Although vital information for diagnosing and treating disease can be obtained by separating complex mixtures of cells, such as those found in a blood sample, researchers may need to search through billions of other cells in order to collect rare cells, such as fetal cells, tumor cells or stem cells.
Sukant Mittal, a graduate student in the Harvard-MIT Division of Health Sciences and Technology (HST), explains:
“You’re basically looking for a needle in a haystack.”
The study by Mittal and his team at MIT and Massachusetts General Hospital (MGH), published in the February 21 issue of Biophysical Journal, reveals a new microfluidic device can be used to isolate target cells considerably faster than current devices. This type of device could be used to personalize medicine and could be used in applications, such as point-of-care diagnostics.
Other researchers of the study are professor William Deen, MIT chemical engineer, Mehment Toner, a professor of biomedical engineering at MGH, HMS and HST, and Ian Wong, a postdoc at MGH and Harvard Medical School (HMS).
Scientists have used several methods in order to sort cells based on electrical properties, density and differences in size. However, because the physical characteristics of cells can differ considerably, these methods risk separating cells wrongly, resulting in an incorrect diagnosis.
Antibodies that attach to specific molecules on the surfaces on the target cells are a more precise way to isolate cells, although this method only works if the antibodies come into contact with the target cells. However, as cells move relatively quickly, this is unlikely to happen.
Wong said:
“Imagine you’re standing on a bridge over a river, and you throw a message in a bottle out in the middle. If the river is moving really slowly, you could imagine that eventually the bottle will drift over to the riverbank and somebody can grab it. But is the river is flowing too quickly, then the bottle is swept downstream without ever approaching the sides.”
The team set out to solve this problem, Wong explained:
“Can we steer the bottle toward the riverbank so that it can get caught?”
The team designed a device that would direct the fluid toward the bottom of the channel as it flows in order to bring the antibodies into more contact with the cells. A vital part of their device is the use of a soft membrane with nanoscale pores, which separates two adjacent microchannels.
The cells enter into one particular channel and as they stream through this channel, the fluid together with the cells are quickly drawn to the porous divider. Although fluid can enter into the other channel, cells can’t. Once the cells reach the surface, they start rolling at a slow enough pace that allows them to bind to the antibodies and get captured, while still rolling fast enough to keep other cells moving. This type of rolling behavior is comparable to how stem cells or white blood cells selectively “home in” to areas of infection and injury in the body.
One possible application for these devices is to separate cancer cells from patient blood samples. In previous studies the team has demonstrated that the number of flowing tumor cells in the bloodstream correlates with the clinical response to treatment the patient receives, indicating the possibility to personalize medicine for individuals suffering from cancer.
Toner explained:
“Considerable validation and testing will be necessary before this early-stage device can be deployed in the clinic. Nevertheless, this novel approach may enable exciting diagnostic and therapeutic opportunities that are not feasible using existing technologies.”
Written by Grace Rattue