1. Microcantilever-based Biodetection Alan, Ben, Sylvester

2. Principle of Microcantilevers The key elements in the detection of a mass are the vibrational frequency and the deflection of the cantilever* Deflection*  Proportional to mass content Resonance frequency*  ω R =(k/m) 1/2 K = spring constant M= mass * Sandeep Kumar Vashist (2007) Review of Microcantilevers for Sensing Applications Journal of Nanotechnology 3: 1-15.

3. Readout Method There are several methods available to observe the deflection and resonance frequency of the microcantilever* Optical* Piezoelectric* Piezoresistive* * Sandeep Kumar Vashist (2007) Review of Microcantilevers for Sensing Applications Journal of Nanotechnology 3: 1-15.

4. Optical Optical method requires the use of a low power laser beam* If microcantilever does not deflect, then no biomolecules have been absorbed* Laser beam hits a specific position on the position sensitive detector (PSD)* Major weakness-high cost* * Karolyn M. Hansen, Hai-Feng Ji, Guanghua Wu, Ram Datar, Richard Cote, Arunava Majumdar, and Thomas Thundat (2001) Cantilever-Based Optical Deflection Assay for Discrimination of DNA Single-Nucleotide Mismatches. Analytical Chemistry 73 (7): 1567-1571

5. Piezoresistive These sensors measure the strain induced resistance change* When the biomolecules are absorbed by the material there is a volumetric change in the sensing material* Volumetric change is measured by resistance change in cantilever* Advantages-Low cost* * Viral detection using an embedded piezoresistive microcantilever sensor. Sensors and Actuators A: Physical 107 (3), 219- 224

6. Piezoelectric These sensors detect the change in the resonance frequency of microcantilever only* Use microactuator to drive the plate into resonance* Microsensor to the determine the frequency of the plate* * S. Zurn, M. Hsieh, G. Smith, D. Markus, M. Zang, G. Hughes,Y. Nam, M. Arik and D. Polla (2001) Fabrication and structural characterization of a resonant frequency PZT microcantilever. Institute of Physics Publishing 10: 252-263

7. Applications Microcantilevers may be used to detect the presence against viruses, or even cancerous cells** Mass detection of Vaccina virus particle* Cancer monitoring** * Amit K. Gupta, Pradeep R. Nair, Demir Akin, Michael R. Ladisch, Steve Broyles, Muhammad A. Alam, and Rashid Bashir (2006) Anomalous resonance in a nanomechanical biosensor. PNAS 103 (36): 13362- 13367 ** Mauro Ferrari (2005) Cancer Nanotechnology: Opportunities and Challenges. Nature Publishing Group 5, 161-171 Figure 1* Figure 2**

8. Simulation (Mode Analysis) f 0 =194,532Hz f 1 =194,483Hz S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

9. Design and optimization Tailoring geometry to improve resonance frequency and shift frequency K m Increase the spring constant Reduce the effective mass at the fee end S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415 ∆f /∆ m=π k 1/2 m -3/2 f=2π k 1/2 m -1/2

10. Design and optimization ∆f=41Hz ∆f=49Hz ∆f=69Hz ∆f=36Hz ∆f=31Hz Conclusion: Increase the clamping width; Reduce the width in free end S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

11. Design and optimization ∆f = 506Hz Another advantage is the relatively uniform stress distributions We can put more piezoresistors on Disadvantage: Not enough room at the tip for capturing bioparticles! S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

12. Design and optimization Final Structure Trapezoid-like cantilever ∆f=150Hz Further improve the frequency shift, how? Higher frequency mode! S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

13. Higher frequency mode Element Model Solid187 6163 Elements overall Material propertiesYoung’s modulusDensityPoisson Ratio Value100 GPa2850 kg/m 3 0.24 S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

14. Higher frequency mode Mode 1 Mode 2 ∆f=150Hz∆f=300Hz

15. Higher frequency mode Mode 3 Mode 4 ∆f=300 Hz∆f=100 Hz

16. Higher frequency mode Mode 5 ∆f=200 Hz Conclusion: Mode 2 has double shift frequency, and its amplitude is big enough for piezoresistors to sense.

17. Sensitivity Analysis The mass of the applied particle is 0.285 pg; while the frequency shift is 300Hz (using cantilever shape G and operating at the second mode) The sensitivity: S = 300Hz/0.285pg=1.05×10 18 s -1 kg -1

18. Fabrication: Phase One o The unaltered SOI wafer o Ion implantation to form piezoresistive element (Boron, dose ~10 14 /cm 2 ) o Deposition of photoresist on upper silicon layer (~1µm) Phase one of the fabrication process Photoresist

19. Fabrication: Phase Two o Photolithography to define tip and electrode o Wet etching to eliminate unexposed photoresist o Further etching to remove exposed photoresist Phase two

20. Fabrication: Phase Three o E-beam deposition of titanium (~5 nm) o E-beam deposition of Au (~150 nm) o Wet etching of remaining photoresist Phase three

21. Fabrication: Phase Four o DRIE to define cantilever o Bulk DRIE to eliminate Si substrate o Wet etching for removal of SiO 2 to free cantilever Phase four

22. Fabrication: Phase Five o Biosensitive film selectively binds to gold, allowing cantilever dipping Cell selectively binding to biosensitive layer* *Images can be found in: Lan, S., Veiseh, M. and Zhang, M. Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity. Biosensors and Bioelectronics, 2005, 20(9), 1697-1708 Cells cultivated on gold with silicon substrate after biosensitive treatment*

23. Fabrication: Phase Six o Piezoelectric actuator stamped on base of cantilever The final product: a MEMS biosensor

24. Summary Portable device with convenient readout and external actuation. Optimized geometry and frequency sensitivity Easy fabrication using SOI wafer

25. Questions?