Microfluidic device aids in study of immune response
By Ben Coxworth
August 31, 2010
Neutrophils are the most abundant type of white blood cell, and are part of the body’s first line of defense at the sites of injuries or infections. They were originally thought to do simple things like releasing antimicrobial proteins and ingesting pathogens. Recently, however, researchers have come to realize that they play a key role in both chronic and acute inflammation, and in the activation of the immune system in response to injury. Of course, the best way to study neutrophils is to get a hold of some, but that hasn’t been particularly easy. Traditional methods have required relatively large blood samples, and take up to two hours. Because neutrophils are sensitive to handling, it is also possible to inadvertently activate them, which alters their molecular patterns. A microfluidic device developed at the Massachusetts General Hospital (MGH), however, allows for neutrophils to be collected from a relatively small blood sample, unactivated, in just minutes.
The team from the MGH Center for Engineering in Medicine already had experience in developing silicon-chip-based cell-capturing devices, having designed ones for obtaining CD4 T cells for HIV diagnosis and isolating circulating tumor cells. For this latest device, they redesigned the geometry, the anti-body based coating, and other aspects of the cell-capture module at the heart of the technology. They were subsequently able to gather a neutrophil-rich sample from a microliter-sized blood sample in under five minutes. Because the procedure took so little time, the neutrophils remained relatively undisturbed. When analyzed, the samples revealed differences in gene and protein activity relevant to the cells' activation status.
To test the device further, six copies of it were sent to various real-world clinical environments, to study the neutrophils’ reaction to traumatic injuries. In analyzing samples from 26 patients, complex gene expression patterns were discovered, that shifted during a 28-day period after the injury. It is assumed that these shifts reflect interactions between various immune system components.
"Until now, it's been logistically impossible to study neutrophils to the extent we have in this paper,” said lead author Kenneth Kotz, of MGH. "This technology – which is much faster and gentler than current approaches to isolating cells – can be scaled and modified to capture just about any cell type, and we're working to apply it to other cell-based assays."
A paper on the device has recently been published in the journal Nature Medicine.