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International Institute for Nanotechnology Northwestern University Nanotechnology Institute for Nanotechnology Northwestern University 2190 Campus Drive Evanston, IL 60208 Chad A. Mirkin SEM image of a molecule-based structure made by DPN at 60 nm resolution

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Page 1: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Nanotechnology

Institute for NanotechnologyNorthwestern University

2190 Campus DriveEvanston, IL 60208

Chad A. Mirkin

SEM image of a molecule-based structure made by DPN at 60 nm resolution

Page 2: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

“Soon researchers will bring us devices that can translate foreign languages as fast as you can talk; materials 10 times stronger than steel at a fraction of the weight; and -- this is unbelievable to me -- molecular computers the size of a tear drop with the power of today's fastest supercomputers.”

President William J. ClintonState of the Union Address

January 27, 2000

The Initiation of the Nanotech Revolution

Page 3: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Lurie Medical Research CenterNUANCE Center

NAMSA Center

Evanston Campus

International Institute for Nanotechnology (IIN)

Chicago CampusOther Collaborators Argonne National Laboratory

Steering Committee

International Research1.US-Ireland 2.US-South Africa

URETIs1. Nanoelectronics and Computing 2. Bioinspired Design & Processin

of Multifunctional Nanoscomposites

NSF AFOSR DOD NASA HSARPA NIH

HSARPA - Encoded Nanostructures for the Analysis of Bioterrorism Threats

MURIs1. Multi-Dimensional Surface

Enhanced Sensing & Spectroscopy

2. Surface Templated Bio-Inspired Synthesis and Fabrication of Functional Materials

3. 3-D Architectures for Future Electrochemical Power Sources

IBNAM1. 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)

Other NIH Awards1. Detection of HIV Targets by Gold

Nanoparticle Probes2. Detection of Category A Pathogens by Gold

Nanoparticles3. Application of TiO2-DNA Nanocomposites

to Cancer Cells (Nat’l Cancer Institute)

DURINTs1. Ultrasensitive & Selective

Chip-Based Detection 2. Nano/Molecular Electronics

NSEC - Integrated Nanopatterning & Detection Technologies

NIRTs1. Evolution and Self-Assembly of Quantum

Dots 2. Interphase Design for Extraordinary

Nano Composites 3. Atomic Layer Controlled Epitaxial

Ferromagnetic Oxide Nanostructures 4. Electrical & Mechanical properties of

Boron and Metal-Boride Nanowires5. Role of Nanoscale Colloids in Particle

Aggregation and Trace Metal Scavenging in Aquatic Systems

6. Synthesis, Characterization & Modeling of Aligned Nanotube Arrays for Nanoscale Devices

7. Novel Nanostructured Carbons from Self-Assembled Block Copolymer Precursors

8. Ultra Nanocrystalline Diamond Films for Multifunctional MEMS/NEMS

9. Design of Nanoporous Molecular Square Catalysts Using Multiscale Modeling

Center for Nanoscale Materials

Pioneer AwardNanostructured Interfaces for Studying Problems in Cellular Biology

CCNE - Nanomaterials for CancerDiagnostics & Therapeutics

NCLT - Developing NSE EducatorsNetwork for Computational Nanotechnology

Page 4: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

IIN unites over ~$250M in nanotechnology research and

education programs and ~$100M for infrastructure under one umbrella

A United Effort

Page 5: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Nanotechnology: What is it?

2. Determining the chemical and physical consequences of miniaturization.

3. Exploiting the ability to miniaturize and its consequences in the development of new technology.

1. Developing tools for making, characterizing, and manipulating materials on the nanometer (nm) length scale.

Page 6: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

200 nm

Au Spheres~100 nm

Ag Nanoprisms~100 nm

Ag Spheres~80 nm

Ag Spheres~40 nm

Au Spheres~50 nm

Ag Spheres~100 nm

200nm (the same for all the images)

Rayleigh Light Scattering of Nanoparticles: Size, Shape, and Composition Matters

Page 7: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Economic Impact Areas

Orden et. al., Nanoletters, August, 2, 2001

“Nanoparticles in Protein Assays”• Diagnostics

• Materials Design0

4 mμ

8

“Nano-features on Silicon”

Mirkin, et. al., Adv. Mater., 12, 1600, 2000

• Electronics/Computers

“Chip-on-a-Stamp”

Manz, et. al., Imperial College, London

• Therapeutics

“Nanotube Assemblies as Antibiotics”

Ghadiri et. al., Nature, 412, 452, 2001• Energy Generation, Conversion, and Storage

Metal Organic Frameworks

Page 8: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Example Business Ventures from IIN Research 12 new companies launched in the past 5 years)

NanoInk, Inc.Student business plan awarded 1st place in 2001 Kellogg Digital Frontier ConferenceCommercializes DPNSecured >$50 Million

Nanosphere, Inc.Develops commercial diagnostic systemsSecured >$108 Million

Ohmx, Inc.Launched Aug 2003Produces point-of-care electronic pathogen detection devicesSecured $3.2 Million

Acumen Pharmaceuticals Inc.Developing the first effective therapeutics and diagnostics for Alzheimer's disease and other memory-related disordersJan. 2004 joined in collaboration with Merck & Co., Inc.Eligible for $48 Million in research funding

Page 9: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Basic Science Research Transitions into New Technologies and Businesses

Nanoparticles in Diagnostics

Tools For Making and Studying Nanostructures

Nanoparticles in Therapeutics: Gene Therapy

Page 10: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

DNA Detection with Nanoprobes

DNA Litmus Test

Collaborator: Bob Letsinger

Page 11: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Advantages of the Nanoparticle-based Bio-Bar-Code Assay

1. Up to one million times more sensitive than conventional ELISAs.

2. Evaluate new biomarkers for diagnosing and following human diseases (e.g. HIV, Cancer, and Alzheimer’s Disease).

3. Single-cell protein expression experiments.

Page 12: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Multiplexed DNA Detection with theBio-Barcode Assay (Bioterrorism Panel)

Page 13: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Field Defining Technologies

Page 14: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Basic Research Fuels the Development of New Technology

Basic Research: How does one use DNA as a a construct in Materials Synthesis?New Material and Property Identification: Distance-dependent plasmon properties, Sharp Cooperative Melting Transitions for DNA Modified Particles, Catalytic PropertiesThe Barcode Assay is Developed as well as a New Paradigm in Molecular DiagnosticsThe Verigene ID System is Launched by Nanosphere(spring 2007)

Page 15: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

15 nm

Example 2: Dip Pen Nanolithography

1.3 Million Probe 2-D Passive Array

2-D Active Probe Arrays Parallel Fabrication with1-D Passive Probe Array

Moving from serial to parallel…

• High-resolution:~10 nm linewidth resolution,~ 5 nm spatial resolution

• Chemically general (both ink and substrate)

• Direct-write = Biocompatible• Software Automated• Parallel

Page 16: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Sol Gel Materials(>100 different oxidescan be patterned)

4μm

290 nm

Dip-Pen NanolithograpyHard Materials

Single Nanoparticle LinesSilicon Nanostructures

12 nm

Nanogap Electrodes

1 μm

500 nm

~45 nm

1 µm

90 nm

85 nm

100 nm135 nm

185 nm

Silver NanostructuresGold Nanostructures

Page 17: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Virus Nanoarrays

Ultrahigh Density DNA Arrays

Combinatorial DPN Templates

Bio-nanoelectricsProtein Nanoarrays

Small Organic MoleculesOrthogonal Assembly of Nanoparticles

100 nm

4μm

Protein Nanostructures

Conducting Polymers

Soft Materials

550 nm550 nm

4 µm

Page 18: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

The NSCRIPTORTM

An Integrated DPN System

Page 19: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

DPN “Pen Systems” Consumables: A 1.3 Million Pen Passive Array

Page 20: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

100 µm

Page 21: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Mask Fabrication,inspection, and repair

Ultra-small-sensitive, and

-selective sensors

Cryptography

Ultrahigh densityGene chips and proteomic arrays

Nanoprintedcatalysts

Crystallization(colloidal crystals,

biostructures)

Molecular electronics(organic, bio-organic

circuits)

A tool for studying the consequences of

miniaturization

Flat panel display repair

DPN Applications

Page 22: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

World Use of Dip Pen Nanolithography

Scripps - Ghadiri

Tufts-KaplanMIT-Stellacci

Lawrence Livermore - DeYoreoTexas Tech - Vaughn, Weeks

Utah - Holz

Washington - Ginger

Purdue-Ivanesivic

Cal Tech - Collier

Duke-Liu, Chilkoti

Cal State - Schwartz

UC Davis - Liu

USARF-Stone, Naik

Texas A&M - Banerjee

Alberta - Buriak

UNC - Zauscher

Northwestern - Mirkin, Vinayak, Espinosa, Wolinsky

Illinois - Liu

USA

Canada

Albany NanoTech - Kossow

NASA - Watkins

RPI - Nalamasu

Sandia - Hsu

Maryland - Gomez

PSU - Weiss

Brookhaven - Ocko

Australia- Nicolau

England- RaymentNetherlands-Reinhoudt

Spain- Garcia, Martinez

India – RaoHarvard - Lieber

Hebrew University- Willner

China (CIST)- HuaChina (Lanzhou)- Li

Singapore- Wee

Seoul Nat. University-Hong

Italy- Levi

France - Joachim

Hong Kong – Xu

Germany - Fuchs

Germany, Lenhert

India - BrarJapan - Ichimiya, Tamura

Taiwan-Sheu, Lin

Brazil

FranceEngland Switzerland

Germany, Austria

Australia

ChinaJapan

S. KoreaTaiwan

India

Singapore

DPN use has more than doubled every year of its existence…

Netherlands

Spain, ItalyIsrael

U. Chicago - Mrksich

Page 23: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Basic Research Fuels the Development of New Technology

Basic Research: The study of the capillary effect lead to the observation that water transport is dynamicDiscover materials other than water can be transported and water can be used to facilitate ink transferDPN is invented as well as the challenge to parallelize molecule-based scanning probe lithographies. The NSCRIPTOR is launched by NanoInk (2002) and sold world-wide.The observation is made that DPN feature resolution is independent of contact force, paving the way for simple and rapid parallelization ---55,000 pen array (2006)

Page 24: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Goals Introduce new genes Inhibit expression of “native”genes (cancers)

Delivery Mechanisms are crudeRecombinant virus mediated Intravenous DNA delivery

Gene Therapy for Human Genetic Diseases? -Friedmann T, Roblin R., Science 1972

Ashanti de Silva, 1990Jesse Gelsinger 1999

“Bubble Boy” 2004

Example 3: Can Nanotechnology be Used for Overcoming Barriers for Gene Therapy?

Page 25: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

DNA functionalizedAu nanoparticles

Shutdown of Protein Production

Traditional Route

“Antisense Nanoparticles” Can Be Used In Cells

Page 26: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Nanoparticles Can Enter Tissues

With H. and V. Band, Evanston Hospital

Page 27: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Killing Cancer Cells

Lung Cancer Cells with nanoparticles

Treated with “Survivin” antisense nanoparticles

Page 28: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University

Basic Research Fuels the Development of New Technology

Basic Research: How do particles enter cells? New Material and Property Identification: Cooperative Melting Transitions for DNA-modified particles suggests that they will be better m-RNA scavenging agents. Demonstrated “Antisense” gene-knockdown capabilitiesLow toxicity, nuclease degradation, more effective transfection.Cancer model demonstrationClinical studies -- many major gene therapy player wantaccess to the technology.

Page 29: Nanotechnologyenhancinginnovation.wustl.edu/Mirkin.pdfElectrochemical Power Sources IBNAM 1. Spectral Markers for Early Detection of Colon Neoplasia (NIH) 2. Regenerative Scaffold

International Institute for NanotechnologyNorthwestern University