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 NSF-MRI, SRC, NSF-NSEC, DARPA, NSF-ECS Center NUANCE Staff Development 1
International Institute for Nanotechnology (IIN)
Steering Committee
Evanston Campus Argonne National Laboratory Other Collaborators Chicago Campus
Center for Nanofabrication & Molecular Self-Assembly Robert H. Lurie Medical Research Center Center for Nanoscale Materials
Central and Surface Facilities (NUANCE, NIFTI, etc.)
NSEC - Nanoscale Science & Engineering Center Integrated Nanopatterning & Detection Technologies (PI: Mirkin)
NCLT - Nanotechnology Center for Learning and Institute for BioNanotechnology in Advanced Teaching Developing NSE Educators DURINTs - Defense University Research Initiative on Medicine (Stupp) NanoTechnology 1. Spectral Markers for Early Detection of Colon 1. Ultrasensitive & Selective Chip-Based Detection Neoplasia (NIH) Northwestern University (PI: Mirkin) 2. Regenerative Scaffold Technologies for CHS Atomic- and Nanoscale NIRTs - Nanoscale Interdiciplinary 2. Nano/Molecular Electronics (Co-PI: Ratner) & Diabetes (NIH) Research Teams 3. Advanced Technologies for Cell Replacement Characterization 1. Evolution and Self-Assembly of Quantum Dots Therapies in Diabetes (Juvenile Diabetes Experimental 2. Interphase Design for Extraordinary Nano Research Foundation) (NUANCE) Center Composites (PI: Brinson) HSARPA Encoded Nanostructures for the Analysis of 4. Incubator Program/Early Career Award (Dravid) 3. Atomic Layer Controlled Epitaxial Bioterrorism Threats (PI: Mirkin) (Baxter) Ferromagnetic Oxide Nanostructures (Co-PI: 5. Bio-Technology for Wound Repair, Soft Tissue Integrated, multi-faceted Chandrasekhar) Engineering & Biosensing (Army) nanotech tools, techniques and facilities 4. Electrical & Mechanical properties of Boron MURIs - Multi-University Research Initiatives for research, education and Metal-Boride Nanowires (Co-PIs: Ruoff, 1. Multi-Dimensional Surface Enhanced Sensing & and outreach Chang) Spectroscopy (PI: Van Duyne) Detection of HIV Targets by Gold Nanoparticle 5. The Role of Nanoscale Colloids in Particle 2. Surface Templated Bio-Inspired Synthesis and Probes (PI: Wolinsky) Nanoscale Integrated Aggregation and Trace Metal Scavenging in Fabrication of Functional Materials (PI: Mirkin) Fabrication, Testing and Aquatic Systems (Co-PI: Jean-Francois 3. 3-D Architectures for Future Electrochemical Instrumentation Gaillare) Power Sources (PI: Poeppelmeier) 6. Synthesis, Characterization & Modeling of Nanostructured Interfaces for Studying Problems in (NIFTI) Aligned Nanotube Arrays for Nanoscale Cellular Biology, NIH Pioneer Award (PI: Mirkin) Devices (Co-PI: Ruoff) Electron Probe Instrumentation Center 7. Novel Nanostructured Carbons from Self- URETIs - Univ Research, Eng & Tech Institutes (EPIC) Assembled Block Copolymer Precursors (Co- • Nanoelectronics and Computing (Co-PIs: Ratner, Detection of Category A Pathogens by Gold PI: Ruoff) Hersam, Ho,Odom,Marks,Chang) Nanoparticles (PI: Wolinsky) Keck-II Surface Science 8. Ultra Nano Crystalline Diamond Films for • Bioinspired Design & Processing of Multifunctional Facility Multifunctional MEMS/NEMS (Co-PIs: Schatz, Nanoscomposites (Co-PIs: Ruoff, Belytschko, Application of Ti-O2-DNA Nanocomposites to (Keck-II) Hersam) Brinson, Daniel, Messersmith, Schatz) 9. Design of Nanoporous Molecular Square Cancer Cells National Cancer Institute (PI: Catalysts Using Multiscale Modeling (PI:Snurr) Woloschak)
International Outreach 1. US-Ireland (Chang) NSF AFOSR DOD NASA HSARPA NIH Network for Computational Nanotechnology 2. Us-South Africa (Kung) CCNE PIs: M.Ratner, G.Schatz (headquartered at Purdue) 3. US-India (Dravid) 4. Ongoing
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 Technique Destructive? Sub-surface? N 1 O TEM Y N M E STM N N T 10 E AFM N N R SEM N/? N/? S 100 NSOM N N/?
1
M Optical I 10 Microscopy N N/? C R Acoustic O 100 Microscopy N Y N S Non-Destructive - Buried/Embedded Structures - 1000 10 - 100 nm spatial resolution
Scanning Near-Field Ultrasound Holography (SNFUH)
r e Near-Field SPM Platform: v r e e il c t u Î Excellent Lateral Resolution n d f >> f a s 2 o C n a tr Ultrasound source: Î Non-destructive and Depth-Sensitive Super resonant acoustic reference waves excitation Holography Paradigm: Î Sensitive to “Phase” Perturbations
Acoustic Surface Standing Wave
Specimen Detection of Perturbation to the Specimen Acoustic Standing Surface Transducer Wave via SPM Probe Detector
Super resonant acoustic SNFUH: Holographic interference of specimen acoustic wave object waves excitation with reference cantilever, allows for extraction “phase’ of acoustic wave – thereby revealing sub-surface nanoscale f1>> fo defects and features (NU patent, 2004, Science, Oct. 7, 2005))
3 Seeing the Invisible: AFM Topography Scanning Near-Field Ultrasound Holography (SNFUH)
Polymer
500 nm
Au 15--20nm Particles PVC 50 nm Silicon SNFUH Phase Image
Implications for Non-Invasive Sub-Surface Imaging
Î Quantitative modulus imaging of polymers/soft- structures
Î Non-invasive monitoring of molecular markers/tags – signal pathways Revealing nanoparticles Î Nanoscale non-invasive 3-D tomography ~ 0.5 microns below the surface!
Î Non-destructive 3-D metrology Science, October 7, 2005
AFM Topography
(A) (C)
SNFUH Phase
(B) (D)
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 Scanning Near-Field Ultrasound Silicon Nitride Holography (SNFUH) 500 nm 500
Typical AFM/SEM Polymer Advantages over 1µm
traditional metrology: 50 nm
• Non-invasive: based SOD on acoustic waves; no electron beams, no cross-sectioning
• Sub-surface: all materials of interest are transparent to Look Ma, acoustic waves plenty of defects • Nano-scale resolution: underneath! detection at the scale of defects - SNFUH Image nanometers Science, October 7, 2005
In-vitro Non-Invasive SNFUH Imaging in Cell Biology
AFM SNFUH
24 hr Î incubation
Malaria Parasites inside RBC AFM SNFUH
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.. System Packaging: Pattern DNA Hybridization e.g., Protein-Protein binding Integration w/CMOS and RF circuits Binding Event
Mechanical Electrical, Optical Signal Transduction Magnetic..
Î High sensitivity & specificity Î Fast response Signal Detection Î Fluid compatibility Î Low cost, reliability, reproducibility..
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
Target Molecule What is New?
Probe Molecule Gold Microcantilever Deflection Silicon Nitride Stresses MOSFET Channel Glass Microcantilever Target Binding - + Deflection, h MOSFET Drain Current Glass Changes with Microcantilever Embedded MOSFET Bending
Gate
Source Drain
+ + Probe Cantilever Reference Cantilever p Channel p
n-type silicon substrate Differential MOSFET Signal
Selectivity: Probe/receptor molecule selection NU patent: 2005 Sensitivity: Extent of bending and its detection Science, March 17, 2006
7 MOSFET-embedded microcantilever sensors
Reference
Probe-Target binding Drain Current (mA)
Drain voltage (V)
Microcantilever bending Change in channel Modulation of Change in the induced stress resistance carrier mobility drain current
NU patent: 2004 Science, March 17, 2006
MOSFET-embeddedMOSFET-embedded microcantilevers Microcantilevers
MOSFETs embedded at the high stress region of a microcantilever
Bashir et al., J Micromech Microeng, 2000
Microcantilever arrays A microcantilever pair MOSFET terminals composed of a gold-coated and a SiNx cantilever
8 Detection of Antibody-Antigen binding
80 Detection of goat anti-rabbit antibodies 60 (secondary IgG, 0.1 mg/ml) by rabbit IgG 40 (primary IgG, 0.1 mg/ml) Reference Au - Rabbit IgG 20 Au - Rabbit IgG - Goat anti-rabbit IgG SiNx - Rabbit IgG - Goat anti-rabbit IgG Goat IgG 0.8 0.6 Rabbit IgG Drain current (mA) 0.4 0.2 V =5 V DTSSP Gold G 0123456 SiNx 80 Drain voltage (V) 70 60 50 Negligible change in ID for the gold coated 40 cantilever with rabbit IgG 30 A change is ID of almost two orders of 0.4 magnitude with target binding 0.3
No change in the SiNx reference cantilever (mA) current Drain 0.2 Change in ID with time reaches a steady- 0.1 V =5 V, V =2 V state 0.0 G D 0246810 Time (min)
Detection of Streptavidin-Biotin binding
80 35 70
70 30 60 Surface stress(mN/m) 60 25 50 50 20 40 40 SiNx
Au 15 30 30 Au - Streptavidin Au - Strep - Biotin (100 fg/ml) 10 20 Drain current (mA) 20 Au - Strep - Biotin (100 pg/ml) Au - Strep - Biotin (100 ng/ml) 5 10 10 SiNx - Strep - Biotin (100 ng/ml) (nm) deflection Cantilever VG=5 V 0 0 0 0123456 10-14 10-13 10-12 10-11 10-10 10-9 10-8 10-7 10-6 Drain voltage (V) Biotin concentration (g/ml)
Streptavidin (10 μg/ml) – Biotin (100 fg/ml Increase in the surface stress with to 100 ng/ml) increasing target concentration
Negligible change in ID of the streptavidin Surface stress sensitivity is of the coated cantilever without target molecules same order as that of optical detection
ID decreases (bending increases) with increasing target concentraion
No change in the SiNx reference cantilever
9 Comparison with current major biosensors
Laboratory configured instrumentation
Surface Plasmon Resonance Enzyme-Linked Immunosorbent Assay (SPR) (ELISA)
Ag-Ab reactions detected by indicator enzyme activity High initial and operational costs Require labeling No reference to compensate for Time consuming sample preparation the background and detection procedure
Label-free High specificity and sensitivity Real-time detection & monitoring Superior dynamic range Versatility Low background - Measure binding kinetics, affinity of the interaction, analyte concentration, etc.
MOSFET-embedded microcantilever sensors
Label- and optics-free, all electronic Direct integration with application-specific microelectronics Miniaturization of the device → Portable, wider-deployment Low-cost by mass-production
Highlights of MOSFET-embedded microcantilever sensors
High sensitivity - Detection of ~5 nm deflection by analyte concentration in ppt range
Simple direct current measurement with Silicon nitride cantilever large signal-to-noise ratio
Label- and optics-free
Deflection Massively parallel signal sensing
Enable creating a portable device
Gold-coated Differential signal minimizes noise silicon nitride cantilever Mass-production at low-cost Embedded MOSFET 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
On-chip microfluidics CMOS Preamplifier and analyte sorting and Reader Embedded MOSFET On-chip Antenna c-Si or a-Si Photovoltaics Sensor
RF MEMS Reference ( Inductor and Si/SiNx Cantilevers tunable capacitors)
Flip Chip Bonding Massively parallel multiplexed array
MOSFET-embedded microcantilevers: A new electronic transduction paradigm comprising two- dimensional 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 Super resonant Î Sensitive to embedded/sub-surface Ultrasonic f2 >>f o sample structures/features vibration:
Î 3-D nanoscale tomography 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