1. BioMEMS Implantable Drug Delivery Systems
Professor Horacio Espinosa – ME381 – Final project
Aaron Alexander
Luke Rogers
Dan Sheehan
Brent Willson

2. Current Technology
Include hypodermic needles, pills, and passive transdermal methods
Disadvantages:
Highly Invasive
Poor Control
Can be Ineffective

3. Drug Delivery by MEMS Advantages Disadvantages Improved Control
More Effective
Less Intrusive
Disadvantages
Biocompatibility Concerns
Biofouling Issues

4. Areas of Research In Vivo Devices Transdermal Devices Within the body
Implanted or Ingested
Transdermal Devices
Acts through the skin

5. Reservoir Devices Passive Active Pourous material allows diffusion
Deteriorating membranes
Active
Electrically activated
Biocompatibilty Issues:
Toxicity and damage to tissue
Functionality (Biofouling)

6. Passive vs. Active Passive Active Simpler to manufacture
No power source needed
Less control
Active
More complex fabrication
Battery required
More biocompatibility concerns
Much more control
Several means to stimulate actuation

7. The “Smart Pill” Built-in sensor to detect when the drug is required
Artificial muscle membrane to release the drug

8. Transdermal Devices Currently available: Improvements: Passive
Can be ineffective and difficult to control
Improvements:
Iontophoresis
Chemical Enhancers
Ultrasound

9. Microneedles
Microneedles are used to improve transdermal drug delivery

10. MicroCHIPS Inc. Implantable Device
Best Device
MicroCHIPS Inc. Implantable Device

11. MicroCHIPS Inc. Implantable Device
Best Device
MicroCHIPS Inc. Implantable Device

12. Why?

13. Why? Many different configurations make it quite Versatile

14. Why? Many different configurations make it quite Versatile
Easy to implement

15. Why? Many different configurations make it quite Versatile
Easy to implement
Simple yet effective

16. Why? Many different configurations make it quite Versatile
Easy to implement
Simple yet effective
Smaller in size than the “Smart Pill”

17. Start with Silicon wafer approx. 300 microns thick
PECVD 3000 angstrom thick Silicon Nitride
Silicon Nitride Patterned with Photolithography and RIE etched
KOH anisotropic etch (Silicon Nitride acts as a mask and stop)

18. Deposit Gold Cathode and Anode Membrane
PECVD Silicon Dioxide used as a
Dielectric
Patterned using PR and etched
with RIE
Etched to gold membrane using RIE

19. Invert and inject drug into reservoir using inkjet technology
Reservoirs capped with Silicon Nitride

20. Steps following fabrication
Integrated Circuitry manufactured
Combined with delivery chip and thin film battery into a compact package

21. Thin Film Battery No toxic materials used

22. Thin Film Battery No toxic materials used
Nothing to leak into the body

23. Thin Film Battery No toxic materials used
Nothing to leak into the body
Can be recharged many times

24. Thin Film Battery No toxic materials used
Nothing to leak into the body
Can be recharged many times
1.5 to 4.5 volts

25. Thin Film Battery No toxic materials used
Nothing to leak into the body
Can be recharged many times
1.5 to 4.5 volts
Size:
.5 to 25 cm2
15 microns thick

26. Battery Cross Section

27. Actuation

28. Oxidation Reduction Reaction
Au + 4Cl-  [AuCl4]- + 3e-
Au + mH2O  [Au(H2­O)m]3+ + 3e-
2Au + 3H2O  Au2O3 + 6H+ + 6e-
2Cl-  Cl2 +2e-
Au2O3 + 8Cl- + 6H+  2[AuCl4]- +3H2O

29. Activation of Redox Reaction
The in vivo environment can be considered as an aqueous NaCl solution with a PH between 6 and 7
When a minimum of .8V is applied [AuCl4]- is the favorable state for gold in this solution.

30. Advantage of Implantable Drug Delivery
Conventional drug delivery such as injection or pills
Much farther from the ideal concentration over the time cycle
MEMS implantable drug delivery systems
Maintains a dosage level very close to the target rate

31. Oxidation (corrosion) of Gold Reservoir Caps
A stimulus voltage is applied for µs to start the oxidation reaction
Gold corrodes and goes into the body as harmless [AuCl4]-

32. Gold Reservoir Cap

33. Developing Technology
Nano-channel Device
Porous Hollow Silica Nanoparticles (PHSNP)
Quantum Dots

34. Nano-channel Device Nano-channel filter Simpler than previous devices
Standard/Mass production
Dimensions optimized for strength

35. Top of Base Substrate
Drug enters entry flow chamber from entry port of top substrate
Enters input fingers, passes through nano-channels
Exits through output fingers and exit flow chamber

36. Glucose Release Solution to constant drug delivery need
Drawback: drugs pass through nano-channels at different rates – electrical integration and control of flow through nano-channels

37. Porous Hollow Silica Nanoparticles (PHSNP)
Used in many different applications
Past drug carriers primarily oil-in-water units, liposomes, and nanoparticles and microparticles made of synthetic polymers and or natural macromolecules
PHSNP diameter = 60-70nm, wall thickness = 10nm
Synthesis of PHSNP involves CaCO3 template
Fig. 3. TEM (Transmission Electron Microscope) image of PHSNP

38. PHSNP to carry Cefradine
Treat bacterial infection by destroying cell walls
Used for infection in airways, kidneys, post-surgery, other
Fig. 1. Molecular structure of cefradine.

39. Distribution of Cefradine in PHSNP
PHSNP and Cefradine mixed vigorously
Fig. 2. Preparation process of drug carrier from PHSNP. (a) PHSNP; (b) suspension of cefradine and PHSNP; (c) PHSNP entrapped with cefradine.
Fig. 4. Distribution of pore diameters in the wall of PHSNP (a) before entrapping cefradine; (b) after entrapping cefradine.

40. Release of Cefradine
Stage one: 76% release in 20 min. – surface of PHSNP
Stage two: 76%-82% release in 10 hours– pores of PHSNP
Stage three: insignificant release from PHSNP hollow center
Gradual release over time can be exploited in drug delievery applications
Fig. 5. In vitro release profile of cefradine from PHSNP

41. Quantum Dots
Crystals containing a group of electrons – usually made of II-VI semiconductor cadmium selenide
Nanometers wide, demonstrate quantum properties of single atoms, absorb and emit specific wavelengths of light
Bind Taxol, a cancer-fighting drug, and a molecule with affinity to folic acid receptors to quantum dots, also effective when bound with antibodies
Cancer cells have high concentration of folic acid receptors and can be targeted
Once excited with IR light, the bond is broken with the drug, Taxol, which is able to attack the cancerous cell

43. IR Illuminated Rat Implanted with tumor
Injected with quantum dots, bound with Taxol
High concentration around tumor
Technique not as effective in humans due to deep internal organs
May be effective for skin and breast cancer