U.S. patent application number 12/140780 was filed with the patent office on 2012-06-28 for matrix assisted ink transport.
This patent application is currently assigned to Northwestern University. Invention is credited to Ling Huang, Fengwei Huo, Sarah J. Hurst, Jae-Won Jang, Joseph J. Kakkassery, Chad A. Mirkin, Lidong Qin.
Application Number | 20120164396 12/140780 |
Document ID | / |
Family ID | 39967826 |
Filed Date | 2012-06-28 |
United States Patent
Application |
20120164396 |
Kind Code |
A1 |
Mirkin; Chad A. ; et
al. |
June 28, 2012 |
MATRIX ASSISTED INK TRANSPORT
Abstract
Provided is a direct write patterning method utilizing a mixture
comprising an ink of choice and an ink carrier matrix. The method
involves disposing the mixture on a tip or stamp and transporting
the mixture from the tip or stamp on a surface to form a pattern
that contains the ink. The method does not require chemical or
physical modification of either the tip or stamp or the surface
prior to transporting the mixture to the surface. The method can be
applied for patterning hard inks such as nanomaterials and
crystallized polymers and soft inks such as biomaterials including
peptides and proteins. Also provided are related biomaterial and
hard ink arrays.
Inventors: |
Mirkin; Chad A.; (Wilmette,
IL) ; Huang; Ling; (Painted Port, NY) ; Huo;
Fengwei; (Evanston, IL) ; Hurst; Sarah J.;
(Evanston, IL) ; Qin; Lidong; (Pasadena, CA)
; Jang; Jae-Won; (Evanston, IL) ; Kakkassery;
Joseph J.; (Evanston, IL) |
Assignee: |
Northwestern University
|
Family ID: |
39967826 |
Appl. No.: |
12/140780 |
Filed: |
June 17, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61047642 |
Apr 24, 2008 |
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60945164 |
Jun 20, 2007 |
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60929314 |
Jun 21, 2007 |
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Current U.S.
Class: |
428/195.1 ;
427/256; 427/265; 977/887 |
Current CPC
Class: |
Y10T 428/24802 20150115;
B01J 2219/00605 20130101; B01J 2219/00729 20130101; C09D 11/30
20130101; B01J 2219/00497 20130101; B01J 2219/00648 20130101; B82Y
30/00 20130101; B01J 2219/00734 20130101; B01J 2219/00722 20130101;
B01J 19/0046 20130101; Y10T 436/2575 20150115; B01J 2219/00725
20130101; B01J 2219/00653 20130101; Y10T 436/143333 20150115; Y10T
436/25 20150115; B01J 2219/00596 20130101; B01J 2219/00585
20130101; B01J 2219/00731 20130101; B01J 2219/00382 20130101; C40B
50/14 20130101; B01J 2219/00387 20130101; B01J 2219/00527 20130101;
C09D 11/03 20130101 |
Class at
Publication: |
428/195.1 ;
427/256; 427/265; 977/887 |
International
Class: |
B05D 5/00 20060101
B05D005/00; B32B 3/10 20060101 B32B003/10 |
Goverment Interests
STATEMENT ON FEDERAL FUNDING
[0002] The present invention was developed with use of federal
funding from NSF-NSEC, Grant No. EEC 0118025; and DARPA-ARD, Grant
No. DAAD 19-03-1-0065; and NSF Grant No. EEC0647560; and ASAF/AFOSR
FA9550-08-1-0124. The federal government reserves rights in the
invention.
Claims
1. A method comprising: providing a tip, providing an ink disposed
at the end of the tip, wherein the ink comprises at least one
polymer and at least one nanomaterial, providing a substrate
surface, and transporting the ink from the tip to the substrate
surface to form a structure on the surface comprising both the
polymer and the nanomaterial.
2. The method of claim 1, wherein the tip is a nanoscopic tip.
3. The method of claim 1, wherein the tip is a scanning probe
microscopic tip.
4. The method of claim 1, wherein tip is an atomic force
microscopic tip.
5. The method of claim 1, wherein the tip is a non-hollow tip.
6. The method of claim 1, wherein the tip is a hollow tip.
7. The method of claim 1, wherein the tip comprises an inorganic
surface.
8. The method of claim 1, wherein the tip is not surface modified
with an organic material.
9. The method of claim 1, wherein a plurality of tips are provided
comprising ink disposed at the end of the tip, and transporting the
ink from the tips to the substrate surface forms a plurality of
structures on the surface comprising both the polymer and the
nanomaterial.
10. The method of claim 1, wherein the tip is heated to effect
transport.
11. The method of claim 1, wherein the tip is an actuated tip.
12. The method of claim 1, wherein the tip is disposed at the end
of a cantilever.
13. The method of claim 1, wherein the nanomaterial comprises a
nanoparticle nanomaterial.
14. The method of claim 1, wherein the nanomaterial comprises a
nanoparticle comprising an average particle size of about 2 nm to
about 100 nm.
15. The method of claim 1, wherein the nanomaterial comprises a
nanoparticle comprising an average particle size of about 2 nm to
about 25 nm.
16. The method of claim 1, wherein the nanomaterial comprises a
substantially spherical material or an elongated material.
17. The method of claim 1, wherein the nanomaterial comprises a
metal nanoparticle, a magnetic nanoparticle, or a fullerene
nanoparticle.
18. The method of claim 1, wherein the nanomaterial comprises a
carbon nanotube.
19. The method of claim 1, wherein the nanomaterial comprises a
nanowire or a nanorod.
20. The method of claim 1, wherein the nanomaterial comprises a
quantum dot.
21. The method of claim 1, wherein the nanomaterial comprises at
least one biological macromolecule.
22. The method of claim 1, wherein the nanomaterial comprises at
least one biomolecule.
23. The method of claim 1, wherein the nanomaterial comprises at
least one protein.
24. The method of claim 1, wherein the nanomaterial comprises at
least one antibody.
25. The method of claim 1, wherein the nanomaterial comprises at
least one crystallized conducting polymer.
26. The method of claim 1, wherein the polymer is a non-biological
polymer.
27. The method of claim 1, wherein the polymer is a synthetic,
linear polymer.
28. The method of claim 1, wherein the polymer is a soluble
polymer.
29. The method of claim 1, wherein the polymer is soluble in water
and organic solvent.
30. The method of claim 1, wherein the polymer is a poly(alkylene
oxide) or a poly(alkylene imine).
31. The method of claim 1, wherein the polymer is polyethylene
oxide having a molecular weight of more than 50,000.
32. The method of claim 1, wherein the ink consists essentially of
the polymer and the nanomaterial.
33. The method of claim 1, wherein the ink further comprises a
solvent for the polymer.
34. The method of claim 1, wherein the polymer is not covalently
bound or chemisorbed to the nanomaterial.
35. The method of claim 1, wherein the polymer does not chemisorb
to or covalently bond with the surface.
36. The method of claim 1, wherein the nanomaterial does not
chemisorb to or covalently bond to the surface.
37. The method of claim 1, wherein the polymer is not chemically
reactive with the nanomaterial.
38. The method of claim 1, wherein the substrate surface is a
semiconductor or metal substrate surface.
39. The method of claim 1, wherein the substrate surface comprises
a nanoelectrodes gap.
40. The method of claim 1, wherein the transporting is carried out
under humidity and environmental conditions providing for a
meniscus between the tip and the surface.
41. The method of claim 1, wherein the transporting is carried out
with at least 40% relative humidity.
42. The method of claim 1, wherein the transporting is carried out
with at least 70% relative humidity.
43. The method of claim 1, wherein the structure has a lateral
dimension of about 1 micron or less.
44. The method of claim 1, wherein the formed pattern is
characterized by a lateral dimension of about 100 nm or less.
45. The method of claim 1, wherein the structure is a dot or a
line.
46. The method of claim 1, wherein the structure has a height of at
least 10 nm.
47. The method of claim 1, wherein the structure has a height which
is at least twice the height compared to a structure substantially
identically prepared except without the nanomaterial.
48. The method of claim 1, wherein the structure has a height which
is at least three times the height compared to a structure
substantially identically prepared except without the
nanomaterial.
49. The method of claim 1, wherein the structure has a height which
is at least four times the height compared to a structure
substantially identically prepared except without the
nanomaterial.
50. The method of claim 1, wherein the structure comprises the
polymer and nanomaterial substantially evenly distributed.
51. The method of claim 1, wherein the polymer is characterized by
a transport rate, and the nanomaterial is characterized by a
transport rate, and the polymer transport rate is faster than the
nanomaterial transport rate.
52. The method of claim 1, wherein the ink is characterized by an
ink transport rate, the polymer is characterized by a polymer
transport rate, and the nanomaterial is characterized by a
nanomaterial transport rate, and wherein the ink transport rate is
more similar to the polymer transport rate than the nanomaterial
transport rate.
53. The method of claim 1, wherein method is repeated to provide a
plurality of structures on the surface.
54. The method of claim 1, wherein method is repeated to provide a
plurality of structures on the surface which are separated from
each other by less than a micron.
55. The method of claim 1, wherein the transporting is carried out
by contacting the tip with the surface and holding the tip
stationary.
56. The method of claim 1, wherein the transporting is carried out
by contacting the tip with the surface and moving the tip with
respect to the surface, or moving the surface with respect to the
tip.
57. The method of claim 1, wherein the transporting is carried out
in a tapping mode.
58. The method of claim 1, further comprising the step of removing
at least some of the polymer from the structure.
59. The method of claim 1, wherein the tip is a nanoscopic tip, the
polymer is a soluble polymer, and the nanomaterial is a
nanoparticle.
60. The method of claim 1, wherein the tip is a scanning probe tip,
the polymer is a synthetic polymer, and the nanomaterial is a
nanoparticle, a protein, or an antibody.
61. The method of claim 1, wherein the tip is an AFM tip, the
polymer is a polyethylene oxide, polyethylene glycol, or
polyethylene imine, and the nanomaterial is a nanoparticle or a
biological material.
62. A method comprising: providing an elastomeric, patterned stamp,
providing an ink disposed on the surface of the stamp, wherein the
ink comprises at least one polymer and at least one nanomaterial,
providing a substrate surface, and transporting the ink from the
stamp to the substrate surface to form a structure on the surface
comprising both the polymer and the nanomaterial.
63. A method comprising: providing a tip or an elastomeric,
patterned stamp, providing an ink disposed on the surface of tip or
the stamp, wherein the ink comprises at least one polymer and at
least one nanomaterial, providing a substrate surface, and
transporting the ink from the tip or the stamp to the substrate
surface to form a structure on the surface comprising both the
polymer and the nanomaterial.
64. A method comprising (A) providing a tip or stamp; (B) providing
a mixture comprising an ink and a carrier matrix, wherein the
carrier matrix is selected from a) polyalkylene oxides having a
molecular weight of more than 50,000 and b) polyalkylene imines;
(C) disposing the mixture at the tip or stamp; (D) providing a
substrate surface; and (E) transporting the mixture from the tip or
stamp to the substrate surface to form a pattern on the substrate
surface such that the pattern comprises the ink.
65. The method of claim 64, wherein the tip or stamp is a
chemically or physically unmodified tip or stamp.
66. The method of claim 64, wherein the tip or stamp is a tip.
67. The method of claim 64, wherein the tip is a scanning probe
microscopic tip.
68. The method of claim 64, wherein the tip is an atomic force
microscopic tip.
69. The method of claim 64, wherein the disposing comprises
immersing the tip in the mixture.
70. The method of claim 64, wherein the disposing comprises
immersing the tip in the mixture and drying the mixture.
71. The method of claim 64, wherein the tip or stamp is a
microcontact printing stamp.
72. The method of claim 64, wherein the ink is a hard ink.
73. The method of claim 64, wherein the ink is a hard ink and the
hard ink is selected from the group consisting of nanoparticles,
carbon based materials and crystallized polymers.
74. The method of claim 64, wherein the ink is a hard ink and the
hard ink is selected from the group of metal nanoparticles,
magnetic nanoparticles and fullerenes.
75. The method of claim 64, wherein the ink comprises at least one
biomolecule.
76. The method of claim 75, wherein the biomolecule is selected
from the group consisting of nucleic acids, peptides and
proteins.
77. The method of claim 64, wherein the ink comprises at least one
protein.
78. The method of claim 77, wherein said at least one protein is an
antibody.
79. The method of claim 64, wherein the polymer is polyethylene
oxide.
80. A method comprising (A) providing a tip or stamp; (B) providing
a mixture comprising a hard ink and a carrier matrix; (C) disposing
the mixture on the tip or stamp; (D) providing a substrate surface;
and (E) transporting the mixture from the tip or stamp to the
substrate surface to form a pattern on the substrate surface such
that the pattern comprises the hard ink.
81. An hard ink nanoarray comprising (A) a substrate and (B) a
plurality of patterns on the substrate, the patterns comprising a
hard ink material and a matrix material.
82. A method comprising (A) providing a tip or stamp; (B) providing
a mixture comprising an ink and a carrier matrix, wherein the ink
comprises at least one biomolecule and the carrier matrix comprises
a material selected from the group consisting of polyalkylene
oxides and polyalkylene imines; (C) disposing the mixture at the
tip or stamp; (D) providing a substrate surface; (E) transporting
the mixture from the tip or stamp to the substrate surface to form
at least one pattern on the substrate surface such that the at
least one pattern comprises the at least one biomolecule.
83. A method comprising (A) providing a tip or stamp; (B) providing
a mixture comprising an ink and a matrix such that a transport rate
of the matrix is greater than a transport rate of the ink; (C)
disposing the mixture on the tip or stamp; (D) providing a
substrate surface; and (E) transporting the mixture from the tip or
stamp to the substrate surface to form at least one pattern on the
substrate surface such that the at least one pattern comprises the
ink.
84. A method comprising: providing a tip, providing an ink disposed
at the end of the tip, wherein the ink comprises at least one
matrix and at least one nanomaterial different from the matrix,
providing a substrate surface, and transporting the ink from the
tip to the substrate surface to form a structure on the surface
comprising both the matrix and the nanomaterial.
85. The method of claim 84, wherein the matrix is a polymer.
86. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple biomolecules
which are simultaneously transported from the tips to the
substrate.
87. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple proteins.
88. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks are characterized by a diffusion
rate which is tuned so that at least two different inks have
similar diffusion rate during transport.
89. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple biomolecules
which are simultaneously transported from the tips to the
substrate, and the ratio between polymer and biomolecule is
different on different tips.
90. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple biomolecules
which are simultaneously transported from the tips to the substrate
to form dots which have an average dot diameter characterized by
less than 7% variation.
91. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple proteins which
are simultaneously transported from the tips to the substrate, and
the ratio between polymer and polymer is different on different
tips.
92. The method of claim 1, wherein the tip is part of a larger
structure comprising a plurality of tips with inks disposed at the
ends of the tips, wherein the inks comprise multiple proteins which
are simultaneously transported from the tips to the substrate to
form dots which have an average dot diameter characterized by less
than 7% variation.
93. The method of claim 1, wherein the nanomaterial is
characterized by a bioactivity which is retained upon transport to
form the structure on the surface.
94. A method comprising simultaneously patterning multiple inks
from tips to a substrate, wherein the inks comprise different
nanomaterials and polymer, and wherein the different nanomaterials
are transported to the substrate at similar rates because the
ratios of nanomaterials and polymer in the inks are tuned.
95. The method of claim 94, wherein the nanomaterials are
biomolecules.
96. The method of claim 94, wherein the nanomaterials are
biomolecules which retain bioactivity upon patterning.
97. The method of claim 94, wherein the nanomaterials are
proteins.
98. The method of claim 94, wherein the patterning produces
dots.
99. The method of claim 94, wherein the patterning produces dots
with similar diameters.
100. A nanoarray comprising: (A) a substrate, and (B) a plurality
of patterns on the substrate, the patterns being in the form of
dots and comprising at least two different biomolecules in
different dots, wherein the dots have similar sizes.
101. The nanoarray of claim 100, wherein the nanoarray is produced
by simultaneous patterning of the different biomolecules.
102. The nanoarray of claim 100, wherein the biomolecules retain
their bioactivity.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional Ser.
No. 60/945,164 filed Jun. 20, 2007, and also to U.S. provisional
Ser. No. 60/929,314 filed Jun. 21, 2007, and also to U.S.
provisional Ser. No. 61/047,642 filed Apr. 24, 2008, all of which
are hereby incorporated by reference in their entireties.
BACKGROUND
[0003] Nanoscience focuses on elucidating the unique chemical and
physical properties of nanoscale materials that analogous bulk
structures do not possess (37, 38). Bottom-up and top-down
approaches have been used to synthesize and fabricate such
nanoscale materials that are metallic (1, 4, 5, 11), magnetic (6,
7), semi-conducting (8, 9), silica-based (18), and carbon-based,
such as fullerenes, and carbon nanotubes, (3, 73) with fine control
over particle size and shape (74, 36). In the last decade,
nanoscale materials have been studied and characterized using a
variety of methods and are becoming better understood.
[0004] Nanoscale materials are beginning to be utilized in a
growing number of novel applications including applications, that
rely mainly on the ability to arrange nano building blocks (NBBs)
into deliberate patterns with controlled feature sizes on surfaces,
such as nanocircuit integration (75), biological micro- and
nano-array fabrication (76), and nanoscale sensing (77, 78).
Current methods for patterning nano building blocks into desired
locations usually include the following two steps: 1) a surface
pattern-generation step and 2) a nanoparticle self-assembly step.
The first step creates pre-patterns on a surface using
photolithography, electron beam lithography (EBL), or focused ion
beam (FIB) lithography (79), while in the second step,
nanoparticles are exposed to and further assembled along the
pre-patterned areas on the surface (39). Unfortunately, such
surface patterning methods can require expensive instrumentation
and may be complicated and time-consuming. For example, avoiding
non-specific binding of nanoparticles to unwanted areas during the
second step may be often a very difficult, if not impossible task.
Such problem can be especially prominent at the sub-100 nm size
regime.
[0005] Dip-pen nanolithography (DPN) is a single-step direct
writing and reading lithography tool utilized for patterning soft
inks, such as small organic molecules, DNA, and proteins (60), in
some cases, at the millimeter and centimeter scale (61, 62). In
some cases, it may be more difficult to directly write hard inks,
such as nanoparticles, fullerenes, or crystallized conducting
polymers, using DPN due to problems with obtaining an even coating
of such hard inks on an AFM tip and controlling the ink's transport
rate. As the result, the nanoparticle patterns may become
inconsistent and have uncontrollable feature sizes. In addition,
hard inks may in some cases have a tendency to dry quickly and
agglomerate during the DPN process, which makes extended writing
times unachievable (63-68).
[0006] Thus, a need exists to develop a single step method for
direct patterning of hard inks on a surface that will provide a
control over the patterned feature size and will allow for longer
writing times. In particular, development of direct patterning
methods for protein-based nanostructures is important for
researchers working in the areas of proteomics and theranostics.
Such methods would allow generating multi-component biological
nanostructures of proteins, oligonucleotides and viruses.
[0007] U.S. Pat. No. 7,005,378 describes patterning of metallic
precursors including use of polyethylene oxide to facilitate
patterning.
[0008] The paper "On-Wire Lithography" (Qin et al., Science, vol.
309, Jul. 1, 2005, 113-115) describes preparation of gap structures
and filling the gap with a mixture of a conductive polymer and
polyethylene oxide.
[0009] US Patent Publication 2003/0162004 (Mirkin et al.,
Northwestern University) describes patterning of sol-gel mixtures
comprising block copolymers.
[0010] US Patent Publication 2004/0142106 (Mirkin et al.,
Northwestern University) describes patterning of precursor magnetic
materials.
[0011] US Patent Publication 2002/0122873 (Mirkin et al.,
Northwestern University) describes patterning of magnetic
nanoparticles using magnetic driving forces.
[0012] US Patent Publication 2004/0026007 (Hubert et al., MIT)
describes deposition of nanoparticles.
SUMMARY
[0013] The present application describes among other things methods
of making, articles, devices, compositions, and methods of
using.
[0014] One embodiment provides a method comprising: providing a
tip, providing an ink disposed at the end of the tip, wherein the
ink comprises at least one matrix and at least one nanomaterial
different from the matrix, providing a substrate surface, and
transporting the ink from the tip to the substrate surface to form
a structure on the surface comprising both the matrix and the
nanomaterial.
[0015] In another example, provided is a method comprising:
providing a tip, providing an ink disposed at the end of the tip,
wherein the ink comprises at least one polymer and at least one
nanomaterial, providing a substrate surface, and transporting the
ink from the tip to the substrate surface to form a structure on
the surface comprising both the polymer and the nanomaterial.
[0016] One advantage for at least one embodiment is that it allows
forming patterns of inks that may be difficult to pattern. Another
advantage for at least one embodiment is that it does not require
chemical or physical modification of the tip or stamp. In addition,
this in many cases does not require chemical or physical
modification of the substrate surface and allows transporting ink
molecules to the surface in a fashion that is independent of the
substrate surface's material. In many embodiments, the method
allows sub-micron and sub 100-nm patterns of hard inks such as
nanomaterials and biomolecules such as proteins or peptides in a
direct write high-throughput manner.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 schematically illustrates patterning of nanomaterials
using matrix assisted Dip-Pen nanolithography (DPN).
[0018] FIGS. 2 (A)-(F) present DPN generated patterns of various
polymers on a variety of substrates as well as selected height
profiles. (A) is a topographic atomic force microscopy (AFM) image
of a pattern of polyethylene glycol (PEG) with molecular weight
(MW) 8,000 on an Au substrate at writing speed of 0.16 .mu.m/s. (B)
is an AFM image of a pattern of PEG (MW 8,000) on a GaAs substrate
at writing speed of 0.022 .mu.m/s. (C) is an AFM image of a pattern
of polyethylene oxide (PEO) with MW 100,000 on a SiO.sub.x
substrate at writing speed of 0.05 .mu.m/s. (D) is an AFM image of
a pattern of PEO (MW 100,000) on an Au substrate at writing speed
of 0.05 .mu.m/s. (E) is an AFM image of a pattern of polyethylene
imine (PEI) with MW 10,000 on InAs at 0.6 and 0.3 .mu.m/s. (F) is
an AFM image of a pattern of a mixture of PEI (MW 10,000) and 2 nm
Au nanoparticles on InAs at 0.6 and 0.3 .mu.m/s.
[0019] FIGS. 3 (A) and 3 (B) present height profiles of line
patterns of: (A) PEI only; (corresponding topographic AFM image n
FIG. 2E) and (B) a mixture of 2 nm Au nanoparticles and PEI on InAs
substrate (corresponding topographic AFM image in FIG. 2F). FIG.
3(C) is a height profile of PEO only line patterns on Au
(corresponding AFM topographic image was shown in FIG. 2D).
[0020] FIGS. 4 (A)-(D) present images DPN generated arrays. (A) is
a topographic AFM image of PEO arrays at contact time of 64, 32,
and 16 seconds from top to bottom, respectively. (B) shows a
topographic AFM image of dot arrays deposited using a mixture 2 nm
Au nanoparticles and PEO, tip substrate contact time is 64, 32 and
16 seconds from top to bottom respectively. (C) is a topographic
AFM image of dot arrays using deposited using a mixture of 5 nm Au
nanoparticles and PEO, tip-substrate contact times 64, 32, 16, and
8 from top to bottom respectively, the inset shows a Transmission
Electron Microscopy (TEM) image of the dot created by DPN on a TEM
grid. (D) shows a topographic AFM image of dot arrays deposited
using a mixture 13 nm Au nanoparticles and PEO, tip substrate
contact time is 64, 32 and 16 seconds from top to bottom
respectively.
[0021] FIGS. 5 (A)-(D) present images of patterns generated by DPN
using a mixture of 4.7 nm magnetic nanoparticle and PEO. (A) is an
AFM image of dot arrays, tip substrate contact time is 64, 32 and
16 seconds from top to bottom respectively. (B) is an AFM image of
diamond shape line arrays, writing speed 0.05 .mu.m/s. (C) is a
magnetic force microscopy (MFM) image of larger scale dot arrays.
The inset shows a single dot scan (G) is a MFM image of an array of
diamond shaped lines created by DPN. The inset shows a single
diamond shape line scan.
[0022] FIGS. 6 (A)-(D) relate to arrays generated by DPN using a
mixture of fullerene and PEO. (A) is an AFM image of dot arrays at
contact times of 16, 8 and 4 seconds from top to bottom
respectively. (B) is a height profile of the dot arrays of (A). (B)
presents line arrays at writing speed of 0.05, 0.1 and 0.2 .mu.m/s
respectively. (C) is a 3-dimensional AFM image of DPN generated
lines crossing through the 500 nm gap nanoelectrode. (F) shows I-V
curves of the lines of (E).
[0023] FIGS. 7 (A) and (B) are respectively a topographic AFM image
(A) and a height profile (B) of fullerene/PEO dot patterns on Au
substrate generated by DPN. Contact times are 64, 32, and 16 sec
from top to bottom of FIG. 7A, respectively. FIG. 7 (C) is a height
profile of fullerene/PEO line patterns on Au substrate generated by
DPN at writing speeds of 0.05, 0.1, and 0.2 .mu.m/s from left to
right, respectively. The corresponding AFM topography image was
shown in FIG. 6B.
[0024] FIG. 8 schematically illustrates generating of protein
arrays.
[0025] FIGS. 9 (A) and (B) present AFM images of anti-chicken IgG
AF 488 nanoarrays on Au (A) and silicon (B) surfaces generated by
matrix assisted (MA)-DPN.
[0026] FIG. 10 shows fluorescence microscopy images of anti-chicken
IgG AF 488 nanoarrays generated by MA-DPN on silicon
substrates.
[0027] FIG. 11. (A) Plots showing the relationship of the
DPN-generated dot sizes with tip-substrate contact time of selected
ink materials, the slopes of the plot reflect the according ink's
diffusion constant. (B) Charts showing the change of the ink
(anti-ubiquitin) diffusion rate with the adding of PEO at different
ratios. (C) Comparison of the diffusion rate of BSA/PEO and
anti-ubiquitin/PEO at ratio of 1:5, the chart shows very close
diffusion rate. (D) Charts showing that the ink diffusion rate of
IgG and .beta.-galactosidase can be tuned to be very close at the
ink/PEG ratio of 1:5 and 1:7.5, respectively.
[0028] FIG. 12. (A) Fluorescent image of DPN generated dot arrays.
The AFM tips were coated one after another with BSA/PEG (green) and
anti-ubiquitin/PEG (red), respectively, both at ratio of 1:5, and
both inks were simultaneously patterned using passive one
dimensional A-26 AFM tip array. (B) Zoomed-in image of the area
within the rectangular in (A), which shows sharp fluorescent signal
contrast. (C) and (E), AFM images of DPN generated nanoarrays
containing IgG/PEG (1:5) and .beta.-galactosidase/PEG (1:7.5),
respectively. (D) and (F), fluorescent images of the nanoarrays in
(C) and (E) after incubating with according fluorescent labeled
antibodies.
[0029] FIG. 13. (A) Overview and (B) zoomed-in area of the inkwell
that used for alternative two ink (BSA/PEG and anti-ubiquitin/PEG)
coating. (C) Optical and (D) fluorescent microscopy images of the
AFM tip array (A-26) used for multiple-ink patterning by DPN. (E)
Overview and (F) zoomed-in area of the inkwell that used for
IgG/PEG and .beta.-galactosidase/PEG coating. Inkwell and tip
arrays available from NanoInk, Inc. (Skokie, Ill.).
DETAILED DESCRIPTION
Introduction
[0030] Priority U.S. provisional Ser. No. 60/945,164 filed Jun. 20,
2007, and priority U.S. provisional Ser. No. 60/929,314 filed Jun.
21, 2007, and also priority U.S. provisional Ser. No. 61/047,642
filed Apr. 24, 2008, are all hereby incorporated by reference in
their entireties, including working examples, figures, claims, and
description of various embodiments.
[0031] Copending application serial No. ______ filed on same day as
this application, "Patterning with Compositions Comprising Lipids,"
to Mirkin et al., is hereby incorporated by reference in its
entirety including figures, claims, working examples, and
description of other embodiments.
[0032] Copending application serial No. ______ filed on same day as
this application, "Universal Matrix," to Mirkin et al., is hereby
incorporated by reference in its entirety including figures,
claims, working examples, and description of other embodiments.
[0033] Nanolithography instruments and accessories, including ink
wells and pen arrays, for direct-write printing can be obtained
from NanoInk, Inc., Chicago, Ill. DIP PEN NANOLITHOGRAPHY.RTM. and
DPN.RTM. are registered NanoInk, Inc. trademarks.
[0034] The following patents and co-pending applications relate to
direct-write printing with use of for example cantilevers, tips,
and patterning compounds are hereby incorporated by reference in
their entirety:
[0035] U.S. Pat. No. 6,635,311 issued Oct. 21, 2003 ("Methods
Utilizing Scanning Probe Microscope Tips and Products Therefor or
Produced Thereby") to Mirkin et al., which describes fundamental
aspects of DPN printing including inks, tips, substrates, and other
instrumentation parameters and patterning methods;
[0036] U.S. Pat. No. 6,827,979 issued Dec. 7, 2004 ("Methods
Utilizing Scanning Probe Microscope Tips and Products Therefor or
Produced Thereby") to Mirkin et al., which further describes
fundamental aspects of DPN printing including software control,
etching procedures, nanoplotters, and arrays formation.
[0037] U.S. patent publication number 2002/0122873 A1 published
Sep. 5, 2002 ("Nanolithography Methods and Products Produced
Therefor and Produced Thereby"), which describes aperture
embodiments and driving force embodiments of DPN printing.
[0038] U.S. patent publication 2003/0185967 to Eby et al.,
published Oct. 2, 2003 ("Methods and Apparatus for Aligning
Patterns on a Substrate"), which describes alignment methods for
DPN printing.
[0039] U.S. Pat. No. 7,060,977 to Dupeyrat et al., issued Jun. 13,
2006 ("Nanolithographic Calibration Methods"), which describes
calibration methods for DPN printing.
[0040] U.S. Patent Publication 2003/0068446, published Apr. 10,
2003 to Mirkin et al. ("Protein and Peptide Nanoarrays"), which
describes nanoarrays of proteins and peptides;
[0041] U.S. Regular patent application Ser. No. 10/307,515 filed
Dec. 2, 2002 to Mirkin et al. ("Direct-Write Nanolithographic
Deposition of Nucleic Acids from Nanoscopic Tips"), which describes
nucleic acid patterning.
[0042] U.S. Patent Publication 2003/0162004 to Mirkin et al.
published Aug. 28, 2003 ("Patterning of Solid State Features by
Direct-Write Nanolithographic Printing"), which describes reactive
patterning and sol gel inks.
[0043] U.S. Pat. No. 6,642,129, issued Nov. 4, 2003, to Liu et al.
("Parallel, Individually Addressible Probes for
Nanolithography").
[0044] U.S. Pat. No. 6,737,646, issued May 18, 2004, to Schwartz
("Enhanced Scanning Probe Microscope and Nanolithographic Methods
Using Same"). U.S. Pat. No. 6,674,074 issued Jan. 6, 2004, to
Schwartz ("Enhanced Scanning Probe Microscope").
[0045] U.S. Pat. No. 7,098,058 issued Aug. 29, 2006.
[0046] U.S. Patent publication 2004/0026681 published Feb. 12,
2004.
[0047] U.S. Pat. No. 7,005,378 issued Feb. 28, 2006.
[0048] U.S. Patent Publication 2004/0175631 published Sep. 9,
2004.
[0049] U.S. Pat. No. 7,034,854 issued Apr. 25, 2006.
[0050] U.S. Patent Publication 2005/0009206 published Jan. 13,
2005.
[0051] U.S. Patent Publication 2005/0272885 published Dec. 8,
2005.
[0052] U.S. Patent Publication 2005/0255237 published Nov. 17,
2005.
[0053] U.S. Patent Publication 2005/0235869 published Oct. 27,
2005.
[0054] U.S. Patent publication 2006/0040057 to Sheehan et al.
(Thermal Control of Deposition in Dip Pen Nanolithography).
[0055] Two dimensional arrays are described in US Patent
publication no. 2008/0105042 to Mirkin et al., filed Mar. 23, 2007,
which is hereby incorporated by reference in its entirety including
figures, claims, working examples, and other descriptive
embodiments.
[0056] In some embodiments, the direct-write nanolithography
methods described herein can be particularly of interest for use in
preparing bioarrays, nanoarrays, and microarrays based on peptides,
proteins, nucleic acids, DNA, RNA, viruses, and the like. See, for
example, U.S. Pat. No. 6,787,313 for mass fabrication of chips and
libraries; U.S. Pat. No. 5,443,791 for automated molecular biology
laboratory with pipette tips; U.S. Pat. No. 5,981,733 for apparatus
for the automated synthesis of molecular arrays in pharmaceutical
applications;
[0057] Direct write methods, including DPN printing, are described
in for example Direct-Write Technologies, Sensors, Electronics, and
Integrated Power Sources, Pique and Chrisey (Eds), 2002.
[0058] Scanning probe microscopy is reviewed in Bottomley, Anal.
Chem., 1998, 70, 425R-475R. Scanning probe microscopes are known in
the art including probe exchange mechanisms as described in U.S.
Pat. No. 5,705,814 (Digital Instruments).
[0059] The inventors developed a method of patterning utilizing a
mixture that comprises a polymer and a nanomaterial. In an
embodiment of the method, the mixture is first disposed on a tip or
stamp and then transported from the tip or stamp on a substrate
surface to form a pattern on the surface that comprises the ink of
choice. The method as applied for Dip Pen Nanolithography printing
is illustrated on FIG. 1.
Ink
[0060] Ink can be transported to a surface whether from a tip or a
stamp or some other transport originating surface. The ink can be a
composite material and can comprise at least two components
including at least one polymer and at least one nanomaterial, the
nanomaterial being different than the polymer. The ink can be
initially formulated with use of a solvent and may further comprise
solvent or at least residual solvent for the polymer. In many
cases, solvent is removed upon disposing the ink at the end of a
tip or on a stamp surface. In other cases, the ink yet comprises
solvent and is used as a liquid. For example, ink can be delivered
by channels to the end of a tip.
[0061] A basic and novel feature can be that the ink consists
essentially of the polymer and the nanomaterial and is
substantially free of components that interfere with transport of
polymer and nanomaterial. In some cases, the ink comprises at least
at least 70%, or at least 90% by weight polymer and nanomaterial.
The ink can comprises less than 30% by weight or less than 10% by
weight material which is not polymer or nanomaterial.
Polymer
[0062] The ink carrier matrix is usually chosen as any material
that can be relatively easily patterned by DPN printing. If a
specific feature size and particular patterns are desired, the
polymer material of the ink carrier matrix can be any material that
can be easily patterned by DPN in a well controlled manner as to
provide the desired feature size and pattern when used by itself.
Preferably, the polymer ink carrier matrix is selected to be such
that it satisfies at least some of the following criteria:
[0063] 1) the polymer ink carrier matrix does not chemically react
with either the molecules of the ink or the material of the tip or
stamp;
[0064] 2) a transport rate of the polymer ink carrier matrix is a
higher than a transport rate of the ink mixed with the matrix;
[0065] 3) the polymer ink carrier matrix does not interfere with
inherent physical or biological characteristics of the ink.
[0066] The ink carrier matrix can be, for example, a polymer
matrix. The polymer can be a non-biological polymer. The polymer
can be a soluble polymer; it can be a linear polymer having a
linear polymer backbone or only small amount of branching. The
polymer can be a copolymer, a block copolymer, a random copolymer,
a terpolymer, or a branched polymer. A polymer can be
functionalized for crosslinking although in many cases this is not
desired, particularly if the polymer is to removed by solvent
washing.
[0067] The polymer can be soluble in both water as well as organic
solvent or non-aqueous solvent.
[0068] A polymer forming the polymer matrix can be, for example,
polyalkylene oxide, polyalkylene glycol, or polyalkylene imine. In
some embodiments, polyalkylene oxide used as a polymer matrix can
be a polyalkylene oxide having a molecular weight over 50,000. Yet,
in some embodiments, a polyalkylene oxide having a molecular weight
of about 50,000 or less can be used.
[0069] In some embodiments, polyethylene oxide (PEO) having a
molecular weight (MW) of about 100,000 can be preferred as a
material for the polymer matrix. Such a polymer has a low melting
temperature and can be easily patterned by itself using DPN.
[0070] In general, PEO does not react with many hard inks or
biomaterials and thus does not effect their chemical, biological or
physical characteristics. In addition, PEO is soluble in a variety
of solvents including both hydrophilic and hydrophobic solvents,
both aqueous and organic solvents, both polar and non-polar
solvents. The good solubility makes PEO compatible with a variety
of inks. For example, fullerenes or carbon nanotubes can be mixed
with PEO using toluene as a common solvent; magnetic nanoparticles
can be mixed with PEO using dichloromethane as a common solvents;
Au nanoparticles or water soluble conducting polymers, such as
sulphonated polyaniline (SPAN) or doped polypyrrole, can be mixed
with PEO using water as a common solvent; quantum dots can be mixed
with PEO using hexane as a common solvent; biomolecules such as
nucleic acids or proteins can be mixed with PEO utilizing an
appropriate biological buffer as a common solvent. Moreover, PEO
can be patterned on a variety of substrate surfaces including metal
surfaces such as Au surface, semiconductor surfaces such as GaAs or
InAs surface or oxide surface such as SiO.sub.x surface. Lower
molecular weight PEO, also sometimes called polyethylene glycol,
can be used.
[0071] The polymer and substrate surface can be adapted so that the
polymer does not chemisorb to or covalently bond with the surface.
Also, the polymer and the nanomaterial can be adapted so that the
polymer is not chemically reactive with the nanomaterial.
Nanomaterial
[0072] Nanomaterials can be particulate types of materials having
at least one lateral dimension of at least about 100 nm or less, or
about 50 nm or less, or about 25 nm or less. The nanomaterial can
be for example a spherical material, or a substantially spherical
material, or an elongated material. For example, a fullerene for
purposes here can be considered a substantially spherical material.
This lateral dimension can be a statistical average for many
distinct units or particles. It can be for example an average
particle diameter for substantially spherical particles or an
average particle length or width for elongated particles. The
nanomaterial can be organic or inorganic, hard or soft, flexible or
rigid. The nanomaterial can be a non-molecular material. In
preferred embodiments, the nanomaterial can be for example a metal
nanoparticle, a magnetic nanoparticle, or a fullerene
nanoparticle.
[0073] While the methods described herein can be applied to
delivery of a wide variety of ink nanomaterials, in many cases, the
ink nanomaterial can be a material that is difficult to pattern by
itself, without a polymer as ink carrier matrix, using DPN printing
for example. For example, the transport rate may be too slow or the
transporting too unreliable.
[0074] For instance, the ink of choice can be a hard ink including
metal nanoparticles such as Au or Ag silver nanoparticles,
semiconductor nanoparticles as quantum dots, oxide nanoparticles
such as silica or alumina particles, magnetic particles,
carbon-based particles such as fullerenes and carbon nanotubes,
crystalline polymers including crystalline conducting polymers.
[0075] The method is not limited to patterning hard inks and can be
used also for patterning soft inks including biomaterials,
biomolecules, or biological macromolecules such as nucleic acids,
DNA, RNA, proteins, peptides, polypeptides, antibodies, and oligo-
and polysaccharides. Crystallized conducting polymer can be
used.
[0076] In an embodiment, the nanomaterial comprises a nanoparticle
nanomaterial. The nanomaterial can comprise a nanoparticle
comprising an average particle size of about 2 nm to about 100 nm,
or about 2 nm to about 25 nm.
[0077] In other embodiments, the nanomaterial can be a carbon
nanotube, whether single, double; or multi-walled. The nanomaterial
can comprise a nanowire or a nanorod. The nanomaterial can comprise
a semiconductor-related material and be for example a quantum
dot.
[0078] The nanomaterial and substrate surface can be adapted so
that the nanomaterial does not chemisorb to or covalently bond with
the surface.
Tips and Stamps
[0079] The tip embodiment will be further described. The stamp
embodiment will also be further described. Many of the parameters
described herein such as the selection of the patterning compound,
surface, and contact conditions can be used for both tip and stamp
embodiments. Tips and stamps are used in other technologies besides
DPN printing and microcontact printing.
[0080] Tips known in art of DPN printing can be used. Sharp tips
can be used which are characterized by a sharp, pointed end. The
tip can be for example a nanoscopic tip. The tip can be for example
a scanning probe microscope tip or an atomic force microscope
tip.
[0081] Tips can be engineered to be useful for scanning probe or
AFM measurements if suitably adapted with for example cantilever
and feedback mechanism. In particular, the tip can be disposed at
the end of a cantilever. The tip can be a hollow tip or a solid tip
or a non-hollow tip. The tip can comprise a channel for delivery of
the ink mixture. Tips including solid, non-hollow, and hollow tips
are further described in for example U.S. Pat. Nos. 6,635,311 and
6,827,979, as well as 2002/0122873, which are herein incorporated
by reference in their entirety. WO 2005/115630 to Henderson et al,
published Dec. 8, 2005, also describes an elongated beam with
elongated aperture for deposition on surfaces. See also US Patent
Publication 2006/0096078 to Bergaud et al. for deposition based on
slit or groove technology; see also, Espinosa et al., Small, 1, No.
6, 632-635, 2005 for nanofountain probe writing; Lewis et al.,
Appl. Phys. Lett., 1999, 75, 2689-2691; Taha et al., Appl. Phys.
Lett., 2003, 83, 1041-1043; Hong et al, Appl. Phys. Lett., 2000,
77, 2604-2606; Meister et al., Microelectron. Eng., 2003, 67-68,
644-650; Deladi et al., Appl. Phys. Lett., 85, 5361-5363.
[0082] Tips can comprise hard inorganic, ceramic materials, or
softer organic materials. Semiconductor materials can be used.
Insulative and conductive materials can be used. Tips known in the
art of AFM imaging, for example, can be used including silicon or
silicon nitride. For example, polymer or polymer-coated tips can be
used. See, for example, US Patent Publication No. 2005/0255237 to
Zhang et al, which is herein incorporated by reference in its
entirety. Polymer tips and cantilevers are described in, for
example, Mirkin and Liu, US Patent Publication No. 2004/0228962,
related to scanning probe contact printing.
[0083] The tip disposed on the cantilever can be part of a larger
structure comprising a plurality of tips disposed on a plurality of
cantilevers. These can be called multipen structures or parallel
pen structures. For example, the multipen structure can have over
20, or over 100, or over 1,000, or over 10,000, or over 100,000, or
over 1,000,000 individual tips. The cantilevers and tips can be
adapted for individual actuation, wherein one tip can be raised or
lowered independently of another tip. Individual actuation is
described in for example U.S. Pat. Nos. 6,867,443 and 6,642,129 to
Liu et al, which are hereby incorporated by reference in their
entirety. Electrostatic or thermal actuation can be used.
[0084] Tips can be thermally heated and activated for temperature
control. In particular, the tip can be heated to effect
transport.
[0085] Tips can comprise an inorganic surface and tips can be used
where they are not modified after fabrication with an organic
material or coating.
[0086] In one embodiment, a plurality of tips can be provided
comprising ink disposed at the end of the tip, and transporting ink
from the tips to the substrate surface forms a plurality of
structures on the surface comprising both the polymer and the
nanomaterial.
[0087] In addition, stamps can be used including stamps for
microcontact printing can be used. See for example Xia and
Whitesides, "Soft Lithography," Angew. Chem. Int. Ed., 1998, 37,
550-575, and references cited therein, for description of
microcontact printing including stamps (pages 558-563). In general,
stamps are fabricated for massive parallel printing using Z
direction motion rather than serial motions with fine XY motion.
Stamps can comprise a single material or can be formed by
multilayering methods including surface treatments to improve
printing. One surface layer can supported which has different
properties than the support, e.g., stiffer. The stamp can comprise
a polymer including an elastomer or a crosslinked rubber, such as,
for example, a hydrophobic polymer, such as a silicone polymer or
siloxane polymer, which is adapted for accepting ink but also
depositing ink. The stamp can be patterned to form lines, including
straight and curvilinear lines, or circles or dots.
[0088] The stamp can be fabricated to have very small structures,
which can be a tip. In addition, surfaces can be used which provide
relief structures. Here, some areas of the surface rise above other
areas of the surface, and the ink primarily coats the raised up
areas.
[0089] One of the advantages of the present method is that it does
not require chemical or physical modification of the tip or stamp.
I.e. in some embodiments, the tip or stamp can be an unmodified tip
or stamp, i.e. a tip or stamp not exposed to chemical or physical
modification prior to having a mixture comprising an ink and ink
carrying matrix being disposed on the tip or stamp.
[0090] The chemical or physical modification of the tip or stamp is
usually used in the prior art methods to promote or enhance ink
coating to the tip or stamp, to promote or enhance ink adhesion to
the tip or stamp and/or to promote or enhance ink transport from
the tip or stamp to the substrate surface. Examples of chemical or
physical modification of the tip or stamp include but not limited
to base treatment to impart a charged surface of the silicon
nitride tip, silinization with amino- or mercaptosilanizing agents,
non-covalent modification with small molecules or polymeric agents
such as polyethyleneglycol (PEG).
Substrate Surface
[0091] The substrate surface can be a surface of any substrate
although the surface can be adapted to function with the ink, the
polymer, the nanomaterial, and the application at hand. Smother
substrates are generally preferred for providing pattern's higher
resolution. For example, the substrate surface can be a surface of
an insulator such as, for example, glass or a conductor such as,
for example, metal, including gold. In addition, the substrate can
be a metal, a semiconductor, a magnetic material, a polymer
material, a polymer-coated substrate, or a superconductor material.
The substrate can be previously treated with one or more
adsorbates. Still further, examples of suitable substrates include
but are not limited to, metals, ceramics, metal oxides,
semiconductor materials, magnetic materials, polymers or polymer
coated substrates, superconductor materials, polystyrene, and
glass. Metals include, but are not limited to gold, silver,
aluminum, copper, platinum and palladium. Other substrates onto
which compounds may be patterned include, but are not limited to
silica, silicon oxide SiO.sub.x, GaAs, InP and InAs.
[0092] One of the advantages of the present method is that it does
not require for a substrate surface to be chemical or physical
modified prior to transporting the mixture comprising the ink and
the ink carrier matrix to the substrate surface. Accordingly, in
some embodiments, the substrate surface can be an unmodified
substrate surface, i.e. a substrate surface, which was not
chemically or physically modified prior to being patterned.
[0093] The chemical or physical medication of the substrate surface
is usually used in the prior art methods to promote ink transport
from the tip or stamp to the substrate surface, to enhance ink
adhesion to the substrate surface or to covalently modify the
substrate surface. Examples of physical or chemical modification of
the substrate surface include but not limited to base treatment of
a charged surface of silicon oxide, silanization with amino or
mercaptosilinizing agents or modification with polymers carrying
chemically reactive groups.
[0094] Another advantage of the present method that it does not
require prepatterning of the substrate surface.
[0095] The substrate can be monolithic or comprise multiple
materials including multiple layers. In a preferred embodiment, the
substrate surface is a semiconductor or metal substrate
surface.
[0096] The substrate surface can present conductive portions,
insulative portions, or both. The conductive portions can be
electrodes for example. The ink can be transported onto or in
between electrodes, establishing contact with electrodes.
Ink Transport
[0097] The mixture can be transported from a tip or stamp to a
substrate surface in several different ways and is not in
particular limited. Known methods in DPN printing and microcontact
printing can be used. For instance, in scanning probe and
AFM-related technology, different modes can be used to have tips
interact with surfaces, which include contact mode, non-contact
mode and intermittent contact mode or tapping mode. Cantilevers can
be oscillated. Known feedback methods can be used for positioning
and alignment the X, Y and Z directions.
[0098] The transporting of the mixture from the tip to the surface
can be carried out by moving the tip only in the Z direction up and
down with respect to the XY plane of the substrate surface to
engage with and disengage with the surface. A contact time can be
used and if contact is what activates ink flow then ink flows
during the contact time. The mixture delivery can be performed
without translating the tip over the substrate surface, without
moving in the XY plane, and holding the tip stationary.
Alternatively, the tip can be translated over the surface, moving
in the XY plane. Either the tip can be moved and the surface held
stationary, or the surface can be moved and the tip held
stationary.
[0099] The transporting can be carried out under conditions such as
humidity, temperature, and gaseous atmosphere which provide for a
water meniscus between the tip and surface. For example, relative
humidity can be at least about 25%, or at least about 40%, or at
least about 50%, or at least about 70%. Conditions can be
controlled with use of environmental chambers. The gaseous
atmosphere can be air, an inert atmosphere, an atmosphere with
controlled humidity, or with the presence of other volatile or
gaseous compounds such as vapors of organic compounds or volatile
solvents such as alcohols like methanol or ethanol. Conditions can
be selected to not favor a water meniscus including, for example,
anhydrous conditions or conditions wherein all reagents and
surfaces are selected to be free of water.
[0100] The transporting can be done manually or by instrument with
computer control. Software can be used which can facilitate pattern
design, calibration, leveling, and alignment. Calibration methods
are described in for example U.S. Pat. No. 7,060,977 to
Cruchon-Dupeyrat et al., which is hereby incorporated by reference.
Alignments methods are describe in for example 2003/0185967 to Eby
et al., which is hereby incorporated by reference.
[0101] The transporting can be done more than once, repetitively,
in either the same spot or at different locations.
[0102] The ink transport can be characterized by an ink transport
rate characterized from transport of mixtures of the polymer and
the nanomaterial. The polymer transport can be characterized by a
polymer transport rate. The nanomaterial transport can be
characterized by a nanomaterial transport rate. The polymer
transport rate can be faster than the nanomaterial transport rate.
Also, the ink transport rate can be more similar to the polymer
transport rate than the nanomaterial transport rate.
[0103] In the present method, a transport rate of the mixture is
dominated by a transport rate of the ink carrier matrix's material,
such as PEO. Accordingly, a size such as length, width, and/or
height of the formed pattern(s) is determined by the transport rate
of the ink carrier matrix's material, which can be controlled
either via varying humidity as discussed above or by changing a
contact time between the tip and the substrate surface. The ability
to write patterns comprising the ink at a rate that can be finely
tuned by controlling the transport rater of the ink carrier
matrix's material, such as PEO, is one of the advantages of the
present method.
Other Lithographies Besides DPN and Microcontact Printing
[0104] Soft lithographic methods including microcontact printing
can be used. See for example Xia and Whitesides, "Soft
Lithography," Angew. Chem. Int. Ed., 1998, 37, 550-575, which is
hereby incorporated by reference in its entirety. Methods using a
patterned elastomeric material as mask, stamp, or mold. Besides
microcontact printing, other methods include replica molding (REM),
microtransfer molding (.mu.TM), micromolding in capillaries
(MIMIC), and solvent-assisted micromolding (SANIM).
Structure
[0105] The structure formed as a result of the ink transport on the
surface can be used as is or treated by additional methods such as
heat, light, drying, vacuum, or chemical reaction. Such additional
treatment can chemically modify the structure or dry the structure.
For example, the polymer can be crosslinked or annealed and
morphologically altered.
[0106] The structure can be washed to remove the polymer, or at
least substantially most of the polymer.
[0107] The structure can be characterized by a lateral dimension
such as length, width, diameter such as for example 1 micron or
less, or 500 nm or less, or 300 nm or less, or 100 nm or less, or
50 nm or less.
[0108] The structure can be a dot or line, and line can be straight
or curvilinear. Arbitrary shapes can be formed including rings,
squares, and triangles.
[0109] The structure can have a height which can be for example at
least about 5 nm, or at least about 10 nm, or at least about 15 nm,
or at least about 20 nm, or at least about 25 nm. The range can be
for example about 5 nm to about 100 nm, or about 10 nm to about 50
nm, or about 10 nm to about 25 nm.
[0110] Height can be used to detect the presence of nanomaterial.
For example, the structure can have a height which is at least two
times, twice, or at least three times, or at least four times, the
height compared to a structure substantially identical prepared
except without the nanomaterial.
[0111] The structure can comprise polymer and the nanomaterial, as
well as residual solvent or moisture. The polymer and the
nanomaterial can be substantially evenly distributed, or they can
phase separate.
[0112] The methods can be repeated to provide a plurality of
structures on the surface including for example array formation
comprising at least two, at least 50, at least 100, at least 500,
at least 1,000, or at least 50,000 structures on a single
surface.
Arrays
[0113] The method can be particularly useful for the preparation of
nanoarrays, arrays on the submicrometer scale having nanoscopic
features when used with DIP PEN.TM. nanolithographic printing.
Preferably, a plurality of dots or a plurality of lines are formed
on a substrate. The plurality of dots can be a lattice of dots
including hexagonal or square lattices as known in the art. The
plurality of lines can form a grid, including perpendicular and
parallel arrangements of the lines.
[0114] The lateral dimensions of the individual patterns including
dot diameters and the line widths can be, for example, about 2,000
or less, about 1,000 nm or less, about 500 nm or less, about 300 nm
or less, and more particularly about: 100 nm or less. The range in
dimension can be, for example, about 1 nm to about 750 nm, about 10
nm to about 2,000 nm, about 10 nm to about 500 nm, and more
particularly about 100 nm to about 350 nm.
[0115] The number of patterns in the plurality of patterns is not
particularly limited. It can be, for example, at least 10, at least
100, at least 1,000, at least 10,000, even at least 100,000. Square
arrangements are possible such as, for example, a 10.times.10
array. High density arrays can be preferred.
[0116] The distance between the individual patterns on the
nanoarray can vary and is not particularly limited. For example,
the patterns can be separated by distances of less than one micron
or more than one micron. The distance can be, for example, about
300 to about 1,500 microns, or about 500 microns to about 1,000
microns. Distance between separated patterns can be measured from
the center of the pattern such as the center of a dot or the middle
of a line.
[0117] The methods described herein can be repeated to provide a
plurality of structures on the surface which are separated from
each other by less than a micron.
[0118] The method can be also applied for forming patterns of
larger scales such as micron scale, millimeter scale or centimeter
scale. Such larger patterns can be prepared, for example, utilizing
microcontact printing for transporting the mixture comprising the
ink of choice and the ink carrier matrix from a microcontact
printing stamp to the substrate surface.
Arrays of Nano-Building Blocks
[0119] The method can be applied for patterning hard inks including
but not limited to metal nanoparticles, such as Au or Ag silver
nanoparticles; semiconductor nanoparticles, such as quantum dots;
oxide nanoparticles, such as silica or alumina particles; magnetic
particles; carbon-based particles, such as fullerenes and carbon
nanotubes, crystalline polymers including crystalline conducting
polymers. The method can be particularly useful for forming hard
ink arrays. Such hard ink arrays comprise a substrate and a
plurality of patterns that comprise a hard ink of choice and a ink
carrier matrix. When the hard ink of choice comprises carbon based
material such as fullerene, the hard ink array can serve as an
electronic device such as a transistor.
Bioarrays
[0120] The method can applied for patterning biomaterials such as
nucleic acids, proteins or oligo or polysaccharides. In this case,
the mixture comprises an ink that is a biomaterial of choice and an
ink carrier matrix which can be a polymer such as polyalkylene
oxide or polyalkylene imine.
[0121] In some embodiments, the biomolecule can comprise various
kinds of chemical structures comprising peptide bonds. These
include peptides, proteins, oligopeptides, and polypeptides, be
they simple or complex. The peptide unit can be in combination with
non-peptide units. The protein or peptide can contain a single
polypeptide chain or multiple polypeptide chains. Higher molecular
weight peptides are preferred in general although lower molecular
weight peptides including oligopeptides can be used. The number of
peptide bonds in the peptide can be, for example, at least three,
ten or less, at least 100, about 100 to about 300, or at least
500.
[0122] Proteins are particularly preferred. The protein can be
simple or conjugated. Examples of conjugated proteins include, but
are not limited to, nucleoproteins, lipoproteins, phosphoproteins,
metalloproteins and glycoproteins. Proteins can be functional when
they coexist in a complex with other proteins, polypeptides or
peptides. The protein can be a virus, which can be complexes of
proteins and nucleic acids, be they of the DNA or RNA types. The
protein can be a shell to larger structures such as spheres and rod
structures.
[0123] Proteins can be globular or fibrous in conformation. The
latter are generally tough materials that are typically insoluble
in water. They can comprise a polypeptide chain or chains arranged
in parallel as in, for example, a fiber. Examples include collagen
and elastin. Globular proteins are polypeptides that are tightly
folded into spherical or globular shapes and are mostly soluble in
aqueous systems. Many enzymes, for instance, are globular proteins,
as are antibodies, some hormones and transport proteins, like serum
albumin and hemoglobin.
[0124] Proteins can be used which have both fibrous and globular
properties, like myosin and fibrinogen, which are tough, rod-like
structures but are soluble. The proteins can possess more than one
polypeptide chain, and can be oligomeric proteins, their individual
components being called protomers. The oligomeric proteins usually
contain an even number of polypeptide chains, not normally
covalently linked to one another. Hemoglobin is an example of an
oligomeric protein.
Types of proteins that can be incorporated into a nanoarray of the
present invention include, but are not limited to, enzymes, storage
proteins, transport proteins, contractile proteins, protective
proteins, toxins, hormones and structural proteins. Examples of
enzymes include, but are not limited to ribonucleases, cytochrome
c, lysozymes, proteases, kinases, polymerases, exonucleases and
endonucleases. Enzymes and their binding mechanisms are disclosed,
for example, in Enzyme Structure and Mechanism, 2.sup.nd Ed., by
Alan Fersht, 1977 including in Chapter 15 the following enzyme
types: dehydrogenases, proteases, ribonucleases, staphyloccal
nucleases, lysozymes, carbonic anhydrases, and triosephosphate
isomerase. Examples of storage proteins include, but are not
limited to ovalbumin, casein, ferritin, gliadin, and zein.
[0125] Examples of transport proteins include, but are not limited
to hemoglobin, hemocyanin, myoglobin, serum albumin,
.beta.1-lipoprotein, iron-binding globulin, ceruloplasmin.
[0126] Examples of contractile proteins include, but are not
limited to myosin, actin, dynein.
[0127] Examples of protective proteins include, but are not limited
to antibodies, complement proteins, fibrinogen and thrombin.
[0128] Examples of toxins include, but are not limited to,
Clostridium botulinum toxin, diptheria toxin, snake venoms and
ricin.
[0129] Examples of hormones include, but are not limited to,
insulin, adrenocorticotrophic hormone and insulin-like growth
hormone, and growth hormone. Examples of structural proteins
include, but are not limited to, viral-coat proteins,
glycoproteins, membrane-structure proteins, .alpha.-keratin,
sclerotin, fibroin, collagen, elastin and mucoproteins.
[0130] Natural or synthetic peptides and proteins can be used.
Proteins can be used, for example, which are prepared by
recombinant methods.
Examples of preferred proteins include immunoglobulins, IgG
(rabbit, human, mouse, and the like), Protein A/G, fibrinogen,
fibronectin, lysozymes, streptavidin, avdin, ferritin, lectin (Con.
A), and BSA. Rabbit IgG and rabbit anti-IgG, bound in sandwich
configuration to IgG are useful examples. Spliceosomes and
ribozomes and the like can be used.
[0131] A wide variety of proteins are known to those of skill in
the art and can be used. See, for instance, Chapter 3, "Proteins
and their Biological Functions: A Survey," at pages 55-66 of
BIOCHEMISTRY by A. L. Lehninger, 1970, which is incorporated herein
by reference.
[0132] One of the advantages of the method is that it does not
require prepatterning of the substrate surface with a patterning
compound prior to transporting a mixture comprising the protein
from the tip to the surface when forming submicron size patterns,
i.e. patterns with features having a lateral dimension of less than
about 1 micron, or sub 100 nm patterns, i.e. patterns having a
lateral dimension of less than about 100 nm.
[0133] Patterning compounds were used by the prior art methods to
improve stability of protein containing submicron or sub 100 nm
features. Examples of patterning compounds include a
sulfur-containing compound such as, for example, a thiol,
polythiol, sulfide, cyclic disulfide, a sulfur-containing compound
having a sulfur group at one end and a terminal reactive group at
the other end, such as an alkane thiol with a carboxylic acid end
group. Additional patterning compounds are disclosed in US patent
publication 2003/0068446 published Apr. 10, 2003, to Mirkin et.
al.
[0134] Non-specific binding of proteins to the regions of the
substrate surface, can be prevented by covering, or "passivating,"
those regions of the substrate surface that were not exposed to the
mixture comprising the biomolecule and the ink carrier matrix with
one or more passivating compounds. Known passivating compounds can
be used and the invention is not particularly limited by this
feature to the extent that non-specific adsorption does not occur.
A variety of passivating compounds can be used including, for
example, surfactants such as alkylene glycols which are
functionalized to adsorb to the substrate. An example of a compound
useful for passivating is 11-mercaptoundecyl-tri(ethylene glycol).
Proteins can have a relatively weak affinity for surfaces coated
with 11-mercaptoundecyl-tri(ethylene glycol) and therefore do not
bind to such surfaces. See, for instance, Browning-Kelley et al.,
Langmuir 13, 343, 1997; Waud-Mesthrige et al., Langmuir 15, 8580,
1999; Waud-Mesthrige et al., Biophys. 1 80 1891, 2001; Kenseth et
al., Langmuir 17, 4105, 2001; Prime & Whitesides, Science 252,
1164, 1991; and Lopez et al., J. Am. Chem. Soc. 115, 10774, 1993,
which are hereby incorporated by reference. However, other
chemicals and compounds, such as bovine serum albumin (BSA) and
powdered milk, that can be used to cover a surface in similar
fashion to prevent non-specific binding of proteins to the
substrate surface. BSA, however, can provide less performance than
11-mercaptoundecyl-tri(ethylene glycol). After passivation, the
resultant array can be called a passivated array of proteins or
peptides.
[0135] After passivation, the matrix can be washed away from the
patterned regions on the surface. The use of polyalkylene oxide as
the matrix allows retaining the biological activity of the
biomaterial in the patterned regions upon washing away the
matrix.
[0136] One embodiment of making protein array according to the
method is illustrated in FIG. 8.
Applications
[0137] Biological, diagnostic, assays, sensors, semiconductor,
electronic, photomask repair, transistor fabrication and repair,
including field effect transistors, flat panel display fabrication
and repair, and magnetic applications can be benefited with use of
the various embodiments described herein.
[0138] Many applications of DPN printing are described in Ginger,
Zhang, and Mirkin, "The Evolution of Dip Pen Nanolithography,"
Angew. Chem. Int. Ed., 2004, 43, 30-45, which is hereby
incorporated by reference in its entirety.
[0139] Applications for microcontact printing are described in for
example Xia and Whitesides, "Soft Lithography," Angew. Chem. Int.
Ed., 1998, 37, 550-575, and references cited therein, which is
hereby incorporated by reference in its entirety. Biological
applications include assays, diagnostics, sensor, protein
microarrays, nucleic acid and DNA microarrays, nanoarrays, cell
adhesion and growth, and the like. Biodiagnostic applications are
described in for example Rose & Mirkin, "Nanostructures in
Biodiagnostics," Chem. Rev., 2005, 105, 1547-1562, which is hereby
incorporated by reference in its entirety. DNA microarrays are
described in DNA Microarrays, A Practical Approach, Ed. Schena,
1999, Oxford University Press. Applications for protein and peptide
nanoarrays are described in for example US Patent Publication No.
2003/0068446 to Mirkin et al., which is hereby incorporated by
reference in its entirety. For example, surfaces can be patterned
with compounds adapted for capturing a variety of proteins and
peptide structures.
[0140] Further assays can be developed including for example
testing for diseases such as HIV. See for example Lee et al,
"Nano-Immunoassays for Ultrahigh Sensitive/Selective Detection of
HIV," NanoLett. 2004, 4, 1869-1872, which is hereby incorporated by
reference in its entirety. This describes patterning of MHA, which
is then deprotonated so features are negatively charged. Monoclonal
antibodies to the HIV-1 p24 antigen are then immobilized on the MHA
and then exposed to plasma samples taken from infected patients.
Nanoparticle probes can be used to detect and amplify the
signal.
[0141] In these and other biological applications, surfaces can be
passivated to prevent non-specific binding including non-specific
protein binding. See also US Patent Publication No. 2005/0009206 to
Mirkin et al, which is hereby incorporated by reference in its
entirety.
[0142] In field effect transistor applications, sources, drains,
gates, electrodes, and channels can be fabricated by methods known
in the arts.
[0143] The invention is further illustrated by, though in no way
limited to, the following working examples.
WORKING EXAMPLES
1. Materials and Instrumentation
[0144] Polyethylene oxide (PEO, MW=100,000), polyethylene glycol
(PEG, MW=8,000), and polyethyleneimine (PEI, MW=2,000) were
purchased from Sigma-Aldrich (Milwaukee, Wis.). Au nanoparticles
(AuNP) solutions were obtained from Ted Pella (Redding, Calif.).
Magnetic nanoparticles (MNP) were synthesized.
[0145] Fullerene was purchased from Mer Corporation (Tucson,
Ariz.). Acetonitrile, dichloromethane, toluene were purchased from
Fisher Scientific (Fairlawn, N.J.). All chemicals were used as
received.
[0146] Si/SiO.sub.x wafer with 500 nm oxide coating layer were
purchased from WaferNet, Inc. (San Jose, Calif.). Gold substrates
were obtained by thermal evaporation of a gold thin film (30 nm) on
a Si/SiO.sub.x substrate pre-coated with a Ti adhesion layer (7
nm). GaAs and InAs wafers were purchased from Wafer World Inc.
(West Palm Beach, Fla.).
[0147] All DPN experiments were performed on a ThermoMicroscopes CP
AFM (Veeco Instruments Inc., CA), which was enclosed in a
humidity-controlled chamber and driven by commercially available
DPN software (NanoInk Inc., Chicago, Ill.). The humidity was
controlled at 70% for all PEO related experiments, and 50% for PEI
experiments. AFM probes (S-1 or S-2) were purchased from NanoInk
Inc., with spring constants of 0.041 N/m and 0.1 N/m, respectively.
MFM data were obtained with a DI multimode SPM (Veeco Instruments
Inc., CA), using a pre-magnetized AFM probe.
Preparation of Inks
[0148] For all DPN experiments, PEO and PEG solutions (16 mg/mL)
were made by dissolving PEO in acetonitrile, dichloromethane,
water, or toluene. To prepare the AuNP/PEO ink, PEO (16 mg/mL) in
acetonitrile was mixed with a AuNP solution at a volume ratio of
1:1 (2 nm AuNP), 2:1 (5 nm AuNP), and 4:1 (13 nm AuNP). To prepare
the 4.7 nm MNP/PEO solution, PEO (16 mg/mL) in dichloromethane was
mixed with a MNP solution at a volume ratio of 2:1. To prepare the
fullerene/PEO ink, PEO (16 mg/ml) in toluene was mixed with a
saturated fullerene solution in toluene at a volume ratio of 1:2.
To prepare the 2 nm AuNP/PEI ink, a 5% diluted PEI water solution
was mixed with a 2 nm AuNP solution at the volume ratio of 1:1.
2. Matrix-Assisted DPN of Nanobuilding Blocks
A. Polymer Only Controls
[0149] FIG. 2 shows control patterns of polyethylene glycol (PEG,
MW 8,000), polyethylene oxide (PEO, MW 100,000), and polyethylene
imine (PEI, MW 2000) created using DPN on several types of
substrates. In particular, FIG. 2A and FIG. 2B present topographic
AFM images of DPN-generated PEG patterns on Au (writing speed of
0.16 .mu.m/s) and GaAs (writing speed of 0.022 .mu.m/s),
respectively. FIG. 2C and FIG. 2D show DPN-generated PEO patterns
on SiO.sub.x and Au respectively with writing speed of 0.05 .mu.m/s
for both. FIG. 2E demonstrates direct patterning of PEI with
writing speeds of 0.6 and 0.3 .mu.m/s on an InAs substrate. The
corresponding height profile in FIG. 3A shows that different
writing speeds result in different pattern heights. The faster
writing speed (0.6 .mu.m/s) produces smaller height (1.75 nm),
while the slower writing speed (0.3 .mu.m/s) produces bigger height
(2.75 nm).
[0150] FIG. 2F demonstrates the ability of PEI to act as a carrier
matrix by presenting DPN patterns of a mixture of PEI and 2 nm Au
nanoparticles on an InAs substrate produced with writing speeds of
0.1 and 0.05 .mu.m/s. The corresponding height profiles in FIG. 3B
demonstrate that 0.1 .mu.m/s writing speed produces pattern having
height of 12 nm, while 0.05 .mu.m/s writing speed produces pattern
having height of 14 nm. Comparison of the height profiles
demonstrates that the pattern of the mixture containing 2 nm Au
nanoparticles is distinctly greater than that of PEI only. This
indicates the presence of Au nanoparticles in the patterns prepared
from the mixture containing Au nanoparticles.
B. Au Nanoparticles
[0151] The capability of these polymers to act as a carrier
matrices was demonstrated for common nanomaterials. Specifically,
FIG. 4 shows arrays of Au nanoparticles (AuNP) generated using
direct single-step patterning process. As a control, FIG. 4A shows
a topographic AFM image of dot arrays produced using PEO only, with
tip-substrate contact times of 64, 32, and 16 seconds from top to
bottom respectively. The feature heights of the obtained dot arrays
are 8.5, 3.3, and 1.7 nm for contact times of 64, 32, and 16
seconds respectively, see TABLE 1. FIG. 4A, FIG. 4B and and FIG. 4C
are topographic AFM images of DPN generated dot arrays of 2, 5, and
13 nm Au nanoparticles mixed with PEO respectively. TABLE 1 lists
the heights of these structures. Clearly, all of the nanoscale
features containing Au nanoparticles are much greater in height
than those of only PEO. The height increase is larger for patterns
containing nanoparticles of bigger diameters. In a similar manner,
a mixture of 5 nm Au nanoparticles and PEO was patterned on a
Transmission Electron Microscope (TEM) grid. The inset of FIG. 3E,
which is a TEM image of a DPN generated dot on the TEM grid,
demonstrates clusters of Au nanoparticles, which proves the
presence of Au nanoparticles in these patterns.
TABLE-US-00001 TABLE 1 Heights of DPN generated dot features, nm
AuNP/ AuNP/ AuNP/ Contact PEO MNP/ PEO PEO PEO C.sub.60/ time, s
only PEO 2 nm 5 nm 13 nm PEO 64 8.5 27.4 20.8 25.8 32.3 21.8 32 3.3
23.1 13.8 16.1 23.5 14.6 16 1.7 18.3 8.6 10.6 18.5 9.8
C. Magnetic Nanoparticles
[0152] Patterns of magnetic nanoparticles (MNP) were also created
using a matrix-assisted DPN. FIG. 5 features the patterns
containing 4.7 nm magnetic nanoparticles (MNP) prepared using PEO
as a carrier matrix. FIG. 5A and FIG. 5B are topography AFM images
of DPN-generated dot arrays with tip substrate contact of 64, 32,
and 16 sec from top to bottom, and diamond-shape line patterns at
writing speed of 0.05 .mu.m/s, respectively. Again, an obvious
height difference was observed when comparing the heights of these
patterns with those of pure PEO, see TABLE 1. The increased height
for patterns prepared from mixtures containing MNPs indicates the
MNPs are embedded in these patterns.
[0153] To further prove the presence of the MNPs inside patterns
prepared from a mixture containing MNPs, the patterns were further
characterized using Magnetic Force Microscopy (MFM), a technique
which shows clear contrast based on the magnetism of the sample. In
the MFM images in FIG. 5C and FIG. 5D, the patterned features
containing MNPs can be undoubtedly distinguished from the
non-magnetic bare SiO.sub.x substrate. This strong contrast even is
observed for a single feature, see insets in FIG. 5C and FIG. 5D
indicating that magnetic particles were evenly distributed
throughout the entire patterned feature. The MFM image of a single
line pattern, see inset in FIG. 5D shows magnetic clusters inside
the pattern. These kinds of clusters are not observed in patterns
of pure PEO. This observation indicates that these clusters are
pockets of MNPs. The large area patterns presented in FIG. 4
(C)-(D) also demonstrate that the matrix assisted DPN can provide
extended writing times as well as smooth and well-controlled ink
transfer rate.
D. Fullerenes
[0154] In addition to Au nanoparticles and magnetic nanoparticles,
DPN patterns of carbon-based nanomaterials (fullerenes) were also
generated using PEO as a carrier. The ability to pattern fullerenes
is particularly important due to their potential application in
nanoelectronics (71).
[0155] FIG. 6 shows DPN-generated nanoarrays of a mixture of
fullerene and PEO. FIG. 6A shows a dot array with tip-substrate
contact times of 16, 8, and 4 s (top to bottom). 80 nanometer
feature sizes were easily created at the 4 second contact time
(FIG. 6A), proving that sub-100 nm features can be obtained easily
using this technique. With contact times of 64, 32, and 16 s,
features of 21.8, 14.6 and 9.8 nm in height were produced, see
TABLE 1 and a topography AFM image and corresponding height profile
in FIG. 7A and FIG. 7B. Again, these heights are greatly increased
compared to those of the corresponding pure PEO patterns,
indicative of the presence of fullerenes in the DPN dot arrays
generated from the mixture containing fullerenes. These same trends
regarding height increases, see FIG. 7C, were observed for
continuous lines produced using the mixture of fullerene and PEO
(writing speeds=0.05, 0.1, and 0.2 .mu.m/s), see FIG. 6B.
[0156] As a proof-of-concept, as well as to further confirm that
fullerene molecules indeed are patterned in these DPN-generated
features, the first fullerene-based transistor was built via DPN.
Lines of the fullerene/PEO ink were generated across an
EBL-generated nanoelectrode with a gap size of 500 nm. The 3D
topographic AFM image in FIG. 6C clearly shows two crossed,
continuous lines wired across these gaps. Current-voltage (I-V)
measurements monitoring the output current of this device at
voltages ranging from -0.7 V to 0.85 V are shown in FIG. 6D. The
black line is a plot of the I-V response of the transistor measured
in a dark environment, while the red (gray) line shows the current
obtained under illumination with a Xe lamp (150 W). The observed
increase in current (.about.6 times more, .about.0.015 pA at 0.85 V
vs. .about.0.10 pA at 0.85 V) is a characteristic response of
fullerene molecules to light illumination (70, 72). Such a response
indicates that the photoactive fullerene molecules are present in
an active state inside the DPN-generated patterns. In addition, the
precise delivery of fullerene/PEO lines within the 500 nm gapped
nanoelectrode also demonstrates a high spatial resolution of
DPN.
3. Protein Nanoarrays
[0157] Nanoarrays of goat anti-chicken IgG Alexafluor 488 were
prepared by a matrix assisted DPN as illustrated in the general
scheme presented in FIG. 8. A low molecular weight polymer
(poly-ethylene glycol, MW=8000) was used as a matrix to transport
anti-chicken IgG AF 488 from the AFM tip to the substrate surface.
PEG is an excellent material to resist non-specific protein
adsorption on surfaces. The use of PEG as a matrix allows one to
wash away PEG after generating protein nanoarray to retain the
biological activity of the protein. DPN was performed at a relative
humidity of 75% and at 25.degree. C. Unmodified NanoInk type A tips
were dip coated with a mixture containing the antibody and PEG and
dried with nitrogen. FIG. 9A and FIG. 9B demonstrate AFM images of
generated nanoarrays of anti-chicken IgG Alexafluor 488 by MA-DPN
method on gold and silicon substrates, respectively. The
anti-chicken IgG Alexafluor 488 nanoarrays were further
characterized by fluorescence microscopy as shown FIG. 10.
[0158] The AFM and fluorescence images clearly indicate that one
can generate uniform nanoarrays of proteins using MA-DPN. The
matrix encapsulated proteins are shown to be biologically active as
indicated by our results with microarrays generated by microcontact
printing.
ADDITIONAL EXAMPLES
[0159] A significant application of this universal ink is the
capability of simultaneous patterning of multiple biomolecules, and
the retaining of their bioactivities. As stated previously, each
ink has its own diffusion rate, which makes it extremely difficult
(if possible) for simultaneous patterning of multiple inks, and
further for feature size control via the tip-substrate contact
time. FIG. 11A shows the ink diffusion rate of PEG as well as four
biomolecules in PBS buffer. One can easily see that the ink
diffusion rate varies dramatically according to different ink
materials selected, which will sequentially become a major issue if
we anticipate very similar or identical feature size during
simultaneous multiple ink patterning. For example, the slope of
pure IgG can be as high as 30.81, while that of anti-ubiquitin is
only 11.30, which means at the same tip-substrate contact time (4
sec), the generated dot size will be 439.0 nm for
.beta.-galactosidase and 144.7 nm for BSA, which indeed varies a
lot. What is more, the different slopes also means that the
increase trend of the dot size is also different.
[0160] However, using the universal ink where PEG works as an ink
carrier, the ink diffusion rate can be easily tuned within a
certain range. In order to prove this point, we have monitored the
ink diffusion rate change of the mixture of anti-ubiquitin/PEG at
different ratios (FIG. 11B). At anti-ubiquitin:PEG ratio of 1:2,
the diffusion rate of the mixed ink jumps to 28.72 from 11.30, and
it further increases to 29.41 at the ratio of 1:5. Plots in FIGS.
11C and 11D not only give more examples of such capability PEG has,
but also show that the diffusion rate of each individual ink can be
tuned within certain range, and what is more, we can make two
different inks have very similar diffusion rate. This is an
important parameter that facilitates the precise control of each
ink's final feature size and the sequential size increase trend
after multiple-ink DPN patterning since the tip-substrate contact
time will always be the same (as the AFM probe array we used is a
passive mode). Except the ink carrier capability, another important
role PEG plays in the universal ink kit is its ability to tune the
ink's diffusion rate.
[0161] One then used one dimensional AFM tip array (Model No.:
A-26, NanoInk Inc., Skokie, Ill.) for simultaneous multiple ink
patterning via DPN. Two composite inks containing fluorescent
labeled BSA (green color) and anti-ubiquitin (red color), were
coated in every other AFM probes, respectively, using the inkwell
(NanoInk Inc., Skokie, Ill.) that specially designed for such
purposes. Both the optical microscopy images of the inkwell we used
and the AFM tip arrays before and after ink-coating are shown in
FIG. 13. The diffusion rates of the two inks were intentionally
tuned very similar following the ratio of 1:5 for both BSA:PEG and
anti-ubiquitin:PEG shown in FIG. 11C. DPN was done under the same
experimental conditions as described in FIG. 11C. The fluorescent
images in FIG. 12A clearly proved that two different kinds of
biomolecules (BSA in green and anti-ubiquitin in red) were
simultaneously patterned into designed array. The zoomed-in image
in FIG. 12B shows more details and clear contrast of the
fluorescent signal. In order to compare the variation of generated
pattern sizes, one took AFM images after DPN experiment to
characterize the generated dot sizes. As a representative, at
tip-substrate contact time of 32 sec, the average dot diameter is
328.3 nm for BSA and 306.1 nm for anti-ubiquitin, which has only
less than 7% variation (AFM images not shown). On the other side,
the generated dot sizes would be 284.3 nm and 223.1 nm if not mixed
with PEG based on the plots shown in FIG. 11A.
[0162] To further prove the bioactivities of the patterned
biomolecules, we first generated IgG and .beta.-galactosidase
patterns individually. FIGS. 12C and 12E are AFM images of
generated IgG and .beta.-galactosidase dot arrays at tip-substrate
contact time of 32 sec. The average dot diameter is 347.2 nm for
IgG and 380.3 nm for .beta.-galactosidase, which has around 8%
variation. Similarly, the generated biomolecular dot sizes would be
251.0 nm and 439.1 nm, respectively, if without PEG according to
FIG. 11A.
[0163] One then incubated the biomolecular arrays into according
antibody buffer solution. The according fluorescent images in FIGS.
12D and 12F indicate that both anti-IgG (green) and
anti-.beta.-galactosidase (red) can successfully bind on the
pre-generated dot arrays of antigen molecules, which means the
patterned IgG and .beta.-galactosidase still remain their
bioactivities.
[0164] All of the publications, patent applications and patents
cited in this specification are incorporated herein by reference in
their entirety.
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