Document 6493361

Outline
How to Detect a Single Virus
A. J. Flewitt 1, L. Garcia‐Gancedo 1, W. I. Milne 1,
G. M. Ashley 2, J. K. Luo 2, X. Zhao 3, J. R. Lu 3
1 Electrical Engineering Division, Cambridge University
2 Centre for Material Research and Innovation, University of Bolton
3 Department of Physics, University of Manchester
Motivation: lab‐on‐a‐chip
•
•
•
•
Motivation
Existing Biosensors
Film Bulk Acoustic Resonator (FBAR) Devices
Improving FBARs
• Piezoelectric Materials: HiTUS Supttered ZnO
• Electrode Materials: Carbon Nanotubes
• Overall Performance
• Conclusions
Biosensor Requirements and Classes
Requirements for high quality biosensors:
• Early disease diagnosis
• Point‐of‐care testing
• Parallel testing
Lab‐on‐a‐chip
•
•
•
•
Cheaper
Faster
Greater sensitivity
New clinical
measurements
1) Very sensitive with a low mass detection limit
2) Easy to use
3) Low cost
4) Robust
5) Disposable
Biosensor classes:
1) Optical based detectors
2) Electrochemical detectors
3) Cantilever based detectors 4) Acoustic wave based detectors
Existing Acoustic Biosensors: QCM
SAW Biosensors: Detection of PSA
A Quartz Crystal Microbalance (QCM) measures a mass per unit area by measuring the change in frequency of a quartz crystal resonator. The resonance is disturbed by the addition or removal of a small mass
QCM have a mass detection limit of a few nanograms, limited by low operation frequency (5 to 20 MHz) due to substrate thickness
Reflection signals
Detection of PSA concentration by
Frequency changes
 D. S. Lee et al., IEDM Conf. Proc. (2007)
1
Standard FBAR structure
Additional various
types of sensing layers
ZnO thin films
(BE contact hole)
• Zinc oxide (ZnO) has received significant attention due to its high piezoelectric coefficient kT and its strong adherence to various substrates • For application in acoustic wave devices, ZnO films must have the following properties:
Top electrode
Bottom
electrode
Piezoelectric
film
Oxide layer
(DRIE stop)
Si
 Ordered crystalline structure – good piezoelectric properties
Trench DRIE
 Smooth surface – surface roughness decreases Q
Oxide layer
 High deposition rate – films thicker than 2 µm are needed
• Finite Element Simulation is a key tool for optimising devices
 Low stress – possibility of using plastic substrates
• Fast prediction of the frequency response of FBAR devices
• Multiple electrode configurations can be tested within a few days (compared to months of equivalent lab work)
• Significant decrease of fabrication costs (due to less lab work needed)
 High resistivity as mobile charges reduce piezoelectric transduction
 Cost effective, repeatable results
Sputtering
HiTUS Sputtering System
 Very easy growth technique
 Easy to optimise
 Established technology
 Low cost
 Ion energy is dependent on rf power
 Samples are also exposed to the ion bombardment plasma
5
8
7
8
7
 High target utilisation
 High deposition rate
8
6
1
2
3
4
5
6
7
8
9
10
Sputter target
3
Shroud
Shutter
Sample stage
13.56 MHz rf power supply
Matching network
Mass flow controllers
Valves
Turbo pump
8
10
Ordered crystallographic orientation
2
3
4
5
6
7
8
9
10
Shutter
3
0
70
80
This is over 1 order of magnitude smaller than magnetron sputtered films
Resistivity
55
Deposition rate
6
10
45
-1
Deposition Rate (nm  min )
Smooth surface
Resistivity (  m)
ZnO
(004)
ZnO
(202)
8
10
ZnO film stress (GPa)
75
Surface roughness RMS <10 nm for 3 µm films
50
60
2 (deg.)
14
14
65
2
40
8
9
High resistivity and deposition rate
Si
(004)
10
10
30
2
1
12
13
15
10
4
3
11
10
10
8
15
3
Sputter target
Earth shield
Gas ring
11
Rotating sample stage
13.56 MHz rf power supply
Matching network
Mass flow controllers
Valves
Turbo pump
10
 Flewitt, A.J., et al., Semicond. Sci. Technol., 24, 085002.1 (2009)
10
Intensity (a.u.)
13
1
 Reduced sample ion bombardment
8
360 nm
800 nm
1390 nm
2200 nm
2800 nm
7
8
High resistivity films (>109 m) are achieved while keeping high deposition rates (>50 nm min‐1) FWHM rocking curve <4° (very small angular dispersion of the crystallites around the c‐axis)
ZnO
(0002)
8
ZnO characterisation
c‐axis normal to the substrate
6
7
4
12
9
8
6
5
 Sample removed from sputtering plasma
4
ZnO characterisation
10
O2 Gas
99.999%
 Independent control of plasma density and sputtering ion energy
 Excellent control of material properties including stress
2
1
Ar Gas
99.999%
2
1
Magnetron sputtering
- as deposited
Remote plasma
sputtering
0
-1
-2
0
Magnetron sputtering after annealing
1000
3000
ZnO film thickness (nm)
Very low stress is achieved
4
10
1.96
1.83
1.72
1.62
Ar : O2 flow ratio
1.53
35
1.45
 García‐Gancedo, L., et al., Int. J. Nanomanufacturing,
7, 371 (2011)
Extrinsic stress is considered negligible Hence stress observed is intrinsic
Very low stress – low defect density –
excellent film performance
2
FBARs characterisation
ZnO characterisation
•
We have implemented the resonant spectrum method and determined the piezoelectric properties of a ZnO thin film sandwiched between two electrodes
0
-5
S 2 1 (d B )
-10
-15
-20
FEA of the FBARs’ deformation at resonance
-25
Three parameters can be deduced based on data from the parallel and series resonant frequency spectra: density ρ, longitudinal acoustic velocity VL and the thickness mode electromechanical coefficient, kT.
Dep.
Method

V
(kg/m3)
(m/s)
(%)
ALD
5625
6336
8.15
Mag. Sputt.
5610
6100
7.95
HiTUS
5673
6184
8.35
k t2
-30
0.8
1
1.2
1.4 1.6 1.8
Frequency (GHz)
2
2.2
2.4
Quality factors higher than 1500 were achieved
Tracking the resonant frequency in real‐time
Measurements set‐up
IFBW 1000
IFBW 3000
Ball-bond
Measured Data − Polynomia
l Fit ─
Signal
Ground
case
“O” ring seal
earth top 50 Ω signal
line.
side
IFBW 300
2
3
1
fitted (polyn
omial) f0
measu
red f0
SMA
connector
FBAR
PCB board
Bovine Serum Albumin (BSA) Mass Loading
Frequency Shift (kHz)
250
holding
screws
Comparison sensitivities QCM/FBAR
Comparison of responses from identical immuno‐
accumulations
on 10MHz QCM and 1.7GHz FBAR
FBAR resonating at 1.5 GHz
wire
bond
1
Quartz plate
200
150
 Frequency changes were
some three orders of
magnitude greater than that of
a QCM for a given BSA load
100
50
0
100
200
300
400
BSA concentraton (mg/ml)

500
600
FBAR has significantly better
mass loading sensitivity!
f
f
 0   f 02
m M
2
FBAR
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Electrode Materials
Fabricating CNT Electrodes
• The electrode material also plays an important role in the FBARs response
• Aluminium (Al), tungsten (W), gold (Au) and platinum (Pt) are the most common metals utilised as electrode materials
• Carbon nanotubes (CNTs) possess low densities in the range of
1‐2 g cm‐3, electrical conductivities of up to 106 S m‐1 and exceptionally high elastic moduli (hence high acoustic impedance), usually higher than 1 TPa
• Thus, thin films of interconnecting CNTs are potentially an excellent choice for the FBARs electrodes material
1)
Iron (Fe) catalyst deposition using sputtering
2)
Growth of Carbon Nanotubes using chemical vapour deposition (CVD)
Catalyst
Heat
Heat
+ Gases
Substrate
Sputtering used to
deposit catalyst
Break up of catalyst
into nanoislands
Carbon Nanotubes
growth using CVD
Gases:
1) Ammonia (NH3)
2) Acetylene (C2H2)
3) Nitrogen (N2)
Device Performance: Higher Frequency and Lower Loss
Resonators with CNTs top electrode
j
0.8j
0.8j
0
-5
0.5j
S11 (dB)
-10
(b)
-15
0j -1
-20
Metal electrodes
CNTs top electrode
-25
-30
-35
1.7
1.72
-0.5
1 0j
0
-0.5j
1.74 1.76 1.78
Frequency (GHz)
1.8
-0.8j
-0.8j
-j
Travelling waves at the surface of the FBAR membrane and produce energy
losses and therefore a decrease on the Q factor.
(a)
(c)
Finite Element Analysis of the Vibration Modes
The travelling waves are greatly attenuated (although not completely
eliminated) by the CNT electrodes
CNT‐FBAR Biosensing
Front-view of FBAR at resonance
3D-view of FBAR at
resonance
Frequency shift (MHz)
4
CNT
electrodes
3
2
Metal
electrodes
1
0
0
200
400
600
800 1000
BSA concentration (g/ml)
1200
 Garcia‐Gancedo, L., et al. in 2010 International Ultrasonics Symposium 301 (2010)
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Conclusions
Sensitivity
 Sensitivity (minimum mass that we are able to detect) is ultimately limited by
the smallest frequency shift we are able to measure.
We are able to detect a mass
in the order of 10-15 – 10-16 g.
Frequency shift (MHz)
12
10
0.25 MHz cm2/ng
• Higher sensitivity
8
6
0.14 MHz cm2/ng
This is the best mass
sensitivity reported to date
4
2
0
0
• There is a demand for high sensitivity biosensors for future generations of healthcare
• Existing acoustic devices run at low frequencies (up to ~200 MHz)
• FBAR Devices can operate at several GHz
CNTs top electrode
Cr/Au top electrode
20
40
60
BSA mass moad (ngcm-2)
80
This allows us to detect the
presence of a single virus
• Novel sputtering of ZnO yields a high Q‐factor
• CNT electrodes gives enhanced sensitivity through higher frequency and lower losses
• World‐leading biosensor technology capable of detecting mass down to below 10‐15 g
• Project funding: EPSRC (EP/F063865/1) and EPSRC Pathways to Impact Cambridge Grant
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