When a patient has sepsis, in which bacteria or fungi multiply too swiftly in a patient’s blood for antibiotics to help, the result is often deadly. However, a new device inspired by the human spleen and developed by a team at Harvard’s Wyss Institute for Biologically Inspired Engineering, Boston, MA, may transform the way that doctors treat sepsis, which is the leading cause of hospital deaths.

Fig. 1 – The Wyss Institute’s spleen-like blood-cleansing device makes use of genetically modified blood proteins coated on magnetic nanoparticles and magnetic forces to pull a variety of pathogens from the blood. (Credit: Harvard’s Wyss Institute)
The device, called a “biospleen,” exceeded the researchers’ expectations with its ability to cleanse human blood tested in the laboratory and increase survival in animals with infected blood. In a matter of hours, it can filter live and dead pathogens from the blood, as well as dangerous toxins that are released from the pathogens, they say.

Sepsis occurs when a patient’s immune system overreacts to a bloodstream infection, which may include urinary tract infections, skin or lung infections, and contaminated IV lines, surgical sites, and catheters.

Identifying the specific pathogen responsible for sepsis can take several days, and if doctors cannot pinpoint which bacteria or fungi are causing the infection, then they treat sepsis patients with broad-spectrum antibiotics, which may fail. In many cases, drug-resistant bacteria increases while the development of new antibiotics lags behind.

How It Works

To combat this, the Wyss team built a fluidic device that works outside the body like a dialysis machine, and removes living and dead microbes of all varieties, as well as toxins. They modeled it after the microarchitecture of the human spleen, which removes pathogens and dead cells from the blood through tiny interwoven blood channels.

Their biospleen is a microfluidic device consisting of two adjacent hollow channels connected to each other by a series of slits. One channel contains flowing blood, and the other has a saline solution that collects and removes the pathogens traveling through the slits. Tiny nanometer-sized magnetic beads coated with a genetically engineered version of a natural immune system protein called mannose binding lectin (MBL) are the key to the device’s success.

In its innate state, MBL has a branch-like “head” and a stick-like “tail.” In the body, the head binds to specific sugars on the surfaces of all sorts of bacteria, fungi, viruses, protozoa and toxins, and the tail cues the immune system to destroy them. However, sometimes other immune system proteins bind to the MBL tail and activate clotting and organ damage, so the team used genetic engineering tools to lop off the tail and graft on a similar one from an antibody protein that does not cause these problems.

The team then attached the hybrid proteins to magnetic beads to create novel beads that could be added to the blood of an infected patient to bind to the pathogens and toxins without having to first identify the type of infectious agent. The sepsis device uses a magnet to pull the pathogen-coated magnetic beads through the channels to cleanse the blood flowing through the device. Then, the clean blood is returned to the patient.

The team first tested their blood-cleaning system using human blood in the laboratory that was spiked with pathogens. The magnets efficiently pulled more than 90 percent of key sepsis pathogens out of the blood when the blood flowed through one device at a rate of about a half to one liter per hour. They say that many devices can be linked together to obtain levels required for human blood cleansing at dialysis-like rates.

Next they tested the device using rats that were infected with E. coli, S. aureus, and toxins to mimic many of the bloodstream infections that human sepsis patients experience. After five hours of filtering, again about 90 percent of the bacteria and toxin were removed from the rats’ bloodstream.

The pathogens did not need to be killed, just captured and removed. And, they reported, 90 percent of the treated animals survived, compared to 14 percent of the controls.