Aha!

Bio-Rad Laboratories
2007 Annual Report

A case of stick-to-itiveness.

The idea of running multiple laboratory tests with a single patient sample is a powerful notion, as the resulting economies of time, cost, and labor are of obvious benefit. If a person has trouble breathing, a single test to measure both acidity (pH) and the levels of oxygen and carbon dioxide in the blood can pinpoint the problem — avoiding the need to perform separate tests to isolate the cause. Perhaps even more importantly, this process could benefit patients further, for example, when testing for multiple biomarkers. When additional markers for a specific disease can be tested, the resulting information provides even greater confidence in the results.

Welcome to the field of multiplex analysis.

In the mid-1990s, when scientists wanted to identify and count T-cells in a blood sample, they used a device called a flow cytometer, a machine that counts, examines, and sorts cells suspended in a stream of fluid. These systems could also be used to run multiple immunoassays of proteins using latex beads — small and uniform. One of the problems researchers faced with this method, however, was that when the beads were isolated in preparation for their run through the instrument, some debris remained behind, which, if large enough, could interfere with the measurements, leading to spurious results.

In 1996, Bio-Rad researchers theorized that beads with an iron layer under their surface, could, in the presence of a magnetic field, adhere to the walls of the container and allow the liquid (and debris) to be removed by aspiration, leaving the purified proteins — precisely what the researchers wanted to measure — behind on the beads. After adjusting the composition of the magnetic beads, the Bio-Rad team successfully developed a highly effective method for flow cytometric-based immunoassay.

But the story of innovation didn’t stop there. Recognizing the potential benefits of multiplexing, Bio-Rad researchers directed their attention to the technology itself, and how it was used in the laboratory. Using magnetic beads, would it be possible to multiplex in a way that was automated and dependable — with the push of a button?

By 1998, Bio-Rad began to develop a system dedicated to the performance of multiplex immunoassays using magnetic beads and incorporating a number of important features that translated into higher reliability, faster throughput, better ease-of-use, and lower costs. The resulting combination represented a powerful new way to commercially test for analytes useful in the diagnosis and treatment of a wide variety of diseases.

The A1Cs of diabetes monitoring.

Given the advancements in diabetes treatment today, it’s easy to forget how far we’ve come from the days when scientists first began to gain a better understanding of diabetes and how patients could minimize long- term complications from this disease.

Since the 1950s, diabetics have managed their disease by monitoring the sugar (glucose) level of their blood to determine the level of insulin their body required at a given time. However, for the many diabetics who manage their disease with a combination of diet, exercise, and medication, monitoring their glucose levels on a regular basis is not the only way of letting them know how effective their therapy is over a longer period of time.

In the 1970s, it was discovered that “glycosylated” hemoglobin (GHb), which contained a protein called hemoglobin A1, showed elevated levels in diabetics. GHb offered insight into average blood glucose levels in diabetics over a several-month period, and therefore provided a more representative baseline for monitoring and controlling their disease. This exciting development was tempered by the fact that testing hemoglobin A1 was a cumbersome and expensive process.

Upon the discovery of hemoglobin A1, Bio-Rad researchers began to think of ways to provide more efficient separation that would be suitable for routine use in the clinical laboratory. By 1978, the Bio-Rad team developed the first commercial test for monitoring hemoglobin A1 in diabetics using a small, disposable, and inexpensive open chromatography column.

Further efficiencies were still to come. The separated hemoglobin A1 still contained impurities that affected the measurement, causing some uncertainty in the results. By 1982, in the process of eliminating these interferences caused by impurities associated with the existing test, Bio-Rad became the first company to measure A1C, a subset of hemoglobin A1 and a more precise indicator of average blood glucose levels over time. As the new test became established as a useful clinical tool, test volumes increased rapidly, and Bio-Rad introduced a series of automated high-performance liquid chromatography (HPLC) platforms to further improve performance and laboratory efficiency.

Today, Bio-Rad advancements continue to lead the way in monitoring treatment regimens for the more than 14 million Americans who have been diagnosed with diabetes and who are part of the approximately 200 million worldwide who suffer from the disease.

What goes best with green fluorescent bugs? Kids.

In the span of just a few short years in the mid-1990s, the world gained a newfound appreciation for the importance of DNA, thanks to a perfect storm of biotechnology events then sweeping through the popular culture: the televised proceedings of a spectacular, forensics-based criminal trial; a best-selling book, which speculated that dinosaurs could be cloned from DNA extracted from a mosquito preserved in amber for millions of years; and the ongoing sequencing of the human genome — a breakthrough that promised untold possibilities for the improved health of our species.

Even as terms like cloning, double helixes, and human genome became part of the vernacular, another revolution, this one under the radar, was quietly brewing. Science teachers around the world were clamoring to find ways to keep their curriculum up to date by integrating this exciting new revolution in biotechnology into their classrooms. What better way, after all, to engage students’ curiosity and observational abilities than with subject matter that could be made relevant to the events going on around them?

Around this time, the answer to that question came to Bio-Rad’s Ron Mardigian: why not a biotechnology outreach program for high schools? Instead of dissecting frogs in biology class, students could learn how real-world methods and applications work on instruments that were actually used in laboratories.

Thus was born a program that would turn into one of private industry’s most successful partnerships with academia. Ron — himself a former high school teacher — and a group of Bio-Rad scientists worked closely with educators to determine appropriate curricula for the program, and bundled lesson materials with corresponding Bio-Rad equipment into comprehensive and hands-on classroom kits, that would, as Ron put it, “emulate real-world science in a way that was fun and engaging.”

The idea resulted in curriculum subjects that spanned the spectrum of popular science. These included the kit in which students use a jellyfish gene to genetically engineer green fluorescent bacteria, one in which they capture their own DNA and turn it into a necklace called “Genes in a Bottle™”, and yet another in which they discover the importance of the diversity of species in a rain forest. It didn’t take long before the program took off, and with it the imagination of students everywhere.

Who knows what they will discover next?