The Power of the Bead
CytoSorbents has developed a unique and powerful blood filtration and purification technology based on its proprietary biocompatible, highly porous polymer bead platform. Each of these spherical beads are approximately the size of a grain of salt and synthesized to contain millions of optimally-sized pores and channels. These pores and channels collectively have a massive surface area that enable the bead to behave like a tiny sponge to safely bind and effectively remove a broad range of inflammatory and toxic substances from whole blood and plasma via pore capture and surface adsorption. Large substances, such as blood cells cannot get into the pores and go around the bead unaffected. Similarly, very small substances, such as electrolytes, are too small to be captured and go through the beads unaffected. But appropriately sized substances migrate into the pores of the beads and get adsorbed to the external and internal surfaces of the pores and channels, never to come out. Variations of these beads form the basis of CytoSorbents’ flagship product, CytoSorb®, for the treatment of deadly inflammation seen in critical illnesses and after cardiac surgery, and HemoDefend™, for the purification of transfused blood products of contaminants that can cause potentially dangerous transfusion reactions.
State-of-the-Art Blood Purification Technology
CytoSorbents’ advanced bead technology combines numerous advantages into a single blood purification platform.
- Proprietary polymer technology: CytoSorbents’ beads are composed of a specially modified, chemically inert, polystyrenic co-polymer protected by 32 issued U.S. patents and multiple applications pending worldwide
- Highly biocompatible: The beads are ISO 10993 certified for biocompatibility, hemocompatibility, no genotoxicity, no cytotoxicity, no acute sensitivity, and no complement activation
- Pure: No residual organics, no leachables, meets USP particulate standards for large parenteral injections
- Massive surface area: A single 300 mL cartridge filled with CytoSorb® beads has more than 40,000 square meters of internal and external surface area on which to adsorb and remove toxic substances
- Selective, multi-modal separation: Blood is composed of a wide range of substances, ranging from water, cells, electrolytes, hormones, sugars, lipids, and proteins. The technology achieves selectivity by using size exclusion as the first step in separation. Next, the hydrophobic “water-fearing” polymer effectively adsorbs hydrophobic substances and excludes hydrophilic “water-loving” ones. Substances that do not adsorb leave the bead, while those that do adsorb will migrate further and further into the beads, lost in the vast network of channels, unable to escape.
- Excellent adsorption of proteins, bioactive lipids, and toxins: Many of the inflammatory mediators that drive the deadly inflammatory process, including cytokines, toxins, activated complement, enzymes, and bioactive lipids, are preferentially removed by the technology
- Superior kinetics: Beads are in direct contact with blood, actively removing substance with no need for them to diffuse across a semi-permeable membrane as with dialysis and hemofiltration
- Concentration Dependent Removal: High concentrations of toxins provide a driving force gradient to push substances into the pores of the bead. Because of this, the technology is very good at removing toxic levels of substances. As the concentration of the substance decreases, so does the ability of the device to extract it. This creates an inherent “self-titrating” aspect to the technology that prevents the excessive removal of substances and makes it difficult to overtreat
- Gamma stable, thermostable, and chemically inert: The polymer is very robust and stable, allowing easy gamma sterilization, stability at a broad range of temperatures, and resistance to chemical change in most physiologic environments
- Rapidly customized: The beads can be easily modified during polymer synthesis to create beads with identical chemical structure, but with very different porous structures. For example, beads can be made with very small pores similar to activated charcoal to remove drugs and small molecules. Alternatively, the pores can be made very large to capture very large antibodies and other substances even larger than 1,000 kDa. In addition, the beads can be further modified to incorporate most major mechanisms to separate substances including polarity, charge, size-exclusion, and affinity
- Broad spectrum “mix and match” capability: The ability to mix and match beads with different extraction capabilities provides a flexibility to remove a broad range of substances that no other technology can match
- High flow, low resistance: Blood can flow rapidly through a bead-filled device with low resistance, achieving flow rates of 100-700 mL/min without causing hemolysis or high pressure drops across the device
- Stable with Long Shelf Life: Solid state chemistry with no cells, biologics or other perishable materials, gamma sterilized with 3-year shelf life at room temperature.
Technology is the Beneficiary of More than $18M in Government Funding
CytoSorbents’ blood and physiologic fluid purification technology aims to solve some of the most important unmet medical needs in medicine, from treating life-threatening illnesses in the intensive care unit, to reducing dangerous complications of surgery, to ensuring the quality and safety of the blood supply. It combines the company’s proprietary hemocompatible porous polymer bead platform with robust and cost-effective manufacturing, compatibility with a worldwide infrastructure of existing dialysis and heart-lung machines, ease of use,
In 2012, the Defense Advanced Research Projects Agency (DARPA) awarded CytoSorbents a $3.8M five year contract as part of its “Dialysis-Like Therapeutics” (DLT) program to treat severe sepsis and septic shock. Sepsis is the result of an overzealous immune response to a serious infection. The DLT program seeks to develop an advanced blood purification system that can remove toxins, cytokines, pathogens and activated white blood cells as a treatment of sepsis. CytoSorbents’ technology was selected to remove cytokines and pathogen-derived toxins. DARPA is a division of the Department of Defense that funds advanced technology and biomedical research, and was responsible for funding the development of such major innovations as the internet, global positioning satellites (GPS), robotic surgery, artificial robotic limbs, a stair-climbing wheelchair, and many others. CytoSorbents collaborates with leading institutions and companies such as Battelle Laboratories, the Harvard Wyss Institute, MIT, and NxStage Medical.
In addition, CytoSorbents is advancing its polymer platform under a $1.15M Phase I and II Small Business Innovation Research (SBIR) contract awarded by the U.S. Army for trauma and burn injury research (2011-present). More recently the FDA approved a U.S. Air Force funded 30 patient human pilot study in trauma and rhabdomyolysis that is currently enrolling. This study is the first human CytoSorb study in critically ill patients in the United States.
CytoSorbents was also awarded a Phase I SBIR contract from the National Heart, Lung and Blood Institute to advance development of its HemoDefend blood purification platform to improve the quality and safety of transfused blood products and to keep fresh blood fresh.
- DARPA (Defense Advanced Research Projects Agency): ~$4 million over 5 years in its “Dialysis-Like Therapeutics” program to treat sepsis and remove inflammatory toxins from blood using blood purification. CytoSorbents is currently in Year 5 of the contract
- U.S. Army SBIR Program: ~$1.7 million in Phase I, II and Phase II enhancement SBIR contracts to treat trauma and burn injury
- U.S. Air Force: Funding a 30-patient randomized controlled pilot study (~$3 million) in the treatment of trauma and rhabdomyolysis
- JPEO-CBD (Joint Program Executive Office for Chemical and Biological Defense): $150,000 in a Phase I SBIR for mycotoxin removal
- U.S. Department of Health and Human Services QTDP Grant: $0.5 million
- National Institutes of Health (NIH): $7 million over 5 years to University of Pittsburgh and Dr. John Kellum to research CytoSorb for the treatment of sepsis
- National Heart, Lung and Blood Institute (NHLBI – a division of National Institutes of Health) and USSOCOM (U.S. Special Operations Command): $1.7 million in a Phase I and II SBIR contract from to advance HemoDefend for purification of pRBCs
- U.S. Army Medical Research Acquisition Activity: $150,000 Phase I STTR contract to develop Universal Plasma
- Defense Health Agency: ~$150K Phase I SBIR contract to develop novel approaches to treat severe hyperkalemia