Econous Systems Inc.

Toronto, Canada

Econous Systems Inc.

Toronto, Canada
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Sheikh S.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Nolan R.,Tyndall National Institute | Thompson D.,Tyndall National Institute | And 3 more authors.
Journal of Colloid and Interface Science | Year: 2015

The connection between antifouling and surface hydration is a fascinating but daunting question to answer. Herein, we use molecular dynamics (MD) computer simulations to gain further insight into the role of surface functionalities in the molecular-level structuration of water (surface kosmotropicity) - within and atop subnanometric organosilane adlayers that were shown in previous experimental work to display varied antifouling behavior. Our simulations support the hypothesized intimate link between surface hydration and antifouling, in particular the importance of both internal and interfacial hydrophilicity and kosmotropicity. The antifouling mechanism is also discussed in terms of surface dehydration energy and water dynamicity (lability and mobility), notably the crucial requirement for clustered water molecules to remain tightly bound for extensive periods of time - i.e. exhibit slow exchange dynamics. A substrate effect on surface hydration, which would also participate in endowing antifouling adlayers with hydrogel-like characteristics, is also proposed. In contrast, the role of adlayer flexibility, if any, is assigned a secondary role in these ultrathin structures made of short building blocks. The conclusions from this work are well in line with those previously drawn in the literature. © 2014 Elsevier Inc.


Thompson M.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Sheikh S.,University of Toronto | Romaschin A.,St Michaels Hospital
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.


Neves M.A.D.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Thompson M.,University of Toronto | Thompson M.,Econous Systems Inc.
Analytical Chemistry | Year: 2016

Aptasensing of small molecules remains a challenge as detection often requires the use of labels or signal amplification methodologies, resulting in both difficult-to-prepare sensor platforms and multistep, complex assays. Furthermore, many aptasensors rely on the binding mechanism or structural changes associated with target capture by the aptameric probe, resulting in a detection scheme customized to each aptamer. It is in this context that we report herein a sensitive cocaine aptasensor that offers both real-time and label-free measurement capabilities. Detection relies on the electromagnetic piezoelectric acoustic sensor (EMPAS) platform. The sensing interface consists of a S-(11-trichlorosilyl-undecanyl)benzenethiosulfonate (BTS) adlayer-coated quartz disc onto which a structure-switching cocaine aptamer (MN6) is immobilized, completing the preparation of the MN6 cocaine aptasensor (M6CA). The EMPAS system has recently been employed as the foundation of a cocaine aptasensor based on a structurally rigid cocaine aptamer variant (MN4), an aptasensor referred to by analogy as M4CA. M6CA represents a significant increase in terms of analytical performance, compared to not only M4CA but also other cocaine aptamer-based sensors that do not rely on signal amplification, producing an apparent Kd of 27 ± 6 μM and a 0.3 μM detection limit. Remarkably, the latter is in the range of that achieved by cocaine aptasensors relying on signal amplification. Furthermore, M6CA proved to be capable not only of regaining its cocaine-binding ability via simple buffer flow over the sensing interface (i.e., without the necessity to implement an additional regeneration step, such as in the case of M4CA), but also of detecting cocaine in a multicomponent matrix possessing potentially assay-interfering species. Finally, through observation of the distinct shape of its response profiles to cocaine injection, demonstration was made that the EMPAS system in practice offers the possibility to distinguish between the binding mechanisms of structure-switching (MN6) vs rigid (MN4) aptameric probes, an ability that could allow the EMPAS to provide a more universal aptasensing platform than what is ordinarily observed in the literature. © 2016 American Chemical Society.


Thompson M.,University of Toronto | Thompson M.,Econous Systems Inc. | Blaszykowski C.,Econous Systems Inc. | Sheikh S.,University of Toronto | Romaschin A.,St Michaels Hospital
Biosensors and Bioelectronics | Year: 2015

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.


Neves M.A.D.,University of Toronto | Blaszykowski C.,Econous Systems Inc. | Bokhari S.,University of Toronto | Thompson M.,University of Toronto | Thompson M.,Econous Systems Inc.
Biosensors and Bioelectronics | Year: 2015

This paper describes a label-free and real-time piezoelectric aptasensor for the detection of cocaine. The acoustic wave sensing platform is a quartz substrate functionalized with an adlayer of S-(11-trichlorosilyl-undecanyl)-benzenethiosulfonate (BTS) cross-linker onto which the anti-cocaine MN4 DNA aptamer is next immobilized. Preparation of the sensor surface was monitored using X-ray photoelectron spectroscopy (XPS), while the binding of cocaine to surface-attached MN4 was evaluated using the electromagnetic piezoelectric acoustic sensor (EMPAS). The MN4 aptamer, unlike other cocaine aptamer variants, has its secondary structure preformed in the unbound state with only tertiary structure changes occurring during target binding. It is postulated that the highly sensitive EMPAS detected the binding of cocaine through target mass loading coupled to aptamer tertiary structure folding. The sensor achieved an apparent Kd of 45±12. μM, and a limit of detection of 0.9. μM. Repeated regenerability of the sensor platform was also demonstrated. This work constitutes the first application of EMPAS technology in the field of aptasensors. Furthermore, it is so far one of the very few examples of a bulk acoustic wave aptasensor that is able to directly detect the binding interaction between an aptamer and a small molecule in a facile one-step protocol without the use of a complex assay or signal amplification step. © 2015 Elsevier B.V.


Pawlowska N.M.,University of Toronto | Fritzsche H.,Chalk River Laboratories | Blaszykowski C.,Econous Systems Inc. | Sheikh S.,University of Toronto | And 3 more authors.
Langmuir | Year: 2014

Neutron reflectometry data and modeling support the existence of a relatively thick, continuous phase of water stemming from within an antifouling monoethylene glycol silane adlayer prepared on oxidized silicon wafers. In contrast, this physically distinct (from bulk) interphase is much thinner and only interfacial in nature for the less effective adlayer lacking internal ether oxygen atoms. These results provide further insight into the link between antifouling and surface hydration. © 2014 American Chemical Society.


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.


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.


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.

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