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…)

2

Development of Hybrid Cochlear Implants(Shen’ s Group) Professor I. Y. (Steve) Shen

Anatomy of Human Ears

Hybrid Cochlear Implant

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 low-frequency 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.Cochlea Electrode Bundle

Electrodes

Piezo ActuatorPressure

Wave

3

Objectives: To develop a minimally invasive glucose sensor using single walled carbon nanotubes with higher sensitivity and specificity.

Glucose sensor

Structure of glucose sensor

Prof. Chung’s Group Nanomanufacturing Lab

Fabricated sensor

0.000

0.004

0.008

0.012

0.016

0.020

1mmol 5mmol 10mmol

Glucose concentration

delta

R/R

Response to glucose

•Sensor using simple electrometry: metallic SWCNT bundles to specifically detect H2

•Insensitive to other gases in a clinically important level

4

•Label-free and immobilization-free immunoassay using a hand-held device•Lyophilized-bead-based approach for long-term stability

Micro-fluidic Chip: Immunoassay

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. coli0157:H7 Positive control) with PBS(1X) and Antibody-Antigen complex (E. coli 0157:H7) with PBS(1x)

Microfluidic device with agglutination of antibody-coated polystyrene beads by immunoreactions

Objective:To develop a field-usable assay capable of detecting diarrheagenic enteric pathogens in stool samples

Chung’s Group

5

Micro-fluidic Chip: Cell Trap, Perfusion, Culture(Gao’s Group) Micro-injection (gene-transfer)

3D View

Profile View

Perfusion withPerfusion withHypertonic SolutionHypertonic Solution

Negative Pressure Applied by Syringe Pump

from OutletFill Inlet with

Cell Suspension

Cells Flow Downstreamand being Trapped

6

7

8

9

10

Diagram shows the flow control of the automatedcell-tissue washing system (Gao’s Group)

11

•Research Objectives: •HIFU-created Hierarchical Structures:

•Selective Ultrasonic Foaming System:

•Cell Culture of Smooth Muscle Cell (SMC):

•Potential Applications:

•Conclusions:

By choosing appropriate HIFU parameters, such as scanning speed and acoustic power, hierarchical porous structures can be created in CO2 saturated PMMA samples.

(1) To develop a novel fabrication process for hierarchically-structured porous polymeric structures.

(2) To understand the mechanisms of the proposed selective ultrasonic foaming process.

Fig 1. A schematic of the experimental setup

The system consists of three major components: a HIFU generation module, a sample positioning module, and a data acquisition module.

Positioning System

Polymer Sample

HIFU Transducer

Thermocouples

Function Generator & Power Amplifier

Acrylic tank filled with distilled water

Computer

Data Acquisition System

Positioning System

Polymer Sample

HIFU Transducer

Thermocouples

Function Generator & Power Amplifier

Acrylic tank filled with distilled water

Computer

Data Acquisition System

(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 2. Hierarchical porous structures of a PMMA sample using the HIFU foaming process: left: 80 μm and right: 150 μm pore size.

Speed: 2.4 in/min Speed: 1.2 in/min

Fig 3. Left: Pore size 200-300 μm; Right: Pore size 50-60 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.

(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.

Professor Wei Li (Li’s Group) Selective Ultrasonic Foaming of Porous Polymer for Biomedical Applications

12

Bio-reactors: stem cell expansion (Gao’s Group)

Niobium-coated carbon

13

Hanahan and Weinberg (2000). Hallmarks of Cancer

Chistoserdov, Chen, Lapidus, and Lidstrom (2003). Growth of Bacterium AM1

Prof. Ao’s Ongoing projects: Systems Biology1. 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.

3. Modeling cancer and normal network dynamics.with Lee Hood, et al.

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.

14

Ovary/Testis Ovary/Testis CryopreservationCryopreservation

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 patientsPatients with infertility

15

16

To Establish the 1st National Primate GameteTo Establish the 1st National Primate Gamete--Stem Cell BankStem Cell Bank

UW ME BioUW ME Bio--preservation Lab and Washington National Primate Centerpreservation Lab and Washington National Primate Center

17

Hemodialysis Process

Two challenges to optimize dialysis therapy:

- Optimize artificial kidney- Optimize dialysis dose

18

SEM image of hollow fiber membrane

(Gao’s Group)

RESEARCH: To Develop Novel Hollow Fiber MembranesInner diameter: ~ 200 µmMembrane thickness: ~ 20 µmMaterial: Cellulose Triacetate, Polysulfone, Polyamide

Polyethersulfone

Membrane cross-section

Membrane surfacePore size: ~ 5 nm

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)

urine

Hemofilter

RAD (Renal Assist Device)

filtrate

Post RAD blood

blood

membranekidney cell layer

Post Hemofilter blood

Bio-artificial Kidney

20

Local Collaborations and Resources

Bio-Tech Research In ME

UW Medical Center/NIH Primate Center/FHCRC

Revenue

ZooIndustriesRevenueRevenue

• 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

EE BME CE