Interdisciplinary Nanomechanics:
From Acoustic Holographic Imaging to
Microcantilever-based Bio-Chem Sensing
Vinayak P Dravid
Dept. of Material Science & Engineering
Director, NUANCE Center
International Institute for Nanotechnology
Northwestern University
Acknowledgments:
NUANCE
Center
1
NSF-MRI, SRC, NSF-NSEC, DARPA, NSF-ECS
NUANCE Staff Development
International Institute for Nanotechnology (IIN)
Steering Committee
Evanston Campus
Other Collaborators
Argonne National Laboratory
Chicago Campus
Center for Nanofabrication & Molecular Self-Assembly
Center for Nanoscale Materials
Robert H. Lurie Medical Research Center
Central and Surface Facilities (NUANCE, NIFTI, etc.)
NSEC - Nanoscale Science & Engineering Center
Integrated Nanopatterning & Detection Technologies
(PI: Mirkin)
NCLT - Nanotechnology Center for Learning and
Teaching Developing NSE Educators
NIRTs - Nanoscale Interdiciplinary
Research Teams
1. Evolution and Self-Assembly of Quantum Dots
2. Interphase Design for Extraordinary Nano
Composites (PI: Brinson)
3. Atomic Layer Controlled Epitaxial
Ferromagnetic Oxide Nanostructures (Co-PI:
Chandrasekhar)
4. Electrical & Mechanical properties of Boron
and Metal-Boride Nanowires (Co-PIs: Ruoff,
Chang)
5. The Role of Nanoscale Colloids in Particle
Aggregation and Trace Metal Scavenging in
Aquatic Systems (Co-PI: Jean-Francois
Gaillare)
6. Synthesis, Characterization & Modeling of
Aligned Nanotube Arrays for Nanoscale
Devices (Co-PI: Ruoff)
7. Novel Nanostructured Carbons from SelfAssembled Block Copolymer Precursors (CoPI: Ruoff)
8. Ultra Nano Crystalline Diamond Films for
Multifunctional MEMS/NEMS (Co-PIs: Schatz,
Hersam)
9. Design of Nanoporous Molecular Square
Catalysts Using Multiscale Modeling (PI:Snurr)
Network for Computational Nanotechnology
PIs: M.Ratner, G.Schatz (headquartered at Purdue)
DURINTs - Defense University Research Initiative on
NanoTechnology
1. Ultrasensitive & Selective Chip-Based Detection
(PI: Mirkin)
2. Nano/Molecular Electronics (Co-PI: Ratner)
HSARPA Encoded Nanostructures for the Analysis of
Bioterrorism Threats (PI: Mirkin)
MURIs - Multi-University Research Initiatives
1. Multi-Dimensional Surface Enhanced Sensing &
Spectroscopy (PI: Van Duyne)
2. Surface Templated Bio-Inspired Synthesis and
Fabrication of Functional Materials (PI: Mirkin)
3. 3-D Architectures for Future Electrochemical
Power Sources (PI: Poeppelmeier)
URETIs - Univ Research, Eng & Tech Institutes
• Nanoelectronics and Computing (Co-PIs: Ratner,
Hersam, Ho,Odom,Marks,Chang)
• Bioinspired Design & Processing of Multifunctional
Nanoscomposites (Co-PIs: Ruoff, Belytschko,
Brinson, Daniel, Messersmith, Schatz)
International Outreach
1. US-Ireland (Chang)
2. Us-South Africa (Kung)
3. US-India (Dravid)
4. Ongoing
Institute for BioNanotechnology in Advanced
Medicine (Stupp)
1. Spectral Markers for Early Detection of Colon
Neoplasia (NIH)
2. Regenerative Scaffold Technologies for CHS
& Diabetes (NIH)
3. Advanced Technologies for Cell Replacement
Therapies in Diabetes (Juvenile Diabetes
Research Foundation)
4. Incubator Program/Early Career Award
(Baxter)
5. Bio-Technology for Wound Repair, Soft Tissue
Engineering & Biosensing (Army)
Northwestern University
Atomic- and Nanoscale
Characterization
Experimental
(NUANCE) Center
(Dravid)
Integrated, multi-faceted
nanotech tools,
techniques and facilities
for research, education
and outreach
Detection of HIV Targets by Gold Nanoparticle
Probes (PI: Wolinsky)
Nanoscale Integrated
Fabrication, Testing and
Instrumentation
(NIFTI)
Nanostructured Interfaces for Studying Problems in
Cellular Biology, NIH Pioneer Award (PI: Mirkin)
Electron Probe
Instrumentation Center
(EPIC)
Detection of Category A Pathogens by Gold
Nanoparticles (PI: Wolinsky)
Keck-II Surface Science
Facility
(Keck-II)
Application of Ti-O2-DNA Nanocomposites to
Cancer Cells National Cancer Institute (PI:
Woloschak)
CCNE
NSF
AFOSR
DOD
NASA
HSARPA
NIH
1
International Institute for
Nanotechnology (IIN)
Collaborations in 18 Countries
Active exchange program with Ajou University
Sponsorship from Saarland, Germany government
MoU with IIT Bombay, India
Outline
• Seeing the Invisible:
– Scanning Near-Field Ultrasound Holography
(SNFUH)
ÎNanomechanical response to acoustics
• MOSFET-embedded microcantilevers:
– Translating bio-chem binding into nanomechanics
– Translating nanomechanics to electronic signal
2
0.1
N
A
N
O
M
E
T
E
R
S
Technique
Destructive? Sub-surface?
1
10
100
TEM
Y
N
STM
N
N
AFM
N
N
SEM
N/?
N/?
NSOM
N
N/?
1
M
I
C
R
O
N
S
10
Optical
Microscopy
N
N/?
100
Acoustic
Microscopy
N
Y
1000
Non-Destructive - Buried/Embedded Structures 10 - 100 nm spatial resolution
Scanning Near-Field Ultrasound Holography
(SNFUH)
Near-Field SPM Platform:
Î Excellent Lateral Resolution
f2>> fo
Ultrasound source:
Î Non-destructive and Depth-Sensitive
er
ev er
til uc
n
d
Ca ns
tra
Super resonant
acoustic reference
waves excitation
Holography Paradigm:
Î Sensitive to “Phase” Perturbations
Acoustic Surface
Standing Wave
Detection of Perturbation to the
Acoustic Standing Surface
Wave via SPM Probe Detector
SNFUH: Holographic interference of specimen acoustic wave
with reference cantilever, allows for extraction “phase’ of
acoustic wave – thereby revealing sub-surface nanoscale
defects and features (NU patent, 2004, Science, Oct. 7, 2005))
Specimen
Specimen
Transducer
Super resonant acoustic
object waves excitation
f1>> fo
3
Seeing the Invisible:
AFM Topography
Scanning Near-Field Ultrasound Holography
(SNFUH)
Polymer
500 nm
Au
Particles
15-- 20 nm
PVC
50 nm
Silicon
SNFUH Phase Image
Implications for Non-Invasive Sub-Surface
Imaging
Î Quantitative modulus imaging of polymers/softstructures
Î Non-invasive monitoring of molecular
markers/tags – signal pathways
Revealing nanoparticles
~ 0.5 microns below the surface!
Î Nanoscale non-invasive 3-D tomography
Î Non-destructive 3-D metrology
Science, October 7, 2005
AFM
Topography
(A)
(C)
(B)
(D)
SNFUH
Phase
Figure 2: (A) Typical AFM (topography) image shows featureless top polymer surface, while the phase image of
SNFUH clearly reveals the buried gold nanoparticles with high definition.
This is schematically explained in (C) and (D). In (C) no sub-surface scattering is present which does not perturb
the standing wave while (D) shows perturbation to standing beat frequency due to sub-surface scattering, which
is monitored by SPM tip.
4
Typical AFM/SEM
500 nm
Silicon Nitride
Polymer
Scanning Near-Field Ultrasound
Holography (SNFUH)
Advantages over
traditional metrology:
1µm
SOD
50 nm
• Non-invasive: based
on acoustic waves; no
electron beams, no
cross-sectioning
• Sub-surface: all
materials of interest
are transparent to
acoustic waves
Look Ma,
plenty of
defects
underneath!
• Nano-scale resolution:
detection at the scale
of defects nanometers
SNFUH Image
Science, October 7, 2005
In-vitro Non-Invasive SNFUH Imaging in Cell Biology
AFM
SNFUH
24 hr
Î
incubation
AFM
SNFUH
Malaria
Parasites
inside
RBC
4 hr
Î
incubation
5
• Seeing the Invisible:
– Scanning Near-Field Ultrasound Holography
(SNFUH)
ÎNanomechanical response to acoustics
• MOSFET-embedded microcantilevers:
– Translating bio-chem binding into nanomechanics
– Translating nanomechanics to electronic signal
Systems Approach to Sensing & Diagnostics
DNAs, Proteins,
Receptors..
Pattern
System Packaging:
DNA Hybridization
Protein-Protein binding
e.g.,
Integration w/CMOS
and RF circuits
Binding Event
Signal Transduction
Î High sensitivity & specificity
Î Fast response
Î Fluid compatibility
Î Low cost, reliability,
reproducibility..
Mechanical
Electrical, Optical
Magnetic..
Signal Detection
6
1. GIVE ME A PLACE TO STAND AND I WILL MOVE THE EARTH
2. GIVE ME A LEVER LONG ENOUGH AND I WILL MOVE THE EARTH
New All-Electronic Label-Free Transduction
via MOSFET- Embedded Microcantilevers
What is New?
Target Molecule
Probe Molecule
Gold
Silicon Nitride
Microcantilever
Glass
Microcantilever Deflection
Stresses MOSFET Channel
Target Binding
+ Deflection, h
Glass
Embedded
MOSFET
MOSFET Drain Current
Changes with Microcantilever
Bending
Gate
Source
Probe Cantilever
Reference Cantilever
p+
Drain
Channel
p+
n-type silicon substrate
Differential MOSFET Signal
Selectivity: Probe/receptor molecule selection
Sensitivity: Extent of bending and its detection
NU patent: 2005
Science, March 17, 2006
7
Drain Current (mA)
MOSFET-embedded microcantilever sensors
Reference
Probe-Target binding
Drain voltage (V)
Microcantilever bending
induced stress
Change in channel
resistance
Modulation of
carrier mobility
Change in the
drain current
NU patent: 2004
Science, March 17, 2006
MOSFET-embedded
microcantilevers
MOSFET-embedded
Microcantilevers
ƒ MOSFETs embedded at the high stress
region of a microcantilever
Bashir et al.,
J Micromech Microeng,
2000
ƒ Microcantilever arrays
ƒ A microcantilever pair
composed of a gold-coated
and a SiNx cantilever
ƒ MOSFET terminals
8
Detection of Antibody-Antigen binding
Goat IgG
Rabbit IgG
Gold
SiNx
60
40
Reference
Au - Rabbit IgG
Au - Rabbit IgG - Goat anti-rabbit IgG
SiNx - Rabbit IgG - Goat anti-rabbit IgG
20
0.8
0.6
0.4
0.2
VG=5 V
0
ƒ Negligible change in ID for the gold coated
cantilever with rabbit IgG
ƒ A change is ID of almost two orders of
magnitude with target binding
ƒ No change in the SiNx reference cantilever
ƒ Change in ID with time reaches a steadystate
Drain current (mA)
DTSSP
Drain current (mA)
80
Detection of goat anti-rabbit antibodies
(secondary IgG, 0.1 mg/ml) by rabbit IgG
(primary IgG, 0.1 mg/ml)
1
2
3
4
Drain voltage (V)
80
70
60
50
40
30
0.4
0.3
0.2
0.1
0.0
5
6
VG=5 V, VD=2 V
0
2
4
6
Time (min)
8
10
Detection of Streptavidin-Biotin binding
60
50
40
30
20
10
VG=5 V
0
0
1
SiNx
Au
Au - Streptavidin
Au - Strep - Biotin (100 fg/ml)
Au - Strep - Biotin (100 pg/ml)
Au - Strep - Biotin (100 ng/ml)
SiNx - Strep - Biotin (100 ng/ml)
2
3
4
Drain voltage (V)
5
6
ƒ Streptavidin (10 μg/ml) – Biotin (100 fg/ml
to 100 ng/ml)
ƒ Negligible change in ID of the streptavidin
coated cantilever without target molecules
ƒ ID decreases (bending increases) with
increasing target concentraion
ƒ No change in the SiNx reference cantilever
Cantilever deflection (nm)
70
35
70
30
60
25
50
20
40
15
30
10
20
5
10
Surface stress (mN/m)
Drain current (mA)
80
0
0
-14
-13
-12
-11
-10
-9
-8
-7
-6
10 10 10 10 10 10 10 10 10
Biotin concentration (g/ml)
ƒ Increase in the surface stress with
increasing target concentration
ƒ Surface stress sensitivity is of the
same order as that of optical detection
9
Comparison with current major biosensors
Laboratory configured instrumentation
Surface Plasmon Resonance
(SPR)
Enzyme-Linked Immunosorbent Assay
(ELISA)
Ag-Ab reactions detected by indicator
enzyme activity
ƒ High initial and operational costs
ƒ No reference to compensate for
the background
ƒ Require labeling
ƒ Time consuming sample preparation
and detection procedure
ƒ Label-free
ƒ Real-time detection & monitoring
ƒ Versatility
- Measure binding kinetics, affinity
of the interaction, analyte
concentration, etc.
ƒ High specificity and sensitivity
ƒ Superior dynamic range
ƒ Low background
MOSFET-embedded microcantilever sensors
ƒ Label- and optics-free, all electronic
ƒ Direct integration with application-specific microelectronics
ƒ Miniaturization of the device → Portable, wider-deployment
ƒ Low-cost by mass-production
Highlights of MOSFET-embedded microcantilever sensors
ƒ High sensitivity
- Detection of ~5 nm deflection by analyte
concentration in ppt range
Silicon nitride cantilever
ƒ Simple direct current measurement with
large signal-to-noise ratio
ƒ Label- and optics-free
Deflection
ƒ Massively parallel signal sensing
ƒ Enable creating a portable device
Gold-coated
silicon nitride cantilever
Embedded MOSFET
ƒ Differential signal minimizes noise
ƒ Mass-production at low-cost
ƒ Direct integration with application-specific
microelectronics
MOSFET-embedded microcantilevers may overcome the limitations imposed
by currently available signal transduction and detection mechanisms
10
MOSFET-Embedded Microcantilever System:
Vision for Wider Deployment for Remote-addressing
and Networking
CMOS Preamplifier
and Reader
On-chip microfluidics
and analyte sorting
Embedded MOSFET
Antenna
On-chip
c-Si or a-Si
Photovoltaics
RF MEMS
( Inductor and
tunable capacitors))
Flip Chip Bonding
Sensor
Reference
Si/SiNx Cantilevers
Massively parallel
multiplexed array
MOSFET-embedded microcantilevers: A new electronic transduction paradigm comprising twodimensional microcantilever arrays with embedded-MOSFETs. An adsorption-induced surface stress at
the functionalized cantilevers leads to precise, measurable and reproducible change in the MOSFET
drain current. It can be readily integrated with application-specific on-chip microelectronics platform.
11
Combining MOSFET-Cantilevers and SNFUH:
Summary and Vision
Î Non-destructive
Î Nanoscale resolution
Î Sensitive to embedded/sub-surface
structures/features
Î 3-D nanoscale tomography
f 2 >>f o
Super resonant
Ultrasonic
sample
vibration:
f1 >> fo
Î Fast scanning with multiple
SPM probes
Î Integrated turn-key system
with embedded software
architecture
Further (Collaborative) Opportunities
Non-invasive sub-surface imaging with SNFUH:
• 1-D and 2-D parallel multi-probe SNFUH array
• Higher frequency piezo’s
• Fundamentals of ultrasound-scattering in near-field regime:
modeling, simulation and 3-D tomography
MOSFET-embedded microcantilevers for bio-chem sensing:
• MOSFET-embedded parallel/multiplexed 1-D and 2-D array
• On-chip lock-in, read-out and RF circuit for remote-sensing
• Back-end microfluidics, sampling and integration
Applications to hard, soft (biological/polymer) and hybrid structures
12