Developing Biosensors for Early Disease Detection
Many cancers and other diseases are diagnosed when they become symptomatic or are detected through screening. Symptomatic diagnosis also carries the probability of advanced malignancy and poor patient prognosis. However, successful patient outcomes typically go hand-in-hand with early detection, and it appears that early disease detection can be enhanced by routinely screening for important disease biomarkers.
“Early disease diagnosis is paramount for successful patient outcomes, and by developing instruments that can screen for several biomarkers at once we feel we’re preparing a necessary component to drive this paradigm,” says Marc Porter, USTAR professor of chemical engineering, chemistry, bioengineering and pathology, and director of the Nano Institute of Utah. USTAR (Utah Science, Technology and Research Initiative) is a legislative initiative designed to strengthen technological research and stimulate economic development in Utah.
Porter and his collaborators have been awarded a multi-million dollar federal grant to develop a nanotechnology-based platform for the early detection of pancreatic cancer. His collaborators include professor Sean Mulvihill and research assistant professor Matt Firpo from the School of Medicine and senior research scientist Michael Granger from the Nano Institute.
Pancreatic cancer is particularly deadly — it is the fourth leading cause of death from cancer in the United States. Less than 5 percent of patients live longer than five years after diagnosis. “Pancreatic cancer is usually asymptomatic in the initial stages of progression,” Porter says. “An individual may feel like he has a cold or some pain in his lower back, but he may attribute these symptoms to something other than cancer. By the time the cancer is diagnosed, it is often too late for surgery.”
He adds, “But on the other hand, we know that early diagnosis of pancreatic cancer can save lives. A real-life success is [Supreme Court Justice] Ruth Bader Ginsburg whose asymptomatic pancreatic cancer was found at an early stage through a routine CAT scan. Due to the early resection of the tumor, she is still in remission.”
Microarray Biosensors
Porter and his associates are seeking to advance the early detection of cancers and other diseases through the development of nanotechnology “biosensors” — devices that detect biological materials at ultra-low levels. “Nano” refers to the tiny, molecular scale of the technology. By screening for combinations of biomarkers that are indicative of specific diseases, they hope to bring early disease detection closer to reality.
Porter is developing microarray biosensors that consist of one or more antibodies affixed to glass slides. Each antibody corresponds to a particular biomarker. When the array is exposed to a blood or urine sample, antigens bind to complementary antibodies and indicate the possibility of a particular disease.
“The eventual deployment of the technology — for instance, in your primary caregiver’s office — would mean that test results are logged in a secure databank, so that the caregiver could monitor biomarker fluctuations over time to see how they are doing,” says Porter, who would like to make the tests accessible and affordable to patients. “What if we could make these tests readily available, much like checking your blood pressure at your family doctor’s office or a pharmacy?”
One of the challenges to this technology, however, is reliability. Researchers dispute how much of the data obtained from this type of biosensor is accurate with some arguing that only 30 to 40 percent of the information can reliably be used. “We need to find the right biomarkers that are clear signatures of a particular disease, so that we can improve the accuracy in early detection,” Porter says. “We also hope to realize breakthroughs in the detection of tuberculosis and invasive fungal infections and to enable the development of new and improved vaccines for these and other diseases.”
Porter and his associates are also working on the next generation of diagnostic biosensors using gold nanoparticles, which are coated with antibodies so that specific biomarkers will bind to them. Gold nanoparticles can dramatically affect the way light is scattered and enhance optical signals. “If we can detect a signal from one nanoparticle, then we can detect ultra-low biomarker levels and increase the probability of earlier disease detection,” he says.
Magnetoresistive Sensors
Aside from optical disease marker detection, another area of Porter’s research, magnetoresistive (MR) sensors, centers on developing disease detection methods using the same magnetic principles common to a computer hard drive. He and his team have successfully created a sensitive prototype device that could potentially test for hundreds of diseases simultaneously by acting like a credit card swipe machine to scan a card loaded with blood, saliva or urine samples.
The prototype card swipe device consists of an MR “read head” and sample stick. When the device is developed commercially, the MR sensor device could look like a credit card reader or floppy disk drive reader. “Think how fast your PC reads data on a hard drive, and imagine using the same technology to monitor your health,” he says. “Unlike lab tests today, results could be available in minutes, not days or weeks.”
Magnetoresistance is the change in a material’s resistance to electrical current in the presence of an external magnetic field. That change is usually less than 1 percent. However, Porter uses thin magnetic materials fabricated as multilayers to display a change in resistance of as much as 20 percent at room temperature. This method is very sensitive, detecting as few as 800 microscopic particles on an address. With further development, Porter believes they can achieve single-particle detection to test blood or other samples for viruses that can cause disease in minute concentrations.