When Analyzing Cancer at the Molecular Level, Microliters Matter

By Genomic Health | Case Study

Laboratory Challenge

Over 1.4 million Americans are expected to be diagnosed with cancer this year. 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

GH1But Genomic Health is on the case. A life science company based in Redwood City, California, 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, Genomic Health launched its first test, Oncotype DXTM, 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.

As a company aiming to analyze cancer at the molecular level, it is essential that Genomic Health’s liquid handing devices perform accurately at the microliter level.

“We do a substantial amount of pipetting using our automated liquid handlers and, due to the quantitative nature of our assays, accuracy is critical,” says 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.”

The development of the Oncotype DX relied heavily on liquid handling, as do current analyses performed with it.  Automated liquid handlers are used in almost every step needed for sample analysis conducted at Genomic Health’s commercial laboratory, 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.

Genomic Health’s previous liquid handler verification process was painstaking. One method involved photometric measurement using tartrazine dyes. This process was time-consuming due to lengthy reagent preparation and did not provide accuracy information.

To derive accuracy and precision information, 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 has limitations at low volumes, and is affected by vibration, evaporation, and other environmental conditions.

Solution

Now, to strengthen confidence in results and quickly verify the performance of its automated liquid handlers, Genomic Health relies on the Artel MVS® Multichannel Verification System. The MVS is a standardized platform that produces accuracy and precision measurements in minutes.

“A huge advantage of the MVS is its provision of both accuracy and precision information in one rapid run,” says Volk.

Additionally, due to the 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. Traceability also allows Genomic Health to meet regulatory requirements, including the Clinical Laboratory Improvement Amendments (CLIA).

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. The system’s software automatically records the photometric measurements taken by the MVS and rapidly verifies volume delivered from each individual tip of the device being tested.

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 switch to a previously qualified tip to avoid a lag in productivity.

Results

With the MVS in place, Genomic Health is able to streamline its liquid handling quality assurance program and strengthen confidence in results. The MVS’ speed and ease-of-use permit frequent monitoring to ensure that Genomic Health has ongoing performance data on its robots and reduce risk of error.

“The MVS has made a big difference in our laboratories, both from an efficiency point of view, as well as from a confidence standpoint,” summarizes 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.


About Genomic Health

Genomic Health, Inc., a life science company founded in August of 2000 and located in Redwood City, California, conducts sophisticated genomic research to develop clinically validated molecular diagnostics, which provide individualized information on the likelihood of disease recurrence and response to certain types of therapy. These diagnostic technologies generate information that physicians and patients can use in making treatment decisions. For more information, contact Genomic Health at 301 Penobscot Drive, Redwood City, CA 94063; Tel: (650) 556-9300; Fax: (650) 556-1132; Website: www.genomichealth.com.


Reference

1 “Cancer Facts and Figures 2007.”  American Cancer Society. www.cancer.org.