University of California, Irvine
The Integrated Micro/Nano Summer Undergraduate Research Experience
(IM-SURE)
Single-Cell Platforms for
Microbiomechanics
Minh Guong Nguyen
Biomedical Engineering
University of California, Irvine
 Mentor:
Professor William C. Tang
 Grad Student: Yu-Hsiang (Shawn) Hsu
OUTLINE
• Background
– cytoskeleton
– purposes
• Introduction
– QCM
– our piezoelectric transducer
• My responsibilities
– design and develop experiments
– collect and analyze resulting data
• Problems and future work
CYTOSKELETON COMPONENTS
Intermediate filaments
Intermediate
filaments
protect cells and tissues from
disintegration by mechanical stress
Microtubules
essential component of
cell division
Actin filaments
responsible for
cell migration
Fig. 1: Three types of protein filaments form the cytoskeleton
Alberts, Bruce, et al. Essential Cell Biology. 2nd ed. New York & London: Garland Science, 2004
ACTIN FILAMENTS
Fig. 2: Forces generated move a cell forward
Alberts, Bruce, et al. Essential Cell Biology. 2nd ed. New York & London: Garland Science, 2004
WHY SINGLE-CELL PLATFORMS ?
PURPOSE
– mechanical changes of the
cytoskeleton
– parallel drug screening
– cancerous cells identification
and qualification
– others
COMPARISON
Traditional Method
Fig 3: Sketch of the quartz crystal
microbalance (QCM) experimental
setup
Our method
Fig. 4: A Single Cell Platforms
for Microbiomechanics
• Cannot detect 1 single cell mechanical
property
• Detect 1 single cell mechanical
property
• Not a precise result
• A precise result
Jing Li, Christiane Thielemann, Ute Reuning, and Diethelm
Johannsmann. “Monitoring of integrin-mediated adhesion of human
ovarian cancer cells to model protein surfaces by quartz crystal
resonators: evaluation in the impedance analysis mode.” BioSensors &
BioElectronics 20 (2005): 1333-1340.
Online posting. http://www.wctgroup.eng.uci.edu/
EXPERIMENTAL SETUP
The Agilent 4395A
The probe
Picture is taken by Minh Guong Nguyen, BME student, UCI
CROSS SECTION OF OUR DEVICE
cell
Au
ZnO
SiO2
Au
Si
200 µm
Cross section of our device, drawing by Yu-Hsiang (Shawn) Hsu, Ph.D candidate, Dept of BME, UCI
TOP VIEW OF OUR DEVICE
200 µm in Diameter
(our device)
15 µm thin lines
1 mm square
top electrode
Top view of our device, drawing by Yu-Hsiang (Shawn) Hsu, Ph.D candidate, Dept of BME, UCI
OUR DEVICE’S IMPEDANCES
Impedance vs. Frequency
Anti-resonance
frequency
Impedance (Ω)
Anti-resonance
frequency
Resonance
frequency
Resonance frequency
Frequency (MHz)
Fig. 6: The graphs Impedance vs. Frequency of our device
Data is collected by our experiments
THE QUALITY FACTOR
2
fa
QM 
2
2
2  f r Z r C f a  f r

•
•
•
•
•
QM:
fa:
f r:
Zr:
C:

The quality factor
The anti-resonance frequency (MHz)
The resonance frequency (MHz)
The impedance at resonance frequency (Ω)
The static capacitance (pF)
http://www.morganelectroceramics.com/tutorials/piezoguide15.html
TABLE OF VALUES OF OUR DEVICES
Device
Anti-resonance
frequency fa
(MHz)
Resonance
frequency fr
(MHz)
Impedance at
resonance
frequency Zr
(Ω)
Static
capacitance
C (pF)
6-A
5.562
5.081
1689.3
25
7-A
5.499
5.085
1063.9
25
8-A
5.531
5.094
1084.7
25
8-B
5.540
5.112
1059.6
25
9-B
5.522
5.103
1062.6
25
10-B
5.522
5.103
1057.2
25
2-C
5.558
5.103
1232.0
25
4-C
5.531
5.094
1325.1
25
5-C
5.526
5.085
1271.4
25
Data is collected by our experiments
THE QUALITY FACTORS (QM)
OF OUR DEVICES
2
fa
QM 
2
2
2  f r Z r C f a  f r


Device
Quality factors
(QM)
7-A
8.1209
8-A
7.5990
8-B
7.9203
9-B
8.0410
The average
10-B
8.0911
is 7.3585
2-C
6.4500
4-C
6.2203
5-C
6.4259
Calculation is based on our data obtained from experiments
COMPARISION OF OUR DEVICE WHEN
TREATED WITH AND WITHOUT WATER
Impedance vs. Frequency
460
Impedance (Ω)
440
Without Water
With Water
420
400
380
360
340
320
33.0
34.0
35.0
36.0
37.0
38.0
39.0
40.0
Frequency (MHz)
Fig. 8: Comparison of our device when treated with and without water
The graph is based on our data collected form experiments
DATA ANALYSIS
Device
Resonance
frequency
fr (MHz)
Antiresonance
frequency
fa (MHz)
Impedance
at
resonance
frequency Zr
(Ω)
Viscosity
(cP)
Quality
factor QM
Frequency
shift
Without
water
3.6144
3.8141
350.17
0.0185
(air)
4.933
0.26
With
water
3.6050
3.8366
333.74
0.982
4.519
The frequency shift is related to the weight of water.
The quality factor is related to the viscosity of water.
PROBLEMS AND FUTURE WORK
GOOD
Noise interferes the signal
Impedance vs. Frequency
Impedance vs. frequency
Impedance (Ω)
Impedance (Ω)
510
490
W11-0
W6-1
W6-0
WA6-REF
W10-0
470
450
430
410
390
23
24
25
26
27
Frequency (MHz)
Frequency (MHz)
Fig. 10: Graph of impedance
vs. frequency
Fig. 11: Graph of impedance
vs. frequency
ACKNOWLEDGEMENTS
• Dr. William C. Tang
• Yu-Hsiang Hsu and John Lin
• Wyman Wong
•
•
•
•
Said M. Shokair
Edward M. Olano
Sarah R. Martin
UROP Fellows
• National Science Foundation
ALL FOR YOUR SUPPORT
QUESTIONS?
Back up slide
Comparison of our device when treated with and without water
Back-up slide
Impedance vs. Frequency
Impedance of
Resistor:
ZR = R
Impedance (Ω)
Impedance of
Inductor:
ZL = j ω L
Impedance of
Capacitor:
Zc =
Frequency (MHz)
ω = 2 () (f)
The graphs of impedance vs. frequency of our devices zoom-in
Butterworth-Van-Dyke (BVD) equivalent circuit
Inductor
Capacitor
Resistor
Capacitor
Fig 6: The BVD equivalent circuit
Fig. 7: Lumped-element equivalent circuit
Joachim Wegener, Jochen Seebach, Andreas Janshoff, and Hans-Joachim Galla. « Analysis of the Composite Response of
Shear Wave Resonators to the Attachment of Mammalian Cells.» Biophysical Journal. Volume 78. June 2000: 2821-2833.