細胞晶片研究發展的國際 合作經驗

1. 細胞晶片研究發展的國際合作經驗 Prof. Ching-Hsing Luo (羅錦興) Department of Electrical Engineering National Cheng Kung University Tainan, Taiwan

2. From Tissue To Single Cells • Tissue is a group of cells, cannot see single one easily. • Basic researches of DNA and virus move on the investigation of single cells. • Nanotechnologies can see inside the single cells and operate DNA easily. • Computing power enables the simulation easily in comparison to experiments.

3. International CollaborationNecessary Conditions • Have the niche, replaceable not easily. • Have a teamwork in Taiwan to collaborate with. • Find the mutual needs in the project. • Not just learn their techniques. • Open the mind if you can.

4. My Niche: Single Heart Cell ModelLuo-Rudy model in 1991 &1994 Circ. Res. 3 papers with SCI cited 333, 410, 186 in total and 184, 280, 88 in recent five years

5. Action Potential by Model Simulation • A standard procedure of model simulation has been developed to • evaluate the accuracy of simulation results • 2. A physiological simulation fake is discussed.

6. Drug screening Platform- 1st projectInvited by Prof. Miqin Zhang, UW by Miqin Zhang High performance of integrated cell-based sensors for drug screening with impedance measurement only.

7. Mission • Medical Researches Stem cell, Neuron cell, Cancer cell for Drug screening, Differentiation or cultivation control, Gene therapy • Engineering Technologies Chip – micro/nano (channel and pumping) Sensor and actuator – micro/nano scale Cell Modeling – Ischemia, drug effects

8. Team Up Domestic: • Cell-based microchip platform –李清庭、羅錦興、魏憲鴻、 鍾宜璋 • Cell Model -羅錦興、吳勝男、鄧君豪 • Bio-application – 宋瑞珍副校長、林茂村院長、吳勝男 International: Univ. of Washington • Miqin Zhang: drug screening • Meldrum: HIV, AIDS applications

9. Commercial Microarray chip

10. Microfluid Flow Single Cell Microelectrode Micromixer Microchannel Microelectrode Microvalve Micropump Microvalve Flow sensor 1. Automatic Protocol control (concentration clamp) 2. Voltage clamp for ionic channel measurement Micropump Single Cell Chip Platform

11. Passive Mixing in Microfluidic Channelby Prof. Wei q Channel Width Setup Width 300 mm Open angle q=60

12. Mixing Results-1

13. α q R Mixing Results-2

14. Silicon oxide Differentiation or cultivation protocols Electrode Sucking pressure Silicon Glass Cell Clamping Microchip Platform

15. Cell Electrode Channel Cell Attachment and Rejection Cell Rejection Compound

16. PDMS Cell-Attachment Technique by Nano-Imprinting.by Prof. Chung and Prof. Luo • Using flat PDMS imprint SH-(CH2)11COOH on Au cell favoring coating Imprinting： Time≒ 60sec Chemical bond: SH-(CH2)11COOH Au

17. Attachment Structure flowing Platform (a)Before adhering cell 1.6 μm silicon cell (b) After adhering platform Au on silicon base

18. Electrode Shape Effect • Cell name : human CD34+ Progenitor Cell provided by Prof. Lin, Chi-Mei Medical center. • Cell is stretched to platform corner • μmdiameter • circle platform 18x18 μm2 square platform 18x36 μm2 ellipse platform

19. Budget Consideration • Usually not a big funding, just initiate the collaboration with let-go rule. • 應用於藥物篩選的細胞微晶片平台和細胞模型 NSC 94-2614-B-006 -037, $1,200,000 per year for six professors. • Work together and come up something for future budget application in both sides. • International collaboration experiences are important to open your territories and mind.

20. Nano-tag studies on LDL atherogenic effects on VEC- 2nd project • Applying Nano National-type Project, passed the first phase with good order. • Initiated by Prof. Chen, Baylor College of Medicine, Huston, USA. • Team up by Prof. Tzeng, Director of Nano center, NCKU. • Hosted by Prof. Chen, Vice-Dean of NTU hospital.

21. Aim-1: Determine the receptors for L5 on EC membrane • L5 or LDL5 is invented by Prof. Chen’s team at Baylor College of Medicine. • Prof. Chen’s team provides L5 to NTU and NCKU team for single-cell and clinical studies. PAFR and LOX-1 may be activated by L5 signals sequentially

22. Aim-2: Temporal tracing of L5 localization in EC • Nano-tag on L5 by Prof. Yeh, NCKU • High-resolution Optical Microscope by Prof. Tzeng, NCKU Nano center. Left panel: aggregates of L5-nano tagged Right panel: a single L5 molecules-nano tagged

23. L5 ? ? ? ? KATP NSC SOC TRPC BKCa NCX LoX-1 SKCa KCa ? PAFR ? IRK ER [Ca2+]i ? VRAC IKCa+ BCl SERCA Mitochondria Cl- CaCC GPCR SERCA RACC CFTR CNG SERCA Na+ Ω M Caveolar (GPCR, VAMP-2) Ca2+ mechanical sensor Na+/Ca2+ Aim-3: Determine calcium-signaling effects during L5 apoptotic process • Build up VEC model to find the ionic activities during L5 apoptotic process. • Create a transparent single-cell platform for L5-tagged VEC studies. An EC model with ion channels and organelles.

24. 60 GHz 無線生醫感測網路晶片系統-3rd project • International Collaboration by CRC (Canada), CIC, NTU, NTHU, NCTU, NCKU. • 60 GHz GaAs experiences from CRC (Canada) exchanged with 60 GHz CMOS experiences from universities and CIC in Taiwan. • Invited talk at IEEE conference about this project. • Leaded by 呂學士教授, EE, NTU, honored by solicited invitation talk in 2006 ISSCC.

25. 60 GHz Antenna Design and Temperature RFIC • 60 GHz antenna design in LTCC and CMOS • Near-body communication RFIC design • In-body communication RFIC design. • Physiological Signal RFIC design for portable devices.

26. Good luck to All of You! andThanks for Your Attention