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To clot or not
Anya Yermakova , 2008 Amgen Scholar, creates a biomedical tool from scratch

When Amgen Scholar Anya Yermakova first arrived in Danilo Pozzo’s Chemical Engineering lab last summer, her new mentor handed her a sheet of paper with some background information and a rough sketch. The 10-week mission: to design and create a portable microfluidics ‘chip’ that assesses the ability of blood to clot.

Then a senior at Northwestern, she had created her own curriculum consisting of a triple major in music (she has won national awards for piano), biochemistry, and the philosophy of science and logic. Although Yermakova had spent her previous summers in engineering labs, she had never before created a biomedical tool from scratch. A summer with the Amgen Scholars Program at the University of Washington in Seattle would give her the chance. 

The project was also new for Pozzo, an assistant professor of chemical engineering at the University of Washington in Seattle. His main research focus is the relationship between the structure and the mechanical properties of blood clots. His group studies them using a number of engineering techniques, such as neutron and light scattering. But Pozzo had wanted to put his basic knowledge about blood to work, in a chip that might ultimately assess a patient’s ability to clot blood. The timing was fortunate: Yermakova requested to work in his lab because she admired the way his research tied together areas of engineering and biology.

Training for tweaks:
Like many other Scholars, Yermakova spent the first week learning how to use the lab equipment and reading a stack of articles. Then, with some input from Pozzo and graduate student Katie Wiegandt, she started designing the chip.

First, she researched the properties of two artificial blood components -- fibrinogen and thrombin -- which she would use to calibrate her chip. Fibrinogen is the main protein substrate involved in blood clotting, and thrombin is the enzyme that converts fibrinogen into long strands of fibrin. Because she was using the solutions in place of blood, "the concentrations had to be biologically relevant,” she says.

She then used the department’s laser to engrave channels on various plastics. But she quickly realized that the laser wasn't precise enough to make the tiny grooves she'd need on the chip. The winding channels had to be no more than 200 µm wide, or approximately the width of two human hairs.
So Pozzo and Weigandt suggested Yermakova try manufacturing the chip using photolithography, a technique used to transfer three-dimensional shapes to the surface of a malleable, silicon-based plastic. “I had never done that, so it was really exciting and totally new,” Yermakova says. She went through a two-day training session and immediately started fabrication. “The whole process of creating the chip is very meticulous,” she says. “So if there’s one thing you mess up even a little bit, you have to do the whole thing over again.”

The idea was to create a chip that contained two separate wells into which she would load the fibrinogen and thrombin. When she pressed a button, the fluids would combine by flowing together in a long channel. The higher the concentration of fibrinogen, the quicker the clot would form along the length of the channel, revealing the quantifiable “clottability” of the sample. 

Once the chip was fabricated, getting it to work was another challenge entirely. In some cases, bubbles would appear and stop the flow of fluid through the channel. Despite this problem, Yermakova was able to create 10 chips that consistently assessed the clottability of physiologically relevant concentrations of fibrinogen solution.

Ideas abound:

During the 2008 Amgen Scholars U.S. Symposium at the University of California, Los Angeles, she showed an early prototype of the chip to her colleagues. Although she hadn't worked out all of the experimental kinks, she documented the work in a 10-page protocol, which will be used to continue the development of the chip. “I had all these other ideas of how to solve the bubble problem,” she says. “I just didn’t have time to try all of them.”

Yermakova says her experience with the Amgen Scholars Program triggered her interest in systems biology, which she is pursuing during doctoral studies in mathematical biology at the University of Oxford. She is one of only 32 Rhodes Scholars selected from the U.S. last year, out of 769 students nominated by their schools across the globe.

There’s no telling what Yermakova will ultimately do with her skill set. “She has a particular combination of personal characteristics and abilities that have enabled her to develop her potential in more diverse areas than perhaps anyone I’ve ever met,” says John Alongi, a senior lecturer in Northwestern’s math department who instructed Yermakova in two courses. “A lot of people dip their toes in various interests and disciplines but she actually yearns and has the potential to be a universalist,” he adds.

Yermakova approaches her diverse areas of interest in math and science with the same mixture of rigor and imagination. “Though science aims for precision, the process of discovery has to be creative,” she says.

As a 2008 Amgen Scholar, Anya Yermakova performed her summer research in Danilo Pozzo's laboratory at the University of Washington in Seattle. She has since graduated from Northwestern University, and is currently pursuing a doctorate in mathematical biology  at the University of Oxford on a Rhodes Scholarship.