This year, more than 1.4 million Americans will be
diagnosed with cancer. An extremely complex disease
family, cancer affects all types of people, from
all nationalities and genetic make-ups. Yet a lack of
knowledge and insight at the time of diagnosis often
results in a one-size-fits-all approach to treatment.
While improvements in disease detection, diagnosis,
and therapies are continually increasing the survival
rate, cancer is the second leading cause of death in
the United States, killing more than 550,000 Americans
each year.1
But Genomic Health is on the case. A life science
company based in Redwood City, CA, Genomic
Health is focused on the development and commercialization
of genomic-based clinical laboratory
services for cancer that allow physicians and patients
to make individualized treatment decisions. In 2004,
the company launched its first test, Oncotype DX™,
which has been shown to predict the likelihood of
breast cancer recurrence and the likelihood of chemotherapy
benefit in a large portion of early-stage
breast cancer patients. This knowledge enables treatment
options to be tailored to better fit patient needs
and increase the chances of survival.
Figure 1 - ARTEL MVS.
Core to Genomic Health’s success are laboratory
efficiency and quality, helping the company speed
development, and delivery, of new technologies
for cancer patients who simply do not have the
luxury of time. Given that its automated liquid handlers are used in a large number of its critical
processes and tasks, Genomic Health maintains
a rigorous liquid handling quality assurance program
using the MVS® (Multichannel Verification
System) from ARTEL (Westbrook, ME) (Figure
1). The MVS employs a rapid, robust technology
that can quickly measure the volume transfer performance
of liquid handling devices. This system
provides data on liquid handling accuracy as well
as precision, even at very small volumes. And this
has helped Genomic Health grow confidence in its
liquid handling operations.
The impact of one microliter
As a company aiming to analyze cancer at the
molecular level, it is essential that Genomic
Health’s liquid handling devices perform accurately
at the microliter level. This is true for both
its commercial and R&D laboratories.
Genomic Health’s diagnostic innovations are born
in its research and development laboratory. Here,
scientists conduct research and clinical studies to
develop new innovations and product features to further
the company’s efforts to improve cancer treatment.
The commercial laboratory is tasked with
analyzing tumor samples using the company’s proprietary
diagnostic kits, and providing detailed reports
to oncologists to guide patient treatment.
“We do a substantial amount of pipetting using our
automated liquid handlers and, due to the quantitative
nature of our assays, accuracy is critical,” according
to Keith Volk, Assay Development Engineer,
Genomic Health. “Inaccuracies of one microliter
can make a large difference in results, with errors
resulting in inefficiency and loss of productivity.”
To illustrate the prevalence and importance
of liquid handling at Genomic Health, consider
the company’s first commercial diagnostic
assay, the Oncotype
DX. The development
of this product, which quantifies
the likelihood of distant breast cancer recurrence
and allows for better treatment selection,
relied heavily on liquid handling, as do
current analyses performed with it.
The analysis process starts once a mass in a
patient’s breast is identified by a physician
as malignant, at which point the tumor is
sent to a pathology laboratory. This laboratory
preserves the tumor, embeds it in
paraffin, and sends it to Genomic Health
for further analysis using the Oncotype
DX specimen kit. Genomic Health’s commercial
laboratory extracts tiny amounts
of RNA from the paraffin-embedded
tumor specimen and the diagnostic process
begins.
Automated liquid handlers are used in almost every
step needed for sample analysis, from quantifying
the RNA and checking for DNA contamination
to reverse transcription and qPCR testing. The
objective of the process is to measure the expression
levels of the RNA in the given panel of genes, and
this measurement is used to determine the percent
chance of disease recurrence in a given period of
time. An accurate measurement of expression levels
is contingent upon accurately quantifying the
amount of starting material. If only half of the desired
sample material is initially dispensed, the measured
expression level could quite possibly be affected.
The R&D laboratory uses many of the same processes
as the commercial laboratory. Here, automated liquid
handlers are used to continually run patient samples
to develop new products and conduct validation
studies. Although results from the R&D laboratory
are not used for patient treatment, accurate and precise
volume deliveries are critical to correctly steer
development efforts and eliminate inefficiency.
Quality assured
To strengthen confidence in results and quickly verify
the performance of its automated liquid handlers,
Genomic Health relies on the ARTEL MVS. The
MVS is a standardized platform that produces traceable
accuracy and precision measurements in minutes,
providing the ability to quickly rule out errors
in liquid handling processes. Additionally, due to the
standardized, traceable data provided by the MVS,
Genomic Health’s liquid handlers all can be directly
compared for dispensing the same critical volumes in
their assays, which is especially important when different
liquid handlers are performing identical tasks.
“We have extensive quality control processes in
place to ensure accurate and precise diagnostic test
results,” said Volk. “And the MVS is an important
part of that process. The system gives us confidence
that our robots are pipetting what we asked them to
pipet across all volume ranges.”
The MVS is based on ratiometric photometry,
ARTEL’s proprietary technology that measures the absorbance of light by two specially formulated dyes
to verify volume. Bar codes on the MVS’s microtiter
plates, reagents, and calibrator plate contain metrological
information that is passed to the system’s
software through scanning. The software also automatically
records the photometric measurements
taken by the MVS and rapidly determines both
the accuracy and precision of the volume delivered
from each individual tip of the device being tested.
In addition to automated documentation, the system
provides results traceable to the NIST. As well
as instilling an additional level of confidence in data
integrity, traceability also allows Genomic Health to
meet regulatory requirements, including those set forth
in the Clinical Laboratory Improvement Amendments
(CLIA), which the company is required to follow.
The importance of accuracy
Laboratory life before the MVS was not so easy.
While Genomic Health always took care to ensure
quality in its liquid handling operations, its previous
verification process was more painstaking.
One method involved photometric measurement
using tartrazine dyes. This process was time consuming
due to lengthy reagent preparation. A more
critical drawback of the tartrazine method was its
inability to provide accuracy information. While
the method measured how close the dispensed
volumes—from each channel of the liquid handler—were to each other, it was not able to determine how
close the dispensed volumes were to the required
target volumes. “A huge advantage of the MVS is its
provision of both accuracy and precision information
in one rapid run,” explained Volk.
To derive accuracy and precision information
before it implemented the MVS, Genomic Health
employed gravimetric calibration, which uses a balance
to weigh dispensed liquid quantities to determine
volume. This process was time-consuming,
requiring multiple dispenses to verify each individual
channel in an automated liquid handler. Gravimetric
calibration also has limitations at low volumes,
and is affected by vibration, evaporation, and other
environmental conditions.
Streamlined process
With the MVS in place, Genomic
Health is able to streamline its liquid
handling quality assurance program
and strengthen confidence in
results. The company verifies the
performance of its automated liquid
handlers on a quarterly basis. This
frequent monitoring schedule, permitted
by the MVS’s speed and ease
of use, ensures that Genomic Health
has ongoing performance data on
its robots and reduces risk of error.
“The MVS is easy to use, facilitating
a frequent performance monitoring
schedule,” said Volk. “Training new
employees is a painless process.”
The rapid performance of the MVS
also allows Genomic Health to
calibrate new liquid handlers with
a range of volumes and specific tip
types. If a tip vendor goes out of business
or runs out of stock, the company
will be able to easily and rapidly
switch to a previously qualified tip to
avoid a lag in productivity.
The MVS is also used after instrument
maintenance to ensure that
newly installed parts are functioning
properly. Multiple calibrations
are run until all parts are properly
installed. “The MVS has made a
big difference in our laboratories,
both from an efficiency point of
view, as well as from a confidence
standpoint,” summarized Volk.
With a stringent liquid handling
quality assurance program in
place, Genomic Health scientists
can focus their efforts on
more important issues, like analyzing
cancer.
Reference
- Cancer Facts and Figures 2007.
American Cancer Society, www. cancer.org.