1. Chien-Yu ChenMSCL1 A spherical micropump actuated by cultured cardiomyocytes Teacher : Cheng-Hsien Liu Student : Chien-Yu Chen ( 陳鍵瑜 ) Date : 05/16/2007 Reference : FABRICATION OF PREMITIVE SPHERICAL MICROPUMP POWERED BY CARDIOMYOCYTES:MICRO SHERICAL HEART, μTAS2006, p.1133-1135

2. Chien-Yu ChenMSCL2 Outline  Introduction  Design concept & fabrication setup  Experiment result  Conclusion

3. Chien-Yu ChenMSCL3  Efficient biochemical devices incorporating cells into a miniaturized mechanical system have been frequently reported.  Biochemical reactors or analysis systems exploiting cellular biochemical functions are the mainstream. Introduction Schematic view : Cross-sectional view along line A–B : Design of a bio-actuated pump on a microchip powered by a cultured cardiomyocyte sheet.

4. Chien-Yu ChenMSCL4 Design concept Design of a micro spherical heart. A cardiomyocyte sheet covers the hollow sphere entirely. Schematic view : Cross-sectional view along line A-B.

5. Chien-Yu ChenMSCL5 Fabrication setup (A)Threading a capillary through a hole on a sugar ball, and applying melted glucose around the hole to prevent penetration of PDMS prepolymer. (B)PDMS dispense and solidification while rotating above a hotplate at 100ºC. (C) Drawing and insertion of capillaries to make them be into the sphere partly and attachment of them to the sphere by glue. (D) Dissolving the sugar ball by water.

6. Chien-Yu ChenMSCL6 Experiment result A fabricated PDMS hollow sphere before transplantation of a cardiomyocyte sheet. (About 5 mm in diameter, 250 μm in thickness) A fabricated PDMS hollow sphere before transplantation of a cardiomyocyte sheet. (About 5 mm in diameter, 250 μm in thickness) A hollow sphere immersed in medium after transplantation of a cardiomyocyte sheet. A hollow sphere immersed in medium after transplantation of a cardiomyocyte sheet. 1. Washed with ethanol. 2. Sterilized using UV light for 15 min. 3. Immersed for fibronectin (from bovine serum, Sigma) solution in phosphate buffered saline (PBS) to promote cardiomyocyte attachment.

7. Chien-Yu ChenMSCL7 Experiment result Schematic view describing the observation method and a measured parameter (x). Schematic view describing the observation method and a measured parameter (x). Displacement time-course of one particle near the center of the capillary for 5 s at 37°C. Gray and black plots indicate particle displacement before and after cardiomyocyte sheet transplantation, respectively. Displacement time-course of one particle near the center of the capillary for 5 s at 37°C. Gray and black plots indicate particle displacement before and after cardiomyocyte sheet transplantation, respectively. Fluid oscillating frequency : 0.4 Hz Maximum displacement : 70 μm Fluid oscillating frequency : 0.4 Hz Maximum displacement : 70 μm

8. Chien-Yu ChenMSCL8 Conclusion  Regular fluid motion in a capillary connected to the hollow pumping sphere wrapped a beating cardiomyocyte sheet was confirmed, with the device working continuously over 5 days.  This bio/artificial hybrid fluidic device is a fully integrated, wireless mechanochemical converter, exploiting a spherical heart-like pumping structure.  Pumping action is driven with only chemical energy input from culture milieu without any requirement for coupled external energy sources, unlike conventional actuators.  Critical issue to discuss : How to control the flow rate ?

9. Chien-Yu ChenMSCL9 Thank you !

10. Chien-Yu ChenMSCL10 1. Y. Tanaka, K. Morishima, T. Shimizu, A. Kikuchi, M. Yamato, T. Okano, T. Kitamori, Lab Chip, 6, 362-368, (2006). 2. T. Shimizu, M. Yamato, Y. Isoi, T. Akutsu, T. Setomaru, K. Abe, A. Kikuchi, M. Umezu, T. Okano, Circ. Res., 90, e40- e48, (2002). Other references :