Division of Research

Available Technologies

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Advanced Manufacturing

Toolholder: A Wayne State University researcher has developed a novel toolholder device used to connect a cutting tool with the main structure of a machine tool, such as a machining center or turret of a lathe. The toolholder provides a reliable tool clamping design, ensuring that required power can be transmitted to the cutting zone. In addition, the design yields a precise connection in terms of coaxiality between the tool and the toolholder. The toolholder has an all-mechanical design, and does not require hydraulics, bushings, or heat clamp joints. The design employs a clamping sleeve that is integral with toolholder body. The sleeve has tapered external surface separated from a tapered internal surface by a thin rubber layer. Tools are clamped by turning an actuating nut, in a threaded engagement with toolholder body. An actuating sleeve is pushed along clamping sleeve to generate a radial distributed force between the clamping sleeve and the tool. An antifriction bearing or a sliding bearing reduces friction. The axial motion of the actuating sleeve shears deformation in elastomeric layer (laminate) and creates significant mechanical advantage since the wedge-like interaction between tapers of the internal surfaced of the holder takes place without any friction.

Bioengineering

Magnetic Resonance Force Microscopy for the Study of Biological Systems: Magnetic Resonance Force Microscopy (MRFM) is an emerging technology that combines the strengths of magnetic resonance and force microscopy to achieve high resolution three-dimensional sub-surface imaging of a test substance. WSU researchers have adapted and refined MRFM to study biological systems, such as isolated cells, sub-cellular organelles and other sub-cellular structures, or cellular receptors and proteins, at resolutions ranging from 1 micron to 1 angstrom. MRFM has the potential to significantly impact biomedical research and biotechnology, including the potential to replace x-ray crystallography by directly imaging single-copy molecules.
Method for engineering polar drug particles with surface-trapped hydrofluoroalkane-philes: The invention disclosed is a novel method for preparation of spheroidal/spherical polar drug particles with surface-trapped hydrofluoroalkane-philes. This approach can impart long-term physical stability to drug particles dispersed in hydrofluoroalkane (HFA) for use in pressure metered-dose inhalers (pMDI). This advanced technology has advantages compared to what is currently the industry standard, where co-solvents have to be used alongside surfactants to attain similar (or inferior) stability of the dispersion-based formulation. The method is also superior in that no free stabilizers remain in solution thereby reducing toxicity. This invention is expected to be applicable to small molecules and biomolecules that can be formulated free of environmentally toxic chlorofluorocarbons (CFCs).
Method to Stabilize Suspension-Based Formulations in Hydrofluoroalkane Propellants with Nanoparticles: This invention is a new method for engineering porous drug particles with enhanced physical stability and aerosol characteristics in hydrofluoroalkane (HFA) propellants for use in pressure metered-dose inhaler (pMDI) formulations. The approach consists of preparing drug particles containing excipients, which are later remove, resulting in the generation of a porous drug structure. The HFC propellant is capable of penetrating into porous drug particles, thus enhancing the physical stability of the otherwise unstable formulation. This stabilization effect is a significant improvement over existing commercial formulations. Furthermore, this invention enables a wide variety of drugs to be formulated free of environmentally toxic chlorofluorocarbons (CFCs).
Nanoparticle Drug Delivery Compounds for Hydrophilic Drugs: WSU researchers have developed a nanoparticle formulation for the encapsulation of hydrophilic drugs with high efficiency. Encapsulation efficiency close to 100% has been achieved. Further, these nanoparticles demonstrate sustained release of hydrophilic drugs over a period of weeks (~60-80% of encapsulated drug released over a period of 4 weeks). As a comparison, published studies that investigate the use of other state of the art nanoparticles with water-soluble drugs report sustained release only over a period of few hours. Additionally, due to high surface area afforded by nanoparticles, the efficiency of encapsulation of water-soluble drugs to date has been very poor (<50%). The WSU technology is differentiated by the observed ability to encapsulate hydrophilic drugs in nanoparticles with high efficiency and to sustain the release of hydrophilic drugs from the nanoparticles over a period of weeks to months.
An In-Vitro Model System for Studying Development of Human Pre-neoplastic Breast Disease: Wayne State University researchers have developed a novel model/assay system that recapitulates in vitro the in vivo processes that lead to breast cancer development and progression from preneoplastic tissue. This model is the first that demonstrates in vitro the de novo development and neoplastic conversion of functional alveolar units. Advantages of this model include the fact that it requires only about 7 days for alveolar morphogenesis to occur compared to 8-10 weeks in vivo. This permits the use of this system for relatively high throughput drug screening. In this model, preneoplastic human breast epithelial cells interact with two major stromal components, endothelial cells and fibroblasts, on a reconstituted basement membrane and undergo alveolar morphogenesis, a critical step in breast tissue morphogenesis. The inventors have shown for the first time using this model the biological requirements and/or contribution from epithelial cells and stromal components for formation of functional ductal lobular units, and processes that allow neoplastic conversion.

Biofuels

Cetane Improver for Ultra Low Sulfur Diesel (ULSD) Fuel: Cetane improvers, or ignition accelerators, initiate the combustion process under compression ignition conditions. They are added to biodiesel fuel blends to meet the cetane number demands of most diesel engines. Most widely used cetane improvers in the market today accelerate the autoignition of diesel fuel via a free radical mechanism.These free radicals can damage hydrocarbon chains in diesel fuel under long term storage. This problem is severe when ULSD is blended with biodiesel fuel. The cetane improver developed by WSU researchers: - minimizes fuel filter plugging and injector coking due to oxidation of fuel hydrocarbons - reduces smoke during cold start, decrease NOx formation and increase engine durability - won’t oxidize biodiesel in ULSD blends - won’t interfere with the actions of antioxidants additives
Austenitic (Non-magnetic) Structural Steel Composition: Wayne State University research has yielded both a novel composition and a lower cost processing technique for the creation of austenitic, non-magnetic structural steel. This steel has advantages that include a high work hardening rate, good corrosion resistance, combination of strength and ductility and good creep resistance. It has applications in naval structures, ship construction, petrochemical and food processing industries. Use of this steel in energy generation devices will reduce magnetic permeability and thus reduce power loss.
Antioxidant Additives to Improve the Oxidative and Thermal Stability of Biodiesel Fuel: A significant problem associated with the commercial acceptance of biodiesel fuel is poor oxidative stability. The presence of high levels of unsaturated fatty acid methyl esters (FAME) make biodiesel very susceptible to oxidations as compared to petroleum diesel. Oxidative processes can lead to the formation of insolubles which can potentially plug fuel filters and injection systems. The increased acidity and increased peroxide value as a result of oxidation reactions can also cause the corrosion of fuel system components, hardening of rubber components, and fusion of moving components. Researchers at WSU’s National Biofuels Energy Laboratory have identified antioxidant additives for biodiesel fuel made from a variety of feedstocks that improve the long term storage stability of B20 and B100 fuels and enable them to exceed the ASTM D6751-07 standard by as much as four times.
Heterogeneous Biodiesel Catalyst for Simultaneous Transesterification and Esterification of Low-Cost, Unrefined Oils: This catalyst significantly reduces the cost of producing biodiesel fuel by enabling continuous biodiesel production using multiple, low-cost, non food grade feed stocks, including waste oils, without pretreatment to produce high quality biodiesel fuel. Feed stocks such as waste cooking oil, crude oils and rendered animal fat with free fatty acid levels up to 15% and 5% water can be directly converted to biodiesel without costly and time-consuming pretreatment. This catalyst: - minimizes hydrolysis reaction enhancing the yield - is highly active, easy to separate and recover from biodiesel products - minimizes the environmental issues and costs of caustic homogeneous catalysts such as water washing of caustic catalysts, disposal of hazardous waste generated in the washing and soap formation - can be used in batch or continuous biodiesel processing equipment This catalyst operates at 180-2000C and 1-10 atm.
Low Temperature Heterogeneous Biodiesel Catalyst: This solid base heterogeneous catalyst reduces the capital equipment and operating costs of biodiesel production by enabling a one-step conversion of feed stocks with Free Fatty Acid (FFA) levels up to 3.5%. This catalyst operates at 58-800C and 1 atm and: - can be used in existing batch equipment or continuous industrial biodiesel processing equipment - minimizes hydrolysis reaction enhancing the yield - is highly active, easy to separate and recover from biodiesel products - minimizes the environmental issues and costs of caustic homogeneous catalysts such as water washing of caustic catalysts, disposal of hazardous waste generated in the washing and soap formation.

Biologics

Self-Cleaning Transparent Material Structure: A Wayne State University Professor has developed a material with unique self-cleaning properties that may serve a number of applications, from self-cleaning automobile windshields, eyeglasses and optics to laboratory glassware, mirrors and sensors. Highly water-repellant materials (also known as “Superhydrophobic Surfaces”) have been created and employed in a number of applications. However, their widespread use to date has been hampered by the fact that such materials are generally non-transparent. As such, these materials have not been suitable for windows, windshields, camera lenses, and other optical devices. The material developed at the Wayne State University College of Engineering has the unique property of being completely transparent, and as such could be used in applications which to date have not been served by opaque superhydrophobic materials. The invention is a new material structure capable of repelling water and self-cleaning as well as its fabrication methods. Liquid repellency of solid surfaces is critical for many applications, including the prevention of the adhesion of moist and ice to windows, self-cleaning traffic indicators, stopping clotting in artificial blood vessels, and stain-resistant textiles. The hydrophobicity of a surface can be enhanced by a chemical modification that lowers the surface energy. A superhydrophobic surface results from the increase of the surface roughness. This effect can be observed in nature on the leaves of the sacred lotus. The surfaces of these leaves have micrometer-scale roughness (10-100 ìm), resulting in water contact angles up to 170°, because air that is trapped between the droplets and the wax crystals at the plant surface minimizes the contact area. Superhydrophobic surfaces that have water contact angles larger than 150° have been obtained by controlling the surface topography of expensive hydrophobic materials using various processing methods, such as machining and etching. Since all these surfaces have micrometer-scale roughness, they are not optically transparent due to diffraction scattering.

Biotechnology

New Technology and Reagents to Study Protein Structure and Folding in Mammalian Cells: This invention is a new protein transduction method for efficient delivery of exogenous proteins into mammalian cells. In contrast to known protein transduction methods, this new approach has the capability of targeting transduced proteins to different cellular compartments, as well as protecting the proteins from degradation by cellular proteases. The reagent for delivery of the proteins is composed of cationic agents, lipids and enhancer in a carrier. The Approach uses bacteria to produce recombinant proteins that are then modified with the reagent and delivered into mammalian cells. The mammalian cell machinery folds and post-translationally modifies the transduced proteins to produce native functional proteins that can be easily purified from the cells. The final high yield of properly folded and modified protein can be 35-60% of added bacterial expressed proteins. This discovery provides a foundation for future applications of protein transduction technology, atomic resolution cell biology and protein drug therapy to treat human disease to name a few applications.
Mechanically Induced Invasion Assay: This novel assay addresses an unmet need of measuring the mechanical stimulation required to induce cancer cells to leave the tumor and metastasize. The assay has applicability in the pharmaceutical industry where it can be used to screen for inhibitors of mechanically induced invasion/metastasis. Additionally, the assay can have clinically utility in assess a solid tumor’s potential to metastasize and priming normal cells for transplantation.
Method to Identify Anti-Epileptic Targets and Drugs: The invention is a two-step process/method to identify new targets and drugs to prevent and treat epilepsy. The first step is to identify targets for the disease through statistical analysis of human brain gene expression from patients with epilepsy vs. controls. The second step is to test drugs known to affect these targets in a novel animal model of epilepsy that focuses on interictal spiking. This approach has already identified a potential drugable pathway that can be modified with existing drugs to treat the disease.
Repurposing AKT Inhibitors for the Treatment of Protein Misfolding and Protein Trafficking Diseases: WSU investigators have demonstrated that inhibition of pro-survival kinase, AKT, using the transgene, Trb3, expressed in oligodendrocytes, leads to less brain white matter than controls. Moreover, Trb3 introduction into an animal model of the human disease, Pelizaeus Merzbacher disease (PMD) leads to less myelin thickness and fewer disease symptoms than untreated animals. These results suggest inhibiting AKT msy ameliorate the symptons of PDM and other diseases with similar or analogous pathophysiology such as Alzheimer and Parkinson’s disease to name a few.
Novel Target for Drug Screen and Therapeutic Intervention in Infectious Disease: WSU scientists have discovered that the interaction between cytochrome c (CYC) and cytochrome c oxidase (COX) is a novel target for therapeutic intervention in infectious disease. The discovery demonstrated that although the reaction between CYC and COX is highly conserved through nature, it is possible to develop selective therapies that could be effective against a variety of infectious agents without harm to humans. For example, with this system it is possible to isolate novel antibiotics to anti-malaria agents.
Biomarkers in Neocortical Epileptic Tissue: Epilepsy, a disease of recurrent seizures that can develop after a wide range of brain insults, affects up to 1% of the population. While single gene defects are associated with some forms of epilepsy, these mutations do not account for the majority of affected patients. Those patients who do not respond to medications can benefit from removal of the brain regions in which the seizures originate. Little is known about how the often normal-appearing epileptic brain regions become and remain epileptic. The foci, regardless of original insult, show a similar pattern of localized, abnormal electrical discharges that become rhythmic and spread. The inventors applied functional genomic methods to electronically mapped brain tissue.Microarray studies identified activity-dependent genes by comparing electrically active epileptic neocortex to control (normal) neocortex from the same patient. The approach reduced the effects of genetic heterogeneity, medications and anatomical locations. By comparing local gene expression changes within the same individual, the inventors were able to identify a small group of differentially expressed genes, which are a common link to an otherwise heterogeneous disease. Access to these markers overcomes one of the major limitations in developing treatments for patients with epilepsy, that is, the lack of specific targets. Whether the markers are the cause or the result of ongoing epileptic activity will require further research, however, their identification is clearly relevant for the human epileptic condition.
A Diagnostic Marker for Matrix Metalloprotease (MMP)-2 and -9 Activity in Cancer Tissue: This invention is a method for the identification of MMP enzyme activity in tissue. MMPs are involved in tumor progression and therefore are targets for anti-cancer drug therapies. However, most drug therapies directed at inhibition of MMPs have failed, in part, because there is no reliable biomarker to determine MMP activity in tissue. This invention provides a reliable diagnostic tool to monitor MMP activity for clinical trials of MMP inhibitors.
A Single Nucleotide Polymorphism Predicts Human Cancer Risk Associated with Racial Disparity: This invention is a new diagnostic tool which allows prediction of cancer risk based on a single nucleotide polymorphism of a gene whose protein is over-expressed in various cancers. The polymorphism results in a single amino acid change. DNA analysis demonstrated that 98% of cancer patients tested had the mutation while normal donors did not. The extreme high frequency of the mutation suggests that it can be used to custom tailor the frequency of screening tests such as mammograms depending on whether or not an individual carries the mutation. Analysis of this mutation may also provide information to clinicians in evaluating the risk of tumor transition from benign to malignant,potentially affecting the decision to perform surgical procedures. Detection of the mutation can be carried out using routine clinical laboratory methods.
A Novel Cell Cyle and Apoptosis Regulatory Protein and Antibodies Thereto: Retinoic acid and its synthetic derivatives participate in many biological processes including development, cellular proliferation and differentiation. Retinoids mediate their actions by binding to the nuclear retinoic acid receptors and retinoid X receptors. Wayne State University researchers found that retinoid induced cell cycle arrest and apoptosis in several human breast carcinoma cell lines is independent of tumor suppressor p53 and estrogen receptor status, via an undefined mechanism. This led to the identification of a novel cDNA which encodes a 130 Kda protein referred to as CARP-1 (Cell Cycle and Apoptosis Regulatory Protein-1). CARP-1 is expressed in many cancer cell types including breast and colon carcinoma cells. Working with polyclonal antibodies to CARP-1, it was demonstrated that CARP-1 controls cell cycle progression by inhibiting genes such as c-Myc and cyclin B1. CARP-1 is elevated when cells undergo apoptosis in the presence of CD437 or chemotherapeutic drugs. Additionally, CARP-1 is abundant in the benign tissues of colon and breast as well as certain hematopoetic progenitor cells. The polyclonal antibodies to CARP-1 are available for non-exclusive biological materials licensing. A development partner is needed to investigate whether the antibodies may be useful as diagnostic and prognostic tool. Research references: Blood. 2002 Oct 15; 100(8):2917-25; J Biol Chem. 2003 Aug 29;278(35):33422-35.
Neoepitope Detection of Cancer using Protein Arrays: This technology is a new diagnostic chip technology with the express aim of developing new commercial products for the early detection of ovarian cancer and other diseases. The technology employs pattern recognition as a diagnostic rather than a single marker using specialized informatics techniques to interpret the results on numerous markers using biochip technology and specialized laser scanning instrumentation. The diagnostic epitope markers are identified by exploiting the immune system’s reaction to a tumor as a foreign entity. The epitope markers are spotted on a microarray and then exposed to the patient’s diluted serum. This new technology can quantitatively identify the presence of cancer-specific antibodies by measuring the fluorescence of a labeled anti-human antibody recognizing the patient’s own antibodies bound to the epitope clones. The advantages of this microarray biochip technology are its greater sensitivity, its quantitative capacity and small serum requirement.
Chicken Interleukin-2 for use as Vaccine Adjuvant: WSU researchers have cloned and patented chicken IL-2 and related avian lymphokines for use as avian vaccine adjuvants. The inventors have shown experimentally that chicken IL-2 can enhance vaccine effectiveness in chickens. Future research to further enable this technology will likely include optimization of delivery methods. IL-2 has a short serum half-life, and for maximum efficacy must be attached to, or closely associated with, the vaccine antigen(s). Various studies have utilized chicken IL-2 fused to antigen, expressed by viral vaccine vectors and expressed in DNA vaccines. In general, the addition of IL-2 has enhanced both the magnitude and the quality of immune responses.
Enzyme-Activated Nitric Oxide Donors: WSU researchers designed and synthesized a series of new pro-drug nitric oxide donor compositions which are activated by particular glycosidases. Using these compounds, site-specific and controlled-release of nitric oxide can be achieved and thus may be useful for regulating many physiological processes. These drugs have shown anti-cancer and anti-viral effects in vitro and may also have applications as vasorelaxants, antithrombotics, or cytostatic or genotoxic compounds.
Cytokine Attachment for Enhanced Vaccine Effectiveness: Wayne State University researchers have developed a method to produce immunostimulatory cytokine proteins and tether them to the membrane of enveloped virus vaccines produced in cell culture. In vivo results to date indicate that this technology improves vaccine efficacy. Cytokines, as soluble proteins, have proven to be effective as adjuvants for experimental viral vaccines, since they boost immune responses, induce T cytotoxic cells and shift Th2 to Th1 responses. However, there are limitations in formulations currently used to coadminister soluble cytokines: 1. It is difficult to maintain effective cytokine concentrations in close proximity to the virus, 2. The cost of producing recombinant cytokine is high and 3. The in vivo half-life of soluble cytokines is very short. To address these problems, WSU researchers have developed a technology to efficiently and cost-effectively produce membrane-bound cytokines that are expressed on the surface of enveloped viruses.
Novel Source of Pluripotential Stem Cells in the Adult: The existence of multipotent stem cells within the adult brain has been debated for some time. While the identity of this cell has been unknown, it is clear that stem cells reside in specialized tissue (subventricular zone and subgranular zone) and that local microenvironments regulate their differentiation and self-renewal. WSU researchers have identified capillary pericytes as possessing pluripotent stem cell capability. One set of culture conditions result in the differentiation of pericytes along a mesenchymal lineage, forming bone, muscle cells, adipocytes, chondrocytes, as well as dendritic cells. In another set of culture conditions, pericytes differentiate along a neuronal lineage into oligodendrocytes, neurons, and astrocytes. Capillary pericytes from tissues of non-CNS origin are also shown to have similar potential. This technology provides a new source of pluripotential stem cells and could be important to future research studies and therapeutic strategies.
Novel DNA-based Therapeutic Cancer Vaccine: Traditional cancer therapy includes radiation, surgery and chemotherapy, with a few recently developed options for certain types of cancer, such as bone marrow transplant, hormone, antibody and targeted small molecule therapies. Another approach- cancer vaccines- harnesses the body’s own defense mechanism by turning on the production of antibodies, T cells and other immune cells to destroy cancer cells, thus preventing the disease (i.e. preventive vaccine), or controlling the disease (i.e. therapeutic vaccine), without the severe side-effects of conventional therapy, such as those from surgery, radiation and chemotherapy. When successfully vaccinated, the immune system develops a memory to provide long-term protection from disease recurrence. The targeted killing of tumor cells, long term protection from and tremendous economy compared to current therapy are compelling reasons to develop cancer vaccine technology. Until recently, cancer vaccines have demonstrated little success for lack of plausible target molecules and the inability to trigger immune response to self molecules which are found on tumor cells. Wayne State University has developed a novel DNA-based therapeutic cancer vaccine which targets receptors which, when engaged by antibodies, triggers programmed cell death in tumor, but not normal cells. Using a DNA vaccine targeting a specific mouse receptor, the researchers showed the feasibility to induce anti-mouse receptor antibodies by electrovaccinating mice with naked DNA encoding a fusion protein of the mouse receptor fused to a highly immunogenic, but non-toxic fragment of tetanus toxin. WSU recently received funds to advance the proof of concept of this technology by producing the human equivalent of the mouse vaccines for commercialization. This vaccine design follows the process established in the inventor’s lab for human Her-2 vaccine development. Her-2 vaccine construction initiated in 1996 has resulted in a Phase I clinical trial in patients with advanced breast cancer in 2003. The safety of the Her-2 vaccine was demonstrated and the process of constructing and testing this DNA vaccine is in place.
Genus-Wide Chlamydia Peptide Vaccine Candidates: Chlamydia trachomatis is the most prevalent sexually transmitted disease (STD) worldwide; approximately 60 million new cases of C. trachomatis cases occur annually. The actual numbers may be higher, since many cases are asymptomatic. The Institute of Medicine estimates that the U.S. total annual healthcare costs related to these STDs exceeds $2billion. It is estimated that by the age of 30, half of all sexually active women have been infected. Chlamydia genital infection occurs in 5-15% of pregnant women, and 50% of their babies will develop inclusion conjunctivitis or respiratory infections making C. trachomatis the most common ocular pathogen in infants. If women are left untreated, 40% of these infections will progress to pelvic inflammatory disease with permanent damage, resulting in chronic pain, infertility, and potentially fetal death. Wayne State University inventors have developed several peptide vaccine candidates that are genus specific; conformational; and easy to manufacture. These benefits overcome several of the prior impediments to the development of a Chlamydia vaccine: antigenically diverse surface proteins; enhanced survival within host cells; biphasic development cycle; reduced inflammatory responses; and the ability to persist. Research results include antibody responses of peptide-immunized mice against individual peptides; adoptive transfer of spleen cells from immunized mice to SCID which was subsequently challenged with C. trachomatis. Additional challenge studies are being done.
Creation of a Transgenic Bone with an Altered Microenvironment using SCID-Human Model: Metastasis of prostate cancer to bone causes pain, compression fractures, spinal cord compromise, and other complications. The presence of prostate cancer cells in bone leads to a tremendous increase in the turnover of the bone extra cellular matrix. A greater understanding of the interactions between prostate cancer cells and the bone environment is a prerequisite for the development of new, biologically-based therapeutic strategies for patients with skeletal metastases. We developed a “SCID-human” model of prostate cancer metastasis to bone. In this model, macroscopic (1cm) human fetal bone fragments (femurs, humeri) are implanted subcutaneously into immunodeficient (SCID) mice. A few weeks later, after the fragments have successfully engrafted, human prostate cancer cells are injected into the mouse either intravenously or directly in the implanted human bone. This model mimics real bone metastasis on several levels. First, human prostate cancer cells are placed in a human bone environment. Second, we showed that prostate cancer cells grow more rapidly in human bone as compared to other human or mouse organs. Third, the bone’s response to the presence of prostate cancer cell ranges from predominantly osteolytic to predominantly osteoblastic depending on the type of prostate cancer cells used. The SCID-human model is thus relevant to the study of the biology of bone metastasis and to the development of new therapeutic approaches targeting the interaction between human prostate cancer cells and human bone.
GRP94 under the Control of the Polyhedron Promoter in Insect Cells: GRP94 is an inducible resident endoplasmic reticulum/sarcoplasmic reticulum glycoprotein that functions as a protein chaperone and calcium regulator. This protein is upregulated when a cell is under stress, can be present on the cell surface under certain conditions and has been shown to act as a receptacle for cell surface antigens. Collaborators at Wayne State University and Indiana University have cloned the canine GRP94 gene into a baculovirus under the control of the polyhedron promoter. This recombinant baculovirus can be used to produce significant quantities of the canine GRP94 protein in insect cells. Available non-exclusively.
Combined Heterogeneous and Homogeneous Catalytic Process for Continuous Industrial Biodiesel Production Process: WSU researchers developed a combined heterogeneous and homogeneous catalyst that reduces overall production costs, expands feedstock options, and enables large volume production in a continuous process as compared to traditional homogeneous biodiesel catalysts. This unique catalytic transesterification process works better with ethanol compared to methanol can be used in continuous or batch biodiesel production processes and has advantages over existing homogeneous catalyst processes including: - Eliminates use of caustic catalysts that generate significant soap formation and environmental issues - Eliminates large volume of water used to remove homogeneous catalysts and soap by-product - Simplifies the catalyst and biodiesel/glycerol separation process - Catalyst can be recycled
Experimental Bone Metastatic Prostate Tumor Model: A Wayne State University researcher has derived new tumorigenic cell lines from the human prostate carcinoma cell line PC-3. These cell lines, known as PC-3/IF, when implanted in the femurs of nude mice, provide a xenograft tumor model of bone metastatic prostate carcinoma. The PC-3/IF cell lines are highly tumorigenic, with tumor cells replacing the marrow cells in the bone cavity, invading adjacent bone and muscle tissue to ultimately form a palpable tumor at the hip joint.
Experimental Metastatic Prostate Tumor Model: A Wayne State University researcher has developed new tumorigenic cell lines from the human prostate carcinoma cell line PC-3. These cell lines, known as PC-3/PI, are highly tumorigenic when implanted in the prostate of nude mice, providing a xenograft tumor model of prostate carcinoma. In this model, lymph node metastases form from the primary tumor as in human prostate carcinoma. Available non-exclusively via biological materials licensing.
Experimental Renal Cell Carcinoma Tumor Model: A tumor cell line from a primary papillary renal cell carcinoma (RCC) (nuclear grade III/IV) was developed by WSU researchers. This cell line, known as KCI-18, when implanted in the kidney of nude mice provides a xenograft tumor model of RCC. The KCI-18 cell line is highly tumorigenic, with lung metastases forming from the primary tumor as in human renal cell carcinoma. Available non-exclusively via biological materials licensing.
Assessment of the Induction and Course of Cellular Programmed Cell Death over Time: Researchers at Wayne State University have developed a novel method to identify and analyze the process of programmed cell death (apoptosis) in living cells over time—without killing the cells. The method has initially been applied to the analysis of PCD in neurons but could be used in the study of any disease process and of PCD in a number of different cell types.
Novel Mammalian Gene Encoding a Putative Phosphatidyl 4-Phosphate 5-Kinase: Researchers at Wayne State University have discovered a novel mammalian gene which may be involved in membrane trafficking, more specifically, insulin-induced translocation of the fat/muscle-specific glucose transporter GLUT4. This material is a potentially valuable research tool for investigation relating to the diagnosis or therapy of diabetes.
B3 Adrenergic Receptor Protein and DNA Encoding Same: The B3-Adrenergic receptor protein and DNA which encodes same, vectors containing the DNA, host cells transformed with the vectors and methods of using the protein, the DNA and the transformed host cells.
Comprehensive set of Campylobacter jejuni Open Reading Frames: A set of proprietary biological materials in the form of bacterial clones is available from Wayne State University. The materials are clones for most of the predicted open reading frames from the bacterial pathogen, Campylobacter jejuni. Each clone consists of the DNA encoding an ORF. Clone sets such as this have several uses, including construction of DNA arrays and microarrays for RNA expression profiling and for genotyping; expression and identification of C. jejuni proteins for various structural and biochemical assays including protein microarrays and complex determinations; and production of proteins for use in development of diagnostic assays, immunotherapies, drugs or vaccines. This technology was developed with Michigan Life Sciences Corridor funding and thus licensees are required to work with the MLSC Purchasing Consortium and the Michigan Economic Development Corporation to provide Michigan companies and researchers with price reductions.
Shutter Vector, Resistance Genes and Candida Albicans Transformant Library for Identification and Cloning of Resistance and Virulence Genes: Currently, C. albicans genes are analyzed by disrupting both copies, one at a time. This approach is laborious and may not reveal a particular phenotype if the gene is redundant. Additionally, deletions of many genes can be lethal. This WSU technology involves a functional genomics approach to C. albicans research, by studying the effect of overexpression of a single gene on phenotype. The process introduces normal genes back into C. albicans at a high copy number, so that the gene is overexpressed and changes the phenotype of the recipient cell. Biological materials available through this technology platform include the shuttle vectors themselves; the transformants; genes in vectors libraries; and individual plasmids with tailored genes. Biological materials licensing is available.
Simple, Inexpensive Regulated Expression of Proteins in Yeast: WSU faculty has developed a new method to regulate protein in expression in yeast, including a set of plasmids and yeast strains which can be used alongside other regulated expression systems. Expression systems that can be regulated are particularly useful because they allow an experimenter to control the timing and levels of gene expression. This approach can aid high throughput yeast two-hybrid assays, which rely on maintaining large libraries of expression strains, which are eventually mated to conduct assays for protein interactions. The technology is described in Finley, et.al, “Regulated expression of proteins in yeast using the MAL61-62 promoter and mating scheme to increase dynamic range,” Gene, Vol. 285 (1-2) (2002) pp. 49-57.
Mug Protein Reagents to Assess DNA Damage and Repair: WSU researchers have cloned the gene in E. coli which codes for the Mug Protein, the enzyme that removes ethenocytosine from damaged DNA in the first step in DNA repair. The presence of ethenocytosine can be used as a biomarker for cancer, to evaluate potential carcinogens and to evaluate environmental toxins. The following biological materials are available for license on a non-exclusive basis: clone encoding the Mug DNA sequence, purified Mug protein, mug- strains, anti-Mug antibodies and antisera. These reagents can be used to assess DNA damage and repair, mutations and environmental toxicology and should be of interest to cancer researchers, toxicologists and molecular biologists.
Antibodies to Human SIRT2: Studies of yeast have shown that the SIR2 gene family is involved in chromatin structure, transcriptional silencing, DNA repair, and control of cellular life span. Functional studies of human SIRT2, a homolog of the product of the yeast SIR2 gene, indicate that it plays a role in mitosis. Further discussion of this research can be found in Mol Cell Biol. 2003 May; 23(9): 3173–3185.
Novel RNAi Vector for use in Plants: A novel RNAi vector to silence, post transcription, a target gene in plants is available from Wayne State University. The presence of the vector in the plant is transient and therefore not passed on to subsequent generations. F1 generation plants do not contain the vector. Plants are treated by the standard biolistics method using vector coated tungsten particles. This vector should be applicable to species from 44 plant families which include Chenopodiaceae (spinach, beets, swiss chard), Solanaceae (tomato, potato, pepper, tobacco, petunia), Brassicaceae (mustards), Asteraceae (sunflower, zinnia), Caryophyllaceae (carnation), Ranunculaceae (anemone, delphinium), Fabaceae (beans), Cucubitaceae (cucumber, melon), and Malvaceae (hibiscus). Advantages of this vector can be realized in hybrid seed production. It is possible to knock out the genes which produce male plants and thus generate female stock for seed production. Since significant quantities of seeds could thus be gathered from F1 generations appropriately treated, seed producers will benefit from the shorter time frames, smaller space needs and uniform F1 genome. The vector can also be used to reduce or block the synthesis of allergens in animal or human food plants.
Fluorescence-Based Assay for Demethylation: WSU researchers have developed a fluorescence-based assay for the dealkylation activity of the non-heme iron (II) a-ketoglutarate-dependent dioxygenase family of enzymes. This assay uses formaldehyde dehydrogenase to convert formaldehyde to formic acid and monitors the creation of an NADH analog using fluorescence. The technology is a great improvement over the existing assays for DNA demethylation in that is continuous, rapid and does not require radioactively labeled material. Additionally, this assay may also be utilized to study the demethylation of histones. This invention has been reported in T. W. Roy and A. S. Bhagwat, “Kinetic studies of E. coli AlkB using a new fluorescence-based assay for DNA demethylation,” Nucleic Acids Research, 2007, Vol. 35, No.21.

Computer Hardware & Software

Anesthesia Depth Diagnosis Assistance System: A novel information processing methodology has been developed to assist in anesthesia administration. Based on signals from commonly used anesthesia monitoring and administration equipment, the method combines expert knowledge of the anesthesiologist and real-time data collected during the surgery to establish and update individual patient models that relate multiple drug infusion rates to their impacts on anesthesia depth and physiological variables. These models are then used to predict the results of drug infusion decisions on the outcome during the operation or other anesthesia procedures. It is envisioned that these predictions could serve as valuable decision-making assistance tools for the anesthesia administrator. The methodology is based on clinical modeling, fast identification and knowledge-based information processing, and stochastic analysis. The research team is currently developing and testing prototype devices.
Sleep Apnea Diagnostic and Treatment Algorithm: Wayne State University inventors have developed practical software models and monitoring methods that could speed and improve the diagnosis and treatment of inspiratory flow limitation and sleep apnea. A model has been developed that can accurately and rapidly analyze clinical lab data to detect inspiratory flow limitation and sleep apnea. This model replaces conventional manual analysis methods that are subjective and take several hours with software that analyzes the same data in a matter of seconds. This invention could save time, increase throughput and improve accuracy in sleep clinic environments. Complementary technology from the same inventors eliminates the need to invasively measure pressure changes in a patient’s throat, an unfortunate necessary element of current state of the art diagnostic practice. Additionally, the inventors have developed a method to accurately predict pharyngeal cross-sectional area (CSA) during sleep non-invasively using finite element analysis (FEA). Used in conjunction with the previous invention, these improvements could lead to more comfortable diagnostic tests that are easy to operate, and highly accurate self-administered tests for home diagnostics. Furthermore, these inventions may allow for significant algorithm improvements for therapeutic devices that expertly adjust flow rate during operation to insure ideal breathing profile for patients throughout the night.

Diagnostics

Biomarker and Potential Therapeutic Target in Amplified Cancer: This invention identifies a new biomarker for breast and other cancers that carry certain gene amplifications. The biomarker could also be useful for diagnosing a patient’s responsiveness to certain cancer therapies and on its own be a possible target for therapeutic intervention in certain cancers. This biomarker can be easily detected/measured using reagents developed by the WSU inventors.
Biomarkers in Neocortical Epileptic Tissue: Epilepsy, a disease of recurrent seizures that can develop after a wide range of brain insults, affects up to 1% of the population. While single gene defects are associated with some forms of epilepsy, these mutations do not account for the majority of affected patients. Those patients who do not respond to medications can benefit from removal of the brain regions in which the seizures originate. Little is known about how the often normal-appearing epileptic brain regions become and remain epileptic. The foci, regardless of original insult, show a similar pattern of localized, abnormal electrical discharges that become rhythmic and spread. The inventors applied functional genomic methods to electronically mapped brain tissue.Microarray studies identified activity-dependent genes by comparing electrically active epileptic neocortex to control (normal) neocortex from the same patient. The approach reduced the effects of genetic heterogeneity, medications and anatomical locations. By comparing local gene expression changes within the same individual, the inventors were able to identify a small group of differentially expressed genes, which are a common link to an otherwise heterogeneous disease. Access to these markers overcomes one of the major limitations in developing treatments for patients with epilepsy, that is, the lack of specific targets. Whether the markers are the cause or the result of ongoing epileptic activity will require further research, however, their identification is clearly relevant for the human epileptic condition.
A Diagnostic Marker for Matrix Metalloprotease (MMP)-2 and -9 Activity in Cancer Tissue: This invention is a method for the identification of MMP enzyme activity in tissue. MMPs are involved in tumor progression and therefore are targets for anti-cancer drug therapies. However, most drug therapies directed at inhibition of MMPs have failed, in part, because there is no reliable biomarker to determine MMP activity in tissue. This invention provides a reliable diagnostic tool to monitor MMP activity for clinical trials of MMP inhibitors.
A Single Nucleotide Polymorphism Predicts Human Cancer Risk Associated with Racial Disparity: This invention is a new diagnostic tool which allows prediction of cancer risk based on a single nucleotide polymorphism of a gene whose protein is over-expressed in various cancers. The polymorphism results in a single amino acid change. DNA analysis demonstrated that 98% of cancer patients tested had the mutation while normal donors did not. The extreme high frequency of the mutation suggests that it can be used to custom tailor the frequency of screening tests such as mammograms depending on whether or not an individual carries the mutation. Analysis of this mutation may also provide information to clinicians in evaluating the risk of tumor transition from benign to malignant,potentially affecting the decision to perform surgical procedures. Detection of the mutation can be carried out using routine clinical laboratory methods.
Early Lung Cancer Marker: Lung cancer is the leading cause of cancer-related death in most developed countries and a form of cancer that has a particularly poor prognosis, based in part on the difficulty of detecting the disease in its early stages. Wayne State University researchers have identified a lung-specific marker for the early diagnosis of lung cancer. Preliminary experiments show that the marker is developmentally regulated; its promoter contains a novel and conserved oxygen sensing element and the marker is dramatically down regulated in all lung cancers tested. While testing has been performed in lung biopsy specimens, researchers are developing a novel assay that will be capable of testing sputum, saliva and bronchoalveolar lavage samples. There is potential for use of a non-invasive test like this for screening smokers as a high-risk population for developing lung cancer.
A Novel Cell Cyle and Apoptosis Regulatory Protein and Antibodies Thereto: Retinoic acid and its synthetic derivatives participate in many biological processes including development, cellular proliferation and differentiation. Retinoids mediate their actions by binding to the nuclear retinoic acid receptors and retinoid X receptors. Wayne State University researchers found that retinoid induced cell cycle arrest and apoptosis in several human breast carcinoma cell lines is independent of tumor suppressor p53 and estrogen receptor status, via an undefined mechanism. This led to the identification of a novel cDNA which encodes a 130 Kda protein referred to as CARP-1 (Cell Cycle and Apoptosis Regulatory Protein-1). CARP-1 is expressed in many cancer cell types including breast and colon carcinoma cells. Working with polyclonal antibodies to CARP-1, it was demonstrated that CARP-1 controls cell cycle progression by inhibiting genes such as c-Myc and cyclin B1. CARP-1 is elevated when cells undergo apoptosis in the presence of CD437 or chemotherapeutic drugs. Additionally, CARP-1 is abundant in the benign tissues of colon and breast as well as certain hematopoetic progenitor cells. The polyclonal antibodies to CARP-1 are available for non-exclusive biological materials licensing. A development partner is needed to investigate whether the antibodies may be useful as diagnostic and prognostic tool. Research references: Blood. 2002 Oct 15; 100(8):2917-25; J Biol Chem. 2003 Aug 29;278(35):33422-35.
Sleep Apnea Diagnostic and Treatment Algorithm: Wayne State University inventors have developed practical software models and monitoring methods that could speed and improve the diagnosis and treatment of inspiratory flow limitation and sleep apnea. A model has been developed that can accurately and rapidly analyze clinical lab data to detect inspiratory flow limitation and sleep apnea. This model replaces conventional manual analysis methods that are subjective and take several hours with software that analyzes the same data in a matter of seconds. This invention could save time, increase throughput and improve accuracy in sleep clinic environments. Complementary technology from the same inventors eliminates the need to invasively measure pressure changes in a patient’s throat, an unfortunate necessary element of current state of the art diagnostic practice. Additionally, the inventors have developed a method to accurately predict pharyngeal cross-sectional area (CSA) during sleep non-invasively using finite element analysis (FEA). Used in conjunction with the previous invention, these improvements could lead to more comfortable diagnostic tests that are easy to operate, and highly accurate self-administered tests for home diagnostics. Furthermore, these inventions may allow for significant algorithm improvements for therapeutic devices that expertly adjust flow rate during operation to insure ideal breathing profile for patients throughout the night.
Neoepitope Detection of Cancer using Protein Arrays: This technology is a new diagnostic chip technology with the express aim of developing new commercial products for the early detection of ovarian cancer and other diseases. The technology employs pattern recognition as a diagnostic rather than a single marker using specialized informatics techniques to interpret the results on numerous markers using biochip technology and specialized laser scanning instrumentation. The diagnostic epitope markers are identified by exploiting the immune system’s reaction to a tumor as a foreign entity. The epitope markers are spotted on a microarray and then exposed to the patient’s diluted serum. This new technology can quantitatively identify the presence of cancer-specific antibodies by measuring the fluorescence of a labeled anti-human antibody recognizing the patient’s own antibodies bound to the epitope clones. The advantages of this microarray biochip technology are its greater sensitivity, its quantitative capacity and small serum requirement.
Role of Truncated Integrins in Cancer: Researchers have discovered that cell adhesion receptors such as integrins may be secreted into the blood. Specifically, cancer patients may secrete truncated integrins. Detection of such markers by ELISA or other methods could be of diagnostic or prognostic value. Wayne State University researchers have discovered that, in addition to the expression of an authentic wild type integrin, there is a novel alternately spliced variant expressed in certain cancer cells. This variant is a truncated version because it does not code for the transmembrane and cytoplasmic portions and, therefore, could exist as a soluble marker. An antigen was designed based on a unique sequence that is specifically expressed in the truncated gene product, but not present in the wild type integrin. An antibody was raised to this peptide sequence and used in Western blotting. Further studies revealed that several human tumor cells such as prostate adenocarcinoma, melanoma, and erythroleukemia, express the truncated integrin.
Molecular Targets of Cancer and Aging: WSU faculty developed an approach to identify gene-expression changes in spontaneously immortalized human cell lines as compared to non-immortal cells. This approach led to the identification of molecular targets required for the long lifespan spontaneously acquired by cancer cells. These targets may provide a potential means to intervene in the process of aging or cancer development of a series of genes involved.
Assessment of the Induction and Course of Cellular Programmed Cell Death over Time: Researchers at Wayne State University have developed a novel method to identify and analyze the process of programmed cell death (apoptosis) in living cells over time—without killing the cells. The method has initially been applied to the analysis of PCD in neurons but could be used in the study of any disease process and of PCD in a number of different cell types.
Antibodies to Human SIRT2: Studies of yeast have shown that the SIR2 gene family is involved in chromatin structure, transcriptional silencing, DNA repair, and control of cellular life span. Functional studies of human SIRT2, a homolog of the product of the yeast SIR2 gene, indicate that it plays a role in mitosis. Further discussion of this research can be found in Mol Cell Biol. 2003 May; 23(9): 3173–3185.
Fluorescence-Based Assay for Demethylation: WSU researchers have developed a fluorescence-based assay for the dealkylation activity of the non-heme iron (II) a-ketoglutarate-dependent dioxygenase family of enzymes. This assay uses formaldehyde dehydrogenase to convert formaldehyde to formic acid and monitors the creation of an NADH analog using fluorescence. The technology is a great improvement over the existing assays for DNA demethylation in that is continuous, rapid and does not require radioactively labeled material. Additionally, this assay may also be utilized to study the demethylation of histones. This invention has been reported in T. W. Roy and A. S. Bhagwat, “Kinetic studies of E. coli AlkB using a new fluorescence-based assay for DNA demethylation,” Nucleic Acids Research, 2007, Vol. 35, No.21.

Energy

High Voltage Vibration Energy Harvesting Device: Current vibration energy harvesting devices typically employ piezoelectric bimorph or a bimorph with a shim in the middle. Wayne State University researchers have designed an energy harvesting device using an air-space piezoelectric cantilever instead of the piezoelectric bimorph. The use of the air-space cantilevers produces the following advantages over current energy harvesting device design: - Significant increase in voltage generated - Increase in efficiency of converting vibration mechanical energy to electrical energy (<90%) A prototype of this design has been built and successfully tested confirming the analytical advantages above. This invention will be valued in a variety of applications including PDAs, cell phones, vehicle tire pressure sensor monitors, wireless sensor network as well as medical devices such as pace makers.

Environmental

Device and Method to Remove Arsenic from Drinking Water: WSU faculty developed an innovative biological technology that has promise to cost-effectively remove arsenic from drinking water. The technology employs the use of a genetically engineered strain of yeast with the ability to hyper-accumulate arsenic without releasing the arsenic back into the environment. The yeast is being optimized for arsenic accumulation; the next step will be the development of bioreactors to remove arsenic from natural groundwater supplies. While federal legislation is still in flux regarding the implementation date for new maximum contaminant levels for arsenic, several federal funding opportunities are available from the NIH, the EPA and the NSF. WSU is searching for a development partner to advance this technology.
Novel RNAi Vector for use in Plants: A novel RNAi vector to silence, post transcription, a target gene in plants is available from Wayne State University. The presence of the vector in the plant is transient and therefore not passed on to subsequent generations. F1 generation plants do not contain the vector. Plants are treated by the standard biolistics method using vector coated tungsten particles. This vector should be applicable to species from 44 plant families which include Chenopodiaceae (spinach, beets, swiss chard), Solanaceae (tomato, potato, pepper, tobacco, petunia), Brassicaceae (mustards), Asteraceae (sunflower, zinnia), Caryophyllaceae (carnation), Ranunculaceae (anemone, delphinium), Fabaceae (beans), Cucubitaceae (cucumber, melon), and Malvaceae (hibiscus). Advantages of this vector can be realized in hybrid seed production. It is possible to knock out the genes which produce male plants and thus generate female stock for seed production. Since significant quantities of seeds could thus be gathered from F1 generations appropriately treated, seed producers will benefit from the shorter time frames, smaller space needs and uniform F1 genome. The vector can also be used to reduce or block the synthesis of allergens in animal or human food plants.

Instrumentation

Method for Infrared Imaging of Ultrasonically Excited Subsurface Defects in: A thermal imaging system for detecting cracks and defects in a component has been developed. An ultrasonic transducer is coupled to the specimen to be evaluated through a malleable coupler. Ultrasonic energy causes the defects to heat up and the defects are easily detected by a thermal camera. This technology has already generated a substantial amount of interest within industry and in the field of non-destructive evaluation.
Method and apparatus for ultrasensitive heterodyne detected surface-selective nonlinear optical spectroscopies: This invention describes a new method for performing surface-selective spectroscopic detection with high sensitivity and detection limits particularly in the visible and fingerprint mid-infrared spectral regions. The method offers a substantial improvement, 10-fold or more, over existing techniques. Detection of absorbed molecules at interfaces is of vital importance in many areas of chemistry, physics and biology. Some specific applications of this technology relate to surface functionalization chemistry, semiconductor passivation, biofouling and cell membrane biology. This invention has already been reduced to a functioning prototype. Unlike other spectrometers in its class, this invention achieves superior performance without the need for surface enhancements, use of additional substrates or fluorescent labels.
Coupled electrostatic ion and electron traps for electron capture dissociation-tandem mass spectrometry: Electrostatic ion traps have recently emerged as a simple means of trapping ions for high resolution mass spectrometry. By properly joining these with an analogous electron trap, electron capture dissociation may be achieved with high efficiency. This is important for applications in proteomics. Currently, electron capture dissociation (ECD) may be achieved only in expensive FT-ICR mass spectrometers. ECD is important to further advances in proteomics in that it provides non-ergodic fragmentation for protein sequencing. The approach developed by a Wayne State University researcher is simple and powerful and provides an avenue to develop ECD based tandem mass spectrometers at reduced cost and increased versatility.
Velocity imaging tandem mass spectrometer: Currently, tandem mass spectrometry is typically performed by selecting a single mass peak in a time of flight or quadrupole mass spectrometer, which is then fragmented through collision, after which the products are mass-selected in a quadrupole or similar secondary mass spectrometer. A Wayne State University researcher has developed an alternative approach which records the full 2-D tandem mass spectrum at once, revealing the correlations between the mass speaks formed in the first and second step. Velocity map imaging is coupled with pulsed electric deflection in a reflectron configuration to achieve spatially-resolved mass dispersion without the use of magnetic fields. Furthermore, when orthogonal deflection pulses are employed with an intervening fragmentation step such as laser induced fragmentation, then a two-dimensional image of the full tandem mass spectrum is obtained at once.
Magnetic Resonance Force Microscopy for the Study of Biological Systems: Magnetic Resonance Force Microscopy (MRFM) is an emerging technology that combines the strengths of magnetic resonance and force microscopy to achieve high resolution three-dimensional sub-surface imaging of a test substance. WSU researchers have adapted and refined MRFM to study biological systems, such as isolated cells, sub-cellular organelles and other sub-cellular structures, or cellular receptors and proteins, at resolutions ranging from 1 micron to 1 angstrom. MRFM has the potential to significantly impact biomedical research and biotechnology, including the potential to replace x-ray crystallography by directly imaging single-copy molecules.

Materials

Fabrication Method for Anti-Reflection Surface on Electric Display Screens: Electronic display screens are difficult to see when light reflects off their surface. Glare, caused from reflected light, reduces the quality of displayed text and images on screens made of glass or plastic. Currently, anti-reflection (AR) screens are made by using a MgF2 coating that reduces reflected light by lowering the refractive index of the surface of the display screen to a refractive index closer to that of air. This process is known as index matching. This coating process has several drawbacks, including: - There are very few transparent substrates that produce an AR surface with this coating limiting a manufacturer’s ability to optimize substrate selection for cost or durability - Adhesion issues often arise between the substrate and coating restricting substrate selection to even fewer candidates - Coating material (MgF2) cost and deposition processing cost, time and complexity Wayne State University researchers have developed a fabrication method that uses optical nanostructures as artificial materials that match refractive indices of a wide range of transparent substrates. The resulting surface is optically transparent and exhibits qualities required to see images and text clearly on an electronic display screen in a wide variety of light conditions. This novel fabrication process is superior to the current AR process in several ways: - Produces excellent reflection of light across a wide range of transparent substrates - Reduces fabrication cost due to a faster, simpler process - Eliminates adhesion issues This fabrication technology will benefit a number of applications and industries including display screens for TVs, computer monitors, cell phones, PDAs, optical sensors used in military, industrial and medical applications as well as solar panels.
High strength High Toughness Bainitic Steel: This invention is a unique composition of steel, when subjected to a non-conventional austempering process, results in the following physical property advantages over high strength low alloy (HSLA) steel: - Twice the strength - Almost three times the fracture toughness Austempering is a process typically used to produce specialty cast iron products but is not employed in the processing of steel. The austempering process that is unique to this invention alters both the temperature and time profiles of iron austempering to increase nucleation sites resulting in a finer grain microstructure that is responsible for the superior physical properties of this High Strength High Toughness (HSHT) Bainitic Steel. HSLAs are used in a number of applications and structures that are required to handle large amounts of stress, often at very low temperatures. Examples included automotive and agricultural components, bridges, railway, defense, construction and mining applications. This invention will be valued in those applications that will benefit from even greater strength and fracture toughness than HSLA.

Medical Devices

Ring Shaped Stent for Blood Flow Reduction in an Aneurysm Sac: Irregularly shaped and wide-necked aneurysms limit the effectiveness of current stent technology. Studies of aneurysm models have shown complex blood flow changes in an aneurysm after the placement of a stent across the aneurysm neck. Sub acute thrombosis is a risk after placement of a stent to block an aneurysm, especially using a stent that isn’t well matched to the size and shape of the blood vessel. Wayne State University researchers have developed a ring-shaped stent to be used for arteries with complex shapes near aneurysm sacs where traditional stents don’t fit very well. This stent invention creates a shear layer to reduce flow going into the aneurysm sac using unique stent geometry with an internal obstacle that reduces the vorticity of blood flow downstream of the stent and aneurysm. Blood flow fluid dynamics modeling has confirmed the effectiveness of this geometry over a wide range of comparison geometries.
Bypass Graft Design to Reduce Formation of Intimal Hyperplasia: Vascular disease with narrowing peripheral arteries is a common manifestation of arteriosclerosis and atherosclerosis. Bypass grafting is commonly employed to restore circulation to the lower extremities. One of the principal causes of failure of bypass grafts is anastomotic intimal hyperplasia (IH) which causes the gradual narrowing of the vessel lumen. While the exact mechanism of IH remains uncertain, there are indications that mechanical factors, such as fluid dynamics, have an influence on the initiation and development of IH. Wayne State University researchers, using fluid dynamics modeling of blood flow, have created a laterally diffused bypass graft configuration that offers an optimal geometry for the anastomosis as a function of hemodynamic properties. By optimizing blood flow from the bypass graft to the artery, formation of IH may be reduced along with unobstructed vessels and decreased morbidity.
3D Neural Probes with Electrical and Chemical Interfaces for Neurostimulation and Drug Delivery: Neural probes are critical devices for many neuroscience researches, neural prosthesis applications, and treatment of various neural disorders. They can be surgically implanted in the target area of the brain as determined by the disorder to provide neurostimulation. While 3D neural probes are advantageous over 2D in many cases, they have been difficult and costly to produce. A desirable feature of neural probes is the integration of microfluidic channels for the delivery of chemicals. These micro-channels can deliver neurotransmitters for chemical stimulation or regulation of neurons and also deliver drugs to reduce tissue inflammation, prevent biofouling, promote neuron growth, and treat certain disease. Integration of micro-channels with electrodes has proven challenging in 3D space. WSU researchers have developed a unique design for a 3D neural probe with both electrical and chemical interfaces that simplifies the fabrication process, increases the yield and lowers overall cost.
Stool/Tissue Preservation Device: WSU inventors have designed devices that enable small pieces of human tissue or stool to be rapidly immersed and preserved at room temperature in toxic preservatives without exposing the end user to the toxicants. Samples contained in the device can be safely stored or used for biochemical, molecular and structural analysis. The device design makes them very easy and safe to operate. They can be used at home, hospital or out in the field for forensic sample collection without the need for refrigeration. Furthermore, the provider/manufacture of the device has the flexibility of using any preservative of choice thereby greatly expanding the types of tissue to be preserved and the tests that can be performed. Several working prototypes of the device have been built in the inventor’s laboratory and we are seeking industrial partners to further refine the designs into marketable devices.
Anesthesia Depth Diagnosis Assistance System: A novel information processing methodology has been developed to assist in anesthesia administration. Based on signals from commonly used anesthesia monitoring and administration equipment, the method combines expert knowledge of the anesthesiologist and real-time data collected during the surgery to establish and update individual patient models that relate multiple drug infusion rates to their impacts on anesthesia depth and physiological variables. These models are then used to predict the results of drug infusion decisions on the outcome during the operation or other anesthesia procedures. It is envisioned that these predictions could serve as valuable decision-making assistance tools for the anesthesia administrator. The methodology is based on clinical modeling, fast identification and knowledge-based information processing, and stochastic analysis. The research team is currently developing and testing prototype devices.
Pulsed Magnetic Field Anti-inflammatory Device: Wayne State University and University of Michigan researchers have developed methods and devices which employ the use of electrical and magnetic fields to mitigate cellular responses to inflammation. Via the application of certain electric or magnetic fields, changes and conversions of cell types are achieved along with modification of the physiological function of these cells, thereby yielding a therapeutic effect. This approach affects neutrophils, macrophages, lymphocytes, platelets and retinal cells and thus has the potential to provide therapeutic benefit to many diseases and conditions, including immunological and inflammatory diseases and nerve generation.
Apparatus to Activate Molecules which Stimulate Neurological Tissue: This invention, developed by a multi-disciplinary team at WSU, is a drug delivery system including a multitude of activation sites, a micro-fluidic channel for delivery of a drug to the activation sites, and a wave guide for delivering light to an area near one of the activation sites. A fiber optic cable may also be used to deliver light. The drug delivery system selectively delivers drugs to various types of neurological cells. In operation, a solution of photoactivatable neuro-active drug is delivered to a pre-selected area in vivo and photoactivated in the solution at the pre-selected area to stimulate neurological tissue. The neuro-active drug may be either an agonist or an antagonist of neuronal activity.
Device and Method to Remove Arsenic from Drinking Water: WSU faculty developed an innovative biological technology that has promise to cost-effectively remove arsenic from drinking water. The technology employs the use of a genetically engineered strain of yeast with the ability to hyper-accumulate arsenic without releasing the arsenic back into the environment. The yeast is being optimized for arsenic accumulation; the next step will be the development of bioreactors to remove arsenic from natural groundwater supplies. While federal legislation is still in flux regarding the implementation date for new maximum contaminant levels for arsenic, several federal funding opportunities are available from the NIH, the EPA and the NSF. WSU is searching for a development partner to advance this technology.
Method for Infrared Imaging of Ultrasonically Excited Cracks in Teeth: A thermal imaging system for detecting cracks and defects in a component. An ultrasonic transducer is coupled to the specimen to be evaluated through a malleable coupler. Ultrasonic energy causes the defects to heat up and the defects are easily detected by a thermal camera. This technology has already generated a substantial amount of interest within industry and in the field of non-destructive evaluation. Non-exclusive licenses available. The invention is an application of this method to dentistry to detect cracks in teeth which cannot be detected visually or by x-rays.
Magnetic Resonance Force Microscopy for the Study of Biological Systems: Magnetic Resonance Force Microscopy (MRFM) is an emerging technology that combines the strengths of magnetic resonance and force microscopy to achieve high resolution three-dimensional sub-surface imaging of a test substance. WSU researchers have adapted and refined MRFM to study biological systems, such as isolated cells, sub-cellular organelles and other sub-cellular structures, or cellular receptors and proteins, at resolutions ranging from 1 micron to 1 angstrom. MRFM has the potential to significantly impact biomedical research and biotechnology, including the potential to replace x-ray crystallography by directly imaging single-copy molecules.
Programmable Anti-Siphon Shunt: Wayne State University researchers have developed a surgically implantable shunt system for controlling fluid flow from a relatively high-pressure region to a low-pressure region. This device can be used in the management of patients with hydrocephalus and is particularly useful to counteract postural intracranial hypotension related to over drainage of cerebrospinal fluid. The shunt allows for the non-invasive adjustment of the drainage pressure in order to suit the individual pressure requirements of each patient.
Apparatus and Method for Continuous Monitoring of Gastric Tissue Oxygenation Using Capnometric Recirculating Gas Tonometry: The drawbacks of conventional tonometry led two Wayne State University physicians to develop and test an apparatus and method to allow continuous measurement of tissue pH and pCO2 using capnometric recirculating gas tonometry (CRGT). Their objective was to develop a method for continuously monitoring gastric intramucosal pCO2 and pH using balloon-tipped nasogastric catheters, capnometry, and closed system recirculating gas tonometry.
Apparatus and Method for Making a Diffusing Tip in a Balloon Catheter System: An apparatus and method are disclosed for making a laser balloon catheter having a diffusing tip for propagating a uniform cylindrical pattern of laser energy. Included in the catheter is an elongated flexible tube with an inflatable balloon connected to the tube and means for inflating and deflating the balloon. An optical fiber with the diffusing tip at its distal end delivers laser radiation through the balloon to tissue to be treated. The method comprises the steps of etching the optical fiber, cladding the etched portion with a medium which secures the optical fiber to the central channel, and microballoons which diffuse the laser radiation radially from the optical fiber, thereby substantially avoiding axial propagation and heating of blood forward of the optical fiber

Nanotechnology

A Novel Technology to Introduce Polyethylene Glycol and Targeting Ligands on Nanoparticle Surface: Nanoparticle drug delivery systems are expected to have significant commercial interest from both pharmaceutical and biotechnology industries. From a commercial perspective, novel drug delivery technologies such as nanoparticles represent a strategic tool for expanding drug markets and enhancing the effectiveness of current therapeutic compounds. WSU researchers have researched nanoparticle delivery systems, and identified methods to alter the surface of nanoparticles with polyethylene glycol and specific ligands so as to enhance tissue targeting. Preliminary in vivo results indicate roughly a 4-fold increase in tumor targeting with folic acid conjugated nanoparticles fabricated using this technology.
Nanoparticles for Brain-targeted Drug Delivery: Movement of compounds from circulating blood into the brain is tightly controlled by the brain capillary endothelium, which forms the blood brain barrier (BBB). The BBB denies entry to many therapeutic drugs that have the brain as their site of action. It is estimated that 98% of newly developed small molecules will not cross the BBB. As a result, many diseases that afflict the brain such as cancer, infection, stroke and CNS disorders remain difficult to treat. WSU researchers have developed a novel nanoparticle formulation to enhance brain delivery of therapeutic compounds. Preliminary in vivo results indicate that these nanoparticles increase the brain delivery of encapsulated drugs following systemic injected administration.

Pharmaceuticals

Dendrimer and Polymer Drug Delivery Technology: WSU researchers have developed technology that can significantly improve the economics and functionality of current dendrimer technology. Current dendrimer technology allows for binding of approximately 5-10% functional compound by weight. Conceptual models achieving as high a payload as 25% have been claimed. WSU technology has been developed that shows dendrimer conjugates with a 50% - 70% functional compound payload in animal studies, more than twice that of any technology in the literature. It is hypothesized that the dramatic increase in functional compound payload achieved by utilization of this technology would allow significant competitive advantage in the functionality and economics of the dendrimers produced.
Novel Dual and Triple Acting CNS Compounds with Potential as Antidepressants, Medications for Attention Deficit Disorders and other Related Neuro-disorders: Wayne State University researchers have identified compounds with a unique molecular template exhibiting reuptake inhibition activity for both at the norepinephrine and serotonin transporters in the CNS. In addition, some of these molecules also exhibit triple reuptake activity for the dopamine, serotonin and norepinephrine transporters. These compounds have shown impressive dual and triple uptake inhibition activity in vitro, have exhibited in vivo antidepressant activity in forced swimming test model in both mice and rats. Lead compounds will be tested in additional in vivo models, and is currently being screened for other CNS receptors under the NIMH PDSP program. These compounds are not derivatives or analogs of any known antidepressant compounds. Because of the atypical structure, it is hypothesized that there will be insignificant interface of these compounds with non-targeted receptors, such as the histamine receptor, which may alleviate the drowsiness and sedation side effects found in other dual active compounds.
CNS Compounds Specific for the Monoamine Transporter Systems: The dopamine transporter (DAT) plays an important role in pathophysiological processes in the central nervous system. In cocaine addiction, binding of cocaine to the DAT and consequent blockage of dopamine uptake appears to be related to the reinforcing properties of the drug. Also associated with the transport function is concentration of neurotoxic chemicals in dopaminergic neurons which is implicated in Parkinson’s disease. Potent, yet selective ligands for the DAT have potential for in vivo monitoring of primary targets of cocaine in the brain, for the characterization of cocaine binding sites, for pharmacotherapeutic agents for the treatment of cocaine addiction and for monitoring of Parkinson’s disease. Novel compounds have been developed in a few different molecular templates. These compounds have exhibited neuropharmacological activity with respect to their interaction with the dopamine transporter, the serotonin transporter (SERT) and the norepinepherine transporter (NET). Preferred lead compounds exhibit low nanomolar activity with respect to the DAT, and high differential binding activity with respect to the DAT compared with that for the SERT and for the NET. These compounds have utility in treating central nervous system disorders, including cocaine addiction, depression and Parkinson’s disease.
Novel D3 Receptor Compounds – Potential Therapeutics for Parkinson’s and other CNS Disorders: A series of compounds derived from 2-aminotetralin and piperazine fragments have been synthesized, which exhibit high CNS activity in vivo and in vitro. Some of the selected lead compounds have exhibited potent in vivo activity in a Parkinson’s disease animal model with long extended duration of action. In particular, these compounds show high D3 receptor affinity and/or high D3/D2 selectivity. In addition to the potential therapeutic treatment of Parkinson’s disease and depression, these novel compounds have possible application in the treatment of a number of other neurological disorders such as cocaine addiction, restless leg syndrome or as an atypical antipsychotic agent.
Inhibitors of Matrix Metalloproteinases: Wayne State University researchers and academic collaborators have prepared the first reported mechanism-based inhibitors for matrix metalloproteinases (MMPs). One of the novel compounds (SB-3CT) shows selectivity for the gelatinases (two members of the MMP family), which have been implicated in various pathological conditions including, but not limited, to the process of tumor metastasis and angiogenesis, cardiovascular diseases and neurological conditions. In vivo results from WSU and academic collaborators have shown promise in cancer therapy (in T-cell lymphoma and prostate cancer models), in stroke treatment, and in cardiovascular disease therapy.
Novel Aminoglycoside Antibiotics: Wayne State University researchers have synthesized a series of novel aminoglycoside antibiotics that have shown enhanced antibacterial activity, low susceptibility to existing resistance mechanisms and low toxicity when compared to currently marketed aminoglycosides. Aminoglycoside antibiotics have been used against a wide variety of bacterial infections caused by Gram-positive and Gram-negative bacteria. The activity of the aminoglycosides is due to binding to bacterial RNA. Currently marketed aminoglycoside antibiotics are indicated for treatment of serious bacterial infections, but are limited in use due to concerns of serious adverse reactions in the inner ear and kidney. The WSU compounds have shown impressive effectiveness and low likelihood of toxicity in research to date.
Functional Improvements in Fahr’s Disease: Idiopathic cerebral calcification (a.k.a. “Brain Stones”) can be associated with a progressive neurological disorder for which there is no known treatment. This invention is a repurposing of an existing FDA approved compound for a new use. It relates to the treatment of Fahr’s Disease by the administration of a class of drugs called bisphosphonates, specifically the FDA approved drug disodium etidronate (used for treatment of osteoporosis).
Mannich Bases of Conjugaged Styryl Ketones: Human infectious diseases caused by fungi have increased markedly during the past 10 years, due mainly to advances in medical care that involve prolonged immune suppression, increased use of cytotoxic drugs in cancer chemotherapy, and the advent of AIDS. As a result, organisms such as Candida albicans have become opportunistic pathogens capable of causing severe systemic infection. Consequently, as high as 10% of hospital-acquired bloodstream infections are currently caused by fungi yet there have been few major improvements in the treatment and management of fungal infections. The emergence of resistance to commonly used antifungals has exacerbated this situation. Researchers at the University of Saskatchewan, working in cooperation with Wayne State University, have developed novel antifungals which are more effective than Fluconazole against several yeasts and molds. Of particular interest is the activity of certain of the compounds against C. krusei, C. gabrata, C. lusitaniae, and A. fumigatus isolates that are resistant to conventional antifungal agents.
Folate Receptor Targeted Therapeutics for Cancer: Collaborative researchers at WSU and Duquesne University have developed a series of novel folate analogs that show selective toxicity toward tumor cells expressing high levels of the surface protein folate receptor. Typically, normal cells express low levels of folate receptors or such receptors exhibit apical localization and are not exposed to the blood. In additional to the folate receptor selectivity, these compounds are potent inhibitors of glycinamide transformylase (GARTFase), a purine nucleotide biosynthetic enzyme. This is the first description of a compound exhibiting both characteristics of folate receptor and GARTFase targeting. Studies are underway with human tumor xenografts in SCID mice to assess toxicity toward non-tumor tissues.
A Novel Technology to Introduce Polyethylene Glycol and Targeting Ligands on Nanoparticle Surface: Nanoparticle drug delivery systems are expected to have significant commercial interest from both pharmaceutical and biotechnology industries. From a commercial perspective, novel drug delivery technologies such as nanoparticles represent a strategic tool for expanding drug markets and enhancing the effectiveness of current therapeutic compounds. WSU researchers have researched nanoparticle delivery systems, and identified methods to alter the surface of nanoparticles with polyethylene glycol and specific ligands so as to enhance tissue targeting. Preliminary in vivo results indicate roughly a 4-fold increase in tumor targeting with folic acid conjugated nanoparticles fabricated using this technology.
Tumor Targeting Small Molecule Therapeutics for a Proton-Coupled Folate Transporter (PCFT): WSU and Duquesne University scientist have isolated a unique series of pyrrolopyrimidine antifolate analogs that show selective cytotoxicity toward solid tumors such as ovarian, prostate or breast cancer cells that express the low pH “proton-coupled folate transporter” (PCFT). The acidic pH optimum (pH 5.5-6.5) of PCFT makes it an ideal target since many solid tumors exist in an acidic environment.
Nanoparticles for Brain-targeted Drug Delivery: Movement of compounds from circulating blood into the brain is tightly controlled by the brain capillary endothelium, which forms the blood brain barrier (BBB). The BBB denies entry to many therapeutic drugs that have the brain as their site of action. It is estimated that 98% of newly developed small molecules will not cross the BBB. As a result, many diseases that afflict the brain such as cancer, infection, stroke and CNS disorders remain difficult to treat. WSU researchers have developed a novel nanoparticle formulation to enhance brain delivery of therapeutic compounds. Preliminary in vivo results indicate that these nanoparticles increase the brain delivery of encapsulated drugs following systemic injected administration.
Method to Identify Anti-Epileptic Targets and Drugs: The invention is a two-step process/method to identify new targets and drugs to prevent and treat epilepsy. The first step is to identify targets for the disease through statistical analysis of human brain gene expression from patients with epilepsy vs. controls. The second step is to test drugs known to affect these targets in a novel animal model of epilepsy that focuses on interictal spiking. This approach has already identified a potential drugable pathway that can be modified with existing drugs to treat the disease.
Repurposing AKT Inhibitors for the Treatment of Protein Misfolding and Protein Trafficking Diseases: WSU investigators have demonstrated that inhibition of pro-survival kinase, AKT, using the transgene, Trb3, expressed in oligodendrocytes, leads to less brain white matter than controls. Moreover, Trb3 introduction into an animal model of the human disease, Pelizaeus Merzbacher disease (PMD) leads to less myelin thickness and fewer disease symptoms than untreated animals. These results suggest inhibiting AKT msy ameliorate the symptons of PDM and other diseases with similar or analogous pathophysiology such as Alzheimer and Parkinson’s disease to name a few.
Novel Target for Drug Screen and Therapeutic Intervention in Infectious Disease: WSU scientists have discovered that the interaction between cytochrome c (CYC) and cytochrome c oxidase (COX) is a novel target for therapeutic intervention in infectious disease. The discovery demonstrated that although the reaction between CYC and COX is highly conserved through nature, it is possible to develop selective therapies that could be effective against a variety of infectious agents without harm to humans. For example, with this system it is possible to isolate novel antibiotics to anti-malaria agents.
Method for engineering polar drug particles with surface-trapped hydrofluoroalkane-philes: The invention disclosed is a novel method for preparation of spheroidal/spherical polar drug particles with surface-trapped hydrofluoroalkane-philes. This approach can impart long-term physical stability to drug particles dispersed in hydrofluoroalkane (HFA) for use in pressure metered-dose inhalers (pMDI). This advanced technology has advantages compared to what is currently the industry standard, where co-solvents have to be used alongside surfactants to attain similar (or inferior) stability of the dispersion-based formulation. The method is also superior in that no free stabilizers remain in solution thereby reducing toxicity. This invention is expected to be applicable to small molecules and biomolecules that can be formulated free of environmentally toxic chlorofluorocarbons (CFCs).
Method to Stabilize Suspension-Based Formulations in Hydrofluoroalkane Propellants with Nanoparticles: This invention is a new method for engineering porous drug particles with enhanced physical stability and aerosol characteristics in hydrofluoroalkane (HFA) propellants for use in pressure metered-dose inhaler (pMDI) formulations. The approach consists of preparing drug particles containing excipients, which are later remove, resulting in the generation of a porous drug structure. The HFC propellant is capable of penetrating into porous drug particles, thus enhancing the physical stability of the otherwise unstable formulation. This stabilization effect is a significant improvement over existing commercial formulations. Furthermore, this invention enables a wide variety of drugs to be formulated free of environmentally toxic chlorofluorocarbons (CFCs).
Novel Compounds with Activity against Breast, Prostate and Pancreatic Cancers: Using techniques of parallel syntheses based on combinatorial approaches, researchers have built proprietary libraries of putative molecules which are capable of facile cellular internalization and targeting specific signal transduction processes leading to apoptotic cell death through multiple routes involving inhibition of specific kinases. The compounds have been screened against breast, prostate and pancreatic cancer cell lines having varied molecular make-up including estrogen/androgen dependence as well as independent status. The lead compounds have been optimized via additional proprietary technology, which are found to exhibit synergistic enhancement in their anti-proliferative and pro-apoptotic activities. The most promising compounds are presently being examined in standard animal models and the researchers have found the results of preliminary experiments to be very encouraging.
Chicken Interleukin-2 for use as Vaccine Adjuvant: WSU researchers have cloned and patented chicken IL-2 and related avian lymphokines for use as avian vaccine adjuvants. The inventors have shown experimentally that chicken IL-2 can enhance vaccine effectiveness in chickens. Future research to further enable this technology will likely include optimization of delivery methods. IL-2 has a short serum half-life, and for maximum efficacy must be attached to, or closely associated with, the vaccine antigen(s). Various studies have utilized chicken IL-2 fused to antigen, expressed by viral vaccine vectors and expressed in DNA vaccines. In general, the addition of IL-2 has enhanced both the magnitude and the quality of immune responses.
Enzyme-Activated Nitric Oxide Donors: WSU researchers designed and synthesized a series of new pro-drug nitric oxide donor compositions which are activated by particular glycosidases. Using these compounds, site-specific and controlled-release of nitric oxide can be achieved and thus may be useful for regulating many physiological processes. These drugs have shown anti-cancer and anti-viral effects in vitro and may also have applications as vasorelaxants, antithrombotics, or cytostatic or genotoxic compounds.
Cytokine Attachment for Enhanced Vaccine Effectiveness: Wayne State University researchers have developed a method to produce immunostimulatory cytokine proteins and tether them to the membrane of enveloped virus vaccines produced in cell culture. In vivo results to date indicate that this technology improves vaccine efficacy. Cytokines, as soluble proteins, have proven to be effective as adjuvants for experimental viral vaccines, since they boost immune responses, induce T cytotoxic cells and shift Th2 to Th1 responses. However, there are limitations in formulations currently used to coadminister soluble cytokines: 1. It is difficult to maintain effective cytokine concentrations in close proximity to the virus, 2. The cost of producing recombinant cytokine is high and 3. The in vivo half-life of soluble cytokines is very short. To address these problems, WSU researchers have developed a technology to efficiently and cost-effectively produce membrane-bound cytokines that are expressed on the surface of enveloped viruses.
Nanoparticle Drug Delivery Compounds for Hydrophilic Drugs: WSU researchers have developed a nanoparticle formulation for the encapsulation of hydrophilic drugs with high efficiency. Encapsulation efficiency close to 100% has been achieved. Further, these nanoparticles demonstrate sustained release of hydrophilic drugs over a period of weeks (~60-80% of encapsulated drug released over a period of 4 weeks). As a comparison, published studies that investigate the use of other state of the art nanoparticles with water-soluble drugs report sustained release only over a period of few hours. Additionally, due to high surface area afforded by nanoparticles, the efficiency of encapsulation of water-soluble drugs to date has been very poor (<50%). The WSU technology is differentiated by the observed ability to encapsulate hydrophilic drugs in nanoparticles with high efficiency and to sustain the release of hydrophilic drugs from the nanoparticles over a period of weeks to months.
Farnesol and Geranylgeraniol Analogs as Inhibitors of Protein Prenylation: A series of farnesol and geranylgeraniol analogs that block the prenylation of proteins in cells is available for licensing. The diphosphate derivatives of these compounds are potent inhibitors of protein prenyltransferases in vitro. One allylfarnesol compound specifically inhibits the farnesylation of proteins and one allylgeranylgeraniol compound specifically inhibits the geranylgeranylation of proteins in cells. The allylfarnesol compound is potentially useful as an inhibitor of protein farnesyltransferase. Structurally different protein prenyltransferase inhibitors have demonstrated anticancer properties both in cell culture and in animal studies. It has been recently proposed that a selective protein geranylgeranyltransferase inhibitor, such as the allylgeranylgeraniol compound, may also be useful as an anticancer agent. Furthermore, protein geranylgeranyltransferase inhibitors may also have potential application as inhibitors of restenosis following cardiac catheterization.
67 DHB Grapefruit Inhibitor: The invention comprises a composition and methods for inhibiting cytochrome P450 enzyme activity and, in particular, inhibiting the activity of the cytochrome P450 3A sub-family of enzymes specifically, CYP3A4. It is believed that 6’, 7'-dihydroxybergamottin, a furanocoumarin, is the compound primarily responsible for the inhibitory effects of grapefruit juice on cytochrome P450 enzyme activity. The compound is potentially useful as an inhibitor of cytochrome P450 by incorporating 67DHB into the formulation of a drug for the purpose of improving the bioavailability of the drug. It may also be useful by itself as a chemopreventive agent to reduce cancer risk.
Method for Treating and/or Imaging Breast Cancer using Radioactive Iodide: This invention involves treating a breast cancer patient by the administration of a radioisotope of iodine in a dosage of between 5 and 50 milliCuries over the course of a day. The therapeutic composition is designed for mammary tissue uptake and includes an inorganic radioactive iodide salt (e.g., alkali metal, alkali earth or transition metal iodides) and a parenterally injectible carrier therefore. Adjuvants are optionally added to increase uptake by mammary tissue or inhibit uptake by the thyroid gland. The composition may also have utility as a radioimaging dye.
A Novel Apoptosis Inducer and Inhibitor of Human Breast Cancer Cell Growth: WSU researchers have generated a recombinant plasmid that encodes a mutant protein containing several amino acids of a wild type protein, which has shown to cause apoptosis and cell growth inhibition of human breast and colon cancer cells, in vivo. Early in vivo work for this novel protein shows similar pro-apoptotic and cancer cell growth inhibitory properties.
Novel Protein Treatment for Hematological Malignancies: Wayne State University researchers are developing a novel therapy which causes hematological leukemia cell lines to undergo apoptosis. While research is in the early stages, investigators have shown effectiveness in several cell lines, including pre-B acute lymphoblastic leukemia, diffuse large cell lymphoma, follicular small cleaved cell lymphoma and Waldenström macroglobulinemia. Collectively, these cell lines cover almost the entire phenotypic spectrum of B-cell malignancies. While research is in the early stages, investigators are excited about this potential new chemotherapeutic treatment. Continuing research will focus on showing the effects of this protein on cancer cells via an “intravenous” administration route.
Novel Source of Pluripotential Stem Cells in the Adult: The existence of multipotent stem cells within the adult brain has been debated for some time. While the identity of this cell has been unknown, it is clear that stem cells reside in specialized tissue (subventricular zone and subgranular zone) and that local microenvironments regulate their differentiation and self-renewal. WSU researchers have identified capillary pericytes as possessing pluripotent stem cell capability. One set of culture conditions result in the differentiation of pericytes along a mesenchymal lineage, forming bone, muscle cells, adipocytes, chondrocytes, as well as dendritic cells. In another set of culture conditions, pericytes differentiate along a neuronal lineage into oligodendrocytes, neurons, and astrocytes. Capillary pericytes from tissues of non-CNS origin are also shown to have similar potential. This technology provides a new source of pluripotential stem cells and could be important to future research studies and therapeutic strategies.
Use of Flagellin Polypeptides for use in Treating Inflammation Related Conditions such as Keratitis, Cystic Fibrosis and Asthma: The invention relates to use of flagellin to treat and control keratitis. The invention also relates to the use of flagellin to induce innate protection and reduce inflammation associated with infection in other organs, including the lung, such as treating and preventing cystic fibrosis, asthma, and other diseases and conditions in which inflammation contributes to the pathology and symptoms. Keratitis caused by Pseudomonas aeruginosa is one of the most rapidly developing and destructive diseases of the cornea. Once the bacteria infect the cornea, complex host tissue reactions occur, including inflammation, cellular and humoral immune responses, and degradation of stromal proteins. Current interventions treat the bacterial infection but have proven ineffective in modulating the proinflammatory response in at risk individuals WSU researchers have identified a method to alleviate infectious inflammation in Keratitis by the use of flagellin in the treatment of bacterial infection. The technology has the advantage of reducing the cytokine response, while maintaining the innate immunity. In vivo results are available for review.
Compound for Therapeutic Inhibition of Clostridium difficile Toxin A: Clostridium difficile, an opportunistic pathogen commonly associated with use of broad spectrum antibiotics, causes intestinal disorders collectively referred to as C. difficile Associated Disease (CDAD). It is the most common hospital acquired infection, affecting 20-40% of patients. Unfortunately, the incidence and severity of these infections is rising rapidly. WSU researchers have developed a compound to directly target the virulence factor produced by C. difficile. Advantages to focusing on the toxin, specifically Toxin A, include: less likely to induce resistant strains; infection is present subclinically in many patients; infection is naturally controlled by commensal microbes; reduction of physiological damage and symptoms until patient undergoes probiotic remediation. Research results with the compound show 3T3 cells retain their morphology when treated with the compound prior to exposure to Toxin A. Mouse studies to test in vivo efficacy are underway. Additionally, derivatives of the compound which further enhance efficacy are under development.
Novel DNA-based Therapeutic Cancer Vaccine: Traditional cancer therapy includes radiation, surgery and chemotherapy, with a few recently developed options for certain types of cancer, such as bone marrow transplant, hormone, antibody and targeted small molecule therapies. Another approach- cancer vaccines- harnesses the body’s own defense mechanism by turning on the production of antibodies, T cells and other immune cells to destroy cancer cells, thus preventing the disease (i.e. preventive vaccine), or controlling the disease (i.e. therapeutic vaccine), without the severe side-effects of conventional therapy, such as those from surgery, radiation and chemotherapy. When successfully vaccinated, the immune system develops a memory to provide long-term protection from disease recurrence. The targeted killing of tumor cells, long term protection from and tremendous economy compared to current therapy are compelling reasons to develop cancer vaccine technology. Until recently, cancer vaccines have demonstrated little success for lack of plausible target molecules and the inability to trigger immune response to self molecules which are found on tumor cells. Wayne State University has developed a novel DNA-based therapeutic cancer vaccine which targets receptors which, when engaged by antibodies, triggers programmed cell death in tumor, but not normal cells. Using a DNA vaccine targeting a specific mouse receptor, the researchers showed the feasibility to induce anti-mouse receptor antibodies by electrovaccinating mice with naked DNA encoding a fusion protein of the mouse receptor fused to a highly immunogenic, but non-toxic fragment of tetanus toxin. WSU recently received funds to advance the proof of concept of this technology by producing the human equivalent of the mouse vaccines for commercialization. This vaccine design follows the process established in the inventor’s lab for human Her-2 vaccine development. Her-2 vaccine construction initiated in 1996 has resulted in a Phase I clinical trial in patients with advanced breast cancer in 2003. The safety of the Her-2 vaccine was demonstrated and the process of constructing and testing this DNA vaccine is in place.
Genus-Wide Chlamydia Peptide Vaccine Candidates: Chlamydia trachomatis is the most prevalent sexually transmitted disease (STD) worldwide; approximately 60 million new cases of C. trachomatis cases occur annually. The actual numbers may be higher, since many cases are asymptomatic. The Institute of Medicine estimates that the U.S. total annual healthcare costs related to these STDs exceeds $2billion. It is estimated that by the age of 30, half of all sexually active women have been infected. Chlamydia genital infection occurs in 5-15% of pregnant women, and 50% of their babies will develop inclusion conjunctivitis or respiratory infections making C. trachomatis the most common ocular pathogen in infants. If women are left untreated, 40% of these infections will progress to pelvic inflammatory disease with permanent damage, resulting in chronic pain, infertility, and potentially fetal death. Wayne State University inventors have developed several peptide vaccine candidates that are genus specific; conformational; and easy to manufacture. These benefits overcome several of the prior impediments to the development of a Chlamydia vaccine: antigenically diverse surface proteins; enhanced survival within host cells; biphasic development cycle; reduced inflammatory responses; and the ability to persist. Research results include antibody responses of peptide-immunized mice against individual peptides; adoptive transfer of spleen cells from immunized mice to SCID which was subsequently challenged with C. trachomatis. Additional challenge studies are being done.
Novel In Vitro Approaches and Paradigms to Improve the Drug Development Process-: Many novel compounds which are highly active in vitro or in efficacy models fail to show the desired effect in clinical trials. The failure of compounds in drug development results in lost time, significant financial loss and lost lives. It would be beneficial to have available a new drug development paradigm that is flexible and that bases the selection process on data using projected human exposures. Wayne State University and SRI researchers have developed a suite of technologies that provide drug developers with these tools. One invention utilizes a 4-step process involving selected animal studies and human in vitro tests to guide the selection process. Other results in information regarding the maximum safe human exposure level, bolus PK outcomes, and dosage regimen. One component of this technology suite uses an in vitro cellular assay to predict the maximum tolerated drug level in humans and makes it possible to discover, select, prioritize and optimize lead compounds by therapeutic index. Human toxicology and safety can be predicted with the final technology, utilizing an in vitro assay or panel of assays to assess the adverse chemical effects on the function of human tissue. Benefits include efficiency and economy; more accurate estimates of success or failure; flexibility; scale-up potential; human MTD calculations; resource conservation; and replacement of xenograft/transgenic models with in vitro tests. This technology is available on a non-exclusive basis.
New Role for a Plasma Glycoprotein in Obesity Resistance and Insulin Control of Glucose Homeostasis: WSU researchers have identified novel functions of a plasma glycoprotein opening up new approaches to the treatment of obesity and to the regulation of insulin control of glucose homeostasis. Glucose homeostasis is maintained as a result of a cascade of signaling events, initiated when insulin binds to its cellular receptor, leading to the uptake of glucose into skeletal muscle, liver and adipose tissue. The plasma glycoprotein inhibits insulin-stimulated insulin receptor (IR) autophosphorylation and tyrosine kinase (TK) activity in vitro, in intact cells or when injected into rats. Mice lacking this glycoprotein demonstrate increased insulin sensitivity and enhanced insulin signal transduction. The researchers have also demonstrated that these mice, when fed a high-fat diet, do not experience body weight gain. The findings have significant practical implications for the development of treatments for obesity, type 2 diabetes and several other insulin resistant conditions. The glycoprotein can serve as a target protein for therapeutic approaches for these diseases.
An In-Vitro Model System for Studying Development of Human Pre-neoplastic Breast Disease: Wayne State University researchers have developed a novel model/assay system that recapitulates in vitro the in vivo processes that lead to breast cancer development and progression from preneoplastic tissue. This model is the first that demonstrates in vitro the de novo development and neoplastic conversion of functional alveolar units. Advantages of this model include the fact that it requires only about 7 days for alveolar morphogenesis to occur compared to 8-10 weeks in vivo. This permits the use of this system for relatively high throughput drug screening. In this model, preneoplastic human breast epithelial cells interact with two major stromal components, endothelial cells and fibroblasts, on a reconstituted basement membrane and undergo alveolar morphogenesis, a critical step in breast tissue morphogenesis. The inventors have shown for the first time using this model the biological requirements and/or contribution from epithelial cells and stromal components for formation of functional ductal lobular units, and processes that allow neoplastic conversion.
Experimental Bone Metastatic Prostate Tumor Model: A Wayne State University researcher has derived new tumorigenic cell lines from the human prostate carcinoma cell line PC-3. These cell lines, known as PC-3/IF, when implanted in the femurs of nude mice, provide a xenograft tumor model of bone metastatic prostate carcinoma. The PC-3/IF cell lines are highly tumorigenic, with tumor cells replacing the marrow cells in the bone cavity, invading adjacent bone and muscle tissue to ultimately form a palpable tumor at the hip joint.
Experimental Metastatic Prostate Tumor Model: A Wayne State University researcher has developed new tumorigenic cell lines from the human prostate carcinoma cell line PC-3. These cell lines, known as PC-3/PI, are highly tumorigenic when implanted in the prostate of nude mice, providing a xenograft tumor model of prostate carcinoma. In this model, lymph node metastases form from the primary tumor as in human prostate carcinoma. Available non-exclusively via biological materials licensing.
Experimental Renal Cell Carcinoma Tumor Model: A tumor cell line from a primary papillary renal cell carcinoma (RCC) (nuclear grade III/IV) was developed by WSU researchers. This cell line, known as KCI-18, when implanted in the kidney of nude mice provides a xenograft tumor model of RCC. The KCI-18 cell line is highly tumorigenic, with lung metastases forming from the primary tumor as in human renal cell carcinoma. Available non-exclusively via biological materials licensing.
Assessment of the Induction and Course of Cellular Programmed Cell Death over Time: Researchers at Wayne State University have developed a novel method to identify and analyze the process of programmed cell death (apoptosis) in living cells over time—without killing the cells. The method has initially been applied to the analysis of PCD in neurons but could be used in the study of any disease process and of PCD in a number of different cell types.
Novel Mammalian Gene Encoding a Putative Phosphatidyl 4-Phosphate 5-Kinase: Researchers at Wayne State University have discovered a novel mammalian gene which may be involved in membrane trafficking, more specifically, insulin-induced translocation of the fat/muscle-specific glucose transporter GLUT4. This material is a potentially valuable research tool for investigation relating to the diagnosis or therapy of diabetes.
B3 Adrenergic Receptor Protein and DNA Encoding Same: The B3-Adrenergic receptor protein and DNA which encodes same, vectors containing the DNA, host cells transformed with the vectors and methods of using the protein, the DNA and the transformed host cells.

Sensors

Broad Temperature Range MIS Hydrogen Sensors: There are several uses for a device that detects hydrogen concentration in the presence of other gasses. In the automotive industry, there are ongoing efforts to develop a hydrogen combustion engine and a hydrogen fuel cell. These applications will require a hydrogen sensor that can be operated over a broad range of temperatures, pressures, and gas compositions. In the space shuttle, a mass spectrometer is employed to detect the presence of hydrogen around the shuttle. However, this device is unable to detect the location of a hydrogen leak. Current hydrogen sensors can readily measure hydrogen in an environment devoid of other gases. If a sensor is optimized to overcome the selectivity problem, temperature and pressure requirements are not satisfied. WSU researchers developed hydrogen sensors that differ from previous devices by employing aluminum nitride as an insulator in a metal insulator semiconductor structure. These new structures show a marked specificity for hydrogen under a wide range of conditions. Several prototype sensors with various applications have been tested; results are available for review under the appropriate secrecy agreement.

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