Searching for Signs of Nascent Disease

What if doctors could use a tiny micro-channel device and a simple blood sample to detect cancer very early on — before a patient even shows any symptoms — and avoid invasive biopsy surgeries?

Researcher Larry Cheng combines electrical engineering and biomedicine toward a goal of early cancer detection.
Using a microfluidic biosensor platform, Larry Cheng examines molecular probes that can report the presence of specific bacterial DNA or viral RNA in a few drops of blood. (Photo: Karl Maasdam)

WHAT IF DOCTORS COULD USE a tiny micro-channel device and a simple blood sample to detect cancer very early on — before a patient even shows any symptoms — and avoid invasive biopsy surgeries?

What if a similar device could be used to quickly determine the efficacy of cancer treatments like chemotherapy by revealing biomarkers in the blood and immediately adjusting the dosage?

What if soldiers, firefighters and others could wear tiny microsensors inside their mouths that would track and transmit stress or pain levels in real-time, based on a hormone secreted in their saliva?

Larry Cheng, an electrical and computer engineer at Oregon State University, is focused on developing these devices. His cancer diagnostics research, which blends electrical engineering with biomedicine, seeks to detect mutant circulating tumor DNA or RNA — cancer biomarkers — in the body’s circulatory system.

It’s a challenging goal.

“It’s hard to directly detect low amounts of the targeted mutant genes in the background among high levels of normal sequences,” Cheng says. “And differentiating the minute differences in the mutated sequence is also quite challenging.”

Uncurbed Enthusiasm

The daunting odds have not dampened Cheng’s enthusiasm for the research that could potentially have a huge impact by allowing doctors to diagnose cancer earlier and fine-tune treatment regimens on the fly. Collaboration is key to making the impact Cheng envisions.

“We are engineers and not cancer biologists, so we talk to the biologists and physicians to see what they need, and then figure out a way to help them make their diagnostics more efficient using engineering,” he says.

To develop these devices, researchers have to overcome two hurdles: one, enabling high-speed transport of blood from a sample through a sensor; and, two, achieving efficient and selective capture of target DNA in the blood.

Researcher Larry Cheng is using micro-technologies to look for mutations in blood samples.
Micro-devices may aid early detection of mutations in blood samples. (Photo: Karl Maasdam)

Cheng and his graduate students addressed the first hurdle by incorporating microchannel technology and a sensor into the same device on a microchip. They use microfluidics to efficiently move a lot of blood through the device in very close proximity to the sensor’s surface.

To address the second hurdle, they engineered the sensor’s surface area to attract and bind target DNA to a specific probe. The material glows when excited by light, and its intensity indicates how much of the molecular biomarker is present. The technique will help doctors determine the effectiveness of a current cancer therapy and make quick adjustments, instead of waiting days or weeks for test results to be returned.

Salivary Secretions

In addition to his work on cancer, Cheng just received a $340,000 grant from the National Science Foundation to explore how microsensors can be used to identify certain hormones secreted in saliva when a person is under stress or experiencing symptoms like fatigue.

“The target with this project is to develop a sensor that can support real-time monitoring of salivary biomarkers,” Cheng said. “We’re looking at a trace-associated hormone that boosts heartbeat and is also released into the saliva. We want to detect this biomarker in order to track psychological stress.”

Traditional mouth swab tests for salivary biomarkers take time for the results, but Cheng’s team is working on real-time monitoring that would wirelessly transmit results every minute or two, from a device so small it could be placed inside a person’s mouth.

Unlike DNA or glucose, however, this particular hormone in the saliva carries no charge and has no electrochemical reactivity, so it can’t be tracked using traditional methods. And because it is mounted in the mouth, optical property analysis is not an option, either. So Cheng and his team are working to develop a polymer that will change conductance when it binds to the target hormone molecules.

“Developing this polymer is the key,” Cheng says. “We can’t use optical sensing, because it’s too bulky for a wearable device, and we can’t rely on traditional electrochemical detection the way we measure glucose, so we need to come up with a new method for detection.”

The technology could be used for jet fighter pilots and military drone operators, whose stress levels can impact their response to conditions they encounter. Data from the paper-thin, flexible device could be wirelessly relayed to key personnel to help determine a pilot’s psychological condition before a mission, and make adjustments to duties or workload accordingly. Others working in high-stress jobs, such as firefighters battling wildfires, might benefit from the technology in the same way. In the medical industry, the technology could be used to monitor anxiety in surgical patients and in the self-management of chronic diseases.

As the field of precision health continues to expand, the demand for more engineers with an understanding of both biomedicine and engineering will grow. Because most electrical engineering students have not been exposed to much biotechnology, Cheng has developed a new class called Biosensors and Medical Devices to teach students about how diagnostic tests are performed in terms of chemical, optical and electrical responses. Students also learn how fluids flow through a microdevice, how to move molecules to a sensing surface, and the chemistry that binds molecules to that surface.

“It introduces engineering students to the concepts that are required to develop the types of biomedical devices we’re working on,” Cheng says.

Gregg Kleiner is a freelance writer, journalist and novelist based in Corvallis.