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Credit: Wyss Institute
A device inspired by the human spleen could change the way we treat sepsis, researchers say.
This “biospleen” was able to cleanse human blood in lab tests and increase survival in animals with infected blood.
Experiments showed that, in a matter of hours, the biospleen can filter live and dead pathogens from the blood, as well as dangerous toxins released from the pathogens.
The researchers detailed these experiments in Nature Medicine.
“Sepsis is a major medical threat, which is increasing because of antibiotic resistance,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts.
“We’re excited by the biospleen because it potentially provides a way to treat patients quickly without having to wait days to identify the source of infection, and it works equally well with antibiotic-resistant organisms. We hope to move this toward human testing [by] advancing to large animal studies as quickly as possible.”
The biospleen is a microfluidic device that works outside the body like a dialysis machine and removes living and dead microbes of all varieties, as well as toxins.
It consists of 2 adjacent, hollow channels that are 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 that travel through the slits.
Key to the success of the device are nanometer-sized magnetic beads coated with a genetically engineered version of the protein mannose binding lectin (MBL).
In its innate state, MBL has a branch-like “head” and a stick-like “tail.” 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, other immune system proteins sometimes bind to the MBL tail and activate clotting and organ damage. So Dr Ingber and his colleagues 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 measuring 128 nanometers in diameter. These novel beads could be added to infected blood to bind to the pathogens and toxins without having to first identify the type of infectious agent.
The biospleen has a magnet that pulls the pathogen-coated magnetic beads through the channels to cleanse the blood flowing through the device, which can then be returned to the patient.
The researchers first tested the biospleen using human blood spiked with pathogens. They were able to filter blood faster than ever before, and the magnets efficiently pulled the beads—coated with pathogens—out of the blood.
More than 90% of key sepsis pathogens were bound and removed when the blood flowed through a single device at a rate of about 0.5 L to 1 L per hour. Many devices can be linked together to obtain levels required for human blood cleansing at dialysis-like rates.
Next, the researchers tested the device using rats infected with E coli, S aureus, and toxins—mimicking many of the bloodstream infections human sepsis patients experience. After 5 hours of filtering, about 90% of the bacteria and toxins were removed from the rats’ bloodstreams.
“We didn’t have to kill the pathogens,” said Michael Super, PhD, also of the Wyss Institute. “We just captured and removed them.”
What’s more, 90% of the treated animals survived, compared to 14% of the controls. And the modified MBL prevented the activation of complement factors and coagulation. 
Credit: Wyss Institute
A device inspired by the human spleen could change the way we treat sepsis, researchers say.
This “biospleen” was able to cleanse human blood in lab tests and increase survival in animals with infected blood.
Experiments showed that, in a matter of hours, the biospleen can filter live and dead pathogens from the blood, as well as dangerous toxins released from the pathogens.
The researchers detailed these experiments in Nature Medicine.
“Sepsis is a major medical threat, which is increasing because of antibiotic resistance,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts.
“We’re excited by the biospleen because it potentially provides a way to treat patients quickly without having to wait days to identify the source of infection, and it works equally well with antibiotic-resistant organisms. We hope to move this toward human testing [by] advancing to large animal studies as quickly as possible.”
The biospleen is a microfluidic device that works outside the body like a dialysis machine and removes living and dead microbes of all varieties, as well as toxins.
It consists of 2 adjacent, hollow channels that are 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 that travel through the slits.
Key to the success of the device are nanometer-sized magnetic beads coated with a genetically engineered version of the protein mannose binding lectin (MBL).
In its innate state, MBL has a branch-like “head” and a stick-like “tail.” 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, other immune system proteins sometimes bind to the MBL tail and activate clotting and organ damage. So Dr Ingber and his colleagues 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 measuring 128 nanometers in diameter. These novel beads could be added to infected blood to bind to the pathogens and toxins without having to first identify the type of infectious agent.
The biospleen has a magnet that pulls the pathogen-coated magnetic beads through the channels to cleanse the blood flowing through the device, which can then be returned to the patient.
The researchers first tested the biospleen using human blood spiked with pathogens. They were able to filter blood faster than ever before, and the magnets efficiently pulled the beads—coated with pathogens—out of the blood.
More than 90% of key sepsis pathogens were bound and removed when the blood flowed through a single device at a rate of about 0.5 L to 1 L per hour. Many devices can be linked together to obtain levels required for human blood cleansing at dialysis-like rates.
Next, the researchers tested the device using rats infected with E coli, S aureus, and toxins—mimicking many of the bloodstream infections human sepsis patients experience. After 5 hours of filtering, about 90% of the bacteria and toxins were removed from the rats’ bloodstreams.
“We didn’t have to kill the pathogens,” said Michael Super, PhD, also of the Wyss Institute. “We just captured and removed them.”
What’s more, 90% of the treated animals survived, compared to 14% of the controls. And the modified MBL prevented the activation of complement factors and coagulation.
Credit: Wyss Institute
A device inspired by the human spleen could change the way we treat sepsis, researchers say.
This “biospleen” was able to cleanse human blood in lab tests and increase survival in animals with infected blood.
Experiments showed that, in a matter of hours, the biospleen can filter live and dead pathogens from the blood, as well as dangerous toxins released from the pathogens.
The researchers detailed these experiments in Nature Medicine.
“Sepsis is a major medical threat, which is increasing because of antibiotic resistance,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts.
“We’re excited by the biospleen because it potentially provides a way to treat patients quickly without having to wait days to identify the source of infection, and it works equally well with antibiotic-resistant organisms. We hope to move this toward human testing [by] advancing to large animal studies as quickly as possible.”
The biospleen is a microfluidic device that works outside the body like a dialysis machine and removes living and dead microbes of all varieties, as well as toxins.
It consists of 2 adjacent, hollow channels that are 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 that travel through the slits.
Key to the success of the device are nanometer-sized magnetic beads coated with a genetically engineered version of the protein mannose binding lectin (MBL).
In its innate state, MBL has a branch-like “head” and a stick-like “tail.” 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, other immune system proteins sometimes bind to the MBL tail and activate clotting and organ damage. So Dr Ingber and his colleagues 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 measuring 128 nanometers in diameter. These novel beads could be added to infected blood to bind to the pathogens and toxins without having to first identify the type of infectious agent.
The biospleen has a magnet that pulls the pathogen-coated magnetic beads through the channels to cleanse the blood flowing through the device, which can then be returned to the patient.
The researchers first tested the biospleen using human blood spiked with pathogens. They were able to filter blood faster than ever before, and the magnets efficiently pulled the beads—coated with pathogens—out of the blood.
More than 90% of key sepsis pathogens were bound and removed when the blood flowed through a single device at a rate of about 0.5 L to 1 L per hour. Many devices can be linked together to obtain levels required for human blood cleansing at dialysis-like rates.
Next, the researchers tested the device using rats infected with E coli, S aureus, and toxins—mimicking many of the bloodstream infections human sepsis patients experience. After 5 hours of filtering, about 90% of the bacteria and toxins were removed from the rats’ bloodstreams.
“We didn’t have to kill the pathogens,” said Michael Super, PhD, also of the Wyss Institute. “We just captured and removed them.”
What’s more, 90% of the treated animals survived, compared to 14% of the controls. And the modified MBL prevented the activation of complement factors and coagulation.