Micro Cantilever Bio Detection

Microcantilever-based Biodetection Alan, Ben, Sylvester

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*

ωR =(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.

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 Nanotechnology 3: 1-15.

Journal of

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

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), 219224

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

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): 1336213367

**Mauro Ferrari (2005) Cancer Nanotechnology: Opportunities and Challenges. Nature Publishing Group 5, 161-171

Figure 2**

Simulation (Mode Analysis)

f0=194,532Hz

f1=194,483Hz

S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

Design and optimization 

Tailoring geometry to improve resonance frequency and shift frequency

K

f=2π k m 1/2

-1/2

∆f /∆ m=π k m 1/2

-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

m

Design and optimization

∆f=49Hz

∆f=36Hz

∆f=41Hz ∆f=31Hz Conclusion: Increase the clamping width;

∆f=69Hz

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

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

Design and optimization  Final

Structure

Further improve the frequency shift, how?

Trapezoid-like cantilever

∆f=150Hz

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

Higher frequency mode

Element Model Solid187

6163 Elements overall

Material properties

Young’s modulus

Density

Poisson Ratio

Value

100 GPa

2850 kg/m3

0.24

S Morshed and B.C. Prorok (2007) Tailoring beam mechanics towards enhancing detection of hazardous biological species. Experiment Mechanics 47:405-415

Higher frequency mode Mode 1

Mode 2

∆f=150Hz

∆f=300Hz

Higher frequency mode Mode 3

Mode 4

∆f=300 Hz

∆f=100 Hz

Higher frequency mode Mode 5 400

350

Frequency Shift (Hz)

300

250

200

150

100

50

1

2

3

4

O rder

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

5

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

Fabrication: Phase One o o

o

Photoresist

Phase one of the fabrication process

The unaltered SOI wafer Ion implantation to form piezoresistive element (Boron, dose ~1014/cm2) Deposition of photoresist on upper silicon layer (~1µm)

Fabrication: Phase Two o

o

o

Phase two

Photolithography to define tip and electrode Wet etching to eliminate unexposed photoresist Further etching to remove exposed photoresist

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

Fabrication: Phase Four o DRIE

to define cantilever o Bulk DRIE to eliminate Si substrate o Wet etching for removal of SiO2 to free cantilever

Phase four

Fabrication: Phase Five o Biosensitive

Cells cultivated on gold with silicon substrate after biosensitive treatment*

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

Fabrication: Phase Six o Piezoelectric

actuator stamped on base of cantilever

The final product: a MEMS biosensor

Summary  Portable

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

Questions?