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Device to monitor neurotransmitter in vivo

Device to monitor neurotransmitter in vivo. Chunlan Jiang Zhuohan Zhang Xinghao Wang Dan Ritter. Contents. Introduction System Architecture and Manufacturing Testing Conclusion. Why do we need to monitor the chemicals in brain?. Discovering brain activities

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Device to monitor neurotransmitter in vivo

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  1. Device to monitor neurotransmitter in vivo Chunlan JiangZhuohan Zhang Xinghao Wang Dan Ritter

  2. Contents • Introduction • System Architecture and Manufacturing • Testing • Conclusion

  3. Why do we need to monitor the chemicals in brain? • Discovering brain activities Neural activities – tactile sensations, transmitter Emotion – Depression, etc • Diagnosis of certain diseases Alzheimer's disease, (AD) ParKinson Disease • Drug test Effectiveness, duration, toxicity, etc

  4. Current Methods * Pradyot Nandi, Susan M. Lunte, Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review, Analytica Chimica Acta, 2009 1-14.

  5. Current Methods * Pradyot Nandi, Susan M. Lunte, Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review, Analytica Chimica Acta, 2009 1-14.

  6. Current Methods * Pradyot Nandi, Susan M. Lunte, Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review, Analytica Chimica Acta, 2009 1-14.

  7. Drawbacks • Major injury to the head Inner diameter ave. 200~500 um unacceptable for human tests • Diffusion fluid to prepare and consumed • Extracellular fluid loss * Pradyot Nandi, Susan M. Lunte, Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review, Analytica Chimica Acta, 2009 1-14.

  8. Improvement • Minor cut (injury) diameter less than 100 um 1/3 ~ 1/5 of the size as in dialysis design make applications possible for human • Pump out fluid directly from brain • Minimal sample size • Fast detection and analysis

  9. System Architecture • Sampling – Micro pump • Testing – Capillary electrophoresis (CE) • Connection – constant volume valve valve CE pump

  10. Microscale Pump

  11. The structure of micropump Piezoelectric Cantilevers (Quick-mount Bending Actuator) Sketch: The tip of a Quick-Mount Bender moves in an arc. The different types of cantilevers

  12. Piezoelectric Cantilever Micropositioner Body

  13. Three unique square wave signal sequences sent to each of the cantilever. Signal sequence of micropump valves From Neil J. Graf

  14. Microfabrication

  15. 30:1 PDMS layer Spinner in NFC 30:1PDMS prepolymer was mixed and poured over the surface of glass. And then spinned the glass under a program to control the thickness of layer. It was cured in a convection oven at 80C for 30 mins.

  16. CE-Constant Volume Valve

  17. Testing: Capillary Electrophoresis • Commercial available

  18. Expected results

  19. Expected results control drug

  20. Why a Constant Volume Valve • Issues with Micro pump/CE • CE is not a true continuous measuring device • very difficult to pump a constant volume • quantification requires the total volume to be known • cannot detect total activity change

  21. Key Concepts of Constant Volume Valve Pinch Valve Constant Volume Pump 2. Capacitive sensor

  22. Constant Volume Valve Actuation Layer Elastic Material Pinch Valve Pump CE

  23. Constant Volume Valve Actuation Layer Elastic Material Pinch Valve Pump CE

  24. Pinch Valve Module J. Micromech. Microeng. 19 (2009) 115012

  25. Measuring Module substrate shallow Channel bottom electrode overlay elastic material top electrode S. Satyanarayana et al. / Sensors and Actuators B 115 (2006)

  26. Constant Volume Valve X CE Pump

  27. Constant Volume Valve X CE Pump

  28. Testing • Full Design Verification Testing- 29 samples for a 95/90 confidence/reliability level • Fluid Volume vs Capacitance • Stress the valve • Flow through for biologically representative fluid of the entire system • Test the pump • Use “off the shelf” electrophoresis to eliminate most of the testing required

  29. Testing-Capacitance vs. Volume

  30. Testing- Stress the Valve • Characterization testing for the valve seals

  31. Testing-Flow Through and Pump • Goal is to assess pump capability (similar to valve seals) • System flow through has 2 main goals • Measure fluid output to ensure real time data collection • Observe any systemic issues between the interconnecting parts

  32. Limitations • Flow rates are key • Drive the valves • Provides key benefit over current technology • If clogged the device is worthless • Single Use

  33. Biocompatibility • Governed by ISO10993 and 21CFR814 • Only the probe touches the animal fluids/tissues • Largest requirement for biocompatibility is ensuring constant flow through for system up until the electrophoresis

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