Laurie E. Locascio, Ph.D.

Director, Material Measurement Laboratory

NIST and the Biosciences
Bioscience at NIST beside some discoveries that 

changed the industry 

Radiation Physics Program (1920s)

Partnership with ADA, dosimetry standards (1928-)

Standards for clinical markers(1969-)

Center for Advanced Research in Biotechnology (1988)

NIST plans national effort to support emerging biotechnology 

industry; NIST Biotechnology Division formed (1991)

Bio becomes NIST focus program - Biosciences Div formed

NIST gets strategic in bio (2006)

MML formed with 2 bioscience divisions (‘12)

Partnership with Stanford in synthetic bio/genomics (’14) 

NIST emerging as an influencer- shaping discussion in standards 

for bio (‘15)

1920

1930

1970

1980

1990

2000

2010

2020

• Genome sequenced (’03)

• Next gen Sequencing and 

Omics measurements

• Induced Pleuripotent Stem 

Cells (‘12)

• Technologies for engineering 

biology

• Monoclonal antibodies (’74)

• Antibody based technologies

• PCR (’83)

• DNA analysis techniques 
Vision for NIST bioscience – 2005-2015

Leverage our vast expertise in the quantitative 

physical sciences to provide the measurement 

infrastructure to underpin innovation in the 

biosciences

• Strengthen partnerships with the medical, environmental and 

agricultural communities 

• Grow our in-house knowledge of interdisciplinary bio-related 

fields

• Teach our federal and private partners in the 

biotechnology/healthcare fields about NIST’s broad 

capabilities and strengths
TARGETED AREAS OF STRATEGIC IMPORTANCE FROM 

2005-2015 

Cell and System Analysis

New methods and technologies for probing 

cells and systems including tissue and 

organism level measurements (health)

Biomanufacturing

Develop measurement science, 

standards and technologies for 

biopharma industry focusing on 

protein therapies (health, 

manufacturing)

Omics Measurements

Develop the measurement capabilities to 

support growing needs in genomics, 

proteomics, metabolomics (health)
Targeted Budget Growth for Bioscience at NIST 2005-2015

Budget Initiatives Year Amount

Bioimaging (cell and medical) 2006, 2007 3.8 M (MML, PML)

Bioscience/Health (measurement

assurance for genomics/proteomics)

2009, 2010 7.5 M (MML, ITL)

Biomanufacturing (protein

therapeutics)

2012, 2013, 

2014

9.9 M (MML, PML, NCNR)

Synthetic Biology 2015 1.5 M (MML)

Biomanufacturing (nano) 2015 1.0 M (CNST)

Total 10 year base increase in bio 23.7 M
Who works in bio at NIST

• In 2012 reorganization, bio became 

primary focus area for MML 

• Currently 5 laboratories have 

activities in bio area (MML, PML, 

ITL, NCNR, CNST)
What NIST does

• Performs cutting edge measurement 

science research to support better 

measurements 

• Develops highest quality measurement 

science and standards for confidence in 

biological data 

NMR-readable nanosensors

for potential application in in 

vivo imaging: G. Zabow, S. J. 

Dodd, A. P. KoretskyGenome in a 

bottle reference 

genome: Zook, 

Munro, Salit
New tools and technologies taking 

advantage of our strengths in 

physical sciences

New methods based on existing 

technologies that enhance their 

measurement science capabilities

Measurement Science Research 
Next gen Protein 

Sequencing

NIST-invented technology 

for large scale, massively 

parallel protein sequencing 

to access whole proteome 

without bias (with UMD)

Neutron methods 

provide insight into 

Parkinson’s disease

Using unique NIST facilities 

provide high resolution 

images of protein-protein 

interactions to elucidate 

mechanism of disease (with 

NIH, Carnegie Mellon)

Label-less 3D Chemical 

Imaging for Cells/Tissues 

NIST-invented broadband 

coherent anti-Stokes Raman 

scattering microscopy can 

acquire full chemical 

spectrum at each pixel with 

high speed and without 

chemical labels to provide 

functional and molecular 

information for 

understanding of disease
Algorithms and 

Visualization Tools for 

Qualification of Stem 

Cells for Cell Therapies

NIST-developed algorithms 

to provide objective metrics 

to qualify stem cell colonies 

prior to implantation or 

topical application in order 

to predict successful 

outcome. (with NIH)

Shape shifting Probes

NIST-invented shapeshifting probes are first-ofits-kind for sensitive, highresolution remote biological 

sensing with application to 

deep tissue imaging. (with 

NIH)

Nanofluidic devices for 

cancer diagnosis

NIST-invented technologies 

for measuring ‘circulating 

DNA’ that results from 

tumor growth or 

metastasis. Fluorescence 

intensity and molecular 

diffusivity of DNA molecules 

confined in nanofluidic slits 

independently analyzed as 

orthogonal measures of 

molecular size. 

Score = 4.6

(good)
• Providing standard reference materials, standard 

methods or community based consensus 

methods for measurements of RNA, DNA, 

proteins and cells

Measurement Science and Standards to 

Assure Confidence in Biological Data

from standards for metabolomics to the first 

standard for global monitoring of HIV 
Forensic DNA Typing

An extensive suite of 

standards, analysis tools, and 

teaching tools to ensure 

accurate genotyping. In 

support of the FBI Quality 

Assurance Standards followed 

by all forensic labs, our 

standards underpin that 

Nation’s confidence in DNA for 

forensics. (Partners: FBI, NIJ, 

forensics labs, industry)

Standards for Cell Line 

Authentication

Methods, standards to solve 

problem of contaminated or 

misidentified cell lines used for 

basic research and industrial 

testing protocols. Estimates of 

30% of cells misidentified, 

leading to incorrect research 

interpretation and estimates of 

billions of wasted dollars in our 

research enterprise. (Partners: 

ATCC,DNA Diagnostics Center, 

MedImmune) 

ISO Biotechnology 

Standards Committee

NIST serves as Chair and 

Executive Secretary of US 

Delegation developing 

documentary standards 

for biobanking, 

bioanalytical methods, 

and bioprocessing and 

promoting US agenda in 

international standards 

impacting 

trade.(Partners: FDA, 

USDA, USTR, NIH, DOE, 

ITA, US industry)
DNA Microarray 

Measurements

Reference methods, data analysis 

tools providing confidence in DNA 

microarray measurements 

addressing the wide variability in 

results from different commercial 

platforms. Developed in NIST-led 

consortium with >90 public, 

private, academic partners, 

standard sequences now on 

products of every major 

microarray producer. (Partners: 

NIH, FDA industry)

Medical Imaging

Standards, phantoms, and 

improved contrast agents for 

ionizing and non-ionizing 

(optical and magnetic) 

radiation medical imaging 

technologies to promote 

reproducibility, reduce 

uncertainty associated with 

various imaging modalities. 

First commercially-available 

traceable PET phantoms to 

be shipped with every GE 

Healthcare PET-MRI 

scanner.

NIST MRI Phantoms

Mass Spectral Library

Reference standard mass 

spectra for chemical, 

protein, peptide 

identification- largest 

selling NIST purchased data 

product. World’s most 

widely used MS library 

with validated software for 

spectrum matching. 

Integrated into virtually 

every mass spectrometry 

instrument vendor 

software systems.
For greatest impact, we:

• Develop deep ties with our federal agencies (NIH and FDA are 

key)

• Establish close relationships with our industry stakeholders who 

keep us abreast of current issues affecting the sector

• Strategically partner with US biotechnology leaders to leverage 

federal dollars against private sector investment
Ties with Federal Agencies

• FDA/CDRH: Whole Genome Sequencing - genomic reference materials for personalized 

medicine; FDA used pilot NIST material to aid in approving the first next generation 

sequencer

• FDA/CDER, CBER: Biotherapeutics- ~ 65 FDA scientists and review staff participate in joint 

workshops to reconcile results from different sample processing, chromatographic, and 

mass spectral methods that sponsors use; MML serves on FDA advisory panel for biosimilar

license applications

• NIH/NCI, Early Detection Research Network : Cancer Biomarkers- Validation and verification 

of new biomarkers for early cancer detection conducting Interlaboratory comparisons, 

producing standards, data analysis protocols for miRNA, genetic biomarkers

• NIH/NCI, Clinical Proteomics Tumor Analysis Consortium: Proteomics- Standards and data to 

support ‘Common data analysis pipeline’ (CDAP) for mass spectrometry consortium data in 

proteomics

• NIH/NIDCR: Dental Materials- Standard Reference Materials (SRMs) for measurement 

assurance of calcium phosphate based biomaterials; standardized measurements for 

improved dental materials and oral health care

• NIH/NIGMS, NSF/BIO, NIST: Co-organizing WH Symposium on confidence in data for 

innovation and data sharing (early 2016).
Ties with Federal Agencies

• FDA/CDRH: Whole Genome Sequencing - genomic reference materials for personalized 

medicine; FDA used pilot NIST material to aid in approving the first next generation 

sequencer

• FDA/CDER, CBER: Biotherapeutics- ~ 65 FDA scientists and review staff participate in joint 

workshops to reconcile results from different sample processing, chromatographic, and 

mass spectral methods that sponsors use; MML serves on FDA advisory panel for biosimilar

license applications

• NIH/NCI, Early Detection Research Network : Cancer Biomarkers- Validation and verification 

of new biomarkers for early cancer detection conducting Interlaboratory comparisons, 

producing standards, data analysis protocols for miRNA, genetic biomarkers

• NIH/NCI, Clinical Proteomics Tumor Analysis Consortium: Proteomics- Standards and data to 

support ‘Common data analysis pipeline’ (CDAP) for mass spectrometry consortium data in 

proteomics

• NIH/NIDCR: Dental Materials- Standard Reference Materials (SRMs) for measurement 

assurance of calcium phosphate based biomaterials; standardized measurements for 

improved dental materials and oral health care

• NIH/NIGMS: co-organizing a WH Symposium on reproducibility and confidence in data (early 

2016) working with Jon Lorsch (NIGMS) and Jim Olds (NSF-BIO).

• FDA/CDER, CBER: Biotherapeutics- collaborate to reconcile and 

understand results from different methods that sponsors use in 

FDA applications for approval of new technologies and products; 

serve on panel for biosimilar license applications

• NIH/NIGMS, NSF/BIO, NIST: Co-organizing WH Symposium on 

confidence in data for innovation and data sharing (early 2016).
• NASA: worked with NASA to create strategic plan for materials 

research in the International Space Station including biological 

materials, biomaterials and biomimetics

• DARPA, Living Foundries program: standards for Synthetic Biology

• DHS Office of Science and Technology: Biosecurity Threat DetectionEngineered yeast with known genetic sequences for testing 

detection of unknowns

Ties with Federal Agencies
Working with Industry Stakeholders 

through Consortia

• NIST led consortium with more than 75 

public, private, academic partners

• Developing whole genome reference 

materials and bioinformatics tools for quality 

assurance of whole genome sequencing 

technologies (next gen and next/next gen). 

• FDA used this to approve the first highthroughput DNA sequencer.

NY Times (5/14/15): “The federal government 

opened a new era of genetic medicine on 

Thursday by introducing a standard way to 

ensure the accuracy of DNA tests used to tailor 

treatments for individual patients.”

nSoft consortium

• NIST-led consortium for neutron 

measurement of soft materials

• Developing neutron instrumentation, 

sample environments, data analysis 

methods to attack issues in manufacturing 

of soft materials including polymers, 

colloids, and proteins (biopharma). 

• Issues addressed include understanding 

protein instability in freeze-dried 

formulation; protein aggregation in 

needles (Dupont, Genentech, 

MedImmune, Chevron Phillips, Kimberly 

Clark, Dow, Solvay)
Nanofabrication and NanoBio

20

Multiple projects underway in CNST: 

DNA sequencing; regenerative 

medicine; medical devices; 

medical diagnostics; drug delivery; 

neural probes; imaging (MRI, X-ray, 

& fluorescence); cell sorting and 

manipulation.

One example: 3D imaging of DNA 

transcription

• New method enables simultaneous 

imaging of multiple focal planes in live 

cells 

• Collaborative microscope development 

project with HHMI Janelia Farm

• Diffractive optic produced in the NanoFab 

will dramatically improve throughput

2 μm

Model Structure

Fabricated Structure
• NIST focus area: Biomanufacturing

• Funding: Grant to UMD $2.2M/annual) for 

infrastructure, operations, scientific programs

• IBBR NIST Staff, Associates and Affiliates (~ 50)

Institute for Bioscience and Biotechnology 

Research Partnership with University of 

Maryland System

Precision biomolecular structure/function 

measurements & standards to support 

biopharma and biotechnology

NIST focus areas: Genomics, Synthetic Biology

Funding: 2 grants to Stanford (~2M) for 

research, training, seed funding for metrology

JIMB NIST Staff: 11

Measurements, standards and informatics 

tools for the genomics and the emerging 

synthetic biology enterprise.

Joint Initiative in Measuring Biology 

(JIMB) Partnership with Stanford 

University

Strategic Partnerships
NIST labs reminded me of one of my favorite places, a hardware 

store, where I’m fascinated with all of the small objects in the bins 

and wonder what they are used for. NIST’s bins are no secret to 

chemists, physicists, and engineers, but there hasn’t been much 

for biologists. But now biologists have a bin or two at NIST...

The great news for us is that NIST has decided to help...by 

developing standards we can all use as benchmarks for our 

research and clinical applications. But they won’t make a big deal 

of it; NIST does their work quietly choosing projects not on the 

basis of headline-grabbing potential, but on the potential to 

improve the quality of our science.

Jeanne P. Loring, Ph.D., Scripps Research Institute

Member, NRC Review Panel
What’s next?
How Microbes Defend and Define Us By Carl Zimmer, NY Times 5/12/10

Dr. Alexander Khoruts had run out of options.

Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a 

piece of someone else’s intestines, or a stomach, or any other organ. Instead, 

he gave her some of her husband’s bacteria.

In Good Health? Thank Your 100 Trillion Bacteria By Gina 

Kolatajune, NY Times, 6/13/12 

Dr. Barnett Kramer, director of the division of Cancer Prevention at {the 

NCI} had another image. Humans, he said, in some sense are made mostly 

of microbes. From the standpoint of our microbiome, he added, “we may 

just serve as packaging.”

Microbes and Humans

A. Bouslimani et al., Molecular Cartography of the human skin surface in 3D, PNAS, 3/30/15 
Male cancer patients lose out in deadly research divide, The London Times, Jan 2013

Biological bad luck blamed in two-thirds of cancer cases

Tomasetti said harmful mutations occur for "no 

particular reason other than randomness" as the body's 

master cells, called stem cells, divide in various tissues.

"Thus, we should focus more research and resources on 

finding ways to detect such cancers at early, curable 

stages," Tomasetti added.

By Will Dunham, Reuters, 1/1/15

Tomasetti and Vogelstein, Science, Jan 2 2015

Cancer continued

Thinking Ahead: From 'The Emperor Of All Maladies' To Precision 

Medicine In Cancer

While precision medicine is enhancing oncologists’ capacity to predict 

effectiveness of treatment for individuals with particular mutations, 

this approach is new to most clinicians and doesn’t yet apply in many 

cases.

By Elaine Schattner, Forbes, 3/15
Making, Changing, Editing Biology

The rumors were true: Scientists edited genomes of human embryos for the first 

time 

In March, a rumor surfaced in the scientific community that was intriguing, and 

perhaps a bit chilling: According to those in the know, researchers in China had 

successfully edited the genomes of human embryos, altering their DNA in a way never 

accomplished in our own species.

By Rachel Feltman, Washington Post, 4/22/15

P. Liang et al., CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes, Protein & Cell, 4/18/15

Cloning and Stem Cell Work 

Earns Nobel

By injecting the four agents into an 

adult cell, Dr. Yamanaka showed 

that he could walk the {adult} cell 

back to its primitive, or stem cell, 

form.

Stem cells generated by this 

method, known as induced 

pluripotent cells, or iPS cells, could 

then be made to mature into any 

type of adult cell in the body...By 

Nicholas Wade, NY Times, 10/8/12

Synthetic Biology 2.0

Someday, this scene may find its 

way into The Social Network II* as 

a microcosm of the latest garage 

industry to inundate VC pitch 

meeting schedules from Silicon 

Valley to Cambridge. It’s Biotech 

2.0, with synthetic biology 

techniques offering tinkerers a 

new lens on microbially produced 

materials. Wired, Jeffrey Marlow, 9/3/13
Custom Organs, Printed to Order

Laboratories have successfully 

recreated human ears, noses, skull 

bones, jaw bones, tracheas, ears, 

noses, skin sections, bladders, arteries, 

and fat. Rather than cutting squares of 

healthy skin from a patient to help 

cover an injury, a 3D printer could print 

skin perfectly shaped to fit. Patients 

marred by disfigurement may soon be 

able to customize a nose on a 

computer.

Nova Next, By Jenny Morber, 3/18/15

3-D Printed Body Parts
A 10 YEAR VISION FOR 2015

NIST MEASUREMENT SCIENCE AND 

INNOVATION ENABLE 21ST CENTURY 

HEALTHCARE AND THE BIOECONOMY
In 10 years we have developed strong core 

capabilities in target areas of molecular and 

cellular analysis.

To have impact in the next wave of the 

building bioeconomy requires a great deal of 

additional sophistication to examine systemlevel complexity.
AREAS OF STRATEGIC IMPORTANCE (2015-2020) 

Quantitative Tools for Characterization of 

Complex Biologics 

Define complex biomolecules/biologics 

through quantitative measurements to enable 

prediction of biological function in healthcare 

applications (manufacturing, health)

Microbial Measurements

Develop measurement 

infrastructure for microbial 

measurements (health, 

environment)

Engineering biology

Develop the measurements and models for 

engineering biology to map out the 

fundamental principles that drive development 

of next generation bio-based products (high 

tech manufacturing, health)

Precision Medicine 

Develop measurement science and 

standards to ensure confidence in 

clinical decision-making, and 

ultimately enable adoption of 

precision medicine (health)

Data and Informatics

Provide validated data and 

informatics tools to support 

confident decision-making (all 

sectors)