A Lab in your Pocket
by Marcia Goodrich
If you were feeling a little under the weather on Star Trek, there wasn't a lot of waiting around for a diagnosis. You didn't have to describe your symptoms to your doctor, and you didn't have to yield a vial of blood for shipment out to a lab for tests. Perhaps most importantly, you didn't have to pace the floor for days, wondering if that headache was a brain tumor or allergies. Bones simply scanned you with his medical tricorder and announced (whew!) that you've got hay fever.
Adrienne Minerick doesn't expect that physicians will be wanding patients with gadgets anytime soon. But the associate professor of chemical engineering is now working on a technology that may one day provide a diagnosis from a single drop of blood just as quickly as Dr. McCoy's tricorder.
Minerick's research revolves around a property called dielectrophoresis: the ability of uncharged or polarizable materials (like red blood cells) to scoot around when subjected to an electric field. Particles move in different ways, depending on their structure and properties.
Human red blood cells carry thousands of different proteins, sugars, and other substances that vary widely, even among healthy individuals. They can also carry parasitic infections such as malaria or genetic diseases such as sickle cell anemia and, perhaps, as-yet-unknown markers that signal the presence of hard-to-diagnose maladies such as lupus.
When protein variations occur on cell membranes, they can affect how cells move under dielectrophoresis. Minerick's team has exploited these differences to develop two new microdevices (one AC, one DC) to discern the eight blood types: A-positive, B-positive, AB-positive, O-positive, A-negative, B-negative, AB-negative, and O-negative. "The reason this works is because the ABO antigens are polysaccharides housed on the outside of the cell membrane, while the Rh factor is a protein that goes through the membrane," she says.
The AC blood-type microdevice has electrodes spaced 150 microns apart and can be observed under a microscope. Cells are exposed to a range of electrical frequencies, causing them to arrange themselves in specific patterns around electrodes, like a marching band at half time. "You can actually see the cells line up into chains along the curved field lines," Minerick said.
The second tool is a DC blood-type tester about the size of an iPod nano, with electrodes at both ends. Insulators are placed in the path of the electric field to create a field gradient, essentially changing the shape and intensity of the field. A fork-shaped network of microchannels, each about the width of a human hair, is cast into a flexible polymer, which is capped by a clear, thin glass slide.
A drop of blood diluted in a saline solution is introduced into a small reservoir at the inlet, at the end of the fork's "handle." As the electric field is applied, the cells flow through the microchannels and around the insulator, which deflects them into one of the four outlet channels, depending on their blood type.
Such medical microdevices will one day be portable. "We are engineering these separations at low fields such that they can run off of a small battery," says Minerick.
Each device has its pluses and minuses. The DC tester is not quite as accurate, but it's a continuous flowing system. "You can test as many cells as you want to," Minerick says.
The AC device has a bonus. Tune the frequency just so and you rupture the cells, releasing their contents. That may open the door to even more refined diagnostic tests on these subcellular components. It may also help doctors determine if a given treatment is benefiting the patient.
"For a new drug to be approved by the FDA, pharmaceutical companies only have to show that it works on a majority of the population," says Minerick. Once a course of treatment begins, it can take weeks or even months to determine if it is working. "If there were some way to check the body's response more quickly, physicians could be confident that the drug was working, or they could move on to another treatment."
For now, Minerick's team is working to develop tests for cell membrane molecular expression, like blood type, and is seeking funding to expand into detecting conditions like malaria and sickle cell anemia, which impact the structure of the entire red blood cell.
Ultimately, she aims to be part of a revolution in the practice of medicine.
"We want to develop medical microdevices for doctors that get a result right away using only a single drop of blood," Minerick says.
In developed countries like the US, that would mean huge savings in time and money, not to mention patient angst. For developing countries, it could provide medical services that were once prohibitively expensive or simply unavailable. Because of its portability, it would be easy to use in disaster-struck regions where medical infrastructure has collapsed.
If used routinely, such devices might even detect serious illnesses before symptoms even develop, thus increasing the chances of the treatment's success. So, in the not-to-distant future, Dr. McCoy's tricorder might not seem like such a big deal after all.