1. Converting Elastin-like Polypeptides(ELP) Aggregate to Soluble Form Client: Darin Furgeson PhD School of Pharmacy
Dhaval Desai (Leader)
Lee Linstroth (Communicator)
Malini Soundarrajan (BSAC)
Nathan Kleinhans (BWIG)
Advisor: Naomi Chesler PhD
Department of Biomedical Engineering

2. Overview Problem Statement Background Design Specifications
Alternative design ideas
Design matrix
Future work
Questions

3. Problem Statement
Elastin-Like Polypeptides (ELPs) may serve as promising drug-delivery agents to treat various types of cancers. In order for our client, Dr. Furgeson, to conduct research on ELPs, soluble form of ELP is required. After harvesting ELPs from bacteria, ELPs become aggregated. The purpose of this project is to design a device that will make it easy to convert ELP aggregate into soluble form.

4. Background Current Cancer Treatments Hormonal Therapy: Chemotherapy
Remove hormone producing organs
Inhibit hormone-receptor binding with antagonists
Affect other organs in the body
Chemotherapy
Interfere with the growth and reproductive processes in cancer cells
Destroy normal cells; not tissue specific
Radiation therapy
Use of X-rays, gamma rays, or radioactive implants
Damage the DNA in cancer cells
Harm normal cells

5. Background ELP is a promising non-viral gene/drug carrier
Non-immunogenic
Inverse Temperature Transition
Aggregates above Tt and solubilizes below Tt
Hydrophobic

6. Background

7. Design Specification Resolubilize in PBS Automated Efficient
80% product yield
Less than 20 lbs
Fits in a 1m X 1m X 0.5m lab space
Must operate below Tt

8. Brush Model Commercially available test tube brush: Nylon
Bristles: 20 mm long, 35 mm diameter
Shaft: 150 mm long, powered by motor
Scrape ELP off the sides

9. Brush Model Pros Cons Easy to assemble
High surface area of bristles exposed to the aggregate for ELP-PBS mixing
Cons
Difficult to clean
Product loss

10. Helix Model Two intertwining spirals form a helix
Blades soldered within the helix to break apart aggregate
Made of low gauge wire or thin sheet metal
Powered by external motor

11. Helix Model Pros Cons Resembles current industrial mixer
Easily cleaned
Cost effective
Cons
Difficult to manufacture
Possible low product yield
Safety concerns

12. Dual Scraper Model Utilized metal scraper with slits
Scrapers are in contact with the side of the tube
Slits aid in agitating solution

13. Dual Scraper Model Pros Cons Maximizes product resolubilization
Agitates solution
Cons
Difficult to manufacture
ELP might adhere to the curved scrapers

14. Design Matrix Criteria Brush Model Helix Model Dual Scraper Model
Ease of Cleaning 2 7 6
Product Yield 5
Cost 8
Ease of Manufacturing 4
Prototype Life
Total 22 28 33

15. Future Work Final design/modifications Choose materials
Build prototype
Extensive testing with ELP

16. References
Betre H, Setton LA, Meyer DE, Chilkoti A. Characterization for genetically engineered elastin-like polypeptide for cartilaginous tissue repair. Biomacromolecules Sep-Oct, 3(5):
Chilkoti A, Dreher MR, Meyer DE, Design of thermally responsive recombinant polypeptide carriers for targeted drug delivery. Adv. Drug Deliv Rev Oct 18; 54(8): Review
Chilkoti A, Dreher MR, Meyer DE, Raucher D. Targeted drug delivery by thermally responsive polymers. Adv Drug Deliv. Rev Sep 13; 54(5): Review