Friday, May 23, 2008

Microfiltering Sepsis

A microfluidic device may effectively filter out pathogens that trigger septic shock.

By Jennifer Chu

Blood filter for sepsis: A microfluidic prototype selectively draws out infectious pathogens as blood flows through. The top image shows blood flow from left to right through the device. Without a magnetic field (top), red blood cells (red) and pathogens (yellow) pass in and out of the device together. In the presence of a magnet (bottom), the pathogens bind to magnetic beads (green), separating from blood into different channels. Researchers say that such a device may help clean large volumes of blood, particularly in cases of severe sepsis. Credit: Shannon Xia and Don Ingber

Each year, intensive care units in the United States hospitalize nearly 750,000 patients with severe sepsis, a syndrome that manifests when a body's immune system overreacts to infection. As sepsis sets in, inflammation rapidly spreads through the body, often shutting down organs and potentially leading to death. Antibiotics are often the main course of treatment, but there's a lag time before the drugs kick in, during which inflammation continues to spread.

Now scientists at Children's Hospital Boston are developing a miniature filtration device that can rapidly pump blood out of the body, clearing it of infectious agents before delivering the blood back to the body. Principal investigator Donald Ingber says that the microfluidic device can be used in combination with antibiotics as a first line of defense in treating sepsis before the antibiotics take effect.

"The goal is to clear the blood in a period of hours," says Ingber. "You really have a tipping point, and we want to try to get over that point so that the antibiotics can kick in."

Ingber and his collaborators from Harvard Medical School, Boston University, and the Charles Stark Draper Laboratory have designed a prototype that is able to pull pathogens out of blood as it flows through a microscopic filtration system. Ingber says that the device improves on current blood filtration methods such as hemodialysis. Dialysis machines filter blood by pumping it out through a catheter and into a compartment with a semipermeable membrane. On the other side of the membrane is a compartment with fluid flowing in the opposite direction. Via forces of diffusion and osmosis, small, unwanted molecules from blood cross the membrane, exiting with the fluid as the filtered blood flows back into the body.

While dialyzers can filter small molecules out of blood, larger molecules such as pathogens are too big to cross. Instead, Ingber and his colleagues designed a small microfluidic device that pulls these larger pathogens out of blood.

The device itself contains a pair of microscopic channels--one for blood, the other for a saline-based solution. The two channels meet in a central compartment. The idea is to give the saline solution properties that will selectively draw pathogens out of blood as the two fluids mix.

However, because of their very small scale, microfluidic devices have no moving parts that can mechanically mix fluids together. Even as they come in contact, fluids will remain discrete, retaining their respective molecules. Then Ingber hit upon the idea to use a small magnetic field. He first identified specific molecules that naturally bind to certain pathogens related to sepsis. Ingber and his colleagues then coated these molecules with tiny magnetic beads in solution. They then pumped the solution through one channel as infected blood was pumped through the other. As the two channels funneled into one compartment, the team turned on a small magnet on the side of the magnetic bead solution. As the fluids came in contact, the pathogens from the blood bound with the magnetically coated molecules, which in turn were pulled toward the magnet, away from the blood flow.