The invention is a series of software modules that, together, process information from peptide phosphorylation microarrays. A majority of the modules implement statistical manipulations or transformations of the data. The result of the analysis is peptides which are potentially involved in biologically or therapeutically relevant signaling pathways. The advantages over other techniques are that it takes into account detection noise, technical and biological variation, and known information in pathway and ontology databases.

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Invention:

This invention provides an efficient framework to represent, acquire, and recover signals in seismocardiogram (SCG) systems, based on the theory of compressed sensing. The target market applications include mainly the health care industry, with possible extensions to security and biometric systems. Currently, the competing technology is the electrocardiogram (ECG). However, the SCG has been shown to provide a wider range of disease detection capabilities compared to the ECG.

The seismocardiogram (SCG) measures the acceleration generated by the mechanical contraction and relaxation activities of the heart. It has been demonstrated to facilitate accurate identification of various coronary artery diseases. However, applications involving SCG are severely hampered by the large amount of data to be processed, preventing real-time monitoring and detection of diseases. This challenge is exacerbated in the case of tri-axial SCG, with the increase in data collected. Addressing this challenge, sparse representation and compressed sensing (CS) represent a promising framework to potentially capture and represent signals significantly below the Nyquist rate. To this end, this invention explores the possibility of using CS with SCG systems, by proposing suitable signal processing algorithms, and evaluating these methods with experimental data. The obtained results demonstrate significant reduction in bandwidth, while maintaining accurate signal recovery.

Applications:

Preliminary research has proved that the following cardiac states can also be detected by seismocardiogram in its early stages as compared to electrocardiogram.

1. Coronary  Artery disease
2. Sports   Medical   (serial   testing,   systolic   performance,   diastolic   performance,   mitral   valve   prolapse, hypertrophic  cardiomyopathy)
3. Ischemic  Heart  Diseases (IHD) 
4. Sinus Arrhythmia:  Tachycardia,  bradycardia 
5. Nonsinus  Arrhythmia:  ventricular  & atrial flutter/fibrillation Hypertension 

Advantages over existing technology:

In this work, a Compressed Sensing-based scheme is proposed to efficiently reduce the bandwidth necessary to process tri-axial SCG signals. The obtained results show that it is possible to achieve at least a 1/3-compression ratio, while still maintaining accurate recovery (quantified by a worst-case PSNR=36.9852 dB, based on preliminary experimental data collected for a group of 10 subjects). Furthermore, the scheme does not require stringent preprocessing. In fact, the segmentation can be performed coarsely, by a windowing scheme that takes into account a complete heartbeat. These properties should facilitate practical implementations of the proposed scheme in a wide range of application scenarios involving SCG signals.

Principal Inventors:

Dr. Francis Bui

Professor
Dept. of Electrical & Computer Engineering

Zexi Yu

PhD Candidate

Dept. Electrical & Computer Engineering

Patent Status:

61/987709 US Provisional – Filed May 02, 2015

Contact:

Raj Nayak

Technology Transfer - ICT

Tel: (306) 966-5875

Email: raj.nayak@usask.ca

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A wrist-sized Magnetic Resonance Imager (MRI) has been designed to enable access to medical images without the use of ionizing radiation. This portable MRI uses new approaches to MRI magnet design and radio transmitter design to encode spatial information into the nuclear magnetic resonance (NMR) signal, reducing the mass of the MRI by an order of magnitude over existing approaches. The MRI design mass is less than 5kg, and it is intended for imaging the wrist for clinical assessment of bone and muscle health for indications such as osteoporosis. This new device, when scaled up, will help provide MRI access to remote regions, in primary health care settings, in the emergency room and in the operating room for use with minimally invasive and robotic surgery. The device is also optimally suited for use in space, where there is a need to monitor bone and muscle conditions while considering constraints on the mass and size of imaging tools.

Need for a portable MRI:

A portable MRI would be especially useful in remote locations, for deployment in war and disaster zones and especially space. The availability of an MRI in a northern mining or military base community’s health clinic could reduce cost and improve the quality of health care. The device could also be economically installed in primary health care locations, like x-ray clinics and nursing homes reducing demand for high-field MRIs in hospitals. Portable MRI would also be useful in the emergency room (ER) and, eventually, in air and ground ambulances. In the ER. a portable MRI would complement portable X-ray tomographs currently deployed; MRIs are safer for children than X-ray tomographs which deliver high doses of ionizing radiation that is potentially carcinogenic. Finally portable MRIs will find application in the operating room where they will be useful for minimally invasive and robotic surgery. In this way operating procedures already developed using open MRI systems, including robotic neurosurgery performed with the use of a massive moving MRI will be extended. The benefits of developing the technology are summarized in Fig. 1.

Portable MRI design:

Clinical MRIs use cryogenic superconducting magnets that weigh many tonnes and use imaging gradients that use tens to hundreds of amps of electric current. This is a serious constraint for a portable MRI and may be overcome through use of lower field magnets (B0 = 0.15T as opposed to B0 ≥ 1.5T) which have a wide range of diagnostic utility (Merl et al., 1999). We use lower field permanent magnets with Halbach geometry to reduce the external stray field (Halbach, 1980). A recent Canadian breakthrough in MRI technology also allows for the elimination of the power consuming magnetic gradient field hardware. Instead of using magnetic field gradients to encode spatial information into the nuclear magnetic resonance (NMR) signal, transmit radio frequency (RF) coils may be used if the phase of the transmitted RF magnetic field, B1, varies spatially. This RF encoding method (Sharp et al. 2013), accompanied by published wrist images (Deng et al., 2013) puts our technology at readiness level (TRL) 4 according to NASA and US DoD guidelines. Combining lightweight Halbach magnet geometries with RF image encoding technology enables the design of an MRI that is portable, and potentially less expensive to build and operate.

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OPPORTUNITY

Respirlyte’s lead innovation is a urine‐based diagnostic to detect and monitor asthma. This assay is designed to help physicians distinguish asthma from other respiratory disorders, and provides them with an objective measure of severity of the disease. This technology is well‐positioned to explore the use of metabolomic‐based biomarkers in diagnosing and monitoring various asthma and non‐asthma conditions (e.g. COPD) and has the potential to be a prognostic and companion diagnostic. The company is currently conducting studies to investigate metabolites that predict impending worsening of disease (prognostic), and is interested in developing a companion diagnostic to specific asthma and COPD therapies.

Currently, Respirlyte is seeking research partners to develop and commercialize its lead product, and industry partners to study responder versus non‐responders to specific asthma and COPD therapies.

TECHNOLOGY

Metabolomics is the study of metabolite profiles in biofluids, which is capable of identifying unique biomarkers signatures associated with disease indications. Our hypothesis has been that different airway diseases will change the metabolism of a person in different ways that will be seen in the urine. Using metabolomics technology, a biomarker profile from the metabolome was identified and patented using nuclear magnetic resonance spectrometry (NMR). This biomarker profile is currently being validated on a mass spectrometry platform which has significant advantages with regard to accuracy, sensitivity and commercial potential. The urine‐based NMR test could correctly diagnose blinded patient samples (healthy controls below the 0.5 line, stable asthma in outpatient clinic or unstable asthma in the ED above the 0.5 line) with greater than 90% accuracy. (Fig. 1) Using the same method Respirlyte has also developed a model which correctly classifies asthma and COPD patients.

DIFFERENTIATION

The competitive advantage of Respirlyte’s test is in its ability to detect inflammation caused by asthma through a simple, noninvasive procedure that can be used objectively with patients of all ages. The competing non‐invasive tests on the market today are either subjective in nature (medical history and physical exam), have a low accuracy (pulmonary function tests), or are age restrictive (spirometry and exhaled nitric oxide).

COMPANY

Dr. Darryl Adamko, President and CEO of Respirlyte, is a Pediatric Pulmonary specialist with strong bench research background after training in a Pediatric Pulmonary Fellowship at The John Hopkins University. Dr. Adamko’s research focus has been within the field of asthma, in both understanding the mechanisms of virus induced asthma attacks and in the mechanisms underlying the development of asthma from infancy. In the last seven years, he has been the lead on team grants developing a novel way to diagnose and monitor patients with asthma using nuclear magnetic resonance analysis of urine

Respirlyte Inc. is a privately‐held discovery stage company located in Saskatoon, Saskatchewan, Canada. The Company is focused on developing respiratory diagnostic assays through the use of metabolomic‐based technologies. Having completed a proof‐of‐concept trial with 135 children, Respirlyte has identified a urine‐based metabolite panel that can distinguish asthma from other respiratory conditions, and provide an objective measure of disease severity.

UNMET MEDICAL NEED

Asthma is one of the most common chronic illnesses, especially in children. There are over 235 million asthmatics worldwide, and 10% are in United States with an estimated annual cost of $18 billion. Childhood asthma is the number one chronic disease in infants and children, representing 25% of asthmatics in the U.S.

Compared to most chronic illnesses such as heart disease and diabetes, asthma is unique as it starts at a young age (before the age of five), which makes asthma more important in terms of years of life affected. Proper diagnosis with the right medications and management plan is critical in order to damage to growing lungs. Unfortunately, making the diagnosis of asthma and adjusting medications are more difficult than for other chronic diseases. The symptoms and objective measurements of lung function, often used to guide therapy, are largely based on the inflammation of the airways. Because measuring airway dysfunction and inflammation in a typical clinical setting is difficult, it is often not done. Instead doctors give trials of therapy. Current asthma diagnostic challenges:

• Standard non‐invasive asthma diagnostics are insensitive or age‐restricted (spirometry and exhaled eNO) or too labour intensive for a standard doctor’s office (e.g. sputum analysis)

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OPPORTUNITY

Researchers at the University of Saskatchewan have designed a new canine synthetic antibody library.  We are looking for industry or academic partners who have specific targets for high-affinity canine antibodies.

APPLICATIONS

Therapeutics: cancer, inflammation
Diagnostics: PET-CT imaging: targeted delivery of isotopes

BACKGROUND

The antibody library, uniquely designed for dogs, was synthesized in an antibody phage –display system.

ANTIBODY LIBRARY FEATURES

 Species specific antibodies
 Stable antibody production
 High throughput platform which uses next generation sequencer

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Benefits of flax lignans:

Lignans are naturally occurring biologically active polyphenolic compounds present in flaxseed. The major lignan in flaxseed is SDG (Secoisolariciresinol diglucoside) and flaxseed is the richest known source of this compound (Fig.1). Cell models, animal studies, epidemiological studies, and randomized human clinical trials have all demonstrated significant potential for flaxseed lignan supplementation in management of or risk reduction for a number of chronic diseases including cancer, heart disease, BPH, hypertension, and inflammatory bowel disease.

History of Industry Engagement:

In 2007 Archer Daniels Midland (ADM) began marketing a flaxseed lignan enriched complex (38% SDG) called BeneFlax® with both FDA and Health Canada approval. Later, ADM stopped production of BeneFlax® to focus on soy isoflavanoids. However there has been a growing body of science to support the value of lignan supplementation in management of chronic diseases. Bioactive enriched products like BeneFlax® are likely to show meaningful therapeutic or chemopreventative properties.

Commercial Opportunity:

Archer Daniels Midland has expressed a willingness to work with any company interested in resuming production of BeneFlax®. We are seeking the interest of investors to revive the technology and resume production of BeneFlax® or a BeneFlax® like product. We believe that the market is now more receptive to this product than it was 8 years ago and the new science including the current studies at the University of Saskatchewan supports an expanded range of uses for BeneFlax® including as a sole therapeutic, an adjuvant therapy, or chemopreventative for chronic disease such as risk factors for cardiovascular disease (e.g. hypercholesterolemia, hypertension) and inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease.

Collaborators:

Dr. Alcorn has built a strong collaborative network of researchers and clinician researchers including Dr. Ed Krol (Pharmacy and Nutrition, Dr. Phil Chilibeck (Kinesiology), Dr. Susan Whiting (Pharmacy and Nutrition), Dr. Sharyle Fowler (Medicine), and Dr. Thomas Hadjistavropoulos (U. of Regina), as well as with one of the original inventors of the technology for BeneFlax, Dr. Alister Muir, to create an integrated package of safety, efficacy, and mechanism of action data for the lignans of flaxseed.

Pre clinical Data:

In Dr. Alcorn’s laboratory, animal model studies demonstrate clear anticholesterolemic effects and in vitro analyses may have identified lignan mode of action (a novel mechanism) in the hypercholesterolemic effect of lignans (results pending). Furthermore, in vitro analyses are demonstrating important effects in inflammatory conditions of the gastrointestinal tract. (Fig 2) As well, in in vitro evaluations we have we demonstrated synergism between the lignans and important chemotherapeutic agents used in treatment of breast or prostate cancer (Table 1).

Clinical Data:

Recently completed Phase IIa human clinical trials in healthy and frail older adults indicate good safety and tolerability of BeneFlax®. Current human clinical trials are underway to examine efficacy of BeneFlax® oral supplementation in patients with 1) mild-to-moderate ulcerative colitis and 2) elderly patients with high normal to stage I hypertension. Furthermore, a validated pharmaceutical analytical method has allowed for important pharmacokinetic (PK) characterizations of the flaxseed lignans (e.g. intestinal permeability in Caco-2, phase II metabolism in intestinal and hepatic microsomes, cytochrome P450 inhibition potential (DDI potential), PK of individual flaxseed lignans in animal models, PK of single oral dose and multiple oral dose administration of BeneFlax® in healthy adults (Fig. 3)). The combination of our biomedical studies on safety, efficacy, and mechanism of action, and clinical trials to confirm the biomedical studies, has compiled important information to begin to establish a scientific basis for possible health claims for the flaxseed lignans.

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The Centre for Biologic Imaging Research and Development (C-BIRD) at the University of Saskatchewan, applies the principles of antibody engineering to develop the next generation molecular imaging agents for three main purposes: early and definitive diagnosis, improved disease characterization, and guiding therapeutic intervention.

C-BIRD is built around a vertically integrated infrastructure, covering state-of-the-art imaging technologies, medical radionuclide production, and antibody engineering, which together enable the development and translation of biologic molecular imaging agents from mice to humans in one centre.

Mission: As a leading Canadian innovator, our mission is to develop biologic imaging technologies to visually characterize disease before symptoms appear while engaging industry and the academic scientific community to leverage C-BIRD infrastructure to advance molecular imaging agents and therapeutics from basic research to translation in patients.

Solutions:

C-BIRD has established a size variant antibody fragment platform for development of molecular imaging agents with high affinity and avidity while displaying optimal pharmacokinetics.

This antibody platform enables the development of optimal nuclear, optical or acoustic imaging agents with desired imaging contrast, perfusion and clearance from circulation in the body.

Services:

C-BIRD offers pre-clinical molecular imaging services as an integral part of our targeted imaging probe development and efficacy program.

Advanced Capabilities

Probe Development:

C-BIRD has developed a high throughput antibody platform for producing custom size variant humanized antibodies fragments for diagnostic imaging and therapeutics and making them available to biotechnology, pharmaceutical and academic institutions to advance their innovations or to develop companion diagnostics.

Novel probe development

 Engineered antibodies: Fab, ScFv, ScFv – Fc, Vhh

 Lariat cyclic peptides

Radiotracer development and production using 24MeV or linear accelerator

 Tc-99

 Zr-89

 In-89

 F-18

(Additional radiotracers are available for conjugation)

Optical probes

 Near infrared fluorescence

Radiochemistry (PET and SPECT) -conjugation of radionuclide to biological molecules (peptides, antibodies, proteins) under GMP conditions

 Automated synthesis

 Separation and purification

Probe validation

 In-vitro validation including flow cytometry

 In-vivo fluorescence imaging

 In-vivo small animal biodistribution

 Large animal dosimetry studies

 Small animal toxicology studies

Imaging Modalities

 Hybrid micro PET (Positron Emmission Tomography) / SPECT (Single Photon Emission computed Tomography) / Optical ( 3D Optical) Imaging

 Clinical PET / SPECT

Technology Platform Core:

C-BIRD has established a molecular imaging technology platform core to advance targeted molecular imaging technologies from preclinical development to human application through the following core competencies at the University of Saskatchewan:

 Antibody Development and Engineering: Saskatchewan Therapeutic Antibody Resource (STAR) has developed a high throughput antibody

production platform for producing humanized antibodies and antibody fragments.

 Radionuclide Production and Radiopharmaceutical Development: Canadian Centre for Nuclear Innovation (CCNI) and Linear accelerator (Linac): CCNI houses and operates a recently commissioned 24MeV cyclotron and GMP radiochemical facilities. Canadian Light Source Linac is the first of its kind facility able to produce Technetium 99 and can produce other medical isotopes.

 Animal Imaging: The College of Medicine houses and operates facilities with preclinical and clinical PET, SPECT, MRI, and optical, and acoustic non-invasive scanners for anatomical and functional imaging of living organisms.

 Large Animal Imaging: Western College of Veterinary Medicine (WCVM) operates a large animal vivarium and provides non-rodent animal models of diseases, which enable advances in diagnostics and drug therapies for animal and human health.

 Toxicology and ADME: The College of Pharmacy and Nutrition provides formulation and toxicology analysis infrastructure and expertise.

Facilities

 Vavarium

 cGMP Radiochemistry

 Imaging

Research and Development:

C-BIRD research and development programs consists of multidisciplinary researchers dedicated to the advancement of preclinical biologic molecular imaging agents for pre-clinical and clinical applications.

The center focuses on biologic imaging probe and technology development and collaborates with industry, government, and academic researchers to advance

molecular imaging agents and therapeutics from basic research to translation in patients.

Our research and development programs in oncology, cardiology and inflammatory disease are driven through our own initiated development efforts as well as in partnership with industry, academic and government institutions.