In 2007 a 19-year-old boy came to Massachusetts General Hospital with a tumor behind his lung. One of the treatments available to him had been very successful fighting cancers with a certain mutation, but to know if the mutation was present, his doctors needed a biopsy. The tumor’s location made biopsy impossible, and without proof the boy’s insurance company wouldn’t pay for the treatment.
Sunitha Nagrath was a Harvard postdoctoral researcher working with doctors at Mass General on a method to detect cells from tumor-based cancers in blood samples by running them through a microfluidic chip. Nagrath tested the boy’s blood, positively identified the mutation and provided the proof the doctors needed to start treatment. The case would become part of an article Nagrath published in Nature, the first to show microfluidic chips could be used to detect cancer cells. But even more than that, it showed Nagrath the difference her work could make.
“That day I really thought, ‘If no other paper gets published, I won’t be disappointed with my work.’” said Nagrath, now an assistant professor of chemical and biomedical engineering at Michigan. “That moment of satisfaction will stay with me forever.”
Building on the lessons of that first microfluidic chip, Nagrath has continued to develop devices that apply her broad engineering expertise to the challenges of detecting cancer in the blood.
“There is so much scope to make a difference in cancer,” she said. “It’s become a passion for me because it can affect anybody at any time.”
Certain aspects of cancer diagnosis have changed very little in the past 100 years, Nagrath says. Tissue biopsy is still standard procedure, despite the invasive procedure itself and the emotionally excruciating wait patients endure while the lab produces test results.
Nagrath felt there had to be a better way.
“I think there are already tools existing, we just need to talk to each other to be able to use them effectively,” she said. “Adapting those tools to fighting cancer has certain challenges, but engineers can address them. That’s what excites me. It is challenging, but at the same time, it can make a huge difference.”
Nagrath has used graphene oxide, a material originally developed for semiconductors, to build chips so sensitive they can detect a single cancer cell amid a billion blood cells. That opens the possibility of quickly and non-invasively detecting certain tumor-based cancers – including breast, lung and pancreatic cancer – long before a tumor shows up on a CT scan.
The chip also provides an environment where those few cancer cells can be grown into a workable culture – an out-of-body copy of the cancer that can then serve as a testbed for patient-specific treatments.
Early detection is especially important in pancreatic cancer, which tends to be especially elusive and aggressive, with a 5-year survival rate of less than 10 percent. Nagrath is part of a $1.5 million grant from the Lustgarten Foundation to develop personalized treatments for pancreatic cancer patients using microfluidics.
“The cancer cells are in the blood long before they become really aggressive, so I think the early detection can make a whole lot of difference,” Nagrath said.
Nagrath’s academic background includes a bachelor’s degree in chemical engineering from Sri Venkateswara University in India and a masters in mechanical engineering and PhD in nuclear engineering from Rensselaer Polytechnic Institute. It’s an eclectic blend for someone who now works with microelectronics and nanomaterials to catch cancer cells in blood. The common thread, she says, was an abiding interest in fluid dynamics that eventually led her to study blood flow in arteries.
She decided she wanted to do postdoctoral work with microelectromechanical systems (MEMS) and found a lab at Harvard that was using MEMS to look at other disease markers in blood. A paper about FDA-approved cancer detection piqued her curiosity about using MEMS to detect cancer, and collaborators in the Cancer Center at Mass General opened her eyes to the potential there. She came to Michigan in 2010 and has found a richly collaborative environment in the Biointerfaces Institute.
“When I came to the University of Michigan, I was looking at different universities and I met with the Cancer Center director here. This was the only place where the Cancer Center director took time to meet with me, a faculty candidate in engineering. He thought it was important enough, and I thought, ‘If he has the motivation and passion to support someone who’s coming here in a technology field, the people around him must be like that too.’ And that has proven out since I’ve been here.”
With support from the Coulter Translational Research Program, Nagrath is developing an automatic processor that will enable the graphene oxide chip to be used in hospitals and clinics. She’s already tested it on a small cohort and hopes to have three or four different studies with larger patient groups running at other institutions during 2015-16. Once her results are validated, the Coulter program and the U-M Office of Technology Transfer will help her move the device into the medical mainstream.
Nagrath characterizes her progress as “baby steps” that she hopes will be built upon by the people who now work in her lab. In a department where innovation happens all the time, she tends not to draw a lot of attention to herself. But when she first published about using microfluidics to detect cancer cells, no one else was using the technology that way. Today there are more than 10,000 papers on the subject.
“The field has exploded,” she said. “I would love to think that is because someone showed it is possible.”