A major problem with today’s cancer drugs is that they target not only cancerous cells, but many other fast-growing cells in the body. As a result, patients undergoing radiation, chemotherapy and other anti-cancer drug regimens suffer from myriad side-effects, including weakened immune systems.
Now a new sound wave-driven biochip developed by Boston University Assistant Prof. Matthias F. Schneider (ME) and collaborators in Austria and Germany could enable biomedical researchers to optimize the delivery of drugs for cancer and other diseases, so that they reach targeted cells with far more accuracy. The biochip’s developers describe the new technology in the cover story of the October 7 edition of Lab on a Chip.
“Our technique promises to dramatically increase the precision of therapy and reduce side effects,” said Schneider, a new ENG faculty member and head of the Biological Physics Group, who applies ideas from nanotechnology and physics to optimize drug delivery. “Because our surface acoustic wave (SAW) chip mimics the physical flow conditions of the human body in preclinical tests, it enables scientists to more realistically predict and optimize interactions between candidate drugs and target cells.”
Sized no bigger than a thumbnail, the microfluidic chip could form the basis of a platform to screen the performance of micro- and nano-particle-based drug delivery vehicles under a wide range of physiological flow conditions. Potential applications include anti-cancer drugs, implanted chips that monitor and deliver insulin based on blood glucose levels and drugs aimed at preventing blood clotting and thrombosis.
Tapping the Power of Sound Waves
Conventional preclinical tests of drug-to-cell interactions typically use stationary binding assays, which bring candidate drugs and target cells in contact without simulating the physiological flow conditions that pharmaceuticals actually encounter in animals or humans. Engineered to overcome this limitation, Schneider and his colleagues’ microfluidic chip produces flow in three-dimensional capillaries in which drug-toting particles and cells can interact.
Using a sound wave with an amplitude that spans only a few molecules, the researchers pumped a minute amount of liquid containing protein-coated micro- and nano-particles toward cancerous colon cells on the chip’s surface. “Similar to pumping blood through arteries, the wave is used to create the flow in which the particles are dispersed,” Matthias explained. “It’s the heart of the chip.”
In results that provided far more accurate information than those obtained from stationary binding assays, Schneider and his team found that micro-particles coated with a bio-adhesive protein attached to the targeted cells at a very high rate, whereas those lacking the protein tended to steer clear of the cells.
Exploiting the Advantages of Miniaturization
Because of its compact size, the SAW chip uses between 100 and 1000 times less material than conventional flow chambers, and can be assembled much more rapidly and inexpensively. At the same time, not a micron of real estate on the chip goes to waste.
“The beauty of this technique is that we can use nanotechnology to pump the liquid,” said Schneider. “Consequently, we don’t need any tubing or valves, and we end up with zero dead volume.”
Another advantage of the chips’ small size is that scientists can use them to test multiple variations of a candidate drug in short order and at low cost. “With this technology, we’ve shown that we only need to make very small amounts of the drug to test it,” Schneider maintained. “If you mass-produce the chips and deploy them in parallel, you can screen thousands to millions of drugs per day.”
Toward a High-Throughput Drug Screening Platform
Schneider began to design, develop and test the acoustic wave-driven microfluidic chip at the University of Augsburg in Germany with Achim Wixforth (who has patented the new technology) in 2005. Two years later he advanced this work in collaboration with the Department of Pharmaceutical Technology and Biopharmaceutics at the University of Vienna in Austria under the guidance of Franz Gabor and Christian Fillafer.
“We were trying to develop a drug to target colon cells,” Schneider recalled. “We designed a chip that mimics flow conditions around the colon that’s so open and flexible that you can grow colon and cancer cells in it. Our Austrian collaborators monitored how these cells interacted with candidate drugs, and we optimized the chip over a two-year period.”
Funded by Austrian and German national science foundations, Schneider and his colleagues are now developing a platform of SAW chips that could be used to screen drug candidates in parallel, and a disposable, lab-on-a-chip device that physicians can use to test blood samples for clotting problems and thrombosis. If all goes well, clinical applications from this research could arrive in the marketplace in two years.