By Jonathan Briggs
The miniaturization and integration of electronic and fluidic devices is rapidly changing the look, feel and operation of clinical laboratories. At the same time, devices such as Metrika’s A1cNOW tests, which monitors HbA1c, are bringing just as significant changes to the point-of-care arena.
Photo: Robb Hesley, Metrika’s vice president of research and development, and Michael Allen, founder and CEO, in the Metrika R&D lab with the A1cNOW device.
Company lore has it that Metrika founder and CEO Michael Allen was on a plane when he got the idea for a calculator-like device that could provide quantitative tests results quickly. After all, Allen thought, if Texas Instruments can build a reliable, easy-to-use handheld calculator for just a few dollars, why shouldn’t it be possible to build similar devices to perform medical tests?
When Allen first formed Sunnyvale, Calif.-based Metrika Inc., in 1993, he did not have a specific medical test in mind. By late 1994, with his core development team in place, design work began and the developers started looking at potential markets. One of the first to pop up was HbA1c, the blood marker used to profile glucose control in patients with diabetes.
HbA1c, or glycated hemoglobin, is a specific, stable compound formed when glucose irreversibly binds to hemoglobin. Because the life span of red blood cells ranges from 90 to 120 days, HbA1c values are directly proportional to the concentration of glucose in the blood over a period of about three months. This makes HbA1c an excellent marker for monitoring long-term glycemic control. By monitoring HbA1c, people with diabetes can reduce the frequency of complications associated with the disease and in turn, reduce the cost of care. But putting the test in a pager-size, easy-to-use device was a significant challenge.
“HbA1c is extremely difficult from a chemistry perspective. A number of companies have attempted to develop a high-quality HbA1c test, and have not been successful,” said Robb Hesley, vice president of research and development at Metrika. One difficulty is that an HbA1c result requires measuring two analytes, each with a different test. A patient’s overall hemoglobin is measured by general chemistry and then his HbA1c fraction is measured. Methods to determine HbA1c levels range from electrophoresis and ion exchange chromatography to immunoassays that use very specific and rare antibodies. Until Metrika developed the A1cNow, this meant that the test was done almost exclusively on benchtop equipment that required highly skilled operators, longer turnaround time, or both. “There are very few devices and none in the home point-of care-environment that can do those two different types of test simultaneously,” said Hesley.
“Right from the beginning the concept was for this product to be free-standing and completely disposable. This made people ask, ‘Why did you do that? With all the technology you’ve developed here, you could turn this into a meter strip configuration like a glucose meter,’” recalled Hesley. But HbA1c tests do not have to be performed as often as blood glucose levels. “The best analogy is a pregnancy test — an infrequent test that a person is going to run at home or in a physician’s office. Because it will be used infrequently, they don’t want to keep track of a meter — keep it charged, keep up with the latest calibration information,” explained Hesley.
Performing a test with the A1cnow device is simple. To start the self-activating device, a sample of whole blood (from a finger prick) is diluted in a buffer solution and then placed in the sample port. There is no need to flip switches or push any buttons — in fact, there are none. The device contains all the microelectronics, optics and dry reagent materials (solid- state chemistry) needed to complete the test. There are two dry reagent strips, each with an HbA1c test zone and a total hemoglobin test zone. An internal microprocessor uses reflectance from the strip test zones to calculate the percent of HbA1c. The test result appears in numeric form on a LCD just eight minutes after the blood sample is placed in the port.
In addition to their desire to meet the technical challenge of putting a test like A1c on an easy-to-use, disposable platform, Allen and his Metrika team also were motivated by the fact that such a device would fit right into how diabetes care is done. Most diabetes patient care takes place in physician offices, small clinics and the home. However, most HbA1c testing is done at central labs, which means that physicians and patients usually have to wait several days for the results. Often the patient has to make a second trip to the doctor’s office or clinic to get those results, and more often this important test is not done. The A1cnow provides immediate access to accurate HbA1c results with a test time of eight minutes.
In fact, it was this quick turnaround time that led to the product’s name. Brian Segrin, Metrika’s national director of marketing and sales, reported that during market research physicians and healthcare professionals consistently commented on the A1cNOW’s immediacy and how important it was that the test be conducted during the patient’s office visit.
Of course patients and healthcare professionals were not the only ones who had to approve of the product. For the A1cnow to be approved for use outside a central laboratory, it would need to be granted waived status under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). “Our goal from the very beginning was that the device had to meet the CLIA waiver requirements,” said Hesley.
Michael Allen’s original idea to produce a medical test device that mimics a handheld calculator not only led to the A1cnow, but other single-use, self-contained quantitative tests that use the same platform. The other tests, still under development, include a microalbumin/creatinine urine test and a lipid panel that gives total cholesterol, HDL and direct LDL. The quick, point-of-care results provided by these devices may well provide an additional benefit beyond convenience and ease of use — better care. “We know from studies that if physicians counsel patients while they are there, in the office, patients are much more likely to follow through with changes in their treatment plan,” said Segrin. Even the best test in the world is of little value if nothing is done with the results.
Jonathan Briggs is a freelance writer based in Tijeras, N.M., who specializes in healthcare topics.
