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Toronto, Canada

A surface-modified polymer is described, comprising a polymeric material and a self-assembling monolayer covalently bound thereto. The monolayer comprises monoethylene glycolated-OH (MEG-OH); 2-(3-trichlorosilyl-propyloxy)-ethyl-trifluoroacetate (7-OEG or MEG-TFA); 2,2,2-trifluoroethyl-13-trichlorosilyl-tridecanoate (TTTA); OEGylated TTTA (OEG-TTTA); S-(2-(2-(2-(3-trichlorosilyl-propyloxy)-ethoxy)-ethoxy)-ethyl)-benzenethiosulfonate (OEG-TUBTS); or a combination thereof. Methods are described for forming a surface-modified polymer by surface activation, such as with plasma. By utilizing the surface-modified polymer to make medical equipment or devices for contacting biological fluids, a reduction in surface fouling and thrombus formation can result. Advantageously, polymeric equipment or components so modified may have a reduction in unwanted chemical interactions leading to fouling or clotting. Short trichlorosilane surface modifiers allow films to be deposited onto poly(ethylene terephthalate), polycarbonate, polypropylene, polyvinyl chloride, polyurethane, and other polymers activated using plasma.

An acoustic wave biosensor comprising a surface of a mixed self-assembling monolayer for receiving a probe-biomolecule is described herein. The biosensor surface may comprise a piezoelectric quartz crystal,for detection purposes with the electromagnetic piezoelectric acoustic sensor (EMPAS)upon which a mixed self-assembling monolayer is formed, which includes at least one linker, such as 2,2,2-trifluoroethyl-13-trichlorosilyl-tridecanoate (TTTA); its oligoethylene glycol (OEG) analog OEGylated TTTA (OEG-TTTA); S-(2-(2-(2-(3-trichlorosilyl-propyloxy)-ethoxy)-ethoxy)-ethyl)-benzenethiosulfonate (OEG-TU BTS). Linker/diluent systems for attaching a functionalizing entity to the surface of a biosensor are described, as well as methods for preparing a biosensor surface with an oligoethylene glycol linker.

A coating for a surface of a surgical implant, the coating including a binding protein for capturing cells to the surface via a bi-functional linker molecule. The linker can have a first functional group (such as a trichlorosilyl group) for covalently linking to the surface, and a second functional group (such as a benzothiosulfonate group) for covalently linking to the binding protein. One exemplary linker molecule is S-(11-trichlorosilyl-undecenyl)benzenethiosulfonate. The coating may be a self-assembled monolayer and may also include a spacer molecule, which can be unreactive with the binding protein. The target cells may be endothelial stem cells (such as endothelial progenitor cells). The binding protein may be an antibody, antibody fragment or non-antibody derived antigen binding molecule. The binding protein may bind a cell surface marker specific to target cell type. Coated surgical implants, and methods of forming such a coating are also contemplated.

Fedorov K.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Sheikh S.,University of Toronto | Reheman A.,University of Toronto | And 4 more authors.
Langmuir | Year: 2014

In contemporary society, a large percentage of medical equipment coming in contact with blood is manufactured from plastic polymers. Unfortunately, exposure may result in undesirable protein-material interactions that can potentially trigger deleterious biological processes such as thrombosis. To address this problem, we have developed an ultrathin antithrombogenic coating based on monoethylene glycol silane surface chemistry. The strategy is exemplified with polycarbonate-a plastic polymer increasingly employed in the biomedical industry. The various straightforward steps of surface modification were characterized with X-ray photoelectron spectroscopy supplemented by contact angle goniometry. Antithrombogenicity was assessed after 5 min exposure to whole human blood dispensed at a shear rate of 1000 s-1. Remarkably, platelet adhesion, aggregation, and thrombus formation on the coated surface was greatly inhibited (>97% decrease in surface coverage) compared to the bare substrate and, most importantly, nearly nonexistent. © 2014 American Chemical Society.

Thompson M.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Sheikh S.,University of Toronto | Romaschin A.,Clinical Biochemistry
Biosensors and Bioelectronics | Year: 2014

Sepsis is one of the leading causes of death around the world. The condition occurs when a local infection overcomes the host natural defense mechanism and suddenly spreads into the circulatory system, triggering a vigorous, self-injurious inflammatory host response. The pathogenesis of sepsis is relatively well known, one of the most potent immuno-activator being bacterial lipopolysaccharide (LPS) - also known as 'endotoxin'. Tests exist to detect endotoxin in bodily fluids, but are expensive, not necessarily user-friendly and require reporter molecules. In addition, the situation for safe and effective anti-endotoxin therapy is problematical. At the present time, endotoxin removal through cartridge hemoperfusion is one of the better alternatives to combat sepsis. The capability to both measure endotoxemia levels and offer an adapted response treatment in a timely manner is crucial for better management and improved prognosis, but is currently unavailable. In this context, we describe herein preliminary research towards the development of an alternative LPS biosensor and an innovative LPS neutralization cartridge to be eventually combined in an all-integrated configuration for the theranostic, personalized treatment of blood endotoxemia/sepsis. LPS detection is performed in a real-time and label-free manner in full human blood plasma, using ultra-high frequency acoustic wave sensing in combination with ultrathin, oligoethylene glycol-based mixed surface chemistry imposed on piezoelectric quartz discs. Biosensing platforms are functionalized with polymyxin B (PMB), a cyclic peptide antibiotic with high affinity for LPS. Analogous surface modification is used on glass beads for the therapeutic cartridge component of the combined strategy. Incubation of LPS-spiked whole blood with PMB-bead chemistry resulted in a significant decrease in the production of pro-inflammatory TNF-α cytokine. LPS neutralization is discussed in relation to the perturbation of its supramolecular chemistry in solution. © 2014 Elsevier B.V.

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