These techniques allow for direct-write nanofabrication with high resolution down to 10 nm. Recent developments in PPL and beam pen lithography provide highly parallel printing over large areas for applications like biological studies. Molecular printing tools are becoming more accessible and may enable desktop nanofabrication.

1. Molecular
Printing: A
Chemist’s
Approach to a
“Desktop Fab”
Chad A. Mirkin
Northwestern University
Department of Chemistry and
International Institute for
Nanotechnology

2. Modern Printing Tools Revolutionized
the World
Is It Possible to
Create A “Desk
Top Fab”?
Desk Top Printer
Information transfer, the semiconductor industry, the microelectronics
revolution, and gene chips
It is exceedingly difficult to print with molecules and many materials
on the “nanometer scale”

3. Dip Pen Nanolithography (DPN)
Attributes of DPN:
• Direct-write
• High resolution: 10 nm line width, ~5 nm spatial resolution
• Positive printing
• Writing and imaging with same tool
• Molecule general
• Substrate general
• Serial or massively parallel

4. The NSCRIPTORTM
An Integrated DPN System

5. Scanning Probe Lithography: A
Dichotomy is Emerging
Destructive Constructive
Nanografting Delivery of Delivery of DPN
Nanoshaving Energy Materials
Anodic Oxidation
“Millipede”

6. 85 nm
12 nm
135 nm
90 nm 100 nm
185 nm
Nanogap Electrodes
Gold Nanostructures
Silver Nanostructures ~45 nm Dip-Pen
Nanolithograpy
Hard Materials 290 nm
500 nm Sol Gel Materials
4mm
1 mm
Nanoparticle Arrays Single-Walled Carbon
Silicon Nanostructures Nanotubes

7. Combinatorial DPN Templates
Small Organic Molecules
Polymer resists
4mm
Ultrahigh Density DNA Arrays
Conducting Polymers Soft Materials
Virus Nanoarrays
100 nm
550 nm
550 nm
4 µm
Protein Nanostructures Protein Nanoarrays
Bio-nanoelectrics

8. The Ultimate in High Density Arrays
Conventional Microarray
Robotic Spotter
(1 Dot/200x200 mm2) Feedback Controlled Lithography
(100,000,000,000 Dot/200x200 mm2)
Low Resolution DPN
(50,000 Dot/200x200 mm2)
High Resolution DPN
(100,000,000 Dot/200x200
mm2)
Biological Nanoarrays:
• More than just miniaturization with higher density
• New opportunities for biodetection and studying biorecognition
• Templates for guiding the assembly of larger building blocks
• Open up the opportunity to study multivalency and surface cooperativity

9. Can DPN be Used To Generate Multicomponent
Templates that are Used to Recognize and Larger
Biological structures and Organisms?
120 nm ~20 µm ~15 µm
8.5 nm
Protein Virus Spores Living Cells
(Human IgG) (HIV) (Anthrax)

10. DPN-Generated Biological Nanoarrays
4 mm 5 mm
Single Virus Nanoarrays Multicomponent DNA Phospholipid Arrays
Nanoarrays
80 mm
4 mm Cell Arrays on Nanopatterned Substrates
• Sub 50 nm  many mm resolution
Multicomponent Protein • Large Array Patterning
Nanoarrays
• Multi-component Patterning Capabilities
• Reconstructing the extracellular matrix at the nm scale

11. DPN Generated Positive Photomasks
Au Etch
Au Au Etch
DPN Cr Cr Etch
ODT Quartz
Cr Photomask
Device Characterization
Replicated Au Electrode Empty electrode
0.8 PPY nanotube
PPY nanotube with UV
0.4
Current (nA)
0.0
-0.4
-0.8
-1.0 -0.5 0.0 0.5 1.0
Voltage (V)
Jang et al, Small, 2009, 5, 1850

12. DPN Spot Size Is Independent of
Applied Force
Molecular diffusion from point source is independent of applied
force between tip and surface.

13. NanoPrint Array II: 55,000 tips ~ 1 cm2
Pen fabrication yield >99% (preliminary)
20×90 µm
In collaboration
1.5 mm with J. Fragala, NanoInk

14. 40×40 dots at 400 nm pitch
~88 million features in ~20 min
5 µm
400 nm
100 mm 100 nm

15. Development of Cantilever-Free
Scanning Probe Lithography
Cantilever-Based Cantilever-Free
DPN 1D Multipen 2D 55,000 Pen Polymer Pen Scanning Probe Block Hard-Tip, Soft
(1999) Cantilever Array Cantilever Array Lithography Copolymer LithographySpring Lithography
(2000) (2006) (2008) (2010) (2011)
Key Advance 1: Key Advance 2: Key Advance 3:
Deposition of Use an elastomeric Move the “spring”
materials pyramid on a solid from the tip to a
rather than backing for cantilever- polymer backing
Thermal DPN Beam Pen
energy free printing layer
(2004) Lithography
(2010)
Giam, et al. Angew. Chem. 2011, 50, 7482.

16. PDMS Pen Array Fabrication
Huo, F et al. Science. 2008, 321, 1658.

17. 11 Million Pen Polymer Array
A B
C D
(A)11 million pen array. (B) SEM image of the polymer pen array. (C) An etched gold pattern on a
4 inch Si wafer. (D) Optical microscope image of gold patterns.
Huo, F et al. Science. 2008, 321, 1658.

18. Polymer Pen Lithography (PPL)
High Resolution
High Throughput
Mask-free Nanofabrication
Huo, F et al. Science. 2008, 321, 1658.

19. Printing Circuit Designs on Multiple Scales
100 circuits in
1 cm2 with 500
nm and 100
µm features
100 µm
500 nm
500 nm
100 μm
500 nm
Huo, F et al. Science. 2008, 321, 1658.

20. Feature Size Control
Time Dependence Z-Piezo Dependence
Feature Edge Length vs Dwell Time Feature Size vs Z-Piezo Extension
Huo, F. et al. Science. 2008, 321, 1658.
Liao. et al. Small, 2010, 6, 1082.

21. Tip-Height Sensing: Force Dependence
F1 < F2
Z
F  NELbottom Ltop
H

L feature  Ltop  F
NELtop
Force Dependent Pattern Feature Edge Length vs Force
Liao. et al. Small, 2010, 6, 1082.

22. Leveling the Pen Array by Force
Tilted PPL Array Z Height of the Tilted Pen Array
θ: tilting angle to the y axis
φ: tilting angle to the x axis Z ( N x , N y , ,  )  Z0  DN x sin( )  DN y sin( )
M1, M2 and M3: θ = 0.07°
Motors holding the pen array φ = 0.06 °
Liao. et al. Nano Lett. 2010, 10, 1335.

23. Leveling the Pen Array by Force
Calculated Ftotal vs θ and φ Experimental Ftotal vs θ and φ
F / mN
Ftotal / mN
total
θ/ ° φ/ °
ELbottom Ltop • At the perfect leveling position, the total force
F ( N x , N y , ,  )  Z ( N x , N y , ,  ) reaches its global maximum
H • For each fixed θ, the force reaches its local
maximum when φ=0 and vice verse
Ftotal ( ,  )   F (N x , N y , ,  ) • Around the perfect leveling position, the
Nx N y gradient is very large
Liao. et al. Nano Lett. 2010, 10, 1335.

24. Leveled Patterns
0o
θ = 0°
2.54 ± 0.05 mm
–0.01o
θ = –0.01°
4.68 ± 0.89 mm
+0.01o
θ = +0.01°
5.33 ± 1.03 mm
Liao. et al. Nano Lett. 2010, 10, 1335.

25. Multiplexed Protein Patterning by PPL
Inkjet print multiple Pattern multiplexed Feature size control
protein into inkwells protein arrays
inkwells
Inkwells with different Multiplexed patterning
fluorescent proteins of protein arrays
Zheng, Z et al. Angew Chem. 2009, 48, 7626 .

26. Combinatorial Libraries Generated by
Tilting PPL Array
PPL array
substrate
High contact force
Printed Area
Low contact force

27. Large area patterns
Why PPL?
• Patterns over large areas for
studying thousands to millions of
cells
• Ability to produce combinatorial
arrays with different feature sizes
(micro to nanoscale)
• Ability to level the PPL array and
produce homogeneous features
over large areas
Feature width = 1.34 μm Feature width = 475 nm
Feature pitch = 2 μm Feature pitch = 2 μm

28. MSC Differentiation Studied by PPL-
Generated Combinatorial Arrays
100 μm
CBFα1 actin DAPI

29. Massively Parallel Hybrid Silicon
Pen Nanolithography
10 μm
Z-piezo Glue
Ultra-High Resolution
High Throughput
Mask-free Nanofabrication 1 mm
Easy Alignment

30. Pen Tip Array
500 μm
Si tip
22 nm
Soft backing layer
1 um 100 μm

31. Massively Parallel Hybrid Silicon
Pen Writing
Before contact with the surface
Different light reflection
In contact with the surface

32. Feature Size Control
Time Dependence Z-Piezo Dependence
Z=12 μm
6 μm
10 μm
4 μm
5 μm
8 μm
Feature Edge Length vs Dwell Time Feature Size vs Z-Piezo Extension
1200 1200
Dot diameter (nm)
1000 1000
Diameter (nm)
800 800
600 600
400 400
200 200
0 0
0 1 2 3 4 4 6 8 10 12
1/2
Contact time (s ) Z-piezo Extension (um)

33. Feature Size Resolution
i ii
5 μm 5 μm
ii
i iv
iii 10 μm
iii 5 μm 5 μm
iv
Average Feature
Size = 42 nm

34. Block Copolymer Assisted TBN

35. Block Copolymer (BCP) Patterns
BCP Deposition (Height) BCP Deposition (Phase)
100 nm 90 °
5 µm 5 µm
100 nm AFM Height Profile
50
Height (nm)
30
10
-10
2 µm 0 2 4 6 8 10
Distance (µm)
Cai et al, submitted

36. Single Nanoparticles Formed by
Block Copolymer TBN
SEM of AuNP Array TEM and Diffraction of AuNP
• The spatial resolution is controlled by the piezo-controlled tip position
• Fourier transform analysis confirms uniformity of the AuNP pattern
• Sub-10 nm single crystal Au NPs are formed by the BCP method
• TEM and Diffraction patterns confirm single crystal composition of the
nanostructures
Cai et al, submitted

37. Nanoparticle Size Control
Cai et al, submitted

38. Large-Scale Patterning
1 µm
Au NPs on SiO2
Cai et al, submitted

39. Particle Size Consistency
Au NPs on SiO2
Cai et al, submitted

40. Growth Trajectories: Cryo-TEM Movie of
Ripening Process
2 nm

41. Formation of Single
Nanoparticles Observed
-120 degrees C, ~ 1 min frame interval
FOR OFFICIAL USE ONLY – Not Cleared for Open Release

42. Two Mechanisms are Occurring
• Coalescence observed for particles closer than ~ 5 nm
• Ostwald ripening observed for particles further apart
-120 degrees C, ~ 5 min frame interval
FOR OFFICIAL USE ONLY – Not Cleared for Open Release

43. Beam Pen Lithography (BPL)
Fabricating a Beam Pen Array
BPL array 200 nm Aperture 1 μm Aperture 2 μm Aperture
100 μm 2 μm 2 μm 20 μm
Huo et al, submitted

44. Beam Pen Lithography (BPL)
BPL Scheme Au dot arrays by BPL 10 x 10 dot array
Patterning
150 μm
Arbitrary patterns by BPL Chicago Skyline
Develop
20 μm
Evaporation +
liftoff
100 μm
Huo et al, submitted

45. Mask-Assisted BPL
Mask assisted BPL Patterns of “NU” with selected pens
• Drawbacks:
– Photo mask is needed
– Can not in-situ address the pens
Huo et al, submitted

46. Development of Molecular Printing Tools
Parallel Printing
Woodblock Printing Printing Press
(China ~200) (Gutenberg, 1439)
Movable Type μ-Contact Printing Beam Pen
Polymer Pen
(Bi Sheng, ~1041-1048) (Whitesides, 1993)
Lithography (PPL) Lithography (BPL)
(2008) (2010)
Serial Writing
Hard Tip, Soft Spring Scanning Probe Block
Dip-Pen Lithography Copolymer Lithography
Quill Pen Nanolithography (DPN) (2010) (2010)
(~2000 BC) (Mirkin, 1999)
Ball-Point
(Loud, 1888)

47. A Step Towards “Desktop Nanofabrication”:
Take Home Messages
• DPN and PPL are workhorse molecular printing research
tools, which allow researchers to rapidly prototype and
study molecule-based structures.
• The barrier to scanning probe parallelization is
crumbling; PPL, BPL, and SPBCL open the door for low
cost and rapid nanofabrication procedures.
• The techniques are poised to make the transition from
primarily research tools to high throughput synthesis
and fabrication tools, especially in the life sciences.

48. World Use of Dip Pen Nanolithography
Australia:
Swinburne U. – Nicolau
Canada:
U.of Alberta – Buriak Japan:
China: NAIST– Ushijima
Chinese Acad. of Sci .(Lanzhou) – Li Nagoya U.– Ichimiya
CIST – Hua Korea: MIT – Stellacci
Peking U. – J. Liu , Y Li. Samsung Electronics, Co. NASA Langley – Watkins
Chinese Acad. of Sci. (Shanghai )- Zhang Seoul Nat. U. – Nam, Naval Research – Byers,
Chinese Acad. of Sci.(Beijing) –Z. Liu S. Hong Whitman, Sheehan
Xi’an Jiaotong U. – Zhang, Liu Pusan Nati. U. – Il Kim N. Carolina State U. –
Southwest U. – Tang Sungkyunkwan U. – HJ Kim Narayan
Columbia: Korea U. –Ahn Northwestern U.– Dravid,
Servico Nacional de Aprendizaje (SENA) Yonsei U.–H. Jung United States: Liu, Mirkin, Wolinsky,
France: Netherlands: Air Force Research – Espinosa
CNRS France – Joachim U. of Twente– Reinhoudt, Naik, Stone NYU – Braunschweig UMass Lowell - Mead
Germany: Velders Albany NanoTech – Kossow Ohio State U.– Lee UC Davis – G. Liu
Inst. für NanoTechnologie, Singapore: Brookhaven – Ocko Penn State U.– Weiss UCSB – Hu
Forschungszentrum India: Nanyang Tech–Liu , Huo, Cal.Tech.– Collier Portland State University- U. of Chicago –
Karlsruhe– Fuchs CEERI – Kumar Zhang , Boey, Huang Cal. State – Schwartz Yan, La Rosa Mrkisch
Ludwig Inst.– Bein Jawaharlal Nehru Cen. for Spain: Corning Inc Purdue U. – Ivanesivic U. of Florida – Ren
Max Planck Inst. – Bastiaen Adv. Sci. Research– Rao Inst. Català– Maspoch, Science & Tech Rensselaer Poly.– Nalamasu UIUC – C. Liu,
Great Britain: Indian Inst. Sci. – Brar Garcia, Martinez Duke U. – J. Lui, Chilkoti Sandia NL – Hsu U. of Maryland – Gomez
U. of Cambridge –Rayment Israel: Parc Cientific–Samitier George Mason U. – Espina Stanford U. – Bao U. of N. Carolina –
Imperial College – Cass Hebrew U. – Willner Taiwan: Georgia NanoFab – Lewis Stevens IT – Libera Zauscher
U. of Ulster Italy: Acad. Sinica–Tao Harvard U. – Lieber Texas A & M – Banerjee, U. of Washington –
U. of Strathclyde –Graham Politec. di Milano – Levi Nat. Chiao Tung U.– Sheu Lawrence Berkeley – Batteas Ginger
Hong Kong: U. degli Studi di Milano Nat. Taiwan U.– Lin De Yoreo Texas Tech – Vaughn, Weeks Washington Tech
Xu Bicocca – Sassella Schmidt Scientific Loyola U. – Holz Tufts U. – Kaplan Center – Allen

50. Mirkin Group

51. Acknowledgements
Collaborators
Prof. Chang Liu (NU)
Prof. Harald Fuchs (Münster, Germany)
Dr. Steven Lenhert (Münster, Germany)
Prof. Mark Ratner (NU), Prof. Michael Bedzyk (NU)
Prof. Vinayak Dravid (NU), Dr. Morley Stone (WP AFRL)
Prof. Milan Mrksich (University of Chicago)
Prof. George Schatz (NU), Dr. Rajesh Naik (WP AFRL)
Prof. Hua Zhang (Nanyang Technical University, Singapore)
Joe Fragala (NanoInk)
Funding
AFOSR, ARO DARPA (TBN Program),
HSARPA, NSF, ONR, NIH,
DOD NSSEF Fellowship