Research Highlights (Bio-Health)

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1 Research Highlights (Bio-Health) Bio-instruments, Bio-sensors, Nano-Tech (Shen, Taya, Xu, Reinhall, Wang, Seibel, Chung, Devasia, Gao ) New Bio-compatible and Implantable Materials (Li, Taya, Xu, Gao ) Bio-mechanics/Injury Mechanics (Ching, ) System Biology (Ao ) Artificial organs (Gao ) Cryopreservation and banking of living cells and tissues (including engineered tissues) (Gao ) 1

2 Development of Hybrid Cochlear Implants (Shen s Group) Professor I. Y. (Steve) Shen Anatomy of Human Ears Hybrid Cochlear Implant Pressure Wave Cochlea Piezo Actuator Electrode Bundle Electrodes Current Status Most hearing loss results from sensori-neural impairments due to damage of hair cells. Sensori-neural impairments are permanent. Cochlear implants are seldom used for patients with preserved lowfrequency hearing. New Technology & Challenges Develop a piezoelectric microactuator to generate acoustic stimulation in cochlear. Develop encapsulation to make the device implantable. Transfer technology to industry. 2

3 Prof. Chung s Group Nanomanufacturing Lab Glucose sensor Objectives: To develop a minimally invasive glucose sensor using single walled carbon nanotubes with higher sensitivity and specificity delta R/R Structure of glucose sensor Fabricated sensor mmol 5mmol 10mmol Glucose concentration Response to glucose Sensor using simple electrometry: metallic SWCNT bundles to specifically detect H 2 Insensitive to other gases in a clinically important level 3

4 Chung s Group Micro-fluidic Chip: Immunoassay Objective: To develop a field-usable assay capable of detecting diarrheagenic enteric pathogens in stool samples Microfluidic device with agglutination of antibodycoated polystyrene beads by immunoreactions Pure water, PBS(1X), PB, PBS(10X), E. coli 0157 test kit (negative control), positive control, Monoclonal antibody (E. coli 0157:H7) in PBS(1X), Antigen (E. coli 0157:H7 Positive control) with PBS(1X) and Antibody- Antigen complex (E. coli 0157:H7) with PBS(1x) Label-free and immobilization-free immunoassay using a hand-held device Lyophilized-bead-based approach for long-term stability 4

5 Micro-fluidic Chip: Cell Trap, Perfusion, Culture (Gao s Group) Micro-injection (gene-transfer) Fill Inlet with Cell Suspension Negative Pressure Applied by Syringe Pump from Outlet 3D View Cells Flow Perfusion Downstream with and Hypertonic being Trapped Solution Profile View 5

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10 Diagram shows the flow control of the automated cell-tissue washing system (Gao s Group) 10

11 Professor Wei Li (Li s Group) Selective Ultrasonic Foaming of Porous Polymer for Biomedical Applications Research Objectives: (1) To develop a novel fabrication process for hierarchicallystructured porous polymeric structures. (2) To understand the mechanisms of the proposed selective ultrasonic foaming process. HIFU-created Hierarchical Structures: By choosing appropriate HIFU parameters, such as scanning speed and acoustic power, hierarchical porous structures can be created in CO 2 saturated PMMA samples. Speed: 2.4 in/min Speed: 1.2 in/min Selective Ultrasonic Foaming System: The system consists of three major components: a HIFU generation module, a sample positioning module, and a data acquisition module. Function Generator & Power Amplifier Acrylic tank filled with distilled water Computer Positioning System Data Acquisition System Fig 2. Hierarchical porous structures of a PMMA sample using the HIFU foaming process: left: 80 μm and right: 150 μm pore size. Cell Culture of Smooth Muscle Cell (SMC): HIFU Transducer Polymer Sample Thermocouples Fig 1. A schematic of the experimental setup Potential Applications: (1) The unique processing capability enables co-culture of different types of biological cells. (2) The process has potential in animal-on-a-chip devices. (3) The solvent-free characteristic of the process is preferable for tissue engineering scaffolds. Fig 3. Left: Pore size μm; Right: Pore size μm. Green spots shows live cells. Cells spread more evenly about the smaller pores as compared with the larger pores, where cells clung to the edges of the pores. Conclusions: (1) A novel selective ultrasonic foaming process has been developed to create hierarchical porous structures. (2) The process is promising for fabricating porous polymeric structures for biomedical applications. 11

12 Bio-reactors: stem cell expansion (Gao s Group) Niobium-coated carbon 12

13 Prof. Ao s Ongoing projects: Systems Biology 1. Modeling dynamics of gene regulatory network. Efficiency, robustness and stochasticity of gene regulatory networks in systems biology: λ switch as a working example, Zhu, Yin, Hood, Galas, and Ao, in Introduction to Systems Biology (Humana Press, 2006, in press). 2. Modeling kinetics of metabolic network. with Mary Lidstrom, George Kosaly, et al. Chistoserdov, Chen, Lapidus, and Lidstrom (2003). Growth of Bacterium AM1 3. Modeling cancer and normal network dynamics. with Lee Hood, et al. Hanahan and Weinberg (2000). Hallmarks of Cancer 4. Understanding evolution--the fundamental process in biology. Fundamental theorem of natural selection. Wright s adaptive landscape 5. Developing mathematical/numerical tools dealing with stochastic processes. New stochastic integration method. Universal construction of Lyapunov function. 13

14 Ovary/Testis Cryopreservation Cancer patients: Recent advances in chemo/radio therapy have significantly improved the long-term survival of young cancer patients. However, infertility caused by such therapy produces significant physiological and psychological impact on these patients. In Hodgkin s lymphoma, chemo causes nearly 100% permanent infertility. Patients with premature ovarian failure? Post-menopause patients Patients with infertility 14

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16 To Establish the 1st National Primate Gamete-Stem Cell Bank UW ME Bio-preservation Lab and Washington National Primate Center 16

17 Hemodialysis Process Two challenges to optimize dialysis therapy: - Optimize artificial kidney - Optimize dialysis dose 17

18 RESEARCH: To Develop Novel Hollow Fiber Membranes Inner diameter: ~ 200 µm Membrane thickness: ~ 20 µm Material: Cellulose Triacetate, Polysulfone, Polyamide Polyethersulfone Membrane cross-section SEM image of hollow fiber membrane (Gao s Group) Membrane surface Pore size: ~ 5 nm 18

19 Tissue Engineering: Bio-Functional Artificial Kidney - culture kidney cells in the hollow fiber to secrete hormone and re-absorb useful solutes (cryopreserved kidney cells) membrane kidney cell layer RAD (Renal Assist Device) filtrate Post Hemofilter blood urine Hemofilter Post RAD blood blood 19 Bio-artificial Kidney

20 Local Collaborations and Resources EE BME CE Industries Revenue Bio-Tech Research In ME Revenue Revenue Zoo UW Medical Center/NIH Primate Center/FHCRC Bio-instruments and Bio-Sensors Organ/tissue/cell Transplantation Infertility (IVF, Artificial Insemination) Kidney Disease (Artificial Kidney) Hearing, Vision, Bio-imaging, Diagnosis Bio-mechanics New Materials Bio-fluids, Blood, Cardiovascular System 20