrode. The DNA sequence is 

determined by measuring how and when 

electrical blips vary over time. To detect 

all four bases, four nanoribbons, each 

with a different base attached to the pore, 

could be stacked vertically to create an 

integrated DNA sensor. 

NIST’s proposed design for a DNA sequencer based on an electronic motion sensor. A nanoscale ribbon of molybdenum 

disulfide is suspended over a metal electrode and immersed in water. Single-stranded DNA, containing a chain of 

bases (bits of genetic code), is threaded through a hole in the ribbon, which flexes only when a DNA base pairs up with 

and then separates from a complementary base affixed to the hole. The membrane motion is detected as an electrical 

signal. Numerical simulations and theoretical estimates show the membrane would be 79 to 86 percent accurate in 

identifying DNA bases in a single measurement at speeds up to about 70 million bases per second. Credit: NIST

The molybdenum disulfide ribbon is 

flexible enough to deform measurably in 

response to the forces required to break 

up a DNA pair, but rigid enough to have 

less ongoing, meaningless movement than 

graphene, potentially reducing unwanted 

noise in the sequencing signals. The 

deflection of the ribbon is exceedingly 

small, on the order of one angstrom, the 

size of a hydrogen atom. Its pulling force 

is on the order of 50 piconewtons, or 

trillionths of a newton, enough to break up 

the delicate chemical bonds between DNA 

bases. 

Researchers estimated how the device would 

perform in an integrated circuit and found 

the peak currents through the capacitor 

were measurable (50 to 70 picoamperes), 

even for the small nanoribbons studied. The 

current peaks are expected to be even larger 

in physical systems. The device size could be 

tweaked to make it even easier to measure 

sequencing signals.

The NIST authors hope to build a physical 

version of the device in the future. For 

practical applications, the chip-sized DNA 

sequencing microfluidic technology might 

be combined with electronics into a single 

device small enough to be handheld. 

The research was funded in part by the 

Materials Genome Initiative. 

A. Smolyanitsky, B.I. Yakobson, T.A. Wassenaar, E. Paulechka 

and K. Kroenlein, A MoS2-based capacitive displacement 

sensor for DNA sequencing, ACS Nano, September 13, 2016, 

http://dx.doi.org/10.1021/acsnano.6b05274
| 7

LET’S ROLL: MATERIAL FOR POLYMER SOLAR CELLS MAY LEND ITSELF TO LARGE-AREA 

PROCESSING 

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For all the promise they have shown in 

the lab, polymer solar cells still need to 

“get on a roll” like the ones employed in 

printing newspapers so that large sheets of 

acceptably efficient photovoltaic devices 

can be manufactured continuously and 

economically. Polymer solar cells offer 

advantages over their traditional siliconbased counterparts in numerous ways, 

including lower cost, potentially smaller 

carbon footprint and a greater variety of 

uses.

New research results reported by an 

international team led by NIST indicate 

that the “sweet spot” for mass-producing 

polymer solar cells—a tantalizing prospect 

for decades—may be far larger than 

dictated by the conventional wisdom. In 

experiments using a mock-up of a highvolume, roll-to-roll processing method, 

the researchers produced polymer-based 

solar cells with a “power conversion 

efficiency” of better than 9.5 percent, just 

shy of the minimum commercial target of 

10 percent. 

That’s almost as good as the smallbatch devices made with spin-coating, a 

method that produces high-quality films 

in the laboratory but is commercially 

impractical since it wastes up to 90 

percent of the initial ink. 

Somewhat surprising to the researchers, 

their mass-produced versions exhibited 

molecular packing and texture that only 

slightly resembled that of lab-made 

varieties, which at their best convert 

about 11 percent of incident sunlight into 

electrical energy. 

“The ‘rule of thumb’ has been that highvolume polymer solar cells should look 

just like those made in the lab in terms 

of structure, organization and shape at 

the nanometer scale,” said Lee Richter, a 

NIST physicist who works on functional 

polymers. “Our experiments indicate 

that the requirements are much more 

A demonstration solar park based on polymer solar cells at the Technical University of Denmark in Roskilde, 

Denmark. Credit: DTU Energ

flexible than assumed, allowing for greater 

structural variability without significantly 

sacrificing conversion efficiency.” 

“Efficient roll-to-roll fabrication is 

key to achieving the low-cost, highvolume production that would enable 

photovoltaics to scale to a significant 

fraction of global energy production,” 

explained He Yan, a collaborator from 

Hong Kong University of Science and 

Technology. 

The team experimented with a coating 

material composed of a fluorinated 

polymer and a fullerene (also known as 

a “buckyball”). Going by the technical 

name PffBT4T-2OD, the polymer 

is attractive for scaled production—

achieving a reported power conversion 

efficiency of more than 11 percent. 

Importantly, it can be applied in relatively 

thick layers—conducive to roll-to-roll 

processing. 

However, the top-performing solar cells 

were produced with the spin-coating 

method, a small-batch process. In 

spincoating, the fluid is dispensed onto 

the center of a disk or other substrate, 

which rotates to spread the material 

until the desired coating thickness is 

achieved. Besides generating lots of waste, 

the process is piecemeal—rather than 

continuous—and substrate size is limited. 

So the research team opted to test 

commercially relevant coating methods, 

especially since PffBT4T-2OD can be 

applied in relatively thick layers of 250 

nanometers and more, or roughly the size 

of a large virus. They started with bladecoating—akin to holding a knife edge at a 

fraction of a hair’s breadth above a treated 

glass substrate as it slides by, painting the 

PffBT4T-2OD onto the substrate. 

A series of X-ray-based measurements 

revealed that the temperature at which 

the PffBT4T-2OD was applied and dried 

significantly influenced the resultant 

coating’s material structure—especially the 

orientation, spacing and distribution of the 

crystals that formed. 

The substrates blade-coated at 90° Celsius 

(194°F) were the highest performing, 

achieving power conversion efficiencies 

that topped 9.5 percent. Surprisingly, at 

the nanometer level, the end products 

differed significantly from the spin-coated 

“champion” devices made in the lab. 

Detailed real-time measurements during 

both blade-coating and spin-coating 

revealed that different structures arose from 

the rapid cooling during spin-coating versus 

the constant temperature during bladecoating. 

Continued on page 15 
8 |

NOVEL 3-IN-1 “RHEO-RAMAN” MICROSCOPE ENABLES INTERCONNECTED STUDIES OF 

SOFT MATERIALS

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An innovative three-in-one instrument 

that allows scientists to correlate the 

flowability of soft “gooey” materials 

such as gels, molten polymers and 

biological fluids with their underlying 

microstructure and composition has been 

developed by scientists from NIST and 

Thermo Fisher Scientific.

Simultaneous measurements yield a 

clearer picture of how structural makeup and flow behavior during processing 

dictate the macroscopic properties—

such as strength, hardness, or electrical 

conductivity—that make so-called soft 

materials desirable for certain products or 

applications.

A novel combination of off-the-shelf 

instruments, the new research tool—

called the rheo-Raman microscope—

integrates:

• a Raman spectrometer, which shines 

a laser on the sample and measures 

the tiny portion of scattered light 

that reveals vibrational energy levels 

of molecules in the sample, providing 

the equivalent of molecular 

fingerprints showing how atoms are 

arranged;

• a rotational rheometer to track and 

measure how a liquid, suspension or 

slurry flows in response to stress—or, 

put another way, the degree to which 

the sample deforms; and

• an optical microscope that collects 

polarized light reflected from a 

sample to increase contrast, enabling 

measurements of a specimen’s 

structural features at microscopic 

scales.

The new instrument is designed for 

“multitasking,” said Anthony Kotula, a 

NIST materials scientist. “It allows you 

to trace the evolution of microstructure 

across a range of temperatures and to do 

it in one controlled experiment rather 

than in two or three separate ones. It 

provides insights that would be very 

difficult to obtain through measurements 

made one at a time.”

Homing in on the flow behavior is 

especially important, because it is intimately 

coupled with the microstructure and 

ultimate properties, Kotula explained.

Soft materials share features of liquids and 

solids. They range from plastics to liquid 

crystal displays and from contact lenses 

to biopharmaceuticals. For these “inbetween materials,” even slight variations 

in processing conditions can alter internal 

structures and drastically change material 

properties, which can open the way to 

improved performance or entirely new 

technological applications.

As they report in the Review of Scientific 

Instruments, the team used their prototype 

rheo-Raman microscope to follow and 

measure changes before, during and after 

melting a cosmetic material composed 

of coconut and almond oils and about 

10 other ingredients. They also present 

simultaneous “melt” measurements taken 

on high-density polyethylene, which is used 

to make plastic bottles, corrosion-resistant 

pipes and many other items, as liquid 

molecules arrange and solidify into crystals.

Both demonstrations yielded a detailed, 

unfolding picture of how flow behavior 

and other phenomena during melting and 

crystallization correspond to changes in the 

shape and arrangement of molecules due to 

processing conditions.

“Based on the possibilities for direct 

correlation between chemical, structural 

and mechanical properties, we expect the 

rheo-Raman microscope to be critically 

relevant to both academic and industrial 

interests,” the researchers concluded in their 

article.

“The rheo-Raman microscope is a general 

purpose instrument with lots of potential 

uses,” Kotula said. “At NIST, one of our 

first applications pertains to 3D printing. 

We’ll use it to better understand how 

polymer crystallization proceeds during the 

layer-by-layer printing process.”

A.P. Kotula, M. Meyer, F. De Vito, J. Plog, A.R. Hight Walker 

and K.B. Migler, The rheo-Raman microscope: Simultaneous 

chemical, conformational, mechanical, and microstructural 

measures of soft materials, Review of Scientific Instruments, 

October 4, 2016, http://dx.doi.org/10.1063/1.4963746

NIST’s Anthony Kotula using the new rheo-Raman microscope, a three-in-one instrument that enables 

researchers to measure the flow properties of a material along with its microscopic structure and 

composition.Credit: Denease Anderson/NIST
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NIST UNVEILS FORENSIC TECHNIQUE TO MEASURE MECHANICAL PROPERTIES OF 

EVIDENCE

You may have seen it on CSI: The star 

examines hair from a crime scene and 

concludes its color or texture looks like 

the defendant’s hair, or maybe his dog’s. 

Case closed.

But looks can be deceiving, as well as 

vague and subjective. In real life, the 

FBI is now reviewing thousands of 

cases involving hair comparisons going 

back to the 1980s because traditional 

identifications—often based on looks 

alone—have been called into question.

Instead, what if investigators could 

precisely measure a hair’s mechanical 

properties—its stiffness and stickiness? 

In fact, they can, according to recent 

experiments at NIST, which is developing 

science-based methods to help ensure 

rigorous forensic practices.

“Lots of forensics is based on how the 

evidence looks,” NIST engineer Frank 

DelRio says. “We are trying to add 

another dimension, how things feel. 

How an object feels—its mechanical 

response—depends on the material and 

the object’s history.”

DelRio is an expert in atomic force 

microscopy (AFM), a precision tool with 

a mechanical probe typically used in basic 

sciences for imaging but also to measure 

responses to force, or pulling. He usually 

measures industrial materials like silicon. 

But he also watches a lot of CSI and 

thought his expertise could help answer 

national calls to enhance the accuracy, 

reliability and statistical rigor of forensics.

DelRio and NIST physicist Robert 

Cook recently used AFM to demonstrate 

quantitative methods for measuring—

nondestructively and at the nanometer 

size scale—the mechanical properties of 

four types of evidence: hair, documents, 

fingerprints and explosives.

NIST researchers used atomic force microscopy (AFM) 

to measure the stickiness (pull-off force) and stiffness 

(plane strain modulus) of hair that was untreated 

(top), bleached (middle), and conditioned (bottom). 

The clear differences in the measured results for 

various hair treatments suggest that AFM might be 

used to analyze forensic evidence. The measured 

forces are very small, in units of nanonewtons or 

nN (1 nanonewton is about the weight of a pollen 

grain). Modulus is in units of gigapascals or GPa and 

ranges from 1-5 for the hair samples (for comparison, 

the plastic lens material polycarbonate measures 

about 3).Credit: DelRio/NIST

The measurement results clearly 

distinguished various treatments of hair, 

types of ink, age of fingerprints and 

composition of fabrics, and related these 

data to the structure of the sample such as 

broken bonds in the hair and the smooth 

ballpoint ink versus the rough printer 

ink. Importantly, the measurements were 

rigorous—that is, precise enough to allow 

for tests and quantitative specifications of 

the statistical significance of the similarities 

or differences in properties. DelRio 

imagines that someday AFM might be 

used, for example, to measure old hair 

evidence and determine the probability that 

a criminal used a certain shampoo.

“This is all theoretical at this point,” DelRio 

notes. “For this to be an effective practical 

tool, a lot of baseline measurements and 

in-depth studies would need to be done 

to develop a good sense of how these 

properties change over time.”

In addition, DelRio notes that AFM 

calibration methods and standard samples 

or other methods for specifying accuracy 

would need to be developed to enable 

accurate comparison of measurements 

across laboratories. Also crucial would be 

the development of an experience base to 

build trust in AFM techniques, requiring 

widespread availability of instruments, 

training, protocols and standards for 

forensics labs, the paper notes.

F.W. DelRio and R.F. Cook, Quantitative Scanning Probe 

Microscopy for Nanomechanical Forensics, Experimental 

Mechanics, Posted online October 31, 2016, 

http://dx.doi.org/10.1007/s11340-016-0238-y

The researchers measured the stiffness 

and pull-off force (stickiness) for hair 

as a function of treatment, specifically 

conditioning and bleaching. They 

also measured these properties for test 

documents made to mimic forgeries 

marked with both ballpoint ink and 

printer ink, impression and pattern 

evidence such as how fingerprints change 

over time, and interactions of explosive 

particles and surfaces as a function of 

fabric type, rayon versus cotton.
1 0 |

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NIST RELEASES EXPANDED “FRACTOGRAPHY” GUIDE FOR ANALYZING, UNDERSTANDING 

MATERIAL FAILURES

Studying the fractures of industrially 

important materials such as ceramics 

and glasses provides important clues on 

why these materials can fail and how to 

make them more durable. The practice 

of “fractography,” however, has been an 

underutilized science. NIST is working to 

change that. 

NIST has released a new, expanded 

edition of the NIST Recommended 

Practice Guide, “Fractography of 

Ceramics and Glasses” (NIST Special 

Publication 960-16e2). First issued in 

2007, the guide was developed to help 

engineers and scientists analyze the 

patterns in fractures of ceramics and 

glasses used for household items and 

other consumer goods, building materials, 

and medical devices and implants.

Since it was first published, “Fractography 

of Ceramics and Glasses” has been used 

in training courses and by members of 

industry for failure analysis, helping to 

improve production methods and product 

quality. 

The new edition of the guide, which is 

15 percent larger than its predecessor, 

includes 300 new illustrations 

and covers the state of the art in 

fractography, including descriptions 

of new documentary standards. The 

guide, with nearly 1,000 images, covers 

various topics including equipment (with 

updates on new microscopy techniques), 

patterns in glass and ceramic fractures 

(the “fingerprints” that make failure 

analysis possible), an expanded chapter 

on quantitative analysis of fractures, and 

composites—including new materials 

used in dentistry. Actual case studies 

help readers see how the guide is used in 

practice. 

Mechanical engineer George Quinn, 

the author of both the original and 

expanded editions, joined NIST in 1990 

to perform strength testing on ceramic 

materials. In collaboration with ASTM, 

an international standards organization, 

Quinn helped to develop two world-first 

ceramic strength tests. Since formally 

retiring from NIST in 2009, Quinn has 

continued to serve the organization as a 

research associate.

Fracture of a sapphire missile nose cone. Credit: NIST

The guide may be accessed online 

(http://nvlpubs.nist.gov/nistpubs/

specialpublications/NIST.SP.960-16e2.

pdf). Hard copies are available upon 

request (george.quinn@nist.gov).
| 11

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NIST-MADE “SUN AND RAIN” DETAIL HOW NANOPARTICLES CAN ESCAPE FROM PLASTIC 

COATINGS INTO THE ENVIRONMENT

If the 1967 film “The Graduate” were 

remade today, Mr. McGuire’s famous 

advice to young Benjamin Braddock 

would probably be updated to “Plastics 

... with nanoparticles.” These days, the 

mechanical, electrical and durability 

properties of polymers—the class of 

materials that includes plastics—are 

often enhanced by adding miniature 

particles (smaller than 100 nanometers or 

billionths of a meter) made of elements 

such as silicon or silver. But could 

those nanoparticles be released into 

the environment after the polymers are 

exposed to years of sun and water—and 

if so, what might be the health and 

ecological consequences? 

In a recently published paper, researchers 

from NIST describe how they subjected 

a commercial nanoparticle-infused 

coating to NIST-developed methods for 

accelerating the effects of weathering from 

ultraviolet (UV) radiation and simulated 

washings of rainwater. Their results 

indicate that humidity and exposure time 

are contributing factors for nanoparticle 

release, findings that may be useful in 

designing future studies to determine 

potential impacts.

In their recent experiment, the 

researchers exposed multiple samples of 

a commercially available polyurethane 

coating containing silicon dioxide 

nanoparticles to intense UV radiation 

for 100 days inside the NIST SPHERE 

(Simulated Photodegradation via 

High-Energy Radiant Exposure), a 

hollow, 2-meter (7-foot) diameter black 

aluminum chamber lined with highly 

UV reflective material that bears a casual 

resemblance to the Death Star in the film 

“Star Wars.” For this study, one day in the 

SPHERE was equivalent to 10 to 15 days 

outdoors. All samples were weathered 

at a constant temperature of 50 degrees 

Celsius (122 degrees Fahrenheit) with one 

group done in extremely dry conditions 

(approximately 0 percent humidity) 

and the other in humid conditions (75 

percent humidity).

To determine if any nanoparticles were 

released from the polymer coating during 

UV exposure, the researchers used a 

technique they created and dubbed 

“NIST simulated rain.” Filtered water 

was converted into tiny droplets, sprayed 

under pressure onto the individual 

samples, and then the runoff—with any 

loose nanoparticles—was collected in a 

bottle. This procedure was conducted at 

the beginning of the UV exposure, every 

two weeks during the weathering run and 

at the end. All of the runoff fluids were 

then analyzed by NIST chemists for the 

presence of silicon and in what amounts. 

Additionally, the weathered coatings were 

examined with atomic force microscopy 

and scanning electron microscopy to 

reveal surface changes resulting from UV 

exposure.

Both sets of coating samples—those 

weathered in very low humidity and 

the others in very humid conditions—

degraded but released only small amounts 

of nanoparticles. The researchers found 

that more silicon was recovered from the 

samples weathered in humid conditions 

and that nanoparticle release increased 

as the UV exposure time increased. 

Microscopic examination showed that 

deformations in the coating surface 

became more numerous with longer 

exposure time, and that nanoparticles left 

behind after the coating degraded often 

bound together in clusters.

“These data, and the data from future 

experiments of this type, are valuable for 

developing computer models to predict 

the long-term release of nanoparticles 

from commercial coatings used outdoors, 

and in turn, help manufacturers, 

regulatory officials and others assess 

any health and environmental impacts 

from them,” said NIST research chemist 

Deborah Jacobs, lead author on the 

study published in the Journal of Coatings 

Technology and Research.

This project resulted from a collaboration 

between NIST’s Engineering Laboratory 

and Material Measurement Laboratory. 

It is part of NIST’s work to help 

characterize the potential environmental, 

health and safety risks of nanomaterials, 

and develop methods for identifying and 

measuring them.

D.S. Jacobs, S-R Huang, Y-L Cheng, S.A. Rabb, J.M. 

Gorham, P.J. Krommenhoek, L.L. Yu, T. Nguyen and 

L. Sung, Surface degradation and nanoparticle release of a 

commercial nanosilica/polyurethane coating under 

UV exposure, September 2016, Journal of Coatings 

Technology and Research, http://dx.doi.org/10.1007/s11998-

016-9796-2

NIST researchers simulate “sun and rain” to determine if weathering causes polymer coatings to release the 

nanoparticles they contain into the environment. On the left, Li-Piin Sung places a commercially available 

polymer with silicon dioxide nanoparticles into a chamber of the NIST SPHERE, a device for accelerated 

weathering that in one day subjects samples to the equivalent of 10-15 days of outdoor exposure. On the right, 

Deborah Jacobs applies “NIST simulated rain” to the weathered sample to collect any shed nanoparticles in the 

runoff. Credit: F. Webber/NIST
1 2 |

PERFLUORINATED COMPOUNDS FOUND IN AFRICAN CROCODILES, AMERICAN ALLIGATORS

|

American alligators and South African 

crocodiles populate waterways a third 

of the globe apart, yet both have 

detectable levels of long-lived industrial 

and household compounds for nonstick 

coatings in their blood, according to two 

studies from researchers at the Hollings 

Marine Laboratory (HML) in Charleston, 

South Carolina, and its affiliated 

institutions, which include NIST.

Production of some compounds in this 

family of environmentally persistent 

chemicals—associated with liver toxicity, 

reduced fertility and a variety of other 

health problems in studies of people and 

animals—has been phased out in the 

United States and many other nations. 

Yet all blood plasma samples drawn from 

125 American alligators across 12 sites 

in Florida and South Carolina contained 

at least six of the 15 perfluorinated alkyl 

acids (PFAAs) that were tracked in the 

alligator study.

The two studies are first-of-their-kind 

examinations of PFAA levels in “sentinel” 

reptile species, especially useful for 

investigating the impacts of long-lived 

chemicals in the environment. PFAAs 

have been used in products that include 

water-repellent clothes, stain repellents, 

waxes, nonstick pans and fire-suppressing 

foams.

In alligators, plasma levels of 

perfluorooctane sulfonate (PFOS) 

ranged from 1,360 to 452,000 parts per 

trillion. In May 2016, the Environmental 

Protection Agency issued a drinking-water 

health advisory for PFOS and another 

PFAA, recommending a maximum 

exposure level of 70 parts per trillion for 

one of the PFAAs or the sum of the two. 

High PFOS levels reported for alligators 

at several sites may suggest the need to 

test drinking water for contamination 

at those locations, according to the 

researchers.

In a separate study, researchers report 

that all samples drawn from 45 crocodiles 

at five sites in and around South 

Africa’s Kruger National Park contained 

detectable levels of four PFAAs, often 

in different combinations with others of 

the 15 fluorinated organic compounds 

tracked. Present in all plasma samples, 

PFOS levels ranged from 776 to 118,000 

parts per trillion.

“Alligators and crocodiles play a 

dominant role in their ecosystems,” 

said Jacqueline Bangma, of the Medical 

University of South Carolina in 

Charleston. “Similar to humans, they are 

long-lived top predators. They stay in a 

select territory—waterways where runoff 

from human activities accumulates— and 

their PFAA burden increases through the 

consumption of fish.”

To date, field studies of PFAA levels and 

health effects in reptiles have been few, 

focusing mostly on sea turtles. Across 

studies of animals—from rats to frogs 

to marine mammals—plasma levels, 

time required to eliminate PFAAs from 

the body, and health effects vary greatly, 

making it difficult to extrapolate from 

one species to another.

The landmark studies were initiated 

by the Hollings Marine Laboratory, a 

partnership including NIST, NOAA’s 

National Ocean Service, the South 

Carolina Department of Natural 

Resources, the College of Charleston, and 

the Medical University of South Carolina. 

Plans are to continue PFAA monitoring 

on both continents, according to NIST 

research chemist Jessica Reiner.

Both studies identified “hot spots,” where 

PFAA levels were significantly higher 

than in animals tested at other sites, 

an indication that the contaminants 

were emitted by a nearby source. In 

the U.S. study, median plasma levels of 

certain PFAAs were highest in alligators 

on Kiawah Island, an Atlantic Ocean 

barrier island southwest of Charleston, 

South Carolina, and on Merritt Island in 

Florida.

Past use of PFAA-containing foams such 

as those employed in firefighting training 

may account for the higher levels, the 

researchers suggest. High environmental 

concentrations have been reported at 

fire-training sites and at manufacturing 

plants.

In contrast, alligators at two sites in the 

Florida Everglades exhibited some of the 

lowest levels of the two “highest burden” 

PFAAs reported across all adult alligators 

sampled in the U.S. study. The result 

was somewhat unexpected, Reiner said, 

because Everglade’s alligators have been 

reported to have some of the highest 

levels of mercury, a toxic heavy metal, 

among Florida alligators.

Among the South African crocodiles 

tested, PFAA levels were highest for 

animals tested from Flag Boshielo Dam, 

a reservoir on the Oliphants River, just 

upstream from Kruger National Park.

Continued on page 15

This crocodile inhabits waters around Flag Boshielo 

Dam, a reservoir on the Oliphants River, just 

upstream from South Africa’s Kruger National Park. 

Researchers from the Hollings Marine Laboratory 

reported at least four types of perfluorinated alkyl 

acids in plasma samples drawn from 45 crocodiles at 

five sites in and around the park. The highest levels 

were found in animals living in the reservoir. 

Credit: John Bowden/HML
| 1 3

|

NEW NIST REFERENCE MATERIAL HELPS ENSURE ACCURATE MEASUREMENT OF 

CONSTITUENTS IN TOBACCO PRODUCTS

NIST has issued a reference material 

with certified amounts of nicotine and 

two carcinogens to help ensure accurate 

testing of commercial tobacco filler—the 

blended tobacco found in cigarettes.

Prepared in collaboration with the Food 

and Drug Administration’s (FDA) Center 

for Tobacco Products (CTP), NIST’s 

new Standard Reference Material “SRM 

3222 Cigarette Tobacco Filler” helps 

companies meet the federal requirement 

for reporting “harmful or potentially 

harmful constituents” in tobacco products 

and tobacco smoke.

The requirement is in the 2009 Family 

Smoking Prevention and Tobacco Control 

Act, which assigned FDA the authority 

to regulate the manufacture, distribution 

and marketing of tobacco products 

to protect public health. In 2012, the 

agency published a list of 93 substances 

that cause—or could cause—harm from 

tobacco use or exposure to tobacco 

smoke.

“It’s important to make regulatory 

decisions with the best information 

available,” said David L. Ashley, director 

of CTP’s Office of Science. “This tobacco 

standard reference material and others 

help inform the evaluation of data 

on harmful and potentially harmful 

constituents submitted by manufacturers 

and importers.”

NIST SRM 3222 is certified for amounts 

of nicotine, the primary cause of tobacco 

addiction, and two tobacco-specific 

nitrosamines: N-nitrosonornicotine 

(NNN), 4-(methylnitrosamino)-1-(3-

pyridyl)-1-butanone (NNK). These 

nitrogen-containing compounds are 

among the most carcinogenic chemicals 

in cigarette smoke.

NIST research chemist Jeanita Pritchett extracts 

nicotine and tobacco-specific compounds from a 

candidate Standard Reference Material (SRM) created 

in collaboration with the Center for Tobacco Products 

at the Food and Drug Administration. Consisting of 

a low-level nicotine tobacco filler material, the NIST 

SRM is intended for use in evaluating the accuracy of 

measurements of specific compounds and moisture in 

tobacco. Credit: Earl Zubkoff

Levels of each of the three compounds 

in the reference material are certified 

by NIST using a combination of mass 

spectrometry and chromatographic 

methods—techniques for separating 

and analyzing complex mixtures. 

Measurements were made at NIST and 

the Centers for Disease Control and 

Prevention and confirmed subsequently at 

several commercial laboratories.

“The composition of tobacco products 

can vary greatly,” said Lane Sander, the 

NIST researcher who led development of 

the SRM. “It’s influenced by the tobacco 

varieties used in production, growing 

conditions, curing methods and additives. 

This reference material can serve as a 

check on composition measurements 

made during manufacturing and for 

regulatory purposes.”

About 2,500 kilograms (5,500 pounds) 

of American blended tobacco filler were 

procured from a commercial source, with 

established target values for nicotine and 

nitrosamines. The tobacco was processed 

and blended by the manufacturer as a 

cigarette tobacco filler. Dried leaves were 

chopped to lengths roughly equal to the 

diameter of a dime and a width equal to 

the coin’s thickness. Each unit of SRM 

3222 consists of 20 jars, each containing 

about 10 grams of filler tobacco.
1 4 |

|

NIST AND FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH HELP ENSURE 

ACCURATE CLINICAL MEASUREMENTS OF HER2 BREAST CANCER GENE (CONT’D)

The HER2 reference material is the latest 

addition to a growing list of measurement 

tools that NIST has developed to help 

advance genomics-inspired precision 

medicine. NIST also is working with 

Frederick National Lab researchers and 

industry to improve detection and reliable 

measurement of cell-free circulating 

tumor DNA, sometimes called liquid 

biopsies. Circulating tumor DNA has 

been detected in many cancers and might 

be used to monitor patients’ therapeutic 

progress and whether tumors mutate to 

become resistant to treatments.

NIST recently signed a three-year 

Cooperative Research and Development 

Agreement with SeraCare Life Sciences 

to collaborate on an interlaboratory 

study comparing measurements of the 

company’s circulating tumor DNA 

reference material.

In 2015, NIST and its partners in the 

Genome in a Bottle Consortium issued 

NIST Reference Material (RM) 8398 

Human DNA for Whole-Genome Variant 

Assessment, for which about 77 percent 

of the genome is characterized with high 

levels of confidence. The Food and Drug 

Administration used the genome 

reference material as its “truth set” for its 

just-completed PrecisionFDA Consistency 

Challenge, intended to advance quality 

standards for whole human genome 

sequencing.

In May 2016, NIST issued a “Peptide 

Mixture for Proteomics” (RM 8321), 

which contains 440 synthetic peptides, 

or segments of proteins. Proteomics is 

the identification and study of proteins, 

which are encoded by genes and are, 

ultimately, the body’s “doers,” acting 

alone or in groups to drive processes 

involved in health and disease.

H-J. He, J. Almeida, S. Lund, C.R. Steffen, S. Choquette 

and K.D. Cole, Development of NIST Standard Reference 

Material 2373: Genomic DNA Standards for HER2 

Measurements, Biomolecular Detection and Quantification, 

June 2016, http://dx.doi.org/10.1016/j.bdq.2016.02.001

C-J. Lih, H. Si, B. Das, R.D. Harrington, K.N. Harper, 

D.J. Sims, P.M. McGregor, C.E. Camalier, A.Y. Kayserian, 

P.M. Williams, H-J He, J. Almeida, S.L. Lund, S. 

Choquette and K.D. Cole, Certified DNA Reference 

Materials to Compare HER2 Gene Amplification 

Measurements Using Next-Generation Sequencing 

Methods, Journal of Molecular Diagnostics, Available 

online July 25, 2016, http://dx.doi.org/10.1016/j.

jmoldx.2016.05.008

NIST RELEASES NEW “FAMILY” OF STANDARDIZED GENOMES (CONT’D)

|

Sequencing devices take long strings 

of a person’s DNA and randomly 

chop them into small pieces that 

can be individually analyzed to 

determine their sequence of letters 

from the genetic code (A, C, G 

and T representing the four key 

components of DNA that code for 

protein production in living organisms: 

adenine, cytosine, guanine and 

thymine). The sequenced pieces can 

then be compared to a well-defined 

“reference sequence” to identify 

differences between the two codes. The 

differences reveal where mutations may 

have occurred in specific genes.

However, biases and “blind spots” 

for certain sequences contribute 

to uncertainties or errors in the 

sequence analysis. These biases can 

lead to hundreds of thousands of 

disagreements between different 

sequencing results for the same human 

genome. 

To better understand these biases, 

laboratories can now compare their DNA 

sequences to those obtained from the 

DNA in any or all of the human genome 

RMs. The reference materials have been 

extensively characterized with multiple 

techniques, with the results weighted and 

analyzed to eliminate as much bias and 

error as possible.

The new NIST human genome RMs 

increase the ability of DNA sequencing 

laboratories to be more confident in their 

reporting of true positives, false positives, 

true negatives and false negatives, and 

therefore, significantly improve genetic 

tests used for disease risk prediction, 

diagnosis, and progression tracking. They 

also can be used with tools developed by 

the Global Alliance for Genomics and 

Health Benchmarking Team to further 

raise that confidence level.

Similarly, the standardized microbial 

genomes in NIST RM 8375 can be used to 

assess the performance of high-throughput 

methods for microbial DNA sequencing.

All five of the NIST reference materials 

are available for purchase from the NIST 

Standard Reference Material program. 

Each RM sample is characterized for 

homogeneity (ensuring that each vial 

contains similar DNA) and stability 

(ensuring that the DNA ordered now will 

be comparable to samples ordered in the 

future). The original sources for the RMs 

are from the Personal Genome Project, 

whose cell lines are hosted at the Coriell 

Institute for Medical Research.

Future additions to the RM collection may 

include whole genomes from persons with 

Hispanic, African and mixed ancestries, as 

well as a set containing sequenced genes 

of both malignant tumor and normal cells 

from the same individual.
| 1 5

|

PERFLUORINATED COMPOUNDS FOUND IN AFRICAN CROCODILES, AMERICAN 

ALLIGATORS (CONT’D)

LET’S ROLL: MATERIAL FOR POLYMER SOLAR CELLS MAY LEND ITSELF TO LARGE-AREA 

PROCESSING (CONT’D)

|

“Real-time measurements were critical 

to developing a proper understanding 

of the film formation kinetics and 

ultimate optimization,” said Aram 

Amassian, a collaborator from Saudi 

Arabia’s King Abdullah University of 

Science and Technology. 

Encouraged by the results, the team 

performed preliminary measurements 

of PffBT4T-2OD coating formed 

on the surface of a flexible plastic 

sheet. The coating was applied on 

NIST’s slot-die roll-to-roll coating 

line, directly mimicking large-scale 

production. Measurements confirmed 

that the material structures made with 

blade-coating and those made with slotdie-coating were nearly identical when 

processed at the same temperatures. 

“It’s clear that the type of processing 

method used influences the shape of 

the domains and their size distribution 

in the final coating, but these distinctly 

different morphologies do not necessarily 

undermine performance,” said Harald Ade, 

a collaborator from North Carolina State 

University. “We think these findings provide 

important clues for designing polymer solar 

cells optimized for roll-to-roll processing.” 

H.W. Ro, J.M. Downing, S. Engmann, A.A. Herzing, D.M. 

DeLongchamp, L.J. Richter, S. Mukherjee, H. Ade, M. 

Abdelsamie, L.K. Jagadamma, A. Amassian, Y. Liu and H. Yan, 

Morphology changes upon scaling a high-efficiency, solutionprocessed solar cell, Energy & Environmental Science, August 2, 

2016, http://dx.doi.org/10.1039/c6ee01623e

Among the American alligators 

studied, some PFAA levels tended to 

be higher among males, regardless 

of locations. Levels also tended to 

increase with age, as determined by 

snout length. Age- and sex-related 

associations with PFAA levels were not 

found in the crocodiles sampled.

I. Christie, J.L. Reiner, J.A. Bowden, H. Botha, T.M. 

Cantu, D. Govender, M.P. Guillettee, R.H. Lowers, W.J. 

Luus-Powell, D. Pienaar, W.J. Smit and L.J. Guillette Jr., 

Perfluorinated alkyl acids in the plasma of South African 

crocodiles (Crocodylus niloticus), Chemosphere, July 2016, 

http://dx.doi.org/10.1016/j.chemosphere.2016.03.072

J.T. Bangma, J.A. Bowden, A.M. Brunell, I. Christie, 

B. Finnell, M.P. Guillette, M. Jones, R.H. Lowers, T.R. 

Rainwater, J.L. Reiner, P.M. Wilkinson and L.J. Guillette, Jr., 

Perfluorinated alkyl acids in plasma of American alligators 

(Alligator mississippiensis) from Florida and South Carolina, 

Environmental Toxicology and Chemistry, Accepted manuscript 

online: August 20, 2016, http://dx.doi.org/10.1002/etc.3600
1 6 |

OUTREACH AND PARTNERING

WITH NEW CRADA, NIST UPS ITS 

MEASUREMENT R&D IN SUPPORT OF 

PRECISION MEDICINE DIAGNOSTICS

NIST’s efforts to support accurate 

diagnostic testing so that cancer 

treatments can be tailored to the 

tumor DNA and other characteristics 

particular to individual patients continue 

to gain momentum, as the agency 

mounts a multi-laboratory study to 

evaluate candidate reference materials 

for benchmarking measurements of 

circulating tumor DNA—so-called liquid 

biopsies.

The comparative exercise—sometimes 

referred to as an interlaboratory “round 

robin”—benefits from a new three-year 

Cooperative Research and Development 

Agreement (CRADA) with SeraCare Life 

Sciences, of Millford, Massachusetts. 

Under the agreement, SeraCare will 

supply its circulating DNA reference 

material technology to NIST to help 

further development and refinement of 

digital measurement methods. NIST 

will distribute these materials for testing 

at laboratories in the National Cancer 

Institute’s Early Detection Research 

Network and to other research and testing 

organizations.

and full function to patients who have 

experienced severe burns or physical 

trauma.

Because of the complexity of regenerative 

medicine treatments, they have been slow 

to transition from the laboratory to the 

clinic. The traditional measurements of 

efficacy, potency, purity, and quality that 

work with traditional pharmaceuticals 

aren’t always sufficient for regenerative 

medicine treatments.

To address these issues, NIST and 

the SCB, a non-profit founded by the 

Alliance for Regenerative Medicine, 

announced on September 19, 2016 

that they had signed a Memorandum of 

Understanding, forming a partnership 

to explore the regenerative medicine 

industry’s needs and develop standards 

and other products to increase confidence 

in measurements of gene- and cell-based 

therapies and manufacturing processes.

Credit: National Human Genome Research Institute

Scanning electron micrograph of retinal pigment epithelium (RPE) cultured on a nanofiber scaffold. 

RPE and nanofibers were imaged separately and combined. There are two scale bars since RPE and 

nanofibers were imaged at different magnifications. Nanofibers were pseudocolored and shadowing 

was added to the RPE.

Reliably accurate measurements will be 

critical to the successful introduction and 

adoption of liquid biopsies for anticipated 

clinical applications, which include 

monitoring therapeutic progress and 

detecting drug resistance mutations.

NEW PUBLIC-PRIVATE PARTNERSHIP 

TO DEVELOP STANDARDS FOR 

REGENERATIVE MEDICINE

NIST has partnered with the Standards 

Coordinating Body for Gene, Cell and 

Regenerative Medicines and Cell-based 

Drug Discovery (SCB) to develop 

industry-wide standard methods 

and protocols for characterizing and 

manufacturing these cutting-edge 

therapies, with an aim of accelerating 

their use as mainstream treatments for a 

variety of human diseases and injuries.

The field of regenerative medicine 

manipulates genes, cells, and tissues to 

repair or replace diseased, damaged, or 

missing organs, skin, bone, and other 

cells and tissues. Regenerative medicine 

has the potential to alleviate the shortage 

of donor organs and restore appearance 
| 1 7

HARVEY NAMED IAPWS FELLOW

The International Association for the 

Properties of Water and Steam (IAPWS) 

has named Allan Harvey, of MML’s 

Theory and Modeling of Fluids Group, 

an IAPWS Honorary Fellow. The status 

of Honorary Fellow is conferred upon 

select individuals in recognition of 

outstanding contributions to IAPWS and 

has been given to only 47 people in the 

36 years the award has existed. Harvey’s 

citation reads, “For long-standing efforts 

in formulating and improving IAPWS 

releases as member and Chair of the 

Working Group on Thermophysical 

Properties of Water and Steam, and 

Chair of the Editorial Committee. For 

outstanding scientific work in the field 

of fluids and aqueous systems, including 

ab-initio calculation of molecular 

interactions.” He is the fifth NISTaffiliated scientist to receive this honor.

KILPATRICK RECOGNIZED BY AACC MASS 

SPECTROMETRY AND SEPARATION 

SCIENCES DIVISION

Eric Kilpatrick, of MML’s Bioanalytical 

Science Group, was recently awarded 

Outstanding Abstract in the 2016 

Mass Spectrometry and Separation 

Sciences Division Abstract Competition. 

Kilpatrick received the award for his 

abstract entitled “Amino acid analysis 

by mass spectrometry for concentration 

determination of C-reactive protein in 

candidate reference material SRM 2924” 

at the Division Annual Meeting.

AWARDS

WARREN, CICERONE ELECTED AMERICAN PHYSICAL SOCIETY FELLOWS

Director of NIST’s Materials Genome Program Jim Warren (left) and Marcus 

Cicerone of MML’s Biomaterials Group have been elected Fellows of the American 

Physical Society (APS).

Warren is recognized for his seminal contributions to the modeling of microstructural 

development in a broad range of materials. He was elected by the APS Council of 

Representatives at its September 2016 meeting upon the recommendation of the 

Division of Materials Physics. Cicerone is recognized for outstanding contributions to 

the understanding of the dynamics in glassy materials, demonstrating its importance 

in the stabilization of protein therapeutics, and the development of broadband CARS 

microscopy for bioimaging. He was nominated by the APS Division of Polymer 

Physics.

APS Fellowship is a distinct honor for APS members and is a prestigious recognition 

by their peers. Fellowship is reserved for no more than one half of 1% of APS 

members in any given year. 

SOLES SELECTED AS A FELLOW OF THE AMERICAN CHEMICAL SOCIETY

In July 2016, the American Chemical 

Society announced the selection of 

57 members as ACS Fellows, who are 

recognized for outstanding achievements 

in and contributions to science, the 

profession, and the Society. Christopher 

Soles leader of MML’s Functional 

Polymers Group Christopher Soles was 

named as one of the new ACS Fellows. 

He is recognized for “significant 

contributions to elucidating the 

structure and properties of confined 

polymeric materials, nanoporous films, 

and nanoscale structures that impact 

emerging technology areas,” and 

“admirable service to the Polymeric 

Materials: Science and Engineering 

Division admirably as Chair-elect, 

Vice Chair, Treasurer, and Technical 

Program Chair, including initiating 

new program development and fiscal 

reforms.” 
1 8 |

FOR LABORATORY USE ONLY

NIST STANDARD STORY

WHAT

Standard Reference Material® 1946 Lake 

Superior Fish Tissue, and 1947 Lake 

Michigan Fish Tissue

Mark Cronise isn’t lying about the 

hundreds of pounds of trout that the 

and two colleagues helped to fillet, ice, 

and prepare for shipment to NIST after 

driving the length of Michigan’s upper 

peninsula all night. (The collection of 

Lake Michigan’s trout, scheduled for the 

same trip, was delayed, so it was shipped 

to NIST unescorted.) Upon arrival at 

NIST, each lake’s batch of fish was further 

frozen to -120 degrees Celsius (-184 

degrees Fahrenheit) in liquid nitrogen 

freezers, then ground to a powder, 

homogenized in a spinning drum, and 

bottled, all while still frozen. Each SRM is 

sold as five bottles of about 8 grams (0.28 

ounces) of powdered fish tissue stored 

at -80 degrees Celsius (-112 degrees 

Fahrenheit). They are each certified—

meaning that NIST and collaborators 

have performed sophisticated chemical 

analysis and shown that those results 

can be repeated—for more than a half 

dozen elements including mercury, 

plus a selection of industrial chemicals, 

pesticides, and fatty acids. NIST 

continues to test for and add values for 

chemicals, adding to the utility of the 

SRMs.

WHY

The U.S. Environmental Protection 

Agency (EPA) has monitored the Great 

Lakes water quality and ecosystem 

since the late 1970s. With more than 

94,000 square miles of surface area and 

30 million people living along their 

shores, there’s not much that doesn’t 

end up in the waters of the Great Lakes, 

from industrial contaminants like 

polychlorinated biphenyls (PCBs), to 

mercury, to agricultural pesticides, to 

other chemicals like the flame retardants 

used in couches and chairs. (Because 

Lakes Superior and Michigan differ in 

the types and amounts of chemicals they 

contain, NIST developed a fish tissue 

SRM for each.) PCBs and mercury have 

been shown to harm people and wildlife. 

The other substances have been shown 

to harm animals, although their effects 

on humans are not well understood. 

While NIST first developed the fish tissue 

SRMs to assist the EPA, they are used by 

environmental monitoring labs around 

the world to check their sample processes 

and test methods. The EPA, in particular, 

is interested in an accurate picture of 

the lakes’ recovery from now-banned or 

regulated PCBs and other chemicals, and 

helping localities give data-backed advice 

to their residents about how much Great 

Lakes fish is safe to eat. 

In addition to aiding environmental 

monitoring efforts, the Great Lakes 

NIST scientists have thoroughly measured and characterized more than 1,300 physical products, NIST Standard Reference 

Materials®, to help people in industry, academia, and government agencies calibrate instruments, verify their test methods, and 

develop new measurement methods. NIST reference materials, for example, help manufacturers make interoperable parts in far-flung 

facilities, medical labs check the accuracy of cholesterol and other clinical tests, and scientists monitor environmental threats.

fish tissue SRMs help food industry 

labs check their analytical methods for 

measuring fatty acids.

WHO

Each year, the EPA collects predator fish 

from the top of the lakes’ aquatic food 

chain from each of the Great Lakes. Top 

predators—the same types of fish usually 

eaten by people—accumulate toxins 

ingested by organisms lower in the food 

chain, so they are good indicators of the 

chemicals in their environments. Bernard 

Crimmins of Clarkson University oversees 

some of the analyses conducted as part 

of the EPA’s Great Lakes Monitoring 

Program.

HOW

Crimmins and Clarkson students rely on 

NIST fish tissue SRMs to diagnose any 

problems with their laboratory methods. 

“These SRMs are great because it’s the 

actual fish tissue, the same as what we 

measure,” Crimmins says, adding that 

just enriching a control with a known 

amount of chemical doesn’t represent 

the full complexity of the real-world 

analytical problem. The NIST SRMs also 

help the Clarkson students determine 

whether levels of emerging potential 

contaminants, such as new flame 

retardants, have increased compared 

to the historical levels preserved in the 

nearly-20-year-old NIST SRMs. Despite 

their age, the fish tissue SRMs have legs: 

If kept properly frozen, the SRMs will be 

good on your shelf until December 2026.

Learn more:

https://www-s.nist.gov/srmors/view_

detail.cfm?srm=1946

https://www-s.nist.gov/srmors/view_

detail.cfm?srm=1947

Technical Contact:

John Kucklick, john.kucklick@nist.gov

Mark Cronise (left) of NIST’s Office of Reference 

Materials assists a fisherman in the gutting and 

filleting of trout from Lake Superior. With further 

processing back at NIST, the fish tissue is transformed 

into a reference material that helps environmental 

monitoring labs with quality control. 

Credit: Mark Cronise/NIST.
| 1 9

PUBLICATIONS

M. A. Blanco Medina, V. K. Shen, “Effect 

of the Surface Charge Distribution on the 

Fluid Phase Behavior of Charged Colloids 

and Proteins” Journal of Chemical Physics, 

Vol. 145, pp. 155102-1-155102-13, (21-

Oct-2016) 

J. G. Radney, C. D. Zangmeister, “Light 

Source Effects on Aerosol Photoacoustic 

Spectroscopy Measurements” Journal of 

Quantitative Spectroscopy and Radiative 

Transfer, Vol. 187, pp. 145-149, (06-Oct2016) 

W. Fortunato de Carvalho Rocha, D. A. 

Sheen, “Classification of biodegradable 

materials using QSAR modeling with 

uncertainty estimation” Sar and Qsar in 

Environmental Research, (06-Oct-2016) 

A. P. Kotula, M. Meyer, F. De Vito, 

J. Plog, A. R. Hight Walker, K. D. 

Migler, “The rheo-Raman microscope: 

Simultaneous chemical, conformational, 

mechanical, and microstructural measures 

of soft materials” Review of Scientific 

Instruments, 8 pp., (04-Oct-2016) 

N. A. Schneck, K. W. Phinney, S.B. 

Lee, M. S. Lowenthal, “Quantification 

of Antibody Coupled to Magnetic 

Particles by Targeted Mass Spectrometry” 

Analytical and Bioanalytical Chemistry, pp. 

1-8, (30-Sep-2016) 

R. C. Quardokus, V. K. Tewary, F. W. 

DelRio, “Ullmann-like reactions for the 

synthesis of complex two-dimensional 

materials” Nanotechnology, Vol. 27, 4 pp., 

(28-Sep-2016)

M. M. Schantz, C. Powers, S. Rosemary, 

J. Betz, S. A. Wise, “Interlaboratory 

Analytical Comparison of Fatty Acid 

Concentrations in Serum or Plasma” 

Clinica Chimica ACTA, pp. 148-152, 

(20-Sep-2016) 

F. R. Bieber, J. Buckleton, B. Budowle, 

J. M. Butler, M. D. Coble, “Evaluation 

of Forensic DNA Mixture Evidence: 

Guidelines for Evaluation, Interpretation, 

and Statistical Calculations using the 

Combined Probability of Inclusion” 

Forensic Science International: Genetics, 

Vol. 17, No. 125, 15 pp., (31-Aug-2016) 

R. F. Cook, A. J. Gayle, “Mapping 

Viscoelastic and Plastic Properties 

of Polymers and Polymer-Nanotube 

Composites using Instrumented 

Indentation” Journal of Materials Research, 

14 pp., (15-Aug- 2016) 

L. J. Richter, J. Downing, S. Engmann, 

H.W. Ro, A. A. Herzing, D. M. 

DeLongchamp, S. Mukherjee, H. 

Ade, M. Addelsamie, A. Amassian, Y. 

Liu, H. Yan, “Morphology-insensitive 

Performance Facilitates Transition from 

Spin-Coating to Roll-to-Roll Coating For 

High-Performance, Solution-Processed 

Solar Cells” Energy and Environmental 

Science, Vol. 9, pp. 2835-2846, (02-Aug2016) 

R. B. Wagner, T. J. Woehl, R. R. Keller, 

J. P. Killgore, “Detection of Atomic Force 

Microscopy Cantilever Displacement 

with a Transmitted Electron Beam” 

Applied Physics Letters, (29-Jul-2016) 

W. N. Vreeland, A. H. Abouzeid, S. 

Muro, R. Ghaffarian, “Endocytosis of 

monomeric ICAM-1 targeting moieties 

provides intracellular transport of active 

enzyme conjugates” Journal of Controlled 

Release, Vol. 238, pp. 221-230, (27-Jul2016) 

J. P. Marino, K. T. Briggs, G. G. Giulian, 

J. Kao, G. Li, “A New Molecular Model 

for Lithiums Biological Interactions” 

Science/AAAS, Vol. 111, No. 2, pp. 294-

300, (26-Jul-2016) 

W. B. Wilson, L. C. Sander, M. J. Lopez 

de Alda, M. Lee, S. A. Wise, “Retention 

behavior of alkyl-substituted polycyclic 

aromatic sulfur heterocycles in reversedphase liquid chromatography” Journal of 

Chromatography A, pp. 120-130, (24-Jul2016) 

J. L. Reiner, J. A. Bowden, I. Christie, M. 

P. Guillette, T. M. Cantu, R. H. Lowers, 

H. Botha, W. Luus-Powell, W. J. Smit, D. 

Govender, D. Pienaar, L. J. Guillette Jr., 

“Perfluorinated Alkyl Acids in the Plasma 

of South African Crocodiles (Crocodylus 

niloticus)” Chemosphere, No. 154, pp. 72-

78, (01-Jul-2016) 
|

The Material Measurement Laboratory supports the NIST mission by serving as the national 

reference laboratory for measurements of matter, providing broad support for chemical, 

biological, and materials sciences. Our fundamental and applied measurement science 

research expands possibilities for determining the composition, structure, and properties 

of manufactured, biological, and environmental materials, and the processes that create 

them. In addition, MML drives the development and dissemination of tools—including 

measurement protocols, certified reference materials, critically evaluated data, and best 

practice guides—that help assure quality measurements of matter. Our research and 

measurement services support progress in areas of national importance including advanced 

materials, energy, environment, food safety and nutrition, forensic science, health care, 

manufacturing, physical infrastructure, and safety and security. MML also coordinates the 

NIST-wide Standard Reference Materials® (SRM) and Standard Reference Data programs. 

TO LEARN MORE, CONTACT:

Material Measurement Laboratory

100 Bureau Drive, M/S 8300

Gaithersburg, MD 20899-8300

Tel: 301-975-8300

Fax: 301-975-3845

mmlinfo@nist.gov

or visit http://www.nist.gov/mml