Detecting disease with nanostructured electrodes

Dr. Shana Kelley and Dr. Jennifer Flexman

Most futuristic visions of medical diagnosis feature hand-held devices that can discern the state of our bodies and quickly identify any problems. Those visions get a bit murkier, however, when it comes to the question of how such devices will operate. Researchers who are exploring the considerable technical challenges are beginning to make substantial progress.

Among the most promising ventures is a technology being developed by Xagenic Inc., a Toronto-based, privately held company founded by Dr. Shana Kelley and Dr. Ted Sargent, both Professors at the University of Toronto and both winners of the prestigious Steacie Prize, in 2011 and 2012 respectively. Dr. Kelley has cross-appointments with three faculties: Pharmacy, Medicine (Biochemistry), and Arts and Sciences (Chemistry), in addition to participation in the multidisciplinary Institute of Biomaterials & Bioengineering. At the Faculty of Applied Science & Engineering, Dr. Sargent is the Vice-Dean (Research), has a research group in the Department of Electrical & Computer Engineering and also holds the Canada Research Chair in Nanotechnology.

Kelly, Sargent and their research teams are bringing together their diverse fields of knowledge to refine a patented approach to designing chips that have very tiny biosensors—nanostructured electrodes constructed from nanomaterials—each of which can host different types of probe materials that bind to a particular type of biochemical agent.

“The real innovation of the technology is how you build the electrodes,” says Dr. Jennifer Flexman, the Director of Research, Development, and Commercialization in both Dr. Kelley’s and Dr. Sargent’s groups.

Ordinarily the tip of an electrode would contain only a small amount of probe material. As a result, the interaction of the probe with a low concentration of molecules found in a biological sample would yield a current too small for reliable detection. To overcome this problem, the biological materials are usually amplified to create a larger volume, but this step is time-consuming and energy-intensive.

“Our breakthrough consists of taking the probe surface and multiplying its area by an order of magnitude,” Flexman explains, describing an intricate design where electrodes extend from the chip’s surface in spikes resembling flower petals. “And you can build this nanostructured surface in different ways to tune the sensitivity of your electrode. It marries nanotechnology fabrication with biological interactions.”

The resulting capability of this system is remarkable. A single chip could contain upward of 100 distinct electrodes, each of which can carry out its own sample analysis. If they are exposed to blood from a patient, for example, the chip can confirm the presence of various disease-marking molecules—even rare ones—in a matter of 15 to 20 minutes.

This kind of speed and sensitivity would provide public health officials with a powerful tool for assessing and containing the outbreak of bacterial disease. Similarly, patients who currently endure stressful waits for a cancer diagnosis will be able to receive and digest the news almost immediately, and begin any therapy that much sooner.

Shana Kelley, a biochemist who became the founder and CTO of Xagenic, glimpsed this prospect emerging from her research as early as 2006. By 2010, Xagenic had been formed, and now employs over 15 people.

“We had this nice platform where we could make the same chip over and over again, and get the reproducibility where it needed to be,” recalls Kelley. Xagenic has relied heavily on the expertise available from CMC Microsystems, help that she credits with the considerable progress that has been made with the technology. “I don’t think the company would be in existence if it wasn’t for CMC,” insists Kelley. “They helped us get our first chips fabricated, drawing on CMC's pool of suppliers that could manufacture bioelectric custom designs, and gave us quite a bit of support as we were making different prototypes and trying to come up with the most effective one.” Above all, that help came at the initial stages of the research, even as the viability of concept was still being demonstrated. This assistance has provided the company with the necessary momentum to raise over $10 million in financing, pointing the way to those hand-held devices of the future.

“Being able to do direct detection of molecules is highly desirable,” concludes Flexman. “This technology is potentially revolutionary in that it would remove the need for amplification of your sample. And that opens up a whole new way of doing diagnostics, because it’s much cheaper, it’s potentially portable, and it’s easy to use.”

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