1 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab International Collaboration Necessary 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab My Niche: Single Heart Cell Model Luo-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 - Virtuoscope & Wireless Mixed Signal Biochip Lab Action Potential by Model Simulation 1.A standard procedure of model simulation has been developed to evaluate the accuracy of simulation results 2. A physiological simulation fake is discussed.

6 - Virtuoscope & Wireless Mixed Signal Biochip Lab Drug screening Platform- 1st project Invited by Prof. Miqin Zhang, UW by Miqin Zhang High performance of integrated cell-based sensors for drug screening with impedance measurement only.

7 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab Team Up Domestic: 1.Cell-based microchip platform – 李清庭、羅 錦興、魏憲鴻、 鍾宜璋 2.Cell Model - 羅錦興、吳勝男、鄧君豪 3.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 - Virtuoscope & Wireless Mixed Signal Biochip Lab Commercial Microarray chip

10 - Virtuoscope & Wireless Mixed Signal Biochip Lab Single Cell Chip Platform Microfluid Flow Micromixer Micropump Single Cell Microchannel Microelectrode Microvalve Flow sensor 1. Automatic Protocol control (concentration clamp) 2. Voltage clamp for ionic channel measurement

11 - Virtuoscope & Wireless Mixed Signal Biochip Lab Passive Mixing in Microfluidic Channel by Prof. Wei Setup Width 300  m Open angle  =60  Channel Width

12 - Virtuoscope & Wireless Mixed Signal Biochip Lab Mixing Results-1

13 - Virtuoscope & Wireless Mixed Signal Biochip Lab Mixing Results-2 R α 

14 - Virtuoscope & Wireless Mixed Signal Biochip Lab Cell Clamping Microchip Platform Differentiation or cultivation protocols Silicon oxide Electrode Sucking pressure Glass Silicon

15 - Virtuoscope & Wireless Mixed Signal Biochip Lab Cell Attachment and Rejection Cell Electrode Channel Cell Rejection Compound

16 - Virtuoscope & Wireless Mixed Signal Biochip Lab Cell-Attachment Technique by Nano-Imprinting. by Prof. Chung and Prof. Luo Using flat PDMS imprint SH-(CH 2 ) 11 COOH on Au cell favoring coating PDMS Time ≒ 60sec SH-(CH 2 ) 11 COOH Au Imprinting ： Chemical bond:

17 - Virtuoscope & Wireless Mixed Signal Biochip Lab Attachment Structure flowing cell platform Au on silicon base (a)Before adhering (b) After adhering 1.6 μm Platform silicon

18 - Virtuoscope & Wireless Mixed Signal Biochip Lab Electrode Shape Effect 18x18 μm 2 square platform Cell name : human CD34+ Progenitor Cell provided by Prof. Lin, Chi-Mei Medical center. Cell is stretched to platform corner 18μm diameter circle platform 18x36 μm 2 ellipse platform

19 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 B , $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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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. SERC A ? TRPC NSC SOC NCX M Ca 2+ mechanical sensor LoX-1 ER Mitochondria L5 ? [Ca 2+ ] i PAFR Na + /Ca 2+ ? ??? VRAC B Cl CaCC RACC K ATP BK Ca SK Ca K Ca IRK Cl - CNG GPCR CFTR SERCA IK Ca + ? Na + Ω Caveolar (GPCR, VAMP-2) An EC model with ion channels and organelles.

24 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab 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 - Virtuoscope & Wireless Mixed Signal Biochip Lab Good luck to All of You! and Thanks for Your Attention