1. A Wireless Bio-MEMS Sensor for C-Reactive Protein/ECG Detection Based on Nanomechanics Long-Sun Huang and Shey-shi Lu Y. H. Wang* and N. K. Chou* National Taiwan University *National Taiwan University Hospital

2. 2 This talk is based on the presentation at ISSCC 06 This presentation is also Taiwan’s first bio- related paper at ISSCC.

3. 3 Outline  Introduction  Design of Wireless BioMEMS Sensor  Measured Results  Conclusions

4. 4 You can check outyour beloved persons’ health conditions You can check out your beloved persons’ health conditions on Web anytime any where! To develop miniaturized wearable/implantable BMW (BioMedical Wireless) sensor for personalized health care and beyond-hospital applications. Our Vision and Goal

5. 5  Label free - Fluorescent labeling is not needed  CMOS compatibility - High integration - Potentially low cost  Safe reusability - Electrical technique vs. acid/base  Portability - Wireless communication for personal health care - Beyond hospital application to epidemic and disaster zones such as hurricane and Tsunami Design Objectives

6. 6 Outline  Introduction  Design of Wireless Bio-MEMS Sensor  Measured Results  Conclusions

7. 7 Translating Molecular Recognition into Nanomechanics Ref: J. Fritz et al., Science, 2000. Antigen (eg., CRP) 10 nm Binding sites Antibody Specific binding  X, Deflection

8. 8 Conventional Reuse Technique (removing CRP by acid) + acid

9. 9  Label free - Fluorescent labeling is not needed  CMOS compatibility (translating bio-tecn. into cash) - High integration - Potentially low cost  Safe reusability - Electrical technique vs. acid/base  Portability - Wireless communication for personal health care - Beyond hospital application to epidemic and disaster zones such as hurricane and Tsunami Design Objectives

10. 10  Acute phase protein - Normal concentration of CRP is ＜ 1  g/mL  Acute phase response - Inflammation biomarker: increase ~ 500 folds in 14-26 hr C-Reactive Protein (CRP)

11. 11 Cardiovascular Disease Related to CRP  Cardiovascular disease is the leading cause of death in USA  Elevated CRP levels is correlated to high incidence of cardiovascular disease

12. 12 Antigen: C-Reactive Protein (CRP) 12 nm Ref: M. A. M. Ramadan et al., Acta Cryst., pp. 992, 2002.

13. 13 Wireless Nanomechanics-based Sensor for CRP Detection

14. 14 Biosensor Design

15. 15 Sensor Geometry Design  Flow field - V-shaped cantilever  Spring constant -  Au-coated effect - Residual stress induced

16. 16 Microfluidic Channel Design Au Si x N y Si PDMS  Volume: 50  L

17. 17 Wireless ASK Architecture

18. 18 Die Photo of the wireless ASK

19. 19 Outline  Introduction  Design of Wireless Bio-MEMS Sensor  Measured Results  Conclusions

20. 20 Measurements by the Wireless Sensing System

21. 21 Measurements by the Wireless Sensing System (different concentrations)

22. 22 Conventional Reuse Technique (removing CRP by acid) + acid

23. 23 Proposed Reuse Technique (removing CRP by electric field) CRP removal by electric field Before CRP removal

24. 24 Measurements by the Wireless Sensing System (CRP removal by electric technique ) Before CRP removal

25. 25 Wireless Bio-MEMS Sensing System CD Player

26. 26 NTU BMW SOC Sensor BioMEMS sensorWireless ASK ckt 1 mm BMW: Bio-Medical Wireless

27. 27 ECG Experiment Setup

28. 28 ECG Waveform Recovered on PC

29. 29 ECG on PDA

30. 30 Outline  Introduction  Design of Wireless BioMEMS Sensor  Measured Results  Conclusions

31. 31 Conclusions  A wireless Bio-MEMS sensing system for label- free CRP assay is successfully demonstrated  Clinically relevant CRP concentrations are detected in a short time for cardiovascular disease diagnosis  The electrical means for CRP removal is proven to achieve safe reusability  The demonstrated CMOS compatible CRP sensor provides a potential SOC-based biosensors for biomedical diagnosis