Medical Device Daily National Editor

Magnetism is pretty interesting stuff, says Don Ingber, MD, PhD, a professor at Harvard Medical School and Director of Harvard's new Wyss Institute for Biologically Inspired Engineering. "It's behind all kinds of tricks when you're a kid. And it's really intriguing to see the techniques and capabilities it has enabled, that you might not have expected."

Ingber, his associate Chong Yung, PhD and their collaborators at Children's Hospital Boston (Boston) and Draper Laboratories (Cambridge, Massachusetts) are pursuing one of the more unexpected and intriguing capabilities of magnetism along with an unexpected feature of microfluidic technology. In using these to perform a kind of disappearing act in the blood, they aren't just playing around.

They have developed a microfluidic system as a type of artificial spleen to battle the devastating effects of sepsis, a condition in which the bloodstream carries pathogens throughout the body to launch a wide-ranging inflammatory attack. Those that can't withstand this sort of systemic attack are most often newborns, the elderly and those that have already compromised immunity.

And the current therapies for these attacks most often necessary in the intensive care unit though multiple, are often insufficient for beating off the change from serious to massive infection.

The result: more than 200,000 die of sepsis infection every year in the U.S.

Rather than simply trying to kill the sepsis pathogens with antibiotic drugs, Ingber and his collaborators are developing a second line of defense a microfluidic system for removing the patient's blood, using magnetism to pull out the threatening pathogens and then returning the cleansed blood to the body.

Key to this system, Ingber told Medical Device Daily, is a "counter-intuitive" property of the small channels of microfluidic systems, enabling two streams of liquid to be in side-by-side contact but still remaining separate.

One of those streams in the device developed by the researchers is the blood removed from the body. They then add tiny magnetic beads, pre-coated with antibodies which attach to specific pathogens that may inhabit the blood.

The second stream sent through the device is a saline-based "collection" fluid which runs beside the blood. As the two streams flow in the device, a magnetic field is then used to pull the magnetized bead/pathogen clumps out of the blood and into the collection fluid.

That fluid is then thrown away, the cleansed blood returned to the patient.

Explaining the counter-intuitive process behind this procedure, Ingber reminds the MDD reporter of some basic physics specifically how, for instance, when two tributaries of streams or rivers merge, they mix, that mixture resulting in turbulence, an effect unwanted in the researchers' anti-sepsis device.

Instead, the small channels which are the primary features of microfluidic devices enable the two streams to be in contact but remain "laminar," Ingber said, that is, continuing on without mixing or becoming turbulent.

This is the counter-intuitive and all-important characteristic of the system, he said, since any "compromising" of the blood by clotting or loss of blood cells or any other change in its composition would render the cleansing process ineffective.

Another key problem, he noted, is to avoid too strong a magnetic pull.

That too, he said, would result in turbulence in the flow of liquids as the result of "a big pile of beads forming in the flow path, and clogging the vessel."

"The trick is to produce an unlimited capacity for clearance," Ingber said. "You don't want to compromise the blood in any way."

The researchers report that a device with four parallel collection modules achieved more than 80% clearance of fungi from contaminated samples of blood in a single pass, at a flow rate and separation efficiency that would be viable for clinical applications.

And Ingber and his collaborators estimate that a scaled-up system with hundreds of channels could totally cleanse the blood of an infant within several hours.

"This blood-cleansing microdevice offers a potentially new weapon to fight pathogens in septic infants and adults ... by removing the source of the infection and thereby enhancing the patient's response to existing antibiotics," Ingber said, thus highlighting the device's usefulness in conjunction with antibiotic therapy.

The next step in the research, he said, is to test the device in rabbits, not just laboratory blood rabbits essentially offer close to the same blood volume as a newborn while also developing various device designs.

Ultimately, he envisions the system developed as a cassette that could be easily utilized with the current types of devices used to isolate and filter small chemicals from blood.

Currently, the researchers are binding magnetic beads with one type of molecule, but other more generic types of molecules could be used in the future for broad-spectrum cleansing, or using "multiple types of beads all at once, or molecules that bind many different pathogens."

Ingber said it is difficult to judge when the system might reach clinical practice. But he indicated that if the team's animal research is able to demonstrate efficacy, "it could have a significant impact in saving lives."

As to winning FDA regulatory approval, he added: "Given the life-threatening situation [offered by sepsis], it might be sooner than later."

The researchers at Children's Hospital Boston and collaborators from Draper Laboratories were funded by a grant from the Center for Integration of Medicine and Innovative Technology (CIMIT; Boston); they also recently won a $500,000 grant from CIMIT to advance this work.

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