Engineers, Surgeons Team Up for Disease Detection

Stephen Lee’s background as a geneticist and protein engineer and his interest in nanotechnology gave him a mission to determine whether protein engineering could solve nanoscale problems.

His question has since grown into a much bigger goal: He is working with a team of electrical, mechanical and biomedical engineers, as well as medical and veterinary researchers, to develop a sensor system to track disease progression.

Proteins are key to the research, Lee explains, because different proteins, called analytes when detected by sensing systems, are present in diseased tissues at different levels. Knowing details about critical analytes, doctors can give patients more accurate diagnoses and more effective treatment.

“We work in transplant biology,” Lee says, “building sensors to detect the analyte MIG. Its concentration is directly proportional to inflammation, a key indicator of whether a person’s body is rejecting a transplanted organ.”

The idea of using MIG (monokine induced by interferon gamma) as an indicator of inflammation is not new, Lee says. But available testing methods require taking large tissue samples, which can change the transplanted organ’s inflammatory status, and the testing can take hours. Lee and his colleagues are developing a rapid, minimally invasive, tolerable analysis for MIG.

Using semiconductor heterojunctionfield-effect transistors, called HFETs, which are similar to solid-state electrical components in computers, they fabricated a sensor that detects MIG electrically. The magnitude of the sensor signal is directly related to the MIG concentration in the organ.

“Our idea is to take these FETs and mount them on a biopsy needle at certain distances apart. Each HFET would be independently wired to read analyte concentration at its position on the needle once it is inserted in the organ. The needle is a mapping tool that reads MIG concentration qualitatively and positionally,” Lee says.

Bringing the idea to fruition, however, requires other engineering and medical disciplines. So Leonard Brillson, a professor in electrical and computer engineering, helps provide understanding of the sensor’s electrical behavior, and Wu Lu, associate professor in electrical and computer engineering, provides expertise in processing AlGaN/GaN HFET devices, which replaced the silicon devices Lee and Brillson initially used. Silicon devices lead to incorrect sensor readings in vivo because they are permeable by sodium ions that naturally occur in the body; AlGaN is impermeable to ions.

The device worked, giving quicker results — within seconds instead of hours — than traditional lab testing called ELISA, which uses additional reagents with indicators such as fluorescence or color changes to detect the analytes.

Next, the researchers needed to find less expensive materials than the AlGaN, which, grown on a sapphire substrate, can cost hundreds to thousands of dollars per sensor. That’s where Paul Berger, professor of electrical and computer engineering and physics, came in to determine whether inexpensive silicon-based immunoMOSFETs (metal oxide semiconductor FETs) or polymer-based PFETs could be used. This, however, reintroduced the sodium ion problem.

Berger had independently developed a method that addresses the problem through atomic layer deposition (ALD), depositing ion-impermeable, atomic-level layers of varying chemical composition, morphologies and thickness on FET sensing devices.

Bharat Bhushan, a professor of mechanical engineering and expert in the use of atomic force microscopes and in tribology, the study of friction, is helping the team optimize the protein/polymer film thickness, composition and deposition method and determine whether the abrasion of the sensor surface by tissue as the needle is inserted will be problematic.

If the silicon version of the sensor works, such devices would cost only pennies or dollars per unit, making them viable for commercial uses in clinical and other applications.

“The concept of a MIG sensor for transplants was developed with the late Professor Charley G. Orosz of the OSU Transplant Center,” Lee says, “but it is clear now that the MIG sensor also could be used to monitor many inflammatory diseases like arthritis, cancer and vascular disease. Beyond MIG sensing, the immunoFET sensing mode will be useful in numerous autoimmune, infectious disease and oncology applications. We can’t fully foresee all the applications, but the potential is large.” 

Now moving from proof of concept to clinical experiments, the researchers are working with transplant surgeons Amir Rajibb and Ronald Pelletier and immunologist Gregg Hadley from Ohio State’s College of Medicine and with Chris Adin, from the College of Veterinary Medicine, who is interested in tracking inflammatory responses in tissue over time.

Contact:

Stephen Lee, (614) 688-5447, stephen.lee@osumc.edu