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Microcantilever-based Biodetection

Microcantilever-based Biodetection. Alan, Ben, Sylvester. 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.

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Microcantilever-based Biodetection

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  1. Microcantilever-based Biodetection Alan, Ben, Sylvester

  2. 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* ωR =(k/m)1/2 K = spring constant M= mass Principle of Microcantilevers *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** Figure 1* *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 2**

  8. Simulation (Mode Analysis) f1=194,483Hz f0=194,532Hz 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 f=2π k1/2m-1/2 ∆f /∆m=π k1/2m-3/2 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

  10. Design and optimization ∆f=49Hz ∆f=36Hz ∆f=41Hz ∆f=31Hz Conclusion: Increase the clamping width; Reduce the width in free end ∆f=69Hz 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 Another advantage is the relatively uniform stress distributions We can put more piezoresistors on ∆f = 506Hz 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 Trapezoid-like cantilever • Final Structure Further improve the frequency shift, how? Higher frequency mode! ∆f=150Hz 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 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=1.05×1018 s-1kg-1

  18. Fabrication:Phase One Photoresist • The unaltered SOI wafer • Ion implantation to form piezoresistive element (Boron, dose ~1014/cm2) • Deposition of photoresist on upper silicon layer (~1µm) Phase one of the fabrication process

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

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

  21. Fabrication:Phase Four • DRIE to define cantilever • Bulk DRIE to eliminate Si substrate • Wet etching for removal of SiO2 to free cantilever Phase four

  22. Fabrication:Phase Five Cells cultivated on gold with silicon substrate after biosensitive treatment* 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 • Biosensitive film selectively binds to gold, allowing cantilever dipping

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

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

  25. Questions?

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