U.S. patent application number 12/001564 was filed with the patent office on 2008-05-22 for molded waveguides.
This patent application is currently assigned to President and Fellows of Harvard College. Invention is credited to Rebecca J. Jackman, Enoch Kim, Christian Marzolin, Milan Mrksich, Mara G. Prentiss, Stephen P. Smith, George M. Whitesides, Younan Xia, Xiao-Mei Zhao.
Application Number | 20080116608 12/001564 |
Document ID | / |
Family ID | 26724198 |
Filed Date | 2008-05-22 |
United States Patent
Application |
20080116608 |
Kind Code |
A1 |
Kim; Enoch ; et al. |
May 22, 2008 |
Molded waveguides
Abstract
Chemically or biochemically active agents or other species are
patterned on a substrate surface by providing a micromold having a
contoured surface and forming, on a substrate surface, a chemically
or biochemically active agent or fluid precursor of a structure. A
chemically or biochemically active agent or fluid precursor also
can be transferred from indentations in an applicator to a
substrate surface. The substrate surface can be planar or
non-planar. Fluid precursors of polymeric structures, inorganic
ceramics and salts, and the like can be used to form patterned
polymeric articles, inorganic salts and ceramics, reactive ion etch
masks, etc. at the surface. The articles can be formed in a pattern
including a portion having a lateral dimension of less than about 1
millimeter or smaller. The indentation pattern of the applicator
can be used to transfer separate, distinct chemically or
biochemically active agents or fluid precursors to separate,
isolated regions of a substrate surface. Waveguide arrays,
combinatorial chemical or biochemical libraris, etc. can be made.
Differences in refractive index of waveguide and cladding can be
created by subjecting the waveguide and cladding, made of identical
prepolymeric material, to different polymerization or cross-linking
conditions. Interferometers are defined by coupling arrays of
waveguides, where coupling can be controlled by altering the
difference in refractive index between cladding and waveguide at
any desired location of the array. Alteration and refractive index
can be created photochemically, chemically, or the like. Sensors
also are disclosed, including biochemical sensors.
Inventors: |
Kim; Enoch; (Boston, MA)
; Xia; Younan; (Seattle, WA) ; Mrksich; Milan;
(Chicago, IL) ; Jackman; Rebecca J.; (Boston,
MA) ; Zhao; Xiao-Mei; (Pepper Pike, OH) ;
Smith; Stephen P.; (Medford, MA) ; Prentiss; Mara
G.; (Belmont, MA) ; Whitesides; George M.;
(Newton, MA) ; Marzolin; Christian; (Paris,
FR) |
Correspondence
Address: |
WOLF GREENFIELD & SACKS, P.C.
600 ATLANTIC AVENUE
BOSTON
MA
02210-2206
US
|
Assignee: |
President and Fellows of Harvard
College
Cambridge
MA
02138
|
Family ID: |
26724198 |
Appl. No.: |
12/001564 |
Filed: |
December 12, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10677103 |
Oct 1, 2003 |
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12001564 |
Dec 12, 2007 |
|
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09634201 |
Aug 9, 2000 |
6660192 |
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10677103 |
Oct 1, 2003 |
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09004583 |
Jan 8, 1998 |
6355198 |
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09634201 |
Aug 9, 2000 |
|
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08616929 |
Mar 15, 1996 |
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09004583 |
Jan 8, 1998 |
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60046689 |
May 16, 1997 |
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Current U.S.
Class: |
264/259 |
Current CPC
Class: |
B01J 2219/00382
20130101; B01J 2219/00466 20130101; B29D 11/00663 20130101; H05K
3/061 20130101; A61K 47/6957 20170801; B01J 2219/00416 20130101;
B01J 2219/0043 20130101; B29C 33/42 20130101; B29D 11/00346
20130101; B29C 37/0053 20130101; B01J 2219/00713 20130101; B81C
1/00031 20130101; B81C 99/0085 20130101; B01J 2219/0061 20130101;
H05K 3/0079 20130101; B29C 31/04 20130101; G02B 6/138 20130101;
G01N 21/7703 20130101; B01J 2219/0063 20130101; G01N 2021/7776
20130101; B29C 43/021 20130101; B01J 2219/00648 20130101; B01J
19/0046 20130101; B29K 2105/0002 20130101; B81C 1/00206 20130101;
B82Y 30/00 20130101; B81C 2201/034 20130101; B01J 2219/00659
20130101; B01J 2219/00612 20130101; B01J 2219/00605 20130101; B01J
2219/00619 20130101; B01J 2219/00626 20130101; C40B 60/14 20130101;
B81B 2201/0214 20130101; B01J 2219/00637 20130101; B29C 39/24
20130101; B29L 2011/0016 20130101; B29C 67/246 20130101 |
Class at
Publication: |
264/259 |
International
Class: |
B29C 45/16 20060101
B29C045/16 |
Goverment Interests
STATEMENT AS TO POTENTIAL RIGHTS UNDER FEDERALLY SPONSORED RESEARCH
AND DEVELOPMENT
[0002] Research leading to the invention disclosed and claimed
herein was supported in part by the Office of Naval Research, ONR
Contract No. N00014-93-I-0498, and by the National Science
Foundation, NSF Grant No. PHY 9312572. The U.S. Government has
certain rights to the invention.
Claims
1-67. (canceled)
68. A method comprising: providing an article having a contoured
surface including at least one indentation defining a pattern;
forming at a first region proximate a substrate surface, in a
pattern corresponding to the indentation pattern, a fluid precursor
of a reactive ion etch mask; and allowing the fluid precursor to
harden to form a reactive ion etch mask at the first region of the
substrate surface while leaving a second region proximate the
substrate surface, contiguous with the first region, free of the
species.
69. A method as in claim 68, involving allowing the fluid precursor
to harden to form a reactive ion etch mask at the first region of
the substrate surface in a pattern corresponding to the indentation
pattern and in an area including a portion having a lateral
dimension of less than about 1 mm.
70. A method as in claim 68, comprising forming the fluid precursor
in the pattern on the surface by providing an amount of the fluid
precursor on the substrate surface and pressing the contoured
surface of the article into the precursor against the substrate
surface.
71. A method as in claim 68, further comprising exposing the
substrate to reactive ion etch conditions and allowing at least a
portion of the substrate surface at the second region to be etched
by reactive ion etching.
72. A method as in claim 68, wherein the surface is nonplanar.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 10/677,103, filed Oct. 1, 2003, which is a divisional of
U.S. patent application Ser. No. 09/634,201, filed Aug. 9, 2000
(now U.S. Pat. No. 6,660,192); which is a divisional of U.S. patent
application Ser. No. 09/004,583, filed Jan. 8, 1998 (now U.S. Pat.
No. 6,355,198); which is a continuation-in-part of U.S. application
Ser. No. 08/616,929, filed Mar. 15, 1996 (abandoned); Ser. No.
09/004,583 also claim priority under 35 U.S.C. .sctn.119(e) of the
benefit of co-pending U.S. provisional application Ser. No.
60/046,689 filed May 16, 1997, all of which are incorporated herein
by reference.
FIELD OF THE INVENTION
[0003] The present invention relates generally to microprocesses at
surfaces, and more particularly to the formation of micropatterned
articles such as waveguides, sensors, and switches on substrates
from fluid precursors, and mechanisms for micro-scale positioning
of biologically active agents at predetermined regions of a
surface.
BACKGROUND OF THE INVENTION
[0004] In the fields of chemistry, biology, materials science,
microelectronics, and optics, the development of devices that are
small relative to the state of the art and conveniently and
relatively inexpensively reproduced is important.
[0005] A well-known method of production of devices, especially in
the area of microelectronics, is photolithography. According to
this technique, a negative or positive resist (photoresist) is
coated onto an exposed surface of an article. The resist then is
irradiated in a predetermined pattern, and portions of the resist
that are irradiated (positive resist) or nonirradiated (negative
resist) are removed from the surface to produce a predetermined
pattern of resist on the surface. This is followed by one or more
procedures. According to one, the resist may serve as a mask in an
etching process in which areas of the material not covered by the
resist are chemically removed, followed by removal of resist to
expose a predetermined pattern of a conducting, insulating, or
semiconducting material. According to another, the patterned
surface is exposed to a plating medium or to metal deposition (for
example under vacuum) followed by removal of resist, resulting in a
predetermined plated pattern on the surface of the material. In
addition to photolithography, x-ray and electron-beam lithography
have found analogous use.
[0006] In an article entitled "Materials for Optical Data Storage",
by Emmelius, et al., Angewandte Chemie, Int. Ed. (English), 28, 11,
1445-1600 (November, 1989), a review of methods of making CD/ROM,
WORM, and EDRAW optical storage disks is presented. According to
one method, photolithography is used to create a pattern of
protrusions on a surface that can serve as a master for fabrication
of articles that have a surface including a series of ridges and
protrusions complementary to the photolithographically-produced
master. These articles, including microridges and grooves at one
surface, can be combined with other materials in a layered
structure to form an optical storage device. An article in the
Phillips Technical Review, volume 40, number 10 (1982), entitled
"Manufacture of LaserVision Video Disks by a Photopolymerization
Process", by Haverkorn, et al., discusses similar technology. U.S.
Pat. No. 5,170,461 (Yoon, et al.), U.S. Pat. No. 4,959,252
(Bonnebat, et al.) and U.S. Pat. No. 5,141,785 (Yoshinada, et al.)
describe optical elements such as waveguides and optical recording
media. Yoshinada, et al. describe a process involving coating a
substrate with a polymer or prepolymer, pressing a contoured stamp
into the polymer or prepolymer to create a contoured pattern in a
surface of the polymer or prepolymer complementary to the contoured
surface of the stamp, removing the stamp, and adding a reflective
layer to the contoured surface of the polymer or prepolymer for use
as an optical device.
[0007] Photolithographic techniques for fabricating surfaces with
positional control of chemical functionalities at submicron
resolution is described in an article entitled "Patterning of
Self-Assembled Films Using Lithographic Exposure Tools", by
Dressick, et al., Jpn. J. Appl. Phys., 32, 5829-5839 (December,
1993). The technique involves exposure of a self-assembled film to
deep UV irradiation through a mask. According to one technique,
photochemical cleavage of an organic group occurs in exposed
regions followed by chemical reactivity selectively at those
regions.
[0008] Photolithography has found application in the biological
arena as well. Sundberg, et al. describe a method for patterning
receptors, antibodies, and other macromolecules at precise
locations on solid substrates using photolithographic techniques in
combination with avidin or streptavidin/biotin interaction in an
article entitled "Spatially-Addressable Immobilization of
Macromolecules on Solid Supports", J. Am. Chem. Soc., 117,
12050-12057 (1995).
[0009] Reactive ion etching is a process that is useful in the
semiconductor industry and other arenas for forming very small
structures having a very high aspect ratio (a very high
height/width ratio of features). Reactive ion etching is a dry
process in which a gas is accelerated towards a surface to effect
etching, in contrast to wet etching processes in which a liquid is
simply allowed to contact certain regions of a surface and to
chemically react at those regions. In wet etching processes,
etching typically takes place not only in a direction perpendicular
to the surface, but horizontally, as well. That is, with wet
etching it can be difficult to etch relatively precise, vertical
channels in a surface. Instead, the sidewalls of the channel are
etched horizontally also. Reactive ion etching provides an
advantageous alternative for etching channels with good,
near-vertical sidewalls.
[0010] Reactive ion etching masks should have certain
characteristics such as good hardness, inertness to the etchent
species, and in many cases electrical insulating properties. Thus,
materials suitable for reactive ion etching masks are limited. Many
metal masks, such as gold masks, are unsuitable since the metals
can sputter easily. Polymeric masks typically degrade under
reactive ion etching conditions. A typical prior art reactive ion
etching mask is made of silica and is formed by creating a layer of
silica on a surface and etching the layer selectively to create a
silica mask, using photolithography. Such procedures can be costly.
In an article entitled "Poly(siloxane)-based Chemically Amplified
Resist Convertable into Silica Glass", by Ito, et al., Jpn. J.
Appl. Phys., 32, 6052-6058 (1993), a poly(siloxane)-based
chemically amplified resist is reported. A polymeric glass
precursor is converted into silicate glass through a lithographic
procedure.
[0011] Waveguides are generally defined by a core, surrounded by a
cladding, that acts as a guide of electromagnetic radiation. The
waveguide can propagate radiation via total internal reflection of
the radiation within the core. Waveguides have served as important
components of sensors and switches, and have been fabricated from a
variety of materials including inorganic materials such as glasses
and organic materials such as polymers. Polymeric waveguides have
been fabricated using reactive ion etching, ultraviolet (UV) laser
and electron-beam writing, induced dopant diffusion during
polymerization (photo-locking and selective polymerization),
selective poling of electro-optically active molecules induced by
an electric field, and polymerization of self-assembled
prepolymers. One common technique for forming polymeric waveguides
is injection molding. For example, voids in a cladding material (or
substrate) can be filled, via injection molding, with a core
material. However, problems associated with this technique include
softening and deformation of the cladding or substrate under
temperatures required for injection molding. Fabrication with
precision is compromised, typically. In an additional prior art
technique, a polymeric film is spun onto a substrate and portions
of the film are subsequently exposed to light by a
photolithographic process, thereby changing the refractive index of
a polymeric film and creating a waveguide in the film. This
technique requires expensive and complicated photolithographic
systems for base formation of the waveguide array, and subsequent
multi-step processing is required such as removal of the polymeric
film from the substrate, lamination processing, curing processing,
and other processing steps.
[0012] U.S. Pat. No. 5,136,678 (Yoshimura) describe fabrication of
an optical waveguide array by providing a clad substrate having a
number of grooves arranged in lines on a surface of the substrate,
the substrate being resistant to a UV-curable resin. A UV-curable
resin is used to fill the grooves in the substrate and is UV cured
to form a core material, and a covering clad portion is formed over
the structure of a material that is the same as or close to the
material used as the substrate "cladding".
[0013] U.S. Pat. No. 5,313,545 (Kuo, et al.) describes a technique
in which a two-part mold made of stainless steel, aluminum,
ceramic, or the like is used to mold a polymeric waveguide core
material via injection molding. The mold is opened via removal of
the two portions, and the waveguide is placed in a second mold into
which is injected a cladding material. Kuo, et al. report that a
post-mold curing process is sometimes needed to maximize optical
and physical qualities of core regions, support apparatus, and end
portions.
[0014] U.S. Pat. No. 5,390,275 (Lebby, et al.) describe a method
for manufacturing a molded waveguide. A first cladding layer is
provided, and channels are formed in the first cladding layer. The
channels in the first cladding layer are filled with an optically
transparent polymer, and a second cladding layer is subsequently
affixed over the channels thereby enclosing them.
[0015] U.S. Pat. No. 5,481,633 (Mayer) describes vertical coupling
structures in which waveguide patterns include sections that lie in
close proximity with other sections, for example one directly above
another, such that the distance between coupling portions is very
small and coupling between different guides can occur.
[0016] Biological and chemical interactions can be studied on the
micro scale using combinatorial chemistry. This technique, as
described in Chemical & Engineering News, 74, 7, 28-73 (Feb.
12, 1996), involves formation of different biological or chemical
species in a grid pattern on a surface and used, for example, to
screen compounds for potential biological or chemical activity. An
article entitled "Combinatorial Chemistry-Applications of
Light-Directed Chemical Synthesis", by Jacobs, et al., Trends in
Biotechnology, 12, 19-26 (January, 1994) describes a
photolithographic process used in a spatially-addressable synthesis
technique for forming a combinatorial library involving
photolithography. A surface is derivatized with amine linkers that
are blocked by a photochemically cleavable protecting group. The
surface is selectively irradiated to liberate free amines that can
be coupled to photochemically blocked building blocks. The process
is repeated with different regions of the surface being exposed to
light and involved in synthesis until a desired array of different
compounds, in a grid pattern on the surface, is prepared. Each of
these compounds then is assayed simultaneously for binding or
activity. Binding "hits" can be identified by the particular
location at which binding on the surface occurs.
[0017] While the above techniques represent, in some cases, useful
advances in the art, many of these techniques require relatively
sophisticated apparatus, are expensive, and generally consume more
reactants and produce more by-products in collateral fabrication
steps than is optimal, and/or lack optimal versatility in
application. It is an object of the present invention to provide a
variety of techniques for modifying a surface chemically and/or
biologically at the micro and nanoscale, and to form very small
scale structures, including waveguides and masks for etching
processes conveniently, inexpensively, and reproducibly.
SUMMARY OF THE INVENTION
[0018] The present invention provides techniques for derivatizing
surfaces, biologically, chemically, or physically, according to
predetermined patterns. The derivatized surfaces find a variety of
uses in a variety of technical areas, or a structure formed on the
surface can be removed from the surface and find utility separate
from the surface. The invention involves, according to one
technique, a method for creating a pattern of a species at a
defined region proximate a substrate surface. The method involves
providing an article having a contoured surface including at least
one indentation defining a pattern and forming at a first region
proximate the substrate surface, in a pattern corresponding to the
indentation pattern, a fluid precursor of the species. The fluid
precursor is allowed to harden at the first region of the substrate
surface in a pattern corresponding to the indentation pattern and
in an area including a portion having a lateral dimension of less
than about 1 mm. A second region proximate the substrate surface,
contiguous with the first region, remains free of the species.
[0019] The invention also provides a method of promoting a chemical
reaction at a defined region proximate a substrate surface. The
method involves positioning an article proximate a substrate
surface and applying, to a first region proximate the substrate
surface via capillary action involving the article, a chemically
active agent. A chemical reaction involving the chemically active
agent then is allowed to take place at the first region proximate
the substrate surface.
[0020] The invention also provides a method of promoting a chemical
reaction at a defined region proximate a substrate surface that
involves providing an article having a contoured surface including
at least one indentation defining a pattern, forming at a first
region proximate the substrate surface, in a pattern corresponding
to the indentation pattern, a chemically active agent, and allowing
a chemical reaction to take place proximate the first region of the
substrate surface. The chemical reaction takes place in a pattern
corresponding to the indentation pattern and in an area including a
portion having a lateral dimension of less than about 1 mm. A
second region proximate the substrate surface, contiguous with the
first region, remains free of the reaction.
[0021] The invention also provides a method of applying a
biochemically active agent to a region proximate a substrate
surface. An article having a contoured surface, as described above,
is used to form, at a first region proximate the substrate surface
and in a pattern corresponding to the indentation pattern, a
pattern of the biochemically active agent. The method can further
involve allowing a biochemical interaction involving the
biochemically active agent to take place proximate the first region
of the substrate surface in a pattern corresponding to the
indentation pattern. The first region can be defined by an area
having a lateral dimension of less than about 1 mm, and a second
region proximate the substrate surface, contiguous with the first
region, can be left free of the biochemical interaction. The
biochemically active agent can be a biological binding partner that
can be used in subsequent binding with other agents.
[0022] The invention also provides a method of creating a pattern
of a species proximate a substrate surface that includes
positioning a forming article proximate a substrate surface and
applying, to a first region proximate the substrate surface via
capillary action involving the article, a fluid precursor of the
species. The fluid precursor is allowed to harden and the forming
article is removed from the substrate surface.
[0023] The invention also provides a method of promoting a chemical
reaction at a defined region proximate a substrate surface. The
method involves transferring a chemically active agent from an
applicator having a contoured surface including at least one
indentation defining an application pattern to a first region
proximate a substrate surface in a pattern corresponding to the
indentation pattern. A second region proximate the surface,
contiguous with the first region, is allowed to remain free of the
chemically active agent. A chemical reaction involving the
chemically active agent can take place at the first region.
[0024] The invention also provides a method of promoting a
biochemical interaction at a defined region proximate a substrate
surface that involves transferring a biochemically active agent
from an applicator having a contoured surface including at least
one indentation defining an application pattern to a first region
proximate a substrate surface in a pattern corresponding to the
application pattern. A second region proximate the surface,
contiguous with the first region, can remain free of the
biochemically active agent. A biochemical interaction involving the
biochemically active agent can be allowed to take place at the
first region.
[0025] The invention also provides a method of applying to a
substrate surface a biochemically active agent that involves
positioning an article proximate a substrate surface and applying,
to a first region proximate the substrate surface via capillary
action involving the article, a biochemically active agent. A
biochemical interaction involving the biochemically active agent is
allowed to take place at the first region.
[0026] The invention also provides a method for applying
essentially instantaneously to a first and a second region
proximate a substrate surface separated from each other by an
intervening region, distinct first and second chemically active
agents, respectively. The intervening region is left essentially
free of the chemically active agent. The method can involve
allowing a chemical reaction involving at least one chemically
active agent to subsequently take place proximate the first or
second region. The method also can involve applying essentially
instantaneously to the first and second regions distinct first and
second biochemically active agents while leaving the intervening
region free of the biochemically active agent.
[0027] The invention also provides a method involving applying
essentially instantaneously to a first and a second region
proximate a substrate surface distinct first and second
biochemically active agents, respectively. The first and second
regions are separated from each other by an intervening region that
remains free of biochemically active agent. The method can be
carried out as well with first and second biochemically active
agents that are the same.
[0028] The invention also provides a method involving applying a
first reactant to a first region proximate a surface and allowing a
first reaction to take place at the first region. A second reactant
then is applied to a second region proximate the surface that is
different from the first region but that includes a portion
intersecting the first region. The first region is blocked except
at the intersecting region during this step, thereby preventing the
first reactant from contacting the first region except at the
intersecting portion. A second reaction is allowed to take place at
the second region, thereby creating a first chemical characteristic
at the first region except at the intersecting portion, a second
chemical characteristic at the second region except at the
intersecting portion, and a third chemical characteristic at the
intersecting portion.
[0029] The invention also provides a method of establishing a first
chemical functionality at a first region proximate a substrate
surface and a different chemical functionality at a second region
proximate the substrate surface contiguous with the first region.
The method involves applying to the first region proximate the
substrate surface a deprotecting species to chemically deprotect
the first region of the substrate surface and thereby render it
chemically reactive, while leaving the second region free of
deprotection. Alternatively, the technique can involve transferring
to the second region of the substrate surface a chemical protecting
species. The method further involves exposing the substrate surface
to a chemically or biochemically reactive species that reacts at
the first region proximate the substrate surface and does not react
at the second region. The technique can be used to create a
combinatorial library via a series of deprotecting/reacting,
re-protecting steps or protecting/reacting/deprotecting steps.
Transfer of protecting or deprotecting species to the surface can
take place essentially instantaneously.
[0030] The invention also provides a method of creating, on a
substrate surface, a patterned, self-assembled monolayer, involving
transferring a self-assembled monolayer-forming species from an
applicator having a contoured surface including at least one
indentation defining an application pattern to a first region
proximate the substrate surface. A self-assembled monolayer
proximate the first region is thereby formed corresponding to the
indentation pattern. A second region proximate the surface,
contiguous with the first region, remains free of the
self-assembled monolayer.
[0031] The invention also provides a method involving providing a
surface carrying a plurality of chelating agents distributed evenly
thereacross and applying to two discrete regions of the surface a
metal ion that is coordinated by the chelating agent, while leaving
a region intervening the two discrete regions free of the metal
ion, thereby creating two discrete regions carrying chelating
agents coordinating metal ions.
[0032] The invention also provides a method involving providing a
surface carrying an essentially even distribution thereacross of
chelating agents coordinating metal ions, and applying to two
discrete regions at the surface a biologically active agent, while
leaving a region intervening the two discrete regions free of the
biologically active agent.
[0033] The invention also provides an article defined by a
substrate having a surface and a self-assembled monolayer on the
surface. The monolayer is formed of at least a first species having
a formula X--R-Ch-M, wherein X represents a functional group and R
represents a spacer moiety that, together, are able to promote
formation at the surface of a self-assembled monolayer. Ch
represents a chelating agent that coordinates a metal ion. M
represents a metal ion coordinated to the chelating agent. The
article further includes a pattern of biological agent coordinated
to metal ion at a first region proximate the surface. A second
region proximate the surface, contiguous with the first region,
remains free of biological agent coordinated to metal ion.
[0034] The invention also provides a method of creating a
patterned, self-assembled monolayer on a substrate surface. The
method involves transferring a self-assembled monolayer-forming
species from an applicator having a contoured surface including at
least one indentation defining an application pattern to a first
region proximate a substrate surface. A self-assembled monolayer is
thereby formed proximate the first region of the substrate surface
corresponding to the indentation pattern. A second region proximate
the surface, contiguous with the first region, is left free of
self-assembled monolayer. The self-assembled monolayer can be
transferred essentially instantaneously to the first region
proximate the substrate surface in this manner.
[0035] The invention also provides a method for providing a surface
carrying a plurality of chelating agents distributed evenly
thereacross and applying to two discrete regions at the surface a
metal ion that is coordinated by the chelating agent. A region
intervening the two discrete regions is left free of metal ion.
[0036] The invention also provides a method involving providing a
surface that carries, essentially evenly distributed thereacross,
chelating agents coordinating metal ions. A biochemically active
agent is applied to two discrete regions at the surface and a
region intervening the two discrete regions remains free of the
biochemically active agent.
[0037] The invention also provides an article including a surface
and a pathway proximate the surface delineating a pattern at a
first region proximate the surface. The pattern includes at least
one region defining a continuous essentially linear portion of
product formed proximate the surface. The product is formed in this
manner via reaction involving a chemically active agent promoting
the reaction that had been transferred proximate the surface from
an applicator. The linear portion of the product has a dimension
parallel to the surface of less than about one millimeter.
[0038] The invention also provides an article as described above,
where the pattern is defined by a plurality of microbeads assembled
at the surface. Any patterns formed in this manner can have at
least one section having a dimension parallel to the surface of
less than about one millimeter.
[0039] The fluid precursors, chemically active agents,
biochemically active agents, and carriers can be any of a variety
of species including prepolymeric species, biological binding
partners, inorganic salts, ceramics, metals, catalysts, colloidal
activating agents, and the like.
[0040] A variety of combinations of the above-described inventive
methods can be carried out, for example formation of a pattern can
be carried out via capillary action, instantaneous transfer can
take place to form a pattern on a surface having a lateral
dimension of less than about 1 mm, and the like. Articles formed by
the methods above, or by any combination of these methods, and
articles formed by other methods are included. The methods can be
carried out on essentially planar or non-planar surfaces.
BRIEF DESCRIPTION OF THE DRAWINGS
[0041] FIG. 1 illustrates schematically an arrangement for
derivatizing a surface in a predetermined pattern according to one
embodiment of the invention;
[0042] FIG. 2 is a schematic illustration of a technique for
transferring a chemically or biochemically active agent or fluid
precursor of an article from essentially linear indentations of an
applicator defining an indentation pattern to a substrate surface
in a pattern corresponding to the indentation pattern;
[0043] FIGS. 3a-3d are photocopies of scanning electron micrographs
(SEMs) of patterned polymeric structures formed from hardenable
fluid precursors in which the patterned structures remain at the
surface (FIGS. 3a-c) or are removed from the surface to form a
free-standing structure (FIG. 3d);
[0044] FIGS. 4a-4h are photocopies of SEM images of inorganic and
organic microstructures patterned on surfaces in accordance with
the invention;
[0045] FIG. 5 is a photocopy of an electron micrograph of
microspheres assembled in a predetermined pattern proximate a
substrate surface from a fluid precursor in accordance with the
invention;
[0046] FIGS. 6a-6c are photocopies of SEM images of metallic
microstructures formed proximate predetermined regions of a
substrate surface in accordance with the invention;
[0047] FIGS. 7a-7c are photocopies of SEM images of a substrate
surface derivatized in a pattern with resist followed by
lithography to etch the substrate surface in a pattern
complementary to the resist pattern;
[0048] FIG. 8 illustrates schematically the formation of a
free-standing article from a fluid precursor, using a substrate
surface and a forming article including a pattern of indentations
in accordance with the invention;
[0049] FIGS. 9a-9d are photocopies of SEM images of a free-standing
article prepared in accordance with the technique schematically
illustrated in FIG. 8 and use of that article as a mask adjacent a
substrate surface in vapor deposition of metal (FIG. 9b) or
creation of a secondary resist formed by a self-assembled monolayer
deposited in a pattern complementary to that of the mask, followed
by removal of the mask and vapor deposition of metal in a pattern
complementary to the secondary resist pattern (FIGS. 9c-d);
[0050] FIGS. 10a-10c illustrate schematically (FIG. 10a), and via
photoreproduction of optical micrographs (FIG. 10b, c), a process
involving derivatizing a surface with resist via micromolding, a
mask so produced, and a substrate surface etched selectively at
regions not covered by the mask;
[0051] FIG. 11 illustrates schematically a technique for transfer
of a chemically or biochemically active agent or a fluid precursor
of an article from an applicator having a discontinuous indentation
pattern to regions proximate a substrate surface in a pattern
corresponding to the indentation pattern;
[0052] FIG. 12 illustrates schematically the transfer, from an
article including an indentation pattern, of a chemically or
biochemically active agent or other fluid species to a nonplanar
substrate surface in a pattern corresponding to the indentation
pattern;
[0053] FIG. 13 illustrates schematically a multi-layered article
formed using successive micromolding techniques of the invention
that can serve as a waveguide, and is a cross-section through line
a-a of FIG. 15;
[0054] FIGS. 14a-14k illustrate schematically the creation of a
combinatorial library in accordance with the invention;
[0055] FIG. 15 illustrates schematically several techniques of the
invention for forming a waveguide array or other structure, from a
fluid precursor, on a substrate surface followed by formation of a
cladding layer over the waveguide array;
[0056] FIG. 16 illustrates a technique for forming a multi-layer
waveguide structure;
[0057] FIG. 17 is a schematic illustration of one type of prior art
waveguide coupler;
[0058] FIG. 18 is a schematic illustration of another type of prior
art waveguide coupler, namely an evanescent coupler;
[0059] FIG. 19 is a schematic illustration of a coupling region,
switch, or sensor using a waveguide array of the present
invention;
[0060] FIG. 20 illustrates formation of an interference pattern via
coupling among a five-waveguide array in accordance with the
invention;
[0061] FIG. 21 is a photocopy of a scanning electron micrograph
(SEM) image of an unclad array fabricated in accordance with the
invention;
[0062] FIG. 22 is a photocopy of an SEM image of a clad array
fabricated in accordance with the invention;
[0063] FIG. 23 is a schematic illustration of an optical system
used to couple light into waveguide arrays of the invention and to
determine interference patterns formed via coupling among the
waveguides of the arrays;
[0064] FIGS. 24a-24g show a variety of waveguide arrays and
interference patterns of light emerging from various waveguide
arrays and created via coupling between waveguides of the
arrays;
[0065] FIG. 25 illustrates schematically another technique of the
invention for forming a structure from a precursor, on a substrate
surface;
[0066] FIG. 26 is a photocopy of a SEM image of an aluminosilicate
structure that can serve as a waveguide;
[0067] FIG. 27 is a photocopy of a SEM image of a borosilicate
structure that can serve as a waveguide; and
[0068] FIG. 28 is a photocopy of a SEM image of the structure of
FIG. 27 at a different stage of annealing.
DETAILED DESCRIPTION OF THE INVENTION
[0069] U.S. patent application Ser. No. 09/634,201, filed Aug. 9,
2000 and U.S. patent application Ser. No. 09/004,583, filed Jan. 8,
1998 (now U.S. Pat. No. 6,355,198) and U.S. application Ser. No.
08/616,929, filed Mar. 15, 1996 and U.S. provisional application
Ser. No. 60/046,689 filed May 16, 1997, all are incorporated herein
by reference.
[0070] The present invention provides, in one aspect, techniques
for placement, at regions proximate a substrate surface, of
chemically or biochemically active agents, fluid precursors of
articles such as waveguides to be immobilized proximate a substrate
surface, and/or other species desirably transferred to a region or
regions proximate a substrate surface in a pattern. "Fluid
precursor", as used herein, means a material that is fluid enough
that it can be formed into a pattern using a forming article, using
techniques described herein. The invention utilizes an applicator
having a pattern of indentations that can be used to transfer such
a species from the indentations to a region proximate the substrate
surface or that can serve as a mold that when, positioned proximate
a substrate surface, can define a region in which such a species is
positioned. In one set of preferred embodiments the applicator is
used to transfer a fluid precursor from the indentations to a
region proximate a substrate surface where the precursor is
hardened to the point it is self-supporting and the applicator can
be removed. "Self-supporting, in this context, means that the
precursor does not lose its form unacceptably upon removal of the
forming article and can retain its form during a further hardening
procedure. Alternatively, the applicator can be used to transfer a
fluid precursor to a substrate surface and the applicator can be
removed prior to hardening the fluid, but maintaining the fluid
within channels defined between indentations in the contoured
applicator surface and the substrate surface until the fluid is
hardened is preferred, since the ultimate shape of features of the
pattern on the substrate is thereby better-controlled.
[0071] FIG. 1 illustrates schematically a technique for
derivatizing a substrate surface according to a pattern of, for
example, a polymeric article, a pattern of microbeads optionally
carrying a chemical or biochemically active species, a catalyst or
other activating agent for promoting a chemical reaction such as
metal plating at the surface, a fluid carrying a dissolved or
suspended species to be deposited or precipitated, or the like. For
purposes of illustration, the procedure schematically illustrated
in FIG. 1 will be described with respect to a hardenable
prepolymeric fluid that is hardened at the surface to form a
patterned polymeric article. An article 20 includes an application
surface 22 having formed therein a plurality of indentations 24
that together define a linear, patterned array of indentations 24
that are contiguous with a contact surface 26. Article 20,
according to one embodiment, is an applicator used to transfer a
species, in a pattern, to a region or regions proximate the
substrate surface, or a forming article or micromold placed
proximate a substrate surface and used to guide a fluid species so
as to position the species in a pattern at a predetermined region
or regions proximate the substrate surface. As used herein, the
term "proximate" is meant to define at a substrate surface, that
is, in contact with a substrate surface, or at a position near a
substrate surface and fixed relative to the substrate surface. For
example, if a substrate surface carries an adhesion promoter, for
example a self-assembled monolayer, activity at the surface of the
self-assembled monolayer is intended to mean activity proximate the
substrate surface. When forming article 20 is placed proximate a
surface 28 of a substrate 30, contact surface 26 of the article
seals portions of surface 28 that it contacts, thereby forming
channels 32 defined by indentations 24 and portions 34 of substrate
surface 28 not contacted by contact surface 26. In this manner a
micromold is created, which is defined by article 20 and substrate
surface 28.
[0072] A fluid 36 that, according to the embodiment illustrated, is
a precursor of a patterned, polymeric structure (but can be one of
a variety of species such as a carrier of a chemically or
biochemically active agent, etc., as described herein) is placed
adjacent one or more openings of channels 32 and introduced into
the channels and allowed to flow adjacent portions 34 of substrate
surface 28 in register with indentations 24. Fluid precursor 36 can
be urged to flow via, for example, pressure applied to the fluid as
it is positioned so as to enter the channels, or vacuum created
within the channels by, for example, connection of the outlets of
the channels to a source of vacuum. Alternatively, according to one
aspect of the invention, the fluid can be allowed to flow into the
mold via capillary action. Capillary filling of the mold is
especially useful when the mold is of very small dimension (in
particular in the micro scale) and is defined herein to mean that
when a fluid precursor is positioned adjacent an opening or channel
32 formed by a portion 34 of the substrate surface and an
indentation 24 of article 20, the fluid precursor will flow into at
least a portion of the channel spontaneously.
[0073] Subsequent to introduction of the fluid precursor into the
mold defined by channels 32, the fluid precursor can be hardened
before or after removal of applicator 20 from substrate surface 28
(or where the fluid is a carrier of a species to be deposited or
precipitated, the fluid can dissipate, i.e., evaporate, be absorbed
into applicator 20, or the like). Where the fluid is viscous
enough, or is allowed to reach a particular level of viscosity, the
applicator can be removed and the precursor hardened at the surface
without unacceptable loss of dimensional integrity. In particularly
preferred embodiments, the fluid precursor is hardened to the
extent that it is self-supporting (dimensionally-stable) prior to
removal of Article 20 from the substrate surface.
[0074] According to one embodiment, the fluid precursor is a
solution of monomer in a fluid carrier and is polymerized at the
surface with article 20 in place. Article 20 then is removed. A
structural article 38, in a pattern corresponding to the
indentation or mold pattern 24 of article 20, results on substrate
surface 28 from the described procedure. According to the
description of the process illustrated in FIG. 1, structure 38 is a
polymeric structure formed from a fluid prepolymeric precursor.
[0075] Where the structure 38 formed according to this embodiment
is a polymeric structure, it can be thermally polymerized on
substrate surface 28 via application of heat to the substrate
and/or article 20 or, if article 20 is removed prior to
polymerization, via convective or radiative heat; photopolymerized
if substrate 30 and/or article 20 are transparent to radiation, or
subsequent to removal of article 20. Free-radical polymerization
can be carried out as well. These and other forms of polymerization
are known to those of ordinary skill in the art and can be applied
to the techniques of the present invention without undue
experimentation. All types of polymerization, including cationic,
anionic, copolymerization, chain copolymerization, cross-linking,
and the like can be employed, and essentially any type of polymer
or copolymer formable from a fluid precursor can be patterned on
surface 28 in accordance with the invention. An exemplary,
non-limiting list of polymers that are suitable include
polyurethane, polyamides, polycarbonates, polyacetylenes and
polydiacetylenes, polyphosphazenes, polysiloxanes, polyolefins,
polyesters, polyethers, poly(ether ketones), poly(alkylene oxides),
poly(ethylene terephthalate), poly(methyl methacrylate),
polystyrene, and derivatives and block, random, radial, linear, or
teleblock copolymers, cross-linkable materials such as
proteinaceous material and/or blends of the above. Gels are
suitable where dimensionally stable enough to maintain structural
integrity upon removal of article 20 from substrate surface 28.
Also suitable are polymers formed from monomeric alkyl acrylates,
alkyl methacrylates, alpha-methylstyrene, vinyl chloride and other
halogen-containing monomers, maleic anhydride, acrylic acid,
acrylonitrile, specifically, methyl methacrylate, imides,
carbonates, hexafluoroisopropyl methacrylate, acrylonitrile,
bromophenyl acrylates or bromophenyl methacrylates, and the like.
Monomers can be used alone, or mixtures of different monomers can
be used to form homopolymers and copolymers. Non-linear and
ferroelectric polymers can be advantageous. Gels are suitable where
dimensionally stable enough to maintain structural integrity upon
removal of article 20 from substrate surface 28. The particular
polymer, copolymer, blend, or gel selected is not critical to the
invention, and those of skill in the art can tailor a particular
material for any of a wide variety of applications. The particular
polymer, copolymer, blend, or gel selected is not critical to the
invention, and those of skill in the art can tailor a particular
material for any of a wide variety of applications.
[0076] According to one embodiment, a polymerizable or
cross-linkable species (optionally in a fluid carrier) including an
admixed biochemically active agent such as a protein can be made to
form a pattern on substrate surface 28 according to the described
technique. For example, carboxylated Dextran.TM. can carry admixed
protein, be introduced into channels 34, and hardened to form
articles 38. Where the Dextran.TM. carries admixed biologically
active agent, the article can be exposed to a medium suspected of
containing a biological binding partner of the biochemical agent,
and any biochemical binding or other interaction detected via, for
example, diffraction, or via a change in coupling between waveguide
cores as described more fully below. Where article 38 defines
diffraction grating, the degree of diffraction can be affected by
biological binding between the biological agent compounded within
article 38 and an analyte that is a biological binding partner of
the compounded agent. Determination of a change in diffraction at
surface 28 is indicative of the presence of analyte in the medium
brought into contact with article 38. According to another
embodiment, a species such as polymerizable or cross-linkable
species can entirely coat surface 28, article 20 can be placed
adjacent surface 28, a biological agent can be introduced into
channels 34 and allowed to admix with the polymerizable or
cross-linkable species, and prior to or subsequent to removal of
article 20 species on surface 28 can be polymerized or
cross-linked. In this manner, a surface having a pattern of
biological agent compounded therein is produced, and can serve as a
sensor for a biological binding partner of the biological agent via
change in refraction or diffraction of light at the surface.
[0077] Where electrical conductivity is desired, an
electrically-conductive polymer can be selected, and this can have
significant application in the microelectronics industry, as would
be recognized by one of ordinary skill in the art.
[0078] The invention is intended to encompass creation of a wide
variety of structures or patterns of species on substrate surfaces
from fluid precursors. The precursor can be any fluid that can flow
into the mold defined by indentations 24 and portions 34 of
substrate surface 28, and those of ordinary skill in the art can
determine, without undue experimentation, which fluids will readily
flow into such a mold based upon dimension of the mold and
viscosity of the fluid. In most instances, the viscosity of the
fluid can be adjusted, by for example diluting or concentrating the
fluid, to achieve a level of viscosity suitable for flow into the
mold at a desired rate. The polarity of the fluid can be tailored
as well, with reference to the chemical characteristic of the
substrate surface or micromold, to facilitate fluid carrier
flow.
[0079] According to one embodiment of the invention, patterned
article 38 is not a polymer or cross-linked organic species as
described above, but is a non-polymerized organic species that is
dissolved or dispersed in a fluid carrier to form fluid precursor
36 which is introduced into mold channels 32, whereupon the fluid
carrier or solvent dissipates (e.g., is removed via evaporation
from the mold channels and/or absorption into the substrate or
applicator 20). According to yet another embodiment, patterned
structure 38 is an inorganic structure, such as a salt or ceramic.
A salt soluble in a fluid precursor can be prepared as a solution
36 defining a fluid precursor that is introduced into mold channels
32 and precipitated as a patterned salt structure 38 by removal of
solvent via evaporation, adsorption, or other physical or chemical
change to the surrounding environment. Inorganic salts or ceramics
can be carried as a suspension in a fluid carrier, flowed into
channels 32, and precipitated or deposited. Metals, such as those
commonly deposited from pastes in accordance with thick-film
silk-screening techniques, can be applied to defined regions of
substrate surface 28 where a paste is sufficiently fluid, or the
paste and/or metal can be carried in a fluid as a suspension or sol
in fluid precursor 36. Those of ordinary skill in the art will
recognize that a wide variety of non-electrically conductive,
electrically semi-conductive, and electrically-conductive
structures can be patterned proximate a substrate surface according
to the inventive technique. Fluid precursors of inorganic
materials, such as solutions from which materials can be
precipitated, or suspensions from which a fluid carrier can be
removed by dissipation or evaporation, can be used to form
structures, such as waveguides, from materials such as TiO.sub.2,
TiO.sub.2/SiO.sub.2, ZnO, Nb.sub.2O.sub.5, Si.sub.3N.sub.4,
Ta.sub.2O.sub.5, HfO.sub.2, ZrO.sub.2, or the like. U.S. Pat. Nos.
5,009,483, 5,369,722, and 5,009,483, each incorporated herein by
reference, describe many suitable precursor and waveguide
materials. Dye-doped fluid precursors can be used, and are
advantageous in many situations.
[0080] Another fluid precursor can be a sol-gel precursor, and
sol-gel techniques known to those of skill in the art can be used
to create the solid structures in patterns, according to the
invention. Ferroelectric and electrooptic materials and sol-gel
processing of a variety of precursors to form a variety of species
is well known to those of ordinary skilled in the art and can be
applied and exploited by the method of the invention. For example,
materials such as PbScTaO.sub.3, (Pb, La)TiO.sub.3 (PLT),
LiNbO.sub.3, KNbO.sub.3, LiTaO.sub.3, potassium diphosphate,
potassium triphosphate, PbMoO.sub.4, TeO.sub.2, Ta.sub.2O.sub.5
BaTiO.sub.3, BBO crystals, Ba.sub.1-xSr.sub.xTiO.sub.3,
Pb(Zr,Ti)O.sub.3, SrTiO.sub.3, bismuth strontium tantalate, and the
like. Other examples of sol-gel precursors that can define fluid
precursors of the invention include precursors of multicomponent
glasses or ceramics containing at least one oxide, such as silicate
glasses or ceramics containing the oxides of aluminum, boron,
phosphorus, titanium, zirconium, sodium, etc. Other sol-gel
precursors appropriate for use are precursors of hybrid materials
or organically modified ceramics, such as precursors of silicon
oxycarbide or ORMOCERs. Other sol-gel precursors appropriate for
use are described by Brinker and Scherer, in Sol-Gel Science;
Academic Press, San Diego, 1990; Dislich, Transformation of
Organometallics into Common and Exotic Materials; Nijhof,
Dordrecht, 1998, volume 141; Pani, et al., J. Am. Ceram. Assoc.,
1994, 77, 1242; Ramamurthi, et al., Mat. Res. Soc. Symp. Proc.,
1992, 271, 351; Peiying, et al., Sensors and Actuators, 1995, A49,
187; Rao, J. Electrochem. Soc., 1996, 143, 189; Li, et al., Solar
Energy Materials and Solar Cells, 1995, 39, 179, each of which is
incorporated herein by reference. Where a sol-gel precursor is
used, a hydrolysis and polycondensation reaction takes place,
preferably a two-step reaction. The working examples described
herein use tetramethylorthosilicate as the main constituent in
glasses formed according to this reaction. Other alkoxides react
similarly. Sol-gel precursors that include mixtures of glasses or
glasses that are mixtures of compounds. These structures can be
deposited in any pattern that corresponds to an indentation pattern
formable in an applicator or micromold 20 and can include
dimensions through a wide range as described below.
[0081] The present invention, according to one aspect, involves the
fabrication and use of reactive ion etch masks from sol-gel
precursors. Dielectric materials such as aluminia, zirconia, and
silica glasses and mixed glasses such as aluminosilicates can be
fabricated simply, conveniently, and relatively inexpensively using
the techniques of the invention. A sol-gel precursor can be formed
into a pattern using any of the molding techniques as described
herein, with reference for example to FIGS. 1, 2, 8, 10, 15, 16,
and 25, and can be carried out directly on a surface that is
desirably etched via reactive ion etching. That is, an article is
provided that is desirably etched via reactive ion etching, and a
reactive ion etch mask is formed on a surface of the article via
molding according to any of the techniques described herein from a
precursor of a reactive ion etch mask. The reactive ion etch mask
is formed from the precursor using the mold defined in part by the
forming article of the invention on a first portion of the article
surface, in a pattern, while leaving a second portion of the
substrate surface free of the mask material. The surface of the
article then is exposed to reactive ion etch conditions (known to
those of ordinary skill in the art, e.g., 0.sub.2 plasma), and
etching takes place at the second portion of the substrate surface.
Typically, the first portion of the substrate surface will be a
pattern of separated lines or portions that can be isolated or
interconnected, and the second portion will be complementary to the
first portion. The second portion is "free" of reactive ion etch
mask when the second portion contains no reactive ion etch mask
material or is covered by so little reactive ion etch mask material
that exposure to reactive ion etching conditions causes reactive
ion etching at the second portion.
[0082] Formation of dielectric, or ceramic materials in accordance
with this aspect of the invention can find use not only in reactive
ion etching masks but in integrated optics, non-linear optics and
other microelectronic arenas as would be understood by those of
ordinary skill in the art.
[0083] According to yet another embodiment, a biologically active
agent can be dissolved or suspended in a fluid carrier as a fluid
precursor 36 and introduced into channels 32 adjacent portions 34
of surface 28 and, prior or subsequent to removal of micromold 20,
allowed to engage in a biochemical interaction proximate regions 34
of substrate surface 28. For example, a biochemical agent can
include a biotin linker while substrate surface 28 carries
immobilized avidin, and biochemical interaction can be allowed to
take place at regions 34 of substrate surface 28 in this manner,
linking the biochemical agent to the substrate surface at regions
34. Biochemical agents can be immobilized proximate regions 34 of
the substrate surface according to other techniques as well. For
example, where substrate surface 28 exposes a hydrophobic
functionality, a biological agent such as a protein can be
non-covalently immobilized at regions 34 of the substrate surface.
To control orientation of a protein or other biochemical agent
immobilized at a substrate surface via hydrophobic interaction, a
hydrophobic chemical moiety can be coupled to the biochemical agent
at a region of the agent remote from its active site. In this
manner, the agent can be hydrophobically coupled to the surface and
maintain exposure, away from the surface, of its biochemically
active region. One of ordinary skill in the art can conduct a
simple test to determine whether a biochemical agent is suitable
for use with the described technique. The binding constant of a
candidate biochemical agent for a target species can be determined
using standard ELISA techniques. Then, the candidate biochemical
agent can be hydrophobically immobilized (or immobilized in any
other manner described herein or known to those of ordinary skill
in the art, for example via a polyamino acid tag coupled to a metal
ion immobilized at the surface by a chelating agent) at a variety
of surfaces, and then assays can be performed to determine whether
the agent has retained its ability to biologically bind to the
target species or has been denatured and is unable to bind (this
exemplary test is particularly useful in connection with biological
agents that, in their native form only, bind target species, but
when denatured do not bind the target species).
[0084] Biochemical recognition can be exploited in immobilization
of a particular biochemical agent desirably patterned on substrate
surface 28. For example, a first agent can be immobilized (for
example using hydrophobic coupling) at regions 38 of the substrate
surface, and a second agent (which is a biological binding partner
of the first agent) then can be immobilized at regions 34. The
second step in which the desired agent is immobilized at regions 34
can be carried out with or without micromold 20 proximate the
substrate surface. Biochemical recognition involving partners also
can be exploited to trap biological agents at regions 34 of the
substrate surface using other biological agents that have been
immobilized at regions 34. Biochemical recognition involving
partners such as antibody/antigen, antibody/hapten,
enzyme/substrate, enzyme/inhibitor, enzyme/cofactor, biotin/avidin,
binding protein/substrate, carrier protein/substrate,
lectin/carbohydrate, receptor/hormone, receptor/effector,
complementary strands of nucleic acid, repressor/inducer, and the
like can be exploited in connection with the technique. Those of
ordinary skill will recognize a variety of uses for placement of
such biochemically active agents at predetermined portions of a
substrate surface in a pattern, for example as discussed below with
reference to FIG. 14 and as disclosed in co-pending, commonly-owned
U.S. Pat. No. 5,512,131 of Kumar, et al. and International Patent
Application Publication No. WO 96/29629, both incorporated herein
by reference.
[0085] According to embodiments in which the biochemical activity
of a biologically active agent can be detrimentally affected by
environmental factors, a fluid carrier of the biologically active
agent should be selected so as not to detrimentally affect the
biochemical activity of the agent. For example, if a protein is to
be patterned on the surface and used in an interaction that cannot
take place (or takes place at an unacceptably low level) when the
protein is denatured, a fluid carrier should be selected that does
not denature the protein or otherwise detrimentally affect the
biological binding interaction of the protein that is to be
exploited. Additionally, a micromold 20 should be selected and/or
fabricated in a manner such that the surfaces of indentations 24
that can come into contact with a biologically active agent will
not detrimentally affect the performance of the agent. For example,
if micromold 20 is fabricated from a material that could denature a
protein, then if used with the protein the interior surfaces of
indentations 24 can be chemically altered, for example via grafting
with polyethylene glycol, to render the surfaces non-destructive of
the agent.
[0086] According to yet another embodiment, fluid precursor 36
carries a suspended or dissolved chemically active agent that is an
activating agent as described in a co-pending, commonly owned U.S.
application Ser. No. 08/616,692 of Hidber, et al. entitled
"Microcontact Printing of Catalytic Colloids", referenced above.
When a fluid carrier is used in this and other embodiments, it can
form part of a species or article immobilized proximate the
substrate surface or can dissipate, for example via evaporation or
adsorption into the applicator or substrate surface, leaving the
species carried in the fluid carrier immobilized at the
surface.
[0087] A non-limiting list of chemically active agents that can be
patterned on a surface in accordance with the invention includes
agents as described by Lando (U.S. Pat. Nos. 3,873,359; 3,873,360;
and 3,900,614) which can render a substrate surface amenable to
metal plating, catalytic activating agents such as finely
distributed metal particles and clusters such as conventional metal
powders, substrate-fixed metal clusters or multimetallic clusters
that are well known as valuable heterogeneous and homogeneous
catalysts in organic chemistry, inorganic chemistry, and
electrochemistry, etc. With reference to the application of Hidber,
et al., such agents can include those capable of being carried by
an applicator, transferred from the applicator to a surface in a
form in which it can effect a chemical reaction (such as a metal
deposition reaction), and immobilized at the surface with a degree
of adhesion and for a period of time sufficient to participate in
the desired chemical reaction. As such, one class of activating
agents provided in accordance with the invention are distinguished
from prior art agents applied with an applicator such as a stamp,
for example as disclosed by Lando (U.S. Pat. Nos. 3,873,359,
3,873,360, and 3,900,614), in that the activating agent of the
present invention is in a form suitable for effecting reaction such
as metal plating or catalytic action when transferred to the
surface. According to preferred embodiments, further chemical
reaction at the surface to convert a precursor to a suitable agent,
as necessitated in the referenced prior art methods, is not
required. Metal deposition reactions contemplated include
electrochemical deposition and electroless deposition, generally
involving reduction of a metal cation to create the metal,
facilitated in part by the lowering of the electrochemical
potential involved in the deposition.
[0088] Activating agents that are finely distributed metal
particles and clusters, such as conventional metal powders,
including substrate-fixed metal clusters or multimetallic clusters
are suitable for use as activating agents in accordance with the
invention, and are well known as valuable heterogeneous and
homogeneous catalysts in organic, inorganic, and electrochemistry.
Exemplary activating agents include one or more metals of periodic
table groups Ib, IIb, III, IV, V, VI, VIIb, VIII, lanthanides, and
actinides, preferably copper and any metal more noble than copper,
in particular Pd, Au, Ag, Pt, and Cu. Hydrogenation catalysts for
example those effective in hydrogenating olefins or aromatics, as
in the partial hydrogenation of benzene to form cyclohexene, with a
substrate-fixed ruthenium activating agent or bimetallic activating
agent (e.g. Ru/Sn) are contemplated. Zirconium and titanium
catalysts, among others, are suitable for use in the invention that
catalyze polymerization, such as polymerization of olefins such as
ethylene, and these are intended to form part of the invention.
Other examples of catalytic activating agents include those used in
Heck reactions, e.g. in the Pd-catalyzed reaction of bromobenzene
and styrene to form stilbene. Activating agents that are
heterogeneous catalysts are also useful as electrocatalysts in fuel
cells (in particular substrate-fixed Pt and Pt/Ru clusters).
Activating agents prepared according to the invention can be
homogeneous catalysts, such as those used in two phase systems (for
instance H.sub.2O/toluene), such as e.g. betaine-stabilized Pd
clusters soluble in H.sub.2O. Activating agents that are embedded
in polymers can be used to prepare materials for electronic,
optical and magnetic applications. Suitable embedding polymers
include organic polymers, such as poly-p-phenylene-vinylene,
polymethyl methacrylate, polysilanes, and polystyrene, or inorganic
polymers, such as zeolites, silicates, and metal oxides. The
well-known sol-gel process can be used to incorporate metal
clusters in amorphous metal oxide materials (e.g. SiO.sub.2) as
activating agents.
[0089] Soluble metal clusters that are activating agents can also
be surface-deposited to prepare novel materials for applications in
optics and electronics, e.g. Pd on HOPG (highly oriented pyrolytic
graphite).
[0090] Particulate activating agents having particle sizes on the
order of nanometers are preferred, for example particulate matter
having particle size of less than about 100 nm, preferably less
than about 50 nm, more preferably less than about 25 nm, and most
preferably from about 2 to about 20 nm. The size of the particles
is not critical except to the extent that where excellent edge
resolution of a structure deposited in a reaction involving the
particle is desired, the upper limit in size of the particle is
reduced.
[0091] Especially preferred as activating agents in accordance with
the invention are colloidal activating agents. As used herein,
colloidal activating agent is meant to define particulate matter
capable of being involved in a desired chemical reaction, such as a
catalytic reaction and including plating of metal at surfaces, that
is carried or surrounded by molecules that prevent agglomeration of
the individual particles and that render the particulate soluble
in, or at least able to be carried in, an organic or aqueous
liquid. Suitable colloid-forming species and colloids are described
in European patent publication no. 672765 by Reetz et al.,
published Sep. 20, 1995, and incorporated herein by reference.
According to one embodiment the activating agent comprises one or
more metals of groups Ib, IIb, III, IV, V, VI, VIIb, VIII,
lanthanides, and/or actinides of the periodic table prepared by
cathodic reduction in the presence of a stabilizer. One method of
preparation of such colloids is reduction, optionally with a
supporting electrolyte, in organic solvents or in solvent mixtures
of organic solvents and/or water within a temperature range of
between about -78.degree. C. and about 120.degree. C. to form metal
colloidal solutions or redispersible metal colloid powders,
optionally in the presence of inert substrates and/or soluble metal
salts of the respective metals. These colloids are soluble or
redispersible in a suitable fluid that facilitates their
application to an applicator such as a stamp. The following
articles, incorporated herein by reference, describe as well
exemplary activating agents suitable for use in connection with the
invention. Vargo, et al., "Adhesive Electroless Metallization of
Fluoropolymeric Substrates" Science, 262, 1711-1712 (Dec. 10,
1993); Bonnemann, et al., "Preparation and Catalytic Properties of
NR.sub.4.sup.+ Stabilized Palladium Colloids", Applied
Organometallic Chemistry 8, 361-378 (1994); Reetz, et al.,
"Size-Selective Synthesis of Nanostructured Transition Metal
Clusters" J. Am. Chem. Soc. 116, 7401-7402 (1994); Reetz, et al.,
"Visualization of Surfactants on Nanostructured Palladium Clusters
by a Combination of STM and High-Resolution TEM", Science, 267,
367-369 (Jan. 20, 1995); and Meldrum, et al., "Formation of Thin
Films of Platinum, Palladium, and Mixed Platinum Palladium
Nonocrystallites by the Langmuir Monolayer Technique" Chem. Mater.,
7, 111-116 (1995).
[0092] Electrochemical methods are described in EP 672765,
referenced above, for synthesis of soluble metal colloids by
operating in an inert organic, aprotic solvent, with surface-active
colloid stabilizers being added as the supporting electrolyte which
will both prevent plating of the metal and protect, or stabilize,
small metal nuclei in the cluster stage. A metal sheet serves as
the anode to be dissolved and a metal or glassy carbon electrode
serves as the cathode. After dissolution at the anode, the released
metal salts are reduced again at the cathode, with
tetraalkylammonium salts serving as stabilizers. Standard organic
solvents can be employed.
[0093] Suitable exemplary stabilizers, or carriers, for the
colloids, and at the same time as the supporting electrolyte, are
quaternary ammonium or phosphonium salts
R.sup.1R.sup.2R.sup.3R.sup.4N.sup.+X.sup.- and
R.sup.1R.sup.2R.sup.3R.sup.4P.sup.+X.sup.-, respectively. A wide
variety of combinations of R.sup.1, R.sup.2, R.sup.3 and R.sup.4
are possible. Examples include the symmetrical tetraalkylammonium
salts with R.sup.1=R.sup.2=R.sup.3=R.sup.4=n-butyl or n-octyl,
mixed tetraalkylammonium salts with R.sup.1=R.sup.2=R.sup.3=methyl
and R.sup.4=cetyl, or chiral tetraalkylammonium salts having four
different residues. Aryltrialkylammonium salts may also be used.
Suitable counter ions include various anions, e.g. halogenides
(Cl.sup.-, Br.sup.-, I.sup.-), hexafluorophosphate
(PF.sub.6.sup.-), carboxylates R'CO.sub.2.sup.- (R'=alkyl, aryl),
or sulfonates R''SO.sub.3.sup.- (R''=alkyl, aryl). A similar
variety of phosphonium salts may be used, including
tetraarylphosphonium salts, such as tetraphenylphosphonium bromide.
Preferably, tetrabutylammonium chloride, bromide or
hexafluorophosphate, tetraoctylammonium bromide, or
tributylhexadecylphosphonium bromide can be employed. As metals,
any of those listed above, in particular transition metals such as
Fe, Co, Ni, Pd, Pt, Ir, Rh, Cu, Ag, or Au, are suitable. Suitable
solvents are aprotic organic solvents, such as tetrahydrofuran
(THF), toluene, acetonitrile (ACN), or mixtures thereof. The
temperature in the electrolytic cell may be in the range between
-78.degree. C. and +120.degree. C., preferably 15-30.degree. C. or
room temperature.
[0094] A preferred activating agent is a colloidal catalyst that
promotes deposition, for example electroless deposition, of a metal
at region 34 of substrate surface 28 to which the colloidal
catalyst is applied. For example, where fluid precursor 36 includes
a suspension of a colloidal palladium catalyst, the fluid can be
evaporated or adsorbed as described above, resulting in deposition
of catalyst at regions 34 of substrate surface 28. Subsequently, an
electroless copper plating bath can be introduced into channels 32
and deposition of copper allowed to take place at regions 34 of
surface 28. Alternatively, micromold 20 can be removed from surface
28 and the entire surface 28 exposed to an electroless copper
plating bath. Copper will plate only at those regions 34 of
substrate surface 28 to which colloidal palladium catalyst had been
applied. Electrochemical metal plating can be carried out as well.
The chemically active agent of the invention can be any agent that
can find use in chemical reaction, attraction, or other interaction
proximate a substrate surface. Those of ordinary skill in the art
will recognize a variety of agents that can be used in accordance
with the invention, including, but not limited to solutions or
suspensions of a very small species such as catalytic colloids,
monomers, dissolved or suspended salts or ceramics or their
precursors or other species.
[0095] According to yet another embodiment of the invention a
suspension of particulate species in a fluid carrier 36 can be
introduced into channels 32, followed by removal of the fluid
carrier via dissipation, as discussed. The particulate species can
be organic, inorganic, or polymeric material as described above,
for example finely-ground polymeric, ceramic, or crystalline
material, or can be in the form of microspheres. The application of
microspheres in a predetermined pattern to a substrate surface can
serve a variety of purposes that will be apparent to those of
ordinary skill in the art upon reading the present disclosure, in
light of the state of the art as set forth in several publications.
An article by Lenzmann, et al., entitled "Thin-Film Micropatterning
Using Polymer Microspheres", Chem. Mater., 6, 156-159 (1994),
incorporated herein by reference, describes formation of
densely-packed monolayers of monodisperse polystyrene microspheres
deposited on a glass substrate. The spheres serve as a mask for
zinc sulfide deposition on the substrate as a thin film by thermal
evaporation in vacuum. The mask (microspheres) are removed from the
substrate surface after evaporative deposition leaving behind a
surface with zinc sulfide features located in the interstitial
spaces of the densely-packed spheres. For 2-micron diameter
spheres, the lattice spacing of the resulting pattern is
approximately 900 nanometers with individual trigonal pyramidal
peaks. According to the present invention, a particular
concentration of polymeric microspheres in a fluid carrier can be
selected without undue experimentation that, when introduced into
channels 32, followed by evaporation of the fluid carrier, would
result in a monolayer of microspheres selectively patterned at
regions 34 of substrate surface 28. Removal of micromold 20,
followed by chemical vapor deposition, results in a well-ordered
pattern of isolated, nano-scale regions of deposited material
within the confines of region 34 of substrate surface 28.
[0096] An article by Dushkin, et al. entitled "Colored Multilayers
From Transparent Submicrometer Spheres", Langmuir, 9, 3695-3701
(1993), incorporated herein by reference, discusses optical
phenomena associated with polymeric beads at surfaces. Ordered
multilayers are formed by evaporating the water carrier from
polystyrene latex suspensions of diameter smaller than the
wavelength of visible light. The spheres exhibit color when
illuminated with polychromatic light. Accordingly, arrangement of a
pattern of microspheres at regions 34 of substrate surface 28 in
accordance with the invention can result in various radiative and
calorimetric phenomena. An article by Hayashi, et al. entitled
"Imaging by Polystyrene Latex Particles", Journal of Colloid and
Interface Science, 144, 2, 538-547 (July, 1991), incorporated
herein by reference, describes microarrays of identical images
produced by polydispersed polystyrene particles at a surface.
Microparticles and microbeads, especially polymeric particles and
beads such as latex or polystyrene beads, find use in the field of
biochemistry as solid supports for biochemical interaction. For
example, a chemically or biochemically active agent can be coupled
to a microbead or microparticle and optionally used in turn to
immobilize a second agent that reacts with the immobilized agent,
thereby immobilizing the second agent at a region at which the
microbead is immobilized. That is, microbeads carrying a particular
agent can be immobilized at a surface in a pattern using techniques
of the invention and the patterned, immobilized beads can serve as
locations for chemical reaction or biochemical interaction on the
micro scale, for example as microreactors. Those of ordinary skill
will recognize a variety of uses for patterned microparticles or
microbeads carrying chemical or biochemical agents such as, for
example, biochemical assays.
[0097] The pattern of parallel indentations 24 formed in surface 22
of micromold or applicator 20 is for illustrative purposes only.
Any pattern, for example a pattern defined by a single indentation
or many indentations, one or more of the indentations defining a
non-linear pathway of uniform or non-uniform depth is intended to
fall within the scope of the invention. Various patterns are
illustrated in subsequent figures. The indentation pattern can be
of a variety of dimensions and, according to one aspect of the
invention, includes a region having a lateral dimension of less
than 1 millimeter. "Lateral dimension" is meant to define a
dimension parallel to application surface 22. According to
preferred embodiments, the indentation pattern includes a portion
having a lateral dimension of less than about 500 microns or less
than about 100 microns, in one set of embodiments more preferably
less than about 50, 20, or 10 microns, and more preferably still
less than about 5 microns. According to a particularly preferred
embodiment, an indentation pattern having a portion including a
lateral dimension on the order of 1 micron is provided. The
dimension of the indentations can be altered, as described in
international patent publication number WO 96/29629, published Jun.
26, 1996 of Whitesides, et al., entitled "Microcontact Printing on
Surfaces and Derivative Articles", incorporated herein by
reference, by deforming article 20. Where waveguides are fabricated
in accordance with the invention, it is an advantage that, for
example, branched sections and/or evanescent coupling sections, as
shown in FIGS. 17 and 18 can be included in the pattern. Those of
ordinary skill in the art can select suitable dimensions, depending
upon the frequency of electromagnetic radiation being guided.
Typically, the waveguide will have a width on the order of microns.
The technique can be carried out where micromold 20 includes an
indentation pattern where the indentations have depths and widths
on the order of 100 microns to less than 1 micron,
controllably.
[0098] Where micromold 20 is placed adjacent a substrate surface
and a fluid precursor fills channels 32, article or articles 38
resulting from the technique can have lateral dimensional features
that correspond to the lateral dimensional features of indentations
32 of the micromold.
[0099] According to another embodiment, the fluid precursor need
not completely fill channels 32, and this is preferred according to
embodiments in which the lateral dimension of article 38 formed
from the fluid precursor is to be minimized. According to this
embodiment, fluid precursor 36 is introduced into channels 32 in an
amount small enough that the fluid precursor wets only the corners
of the channels. When a fluid precursor, substrate, and micromold
are selected such that the fluid precursor will wet the micromold
efficiently via capillary action, when a small amount of fluid
precursor is supplied to the mold channel or channels, the
precursor will selectively wet portions of the channels having an
interior angle relatively low relative to the rest of the channel
(such as corners 40 defined by the abutment of contact surface 26
against substrate surface 28 at the edge of region 34 of the
substrate surface). When the fluid precursor wets the corners
selectively and the fluid is hardened, evaporated, or adsorbed, a
resulting structure can define a pattern having a dimension smaller
than that of the lateral dimension of indentation 24. According to
this embodiment the lateral dimension of structure 38, at its
narrowest, is narrower than the narrowest lateral dimension of
channel 24 of the micromold, and can have a height significantly
less than the height of the channel. The lateral dimension of
article 38 according to this embodiment can be on the order of less
than or equal to about 100 microns or 50 microns, or preferably
less than about 20 or 10 microns, more preferably less than about 5
microns or 1 micron, and according to a particularly preferred
embodiment less than approximately 0.2 micron. According to this
aspect, any of the species described herein that can be patterned
proximate a substrate surface can be patterned so as to have
lateral dimensions as described above. This aspect of the invention
is illustrated in FIG. 6c, and discussed below.
[0100] In an alternate technique, any of the species described
herein that can be used to form patterned articles and the like on
a substrate surface (such as fluid precursor 36) can be made to
coat substrate surface 28, and then article 20 can be pressed
against substrate surface 28 to displace precursor 36 at regions in
register with contact surface 26. Precursor 36 will be formed in
channels 32 as illustrated in FIG. 1, and procedures described
above carried out.
[0101] Any suitable material can define substrate 30 of the
invention. Substrate surface 28 can be of the same material as the
bulk material of substrate 30, or a different material. Substrates
exposing a variety of functional surfaces such as hydrophobic,
hydrophilic, and biologically compatible or non-compatible surfaces
are known, and are suitable for use with the invention. Substrates
that are somewhat fluid are known as well, and are acceptable for
use in the invention to the extent that a useful pattern can be
formed thereupon. Article 20 similarly can be formed of essentially
any material. For example, ceramic, polymeric, elastomeric, and
other materials can be used. According to a preferred embodiment,
substrate surface 28 and/or contact surface 26 of article 20 is an
elastomer or other conformable material. Preferably, contact
surface 26 and more preferably, for ease of fabrication, the entire
article 20, is formed of an elastomer. When an elastomer defines
substrate surface 28 or contact surface 26, or preferably micromold
20, an optimal seal is created between contact surface 26 and
portions of substrate surface 28 adjacent and contiguous with
portions 34 that with indentations 24 define channels 32. This
results in optimal confinement of fluid precursor 36 to channels
32. According to the invention pressure can be applied to micromold
20 against substrate 30 during micromolding, but according to
embodiments in which an elastomer is used as described, pressure
need not be applied as the elastomer conforms well to the surface
against which it mates thus sealing channels 32. The micromold 20
can be fabricated of an elastomer in a manner analogous to the
fabrication of a stamp from an elastomer as described in
co-pending, commonly-owned U.S. Pat. No. 5,512,131, issued Apr. 30,
1996 by Kumar, et al, entitled "Formation of Microstamped Patterns
on Surfaces and Derivative Articles", and as described in
International Patent Publication No. WO 96/29629 of Whitesides, et
al., entitled "Microcontact Printing on Surfaces and Derivative
Articles", published Jun. 26, 1996, both of which are incorporated
herein by reference.
[0102] FIG. 2 illustrates another embodiment of the invention in
which, rather than applying article 20 to substrate surface 28
followed by introduction of fluid precursor 36 into channels 32 so
defined, article 20 is used as an applicator to transfer a
chemically or biochemically active agent (optionally in a fluid
carrier), fluid precursor of an article such as microparticles or
microbeads in suspension, catalytic colloid, prepolymer fluid, or
the like to substrate surface 28. Described below with reference to
FIG. 15 is a set of transfer molding techniques particularly
preferred in the fabrication of waveguides and other articles where
the final shape of the formed article is essentially identical to
the shape of the interior of the mold. In FIG. 2 and subsequent
figures, components common to the various figures are given common
numerical designation. In FIG. 2, fluid precursor 36 is first
applied to indentations 24 of micromold 20, and then application
surface 22 is brought into proximity of substrate surface 28 to
allow fluid precursor 36 to be transferred to substrate surface 28.
The fluid precursor can be applied to the indentations by bringing
the indentations into contact with the fluid precursor and allowing
capillary action to cause the indentations to be filled, or the
precursor can be applied via micropipetting or the like to the
indentations. In this way, separate fluid species can be applied to
separate indentations if desired. In can be advantageous, with
these techniques, to select a material exposed by the contoured
application surface and the fluid species applied thereto such that
the fluid species rapidly is positioned within the indentations,
rather than spreading over the entire surface. Those of skill in
the art can carry out such selection, using contact angle
measurements or the like.
[0103] Where fluid precursor 36 protrudes from indentations 24
prior to transfer, application surface 22 need not contact
substrate surface 28 for transfer to take place. Typically,
however, application surface 22 will be brought into contact with
substrate surface 28 to transfer a pattern of the fluid precursor
38 to regions proximate the substrate surface in a pattern
corresponding to the indentation pattern 24. As illustrated, some
fluid precursor remains in indentations 24, and the fluid precursor
transferred to substrate surface 28 has been converted into
hardened article 38. However, according to several embodiments
discussed above, the fluid precursor will not result in a hardened
article, but will serve to transfer a biochemical agent or chemical
agent to a surface. According to the embodiment illustrated in FIG.
2, the chemical or biochemical agent, prepolymer, fluid carrier
containing a suspension of particulate matter, microbeads, or the
like serves to transfer essentially instantaneously the desired
species to the surface. As with all embodiments of the invention,
the pattern of species so transferred can include a single
indentation that is of any shape including a non-linear or linear
pathway, a plurality of linear indentations as illustrated in FIG.
2, or a plurality of indentations of any shape, one or more
indentations having dimensions as described above. Where a
plurality of indentations are formed in application surface 22,
each indentation can be made to carry a different chemical or
biological agent or precursor. According to that embodiment, when
application surface 22 of the micromold is brought into contact
with substrate surface 28, distinct first and second species such
as distinct first and second chemically or biochemically active
agents, precursors, particulate species, or the like can be
transferred essentially instantaneously to distinct first and
second regions 42 and 44 proximate the substrate surface, in a
pattern corresponding to the indentation pattern, and separated
from each other by intervening region 46 of the substrate surface
that remains free of the agent or precursor.
[0104] FIGS. 3a-d are photocopies of SEM images of polymeric
structures formed on substrates according to the method described
above and illustrated in FIG. 1, in which a fluid polymeric
precursor was allowed to fill channels formed by indentations in
micromold 20 and regions of the substrate. FIG. 3a shows
polyurethane articles 48 formed on Si/SiO.sub.2 substrate 50 by
capillary filling of a micromold having a surface with indentations
placed adjacent substrate 50. The indentations correspond to the
pattern of articles 48. A liquid polyurethane prepolymer was placed
adjacent openings of channels formed between the micromold and the
substrate surface and filled the channels via capillary action. The
micromold was made of polydimethylsiloxane (PDMS). FIG. 3b is a top
view of a polyurethane article 52 having a complex, interconnected
pattern formed on Si/SiO.sub.2 substrate 50. A PDMS micromold
having an indentation pattern corresponding to the pattern of
article 52 was used, and a liquid polyurethane prepolymer was
allowed to fill the mold channels via capillary action. FIG. 3c
shows a quasi three-dimensional array of microstructures
interconnected through channels. Again, a polyurethane liquid
prepolymer was allowed to fill channels formed by a micromold
having an indentation pattern corresponding to the pattern of
polyurethane article 54. Polyurethane article 54 is formed on a
Si/SiO.sub.2 substrate 50. FIG. 3d shows a free-standing patterned
polyurethane article 52 formed by removal of the article from the
substrate (FIG. 3b).
[0105] FIGS. 4a-h illustrate structures formed on substrates using
the micromolding technique illustrated in FIG. 1 in which liquid
precursor 36 is a precursor of inorganic materials. Photocopies of
SEM images are shown. In FIG. 4a, KH.sub.2PO.sub.4 structures
precipitated from aqueous solution on Si/SiO.sub.2 are shown. FIG.
4b shows KH.sub.2PO.sub.4 structures as well, crystallized more
rapidly. FIG. 4c shows Cu(NO.sub.3).sub.2 on the same substrate
crystallized from aqueous solution. FIG. 4d shows structures formed
of the same material on the same substrate, but crystallized from a
much more dilute solution. FIG. 4d illustrates the derivatization
in a pattern that is formed within the boundaries of a region of
the substrate surface corresponding to the indentation pattern of
the micromold, but that does not fill that region. A series of
isolated regions of product on the order of 4 microns in lateral
dimension are shown. FIG. 4e shows CuSO.sub.4 structure on glass.
FIG. 4f shows K.sub.3Fe(CN).sub.6 structures on Si/SiO.sub.2. FIG.
4g shows a fractured view of amaranth on glass. The structures are
approximately 0.4 micron in height. FIG. 4h is a section of FIG. 4g
at higher magnification.
[0106] Ceramic structures formed in accordance with the invention
can find use, for example, as mechanical ceramics such as abrasion
tools. Current methodologies involve, typically, chemical vapor
deposition to form ceramic patterns having small dimensions for
such uses.
[0107] FIG. 5 is a photocopy of an electron micrograph showing a
packed, ordered array of polystyrene microspheres 70 on a
Si/SiO.sub.2 substrate 72. The ordered array of microspheres was
formed by allowing a latex solution containing polystyrene
microspheres to fill, via capillary action, channels formed between
a micromold and the substrate surface in a pattern corresponding to
the pattern of microbeads shown. The PDMS micromold was removed
following crystallization of the microspheres via dissipation of
the fluid carrier.
[0108] FIGS. 6a-c are photocopies of SEM images of copper
structures formed via electroless deposition on Si/SiO.sub.2
substrates. For the structure in FIG. 6a, a gold surface was
provided. A PDMS micromold having an indentation pattern
corresponding to the pattern of copper structures illustrated was
placed adjacent the gold substrate (as illustrated schematically in
FIG. 1) and the channels 32 were filled with a plating bath for
electroless deposition of copper, defining a fluid precursor of
copper according to one aspect, and a chemically active agent
according to another aspect. The copper electroless plating
solution was allowed to remain in contact with the surface for a
period of time sufficient to plate copper structures 74 in a
pattern corresponding to the indentation pattern of the micromold,
while portions of gold surface 76 corresponding to contact surface
26 of the micromold remained free of copper deposition. For the
structure illustrated in FIGS. 6b-c, a PDMS micromold having an
indentation pattern corresponding to the pattern of copper
structures illustrated was placed adjacent the substrate and the
channels 32 were filled with a precursor solution 36 containing
catalytic colloids. The solvent in which the catalytic colloids
dissipated, resulting in formation of the catalytic colloids as a
chemically active agent formed on regions of the substrate surface
corresponding to the indentation pattern of the micromold. The
micromold was removed, and the surface exposed to an electroless
copper plating bath. Specifically, in FIG. 6b, copper structures 78
were formed on a Si/SiO.sub.2 substrate 80 coated with a
self-assembled monolayer of siloxane on the Si/SiO.sub.2 substrate.
CH.sub.3CH.sub.2O).sub.3Si(CH.sub.2).sub.3NH.sub.2 defined the
self-assembled monolayer. A micromold having an indentation pattern
corresponding to the ultimate copper pattern 78 was placed on the
self-assembled monolayer-derivatized silicon substrate. A DMF
solution containing palladium colloids as a fluid precursor 36 was
allowed to fill the channels. Dissipation of DMF resulted in the
chemically active agent (specifically, palladium colloid) forming
structures in a pattern corresponding to pattern 78. The substrate
was exposed to an electroless copper plating bath to plate copper
at patterned region 78. FIG. 6c illustrates an aspect of the
invention in which articles of very small lateral dimension can be
formed by allowing a small volume of fluid precursor 36 to enter
channels 32 defined by the micromold indentations and the substrate
surface. The substrate was prepared as described in connection with
FIG. 6b. A region 82 of the substrate surface corresponds to the
indentation pattern of the micromold. The fluid precursor 36 wetted
only the corners defined between the substrate surface 84 and the
micromold channels thus, when the fluid carrier dissipated, the
catalytic colloid was solidified only in those portions of the
indentation pattern that were wetted, namely, the corners. When the
surface was exposed to an electroless copper plating bath, copper
was plated at the regions 86 to which the catalytic colloid had
been deposited. A copper pattern of very small lateral dimension
resulted.
[0109] FIGS. 7a-c illustrate the application of a patterned
structure to a surface from a fluid precursor using micromolding as
illustrated in FIG. 1, followed by use of the structure as a resist
in a chemical etch. A polymeric structure 88 (polyurethane) was
formed from a fluid prepolymer in a pattern corresponding to an
indentation pattern on a 200 nm, thermally grown oxide layer 90 of
a silicon substrate 92 (FIG. 7a). Following exposure of the
substrate to a solution (aqueous HF/NH.sub.4F for about 2 minutes)
that etches silicon dioxide, but to which the polymeric structure
88 was resistant, the silicon dioxide layer was removed at regions
of the substrate intervening the regions covered by the patterned
structure 88, that is, regions that had been contacted by contact
surface 26 of the micromold (FIG. 7b). Subsequently, the substrate
surface was exposed to a solution (400 ml H.sub.2O, 92 g KOH, 132
ml 2-propanol for about 15 minutes at 65.degree. C.) that etches
silicon, but to which silicon dioxide is resistant. FIG. 7c shows
resultant channels 94 anisotropically etched in the silicon
substrate between patterned regions of silicon dioxide 90 that
correspond to the pattern of polymeric structure 88 formed on the
substrate surface via the micromolding technique.
[0110] FIG. 8 illustrates schematically a technique for forming a
mask, for use in lithography or the like, via the micromolding
technique of the invention. A micromold 96 having a molding surface
98 including a plurality of indentations 100 in a grid-like pattern
is applied to a surface 102 of a substrate 104. A fluid polymeric
precursor 106 is placed adjacent openings of channels formed
between the substrate surface and the indentations of the
micromold, and allowed to flow, via capillary action, into the
channels. Where a PDMS micromold was used, the polymeric precursor
could be placed so as to cover all channel openings, and flowed
into and made to fill the channels completely. Gas escaped
presumably via diffusion through the micromold. Once the polymeric
precursor was hardened, via thermal or photolytic polymerization or
the like, the micromold was removed. The substrate then was
separated from the resultant patterned article 108. The patterned
article had a "frame" 110 completely surrounding it which could be
used for ease of manipulation. The frame could be removed as well,
to form the article 108 in a pattern corresponding to the
indentation pattern of the micromold free of the frame.
[0111] The article 108 could be used as a mask, for example as
illustrated in FIGS. 9a-d, which are photocopies of SEM images.
FIG. 9a shows a polyurethane mask 108 formed as illustrated in FIG.
8, and following formation placed on a Si/SiO.sub.2 substrate 112.
FIG. 9b shows the mask 108 on the substrate 112 following
evaporation of gold onto the substrate. A portion of the mask was
removed and mask 114 and portions 112 of the substrate not covered
by the mask are shown covered with gold. Portions 116 of the
substrate that had been covered by mask 108 remain free of gold.
FIG. 9c shows a surface having a pattern of isolated regions 118 of
gold on a silicon substrate (regions 120 of the silicon substrate
not covered by regions 118 of gold can be seen) formed as follows.
A mask fabricated as described above was placed (with reference to
FIG. 8) on a silicon substrate carrying a thin film of gold. A
self-assembled monolayer-forming species (hexadecanethiol) was
exposed to the surface and formed a self-assembled monolayer
selectively at regions 118 not covered by the mask. The mask then
was removed from regions 120, and the surface exposed to a solution
that etched gold, but to which the self-assembled monolayer was
resistant. The self-assembled monolayer then was removed, resulting
in the regions 118 of gold that had been protected by the
secondary, self-assembled monolayer resist, isolated by regions 120
of the silicon substrate. FIG. 9d shows a surface derivatized as
described with respect to FIG. 9c, but the self-assembled monolayer
was transferred to regions 118 of the surface by placing a flat
PDMS article that had been coated with a self-assembled
monolayer-forming species on top of the mask 108 for one
minute.
[0112] Mask 108 also could be applied to nonplanar surfaces
followed by plating, etching, or the like. It can be advantageous,
when transferring mask 108 to a surface having very fine features,
such as a surface etched as illustrated in FIG. 7c, to transfer
mask 108 to such a surface by floating it in a fluid that is
supported by the surface and allowing the fluid to dissipate or run
off.
[0113] As described in international patent publication number WO
96/29629, published Jun. 26, 1996 of Whitesides, et al., referenced
above, etching or plating at a surface can be made to take place
selectively at predetermined regions, and this technique can be
exploited using the techniques of the present invention as
described herein. Additionally, where a self-assembled monolayer is
patterned, a "protecting species" that is resistant to (for
example, incompatible with) a chemical etch can be placed on top of
a self-assembled monolayer, followed by etching at regions not
covered by the self-assembled monolayer, as described in
publication no. WO 96/29629. Of course, a self-assembled monolayer
can be incompatible with an etch and etching can take place without
the use of a protecting species. The protecting species, according
to this embodiment, is compatible with the self-assembled
monolayer. According to another embodiment, a protecting species is
less compatible with the self-assembled monolayer than with the
substrate surface that is exposed at regions intervening the
self-assembled monolayer. According to this embodiment, after
patterning of a self-assembled monolayer a protecting species is
exposed to the surface and when the surface is exposed to an
etchant, the surface is etched at regions that had been covered by
the self-assembled monolayer.
[0114] FIGS. 10a-c illustrate formation of a mask 122 on a thin
layer 124 of chromium on a glass substrate 126 using the
micromolding procedure as illustrated in FIG. 1, followed by
etching of chromium at regions 128 not covered by the mask. In FIG.
10a, the molding technique described above is used to form a
pattern of polyurethane article 122 on chromium 124 leaving region
128 of chromium uncovered. The surface was exposed to an etchant
(400 ml H.sub.2O, 24 ml of 63% HNO.sub.3, 62 g
NH.sub.4NO.sub.3.Ce(NO.sub.3).sub.3 for about 1 minute) that
removes chromium but to which the polymeric article 122 is
resistant. The result was a glass substrate 126 having thereon a
patterned mask 130 defined by chromium protected from the etch by
mask 122 in the pattern corresponding to mask 122 (and the pattern
corresponding to the indentation pattern of the micromold). FIG.
10b is an optical micrograph of the chrome mask 130, top view. The
chrome mask 130 was removed from the substrate 126 and placed on a
photoresist article. FIG. 10c is a photocopy of an SEM image of a
pattern that was generated in the photoresist film at regions 132
not protected by the mask. Raised portions 134, in a pattern
corresponding to the pattern of the chromium mask, and
corresponding to the original indentation pattern of the micromold
from which the mask 122 was formed, were not ablated in the
photolithography process.
[0115] According to another embodiment a substrate surface such as
a silicon wafer can be spin-coated with photoresist. A micromold
can be placed adjacent to a photoresist and channels defined
thereby filled with a solvent that dissolves photoresist but not
the micromold. A pattern of the silicon wafer not covered by
photoresist, the pattern corresponding to the indentation pattern
of the micromold, is thereby produced. Further processing familiar
to those of ordinary skill in the art can be carried out.
[0116] FIG. 11 illustrates schematically an applicator 136 that can
be used for applying any of the above-described chemically or
biochemically active agents, polymeric precursors, fluid precursors
of solid structures, fluid carriers of particulate matter, and the
like to a substrate surface. Applicator 36 includes a plurality of
isolated indentations 138 separated from each other by intervening
regions of a surface 140 in which the indentations are formed. As
illustrated, two of the indentations contain fluid carrier 142 and
fluid carrier 144, respectively. The fluid carriers 142 and 144 can
be the same or different. A substrate 146 is shown that, for
purposes of illustration, includes a self-assembled monolayer 148
formed thereon which can serve as an adhesion promoter. Fluid
carriers 142 and 144 are transferred to isolated regions proximate
the surface of substrate 146, in particular, regions of the exposed
self-assembled monolayer 148 on the surface of substrate 146. The
transfer typically takes place by bringing the surface 140 of the
applicator into contact with the self-assembled monolayer 148 but,
if the fluid carriers 142 and 144 protrude from the indentations,
the surface 140 need only be placed in close proximity to the
self-assembled monolayer 148.
[0117] Fluid carriers 142 and 144 can be any of the species
described above and, according to a particularly useful embodiment,
carry or define a chemically or biochemically active agent that can
be used in a subsequent assay or the like. For example, a
self-assembled monolayer 148 can be a monolayer of a species
X--R-Ch as described in U.S. Pat. No. 5,620,850, issued Apr. 15,
1997 to Bamdad, et al., entitled "Molecular Recognition at Surfaces
Derivatized with Self-Assembled Monolayers", incorporated herein by
reference. These species have the general formula as above where X
represents a functional group that adheres to a gold surface, R
represents a spacer moiety that promotes formation of a
self-assembled monolayer of a plurality of the molecules, and Ch
represents a bidentate, tridentate, or quadradentate chelating
agent that coordinates a metal ion. The chelating agent includes a
chelating moiety and a non-chelating linker moiety, such that it
can be covalently linked via its linker moiety to the spacer moiety
while allowing the chelating moiety to coordinate a metal ion.
According to a preferred aspect of the invention a metal ion is
coordinated to the chelating agent, and a binding partner of a
target molecule is coordinated to the metal ion. This arrangement
is facilitated by selecting the chelating agent in conjunction with
the metal ion such that the chelating agent coordinates the metal
ion without completely filling the ion's coordination sites,
allowing the binding partner to coordinate the metal ion via
coordination sites not filled by the chelating agent. A
non-limiting exemplary list of suitable chelating agents includes
nitrilotriacetic acid,
2,2'-bis(salicylideneamino)-6,6'-demethyldiphenyl, and
1,8-bis(a-pyridyl)-3,6-dithiaoctane. The binding partner can be a
biological species that includes a polyamino acid tag, such as a
tag made up of at least two histidine residues, that coordinates
the metal ion. In this context the term "adhere" means to chemisorb
in the manner in which, for example, alkyl thiols chemisorb to
gold.
[0118] In this case the fluid carriers 142 and 144 can be carriers
of a nickel ion, resulting in a surface suitable for capture of a
biological binding partner carrying a polyamino acid tag
selectively at regions to which carriers 142 and 144 had been
applied. According to this embodiment, immediately following
application of carriers 142 and 144 to the substrate surface, it
can be advantageous to expose the surface of substrate 146 to a
chelating agent in solution to remove excess nickel ion from the
surface. In this way, stray uncoordinated nickel ion does not
coordinate to the self-assembled monolayer 148 at regions outside
of those regions to which carrier 142 and 144 had been applied. The
latter-applied chelating agent preferably less-strongly coordinates
nickel ion than the chelating agent immobilized at the surface.
Following this application step, a plurality of isolated regions of
self-assembled monolayer 148 include nickel ion. Accordingly, when
the surface is exposed to a polyamino acid-tagged biochemically
active agent, the biochemically active agent will attach
selectively at those regions to which nickel ion had been
applied.
[0119] According to another embodiment, self-assembled monolayer
148 can be a species X--R-Ch-M as described in the above-referenced
co-pending application Ser. No. 08/312,388, and the species 142 and
144 can be polyamino acid-tagged biological binding partners,
optionally contained in a fluid carrier, that are attached to the
surface selectively at those regions corresponding to the
indentation pattern of the applicator. According to this embodiment
the separate, isolated regions can include separate, distinct
biochemically active agents. This can be accomplished, for example,
by placing applicator 136 in register with a plurality of
reservoirs of distinct (different) biochemically active agents to
position distinct biochemically active agents in the respective
indentations of the applicator, then placing the applicator
adjacent the surface of substrate 146 to transfer distinct
biochemically active agents to distinct, isolated regions of the
surface. The procedure can be repeated using fresh substrate
surfaces for each step, thus surfaces carrying distinct regions of
distinct biochemically active agents can be mass produced. In
addition to the species described above, cells can be immobilized
at a substrate surface in this manner as well. Register between the
applicator and the substrate surface can be controlled via
mechanical, electronic, magnetic, and/or optical apparatus.
[0120] According to another embodiment, species 142 and 144 or
species carried by fluid carriers 142 and 144 can be transferred to
a surface carrying a self-assembled monolayer other than the
monolayer of X--R-Ch-M as described above. For example, a
self-assembled monolayer exposing a hydrophobic functionality such
as an alkane functionality can be formed on a surface (e.g.,
hexadecanethiol on gold) and a biochemically or chemically active
agent that adheres to a hydrophobic surface can then be applied to
the surface in discrete regions or in a pattern as described above.
Where the biochemically active agent is a cell or cells, it may be
advantageous to coat the hydrophobic surface with a cytophilic
species such as laminin. Reference can be made to U.S. patent
application Ser. No. 08/131,838 of Sighvi, et al. referenced above,
in connection with the immobilization of cells at surfaces.
[0121] Immobilization of cells and other biochemically active
species can be carried out without a self-assembled monolayer as
well. For example, a hydrophobic surface coated with laminin, and
free of self-assembled monolayer, can serve as a substrate for
immobilization of a pattern of cells in accordance with the
invention.
[0122] According to this and other embodiments, the substrate
surface can carry chelating agent immobilized via other than a
self-assembled monolayer. For example, chelating agents coupled to
dextran at a surface, as is known, can be employed. Although a
self-assembled monolayer 148 is illustrated on the surface of
substrate 146, a self-assembled monolayer is not needed according
to all embodiments. For example, substrate 146 can be adhesive to a
species transferred to it from applicator 136, for example a
biochemically or chemically active agent and fluid carriers 142 or
144, or the like. Additionally, the applicator can be placed in
contact with the substrate surface and allowed to remain in place
while any species present in the fluid precursor is allowed to
harden, the fluid carrier is allowed to dissipate, or the like.
[0123] In accordance with all embodiments of the invention, such as
those illustrated in FIGS. 1, 2, and 11, the species formed
proximate the substrate surface in a pattern corresponding to the
indentation pattern of the article itself can be a self-assembled
monolayer. Suitable self-assembled monolayer-forming species are
described in U.S. Pat. No. 5,512,131 of Kumar, et al., referenced
herein. Self assembled monolayers formed of species X--R-Ch, as
described above, with or without metal ion and/or biological
species coordinated thereto, can be used, as well as other
self-assembled monolayer-forming species disclosed in application
Ser. No. 08/312,388, by Bamdad, et al., referenced above.
[0124] FIG. 12 illustrates schematically a process for applying a
species from indentations in an applicator to a non-planar surface.
An applicator 136 (shown in cross section) includes a plurality of
indentations 138, each filled with a species 150. Each of the
indentations can be filled with the same fluid or different fluids.
Species 150 can be any of the above-described fluid precursors,
chemically or biochemically active agents, or the like. An article
152 having a surface 154 is placed adjacent the application surface
of applicator 136 and rolled against the applicator as described in
commonly-owned, co-pending U.S. patent application Ser. No.
08/397,635 by Whitesides, et al., entitled "Microcontact Printing
on Surfaces and Derivative Articles", and Internation Patent
Application Publication No. WO 96/29629, both incorporated herein
by reference. As the article 152 including nonplanar surface 154 is
rolled against the applicator 136, species 150 is transferred to
surface 154 in a pattern corresponding to the indentation pattern
of the applicator. The indentation pattern can be any pattern as
described above, for example individual, isolated regions or one or
more continuous linear or non-linear indentations. The indentation
or indentations can be of one or more depths. Application to
nonplanar surfaces having various radii of curvature can be carried
out according to the invention, for example, radii of curvature of
less than about one centimeter, preferably less than about one
millimeter, more preferably less than about 500 microns, more
preferably less than about 100 microns, more preferably less than
about 50 microns, and according to a particularly preferred
embodiment printing can occur on substrates with radii of curvature
on the order of about 25 microns or less.
[0125] FIG. 13 illustrates an article 154 created by forming, on a
silicon dioxide surface 156 of a silicon substrate 158, a patterned
structure 160, for example a polymeric structure formed from a
prepolymeric fluid using a micromold as illustrated in FIG. 1.
Subsequently, a second fluid precursor is positioned so as to cover
the patterned structure 160 and allowed to solidify. According to
the embodiment illustrated, a fluid precursor was placed atop the
patterned structure 160 and a micromold having a complex pattern
was placed atop the fluid precursor. The fluid precursor was
hardened to form a structure 162 covering and encompassing the
patterned structure 160 on the substrate surface. The second
structure 162 included an exposed surface 164 having a pattern of
indentations 165 complementary to the indentation pattern of the
second micromold. The overall structure, when structure 160 differs
in refractive index from structure 162, can serve as a waveguide,
the second structure 162 serving as a cladding. The contoured
surface 164 of cladding 162 is lossy. The pattern of surface 164,
in most instances, is not important to the waveguide function.
Waveguides were fabricated from several classes of polymeric
materials (epoxies, polyurethanes, and polyacrylates on
Si/SiO.sub.2 substrates. Waveguides clad with polymers having
slightly lower refractive indices gave single-mode output in the
visible and near infrared regions. A typical waveguide structure
exhibiting single-mode behavior consisted of a trapezoidal
waveguide (n.sub.guide=1.545) clad in a polymeric slab with
n.sub.Cladding=1.52. The waveguide was 0.7 centimeters long and the
wavelength of light was 0.85 micron. Photocurable polymers are
preferred. Waveguides are described in greater detail below.
[0126] Referring now to FIGS. 14a-k, a schematic illustration of a
surface derivatized so as to include discrete regions of differing
chemical functionality is shown. The article schematically
illustrated finds particular use as a combinatorial library. An
article by Jacobs, et al., entitled "Combinatorial
Chemistry-Applications of Light-Directed Chemical Synthesis",
Trends in Biotechnology, volume 12, 19-26 (January, 1994;
incorporated by reference above) describes a photolithographic
process for forming a combinatorial library. Jacobs, et al.
describe derivatizing a substrate with linker molecules that
contain amines blocked by a photochemically cleavable protecting
group. Specific sites on this synthesis surface are
photo-deprotected by illumination through a photolithographic mask.
Those regions exposed to light are deprotected, and may then be
coupled to amino acids of interest using standard peptide-synthesis
conditions. The process is repeated using new masks until an array
of compounds of the desired length and composition are built up.
The patterns of photolysis and order of addition of amino acids
define the products and their locations on the solid support. The
present invention can find application in combinatorial library
synthesis with a minimum of expense and equipment. Those of
ordinary skill in the art will recognize that any of a wide variety
of chemically and biologically active agents can be used in
accordance with the procedure discussed below and illustrated in
FIGS. 14a-k. The criteria for selection of such agents is similar
to selection criteria for those agents described above that can be
positioned on a substrate surface using a forming article or
micromold 20. In a manner analogous to the procedure of Jacobs, et
al., wet chemical protecting groups can be utilized in accordance
with the present invention rather than photochemically cleavable
protecting groups. Orthogonal-stripe methods and binary synthesis
of combinatorial libraries in accordance with the invention, with
reference to FIGS. 14a-k, are described below in the prophetic
example.
[0127] The following prophetic example involves the creation of a
combinatorial library on a substrate surface using the micromold of
the invention. With optional reference to Jacobs, et al.,
"Combinatorial Chemistry-Applications of Light-Directed Chemical
Synthesis", Trends in Biotechnology, 12, 19-26 (January, 1994) and
Chemical & Engineering News, 74, 7, 28-73 (Feb. 12, 1996),
those of ordinary skill in the art can follow the teachings herein
to form a combinatorial library inexpensively.
[0128] Reference will be made to FIGS. 14a-k, which illustrate
schematically top views of a substrate surface. FIGS. 14a-c
illustrate an "orthogonal-stripe" method. According to the
technique, a plurality of micromolds are fabricated, each of which
has a distinct channel pattern. Each micromold is fabricated so as
to cover substrate surface 166, or at least enough of substrate
surface 166 to define a channel or channels necessary for
application of chemically or biochemically active agents to desired
regions of the surface. For purposes of illustration, the
description will assume use of a micromold that completely covers
substrate surface 166, and includes indentations in register with
certain portions of substrate surface 166. One micromold includes
an indentation in register with a portion of the substrate surface
designated "A" in FIG. 14a and includes a contact surface that
contacts the remaining substrate surface at areas designated "B",
"C", and "D". With reference to FIG. 14b, individual micromolds
will be fabricated that include contact surfaces that cover all
portions of the substrate except one of the portions "E", "F", "G",
or "H". That is, each micromold forms a channel through which a
chemically or biochemically active agent (reactant) can be
delivered to the substrate surface at a portion in register with
the channel, while remaining portions of the micromold block
regions proximate the substrate surface from interaction with the
particular chemically or biochemically active agent. Any
combination of micromolds can be used to apply to the surface, in
any combination, various chemically or biochemically active agents.
For example, with reference to FIG. 14a, if a micromold having a
channel in register with region "A" of the substrate surface is
used to apply to the surface a chemically active agent "A" and
then, with reference to FIG. 14b, a micromold is placed adjacent
the substrate surface that has an indentation in register with
region "E" and is used to apply to region "E" a chemically active
agent "E", the substrate surface will include a region carrying
chemically active agent "A" (the region designated "A" in FIG.
14a), a region carrying chemically active agent "E" (the region
designated "E" in FIG. 14b), and at the region where the regions
"A" and "E" intersect both chemically active agents will have been
applied (upper left corner of the substrate surface as viewed in
FIG. 14c). It can be seen that, if all combinations of micromolds
and chemically active agents are employed, the result will be a
grid on the substrate of each combinatorial permutation of the
chemically active agents each confined to a separate region of the
substrate surface (FIG. 14c). As is apparent to those of ordinary
skill in the art, the order of application of active agent to the
various regions of the substrate surface can be used to tailor the
synthesis of the individual species at the various locations on the
substrate surface.
[0129] With reference to FIGS. 14d-k, a "binary" synthesis
technique is described. In FIG. 14d, a first micromold having an
indentation in register with region "A" and a contact surface in
register with region "O" is used to apply to the substrate surface
an active agent "A" selectively at region "A". FIG. 14b shows
surface 166 including a region "B" in register with an indentation
of a second micromold and a region "O" in register with a contact
surface of the second micromold, via which an active agent "B" can
be applied selectively to region "B" of the substrate surface. FIG.
14f shows surface 166 having portions "C" and "O" that are
positionable in register with indentations and contact portions,
respectively, of a third micromold to apply an active agent "C" to
regions "C". In FIG. 14g the surface includes portions "D" and "O"
that are positionable in register with indentations and contact
portions, respectively, of a fourth micromold to transfer agent "D"
selectively to regions "D". The binary technique is less labor
intensive than the orthogonal-stripe method in that only four
transfer or flow steps involving four micromolds are needed to
create a grid of sixteen distinct chemically or biochemically
functional regions on the substrate surface.
[0130] After application of the first micromold and formation of
chemically or biochemically active agent "A" via the channel of the
first micromold, agent "A" is applied to the left side of the
substrate surface 166 and the right side of the substrate surface
remains free of agent as illustrated in FIG. 14h. After application
of agent "B" to the upper portion of substrate surface using the
second micromold, four quadrants of the substrate surface carry
agent "A" plus agent "B", agent "B", agent "A", and no agent,
respectively, as illustrated in FIG. 14i. After application of
agent "C" via the channels of the third micromold, eight regions of
distinct chemical or biochemical functionality exist on the surface
as illustrated in FIG. 14j. After application of agent "D" via the
indentations of the fourth micromold, sixteen distinct chemically
or biochemically active regions are formed as illustrated in FIG.
14k, namely "ABCD", "ABC", "BCD", "BC", "AND", "AB", "BD", "B",
"ACD", "AC", "CD", "C", "AD", "A", "D", and "O". The register
between each micromold and the substrate surface can be controlled
by pins in the substrate that engage each micromold, pins in each
micromold that engage the substrate surface, an X-Y table that
positions the substrate surface identically relative to each
micromold, optical, magnetic, or electronic aligning apparatus, or
other equivalent apparatus that can align each micromold with the
substrate surface. Accurate register at the micron scale is
achieved.
[0131] Those of ordinary skill in the art have the ability to
select, without experimentation or with only routine
experimentation, chemically or biochemically active agents that can
be used to create a myriad of chemically active or biochemically
active combinatorial libraries according to the technique of the
invention. It can be useful to first coat substrate surface 166
with a common chemical linker functionality coupled to a chemical
protecting group, apply a first micromold to the substrate surface,
first deprotect at the region in register with the channel, then
carry out a synthesis step at that region and reprotect, then
remove the first micromold and apply a second, different micromold,
again deprotect at the portion of the substrate surface in register
with the channel of the second micromold, carry out a second
synthesis step, and reprotect, etc. Libraries of peptides,
synthetic molecules such as new drugs, naturally-occurring chemical
and biochemical species, oligonucleotides and the like can be
created. Indeed, any of the chemically or biochemically active
agents, fluid precursors, prepolymeric fluids, or the like as
described above that are transferable from a microapplicator or
that can be applied, for example via capillary action, to a surface
using a micromold as described above, can find use in the
combinatorial arrangement described. Any combination of various
agents can be used.
[0132] As an alternative embodiment to that described above, an
article 20 as illustrated in FIG. 2, having a contoured surface 22
including a plurality of protrusions separated by intervening
indentations 24 can be used as a stamp for forming a combinatorial
library. Stamping as described in U.S. Pat. No. 5,512,131 (issued
Apr. 30, 1996 to Kumar, et al., referenced above) can be employed.
The stamp includes a stamping surface defined by the outer surfaces
of the protrusions. The process is described with reference to
FIGS. 14d-k. A surface 166 carries a protecting group, for example,
a self-assembled monolayer exposing outwardly an azide
functionality. A stamp having a surface including a protrusion in
register with area A of surface 166 (FIG. 14d) is prepared by
applying to the protrusion a deprotecting species such as a
reducing agent for reduction of the azide to a deprotected,
reactive amine. Application of the stamp to surface 166 deprotects
the self-assembled monolayer at region A, but leaves the remainder
of surface 166 (O) protected. Then, chemical reactivity at region A
can take place, followed by reprotection of the entire surface.
Then the stamp can be re-oriented, or a second stamp chosen, so
that region B is deprotected by contact with a stamping surface
(protrusion) of a stamp. Chemical reaction then is carried out a
region B, and the surface re-protected. With reference to FIG. 14f,
a stamp having protrusions corresponding to regions C is used to
deprotect at regions C, followed by chemical reaction at regions C
and re-protection, and the process carried out similarly at regions
D (FIG. 14g). According to a preferred embodiment, the stamping
surface itself, without any auxiliary agent carried thereon, can
deprotect at regions of surface 166 in register with the stamping
surface. For example, a stamp having an acidic stamping surface
such as a hydrogel loaded with a component of low pH can be used.
For example, Dextran.TM. carrying polyphosphoric acid can be
grafted to a surface of a rigid or elastomeric stamp and used to
deprotect surface 166 at regions corresponding to the protrusions
or stamping surface. Other protecting/deprotecting chemistries such
as hydrolysis chemistry can be carried out.
[0133] According to another embodiment, rather than building a
combinatorial library through step-by-step synthesis of various
species at various distinct regions proximate a substrate surface,
distinct species can be synthesized and applied to the substrate
surface after synthesis. A combination of these approaches can be
used as well, involving synthesis of building blocks that are
assembled according to the prophetic example.
[0134] FIG. 15 illustrates a set of particularly preferred
fabrication techniques of the invention in which, rather than
applying article 20 to substrate surface 28 followed by
introduction of fluid precursor 36 into channels 32 so defined,
article 20 is used as an applicator to transfer the fluid precursor
to substrate surface 28. The following description will be made
with reference to fabrication of a structure 38 and other
structures that are waveguides, from a precursor 36 that will be
referred to as a waveguide precursor, although the following
description defines one aspect of the invention that is applicable
to creation of any of a wide variety of structures described herein
and is not limited to waveguides. In FIG. 15, fluid precursor 36 is
first applied to indentations 24 of applicator 20. Excess fluid
precursor then can be removed, by scraping, from application
surface 22. For example, a block of material similar or identical
in composition to that of article 20 can be used to scrape off
excess prepolymer. Alternatively, with appropriate structures, the
excess precursor can be blown off with a brisk stream of gas such
as nitrogen. A brisk stream of gas also can be used to remove
remaining drops of precursor after the bulk excess of precursor has
been scraped away. Applicator surface 22, the indentations of which
are filled with fluid waveguide precursor 36, then is placed in
contact with surface 28 of substrate 30. Applicator 20 then can be
removed, leaving some or all of precursor 36 in contact with
surface 28 where it is subsequently made dimensionally stable or,
according to preferred embodiments, fluid precursor 36 is hardened
to the point that it is dimensionally stable while article 20
remains in place upon substrate surface 28. Where fluid precursor
36 is a fluid prepolymer, and is heat-curable, the precursor can be
heated, for example, by heating substrate 30, article 20, both
substrate 30 and article 20, or applying radiative heat. Where
precursor 36 is a photopolymerizable fluid, it can be exposed to
electromagnetic radiation that causes polymerization. A fluid
precursor 36 can be partially or fully polymerized prior to removal
of article 20, so long as it is polymerized to the extent that it
is dimensionally stable and self-supporting. In preferred
embodiments, as described below, it is often advantageous to only
partially polymerize a fluid prepolymeric precursor 36.
[0135] Where fluid precursor 36 is a fluid carrier of a suspension,
the fluid carrier can be selected in conjunction with the material
of article 20 to allow the fluid to be absorbed into article 20 and
thereby dissipated, resulting in deposition of solid material from
the suspension as the patterned material on substrate surface 28.
Where fluid precursor 36 is a solution of a dissolved precipitating
species, conditions such as temperature, pH, or the like can be
altered to cause precipitation. One advantage of the technique of
FIG. 15 is that the fluid precursor is in contact with article 20
for only a very brief period of time, thus if article 20 adsorbs or
absorbs any components of fluid precursor 36 disadvantageously,
such as adsorption of dyes, this is minimized. Another advantage is
that with a thermally-curable precursor the technique is made much
easier since the time required for the process is very fast
relative to typically curing times.
[0136] Following solidification of fluid precursor 36 to form an
array of waveguides 38, solidification taking place to the extent
that waveguide 38 is dimensionally stable, article 20 is removed
from substrate 30. Following this step, or other steps for forming
an array of waveguides 38 on substrate surface 28 (e.g. as
described with reference to FIG. 1), a cladding can be provided
upon the waveguide array to form a waveguide assembly 44 by adding
a hardenable cladding precursor fluid 40 on top of the array,
optionally forming fluid 40 into a desired shape with a desired
thickness above and beside the waveguide array by, for example,
positioning a cladding mold 42 above the precursor to form the
precursor, allowing the cladding precursor to harden (for example,
via polymerization) and removing cladding mold 42 to form a
cladding 43 that includes a layer of cladding above waveguides 38.
In another embodiment a cladding mold 168 can be used which molds
cladding precursor 40 between waveguides 38 and laterally of
waveguides 38, but does not allow formation of cladding above the
waveguides to form an assembly 172. This can be accomplished where
the cladding mold 168 is a flexible elastomeric mold that conforms
to form a mold resting atop waveguide 38. The cladding precursor is
allowed to harden, and removal of the mold results in a cladding
170 that fills spaces between waveguide 38, and extends laterally
beyond the lateral-most waveguides such that each side of each
waveguide is contacted by cladding, but the top of each waveguide
is exposed. In another embodiment a waveguide assembly 174 can be
formed by applying cladding precursor 40 to waveguides 38, allowing
the cladding precursor to drip off of the waveguides, and hardening
the cladding precursor.
[0137] In each case, subsequently, the substrate/waveguide/cladding
assembly can be cleaved along lines a-a and b-b to define a
waveguide assembly 44, 172 or 174 having a typical waveguide width
x on the order of less than about 100 microns, typically on the
order of from about 1 to about 10 microns, more typically from
about 2 to about 4 microns, a waveguide height y on the order
similar to that of dimension x, more typically slightly less than
x, for example about 1 micron, and, in the case of waveguide
assembly 44, an overall assembly height including cladding of a
dimension z on the order of dimension y to about 10 times dimension
y, for example from about 1 to about 10 microns and a length l of
any of a wide variety of lengths on the order of 100 microns to
centimeters. Larger waveguides can be made as well, for example
waveguides having width or height on the order of 200 or 250
microns, with spacing of similar order. In the case of waveguide
assembly 172 the cladding height equals the waveguide height, and
in the case of 174 the cladding height typically is very slightly
greater than the waveguide height.
[0138] Another technique for fabricating a waveguide assembly 172,
including waveguides 38 and cladding 170 which contacts the sides,
but not the tops of waveguides 38 is as follows. Following
fabrication of waveguides 38, and prior to application of any
cladding, a microcontact printing technique as described in
international patent publication no. WO 97/07429, of international
patent application no. PCT/US96/13223 entitled "Patterned Materials
Deposition Effected with Microcontact Printing" is carried out to
apply a hydrophobic component selectively to the tops, but not the
sides of waveguides 38, followed by addition of a hydrophilic
cladding prepolymeric precursor which assembles within and between
waveguides 38, but not atop waveguides 38, followed by curing of
the cladding precursor. The particular microcontact printing
technique involves coating a flat applicator with a self-assembled
monolayer forming molecular species and applying the flat
applicator to waveguides 38 such that the applicator contacts only
the tops of waveguides 38. Any molecular species transferable in
this manner can be used to create a hydrophobic functionality atop
waveguides 38 such that a hydrophilic prepolymer will assemble
between waveguides 38 and laterally on either side, or the opposite
can be carried out in which a hydrophilic material is applied to
the tops of waveguides 38 and a hydrophobic cladding precursor used
to fill spaces between and laterally of the waveguides where the
waveguides and surface 28 of substrate 30 is sufficiently
hydrophobic. In one technique, surface 28 and waveguides 38 were
subjected to oxidizing treatment, and microcontact printing was
used to transfer a self-assembled monolayer of a
fluorine-terminating molecule to the surface. Specifically,
tridecafluoro-1,1,2,2-tetrahydro(o-octyl)-1-trichlorosilane was
applied to the tops, but not sides, of waveguides 38 and formed a
hydrophobic self-assembled monolayer thereon. A hydrophilic
cladding precursor, in particular a liquid polyurethane prepolymer,
was added and assembled between and laterally of waveguides 38.
Curing of the polyurethane cladding precursor, followed by cleaving
of the waveguide ends, resulted in a waveguide assembly similar to
assembly 172.
[0139] In typical embodiments, cladding is added to waveguides 38
to lower the refractive index difference between waveguides 38 and
their surrounding environments. Without cladding, waveguides 38
typically are very good performers, but support too many modes.
Addition of cladding, which reduces the refractive index difference
at the boundaries of waveguides 38, reduces higher order modes.
[0140] FIG. 13 (discussed above) is essentially identical to a
cross-section through line a-a of waveguide assembly 44 of FIG. 15,
showing a typical substrate 30, optional film 31 of an adhesion
promoter, native oxide layer, or the like on substrate 30 (the top
surface of film 31 defining substrate surface 28 according to this
embodiment), array of waveguides 38, and cladding 43. The waveguide
of FIG. 13 differs from waveguides fabricated in accordance with
the technique of FIG. 15 in that it includes a contoured cladding
surface corresponding to a contoured cladding mold. Precursor 36 is
a material as described above which can serve as a waveguide.
Selection of such materials is within the level of ordinary skill
in the art.
[0141] In embodiments of the invention involving waveguide
fabrication, substrate 30 can be essentially any material including
those materials described above, but should be optically smooth.
Substrate surface 28 can be of the same material as the bulk
material of substrate 30, or a different material. A non-limiting,
exemplary list of substrate materials includes silver, gold, glass,
silicon/silicon dioxide, and the like. The waveguide pattern can be
formed on contoured surfaces, and flexible surfaces. Where
substrate 30 is flexible (for example, a polyvinylchloride film)
the waveguide can be deformed while guiding light. The utility of
this technique will be described more fully below. In embodiments
of the invention involving waveguide fabrication, article 20 can be
as described above, and preferably is elastomeric.
[0142] Selection of materials for waveguide 38, cladding 43, and
substrate 30 (and optional film 31) can be selected by those of
ordinary skill in the art to form a structure that can guide
electromagnetic radiation of a desired frequency. As is known,
total internal reflection of electromagnetic radiation will occur
within waveguide 38 where the electromagnetic radiation propagating
within the waveguide strikes an interior boundary of the waveguide
to form an angle .theta., with a line normal to the interior
boundary, where sin .theta. is .gtoreq.(refractive index of the
cladding)/(refractive index of the waveguide). Those of ordinary
skill in the art can select materials to form the overall system 44
that will serve as a waveguide. In one set of embodiments cladding
43 can be non-existent. That is, the cladding can be the
environment surrounding the waveguide, such as air. In some
embodiments it is useful to have a cladding defined by a material
filling the indentations between and defined by waveguides 38,
where the top surfaces of waveguides 38 are exposed to ambient
conditions. The difference in index of refraction between waveguide
and cladding, and waveguide and the substrate, typically is from
about 0.01 to about 0.001. These and other embodiments can be
useful as sensors, etc., and are described more fully below.
[0143] It is one feature of the invention that waveguides 38 and
cladding 43 can be formed from an identical, or nearly identical
fluid prepolymer, the degree of polymerization of which can be
controlled by the amount of exposure to polymerization conditions
such as heat or radiation. For purposes of the invention,
"polymerization" is meant to encompass cross-linking. This
technique is facilitated by the fact that the refractive index of a
solid typically is greater than the refractive index of a liquid of
similar composition in that the density of a solid typically is
greater than of a liquid. The difference in index of refraction
typically decreases with curing time for a polymer. Thus, the
difference in refractive index can readily be tailored. This
technique provides several advantages that will become apparent
from the discussion below. One advantage is simplicity, since in
this embodiment only a single prepolymer fluid need be used, first
as prepolymer fluid 36 (with reference to FIG. 15) that is
positioned with article 20 against substrate surface 28 and
polymerized, for example photopolymerized, followed by addition of
a common prepolymer (the same prepolymer) cladding precursor 40
which then can be photopolymerized. During polymerization (curing)
of cladding prepolymer 40, waveguide 38 is cured to a greater
extent, and the refractive index difference between cladding 40 and
waveguide 38 decreases during curing of cladding 40. One advantage
of using identical, or nearly identical fluid prepolymers both for
waveguides 38 and cladding 43, the difference in refractive index
being due to different curing times, is that any batch-to-batch
difference between polymers is unimportant as the amount of
exposure to polymerization conditions is the only important
feature. That is, the relative refractive index change in material,
during curing, is what is important, and conditions do not need to
be adjusted because of slight variation in material
composition.
[0144] One advantage of the transfer technique of FIG. 15 is that
it is exceptionally simple experimentally, and very inexpensive. It
can readily be used to produce multiple copies of complex
microstructures. Another advantage of the technique is that many
waveguides can be fabricated essentially simultaneously. Tens or
hundreds of applicators 20 can be fabricated from a single master
which is, in turn, fabricated from a photolithographically-created
surface or the like, and each applicator can be used to fabricate
hundreds or thousands of waveguides. For example, where an
applicator 20 having a dimension perpendicular to the linear
dimension of indentations 24 of approximately 3 centimeters is
used, and indentations 24 each are of approximately 2 microns in
width and spaced approximately 2 microns from each other, one
molding process as illustrated in FIG. 15 can result in more than
4,000 waveguides.
[0145] Another advantage of the transfer molding technique of FIG.
15 is that multiple layers of waveguides can be fabricated readily.
With reference to FIG. 16, applicator 20 first can be used to
transfer fluid waveguide precursor 36 to substrate surface 28 where
it is hardened to form waveguide array 38, as illustrated also in
FIG. 15, and then waveguide array 38 on substrate 30 can be placed
upside down upon another applicator 20 including indentations
filled with fluid waveguide precursor 36, precursor 36 can be
cured, and applicator 20 removed to form a two-layer stacked array
248. The process can be repeated any number of times to form any
number of layers of waveguide arrays, as exemplified by stacked
waveguide array 250, with the waveguides arranged in any
orientation relative to each other in which support for each layer
is provided.
[0146] Yet another advantage is that periodicity in the cladding
structure 43 (FIG. 15) can be readily formed, via a cladding mold
42 including a periodically contoured inner surface, or via
irradiation of cladding 43 through a mask to cure alternating
portions of the cladding to a greater extent relative to
intervening portions. In this manner, a grating can be fabricated
in the cladding, such as a Bragg grating. Gratings also can be
fabricated directly in or onto waveguides 38 by using a mold 20 in
which the indentations that in part define the mold for the
waveguides includes a contoured interior surface. Chirped
waveguides and other periodic structures can be fabricated in the
cladding, or in the waveguide core itself, in this technique.
Attenuation can be achieved in this way, and resident cavities can
be created.
[0147] Another feature of the present invention is the ability to
fabricate waveguide couplers, easily and conveniently, regardless
of the local geometry of the waveguide. FIG. 17 is a schematic
illustration of a prior at "Y" coupler including branched portions
as shown, for example, in U.S. Pat. No. 5,313,545 (Kuo, et al.),
including a coupling region 252 and branching input/output regions
253, 254, 255, and 256. Radiation input from regions 253 and 255
will couple at region 252 and will branch and travel along both
branching portions 254 and 256. Alternatively, radiation input from
branches 254 and 256 can be made to couple at region 252 and branch
into regions 253 and 255, optionally constructively or
destructively interfering to some extent in region 252.
[0148] FIG. 18 is an illustration of a prior art "evanescent"
coupler, the principle of which is used to provide coupling between
guides of U.S. Pat. No. 5,481,633 (Mayer). This coupler operates on
the principle that, depending upon the refractive index between
waveguide and surrounding environment (e.g., cladding) the
waveguide dimensions (size and shape), the wavelength of light, and
separation between waveguides, an "evanescent tail" extends from
each waveguide, the energy of the tail decreasing with distance
from the guide. Where waveguides are close enough to each other,
and the evanescent tail passes into the adjacent waveguide,
radiation can leak into the adjacent waveguide and the waveguides
couple. In the prior art array of FIG. 18, waveguide 258 includes a
coupling portion 260 and non-coupling portions 262 and 264 and
waveguide 266 includes a coupling portion 268 and non-coupling
portions 270 and 272. In the array illustrated, based upon the
selection of materials and dimensions and wavelength of light,
coupling portions 260 and 268 are close enough such that the
evanescent tail of radiation in each guide passes into the adjacent
guide and coupling occurs in these regions. However, non-coupling
portions 262, 264, 260, and 272 each are separated from the
adjacent waveguide by a distance that does not allow coupling.
Coupling thus controllably occurs only at regions 260 and 268,
which thereby defines a coupling junction. The prior art arrays of
FIGS. 17 and 18 are suitable for many purposes, but, as can be
seen, requires significant control and geometry of
construction.
[0149] The particular shape of the waveguide required for either of
the couplers of FIGS. 17 and 18 is limited also by the fact that
curves or corners that form part of the shape of a waveguide should
not exceed a maximum amount of sharpness, or the critical angle of
total internal reflection will be exceeded and loss of
electromagnetic radiation will occur.
[0150] The invention provides a solution to this problem, as
illustrated in FIG. 19 which illustrates an array including
essentially parallel waveguides 274 and 276 and cladding 278 which
can completely envelope and cover waveguides 274 and 276, or the
like. Each of waveguides 274 and 276 and cladding 278 can be formed
from an identical prepolymeric precursor with differences in
refractive index controlled by different curing times. The array of
waveguides 274 and 276 and cladding 278 includes central portion
280 and lateral portions 282 and 284. Curing times are controlled
such that the refractive index ratio between waveguides 274 and
276, and cladding 278, within central portion 280 is relatively
small, while the refractive index ratio between the waveguides and
the cladding in lateral portions 282 and 284 is relatively high,
such that coupling occurs between waveguides 274 and 276 within
portion 280, but does not occur in lateral portions 282 and 284.
Thus, region 280 defines a coupled region of the waveguides that is
functionally similar to the coupled portions 260 and 268 of
waveguides 258 and 266 of FIG. 18, and coupled portion 252 of the
branched structure of FIG. 17. This can be achieved, for example,
as follows. Waveguides 274 and 276 are fabricated from fluid
polymeric precursors as illustrated in FIG. 15, and only partially
cured to the extent that they are dimensionally stable. Then, the
same polymeric precursor, as a cladding precursor, is placed over
waveguides 274 and 276 and cured until dimensionally stable. Where
the refractive index difference at this point in the process is
great, coupling cannot occur through all of portions 282, 280, and
284 of the array. Subsequently, only portion 280 is subjected to
additional photopolymerization conditions, resulting in
significantly decreased refractive index differences between
waveguides 274 and 276 and cladding 278 in that region (280). The
result is that, in regions 282 and 284, coupling does not occur,
but in region 280 coupling occurs. One advantage of the technique
is that coupling can be tailored at any region of the waveguide
array where waveguides designed to carry UV or visible light, of
the type produced by a red He--Ne laser, are separated more than
about 2 microns, for example up to 6 microns, 8 microns, or even 10
microns in region 280, allowing much simpler fabrication that does
not require as much precision. In contrast, the coupling regions of
FIG. 18 are defined by their separation distance, which typically
must be much smaller than the separation distance allowable for the
system of FIG. 19, requiring significantly greater precision and
related expense.
[0151] In another embodiment of the invention the locations of the
regions of coupling between waveguides are tailorable, and the
amount of coupling at those locations is controllable. This can be
accomplished when waveguides 274 and 276 and cladding 278 are
selected such that the refractive index ratio between waveguide and
cladding can be changed, reversibly, after fabrication. For
example, where the refractive index of cladding 278 can be changed
reversibly based upon exposure to specific electromagnetic
radiation (where, for example, cladding 278 is reversibly
photosensitive; such materials are known to those of ordinary skill
in the art) the array can be fabricated and region 280 irradiated
with the specific radiation to cause coupling where no coupling
occurs in regions 282 and 284. Then, the specific radiation can be
discontinued, terminating coupling in region 280, and region 282
can be exposed to the specific radiation resulting in coupling
within region 282 where no coupling occurs in regions 280 and 284.
As can be seen a coupling pattern in a large array can be readily
changed, reversibly, depending upon the pattern of the specific
radiation. In another arrangement, cladding 278 can be one or more
fluids contained in separate chambers that define regions 280, 282,
and 284, and the content of the fluid chambers can be controlled to
control the refractive index ratio between waveguide and
cladding.
[0152] The above technique facilitates a waveguide coupler that can
be used at different wavelengths of light. That is, where the
refractive index difference at the boundaries of waveguides can be
adjusted during use, or between uses, by exposure to different
electromagnetic radiation, electric fields, or the like, the
waveguide can be adjusted for use with different wavelengths of
light. This also can be used to adjust the degree of coupling that
occurs during use. For example, coupling could be adjusted from ten
percent to fifty percent by exposure to electromagnetic radiation
according to this technique.
[0153] The geometrical tailorability of refraction index ratio
between cladding and waveguide facilitates the creation of a
variety of switches and sensors. With reference to FIG. 19, where
cladding 278 is an electro-optical material or other material that
can reversibly change refractive index upon exposure to certain
electric fields, or is a non-linear optical material (e.g., dye)
that changes in refractive index in response to electromagnetic
radiation, the array can be a sensor of that electric field or
electromagnetic radiation since exposure to the field or radiation
will cause a detectable change in coupling between waveguide 274
and waveguide 276. In one arrangement, region 280 can be defined by
a cladding that is reversibly electric field sensitive, while
sections 282 and 284 are not, thus sensitivity to the specific
electric field exists at region 280 only, and coupling at region
280 is indicative of the existence and strength of the field.
[0154] As an example of a sensor of a chemical or biological
species in accordance with the invention, the cladding of region
280 can include, on its exposed surface, a material that is
sensitive to a particular analyte such that when the analyte is
present, the refractive index of the cladding changes in an amount
sufficient to detectably change the coupling characteristic between
waveguides 274 and 276 in region 280. As one example, region 280
can define a flow chamber about waveguides 274 and 276 such that a
desired fluid can be reversibly placed in contact with waveguides
274 and 276 in region 280. The change in the existence of, or
concentration of, a particular analyte in the fluid (such as a salt
or other refractive index-altering substance) can cause
quantitative, or qualitative changes in coupling between guides 274
and 276 at region 280, resulting in quantitative or qualitative
sensing. For example, a cation or anion exchange material can be
provided that a surface, such as a sulfonic, phenolic, phosphoric,
or carboxylic acid group, for capture of ions from solution.
Chelating agents, kryptands, crown ethers, and the like can be
used.
[0155] As another example, the array of FIG. 19 can be constructed
where, at region 280 (or other or all regions) cladding 278
includes an exposed surface that carries an immobilized biological
binding partner of a biological molecule or exposed surfaces of
waveguides 274 or 276 carry an immobilized biological binding
partner. Referring to FIG. 15, where a technique for forming a very
thin cladding on the waveguides is used, the biological molecule
can be provided on the cladding. A more sensitive sensor can result
from a waveguide fabricated, with reference to FIG. 15, including
exposed top surfaces. In a method for sensing the biological
molecule, a medium suspected of containing the biological molecule
is exposed to the surface of cladding 278, waveguide 274 and/or 276
(at region 280) if region 280 carries the biological binding
partner exclusively and, if present, the biological molecule binds
to its immobilized binding partner, changing the refractive index
of cladding 278 (e.g. at region 280) and thereby changing the
refractive index ratio between the waveguides and cladding in that
region, detectably altering coupling. As mentioned, where a
cladding completely covers waveguides 274 and 276 in this
particular embodiment, it is generally desirable that cladding 278
form only a very thin layer above waveguides 274 and 276, such that
biological binding at the outermost surface of the cladding
produces a greater relative effect in change of refractive index
ratio between waveguide and cladding. Alternatively, the cladding
may be non-existent and the biological molecule can be immobilized
directly upon a surface of the waveguide, or the cladding can
partially cover the waveguide surface with remaining portions of
the waveguide surface carrying the immobilized binding partner. In
specific embodiment, any of a variety of biological binding pairs
can be used, one member of the pair immobilized at cladding 278 or
waveguides 274 and 276 and the other member being the analyte. In
this context, the term "biological binding pairs" is as defined
above, referring to a corresponding pair of molecules that exhibit
mutual affinity or binding capacity, typically specific or
non-specific binding or interaction, including biochemical,
physiological, and/or pharmaceutical interactions.
[0156] As mentioned above, substrate 30 can be flexible. This
facilitates a method involving guiding electromagnetic radiation
through a waveguide array of at least two waveguides,
simultaneously, while altering the conformation of the waveguides.
That is, the substrate carrying a plurality of waveguides can be
bent or otherwise deformed during electromagnetic radiation
propagation. This can be useful for a variety of purposes, one of
which is increased sensitivity in a sensor. Where a sensor is
sensitive to changes in a surface of a waveguide or cladding that
occur upon exposure to an analyte, as described above, sensitivity
can be increased as follows. The waveguide can be bent to its limit
of maintaining total internal reflection, which is readily
determined by bending the waveguide too far and then returning the
waveguide to a conformation allowing total internal reflection.
Where the interaction of an analyte with the waveguide decreases
the difference in refractive index between waveguide and cladding,
loss of electromagnetic radiation passing through the waveguide can
be indicative of interaction with an analyte, and is made much more
sensitive where the waveguide is almost at the limit of maintaining
total internal reflection prior to exposure to the analyte. In
another example, where coupling between waveguides is highly
dependent upon the conformation of the waveguides, altering the
conformation of the waveguides (facilitated with a flexible
substrate) can result in operation very near the limits of coupling
where exposure to an analyte will relatively more greatly affect
coupling.
[0157] Referring now to FIG. 20, an array 286 of waveguides 288,
290, 292, 294 and 296, which are essentially linear and parallel,
is illustrated. Where the array is fabricated such that conditions
allow coupling between waveguides, as described above, light
introduced into waveguide 292 can couple into waveguides 290 and
294, and from waveguide 290 can couple back into waveguide 292 and
into waveguide 288, and from waveguide 294 can couple back into
waveguide 292 and into waveguide 296. The result is that an
interferometer is created and an interference pattern defined by
radiation emerging from each of waveguides 288-296 is created and
is distinctive based upon spacing of the waveguides, refractive
index difference between waveguide and cladding, waveguide
dimensions, wavelength of radiation, and propagation length. The
system of FIG. 20 can serve as a sensor since any change in
refractive index differs at the boundaries of one or more
waveguides, for example a difference in refractive index of the
cladding surrounding waveguides 288-296 such as via exposure to an
electric field or electromagnetic radiation, exposure to a fluid,
or exposure to another analyte as described above will alter the
interference pattern emerging from waveguides 288-296.
[0158] A series of working examples were conducted relating to
waveguides. With the exception of cross-linking of the polymer,
synthesis was conducted in a class-100 clean room. A
poly(dimethylsiloxane) (PDMS) elastomeric mold, or applicator, 20
(sylgard 184, Dow Corning, Silicone Elastomer: curing agent=15:1)
was cast from a photoresist pattern made in a standard
photolithographic process (Kumar, et al., Langmuir, 10, 1498
(1994)). With reference to FIG. 15, an array of waveguides 38 was
formed by filling the relief structure (indentations 24) in
applicator surface 22 of applicator 20 with a liquid prepolymer
(polyurethane, NOA-73, Norland Products New Brunswick, N.J.) and
then placing the applicator surface of the filled applicator 20 on
substrate surface 28 of a Si(100) wafer 30 supporting a 2
micron-thick layer of SiO.sub.2. The prepolymer was cross-linked in
situ by irradiating the system for 1 hour at a distance of 1
centimeter with a 450 W medium-pressure Hg vapor lamp (type
7825-34, Ace Glass, Vineland, N.J.). After UV exposure, the
elastomeric mold (applicator 20) was peeled away, leaving an array
of waveguide structures 38 on substrate 30. The technique was
pattern used to generate waveguides with a variety of widths of
2.0, 2.6, 3.0, and 4.0 microns, and spacings of 2.0, 4.0, and 8.0
microns. All waveguides had the same height of approximately 1
micron. The length of the waveguides was determined by the points
at which the wafer was fractured. In one set of embodiments the
waveguide array was left unclad. In embodiments in which cladding
was applied, cladding was made by providing a thick layer of the
same liquid prepolymer and applying it to the waveguides, the
surfaces of which had been slightly oxidized by exposure for about
10 minutes in a UV-ozone cleaner (models 13550 and 13550-2, Boekel
Industries) to render them hydrophilic and improve adhesion. The
system was heated to 85.degree. C. on a hot plate to decrease the
viscosity of the prepolymer, and the excess prepolymer was allowed
to drain to one edge. The thin layer of prepolymer left on the
surface was loosely cross-linked by brief (1 minute) exposure to UV
light (365 nm) from a 4 W hand-held lamp (Blak-Ray UV lamp model
UVL-21, UVP, San Gabrielle, Calif.). The ends of the clad
waveguides were squared by cleaving the substrate. After cleaving,
the cladding was cured completely (30 seconds) with the 450 W
medium-pressure Hg vapor lamp. This procedure allowed the ends of
the waveguides to be cleaved when the cladding layer was in the
liquid phase, preventing the cladding from de-adhering from the
guides.
[0159] FIG. 21 is a photocopy of an SEM image of an unclad
waveguide array, and FIG. 22 is a photocopy of an SEM image of a
clad array, each fabricated according to this technique. In each
case waveguide width was about 2.6 microns, waveguide spacing was
about 2.0 microns, and waveguide height was about 1.0 microns.
[0160] FIG. 23 is a schematic diagram of apparatus used to couple
light into and out of waveguide arrays fabricated as described
immediately above. Light from a He--Ne laser 298 (633 nm) was first
coupled into a single-mode optical fiber 300 which was butt-coupled
to the end of waveguides of array 302 (representative of a variety
of waveguide arrays fabricated as described immediately above, and
tested in accordance with this example) using a precision
3-dimensional translation stage 304. Light also could be coupled
into the waveguide array using focusing apparatus. That is, light
from a laser could be focused, through a lens arrangement, to the
end of waveguides of the array 302. Using this apparatus, light was
selectively coupled into individual waveguides in the array, or
into the cladding between or above the waveguides. The output light
from the waveguides was imaged with a microscope objective 305 and
recorded on a CCD camera 306. The shapes and intensities of the
outputs of the individual waveguides could easily be observed (in
the absence of the objective 305 the far field patterns from
adjacent waveguides overlapped).
[0161] FIGS. 24a-g show the results of a variety of different
waveguide arrays and inputs, and demonstrate tailorable coupling,
using the apparatus of FIG. 23 and waveguide arrays fabricated as
described above. In FIG. 24a, trapezoidal waveguides 38 indicate
the positions, in cross-section, of 3 micron-wide waveguides with
neighboring waveguides separated by 8 microns. The height of each
waveguide was 1 micron. Optical fiber 300 was positioned as
indicated, in alignment with the central of the 5 waveguides. FIG.
24b is a photocopy of a CCD camera frame grab of the output of the
system of FIG. 24a. A single-mode output occurred, with no
evanescent coupling between adjacent waveguides. FIG. 24c is
representative of a second waveguide structure fabricated in
accordance with the technique described above, with waveguides
separated by 4 microns, rather than 8 microns. The UV exposure time
for the array of FIG. 24c was the same as for the array of FIG.
24a. However, the 4 micron spacing was small enough to allow
evanescent coupling between guides and light was observed in 5
adjacent waveguides (FIG. 24d: photocopy of a CCD camera frame grab
of result). Additionally, as the input optical fiber was moved to
adjacent waveguides, this output pattern moved in register. The
reproducibility and symmetry of the pattern established the
uniformity of the coupling between the waveguides in the array. The
low level of light at the exit of the central waveguide was caused
by efficient coupling of light from the central waveguide into
adjacent waveguides.
[0162] FIG. 24e demonstrates the ability to modify the coupling
between adjacent waveguides by controlling the difference in
refractive indices between the guides and their cladding by
manipulating exposure time during UV curing. FIG. 24e is a
photocopy of a CCD camera frame grab of output of the waveguide of
FIG. 24c (which produced the pattern of FIG. 24d) after additional
exposure of the array (waveguides plus cladding) under the 450 W
medium-pressure Hg vapor lamp. This exposure reduced the index
difference between waveguide core and cladding, and increased the
coupling between the waveguides. The change is most easily seen in
the change in brightness of the center waveguide between FIG. 24d
and FIG. 24e. In FIG. 24d, the light coupled out of the center
waveguide into the adjacent waveguides. In FIG. 24e, the light
coupled from the adjacent waveguides back into the center
waveguide. Thus, the center waveguides formed an interferometer.
Light from the single waveguide directly addressed by optic fiber
300 was evanescently coupled into nine waveguides and many
closed-path interferometers were formed.
[0163] FIG. 24g shows the output of the array when light was
coupled into cladding between the waveguides as shown in FIG. 24f.
No waveguide output was observed and very little light was observed
from the output of the cladding. This demonstrated that the
excitation of multiple waveguides as shown in FIGS. 12d-e was the
result of coupling from propagating waveguide mode to propagating
waveguide mode, not from cladding modes to waveguide modes. This
interpretation was supported by numerical simulations.
[0164] Two-micron-high clad waveguides of width 2.0, 2.6, 3.0, and
4.0 microns and spacing of 2, 4, and 8 microns were fabricated.
These taller waveguides had cross-sections approximately equal to
the 3.3 micron mode diameter of the optical fiber 300, and gave a
coupling efficiency of approximately 35% for a 6 millimeter-long
waveguide. Propagation loss was measured in these waveguides to be
less than 0.6 dB/cm, which is the limit of measurement uncertainty
in the system used.
[0165] To demonstrate essentially instantaneous formation of plural
waveguide arrays, a waveguide fabrication technique was carried out
as described above. An array of about 1,000 3-centimeter-long,
two-micron-wide, one-micron-high waveguides were formed over a 0.8
by 3 square centimeter area in a single step taking only five
minutes. The parallelism of this procedure makes it a tremendously
useful technique for the fabrication of complex but low-cost
integrated optical devices.
[0166] FIG. 25 illustrates another embodiment of the invention for
formation of a structure on a substrate surface using a forming
article. In the technique illustrated, fluid precursor 36 is first
placed on substrate surface 28, then forming article 20 is brought
into contact with fluid precursor 36 and pressed against substrate
surface 28 such that the contact surface 26 of the article seals
portions of surface 28 that it contacts, thereby forming channels,
defined by indentations and portions of substrate surface 28 not
contacted by contact surface 26 of the forming article. This is
another embodiment in which a micromold is created, defined by
article 20 and substrate surface 28. In FIG. 25, following
hardening of fluid precursor 36 to the point that it is essentially
self-supporting (if it is not so hardened prior to forming with
article 20), the applicator is removed resulting in structure 38
which, depending upon the material selected, can be further cured
or sintered and which may shrink in the process.
[0167] In the working examples described below, a drop of fluid
precursor 36 (referring to FIG. 25), was placed on a freshly
cleaned substrate and then article 28 was placed face down upon the
substrate. A pressure of roughly 10 psi was applied. The area of
the patterned surface was typically 1-5 cm.sup.2 with feature sizes
in the micron range. Liquid dewetting of the surface upon
application of the applicator was carried out to allow contact of
the contact surface 26 of article 20 and the substrate in regions
where no fluid precursor derived material was desired. Dewetting is
driven by both applied pressure and difference of interfacial
tension between fluid precursor 36 and contact surface 26 of
article 20. More precisely, the dewetting speed is proportional to
S where S=.gamma..sub.LS+.gamma..sub.LE-.gamma..sub.SE;
.gamma..sub.LS is the liquid-substrate interfacial tension,
.gamma..sub.LE is the liquid-elastomer interfacial tension and
.gamma..sub.SE is the substrate-elastomer interfacial tension. (F.
Brochard-Wyart, P.-G. de Gennes, J. Phys.: Condens. Matter, 1994,
6, A9). Since .gamma..sub.SE is fixed, the interfacial tension of
the fluid precursor solution was increased in order to accelerate
dewetting. Although pressure improves the definition of features,
it cannot be increased too much because of the deformations induced
in the mold if deformation is not required. Diluting fluid
precursor with a suitable solvent (in the working examples,
acetonitrile, a polar solvent with low viscosity and high surface
tension that does not swell the mold) allowed satisfactory
dewetting for all patterns used.
[0168] Gelation occurred within about an hour, although the mold
and structure were allowed to remain undisturbed for about 12 h to
allow reasonable consolidation. Gelling time can, however, be
decreased by raising pH of the precursor to about 4-5 before
casting, and some structures were produced in less than 30 minutes
using this technique.
[0169] Working examples of molding of sol-gel fluid precursors
using a forming article of the invention were carried out. In this
set of examples, silicon wafers (Silicon Sense, Massachusetts) were
cleaned briefly in an oxygen plasma cleaner before use.
Tetramethyl-orthosilicate and di-sec-butoxyaluminoxytriethoxysilane
(United Chemicals), titanium isopropoxide and boron triethoxide
(Aldrich), oxalic acid and acetonitrile (Fisher) were used as
received. Patterned Solid: A silica sol-gel precursor was molded
against a silicon wafer that had been patterned by anisotropic
etching with square pyramidal pits. A 50-nm thick gold film was
prepared on a <100> silicon wafer primed with 2 nm of
titanium by e-beam evaporation. A monolayer of hexadecanethiolate
was patterned on the wafer using microcontact printing so that the
resulting pattern presented uncovered 2-.mu.m squares, and the
unprotected gold was removed with a cyanide etch. (A. Kumar, G. M.
Whitesides, Applied Physics Letters 1993, 63, 2002). The native
silica oxide layer was then removed by etching in 2% HF for 30 sec.
The silicon was etched in a 40% by weight solution of KOH in water
and isopropanol; this anisotropic etch generated pyramidal pits.
The remaining gold was removed with aqua regia. The surface of the
resulting textured solid was treated by putting the wafer under
static vacuum with a drop of
(tridecafluoro-1,1,2,2-tetrahydro-octyl)-1-trichlorosilane for 30
min. This compound polymerized on the surface and made a layer that
reduced adhesion to the surface.
[0170] A mixture of 6.5 g TMOS and 1.5 g of water acidified to pH=1
by adding oxalic acid was stirred for 1 min and left at room
temperature for 1 h (sol A). The mold was prepared by putting a 1
cm.sup.2 piece of the textured wafer in a plastic petri dish. Just
before casting in the mold, 5 drops of aqueous ammonia (pH=11) were
added to 3 g of sol A. The wafer was covered with 0.5 ml of this
solution. The preparation was then placed in a closed 100 cm.sup.3
container for 24 h. The solid structure was not adhering to the
mold at this point and was carefully removed. It was then dried
slowly at room temperature for a week, then at 60.degree. C. for 2
days. It was finally annealed at 1100.degree. C. for 10 h.
[0171] The resulting array of silica pyramids prepared by this
technique was analyzed via SEM. The radius of curvature at the tips
of the pyramids was less than 50 nm and the angle of the side of
the pyramid was 54-58.degree.. This value is compatible with that
obtained with this type of silicon etching. (Barycka, et al.,
Sensors and Actuators, 1995, A48, 229). This demonstrates that
shrinkage taking place during annealing is essentially isotropic.
The sol-gel precursor was molded against a Si/SiO.sub.2 wafer whose
surface had been passivated by silanization. The structure was
annealed at 1100.degree. C. It measured 5.times.5.times.0.3 mm.
[0172] Optical waveguides of doped silica on Si/SiO.sub.2 were
formed. The silica was doped with aluminum oxide in order to
increase its refractive index. Low scattering by the edges of the
waveguides can be achieved by an annealing step at a temperature
where the viscosity is low enough to allow relaxation of the
roughness. In the second working example described below, this
temperature was reduced by adding boron oxide to the silica.
[0173] Specifically, 0.5 g of di-sec-butoxyaluminoxytriethoxysilane
was added to 3 g of sol A. After stirring for 6 h, 3 g of
acetonitrile were added to the clear solution (sol B). A solution
of 0.8 g of trimethylborate in 3 g of acetonitrile was added to 3 g
of sol A and left at room temperature for 1 h (sol C).
[0174] One drop of the solution (sol B or C) was placed on a
freshly cleaned silicon wafer bearing a 2-.mu.m thick thermal oxide
layer. A 1-cm.sup.2 elastomeric forming article having a protrusion
pattern complementary to the final pattern of the waveguide
(illustrated schematically in FIG. 25) was immediately pressed
against the surface. The whole structure was placed in a closed
100-cm.sup.3 container with one drop of aqueous ammonia (30%).
After 18 h, the mold was removed and the structure was consolidated
by annealing for 3 h at 1100.degree. C. (for sol B) and 15 min at
800.degree. C. or 900.degree. C. (for sol C).
[0175] FIGS. 26-29 are photocopies of SEM images of waveguides
produced in accordance with this aspect of the invention. FIG. 26
is a photocopy of an SEM image of an aluminosilicate waveguide.
FIGS. 27 and 29 are photocopies of SEM images of borosilicate
waveguides. FIGS. 27 and 28 show borosilicate lines at different
stages of sintering: FIG. 27 shows borosilicate lines after
annealing at 800.degree. C. for 10 minutes. FIG. 28 shows the lines
after annealing at 900.degree. C. for 10 minutes. Whereas pure
sintering seemed to occur at 800.degree. C., the cross section of
the lines changed dramatically after annealing at 900.degree. C.,
due to the melting of the glass, resulting in smoother edges. The
composition of the glass was found by XPS to be 9% B.sub.2O.sub.3
and 91% SiO.sub.2. The waveguiding behavior of the aluminosilicate
lines was characterized by coupling a 633-nanometer light beam into
one end of a 5 mm long line and imaging the other end. The lines
appeared to be single mode waveguides with slight coupling between
adjacent lines.
[0176] Described above are a variety of sensors of biological or
chemical molecules, or the like, that can be made using waveguides
fabricated in accordance with the invention. In another set of
embodiments, sensors of displacement can be provided. For example,
with reference to FIG. 24, where the waveguide array is subjected
to compression or tensile forces in a direction perpendicular to
the waveguides, causing the waveguides to move closer to or farther
apart from each other, coupling between waveguides will change
detectably. This can serve as a displacement sensor, pressure
sensor, tension sensor, or the like. The waveguide array can be
arranged to sense a force by being bent, for example to sense a
force applied to an edge of the waveguide, and when the waveguide
is bent spacing between waveguides will change and the coupling
pattern will change. Waveguides made of glass as described above
may also serve as active devices for integrated optics. For
instance, aluminosilicate waveguides can be doped with rare earth,
like neodymium or erbium. Doped waveguides can be used as
integrated light-amplifiers or lasers when placed in a suitably
geometry. A regular array of doped waveguides fabricated by this
method, when put in a resonant cavity, could exhibit a very
interesting behavior where all the lasers would be in phase,
leading to a much higher intensity light beam.
* * * * *