Centered on Success

CBME fosters biomedical engineering research and education at UNM

A test tube made of water. A "Post-It note" of cells. A diagnostic device smaller than a human cell. Sound futuristic? Actually, they're in development now at the Center for Biomedical Engineering. Established at the School of Engineering in 2005, the CBME is an interdisciplinary center that coordinates research activities in biomedical engineering (BME) among engineers, clinicians, and biologists. The CBME is also a strategic first step toward the ultimate goal of providing a full range of BME educational opportunities at UNM. The center has already fostered research among disciplines and with the high-tech industry, has hired faculty, and developed an outreach program for K-12 students. Each of those efforts supports the CBME's goal of improving New Mexico's educational, research, and economic environment.

In just two years, the center has received $8 million in grants. "We've already produced a 17-to-1 return on the university's investment," says Gabriel Lopez, director of the CBME and professor of chemical and nuclear engineering and chemistry. "We're really proving that this kind of collaboration can be achieved here at UNM."

Here's how some CBME researchers are engineering better medicine:

Droplets of DNA

Imagine a billion glass test tubes lined up, row after row, in a gigantic laboratory. Now, shrink that picture. Way down. Dimiter Petsev, assistant professor of chemical and nuclear engineering is using his expertise in microfluidic devices to fabricate miniaturized test tubes made of water droplets. Jeremy Edwards, assistant professor of molecular genetics and microbiology and assistant professor of chemical and nuclear engineering, plans to use billions of these tiny test tubes to develop a fast, inexpensive way to sequence the DNA of patients with different cancers or even an individual's entire genome.

Each tiny drop, about ten microns in diameter, is loaded with a small fragment of DNA and a bit of reactant. Then, the droplets are suspended in an oil emulsion and used for tests. Once the droplets are floating in the emulsion, Edwards uses a chemical process to break the droplets open. He reads the biochemical results emanating from streams of these broken "test tubes" using a customized microscope, one of only two in the world. The collaboration, which also involves researchers at Harvard University, is organized by the CBME and is part of the National Science Foundation Partnership for Research and Education in Materials: UNM/Harvard Partnership for Leadership in Biomaterials.

Petsev's challenge is to fabricate these minute droplets in a uniform size and shape. With input from Harvard researchers, Petsev has achieved very fast production of highly uniform droplets using microfluidic devices formed using a process called soft lithography. Through this process, a network of channels 10-100 micrometers deep and wide can easily be formed in a silicone rubber material. Petsev then bonds the printed polymer channels on a glass slide and uses pressure or electric fields to force oil and water through separate channels. The droplets form where the channels intersect. Petsev's next challenge is perfecting the process of loading the DNA fragments into the droplets.

Petsev and Edwards have been collaborating through the CBME for a year and a half. Petsev says access to the CBME facilities has been critical, but the opportunity to collaborate is most important. "There's an exchange of information and ideas here which is very beneficial for our multidisciplinary work." Edwards agrees. "I have an engineering background but I don't have the ability to make microfluidic devices. With engineers like Dimiter bringing their skills to the table, we can achieve our goals."

Solution: Smart Surfaces

Angela Wandinger-Ness, professor of pathology at the School of Medicine, needed a better process for one facet of her research. Heather Canavan, assistant professor of chemical and nuclear engineering, had the perfect technique. The CBME brought them together in a successful research collaboration.

Wandinger-Ness studies cells and how therapeutic drugs interact with them. Her goal is to analyze single cells and measure protein levels on their surface using a flow cytometer, a machine that measures particles in a streaming fluid. Currently, Wandinger-Ness uses enzymes to remove cells from surfaces like Petri dishes, on which they are grown. Then she places them into suspension, where they can be analyzed by flow cytometry. Her concern is that the enzymatic process destroys some of the proteins she wants to study.

Canavan's new technique is a perfect fit. She studies "smart surfaces," thermoresponsive polymers with properties that change based on environmental cues like temperature or electrical field. By growing cells on these smart, flexible surfaces, Canavan can create clumps of cells that peel off like a Post-It note, or even isolate single cells that pop off the polymer without changing their structure.

The researchers' ultimate goal is to create an off-the-shelf device that Wandinger-Ness could use to allow accurate cell analysis. Canavan says the research wouldn't have been possible without the CBME. "Gabriel Lopez made the initial connection between the two sides and the CBME provided financial support," says Canavan. "There was both an intellectual and financial contribution that was very significant."

One Bead, Two Innovations

Two sides of campus, two disciplines, two goals, one shared interest: microscopic beads. Gabriel Lopez and Larry Sklar, professor of pathology at UNM's School of Medicine, are collaborating on fluorescent biosensors that use tiny, protein-coated beads the size of a human cell. While their research goals are different, it's a strategic collaboration because the researchers share an interest in the microbiosensors and in biochemistry. "It's technically a natural fit and our work is nicely complementary," says Lopez. The two researchers, along with Tione Buranda, research assistant professor in the Pathology Department, have shared a series of five-year grants during their twelve-year collaboration.

Sklar uses the beads for drug discovery, coating them with a specific protein and suspending them in a fluid that he wants to test. By running the suspension through a flow cytometer, Sklar can evaluate the reaction of the proteins on the surface of the beads with those in the solution. Using this process, Sklar and Buranda can screen molecules involving more than a dozen molecular interactions that contribute to cancer, infectious diseases, and inflammatory diseases. Sklar says collaborating with engineers at the CBME moves the team closer to its goals. "An engineer's skill set is complementary to those of a biomedical scientist," he explains. "One of the biggest factors is the different types of materials that we use for building sensors or instrumentation. Engineering students have different interests in technology than biologists, including materials, fluidics, automation, electronics, and computers."

Lopez and his team use the beads to create diagnostic assays. They make chip-based, microfluidic devices by packing thousands of the protein-coated beads into tiny glass capillaries. Lopez injects a fluid, for example a blood sample, into the bead-packed channels. When he exposes the channels to a laser, the beads that are attached to specific proteins fluoresce, indicating the presence of a toxin or disease marker in the liquid. Lopez and his team are currently testing such devices, using samples from patients with respiratory infections. The devices have already successfully detected several different viruses in one small sample.