title: A novel human detoxification system based on nanoscale bioengineering and magnetic separation techniques.
abstract: We describe the conceptual approach, theoretical background and preliminary experimental data of a proposed platform technology for specific and rapid decorporation of blood-borne toxins from humans. The technology is designed for future emergent in-field or in-hospital detoxification of large numbers of biohazard-exposed victims; for example, after radiological attacks. The proposed systems is based on nanoscale technology employing biocompatible, superparamagnetic nanospheres, which are functionalized with target-specific antitoxin receptors, and freely circulate within the human blood stream after simple intravenous injection. Sequestration of the blood-borne toxins onto the nanosphere receptors generates circulating nanosphere-toxin complexes within a short time interval; mathematical modeling indicates prevailing of unbound nanosphere receptors over target toxin concentrations at most therapeutic injection dosages. After a toxin-specific time interval nanosphere-toxin complexes are generated within the blood stream and, after simple arterial or venous access, the blood is subsequently circulated via a small catheter through a portable high gradient magnetic separator device. In this device, the magnetic toxin complexes are retained by a high gradient magnetic field and the detoxified blood is then returned back to the blood circulation (extracorporeal circulation). Our preliminary in vitro experiments demonstrate >95% first pass capture efficiency of magnetic spheres within a prototype high gradient magnetic separation device. Further, based on the synthesis of novel hydrophobic magnetite nanophases with high magnetization ( approximately 55 emu/g), the first biodegradable magnetic nanospheres at a size range of approximately 280 nm and functionalized with PEG-maleimide surface groups for specific antibody attachment are described here. In future applications, we envision this technology to be suitable for emergent, in-field usage for acutely biohazard exposed victims as both the injectable toxin-binding magnetic spheres and the separator device are made to be portable, light-weight, zero-power, and self- or helper-employed. Details of the technology are presented and the state-of-knowledge and research is discussed.
authors.affiliation: Neurocritical Care and Acute Stroke Program, Department of Neurology, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, MC 2030, Chicago, IL 60637, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kaminski
authors.forename: Xianqiao
authors.initials: X
authors.lastname: Liu
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Mertz
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xie
authors.forename: Michael D
authors.initials: MD
authors.lastname: Torno
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Rosengart
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D001698:Biomedical Engineering / Q000379:methods*; D019921:Biotinylation; D002588:Cesium Radioisotopes; D005374:Filtration; D006801:Humans; D018189:Immunomagnetic Separation / Q000295:instrumentation* / Q000379:methods; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000097:blood / Q000737:chemistry; D008280:Magnetics; D008863:Microspheres; D008954:Models, Biological; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods; D043942:Nanotubes / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D002588:Cesium Radioisotopes; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols