1. Cancer Cell Chemotaxis in Microfluidic Devices Dallas Reilly, Chemistry Carthage College Faculty Mentor: Noo Li Jeon, Biomedical Engineering University of California, Irvine Chemotaxis-movement of cells due to a chemical presence

2. Outline Basics – Cancer Breast Cancer – Epidermal Growth Factor Metastasis – Microfluidic devices can help Microfluidic Devices – What are they? – How I use them My Research – Outline – Experiments – Results – Conclusions Acknowledgements References

3. What is Cancer? “Cancer” is a wide range of diseases involving irregular growth of cells – Normal cells vs. Cancer cells Cancerhelp.org

4. Epidermal Growth Factor (EGF) What is it? EGF and EGF receptor What happens to a cell that binds to EGF? Cancer and EGF Wikipedia.org

5. Metastasis Metastasis- cancer cell migration – Tumors – Cancer cells move through the bloodstream and lymphatic system EGF and metastasis MDA-MB 231 Metastatic Breast Cancer Cells Gary Carlson Vitalex

6. Microfluidics can help Microfluidic devices: – Gradients – Advantages – Modeling the body If scientists can discover how and why cancer cells migrate we can start creating chemicals that stop or prevent them from doing so

7. What is a Microfluidic Device? Many uses and applications: pharmaceuticals, biotechnology, the life sciences, defense, public health, and agriculture Polydimethylsiloxane (PDMS) and soft lithography Gradients George Whitesides group, Harvard Saadi, Jeon, Wang, Lin

8. My Research Goals

9. Cont. Procedure – 10X Hoffman – 3 Hours – Bell-curve gradient Analysis – Metamorph – Excel – Oriana Metamorph images

11. 7/18/06, 7/21/06, 7/25/06 EGF Gradient 48/64 cells moved towards gradient-75% 43/66 cells moved towards gradient-65% 91/130-69% Conditions: 50ng/mL EGF, cells not starved Summary Average P-value:.0115 Average Degree (R/L): 97/262 CI Value (R/L):.13/.12 Standard Deviation (R/L):.12/.04 LHG

12. 7/28/06 and 8/1/06 EGF Gradient 25/51 cells moved towards gradient-49% 18/44 cells moved towards gradient-41% 43/95-45% Conditions: 500ng/mL EGF, cells not starved Summary Average P-value:. 612 Average Degree (R/L): 209/154 Average CI Value (R/L):.38/.01 Average Standard Deviation (R/L):.44/.24 LHG

13. 8/7/06 2 Exp. EGF Gradient 20/43-47% Conditions: 50ng/mL EGF, cells starved (~12 hours) Summary Average P-value:. 695 Average Degree (R/L): 217/23 Average CI Value (R/L):.33/.07 Average Standard Deviation (R/L):.48/.18 8/19 cells moved towards gradient-42% 12/24 cells moved towards gradient-50% RHG

14. 8/8/06 Exp. 3 EGF Gradient 4/5 cells moved towards gradient-80% 8/11 cells moved towards gradient-72.7% 12/16-75% Conditions: 50ng/mL EGF, cells starved (~5 hours)

15. 8/24/06 and 8/25/06 3 Exp. EGF Gradient 67/101-66% Conditions: 50ng/mL EGF, cells starved (1-3 hours) Summary Average P-value:.016 Average Degree (R/L): 106/260 CI Value (R/L):.12/.09 Standard Deviation (R/L):.08/.06 31/46 cells moved towards gradient-67% 36/55 cells moved towards gradient-65% RHG

16. Conclusions EGF High Concentration Starvation

17. The Future (and present) More growth factors Cells Chemo-repellants Devices that better model the body Extracellular matrices

18. Acknowledgements I’d like to thank my mentor, Noo Li Jeon, my graduate student, Carlos Huang, and the rest of the great people in my lab for teaching me such an incredible amount in such a short time and for taking their time to assist my research I’d also like to thank the UROP program, with which this research opportunity would have never been possible, their time and effort

19. References and works cited: George M. Whitesides. The Origins and the Future of Microfluidics. Nature Publishing Group, July 2006. George M.Whitesides, Emanuele Ostuni, Shuichi Takayama, Xingyu Jiang, and Donald E. Ingber. Soft Lithography in Biology and Biochemistry. Annual Review of Biomedical Engineering, 2001 (335-573). Noo Li Jeon, Harihara Baskaran, Stephan K.W. Dertinger, George M. Whitesides, Livingston Van De Water, and Mehmet Toner. Neutrophil Chemotaxis in Linear and Complex Gradients of Interleukin-8 Formed in a Microfabricated Device. Nature Publishing Group, 2002. Stephan K. W. Dertinger, Daniel T. Chiu, Noo Li Jeon, and George M. Whitesides. Generation of Gradients Having Complex Shapes Using Microfluidic Networks. Analytical Chemistry (ACS), 2001. Noo Li Jeon, Stephan K. W. Dertinger, Daniel T. Chiu, Insung S. Choi, Abraham D. Stroock, and George M. Whitesides. Generation of Solution and Surface Gradients Using Microfluidic Systems. Langmuir (ACS), 2000. Shur-Jen Wang, Wajeeh Saadi, Francis Lin, Connie Minh-Canh Nguyen, Noo Li Jeon. Differential Effects of EGF Gradient Profiles oN MDA-MB-231 Breast Cancer Cell Chemotaxis. Elsevier, INC, 2004. Wajeeh Saadi · Shur-Jen Wang · Francis Lin · Noo Li Jeon. A Parallel-Gradient Microfluidic Chamber for Quantitative Analysis of Breast Cancer Cell Chemotaxis. Biomedical Devices (109-118), 2006. Jennifer Ouellette. A new wave of microfluidic devices. The Industrial Physicist (14-17), 2003. Laurie Tarkan. Scientists Begin to Grasp the Stealthy Spread of Cancer. The New York Times, 2006.