Droplets Key to Next Generation Diagnostic Testing Tool

Two Duke electrical engineering postdocs parlayed their graduate work into a new business in the spring of 2004. Advanced Liquid Logic founders Michael Pollack, Ph.D., and Vamsee Pamula, Ph.D., are now carefully cultivating their company at a new business incubator in Research Triangle Park, N.C.

The concept behind Advanced Liquid Logic is simple–— take advantage of a natural property of liquid drops called surface tension. Surface tension keeps drops sphere-shaped instead of flattened out. Pollack and Pamula have created a palm-sized microfluidic processor that uses electrical fields to manipulate nanoliter size droplets. The pair plans to market their technology to automate common clinical diagnostic tests.

“We’re essentially creating a point-of-care device that will enable doctors and clinical care staff to conduct laboratory tests right at a patient’s bedside,” said Pollack.

In the late 1990s, when the concept of a “laboratory on a chip” became the buzz of the business world, researchers began investigating ways to miniaturize the chemical analyses that occur in a full-size laboratory. Some took the approach of creating increasingly smaller pipes, pumps and valves to transport streams of liquid from one place to another.

Pollack saw an opportunity to sidestep pumps and valves completely, and work instead with discrete droplets. He uses sets of electrodes to create electrical fields that manipulate the surface tension of fluid drops. In this way, he can pinch off nanoliter-sized drops from a fluid reservoir, repel or attract the drops to force them along a path, and mix multiple different fluids together.

“It’s like an electronically controlled moving sidewalk for drops,” said Pamula.

The palm-sized microfluidic processor can conduct all the activities that take place in a common clinical diagnostic laboratory. Plus, the volume of liquid needed is very small, so tests don’t require as much chemical volume, and that reduces the overall cost of tests. This approach fully automates the diagnostic testing process and doesn’t require highly experienced users.

The electrode-controlled pathways are sandwiched between two plates and the entire cartridge is filled with oil. Oil maintains a thin film around the droplets, preventing sample evaporation and cross contamination.

“Our platform is highly programmable,” said Pollack. “We can run a single test, multiple runs of the same test, or multiple different diagnostic tests–— all at the same time.” The platform can also run calibrations to validate diagnostic test results as they are being performed.

Pollack and Pamula envision a dizzying array of opportunities for their platform including pharmaceutical drug discovery, human and veterinary medicine, and bioterrorism monitoring applications, but the first commercial application they are working on is for premature babies.

“One of the practical problems with premature, low birth weight babies is that they have so little blood,” explains Pamula. “An extremely low birth weight baby could have as little as 40 milliliters or about 2.5 tablespoons of blood, and that limits the number and kinds of tests doctors can perform.”

Current technology requires an average blood sample size of about 100 microliters. “That’s about 1/400th of 40 milliliters, which doesn’t sound like a huge fraction, but these babies typically require multiple blood transfusions to make up the volume they lose through testing,” said Pollack.

Using the microfluidic processor approach, Pollack and Pamula can work with samples as small as 1 nanoliter. To put that into perspective, there are about 10,000 nanoliters in a drop. “Theoretically, we could perform 10,000 tests on a single drop of blood,” said Pollack.

The team won a Small Business Innovation Research grant from the National Institutes of Health to work on this healthcare issue. They are collaborating with Dr. David Tanaka of Duke Hospital’s Neonatology Division.

Pollack and Pamula ultimately hope to team up with a large medical diagnostics company to create a viable commercial product. “We envision our platform as one part of a test kit. We want to supply the microfluidic processor that controls and runs the diagnostic tests. Our platform could fit inside a larger cartridge that includes reservoirs of the chemical reagents needed for certain diagnostic tests.”

Test result data could be displayed, stored, or wirelessly exported to hospital databases or printers. “We can design the data interface to meet the specific needs of the application,” said Pollack.

“We plan to bring a product to market within the next two years,” said Pollack. The team has research and development funding from two NIH small business grants totaling $350,000, and support from the Duke New Ventures Program. “We are looking for investors and development partners right now,” he said.

For more information about Advanced Liquid Logic, visit their Web site at: www.liquid-logic.com.

Pollack and Pamula both studied under electrical and computer engineering professor Richard Fair. Pollack received his Ph.D. in 2001 and Pamula received his Ph.D. in 2000.