Improving early-stage cancer detection with biosensors

Screening for early-stage cancer could require nothing more than a finger prick, a drop of blood. It could be routine, allowing physicians to catch the disease early, when treatments are most effective. As it is, many procedures are beyond the scope of regular doctor visits (an MRI or CT scan), and the tests often differ for each type of cancer. Even though breast cancer and lung cancer, for example, both involve the thoracic region, the same tests aren’t used for both. Early detection is difficult, yet new biosensors could change that. 

Professor Brian T Cunningham the interim director for the Micro and Nanotechnology Laboratory, recently received a grant through the National Institutes of Health (NIH) Innovative Molecular Analysis Technologies Program, to develop biosensing equipment for early-stage detection of breast cancer and for human papillomavirus, a common precipitate of cervical cancer. Both diseases could be detected with just a minute amount of blood.

“If a person has a tumor, some cancerous cells in their body, those cells will produce proteins that only cancer cells will produce,” Cunningham explained. These proteins circulate through the bloodstream, and although the concentrations are low, they can be identified even in a small blood sample. These characteristic proteins are known as biomarkers. 

Already Cunningham and his graduate students have shown that their prototype device is exceedingly effective at identifying those biomarkers, as well as antibodies (an immune system protein, produced in response to pathogens in the bloodstream). “We have demonstrated that we can use that chip to detect the cancer biomarkers, especially the breast cancer biomarkers, and we published, maybe one, two, three—many papers on that,” said Yafang Tan, one of four graduate students who are currently working on the project. 

The chip she referred to is a small piece of silicon known as a photonic crystal. The surface is nanoengineered with small grooves, such that, when shifted in the light, a prismatic spectrum can be observed. The researchers print a matrix of microscopic dots on the surface of the crystal. Each dot comprises a unique antibody or another biomolecule. The crystal is surprisingly small, less than a centimeter long and two millimeters wide, yet scores of these dots are printed on the surface. 

Then a droplet of blood is flooded across the crystal. If the sample contains a breast cancer biomarker, when it drifts over the corresponding antibody dot, the power of the immune system kicks into play, and the biomarker is bound to the dot. “It’s kind of like a way for the antibodies to grab and sort all of the stuff that’s randomly in the blood sample,” Cunningham explained. “They become stuck.” Inversely, the antibody that the immune system produces in response to human papillomavirus would attach to a dot of the corresponding pathogenic protein.

Once the sample has diffused across the surface of the crystal and the proteins have been allowed time to sort, the fluid is removed, and a chemical solution containing a fluorescent tag is added. If biomarkers or antibodies are present on the dots, the tag will bind to it, causing the dot to shine like a microscopic LED when a laser is directed at the surface of the crystal. 

When the same procedure is done with a regular glass microscope slide, the dots do not fluoresce as brightly. Sometimes they’re almost imperceptible. “What we’ve developed is a surface…that can take energy from a laser and super-concentrate it onto the molecule and make it glow more brightly than it otherwise would,” Cunningham said. 

With the new grant funding, the team will develop a device that automates this process. A clinician could take a small blood sample. It would be placed in the device, which would first filter the sample, removing the red and white blood cells, so that the serum only contained a mix of proteins. Then the whole assay with the photonic crystal and the fluorescent tag would be conducted. This could be performed easily and inexpensively at a clinic or hospital, and the same blood sample could be used to simultaneously test for multiple diseases. 

“The final product will be just a box, or maybe smaller. You could bring it to rural areas, to Africa, where there are maybe no hospitals,” said graduate student Tiantian Tang (BSEE ’13), who also worked with Cunningham as an undergraduate researcher. “It will be easy to use. Just press one button. Insert your blood.” 

Graduate students Haisheng Xu and Chenqi Zhu (BSEE ’13) are also working on fabrication, design, and automation of the equipment. Zhu, like Tang, was also an undergraduate researcher in Cunningham’s lab. 

Eventually their equipment could detect any type of cancer, or, in the case of human papillomavirus, any type of autoimmune disease: Crohn’s disease, Lupus, even allergies. They are all indicated by unique proteins in the bloodstream: a biomarkers or antibody. “They are still a very hot topic,” Tan said of the specific proteins, but there is no doubt that when this device is in the hands of doctors and clinicians, it will revolutionize the way these diseases are identified and treated.