“FirstLook”TechnologyShowcase2009

Guide to Technologies

Office of Enterprise DevelopmentOffice of Technology Management

1. CardiacPatchtoHelpDamagedCardiacTissueRecoverFromaHeartAttackInnovators: William Wagner, PhD

Deputy Director of the McGowan Institute for Regenerative Medicine; University of Pittsburgh—Professor, Department of Surgery; Bioengineering; Chemical and Petroleum Engineering, Swanson School of Engineering

Kazuro Lee Fujimoto, PhDResearch Assistant Professor, University of Pittsburgh, Department of Surgery

Yi Hong, PhDResearch Assistant Professor, University of Pittsburgh, Department of Surgery

Mentor: Robert DicksonVice President and Chief Financial Officer, CardiacAssist, Inc.

Technology Description: A patch has been designed to help damaged cardiac tissue recover from a heart attack. Myocardial infarction causes severe chronic heart failure characterized by ventricular dilation and diminished cardiac performance. The investigators developed a biodegradable, polyester urethane urea (PEUU) patch to preserve cardiac function.

Commercial Application: More people die from cardiovascular disease than the next six leading causes of death combined, and if cardiovascular disease were to be eliminated, the average life expectancy would rise by seven years.

Value Proposition: Muscle tissue is damaged following a heart attack resulting in a reduction in cardiac functionality. In order to preserve cardiac function the investigators have developed a novel cardiac patch. Application of the novel PEUU patch generated substantial contractile smooth muscle tissue and prevented cardiac dilation and dysfunction in a sub-acute myocardial infarction model. This biodegradable heart patch may one day prevent the long-term cardiac damage that so many suffer after a heart attack. The current technology represents a new therapeutic option against post-infarct cardiac failure.

2. Thermoresponsive,Biodegradable,ElastomericMaterialforMedicalUseInnovators: William Wagner, PhD

Deputy Director of the McGowan Institute for Regenerative Medicine; University of Pittsburgh—Professor, Department of Surgery; Bioengineering; Chemical and Petroleum Engineering, Swanson School of Engineering

Kazuro Lee Fujimoto, PhDResearch Assistant Professor, University of Pittsburgh, Department of Surgery

Zuwei Ma, PhDResearch Assistant Professor, University of Pittsburgh, Department of Surgery

Mentor: Susan K. Cohen, PhDAssociate Professor of Business Administration, University of Pittsburgh, Joseph M. Katz Graduate School of Business

Technology Description: The invention is a biodegradable biomaterial that changes from liquid into a semi-solid gel when the surrounding temperature rises to near body tempera-ture. This material is stretchable and strong, mimicking the properties of soft tissues in the body.

Commercial Application: Potential applications include an injectable niche stem cell for bone marrow transplants, delivery vehicles for chemotherapy drugs, bulking agents for cosmetic applications, and wound treatment. A further application may be treating or preventing heart failure by support of damaged heart muscle. In 2006, heart failure cost $29.6 billion in direct care costs, with an incidence of 10 cases/ 1000 people over age 65 in the U.S. As the population ages, this market is expected to increase.

Value Proposition: Various tissues in the body are in a constant state of extension and constriction. Applying therapy to these tissues is a challenge. This responsive biomaterial is designed to stretch with the body while also providing mechanical support at the site of injection or application.

3. IntegratedImplantableMEMSforEarlyDetectionandTreatmentofMyocardialIschemiaInnovators: Marco Zenati, MD

Professor of Surgery, Division of Cardiac Surgery, University of Pittsburgh, School of Medicine; Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh Medical Center; Chief, Cardiac Surgery, VA Pittsburgh Healthcare System; Professor of Biomedical Engineering, Carnegie Mellon University

William Clark, PhDProfessor, Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Swanson School of Engineering

Sung Kwon Cho, PhDAssociate Professor, Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Swanson School of Engineering

Mentor: Louis Klevan, MBAManaging Director in the BMO Capital Markets Debt Products Group

Technology Description: This device is an early warning system to prevent and treat acute coronary syndromes at a very early stage, before symptoms develop. This device will be implanted on the epicardial surface through a minimally invasive approach to evaluate ventricular wall tension changes associated with myocardial ischemia (MI).

The device consists of several integrated components; a micro-electro-mechanical system (MEMS) pressure sensor and a micro fabricated pH sensor that will continuously monitor for metabolic acidosis that results from decreased oxygenation. The product is self-powered using piezoelectric technology that harvests energy from the natural movement and pressure changes of the beating heart.

Commercial Application: Heart attack or MI is the leading cause of mortality throughout the world. Approximately 70% of people experiencing cardiovascular compromise have MI as the first sign of disease. One third of MIs are clinically unrecognized and are called silent, atypical or unrecognized infarctions. Even more striking, 50% of people with MI die before reaching the hospital.

Because the early warning signs for heart attack are misleading, an accurate early warning system would expedite response and therapeutics.

Value Proposition: This innovative technology capitalizes on technological advances in MEMS designed for early detection of myocardial infarction. This small implantable and integrated MEMS device is designed to provide objective data about myocardial health to patients and health care providers. This minimally invasive, self-powered MEMS unit for myocardial pH and pressure change will alert patients of pending cardiovascular insults before the onset of symptoms.

4. ASystemforSelf-InflatingPressurizedInfusionofIntravenousFluidsInnovator: James Menegazzi, PhD

Research Professor of Emergency Medicine, Department of Emergency Medicine, University of Pittsburgh Medical Center

Mentor: Matt BealePresident, Daedalus Excel

Technology Description: This technology is a CO2 activated pressurized infusion device that incorporates an air bladder surrounding an infusate bag containing fluids to be adminis-tered to the body. The self-contained dual-chambered system stays pressurized (without any pumping) as the fluid-containing portion is infused and emptied. When activated, the bladder instantaneously fills with CO2 and applies a uniform pressure to the infusate bag. This pressure will enable a steady flow of fluid to the patient and will eliminate the need for the attending medical professional to continually inflate the device.

Commercial Application: Currently, in order to rapidly infuse fluids in the pre-hospital setting (combat or civilian) a pressure cuff is placed around the bag containing the fluids to be infused. The pressure must be manually pumped to begin fluid infusion. As the fluid empties, the pressure inside the pressure cuff decreases, as does the flow rate for the infused fluids requiring the caregiver to manually maintain pressure throughout the infusion. As a self-contained device, this technology will allow medics and paramedics to administer fluids more rapidly and reduce exposure time in a combat zone or disaster area.

Value Proposition: In the emergency treatment of hemorrhagic shock, the rapid infusion of crystalloid solutions can be a life-saving intervention. This automatic system does not rely on gravitational forces for fluid delivery and frees up medical personnel for more urgent life-saving activities. This technology may also be used for induction of hypothermia and copious irrigation of open wounds.

5. Flowering(Articulating)LaryngoscopeInnovator: James Menegazzi, PhD

Research Professor of Emergency Medicine, Department of Emergency Medicine, University of Pittsburgh Medical Center

Mentor: Tom KubiliusPresident & Founder, Bright Innovation

Technology Description: The ‘flowering’ laryngoscope is a novel device that will aid in patient intubation. This laryngoscope will be constructed from rubber material instead of hard metal making it less likely to break the patient’s teeth or cause soft tissue damage associated with existing laryngoscopes. The key feature is that the laryngoscope will have fiber optic lit ‘fingers’ that spread open or ‘flower’ when the device is deployed, gently retracting and compressing soft tissues in the oral cavity and trachea providing medical professionals with much better illumination of the passageway.

Commercial Application: Laryngoscopes are used to open up airways for the placement of an endotracheal intubation tube. Orotracheal intubation is performed many thousands of times daily in the US and millions of times daily worldwide primarily by EMS paramedics in emergency situations, by anesthesiologists in the process of administering anesthesia, and routinely in emergency rooms to facilitate intubation of patients. All three areas represent reasonably sized opportunities, with the first responder market around $48M, the anesthesia/operation room segment about $65M, and emergency medicine market approximately $20M.

Value Proposition: This device will be easier to use than conventional devices and will minimize soft tissue damage. Instead of prying the airway open with a stainless steel blade, this novel design will have a less abrasive rubber. This gentle procedure would lessen patient damage and discomfort, reducing unnecessary litigation and additional surgeries. This laryngoscope will provide better lighting of the procedural field and enable more space to work.

6. ContinuousColorVisualFeedbackforSafeandAccurateDeviceOperation:TheSmartSyringeInjectionTrainingSystemInnovator: Joseph T. Samosky, PhD

Director, Simulation and Medical Technology Research and Development Center, WISER Center, University of Pittsburgh Medical Center; University of Pittsburgh—Assistant Professor of Anesthesiology, School of Medicine; Assistant Professor of Bioengineering, Swanson School of Engineering

Mentors: Jeff Plowey, ASCP (I), MBATechnology Consultant, University of Pittsburgh, Small Business Development Center

Greg RiceManagement Consultant, University of Pittsburgh, Small Business Development Center

Technology Description: This invention enables the display of continuously-variable color directly on a tool or device as it is being used in order to promote safe and accurate operation of the device without the user needing to look away at a separate information display. The hue (color) is controlled in real time by a measured variable that is relevant to success or failure of the task. The displayed hue provides instant feedback and can be discrete (fixed number of colors) or continuous (spectrum of colors). The inventors have demonstrated the concept with a specific application: the Smart Syringe, a device that trains healthcare personnel to inject medications at correct rates.

Commercial Application: Task performance is enhanced by rapid feedback. This is true across applications ranging from sports training to operating a vehicle to healthcare. In many domains, including life-critical medical procedures, it can be a challenge to display data in a nondistracting manner during execution of a task. This invention, applicable to a wide range of devices, enables a user’s actions to be guided by critical information on task performance while the user looks directly at the device, promoting focused performance with real-time feedback.

Value Proposition: The current invention can reveal to the user performance information that might otherwise be hidden. The technology can be used for training or built in to actual devices. It offers the potential to increase both the efficiency and proficiency of training and use of devices, reduce errors, decrease risk exposure, reduce liability costs and increase accuracy during critical task performance.

7. Real-Time“X-RayVision”forHealthcareSimulation:AnInteractiveAugmented-RealityDisplaySystemInnovator: Joseph T. Samosky, PhD

Director, Simulation and Medical Technology Research and Development Center, WISER Center, University of Pittsburgh Medical Center; University of Pittsburgh—Assistant Professor of Anesthesiology, School of Medicine; Assistant Professor of Bioengineering, Swanson School of Engineering

Mentors: Jeff Plowey, ASCP (I), MBASenior Technology Consultant, University of Pittsburgh, Small Business Development Center

Greg RiceManagement Consultant, University of Pittsburgh, Small Business Development Center

Technology Description: This invention is a real-time interactive projective overlay system that projects video images directly onto the surface of a full-body mannequin human simulator for medical training. These images create the appearance of seeing structures and activity occurring within the body. The key innovation of this work is controlling the projected images by sensing the position and motion of actual devices such as endotracheal tubes or catheters inserted into the mannequin. The illusion can thereby be created that the user has “X-ray vision”, seeing the internal location and motion of a device aligned in correct position and proportion on the body surface.

Commercial Application: This invention addresses a basic but significant limitation of training on real patients: human bodies are opaque. It can be difficult to appreciate the internal consequences of external actions applied to devices such as endotracheal tubes or catheters. An initial important application is to increase the safety and efficiency of training placement of endotracheal tubes or catheters into a patient. The technique can be extended to other devices and procedures.

Value Proposition: Interactive projective overlay in healthcare training will improve clinician understanding of procedural technique and provides immediate performance feedback to trainees and instructors. Therefore, students will better understand the internal repercussions of their external actions and will be able to make necessary changes to their technique in real-time. It holds the potential to decrease the time (and cost) to acquire proficiency, while increasing accuracy and reducing the risk of harm to patients.

8. RetinalBloodVesselSegmentationwithThreeDimensionalSpectralDomainOpticalCoherenceTomographyInnovator: Juan Xu, PhD

Postdoctoral Research Fellow, Department of Ophthalmology, University of Pittsburgh, School of Medicine

Mentor: Larry Miller, MBAExecutive in Residence, Innovation Works

Technology Description: This invention is an automated retinal blood vessel segmenta-tion technique that is based on Three Dimensional Spectral Domain Optical Coherence Tomography (3D SD-OCT). SD-OCT is a new high resolution imaging technique, capable of achieving micrometer resolution that allows detailed imaging of the eye structures. In contrast to conventional 2D image techniques to detect blood vessels, 3D SD-OCT uses a machine learning algorithm to identify blood vessels automatically in a manner that does not rely on and can exclude other processing.

Commercial Application: A blood vessel on a retinal image is an indicator of various eye diseases and also an important feature to register for the same patient taken at different visits. This greatly improves accuracy in the monitoring of eye disease progression. Additionally, the blood vessel can be used as a landmark to measure other normal or abnormal features on the retina.

3D OCT, which can yield 3D images of the retina, is a promising means for automated analysis, early detection, and monitoring the progression of eye diseases, such as glaucoma, diabetic retinopathy and others.

Value Proposition: 3D SD-OCT is fully automated and independent. Veins and arteries have many observable features that can serve as diagnostic indicators.

9. BimodalLuminescenceNanoelectronicOxygenSensorInnovator: Alexander Star, PhD

Assistant Professor, University of Pittsburgh, Department of Chemistry

Mentor: Mel PircheskyPresident, Eagle Ventures

Technology Description: This invention is an oxygen (O2) gas sensor based on an optically active and electrically conductive nano-composite. Specifically, single-walled carbon nanotubes (SWNTs) decorated with a europium ion containing polymer show electrical and optical response to O2 gas after brief periods of illumination with ultraviolet (UV) light. In a sensor configuration, the devices showed linear electrical response to O2 concentrations between 5-27% at room temperature and ambient pressure, and in the current form have a calculated minimum detection limit of ~0.4%. The next step in sensor development will be incorporation of the nano-composite into ultra-compact and low-power microelectronic

platforms using standard semiconductor fabrication techniques for simultaneous measure-ment of the electrical conductivity and luminescence intensity during gas exposure.

Commercial Application: Applications of this technology include wearable gas sensors for personnel working in enclosed environments or low power devices for incorporation into stationary sensor arrays.

Value Proposition: The advantage of this technology is the ability to detect O2 while operating at room temperature, which requires less energy and allows miniaturization—ultimately allowing the development of wearable or ultra-portable devices. Taking advantage of existing semiconductor fabrication technology, incorporation of the nano-composite into microelectronic devices will allow mass-scale production of sensor devices at very low cost per unit.

10. ApparatusforWirelessPowerandDataTransferOveraDistanceInnovator: Mingui Sun, PhD

University of Pittsburgh—Professor of Neurological Surgery, School of Medicine; Bioengineering; Electrical Engineering, Swanson School of Engineering

Mentor: Joseph BarronFounding Creative Director, Malabar Partners LLC

Technology Description: This innovation relies on novel wireless technology capable of transmitting significant levels of energy through walls and spaces without direct cable connections. The power transfer efficiency can be as high as 80% across distances of up to three feet, without the need for perfect alignment between transmitter and receiver. The wireless technology uses directed magnetic fields making it safe for use in close proximity to humans.

Commercial Application: A foreseen application is the transfer of energy from solar panels into a home without the need for complicated or costly installation procedures. The initial target user will be energy/environmental conscious homeowners and small business owners in the U.S. looking to reduce their energy costs and hybridize their homes/businesses in a cost effective and simple means.

By integrating the thin film design in the new wireless technology and the existing flexible solar panels, a mobile power system can be made. It can be wrapped into a small roll for storage/transportation and attached to, or removed from, essentially any surface for converting solar energy to electricity without cable connections.

Value Proposition: Solar energy can be captured by a solar panel placed on a residential home’s exterior wall or roof. Currently, solar panel installation requires a through-wall cable connection and interior/exterior wiring, which represent about 50% of the total cost. This new wireless energy transfer technology offers:

• Easy installation without structural modification

• Decreased installation and per watt energy cost

• Greater flexibility in the use of solar energy

11. NovelLithiumIonBatteryAnodesInnovator: Prashant N. Kumta, PhD

University of Pittsburgh—Edward R. Weidlein Chair, Professor in Departments of Bioengineering, Chemical and Petroleum Engineering, Mechanical Engineering and Materials Science, Swanson School of Engineering

Mentor: Alan Brown, PhD, MBAExecutive Director, Pennsylvania NanoMaterials Commercialization Center

Technology Description: In this invention, nanoscale hybrid silicon/carbon nanotube complex structures are fabricated as lithium-ion battery anodes. Using a liquid-injection based chemical vapor deposition (CVD) system, the vertically aligned Carbon NanoTubes (CNTs) are synthesized on a quartz substrate followed by successive deposition of silicon.

Commercial Application: Due to the ever-increasing needs of a modern information-rich and mobile society with mounting ecological concerns, there is a great need to develop rechargeable lithium ion batteries with higher energy density and longer service life.

Value Proposition: A simple CVD process involving silicon nanoclusters decorating the CNT surface forms a stable interfacial chemical bond creating a unique hybrid lithium-ion battery anode. Such batteries will power an increasing diverse range of complex portable, consumer and automotive applications, such as electronic devices, electric vehicles, intermittent power source storage and implantable energy systems.

12. NovelNanostructuredSmartInjectableBoneCementsforBoneRegenerationInnovator: Prashant N. Kumta, PhD

University of Pittsburgh—Edward R. Weidlein Chair, Professor in Departments of Bioengineering, Chemical and Petroleum Engineering, Mechanical Engineering and Materials Science, Swanson School of Engineering

Charles Sfeir, PhDDirector, Center for Craniofacial Regeneration; University of Pittsburgh—Associate Professor, Department of Oral Medicine and Pathology, School of Dental Medicine; Bioengineering, Swanson School of Engineering

Mentor: Michael Corrado, MDChief Scientific Officer and Chief Regulatory Officer, INC Research

Technology Description: This innovation involves novel, smart injectable cements for bone tissue engineering. This material is an inorganic ceramic cement that incorporates nanopar-ticle carriers which are bound to biological signaling molecules. The cement forms under physiological conditions, and the entire cement reaction can be conducted in the presence of cells and biological molecules. Additionally, the cement has a putty-like consistency, allowing it to be formed and shaped to fit the desired bone injury site. The cement hardens within a few minutes.

Commercial Application: Applications include use in various types of craniofacial and orthopedic-related problems involving long and short bones subject to static and dynamic loads. It also provides a therapeutic option for treatment of congenital bone-related diseases and trauma-associated bone defects, among others, which result in approximately 150,000 civilian deaths per year. Another application involves healing complex bone fractures of combat casualties – considered a primary target market. Overall, the economic burden linked to chronic bone and craniofacial-related trauma spending is approximately $100 billion annually in the U.S.

Value Proposition: This platform technology provides for a safe and effective therapy option for treatment of orthopedic and craniofacial diseases and defects. Because of it’s putty-like character the technology can be tailored to meet the needs of specific clinical injury, including dental applications, and can be extended to provide antimicrobial delivery as well.

13. IsolationandUseofUmbilicalCordDerivedCellsforTissueRegenerationInnovator: Bridget Deasy, PhD

Director, Live Cell Imaging Lab, University of Pittsburgh— Assistant Professor, Department of Orthopedic Surgery, School of Medicine; Department of Bioengineering, Swanson School of Engineering

Mentor: David Smith, JDAttorney at Law, Pepper Hamilton, LLP

Technology Description: The inventor has developed methods to isolate phenotypically-defined, umbilical cord (UC) stem cells to a yield not previously reported. These methods obtain 3.5 x 105 cells per gram of UC tissue. This yield is higher than reports using different isolation methods. The methods also allow for high ex vivo cell growth to generate sufficient numbers for transplantation and are optimized to maintain the stem cell phenotype. Further optimization for higher yields is possible since the entire cord theoretically contains 500 million cells.

Commercial Application: As a readily available and unlimited resource, UC stem cells have the potential to revolutionize the field of regenerative medicine. These cells may be used for un-related donors to treat diseases related to cartilage, bone, muscle or tendons/ligaments. By maximizing the cell harvest yield and developing techniques to store these cells for extended periods, a large stockpile of ready-to-use replacement cells fit for the entire population can be developed.

Value Proposition: Human UC cells derive from the non-controversial primitive tissue and demonstrate excellent capacity for cell growth and secretion of key proteins in cartilage. They can be used allogeneically and do not require an initial biopsy debridement to obtain chondrocytes that have limited growth potential.

14. Lab-On-ChipPlatformforManipulatingNanoscaleParticlesInnovators: Steven P. Levitan, PhD

John A. Jurenko Professor of Computer Engineering, Department of Electrical and Computer Engineering, University of Pittsburgh, Swanson School of Engineering

Donald M. Chiarulli, PhDUniversity of Pittsburgh—Professor of Computer Science, School of Arts and Sciences; Professor of Computer Science-Computer Engineering, Swanson School of Engineering

Mentor: Alan Veeck, PhDPrincipal, Meakem Becker Venture Capital

Technology Description: This technology is a laboratory instrument platform capable of isolating, purifying, and assaying mixtures of nanoscale particles that are significantly smaller than is possible with current technology. This handheld (~1 cm2) lab-on-chip device uses 3D integrated circuit technology to create and control high resolution electric fields with precision that can discriminate slight differences in morphology and composition between particles (e.g., pathogenic and non-pathogenic forms of a virus). This unique platform uses electrode arrays that are 20x more dense and 100x larger than any other device in the marketplace. These arrays, combined with large scale on-chip integrated control, provide a programmable and versatile platform for next generation portable instrumentation for the separation of heterogeneous nanoscale particles for biochemical, cytometric and clinical diagnostic applications.

Commercial Application: The current market size for cellular purification and analysis is projected to be $1B in 2009, in the U.S. alone. Devices called cytometers are typically used on blood cells and other cellular-scale biological particles for research and clinical applications. Our platform will expand this market for a host of new applications that require the manipulation of virus-scale particles and smaller. Primary customers include pharma-ceutical/biotech companies, research institutions, hospitals, and clinical testing facilities.

Value Proposition: competitive advantages:

• Fully integrated: device is low cost, low voltage, and low power, capable of operating in clinical, research, and field mobile configurations.

• Non-destructive: platform supports bio-compatible operation with no need for staining, tagging, or bio-chemical markers. Has no physical contact between electrodes and particles. Is compatible with non-toxic buffer solutions.

• Flexible: fully programmable device that can be configured to operate in multiple operational modes and fit a variety of potential markets and applications.

15. ClassificationofOtitisMediaImagesInnovators: Alejandro Hoberman, MD

Chief, Division of General Academic Pediatrics, Children’s Hospital of Pittsburgh; Professor of Pediatrics and Clinical and Translational Science; Jack L. Paradise Professor of Pediatric Research, University of Pittsburgh, School of Medicine

Jelena Kovacevic, PhDCarnegie Mellon University—Professor, Departments of Biomedical Engineering & Electrical and Computer Engineering; Director, Center for Bioimage Informatics

Mentor: William J. O’ConnorConsultant

Technology Description: Investigators from Children’s Hospital of Pittsburgh have developed and validated a symptom severity scale for children with acute otitis media (AOM). The use of this scale will allow researchers to more easily study the effectiveness of various therapeutic modalities in reducing symptoms of AOM. The ultimate goal for this technology is to develop a software tool to classify images into one of three stringent clinical diagnostic categories: AOM, OME (otitis media with effusion), and NOE (no effusion) or normal ear condition, and validate the algorithm on tympanic membrane (TM) images.

Commercial Application: AOM is the most common infection for which antimicrobial agents are prescribed in children in the U.S. By age seven, 93% of children will have experienced one or more episodes of otitis media. AOM results in significant social burden and indirect costs due to time lost from school and work. Developing an automated and accurate software tool to help classify otitis media images into one of the clinical categories would have a great impact on both clinical care as well as reducing unnecessary prescrip-tions of antibiotics in the U.S.

Value Proposition:

Provides a valid and reliable measurement strategy to measure AOM symptoms in children.

• Correct diagnosis of sub-types of otitis media can help better identify the subtypes that are responsive to antibiotics from those that are not.

• Potential to save on antibiotics and reduce secondary effects

16. IncreasingTumorRadiosensitivityandSimultaneouslyPreventingTissueDamageinNormalTissuebyTargetingCD47Innovator: Jeff S. Isenberg, MD

University of Pittsburgh—Associate Professor of Medicine, Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine; Investigator, Hemostasis and Vascular Biology Research Institute, School of Medicine

Mentor: Paul Kornblith, MDRegional Director, Southwestern Pennsylvania, PA Biotechnology Association (PA BIO)

Technology Description: This invention demonstrates that CD47 (a human protein encoded by the CD47 gene) targeting agents render tumor tissue dramatically more sensitive to radiation therapy and substantially delay tumor regrowth. Using antisense molecules, peptides, and antibodies, all of which can be used as radio-sensitizers for tumors, the invention provides methods for enhancing the killing capacity of radiation on solid tumors in vivo.

Commercial Application: The development of effective radioprotectant molecules is of great importance to populations potentially subjected to accidental, intentional or military exposure to radiation, including ionizing radiation. In addition, the ability to prevent radiotherapy-induced toxicity without affecting antitumor therapeutic efficacy has the potential to enhance the therapeutic benefit for cancer patients without increasing their risk of serious adverse effects.

Value Proposition: These methods render solid soft tissue tumors in animals dramatically more sensitive to radiation through contacting the peri-tumor tissue bed with a therapeuti-cally effective amount of an agent that inhibits the interaction of thrombospondin-1 (TSP1) and CD47 or a radioprotectant CD47 ligand. Consequently, the cancer is sensitized to the effects of radiation and normal tissue is protected from radiation damage.

17. LymphNodesasSitesforTissueRegenerationInnovator: Eric Lagasse, PharmD, PhD

Associate Professor, University of Pittsburgh, Department of Pathology; Director, Cancer Stem Cell Center, McGowan Institute for Regenerative Medicine

Mentor: John Erbey, PhDDirector, Global Marketing—Early Metabolics, Bristol-Myers Squibb

Technology Description: The investigator demonstrates the use of lymph nodes as a new site for liver regeneration. Hepatocytes can engraft and survive in lymph nodes, generating ectopic livers that rescue an animal model of lethal metabolic disorder.

Commercial Application: The American Liver Foundation reports that more than 25 million people are afflicted with liver and gallbladder disease each year. Over 27,000 Americans die from cirrhosis annually, making it the country’s third leading cause of death for people between the ages of 25 and 59. Applications include extra-hepatic tissue for liver diseases; insulin producing tissue for diabetes; other bioengineered tissue for the ectopic production of missing proteins.

Value Proposition: Few treatments are effective for life-threatening liver disease. The generation of ectopic livers in lymphatic sites could be an efficient mode of generating functional hepatic mass for patients affected with liver diseases. No currently available technology for lymph node engraftment has been described in the literature.

18. PersonalizedDrugandDiagnosticCo-DevelopmentinTransplantImmunosuppressionInnovator: Rakesh K. Sindhi, MD

Director, Pediatric Transplant Research, Co-Director, Pediatric Transplantation, Children’s Hospital of Pittsburgh; Associate Professor, University of Pittsburgh, Department of Surgery, Division of Transplantation, Thomas E. Starzl Transplantation Institute

Mentor: Hank Safferstein, PhD, JD, MBAExecutive in Residence, Pittsburgh Life Sciences Greenhouse

Technology Description: This FDA-designated multiparametric immune monitoring assay estimates the instantaneous risk of rejection after solid organ transplantation, and can be used for personalized adjustment of anti-rejection medicines called immunosuppressants. The estimate of rejection risk is highly specific for each transplant recipient because the test recreates the donor-recipient interaction in a test tube using peripheral blood cells from both participants. Reducing immunosuppression doses is important, because complications such as life-threatening infections, malignancies, kidney failure, and high blood pressure limit survival and quality of life. In current practice, such dose adjustments are based on empiric, time-based, minimization protocols. As a result, organ rejection or side effects complicate drug management in over half of all solid organ transplant recipients.

Commercial Application: Roughly 29,000 new solid organ transplants each year in the United States, and >300,000 living solid organ recipients on long-term immunosuppression will benefit from this test. Further, the assay system can be used to measure relative drug efficacy in comparative clinical trials, because more effective immunosuppressants can accelerate reduction of rejection risk in longitudinal follow-up. To this end, qualification of the test system as a potential efficacy endpoint has been initiated with the FDA.

Value Proposition: The technology offers the following advantages:• Personalized specificity• Overnight results• Small blood samples required• It is the only test capable of assessing rejection risk on a lifelong basis.

19. Entromics:PhysicalGenomicsforOptimizationofBiologicDrugDesign,TargetDiscoveryandHumanizationofAnimalModelsInnovator: Petr Pancoska, PhD

Research Associate Professor, University of Pittsburgh, Center for Clinical Pharmacology, School of Medicine

Mentor: Richard Ekstrom, MBAPrincipal, Socius Partners, LLC

Technology Description: The investigator has developed a method of determining the functional significance of positions in DNA sequences, by extracting the footprints of evolutionary history in genome thermodynamics. Results provide novel quantitative tools to identify and engineer important and novel functionality through design of DNA. In practical applications, this provides tools to indentify never observed functional similarities (tau-homology) or hidden differences within genomes of different species (important for animal based disease models) or within a set of sequences of pathway genes. Importantly, the approach is not only a novel tool for analysis, the methods can be used to generate new sequences that result in molecules including proteins with superior functionality.

Commercial Application:

• Biologics drugs and vaccines

• Identification of unique genome signatures of pathogens for applications in detection technologies (defense, bio-terror)

• Identification of active sites of enzymes and therefore drug targets

• Preparation of “technological enzymes” (higher temperature stability, modification of structure flexibility etc.)

Value Proposition: This technology is capable of extracting functionally relevant informa-tion from genome sequence irrespectively of the DNA “type” e.g. coding/noncoding, junk DNA, regulatory/untranslated regions. Biologically relevant information can be extracted from a single sequence. If many sequences are available, comparisons of single sequence results provide a higher level of biological information. The method can be utilized for example to identify novel drug targets and develop more effective drugs and vaccines. The technology can be implemented on a grid computer system enabling high speed parallel processing for analyses of large data sets (i.e. human chromosome) and can also work efficiently on a single computer.

20. SmallMoleculeInhibitorsofHIVNef-SrcFamilyKinaseComplexesasAnti-HIVAgentsInnovator: Thomas Smithgall, PhD

William S. McEllroy Professor & Chair, University of Pittsburgh, Microbiology and Molecular Genetics, School of Medicine

Mentor: Michael Lehman, MD, MBADirector of PantherlabWorks and Student Services, University of Pittsburgh, Institute for Entrepreneurial Excellence, Joseph M. Katz Graduate School of Business

Technology Description: The majority of current AIDS drug therapies target either the viral reverse transcriptase (NRTI, NNRTI) or HIV protease. While these compounds dramatically decrease mortality from HIV-induced disease, the continued emergence of drug-resistant strains of virus makes development of new anti-HIV drugs based on novel mechanism of action highly desirable. The HIV-1 accessory protein Nef is required for viral replication and AIDS progression. Nef functions by interaction with multiple host cell signaling proteins, including Hck, a member of Src protein-tyrosine kinase family. The investigator developed an in vitro screening assay using purified Nef and Hck proteins. They screened five libraries of chemical compounds (12,000 compounds total) and obtained three confirmed hits. Several of these compounds blocked HIV replication in vitro.

Commercial Application: There is a great need for more efficacious drugs to treat patients infected with HIV. Disrupting the interaction between Nef and host cell target proteins such as Hck may be useful in the discovery of new classes of anti-HIV drugs.

Value Proposition: These findings show that 1) the Nef-Hck complex represents a novel target for small molecule anti-HIV drug discovery; 2) a novel in vitro chemical screen using the Nef-Hck complex has the capacity to identify potential anti-HIV lead compounds; 3) diphenylfuropyrimidines discovered with this assay represent a novel class of possible anti-HIV agents directed against cellular targets distinct from those of existing anti- HIV drugs.

21. AutomatedSegmentationofPulmonaryFissuresandLobesDepictedonCTExaminationsInnovators: Jiantao Pu, PhD

Assistant Professor, University of Pittsburgh, Imaging Research Center, Department of Radiology, School of Medicine

David Gur, ScDUniversity of Pittsburgh—Executive Vice Chairman of Radiology; Director, Imaging Research Division; Professor of Radiology, School of Medicine

Mentor: Desmond O’ConnorExecutive in Residence, Innovation Works

Technology Description: Human lungs are divided by fissures into lobes. Early lung diseases may begin in and/or be confined to an individual lobe. Incomplete fissures are a major concern because diseases may spread from one lobe to the adjacent one through incomplete fissures.

This technology is an automated computerized scheme to 1) delineate pulmonary fissures and lobes, 2) quantify the distribution of diseases in local lung regions and 3) examine the integrity of fissures in three dimensional space.

Commercial Application: An automated scheme for lung lobe segmentation and fissure integrity quantification may not only be useful for identifying and characterizing chronic diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), but could also help facilitate pre-operative planning and post-operative assessments as well as intra-patient registration and comparison of sequential imaging procedures.

Value Proposition: Currently, visualization and assessment of the fissures is typically done in a very subjective manner. This manual assessment is extremely difficult and time consuming because of the need to mentally track and reconstruct the three-dimensional contours of pulmonary fissures that often span over multiple CT images. Phenotyping lung abnormalities using in vivo imaging will improve understanding of lung anatomy and function in various individuals and may lead to better therapeutic management of patients. This computer aided diagnosis of lung diseases enables better diagnosis of lung disease and is efficient, robust and insensitive to image noises. A prototype has been developed.

22. AutomatedDetection&SegmentationofLungNodulesDepictedonCTExaminationsInnovators: Jiantao Pu, PhD

Assistant Professor, University of Pittsburgh, Imaging Research Center, Department of Radiology, School of Medicine

David Gur, ScDUniversity of Pittsburgh—Executive Vice Chairman of Radiology; Director, Imaging Research Division; Professor of Radiology, School of Medicine

Mentor: Desmond O’ConnorExecutive in Residence, Innovation Works

Technology Description: This technology is a new computerized scheme to automatically detect and segment lung nodules in computed tomography (CT) images. The detection procedure is conducted by analyzing the shape features of lung anatomical structures as well as the intensity property field of CT images.

Commercial Application: Lung cancer is the leading cause of cancer related deaths in the world. The high mortality is associated primarily with late stage at detection. When assessing the types of lung nodules (benign or malignant) and lung cancer prognosis as well as treatment efficacy, radiologists frequently need to measure nodules size in volume/diameter and changes of nodule size over time. The development of high resolution multi-detector computed tomography (MDCT) makes it possible to screen small nodules; however, it is a very laborious task for radiologists to view, analyze and mark each CT image on a routine basis. As a result, the development of an optimal computerized scheme for automated nodule detection and segmentation has been attracting significant research. This technology would be very useful in early detection and diagnosis of lung cancer.

Value Proposition: This method can be used as an independent system for computer-aided lung nodule detection and segmentation and has the potential for improving overall detection. A prototype has been developed.

23. ConfigurationofInitialAmplificationControlParametersinPhotodetectorsforMulti-ColorFlowCytometryInnovators: Albert D. Donnenberg, PhD

University of Pittsburgh—Professor of Medicine, School of Medicine; Department of Infectious Diseases and Microbiology, Graduate School of Public Health; Director, University of Pittsburgh Cancer Institute Flow Cytometry Laboratory; Laboratory Director, University of Pittsburgh Medical Center Hematopoietic Stem Cell Laboratory; Deputy Director, University of Pittsburgh Cancer Institute Hematopoietic Stem Cell Laboratory

Vera S. Donnenberg, PhDUniversity of Pittsburgh—Assistant Professor of Surgery; Heart, Lung and Esophageal Surgery Institute; Assistant Professor of Surgery and Pharmaceutical Science, School of Medicine

Mentors: Gary GlausserFounding Partner and Chief Financial Officer, Birchmere Ventures

Arun Ranchod, MBABusiness Development Manager, Medrad, Inc.

Technology Description: This technology is an algorithm for optimization of photomultiplier amplification based on modeling the relationships between applied photomultiplier tube (PMT) voltage and measured fluorescence of standard fluorescent beads. The investigators have designed systems and methods for configuration of initial control parameters or amplification control parameters (ACPs) for multiple photodectors with digital electronics utilized in a multi-color flow cytometer.

Commercial Application: The last frontier in flow cytometry standardization is optimization of photomultiplier tube gain. The problem is that spectral overlap of detected fluorochrome emissions is dependent on the relative gains of multiple PMTs. Unbalanced settings require increased spectral compensation, increasing noise and reducing sensitivity. At present, finding a matrix of optimal settings has been a matter of art rather than algorithm and has become increasingly difficult as the number of detectors has increased on modern cytometers. This invention is applicable to optimization of state of the art multicolor flow cytometry and can benefit more routine cytometry by maximizing fluorescence detection sensitivity and providing cross-instrument standardization.

Value Proposition: This technology allows for automated configuration of initial control voltages and photodetectors at startup. Samples are not wasted to optimize settings. This technology also allows data comparison from longitudinal drug studies.

24. EngineeringMicroparticlestoSustainaConstantRateofMacromoleculeDeliveryInnovators: Steven R. Little, PhD

University of Pittsburgh—Assistant Professor and Bicentennial Faculty Fellow, Departments of Chemical Engineering, Bioengineering, Swanson School of Engineering; Department of Immunology, and McGowan Institute for Regenerative Medicine

Sam N. RothsteinUniversity of Pittsburgh—PhD Candidate, Chemical Engineering, Swanson School of Engineering; McGowan Institute for Regenerative Medicine

Mentor: Tom Jones, MBAExecutive in Residence, Carnegie Mellon University

Technology Description: Sustained release formulations have improved patient compli-ance for therapeutics. However, current commercially available formulations for water soluble drugs predominantly sustain release for one or two weeks. The investigators have designed controlled release formulations in silico which should sustain a constant rate of drug delivery lasting from two weeks to 12 months. An example application under development includes a single injection formulation that is capable of matching the multiple immunizing doses of a vaccine.

Commercial Application: The controlled-release drug delivery market was estimated to be worth over U.S. $17 billion globally in 2007. Considerable commercial opportunities exist for the development of controlled delivery of approved and new pharmaceuticals.

Value Proposition: Prior efforts to provide sustained constant rate of drug delivery have focused on the development of novel polymers with potentially dubious biocompatibility. Formulations of the current invention use only FDA approved biodegradable polymers. In addition to improving the duration of release, these formulations maintain a more constant release rate than current sustained release pharmaceuticals, which increases safety by remaining within the therapeutic window, provides for greater effectiveness in the treatment of chronic conditions through more predictable kinetics and decreases costs by efficiently utilizing the drug.

25. SingleStepDiagnostics:UltrasensitiveDetectionofProstateSpecificAntigenUsingBiosensorsInnovators: Joanne Yeh, PhD

University of Pittsburgh—Associate Professor, Structural Biology, School of Medicine; Associate Professor, Department of Bioengineering, Swanson School of Engineering; Director, X-ray Crystallography Facility, School of Medicine

Haibin Shi, PhDResearch Associate, University of Pittsburgh, Structural Biology, School of Medicine

Mentor: Mark Lavender, JDAssociate, K&L Gates

Technology Description: This technology is a biosensor capable of quantifying the level of prostate-specific antigen (PSA) in biological fluids, in one simple step. The investigators have developed biosensors that not only detect but quantify various molecular indicators of diseases, including reactive oxygen species and cancer biomarkers, specifically PSA.

Commercial Application: The U.S. Food and Drug Administration (FDA) has approved the use of the PSA test along with a digital rectal exam to help detect prostate cancer in men 50 years of age or older. The FDA has also approved the use of the PSA test to monitor patients who have a history of prostate cancer to see if the cancer has recurred. If no symptoms to suggest cancer are present, doctors’ may recommend repeating PSA tests regularly to watch for any changes.

Value Proposition: Currently PSA levels are determined as a result of expensive and time consuming laboratory analysis of patients’ blood. The investigators have developed an alternative method of detecting PSA levels using miniaturized sensors, made of natural materials that are cost-effective and biocompatible. Results are consistent with those obtained from ELISA (the method currently employed in laboratory analysis of PSA levels). Additionally, these biosensors are capable of quantifying levels of PSA in urine. The biosensors show great promise as reliable, simple, and inexpensive point-of-care devices, providing powerful means of in-situ detection at unprecedented sensitivities.

These miniaturized devices could lead to a paradigmatic shift in medical diagnostics, enabling individuals to monitor their health, circumventing costly and time consuming laboratory analysis.

26. CancerVaccinesandImmunotherapyInnovators: Olivera Finn, PhD

University of Pittsburgh—Distinguished Professor & Chair, Department of Immunology; Professor, Department of Surgery, School of Medicine; Program Leader, University of Pittsburgh Cancer Institute Immunology Program

Pamela Beatty, PhDResearch Scientist, University of Pittsburgh, Department of Immunology, School of Medicine

Mentor: Don WagnerFounding Partner, Wagner LLP

Technology Description: Tumor associated antigens MUC1 and Cyclin B1 (CB1) elicit strong humoral and cellular immunity and tumor rejection in animals. Safety and immuno-genicity of a peptide of the abnormal form of MUC1 have been tested in Phase I/II trials in over 200 patents with advanced breast, colon, pancreatic and prostate cancer. Abnormal MUC1 is also found in premalignant lesions; a vaccine trial is currently underway in 65 individuals with a history of advanced adenomas, immediate precursors to colon cancer. In addition, a T cell receptor that recognizes abnormal MUC1 on tumor cells has been identified. This receptor can be used for immuno-gene therapy of all adenocarcnomas.

Cyclin B1 peptides have been identified, developed and tested as vaccines in animal models. Anti-CB1 immunity is safe and protective. An FDA approved Phase I/II trial in early stages of lung cancer has been initiated.

Commercial Application: A defective form of MUC1 is present in about half of advanced adenomas and the majority of colorectal cancers. CB1 is abnormally expressed in a range of human tumors and premalignant lesions. The cancer vaccine market has the potential to mirror the growth seen in the monoclonal antibody market, and reach sales above U.S. $5 billion by 2012.

Value Proposition: The MUC1 vaccine, if successful, could obviate the need for repeated colonoscopies in patients at high risk for developing colorectal cancer.

A successful Cyclin B1 vaccine may also be tested as a way to prevent cancer in patients with pre-cancerous lung lesions. Lung cancer kills more Americans than any other kind of tumor.

For more information about any of the technologies presented at this event, please contact Michele Honko in the Office of Enterprise Development: 412-624-3152 or meh74@pitt.edu.

The University of Pittsburgh is an affirmative action, equal opportunity institution. Published in cooperation with the Department of University Marketing Communications. UMC70655-1009