BIOTECHNOLOGY
Affymetrix–GE Healthcare
(formerly Molecular Dynamics)
Helping to Decode
the Genome
View PDF Document Patent Tree
DNA sequencing on a large scale began in the 1980s, and by
the 1990s researchers were uncovering significant links between genes and
disease. To advance knowledge of the body’s genetic makeup, the National
Institutes of Health and the Department of Energy launched the Human Genome
Project (HGP) in 1990 to map the human genome, thought to consist of up to
100,000 genes and 3 billion base pairs. As researchers delved into gene
structure, they found that their diagnostic tools were too cumbersome to enable
the breakthrough discoveries expected.
To develop better tools, the Advanced Technology Program
(ATP) established the “Tools for DNA Diagnostics” focused program in 1994.
Among the first successful applicants were Affymetrix and Molecular Dynamics,
in a joint venture to develop a miniaturized integrated nucleotide diagnostic
device. This would be a handheld device built on microchip technology that
extracts DNA from a blood sample and amplifies and analyzes it. Affymetrix had
developed the industry’s first microarray, based on GeneChip1
technology, by adapting miniaturization and production techniques from the
computer chip industry to enable chemical analysis of clinical samples.
Molecular Dynamics, an engineering company, would build instrumentation
surrounding Affymetrix’s microarray.
As the
project proceeded, market research showed little support for point-of-care
devices. The companies instead developed a series of tools to enable other
genetic testing technologies. Affymetrix produced denser array chips, developed
array technologies and instrumentation, and refined its software to handle the
vast amount of data generated by the arrays. In addition, their methodologies
for gene expression are used extensively in drug discovery and diagnostics.
Affymetrix remains the largest and most prominent producer in the
“lab-on-a-chip” market.
Molecular
Dynamics produced MegaBACE2, the first high-throughput DNA
sequencer. MegaBACE could simultaneously analyze 96 DNA fragments at very high
speed, replacing the slow and error-prone slab gel method in use at the time.
HGP was able to accelerate its timetable, in part because Molecular Dynamics
raised the bar for sequencers’ performance. Molecular Dynamics, now a
component of GE Healthcare, estimates that MegaBACE 1000 mapped about 30
percent of the human genome. This project produced widespread benefits through
its products and its knowledge transferred through patents, publications, and
presentations.
Composite Performance Score
(based
on a four-star rating)
*
* * *
Research and data for Status Report 94-05-0016 were collected
during December 2005–March 2006.
Biotech Research Needs Better
Tools
Large-scale DNA
sequencing began in the 1980s and quickly yielded evidence of the genetic basis
of many diseases. But a decade later, the industry still lacked the tools to
efficiently sequence DNA. Clinicians and researchers were limited to
identifying individual genes in a slow and often discontinuous process. Sample
preparation and amplification were cumbersome, expensive, and inexact. In 1990, the U.S.
Department of Energy and the National Institutes of Health established the U.S.
Human Genome Project (HGP) to determine the sequence of human DNA, estimated to
contain 100,000 genes and 3 billion base pairs. The project also expected to
transfer sequencing and informatics technologies to the private sector. As HGP’s work
progressed, the need for new, more efficient, less expensive diagnostic
procedures, instruments, and tools became ever more pressing.
Nearly 50 companies and research
institutions submitted white papers to ATP on the biotechnology industry, citing diagnostic tools as a critical need. As a result, ATP established the “Tools for DNA
Diagnostics” focused program. The program’s aim was to hasten the development
of cost-effective and efficient technologies for sequencing, storing, and
interpreting DNA.
Scientists at Affymax, a biotechnology company, had adapted
a photolithographic technique used in semiconductors to produce GeneChip
arrays, the world’s first microarray. This was a miniaturized chemical reaction
on a glass wafer the size of a postage stamp. The wafer embedded fragments of
DNA, called probes, on its surface. By introducing a prepared blood sample to
the chip, researchers could analyze matches between the sample and the probes.
This meant that medical researchers could, for the first time, see how cells
responded to disease and to drug treatments on a large scale. The work was described in Science
magazine and won the Intellectual Property Owners Association’s Distinguished
Inventor award in 1993.
That same year, Affymax formed a new company,
Affymetrix, to commercialize GeneChip technology and use it to accelerate drug development,
to capitalize on the demand for point-of-care tools, and to create an
instrument system. As a small start-up company, Affymetrix attracted venture
capital, but was devoting its research and development budget to near-term
opportunities.
Affymetrix had a long-term goal of shrinking the GeneChip array and combining it with
a desktop reader to form a handheld unit, called a miniaturized integrated
nucleotide diagnostic (MIND) device. The company needed help with the
front and back ends of the process: shrinking the sample before introducing it
to the chip and generating a readout on a handheld unit. Affymetrix approached Molecular
Dynamics, a small
engineering company founded in 1988 to develop and produce high-resolution
scanners for bioanalysis. Molecular Dynamics built Affymetrix’s first
scanner.
In 1994, the two
companies submitted a proposal to ATP under the “Tools for DNA Diagnostics”
focused program to develop MIND. In October, ATP awarded the two companies
cost-shared funding. The five-year project, one of ATP’s largest joint
ventures, began in February 1995.
The project's primary focus was the
core science and components of the MIND unit, developing systems to extract,
purify, amplify, and analyze DNA samples. Ultimately, the companies wanted to
find a quick, inexpensive method of analyzing DNA, which they proposed to
accomplish by hybridizing probe arrays and by using a new kind of
electrophoresis that would be quicker and less error-prone.
In probe
arrays, a DNA molecule with a known sequence is labeled to find and mark DNA
sequences with the probes on the chip. GeneChip technology would expand the capacity of DNA probe arrays
so that it could contain thousands of sequences. In addition, they needed to
tackle the challenge of processing samples using microfluidics (fluids
at volumes thousands of times smaller than a droplet). In miniaturizing sample
preparation, the sample volume can become so small that gene expression may not
be readable. The
project would also develop the software and hardware to do the assays and
interpret the results with minimal human intervention. Most of these challenges
had been addressed before, but not in the integrated fashion that the MIND unit
warranted.
During the
first two years of the project, Affymetrix improved its photolithographic
process so that it could be scaled up to industrial production levels. As
Affymetrix increased the density of its arrays, the amount of data from the
chip readout increased exponentially. To cope with increased information,
Affymetrix improved the software that enabled computation and data analysis.
Figure 1.GeneChip Probe Array
In 1996,
Affymetrix began limited marketing of a GeneChip system, which consisted of the
chip, instruments to process the probe arrays, and software to analyze the
information. The company sold nine systems to research laboratories that year
and signed agreements with several companies for projects in drug discovery,
linking genetic variations to disease, and disease management. These
partnerships were outside the scope of the award, but they boosted the chances
of rapid commercialization of the technology that ATP was funding. In addition,
the agreements allowed the companies to raise capital for continuing research
and development (R&D). Affymetrix also entered into an agreement with
bioMérieux to use the arrays to detect microbial contamination in food and
cosmetic products, a transfer of technology from biomedical research to other
industries.
Molecular Dynamics’
High-Throughput Sequencer Advances Race
Meanwhile,
Molecular Dynamics had been working on a sequencer using capillary array
electrophoresis (CAE) to achieve high throughput. The prevailing method of
sequencing was slab gel electrophoresis, which could not handle large volumes
because gel preparation required careful handling and was prone to errors. In CAE,
gel-filled capillary tubes separate DNA fragments, and electrophoresis
distinguishes individual molecules in a mixture by passing electric current
through the capillary tubes; each kind of molecule travels at a different rate,
depending on its electrical charge and size. Molecular Dynamics contracted with
a chemistry professor at the
Molecular Dynamics' CAE machine, called the MegaBACE 1000, had 96 capillary tubes; a laser and scoring system read the samples. The company developed the first high-throughput sequencer for DNA, defined as those that sequence 1 million base pairs per day. The sequencer could read longer DNA fragments with greater accuracy and speed than those developed up to that time. Before MegaBACE, sequencing each DNA fragment on a gel took several days; now, 96 could be done simultaneously. In June 1997, Molecular Dynamics began testing MegaBACE at three sites. By the end of the year, they had delivered 11 systems and sold dozens more.
Figure 2. MegaBACE 1000 DNA
Sequencer (Image courtesy of GE Healthcare)
Molecular Dynamics’ introduction of the MegaBACE 1000 induced the company’s
chief competitor, Applied Biosystems Inc. (ABI), to speed up development of its
CAE sequencer, which it brought to market much sooner than planned. By the end
of 1997, Molecular Dynamics had sold 40 systems and was expecting other large
orders. In mid-1998, Perkin-Elmer (PE) and Celera Genomics announced that they
were planning to sequence the human genome in three years, in direct
competition with HGP. This accelerated timetable was possible in large part
because high-throughput sequencers were available. The PE-Celera team chose
ABI’s sequencer, but other operating arms of HGP ordered MegaBACE to keep up
with the challengers’ genome sequencing.
In January 1998, Affymetrix had
requested that the project’s strategy, timing, and scope be changed.
Point-of-care devices such as the MIND device did not seem economically viable
in the near term. Insurance companies would not reimburse claims for their use,
and doctors were reluctant to cede the ability to make diagnoses to a machine,
even an accurate and comprehensive machine. Manufacturers found they had to
provide so much technical assistance to buyers that it was difficult to make a
profit. Instead, Affymetrix and Molecular Dynamics found that the precursor
technologies they were working on could benefit HGP and benefit from the
research emanating from the project.
In July 1998, Affymetrix and Molecular Dynamics launched the Genetic Analysis Technology Consortium to create standards for read-out, data formats, and reagents to process arrays from multiple sources. A standardized and accessible platform would make array technology available to the community of genomics researchers and would be less expensive and duplicative than the current competing and incompatible systems.
Under a nonexclusive licensing agreement, Molecular Dynamics had rights to some of Affymetrix’s array technology but was developing its own array technology for gene expression and analysis. Seeing this technology as direct competition for GeneChip technology, the companies scaled back their collaboration to prevent the disclosure of competitive information. Instead of meeting quarterly, they reduced their meetings to twice a year and limited the exchange of information to ATP’s minimum reporting requirements, even as they continued to work on their parts of the project. In September 1998, Amersham Pharmacia Biotech acquired Molecular Dynamics.
In
August 1998, Affymetrix entered into an agreement with Beckman Coulter to
develop and commercialize GeneChip and other DNA probe arrays and anticipated
giving other companies and research laboratories access to the technology
through cooperative agreements. The company formed a partnership with Sybase to
develop databases and reached an agreement with Amersham Pharmacia Biotech to
distribute arrays in some countries outside the
That same
month, Affymetrix introduced the GeneChip HuSNP assay, the first in a line of
products to support applications in genotyping. The company was collaborating
with the Whitehead/MIT Institute Center for Genome Research and the
Affymetrix and Amersham took
advantage of market opportunities to introduce products, while continuing to
develop other technologies for sequencing and analytical devices that would lay
the groundwork for the MIND device in particular and point-of-care devices in
general. ATP continued its commitment to the project, assessing the subsidiary
project outcomes and technologies against overall project criteria.
In addition to significant publicity
in the biotechnology and business press, newspapers and magazines such as Popular
Science ran feature articles about the new products. By 1999,
between them Affymetrix and Amersham had marketed 5 initial products, signed
more than 12 agreements with collaborators and customers, and had attracted
substantial additional investment funds. Amersham announced that 20 additional
partners had joined the Microarray Technology Access Program, which included 30
drug and biotechnology companies, institutes, and universities. This program
provided access to proprietary technology.
Development Continues after ATP Funding
ATP funding ended in 2000, the same
year that HGP and the PE-Celera team announced that the mapping of the human
genome was essentially complete. Amersham reported that,
"MegaBACE is now established as the major force behind many public- and
private-sector genome sequencing operations,” and said it had installed more
than 400 systems around the world.
By September 2001, the majority of
the top pharmaceutical companies, more than a dozen biotechnology firms, and
more than 1,000 academic institutions were using GeneChip and other Affymetrix
technologies. According to an economic impact analysis3 in January
2007, “The ATP award had a significant influence on Affymetrix as a company and
on the biotechnology industry as a whole. Receiving the award helped Affymetrix
secure additional funding from venture capitalists and increased interest in
Affymetrix’s initial public offering (IPO) by validating the company’s efforts.
Affymetrix believes the award and the project’s success also invigorated
investor interest in the biotechnology sector.”
The research from the project was
the subject of numerous publications and presentations and generated 29
patents. The two companies had myriad technical accomplishments supported in
part by the ATP-funded research. Both companies developed software for DNA
analysis used for sequencing and diagnosis.
They also developed methodologies for gene expression, used extensively
in drug discovery and diagnostics.
Affymetrix:
·
Produced
DNA arrays for a variety of uses
·
Developed
a prototype disposable cartridge for complete analysis
·
Developed
technologies for dense arrays using photolithographic techniques
Amersham:
·
Developed
array technologies for arrays of long oligonucleotides such as cDNA
·
Developed
instrumentation to fabricate these arrays
·
Demonstrated
electrophoresis in chip format with multiple lanes and unit base resolution out
to 450 bases and beyond
Amersham invested
about $20 million in industrial design and had obtained research funding from
other Federal agencies. It collaborated with other companies, but was no longer
working with Affymetrix. In 2004, the GE Healthcare division of the General
Electric Company acquired Amersham. By then, 1,530 MegaBACE systems had been sold, bringing in
$20 million in revenue, including new models that had been developed to
accommodate larger- and smaller-scale sequencing.
The Molecular Dynamics
team estimated that MegaBACE sequencers were responsible for mapping about 30
percent of the human genome. The new sequencer lowered per-unit operating
costs, eliminated many time-consuming manual processes, and enhanced the
quality of data output. The use of high-throughput sequencers was estimated to
have advanced the sequencing of HGP by three years. Molecular Dynamics said it
would not have begun the research that led to MegaBACE without the ATP award.
The handheld device that was the
original goal of the project was never produced, but the ATP-funded project
contributed to the core science, best practices, processes, and methodologies
that could make such a device possible. The products emanating from the ATP
award have become pre-eminent tools in the diagnostics industry. DNA chips now
enable medical research, which previously took months or was not possible at
all, in HIV, cancer, cystic fibrosis, and sudden threats such as SARS and avian
flu. As in the semiconductor industry, costs are expected to fall even though
features are increasing. In the long term, doctors and other clinicians will
use microarray technologies to help determine the benefits of drug therapies
for patients given their genetic makeup. Researchers use DNA-chip technology to
advance the capability of DNA-based treatments.
The ATP award accelerated
Affymetrix’s microarray technology and the protocols, assays, and software that
enable its practical application. Affymetrix halved the size of DNA probe
features from 50 to 25 microns and developed the information technology
infrastructure for working with the high volume of data output by DNA
microarrays, manufacturing techniques for producing DNA microarrays, proofs of
concept, and new analytical methods. These achievements improved the quality
and ease of the end-use experience and hastened the introduction of better and
faster analysis for the same approximate price.
The introduction of high-throughput
sequencers was a milestone that accelerated HGP and the scientific discoveries
that emanated from sequencing the genome. Both companies attribute their growth
to the ATP-sponsored project. Affymetrix had 66 staff
members at the project outset, grew ninefold to 519 by the end of ATP funding,
and numbered 1,101 in mid-2006. Affymetrix had 82 percent of the DNA microarray market. Molecular Dynamics, also a small company at the project outset, was
acquired by progressively larger companies and is now a component of GE
Healthcare.
Conclusion
In 1990, two Federal
agencies announced a 15-year program to sequence the human genome, known as the
Human Genome Project (HGP). In addition to the knowledge that would be gained
by knowing the entire sequence, the project envisioned accelerating the
technologies that were needed to undertake the task. Before 1994, scientists
used $100 blood tests and other diagnostic procedures to identify individual
genes. That year, Affymax introduced the first GeneChip array, which allowed
the sequencing of several DNA fragments simultaneously. Affymax subsequently
spun off Affymetrix to improve and commercialize the technology. Soon
thereafter, Affymetrix joined with Molecular Dynamics to propose a highly
sophisticated handheld diagnostic device for use in medical offices and
clinics. The companies applied for and received an ATP cost-shared award for a
five-year project that began in 1995.
Affymetrix
improved its photolithographic process for industrial production and increased
the capacity of GeneChip arrays by increasing the probe density. It also
improved the software used to work with the ever more copious data readouts
generated by GeneChip technology. By 1996, Affymetrix began limited marketing
of a GeneChip system that included instruments to process the probe arrays,
software, and the chip itself. As the project proceeded, Affymetrix continued
to improve and vary the chip’s capabilities.
Molecular
Dynamics began work on a sequencer that it called MegaBACE. Using a capillary
array technique combined with electrophoresis, MegaBACE speeded up sequencing
nearly a hundredfold, leading other companies to speed the development of their
sequencers. In 1998, Perkin-Elmer and Celera announced plans to sequence the
human genome in three years, in direct competition with HGP. Although the
rivals would use a different sequencer, laboratories sequencing the genome for
HGP ordered many MegaBACE 1000s to meet the challenge.
This project accelerated
the use of the DNA chip as a robust method of molecular analysis. Both Affymetrix and Molecular
Dynamics, now part of GE Healthcare, have become leaders in the diagnostic
device field. As of 2006, Affymetrix had 82 percent of the DNA microarray
market and had established a licensing program to stimulate the broad
commercialization of genome analysis technologies. The research from the
project resulted in several thousand publications and presentations and 29
patents.
1
Gene Chip is a
registered trademark of Affymetrix Inc.
2 MegaBACE is a registered trademark
of GE Healthcare.
3 O’Connor, Alan et al. Economic Impact of ATP’s Contributions to DNA Diagnostics Technologies.
NIST Advanced Technology Program, GCR 06-898, January 2007.
Project Highlights
Affymetrix-GE
Healthcare (formerly Molecular Dynamics)
Project
Title: Helping to Decode the Genome (Miniaturized Integrated
Nucleic Acid Diagnostic (MIND) Development)
Project: To develop a miniaturized integrated
nucleic acid diagnostic (MIND) device suitable for use in hospitals, clinics,
or doctors’ offices, which could provide the rapid, accurate diagnosis of a
wide variety of diseases.
Duration: 2/1/1995-1/31/2000
ATP
Number: 94-05-0016
Funding
(in thousands):
|
ATP Final
Cost: |
$28,779 |
47.8% |
|
Participant
Final Cost: |
31,487 |
52.2% |
|
Total: |
$60,266 |
|
Accomplishments: With ATP funding both companies developed software for DNA
analysis used for both sequencing and diagnosis, and developed methodologies
for gene expression, used extensively in drug discovery and diagnostics. In addition Affymetrix:
·
Produced
and marketed DNA array chips for a variety of uses
·
Developed
a prototype disposable cartridge for complete analysis
·
Developed
array technologies for dense arrays, with short oligonucleotide probes, using
photolithographic techniques
Molecular
Dynamics (now a component of GE Healthcare) developed the MegaBACE 1000, a
capillary array electrophoresis sequencer that scans and detects DNA in human
samples. It was used by the Human Genome Project (HGP) to determine the
sequence of about 30 percent of the human genome. In addition, the company:
·
Developed
array technologies for arrays using long oligonucleotides such as cDNA
·
Developed
instrumentation to fabricate these arrays
·
Demonstrated
electrophoresis in chip format with multiple lanes and unit base resolution out
to 450 bases and beyond
The following patents for technologies related to the
ATP-funded project were granted:
Assigned to Molecular Dynamics:
·
“Denaturing
separation matrix having hydroxyethyl cellulose for nucleic acid
electrophoresis”
(No. 5,534,123: filed July 10, 1995, granted July 19, 1996)
·
“Aminosilane/carbodiimide
coupling of DNA to glass substrate“
(No. 5,760,130: filed May 13, 1997, granted June 2, 1998)
Assigned to Affymetrix:
·
“Computer-aided
probability base calling for arrays of nucleic acid probes on chips”
(No. 5,733,729: filed September 14, 1995, granted March 31, 1998)
·
“Integrated
nucleic acid diagnostic device”
(No 5,856,174: filed January 19, 1996, granted January 5, 1999)
·
“Synthesis
of oligonucleotide arrays using photocleavable protecting groups”
(No. 6,022, 963: filed April 10, 1996, granted February 8, 2000)
·
“Integrated
nucleic acid diagnostic device”
(No. 5,922,591: filed June 27, 1996, granted July 13, 1999)
·
“Photocleavable
protecting groups and methods for their use”
(No. 6,147,205: filed March 5, 1997, granted November 14, 2000)
·
“Computer-aided
techniques for analyzing biological sequences”
(No. 6,600,996: filed March 28, 1997, granted July 29, 2003)
·
“Computer-aided
probability base calling for arrays of nucleic acid probes on chips”
(No. 6,066,454: filed October 10, 1997, granted May 23, 2000)
·
“Miniaturized
genetic analysis systems and methods”
(No. 6,168,948: filed January 12, 1998, granted January 2, 2001)
·
“Process
for microfabrication of an integrated PCR-CE device and products produced by
the same”
(No. 6,261,431: filed December 28, 1998, granted July 17, 2001)
·
“Techniques
for identifying confirming mapping and categorizing nucleic acids”
(No. 7,099,777: filed January 11, 1999, granted August 29, 2006)
·
“Integrated
nucleic acid diagnostic device”
(No. 6,197,595: filed April 19, 1999, granted March 6, 2001)
·
“Systems
and methods for high performance scanning”
(No. 6,545,264: filed August 26, 1999, granted April 8, 2003)
·
“Products
and methods for analyzing nucleic acids including identification of
substitutions, insertions and deletions”
(No. 6,699,659; filed December 21, 1999, granted March 2, 2004)
·
“System
and method for self-calibrating measurement”
(No. 6,612,737: filed December 29, 1999, granted September 2, 2003)
·
“Computer-aided
probability base calling for arrays of nucleic acid probes on chips”
(No. 6,228,593: filed January 14, 2000, granted May 8, 2001)
·
“Method
of manipulating a gas bubble in a microfluidic device”
(No. 6,326,211: filed March 10, 2000, granted December 4, 2001)
·
“Photocleavable
protecting groups and methods for their use”
(No. 6,566,515: filed March 14, 2000, granted May 20, 2003)
·
“Capillary
array electrophoresis scanner”
(No. 6,554,986: filed May 25, 2000, granted April 29, 2003)
·
“Integrated
nucleic acid diagnostic device”
(No. 6,830,936: filed December 31, 2000, granted December 14, 2004)
·
“Nucleic
acid labeling compounds”
(No. 6,596,856: filed February 9, 2001, granted July 22, 2003)
·
“Computer-aided
probability base calling for arrays of nucleic acid probes on chips”
(No. 6,546,340: filed March 20, 2001, granted April 8, 2003)
·
“Nucleic
acid labeling compounds”
(No. 6,965,020: filed September 11, 2001, granted November 15, 2005)
·
“Capillary
array electrophoresis scanner”
(No. 7,090,758: filed October 31, 2002, granted August 15, 2006)
·
“Biotin
containing C-glycoside nucleic acid labeling compounds”
(No. 6,864,059: filed December 5, 2002, granted March 8, 2005)
·
“Photocleavable
protecting groups and methods for their use”
(No. 6,881,836: filed January 22, 2003, granted April 19, 2005)
·
“Computer-aided
probability base calling for arrays of nucleic acid probes on chips”
(No. 6,957,149: filed April 1, 2003, granted October 18, 2005)
·
“Nucleic
acid labeling compounds”
(No. 6,844,433: filed June 2, 2003, granted January 18, 2005)
Commercialization Status: Although MIND was never developed,
ATP funding for this project brought about Molecular Dynamics' MegaBACE 1000 sequencer,
which achieved sales of 1,530 instruments, amounting to more than $200 million
in revenue. Several successor models allowed both larger and smaller scale
sequencing. GE Healthcare continues to manufacture MegaBACE systems. It
substantially improved Affymetrix's GeneChip system, most notably the software
that allowed efficient handling of the enormous data output of GeneChip arrays.
Further developments stemming from the ATP-funded technology are the GeneChip
HuSNP System, which sequenced and analyzed human DNA, the GeneChip p53 array,
and the GeneChip CYP450 array.
Outlook: Molecular
Dynamics’ MegaBACE sequencer contributed significantly to the HGP. Successors
to the MegaBACE offer sequencing on both larger and smaller scales and have
enjoyed steady sales. Although the product originally envisioned, the MIND
device, has not been developed, the two companies developed and marketed
supporting technologies. The products based on these technologies are selling
well and are likely to remain on the market for several years to come.
Composite Performance Score: * * * *
Focused
Program: Tools for
DNA Diagnostics, 1994
Number
of Employees: 99 at project start; 1,101
as of March 2006 (Affymetrix).
Company:
Affymetrix,
Inc.
3380
Central Expressway
Contact: Robert
Lipshutz
Phone: (408) 731-5000
Company:
GE Healthcare
Contact: Carl Fuller
Phone:
Subcontractors:
·
·
California
Institute of Technology
·
Cepheid
·
·
Madison
·
Scientific
Generics
·
Soane
Biosciences (now Aclara Biosciences, Inc.)
·
·
·
·
·
Whitehead
Institute for
Publications:
Of the several hundred articles about the ATP-funded technology, the
following are a sample.
·
Bashkin,
et al. “DNA Sequencing by Capillary
Electrophoresis with a Hydoxyethylcellulose Sieving Buffer.” Applied and Therapeutic Electrophoresis, Vol.
6, pp. 23-28, 1996.
·
·
Madabhushi,
Vainer, Dolnik, Enad, Barker, Harris, and Mansfield. “Versatile Low-Viscosity
Sieving Matrices for Nondenaturing DNA Separations Using Capillary Array
Electrophoresis.” Electrophoresis, Vol.
18, pp. 140-111, 1997.
·
·
Vainer,
Enad, Dolnik, Xu, Bashkin, Marsh, Tu, Barker, and Mansfield. “Short Tandem
Repeat Typing by Capillary Array Electrophoresis: Comparison of Sizing Accuracy
and Precision Using Different Buffer Systems.” Genomics, Vol. 41, pp. 1-9, 1997.
·
Dolnik,
Xu, Yadav, Bashkin, Marsh, Tu, Mansfield, Vainer, Madabhushi, Barker, and
Harris, “Wall Coating for DNA Sequencing and Fragment Analysis by Capillary
Electrophoresis.” Journal of Microcolumn,
Vol. 10, pp. 175-184, September 1998.
·
Tu,
Knott, Marsh, Bechtol, Harris, Barker, and Bashkin. “The Influence of
Fluorescent Dye Structure of the Electrophoretic Mobility of End-Labeled DNA.” NAR, Vol. 26, pp. 2797-2802, 1998.
·
O’Connor
et al. Economic Impact of ATP’s
Contributions to DNA Diagnostics Technologies. NIST Advanced Technology
Program, GCR 06-898, January 2007.
Presentations:
·
Barker,
D., IBC Meeting on Microarray Technology,
·
Barker,
D., International Rice Genome Conference,
·
Barker,
D., CHI Meeting: Commercial Implications of the Human Genome Project,
·
Barker,
D., Satellite Symposium of the HUGO Meeting,
·
Barker,
D., CHI Meeting on Gene Quantification,
·
Barker,
D., First International Workshop on Advanced Genomics,
Research and
data for Status Report 94-05-0016 were collected during December 2005–March
2006.