1. Presentation By: Malcolm Gibson
Arizona Space Grant Consortium
Ultrasound as a Proposed Drug Release Mechanism in Biomedical Microrobots
Presentation By:
Malcolm Gibson
UA Advanced Microsystems Laboratory
Dept. of Aerospace and Mechanical Engineering

2. Presentation Objectives
Project Introduction
Theory and Goals
Research and Results
Future Plans and Experiments
Conclusion and Acknowledgments
Questions and Discussion

3. Introduction - Biomedical Microrobots
Biomicrorobotics research is focused on building sub-mm sized, untethered robots for in-vivo medical applications.
Building a complete robotic system that “swims” inside the human body is quite a challenge and requires an innovative combination of Micro- and Nano-Technology.
Potential Applications:
Navigating the vitreous humor for retinal surgery.
Targeted drug delivery.
Small scale exploration.
IRIS - ETH Zurich

4. Introduction - Biomedical Microrobots
Research can be divided into two main areas:
Building the microrobots using MEMS/NEMS and robotic micro-assembly technologies.
Applying and controlling the microrobots for in-vivo applications.
Medical Imaging
Steering and Movement
Actuation
IRIS - ETH Zurich

5. Magnetic Steering and Guiding System
Developed by IRIS (Swiss Federal Institute of Technology)
The steering system uses two coaxial pairs of magnetic field generating coils in Helmholtz and Maxwell configurations respectively.
IRIS - Swiss Federal Institute of Technology (ETH Zurich)

6. Co-Fluidic Encapsulation System
Creates uniform alginate droplets extruded in an oil phase.
Allows for encapsulation of microrobots.
Allows one to easily control the droplet size and extrusion rate.
Pictures: MEMS Lab - Stephane Ritty, Dr. Enikov

7. Drug Release Mechanisms
Current Method
Diffusion
Bare Robot
Surface Coating
Proposed Method
Ultrasonically Induced Cavitation
Encapsulated Micro-Droplet
IRIS - ETH Zurich

8. Research - Investigating Ultrasound
Decided to use surface-coated droplets as opposed to bare robots.
Robot Skin
Ferrite Powder
Droplets provided a larger drug entrapment matrix.
Hypothesis: Can ultrasonically induced cavitation be used to destroy the droplet surface-coating (skin) and induce rapid, diffusive drug release to the surrounding fluidic environment.

9. Experimental Procedure
General Procedure:
Create n droplets using the droplet extrusion system.
Create surface coating for all droplets.
Split droplets up into designated sample test tubes.
Sonicate samples for various time intervals using the laboratory aqua-sonic cleaner.
Apply a chromogenic substrate to the sample and measure the absorbance rate using the spectrophotometer.
Calculate HRP (drug substitute) concentration from the Absorbance rate and generate release curve.

10. Experimental Results
Ultrasound
vs.
Diffusion
Skin
vs.
No Skin
Vortex

11. Visual Release Study
Skin
Bare

12. Future Plans and Experiments
Test release with metal robots instead of Fe powder.
Engineer resonant robots that will resonate upon a certain ultrasonic frequency.
Use Piezoelectric elements or speakers to generate sound frequency.
This will allow control of the frequency.
Specific frequency would actuate droplet release.
Design resonant robots incorporating small air pockets to make sonication more effective.
Investigate the use of high-frequency magnetic pulsing to actuate drug release.
Loop Robots
Eddy Currents
IRIS - ETH Zurich

13. Acknowledgements Dr. Eniko T. Enikov (AME) Mentor:
(Advanced Microsystems Laboratory)
Arizona Space Grant Consortium
Swiss Federal Institute of Technology

14. Questions/Discussion
Thank you for your attention.
Questions?
Comments?
UA Advanced Microsystems Laboratory
Dept. of Aerospace and Mechanical Engineering
Malcolm T. Gibson
Dr. Eniko T. Enikov

15. The Chemistry Behind the Droplets
Surface Skin Formation: Starting with a NaAlg. + HRP + Ferrite Powder Droplet
Soaks for 4 min.
Soaks for 5 min.
NaAlg./Fe/ HRP
Droplet
CaCl2 solution
Polyethylenimine solution
Poly-l-lysine solution
Calcium Chloride (Salt)
crosslinks with NaAlg.
Forming a tough, solid
droplet.
Soaks for 15 min.
PEI creates a surface coating
(skin) around droplet shell.
PLL is believed to leak into the
NaAlg.+CaChl.crosslinking and
strengthen it.

16. The Chemistry Behind the Droplets
Sodium Alginate was selected as a drug entrapment matrix because it is easy to process and there is evidence supporting successful magnetic modulation of drug release.
Sodium Alginate is a linear polysaccharide.
Cellulose fiber found in many plant cells.
These fibers have high strength and durability.
Comprised of mannuronic acid (M) and guluronic acid (G) residues.
Chained in a repeating pattern: GG-GM-MM-…

17. The Chemistry Behind the Droplets
HRP Enzyme as a Drug Substitute
Horseradish Peroxidase (HRP).
44,000 Da enzyme protein
Enzymes are proteins that catalyze chemical reactions.
They exert their catalytic activity upon substrates.
HRP readily bonds with hydrogen peroxide (H2O2) (contained in TMB substrate) and the resultant (HRP–H2O2) complex can oxidize a wide variety of chromogenic hydrogen donors, resulting in color change.
This is what is being measured using the spectrophotometer.