U.S. patent application number 12/803612 was filed with the patent office on 2011-02-10 for biopolymer resistant devices using coatings with surface energy gradient.
Invention is credited to Brian David Babcock.
Application Number | 20110034785 12/803612 |
Document ID | / |
Family ID | 43526019 |
Filed Date | 2011-02-10 |
United States Patent
Application |
20110034785 |
Kind Code |
A1 |
Babcock; Brian David |
February 10, 2011 |
Biopolymer resistant devices using coatings with surface energy
gradient
Abstract
A medical device or analytical device comprising a
fluid-impervious surface comprising a base surface, at least one
distinct region of the base surface covered by a mixed monolayer
film, the mixed monolayer film comprising a species having a
functional group M1 and a species having a functional group M2
where M1 and M2 have different surface energies, the mixed
monolayer forming a surface energy gradient wherein at least one of
the species used to form the monolayer on the surface comprises a
biopolymer-resistant domain.
Inventors: |
Babcock; Brian David;
(Bloomington, MN) |
Correspondence
Address: |
BRENDAN BABCOCK
1814 Rock Springs Road
Columbia
TN
38401
US
|
Family ID: |
43526019 |
Appl. No.: |
12/803612 |
Filed: |
June 30, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10494122 |
Aug 12, 2004 |
7790265 |
|
|
12803612 |
|
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Current U.S.
Class: |
600/309 |
Current CPC
Class: |
B82Y 30/00 20130101;
B01L 3/502753 20130101; C12Q 1/6837 20130101; G01N 33/6803
20130101; C12Q 2527/15 20130101; C12Q 2523/308 20130101; C12Q
1/6837 20130101; C12Q 2527/125 20130101 |
Class at
Publication: |
600/309 |
International
Class: |
A61B 5/145 20060101
A61B005/145 |
Claims
1) A medical device comprising one or more tubes, at least one tube
comprising a fluid-impervious surface comprising a base surface, at
least one distinct region of length L and width W of the base
surface covered by a mixed monolayer film, the mixed monolayer film
comprising a species having a functional group M1 and a species
having a functional group M2 where M1 and M2 have different surface
energies, the mixed monolayer forming a surface energy gradient
from a proximal location to a distal location within the region
wherein 1 equals the distance from the proximal location to the
distal location, W is 20 nanometers or greater, and the ratio of
L/W is greater than 2 and wherein any portions of the surface that
border the at least one distinct region along the dimension L have
substantially equal surface energies.
2) The device of claim 1, wherein the mixed monolayer is formed
from species X1-J1-M1 and X2-J2-M2 wherein X1, X2, M1, and M2
represent separate functional groups where M1 and M2 have different
surface energies and J1 and J2 represents spacer moieties, the
species X1-J1-M1 and X2-J2-M2 forming a self-assembled monolayer
onto the base surface from solution.
3) The device of claim 1 wherein the molar concentration of the
species comprising the functional group M2 continuously increases
relative to the concentration of the species comprising functional
group M1 from the proximal location to the distal location of the
region having the mixed monolayer.
4) The device of claim 2 wherein at least one of the species
comprises a biopolymer-resistant domain.
5) The device of claim 1 wherein any portions of the surface that
border the at least one distinct region along the dimension L are
covered by substantially uniform monolayers.
6) The device of claim 5 wherein the substantially uniform
monolayers comprise biopolymer-resistant domains.
7) The device of claim 1 where the ratio of L/W is greater than
10.
8) An analytical device comprising a fluid-impervious surface
comprising a base surface, at least one distinct region of length L
and width W of the base surface covered by a mixed monolayer film,
the mixed monolayer film comprising a species having a functional
group M1 and a species having a functional group M2 where M1 and M2
have different surface energies, the mixed monolayer forming a
surface energy gradient from a proximal location to a distal
location within the region wherein L equals the distance from the
proximal location to the distal location, W is 20 nanometers or
greater, and the ratio of L/W is greater than 2 and wherein any
portions of the surface that border the at least one distinct
region along the dimension L have substantially equal surface
energies and wherein at least one of the regions comprising the
surface energy gradient is defined in a series of channels and
passages.
9) The device of claim 8, wherein the mixed monolayer is formed
from species X1-J1-M1 and X2-J2-M2 wherein X1, X2, M1, and M2
represent separate functional groups where M1 and M2 have different
surface energies and J1 and J2 represents spacer moieties, the
species X1-J1-M1 and X2-J2-M2 forming a self-assembled monolayer
onto the base surface from solution.
10) The device of claim 9 wherein at least one of the species
comprises a biopolymer-resistant domain.
11) The device in claim 8, wherein the surface gradient of channels
and passages are constructed and arranged such that fluid requires
less external energy to move through channels and passages with the
surface gradient than channels and passages without the surface
gradient.
12) The device in claim 8, wherein the surface gradients are
constructed and arranged to deliver fluid to separate wells for
analysis.
13) The device in claim 8, wherein the surface gradients comprise
reactive chemicals for detecting the presence of chemical species,
proteins, and the like as the fluid moves along the surface.
14) The device of claim 8 wherein any portions of the surface that
border the at least one distinct region along the dimension L are
covered by substantially uniform monolayers.
15) The device of claim 14 wherein the substantially uniform
monolayers comprise biopolymer-resistant domains.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a division of and claims the benefit of
U.S. application Ser. No. 10/494,122, filed Apr. 30, 2004, the
contents of which is herein incorporated by reference in its
entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
PARTIES TO A JOINT RESEARCH AGREEMENT
[0003] Not Applicable.
FIELD OF THE INVENTION
[0004] This invention relates to a surface-energy gradient on a
fluid-impervious surface and method of its creation.
BACKGROUND OF THE INVENTION
[0005] Microscopic fluidic devices, ranging from surgical
endoscopes and microelectromechanical systems to the commercial
`lab-on-a-chip`, allow chemical analysis and synthesis on scales
unimaginable a few decades ago (Kataoka and Troian, 1999). Advances
in microfabrication techniques have led to the ability to
manufacture flow channels ranging from a few hundred angstroms to a
few hundred microns (Pfahler, et al, 1990). However, due to the
microscopic scale of the systems involved, fluid transport and
friction losses are problematic. Different methods using
temperature, pressure, or electric potential gradients have been
developed to transport fluid through these systems. Each of these
methods increases the energy required to operate such systems, and
none of the methods solve the problem of fluid friction losses.
[0006] Friction arises from the adhesive forces between two
surfaces in contact In the absence of wear and plastic deformation,
as is the case in fluid transport in microscale systems, friction
is largely attributable to interfacial effects (Krim, 1996). For
laminar flow in channels, fluid friction loss (f) can be estimated
as
f=16/Re where Re=Reynolds Number (.rho. v DC/.mu.) .rho.=density of
fluid v=fluid velocity Dc=effective diameter of channel
.mu.=viscosity of fluid
[0007] Therefore, as Dc begins to approach micron and angstrom
dimensions, friction loss increases greatly.
[0008] Organic thin films have been used to control friction and
wear in a variety of machines. As machines get even smaller, and
lubricating films approach the monolayer regime, self-assembled
monolayer films show great potential for use in such items. SAM
films have been shown to reduce the friction between two surfaces.
By changing the energy of the surface, the SAM can prevent a fluid
such as water from wetting the surface. A reduction in the
attraction between the fluid and the tail group of the SAM will
result in a reduction in friction.
[0009] Several studies have been conducted on the frictional
properties of SAMs. These studies have shown how friction varies
depending on the structure and composition of the SAM. Most of
these studies used Atomic Force Microscopy (AFM) to measure
friction. This measurement is performed by passing the AFM probe
tip over the SAM surface. The frictional response of the surface is
measured by the AFM as the normal force exerted by the probe is
varied. In their 1996 paper, Xiao et al determined how the chain
length of the SAM affected friction. Their work with mica surfaces
showed that longer-chain SAMs reduce friction the most. Longer
chain molecules form films that are typically more densely packed
and more crystalline in structure than shorter chain molecules do.
The enhanced crystalline structure and better packing provide a
lower friction surface (Liu and Evans, 1996). Their work with SAM
films on gold surfaces led to the same conclusions regarding chain
length and crystalline structure.
[0010] The effect of the tail group was then studied. Researchers
determined that frictional behavior closely followed the variation
of the adhesive properties, meaning low-energy surfaces had the
lowest friction while high-energy surfaces such as --NH2 produced
higher amounts of friction loss (Tsukruk and Bliznyuk, 1998). Kim
et al in 1999 found that among low energy surfaces, those with the
smallest head group yielded the surface with the lowest friction.
Specifically, CF.sub.3-terminated films had three times the
friction of CH.sub.3-terminated films.
[0011] In addition to lowering the friction between two surfaces,
SAMs can have a dramatic effect on the ability of a fluid to wet a
surface. For instance, CH.sub.3-terminated SAMs produce low energy,
hydrophobic surfaces that are not wet by water while
CO.sub.2H-terminated SAMs produce high energy, hydrophilic surfaces
that are almost completely wet by water. The contact angle that
water forms with a surface is a good indication of the surfaces
hydrophilicity or hydrophobicity. For instance, water forms a
contact angle of 115.degree. with CH.sub.3 surfaces while it forms
a contact angle of <15.degree. with CO.sub.2H surfaces. In
general, as the contact angle decreases, water has more affinity
for the surface and will more easily wet it (Laibinis et al,
1998).
[0012] A system that reduced friction losses and improved fluid
transport would have a great benefit.
[0013] All US patents and applications and all other published
documents mentioned anywhere in this application are incorporated
herein by reference in their entirety.
[0014] Without limiting the scope of the invention a summary of
some of the claimed embodiments of the invention is set forth
below. Additional details of the summarized embodiments of the
invention and/or additional embodiments of the invention may be
found in the Detailed Description of the Invention below.
[0015] A brief abstract of the technical disclosure in the
specification is provided as well only for the purposes of
complying with 37 C.F.R. 1.72. The abstract is not intended to be
used for interpreting the scope of the claims.
SUMMARY OF THE INVENTION
[0016] The proposed system uses self-assembled monolayer (SAM)
films to modify a surface; a novel design is proposed which
modifies the surface using a mixed SAM surface so that fluids are
transported with minimal or reduced external forces required. The
proposed design will result in microfabricated systems that are
smaller and more energy-efficient.
[0017] In one embodiment a method of derivatizing a
fluid-impervious surface with a mixed monolayer to create a surface
energy gradient comprises the following steps:
a) exposing a base surface having a proximal and a distal portion
to a first solution comprising a plurality of molecules of the
formula X1-J1-M1, wherein X1 and M1 represent separate functional
groups and J1 represents a spacer moiety that, together, are able
to promote formation from solution of a self-assembled monolayer
for sufficient time to form a monolayer surface having a
substantially uniform surface energy on the base surface, b)
removing a portion of the monolayer of step (a) such that a portion
of the base surface is again fully or partially exposed, c)
exposing the portion of the base surface from (b) to a second
solution comprising a plurality of molecules of the formula
X2-J2-M2 and a plurality of molecules of the formula X1-J1-M1
wherein the functional group M2 has a different surface energy from
that of the functional group M1 such that a surface energy gradient
from a proximal location to a distal location is formed.
[0018] In another embodiment, removing a portion of the monolayer
is done while the base surface and monolayer surface are immersed
in either the first solution or the second solution.
[0019] In another embodiment removal of a portion of the monolayer
of (a) is performed using a method or combination of methods
selected from the group consisting of 1) passing an instrument
along the monolayer surface created in (a) with sufficient force to
remove a portion of the monolayer created in (a), 2) etching
chemically the portion to be removed, 3) etching physically the
portion to be removed, 4) cutting with a laser, 5) cutting with
water, 6) etching through thermometric exposure, 7) removing with
grit, 8) drilling, 9) sonic means, and 10) cutting with an
instrument.
[0020] These and other embodiments which characterize the invention
are pointed out with particularity in the claims annexed hereto and
forming a part hereof. However, for a better understanding of the
invention, its advantages and objectives obtained by its use,
reference should be made to the drawings which form a further part
hereof and the accompanying descriptive matter, in which there are
further embodiments of the invention illustrated and described.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 illustrates a blown-up schematic view of the method
for producing a mixed monolayer surface energy gradient;
[0022] FIG. 2 illustrates a blown-up schematic view of the method
during the removal and exposure steps wherein the instrument that
removes the SAM layer also delivers new molecules to the
surface;
[0023] FIG. 3 illustrates a blown-up schematic view of the method
during the removal and exposure steps wherein the instrument that
removes the SAM layer also delivers mixture to the surface;
[0024] FIG. 4 illustrates a blown-up schematic view of the method
during the removal and exposure steps wherein the instrument that
removes the SAM layer also delivers new molecules to the surface
which are mixed in an outside reservoir.
[0025] FIG. 5 illustrates a schematic view of the end condition for
a representative method for reacting a mixed monolayer to
incorporate a gradient of other chemical species. In this figure
the portions of the CH3-CO2H mixed monolayer that do not take part
in the reaction are not shown (e.g. CH3).
[0026] FIG. 6 illustrates a side elevational view of a method for
creating a gradient along the walls of the tube in a direction
along a longitudinal axis through the center of the tube.
[0027] FIG. 7 illustrates a side elevational view of a method for
creating a gradient on the walls of the tube in a strip formed by
rotating the instrument about the longitudinal axis through the
center of the tube.
[0028] FIG. 8 illustrates a schematic view of a spiral surface
energy gradient that might be produced on the inside of a tube when
the movements of FIG. 6 and FIG. 7 are combined.
[0029] FIG. 9 illustrates a side elevational schematic view of a
method for creating a gradient along the outside walls of the
tube.
[0030] FIG. 10 illustrates a cross-sectional schematic view of the
tube and instrument in which the instrument has at least one tip
used in the method for creating a surface energy gradient on the
interior of the tube.
[0031] FIG. 11 illustrates a cross-sectional schematic view of the
tube and instrument in which the instrument has at least one tip
used in the method for creating a surface energy gradient on the
outside of the tube.
DETAILED DESCRIPTION OF THE INVENTION
[0032] While this invention may be embodied in many different
forms, there are described in detailed herein specific preferred
embodiments of the invention. This description is an
exemplification of the principles of the invention and is not
intended to limit the invention to the particular embodiments
illustrated.
[0033] As used herein, the term "tube" is any hollow object open on
two sides without limitation by cross-sectional geometries.
[0034] Turning now to the drawings, FIG. 1 shows a blown-up
schematic view of an embodiment of the method for producing a mixed
monolayer surface energy gradient. The view consists of 6 slides.
Slide (a) shows a base surface 1 having a monolayer 3. The original
monolayer is made up of a plurality of first organic molecules 5.
The base surface 1 having a monolayer 3 can be stored and used
later as well. The first organic molecules 5 are comprised of a
functional group 7 (e.g. thiol) that reacts with the base surface 1
and a low surface energy functional group 9 (e.g. CH.sub.3,
CF.sub.3, etc). The instrument 11 is not in contact with the
monolayer 3 at this point of the process. The instrument 11 in
slide (b) comes into contact with the monolayer 3 and removes some
of the original monolayer 3 as the instrument 11 passes along the
surface 1. At the same time, second organic molecules 13 are added.
The second organic molecules 13 are comprised of a functional group
7 designed to react with the base surface 1 and a high surface
energy functional group 17 (e.g. OH, CO.sub.2H, CONH.sub.2, etc).
Slide (c) shows how some of the second organic molecules 13 are
reacting with the base surface 1 and creating a mixed SAM layer. As
shown in slide (d), this process continues as the instrument 11
continues along the base surface 1. More second organic molecules
13 are being added and are reacting with the exposed base surface
1. This continues through slide (e) and in slide (t) a higher
concentration of high energy groups 17 make up the monolayer 3 and
along the portion of the surface the instrument 11 passed a surface
energy gradient 19 is formed.
[0035] Unlike prior art examples, the surface energy gradient of
this invention is designed to be formed with well-defined
dimensions that correspond to the features of the instrument used
in the process. The length (L) of the gradient will correspond to
the length of the path traced by the instrument while the width (W)
of the gradient will correspond to the width or radius of the
instrument tip used to expose the base layer. Thus, a very long and
thin gradient region can be created with this method with aspect
ratios (length divided by width, L/W) that can vary from 2.0, 10.0,
to essentially an infinite number. Nanografting using an Atomic
Force Microscope (AFM) as the instrument will produce surface
energy gradients with very small width dimensions. As an example,
AFM instruments with a tip radius of 20-nm could be used in the
invention (Liu and Evans, p. 1236, col. 2). Using this instrument,
a surface energy gradient region of 20 nm wide by 1000 nm long
could be created; such a region would have an aspect ratio of 50.
Gradients with higher aspect ratios (10,000 or greater) can be
created by increasing the path length traced by the instrument.
High aspect ratio gradient regions could also be made using AFMs
with tip radii in the 40-500 nm to produce gradient regions with a
larger width W (Tsukruk and Bliznyuk, p. 448, col. 1). Other
instruments such as those commonly used in micromachining
applications can be used. Micromachining applications are capable
of using manufacturing channels with widths in the 100-1000 micron
range while standard machining techniques can produce channels with
widths in the 1.0-10.0-mm range.
[0036] In one embodiment a method of derivatizing a
fluid-impervious surface with a mixed monolayer to create a surface
energy gradient comprises the following steps:
a) exposing a base surface having a proximal and a distal portion
to a first solution comprising a plurality of molecules of the
formula X1-J1-M1, wherein X1 and M1 represent separate functional
groups and J1 represents a spacer moiety that, together, are able
to promote formation from solution of a self-assembled monolayer
for sufficient time to form a monolayer surface having a
substantially uniform surface energy on the base surface, b)
removing a portion of the monolayer of step (a) such that a portion
of the base surface is again fully or partially exposed, c)
exposing the portion of the base surface from (b) to a second
solution comprising a plurality of molecules of the formula
X2-J2-M2 and a plurality of molecules of the formula X1-J1-M1
wherein the functional group M2 has a different surface energy from
that of the functional group M1 such that a surface energy gradient
from a proximal location to a distal location is formed. The X2 and
J2 groups for the molecule in the second solution can be the same
as the X1 and J1 groups for the molecule in the first solution, or
they can be different, depending on the desired final properties of
the mixed monolayer.
[0037] In another embodiment, removing a portion of the monolayer
is done while the base surface and monolayer surface are immersed
in either the first solution or the second solution.
[0038] In another embodiment removal of a portion of the monolayer
of (a) is performed using a method or combination of methods
selected from the group consisting of 1) passing an instrument
along the monolayer surface created in (a) with sufficient force to
remove a portion of the monolayer created in (a), 2) etching
chemically the portion to be removed, 3) etching physically the
portion to be removed, 4) cutting with a laser, 5) cutting with
water, 6) etching through thermometric exposure, 7) removing with
grit, 8) drilling, 9) sonic means, and 10) cutting with an
instrument.
[0039] In another embodiment, removal of the portion of the
monolayer of (a) is performed while at the same time increasing
amounts of a third solution comprising a molecule of the formula
X2-J2-M2 so that a mixed monolayer surface of M1 and M2 moieties is
formed with a molar ratio of M2 to M1 that increases from a
proximal location to a distal location of the surface. The X2 and
J2 groups for the molecule in the third solution can be the same as
the X1 and J1 groups for the molecule in the first solution, or
they can be different, depending on the desired final properties of
the mixed monolayer
[0040] In another embodiment, the third solution has a solvent
different from that of the first solution or the second
solution.
[0041] In other embodiments, multiple n solutions comprising
molecules of Xn-Jn-Mn can be used to create multiple gradients of
mixed monolayers.
[0042] In several other embodiments, the gradient is created on 1)
the inside of a tube, 2) the outside of a tube, 3) on a rectangular
channel having three walls and one side open, 4) on only 1 face of
the channel, 5) on 2 faces of the channel, and 6) on 3 faces of the
channel.
[0043] In another embodiment, the base surface is a metal oxide
comprising a metal oxide from the group comprising silica, alumina,
quartz, glass, or the like. In some embodiments using metal oxide
base surfaces, the functional group X is a carboxylic acid.
[0044] In an additional embodiment, the base surface is a metal
selected from the group comprising gold, silver, copper, aluminum,
cadmium, zinc, palladium, platinum, mercury, lead, iron, chromium,
manganese, tungsten, and any alloys of the above. In some
embodiments using metals for the base surfaces, the functional
group X is a sulfur-containing functional group (e.g. thiols,
sulfides, disulfides, and the like). In other embodiments, the
metal of the base surface is in the form of a metalized film
coating a polymer surface.
[0045] In another embodiment, the base surface is doped or undoped
silicon. In some embodiments using doped or undoped silicon for the
base surface, the functional group X is selected from the group
comprising silanes or chlorosilanes.
[0046] In another embodiment, the base surface is a metal selected
from the group comprising palladium and platinum. In some
embodiments using these metals for the base surface, the functional
group X is a functional group selected from the group comprising
nitrites and isonitriles.
[0047] In another embodiment, the base surface is copper. In some
embodiments using copper for the base surface, the functional group
X is a hydroxamic acid.
[0048] In another embodiment, the base surface is gold. In some
embodiments using gold for the base surface, the functional group X
is at least one sulfur-containing functional group selected from
the group consisting of thiols, sulfides, or disulfides.
[0049] In another embodiment, the functional group M1, M2, . . . Mn
is selected from the group comprising ionic, nonionic, polar,
nonpolar, halogenated, alkyl, aryl or other functionalities,
[0050] In other embodiments, the functional group M1, M2, . . . Mn
can include any one of the following: --OH, --CONHR, --CONHCOR,
--NHR, --COOH, --COOR, --CSNHR, --COR, --RCSR, --RSR, --ROR,
--SOOR, --RSOR, --CONR.sub.2, --(OCH.sub.2CH.sub.2).sub.nOH,
--(OCH.sub.2CH.sub.2).sub.nOR--NR.sub.2, --CN,
--(CF.sub.2).sub.nCF.sub.3, --CO.sub.2CH.sub.3, --CONHCH.sub.3,
--CR, CHCH.sub.2, --OCH.sub.2CF.sub.2CF.sub.3, Cl, Br, olefins, and
the like, and any combination thereof.
[0051] In the above list, R is hydrogen or an organic group such as
a hydrocarbon or fluorinated hydrocarbon. As used herein, the term
"hydrocarbon" includes alkyl, alkenyl, alkynyl, cycloalkyl, aryl,
alkaryl, aralkyl, and the like. The hydrocarbon group may, for
example, comprise methyl, propenyl, ethynyl, cyclohexyl, phenyl,
tolyl, and benzyl groups. The term "fluorinated hydrocarbon" is
meant to refer to fluorinated derivatives of the above-described
hydrocarbon groups.
[0052] In another embodiment, J is a hydrocarbon chain with the
formula-(CH.sub.2).sub.n-where n is between 1 and 22, preferably
between 2 and 18, more preferably between 2 and 12.
[0053] Other embodiments of the invention are 1) a surface that is
a surface energy gradient, 2) a surface utilizing a surface energy
gradient, 3) a surface that is a surface energy gradient as
produced by any of the methods of the claims, and 4) a surface
utilizing a surface energy gradient as produced by any of the
methods of the claims.
[0054] Another embodiment of the invention is a surface as produced
by any of the methods of the claims that is used in lab-on-a-chip
technology.
[0055] In another embodiment, the monolayer surfaces of channels
and passages are constructed and arranged such that a single drop
or multiple drops of fluid requires less external force to move
through channels and passages with the monolayer surface than
channels and passages without the monolayer surface.
[0056] In another embodiment, the monolayer surfaces are
constructed and arranged such that instead of having separate wells
where the fluid is delivered and analyzed, the analysis could be
done while the fluid moves along the channels. Reactive chemicals
can be incorporated into the surface with the surface energy
gradient so that the certain chemicals, proteins, etc. could be
detected in the drop as it moves along the surface.
[0057] In another embodiment, the gradient is created on a standard
micromachined array of channels in silicon. Because silicon oxide
is a high-energy surface, water will wet it very easily, and
friction losses would be high. The high-energy silicon oxide
surface can be converted into a low-energy surface by depositing a
SAM film on the silicon that will repel water and reduce friction.
Based on the details of the experiments discussed in the previous
section, one preferred SAM would be obtained from an
alkylsilane-based surfactant with a silane head group X and a
methyl (--CH.sub.3) tail group M. The silane head group will bond
with the silicon, resulting in a SAM film with a --CH.sub.3
surface. The carbon chain backbone of the SAM should be a single
chain and contain at least 12 carbons. This type of SAM will pack
very closely, resulting in a lowered friction loss. A molecule with
a carbon chain backbone of at least 6 carbons will still pack
tightly as well.
[0058] In addition to reducing friction, another use for SAMs is in
the area of fluid transport. An embodiment of the invention
includes a design which gives a means of transporting liquids
across a surface without using any external forces in some
instances and reduced external forces in other cases. This
self-propulsion of liquid drops allows microfabricated systems to
be much more efficient.
[0059] An embodiment of the inventive method takes advantages of
the ability of SAM films to modify the surface energy of a
substrate. By changing the tail group of a SAM from, for example, a
--CH.sub.3 group to an --OH or --CO.sub.2H group, the surface can
change from a low-energy surface to a high-energy surface. Water
will not wet a low-energy surface, but it will wet a high-energy
surface. Therefore, a surface having a surface energy gradient
allows water to move across the surface from areas of low energy
into areas of higher and higher surface energy. Embodiments of the
SAMs of this invention can be used to create such a surface energy
gradient.
[0060] In an embodiment of the inventive method, a mixed SAM
surface is created on a silicon oxide semiconductor surface using
two separate SAM surfactant solutions, an AFM tip for nanografting,
and a flow controller with picoliter capability for liquid
additions. The system is inventive and unique in that it creates a
fluid-impervious surface with a gradient in surface energies.
[0061] In the first step of this embodiment, the semiconductor
surface is exposed to a toluene solution containing an
octadecyltrichlorosilane (this is the first SAM surfactant
solution) capable of forming a SAM on the surface. FIG. 2 begins
with the step at which this SAM surfactant solution has formed a
SAM on the surface. In this example, five hours is sufficient to
create a modified surface coated with a SAM film that has a methyl
(--CH.sub.3) tail group. This treatment creates a low-energy
surface that repels water. In this embodiment, good results are
obtained when the process is performed under an inert atmosphere
such as nitrogen although it can be carried out under normal
atmospheric conditions also.
[0062] In a specific embodiment, the surface being treated will
remain in solution while an AFM tip passes over the surface and
begins to remove parts of the original SAM and expose the original
semiconductor surface. At the same time the AFM begins to remove
the original SAM film, drops of toluene solution containing an
organotrichlorosilane surfactant with a high-energy tail group such
as --CO.sub.2H will be added to the solution The two surfactants
(one with the high energy tail group the other with the low energy
tail group) will form a mixed SAM on the area where the instrument
scraped the previous SAM away. The instrument will continue to move
along the original surface and remove the original SAM while more
of the CO.sub.2H-terminated surfactant is added to the solution.
This process can continue along the entire length of the channel;
as the instrument passes along the surface, the concentration of
CO.sub.2H-terminated surfactant continually increases in the
solution. As the percentage of CO.sub.2H-terminated surfactant in
solution continually increases, the percentage of CO.sub.2H-groups
continually increases in the mixed monolayer that forms along the
path of the AFM tip. The mixed SAM that forms will have a
continuously increasing --CO.sub.2H concentration at the surface.
Therefore, the surface energy increases along the length of the
channel.
For One Silicon Embodiment
[0063] Octadecyltrichlorosilane
(CH.sub.3(CH.sub.2).sub.17SiCl.sub.3) in toluene can be used as
low-energy surfactant (X1-J1-M1) where
M1=CH.sub.3
J1=(CH.sub.2).sub.17
X1=SiCl.sub.3
[0064] To create the gradient, a molecule (X2-J2-M2) can be used
with any higher-energy surface group for M2 (CO.sub.2H, OH, etc. or
other moiety that has a higher surface energy than CH.sub.3). For
example, even .dbd.CH.sub.2 has a higher energy than --CH.sub.3. X2
and J2 can be the same as X1 and J1 in this embodiment.
For a Gold, Silver, or Copper Embodiment
[0065] Dodecanethiol (CH.sub.3(CH.sub.2).sub.11SH) in ethanol used
as low-energy surfactant (X1-J1-M1) where
M1=CH.sub.3
J1=(CH.sub.2).sub.11
X1=SH
[0066] To create the gradient, another thiol of undecanoic acid
(CO.sub.2H(CH.sub.2).sub.10SH) as high-energy surfactant (X2-J2-M2)
can be used where
M2=CO.sub.2H
J2=(CH.sub.2).sub.10
X2=SH
[0067] Additional materials and functional groups suitable for use
in the present invention can be found in U.S. Pat. No. 5,079,600,
issued Jan. 7, 1992, and incorporated herein by reference.
[0068] The SAM-forming compound may terminate in a second end,
opposite to the end bearing the functional group selected to bind
to the surface material, with any of a variety of functionalities.
That is, the compound may include a functionality that, when the
compound forms a SAM on the surface material, is exposed. Such a
functionality may be selected to create a SAM that is hydrophobic,
hydrophilic, that selectively binds various biological or other
chemical species, or the like. Other groups for M are found in
columns 8 and 9 of U.S. Pat. No. 5,776,748.
[0069] U.S. Pat. No. 4,690,715 contains good examples of chemicals
to use with different surfaces. Other useful patents are U.S. Pat.
Nos. 5,620,850, 5,079,600, 5,512,131, 6,235,340. All of the above
patents are herein incorporated by reference.
[0070] Another embodiment of an inventive method starts with a
silicon or plastic surface that has a gold, silver, or copper
coating on it. With this system embodiment, thiols could be used
instead of silanes and ethanol could be used instead of toluene.
The process could then take place under ambient conditions. Thiols
offer more stability than silanes under many conditions, and
ethanol is less hazardous than toluene. Also, the time required to
form SAM films on gold, silver, and copper from thiols in solution
is often much shorter than the time required to form SAMs from
silanes. It can take as little as five minutes to form SAM films on
gold surfaces using ethanol solutions containing thiols. It should
be noted, that other SAM-forming compounds that work similarly to
thiols or those having at least one sulfur-containing functional
groups (e.g. sulfide or disulfide) can be selected.
[0071] Occasionally, trichlorosilanes or thiols with high-energy
tail groups are difficult to synthesize. This method can still be
used to create a surface energy gradient by using a trichlorosilane
or thiols containing a tail group that has only a slightly higher
surface energy than the tail group used in the first step.
[0072] The mixed-monolayer film that is formed can be reacted with
other reagents to increase the surface energy gradient. For
example, a trichlorosilane or thiols with a .dbd.CH.sub.2 tail
group could be used as the second surfactant M2 in this example.
The resulting surface of --CH.sub.3 and .dbd.CH.sub.2 tail groups
could undergo a series of reactions to convert the .dbd.CH.sub.2
tail groups into --CO.sub.2H groups while leaving the --CH.sub.3
groups unreacted. Thus, this process embodiment allows the surface
energy gradient to be increased further.
[0073] In this embodiment of the invention, the resulting surface
could allow for self-propulsion of water or other aqueous fluid or
drops thereof. Such a drop of water or other aqueous fluid forms a
decreasing contact angle along such a surface and has increasing
forces of attraction to such a surface along its length. An organic
or oil-bearing fluid could be propelled in a similar manner by
starting with a high-energy surface (such as --CO.sub.2H) and
decreasing the surface energy along the length of the surface or
channel using low-energy groups (such as --CH.sub.3).
[0074] In an embodiment using water, if a drop of water is placed
at the beginning of the channel, it will not wet the channel
because of the low-energy methyl surface. However, it is attracted
to the slightly higher energy surface composed of a mixed methyl
and --CO.sub.2H surface. As the CO.sub.2H concentration of the
surface increases, the force of attraction between the water and
the surface increases. The contact angle between the advancing drop
and the mixed-SAM surface decreases along the length of the
channel. Therefore, the drop can propel itself across the surface
without the use of any external forces. By changing the surfactant
additions so that a surface is created with a surface energy
gradient from high-surface energy to low-surface energy, the design
would allow for a low-energy nonpolar molecule such as a drop of
oil to propel itself across the surface. The design could also be
used for systems where one merely wishes to reduce the external
energy required to transfer a liquid across a surface.
[0075] It should be recognized to one skilled in the art that a
multitude of surfaces and surfactants could be used in combinations
to form monolayer films. Such combinations are considered covered
by this invention. It should also be recognized to those skilled in
the art that many different instruments capable of operating at the
nanoscale-scale and smaller level can be used with this invention.
Such uses are also covered by this invention. Means of optimizing
this process by adjusting surfactant concentrations in solution,
solutions used, exposure times, instrument speeds, geometries,
temperatures, substrates, etc. to fit other systems are covered by
this invention.
[0076] It should be noted that in another embodiment of the
invention, the instrument that removes the original SAM film can
also be used to deliver the mixed-SAM solution to the bare surface.
For example, a reservoir inside the instrument could contain a
mixed-SAM solution. This solution could then be delivered to the
surface at an increasing rate of delivery so that the surface
energy gradient is created.
[0077] In another embodiment, the mixing of the SAM solutions could
take place inside the reservoir. The composition of the mixed-SAM
solution would change as one SAM solution is gradually added to the
original solution inside the reservoir. This solution could then be
delivered to the surface at a constant rate of delivery so that the
surface energy gradient is created.
[0078] In another embodiment, the mixing could take place outside
the reservoir and then delivered to the surface by various means,
one embodiment of which is through the removal instrument.
[0079] In another embodiment, it is not necessary for the reservoir
in either example to contain a mixed-SAM solution. It can contain
only one SAM in solution. The rate of delivery of this solution
could be varied to create the surface energy gradient. In another
embodiment, the surface is used for improving fluid flow in
diagnostic systems that incorporate chemical, biological, or
genomic sensors on the surface. It is also useful in making such
systems even smaller and more efficient.
[0080] In some preferred embodiments, at least one of the molecules
of formula (X-J-M) chosen to form the monolayers is resistant to
the adsorption of biopolymers such as proteins, enzymes,
antibodies, polynucleic acids, cells, and other biological
molecules. By the term "resistant to the adsorption of biopolymers"
it is meant that the base surface covered by the monolayer has a
reduction in the amount of a biopolymer adsorbed on the surface,
when contacted with a medium containing biopolymers available for
adsorption, as compared to the amount adsorbed on the same base
surface that is not covered by the monolayer.
[0081] For these embodiments, the J group of the molecule is a
spacer moiety comprising a biopolymer-resistant domain. Suitable
moieties for the biopolymer-resistant domain of the J group are
discussed in U.S. Pat. No. 6,235,340 and include oligoethers,
oligoglycols, oligoalcohols, oligocarbonyls, oligosulfides,
oligosulfones and oligosaccharides. Such moieties typically are
used to produce a monolayer that is both hydrophilic and
biopolymer-resistant.
[0082] In one embodiment, the biopolymer-resistant domain comprises
an oligo-(ethylene glycol) linkage (--OCH.sub.2CH.sub.2--).sub.n
where n is 2 to 4.
[0083] For embodiments with monolayers (either mixed or uniform)
comprising biopolymer resistant molecules, the surface to be
treated may be a blood-contacting surface, or it may be some other
type of surface, e.g. the surface of a biosensor, bioseparation
chamber, or the surface of an electronic device or component or of
an electrochemical detection or analysis device. It may be a
surface of a finished device such as a blood-contacting device or
it may be the surface of a material to be used in forming a
finished device. In the latter case subsequent forming steps are
selected to avoid disrupting the coating formed by the process of
the invention in portions of the device where the coating will
protect the surface in use and to avoid chemical damage, for
instance due to high temperatures, to the coating. Such coated
surfaces therefore have applications in blood contacting devices
and in devices where reduced non-specific protein adsorption is
desirable, for instance in diagnostic devices which require a
specific interaction of an analyte and detector species, e.g.
biosensors, bioseparation membranes and sight correction
devices.
[0084] In one embodiment, the invention can be used for improving
medical or laboratory devices to increase biocompatibility and
resistance to protein binding.
[0085] In another embodiment, the surface gradient is created on
DNA microarray slides, Current slides are composed of single
strands of DNA attached on a glass slide to form discrete dots in
an array pattern. Several hundred or more dots currently can be put
on a slide. A solution containing single strands of DNA is poured
on top of the slide. The DNA strands in solution eventually match
up to the matching stationary strand on the slide. Because the
slides are manufactured so that the specific location and
composition of the stationary strand is known, one can determine
the DNA make-up of the solution by identifying where the DNA
coupling reaction occurs.
[0086] A further embodiment of this invention, would improve the
fluid transport across the slide. Instead of waiting for the DNA
strands to diffuse through solution until it finds its matching
strand, the fluid is directed across the slide so that it is
distributed more efficiently. This would also make the slides much
smaller. Rather than having strands in dots, they could be in a
series of lines along the surface. As the fluid moves across the
surface due to the surface energy gradient, the DNA will react to
the matching strand as it passes over it.
[0087] Another embodiment is the use of this surface in
miniaturized systems that require cooling. The fluid is transported
through coolant channels using the surface energy gradient.
Reducing the surface tension of a fluid allows it to flow into
regions of smaller and smaller dimensions. Any type of
semiconductor, electromechanical, or optoelectronic device that
requires cooling to operate the most efficiently could use this
technology. The invention would also allow such systems to be made
even smaller because the size of the device would not face the heat
transfer limitations that many current devices have.
[0088] Another embodiment is the use of the surface gradient in
medical devices, treatments and artificial organs. Small tubes with
a surface energy gradient on the inside surface are able to
function as capillaries or other blood vessels. The blood would
naturally flow through the tube; surface tension would not prevent
it from moving into recesses and other extremely small
openings.
[0089] Another embodiment is the use of the surface gradient in
depositing metal or other components on hard to reach and surfaces
in corners or deep recesses. For example, an electroless plating
solution could be transported to an inside corner deep within an
object using this invention. Metal could then be deposited in an
area that was previously unable to be coated.
[0090] Another embodiment is the use of the surface gradient in not
only just using these systems to merely detect and analyze
solutions, this invention can be used in objects and devices that
actually treat and/or deliver medical benefits. For instance, a
vein or artery surface (either natural or artificial) could be
treated so that it has a surface energy gradient that causes plaque
or cholesterol particles to be transported to specific areas where
they are reacted with a component that destroys them in solution.
This would prevent cholesterol from building up on the walls.
[0091] Another embodiment is the use of the surface gradient in
integration with biopharmaceutical molecules that recognize a
certain genetic or protein sequence. When virus or cancer or other
disease molecules containing that sequence are transported across
the surface, the reactive chemical recognizes the sequence of
interest and kills the harmful molecule.
[0092] FIG. 2 shows a blown-up schematic view of the method during
the removal and exposure steps wherein the instrument 11 that
removes the SAM layer 3 also delivers new molecules 13 to the base
surface 1. In this manner the mixing of first molecules 5 and
second molecules 13 is performed near the base surface 1 as the
instrument 11 delivers second molecules 13 from the instrument
reservoir 21. The instrument 11 can have the new molecules 13
stored in the instrument reservoir 21 inside the instrument 11 or
added to the instrument 11 by tool 23 as the instrument 11 passes
along the surface 1.
[0093] FIG. 3 shows a blown-up schematic view of the method during
the removal and exposure steps wherein the instrument 11 that
removes the SAM layer 3 also delivers new molecules 13 to the base
surface 1. In this manner the mixing of first molecules 5 and
second molecules 13 is performed inside the instrument reservoir 21
and then the mixture is delivered near the base surface 1 as the
instrument 11 delivers second molecules 13 from the instrument
reservoir 21.
[0094] The instrument 11 can have the new molecules 13 stored in
the instrument reservoir 21 inside the instrument 11 or added to
the instrument 11 by tool 23 as the instrument 11 passes along the
surface 1.
[0095] FIG. 4 illustrates another method of mixing. Here, the
mixing method has similarities to those illustrated in FIG. 2 and
FIG. 3. However the mixing of molecules is performed in an outside
reservoir 25. The mixed molecules are then transferred into the
instrument reservoir 21 by means of a line 27.
[0096] In FIG. 5, the mixed-SAM surface 29 reacts with NHS
(N-hydroxy succinimide) to produce a surface with an increasing
concentration of NHS ester (step b). It should be noted that the
portions of the CH.sub.3--CO.sub.2H mixed monolayer that do not
take part in the reaction are not shown (e.g. CH.sub.3). Various
proteins 31 containing lysine groups can then be adsorbed by
NHS-surfaces 33 (step c). The NHS-surface 33 functions to
self-propel or reduce the external force requirements necessary for
propulsion of a liquid (e.g. blood) while removing protein
molecules from the liquid. Similar designs could have a wide
application in analyzing blood, other protein-bearing liquids, and
liquids containing oligo-strands of DNA, as well as
antigen/antibody combinations. This NHS-surface and other such
surfaces use SAM surfaces such as these, with properties tailored
to adsorb specific molecules, and provides means to effectively
decrease the necessary dimensions of such analytical systems. This
system could also be applied to stent technology so as to remove
harmful proteins or fats from collecting in arteries and other such
body lumens.
[0097] FIG. 6 illustrates a method for creating a surface energy
gradient on the inside of a tube 35. In this instance, the
instrument 11 is in contact with the uniform surface energy
monolayer on the inside walls of the tube 35 and moves along the
inside of the tube 35 in a direction longitudinal to the
longitudinal axis 37 removing the uniform surface energy monolayer.
The second organic molecules having a different functional group
than that of the removed monolayer can be in solution above the
instrument in upper area 39, below in lower area 41, or in both
upper area 39 or lower area 41. The solution can also flow through
a hollow cavity in the instrument 11 so as to reach the surface to
be treated. As more second organic molecules are added a greater
number will react with the portion of the tube which has had the
uniform surface energy monolayer removed. In this way a
longitudinal gradient is created on the inside walls of the tube
35.
[0098] FIG. 7 illustrates a similar method for creating a surface
energy gradient on the inside of a tube 35. However, in this
instance, the instrument 11 is in contact with the uniform surface
energy monolayer on the inside walls of the tube 35 and moves along
the inside of the tube 35 in a rotational direction about the
longitudinal axis 37 removing the uniform surface energy monolayer.
The second organic molecules having a different functional group
than that of the removed monolayer can be in solution above the
instrument in upper area 39, below in lower area 41, or in both
upper area 39 and lower area 41. The solution can also flow through
a hollow cavity in the instrument 11 so as to reach the surface to
be treated. As more second organic molecules are added a greater
number will react with the portion of the tube which has had three
uniform surface energy monolayer removed. In this way a gradient is
created on the inside walls of the tube 35 about a strip on the
radius.
[0099] FIG. 8 illustrates a schematic of the pattern of surface
energy gradient 43 created if the instrument 11 from FIG. 7 is in
contact with the uniform surface energy monolayer on the inside
walls of the tube 35 and moves along the inside of the tube 35 in a
rotational direction about the longitudinal axis 37 and in a
longitudinal direction along the longitudinal axis 37 removing the
uniform surface energy monolayer. The second organic molecules
having a different functional group than that of the removed
monolayer can be in solution above the instrument in upper area 39,
below in lower area 41, or in both upper area 39 or lower area 41.
The solution can also flow through a hollow cavity in the
instrument 11 so as to reach the surface to be treated As more
second organic molecules are added a greater number will react with
the portion of the tube which has had the uniform surface energy
monolayer removed. In this way a gradient is created on the inside
walls of the tube 35 in a spiral type pattern.
[0100] FIG. 9 illustrates a method for creating a surface energy
gradient on the outside side of a tube 35. In this instance, the
instrument 11 is in contact with the uniform surface energy
monolayer on the outside walls of the tube 35 and moves along the
outside of the tube 35 in a direction longitudinal to the
longitudinal axis 37 removing the uniform surface energy monolayer.
The direction of the instrument's movement can also be rotational
about the longitudinal axis 37 or a combination of rotational and
longitudinal movement thereby creating a spiral gradient on the
outside of the tube. The second organic molecules having a
different functional group than that of the removed monolayer can
be in solution above the longitudinal instrument contact point 45
in upper area 39, below in lower area 41, or in both upper area 39
or lower area 41. The solution can also flow through a hollow
cavity in the instrument 11 so as to reach the surface to be
treated. As more second organic molecules are added a greater
number will react with the portion of the tube which has had the
uniform surface energy monolayer removed. In this way a gradient is
created on the outside wails of the tube 35.
[0101] FIGS. 10 and 11 illustrate how the surface energy gradient
can be created on only specific portions of the tube. By employing
the same methods and mechanisms as those of FIGS. 6, 7, 8, and 9
with the addition of teeth or tips 47 even more specific portions
of surface energy gradient can be created on the inside of the tube
35 as in FIG. 10 and the outside of the tube as in FIG. 11.
[0102] While this invention may be embodied in many different
forms, there are described in detail herein specific preferred
embodiments of the invention. This description is an
exemplification of the principles of the invention and is not
intended to limit the invention to the particular embodiments
illustrated.
[0103] For the purposes of this disclosure, like reference numerals
in the figures shall refer to like features unless otherwise
indicated.
[0104] The above disclosure is intended to be illustrative and not
exhaustive. This description will suggest many variations and
alternatives to one of ordinary skill in this art. All these
alternatives and variations are intended to be included within the
scope of the claims where the term "comprising" means "including,
but not limited to". Those familiar with the art may recognize
other equivalents to the specific embodiments described herein
which equivalents are also intended to be encompassed by the
claims.
[0105] Further, the particular features presented in the dependent
claims can be combined with each other in other manners within the
scope of the invention such that the invention should be recognized
as also specifically directed to other embodiments having any other
possible combination of the features of the dependent claims. For
instance, for purposes of claim publication, any dependent claim
which follows should be taken as alternatively written in a
multiple dependent form from all prior claims which possess all
antecedents referenced in such dependent claim if such multiple
dependent format is an accepted format within the jurisdiction
(e.g. each claim depending directly from claim 1 should be
alternatively taken as depending from all previous claims). In
jurisdictions where multiple dependent claim formats are
restricted, the following dependent claims should each be also
taken as alternatively written in each singly dependent claim
format which creates a dependency from a prior
antecedent-possessing claim other than the specific claim listed in
such dependent claim below.
[0106] This completes the description of the preferred and
alternate embodiments of the invention. Those skilled in the art
may recognize other equivalents to the specific embodiment
described herein which equivalents are intended to be encompassed
by the claims attached hereto.
[0107] Such information as may be found relating to portions of
this application include: [0108] Kataoka, Dawn E. and Troian,
Sandra M., "Patterning Liquid Flow on the Microscopic Scale,"
Nature, Vol. 402, December 1999, pp. 794-797. [0109] Kim, H.,
Graupe, M., Oloba, O., Koini, T., Imaduddin, S., Lee, T., and
Perry, S., "Molecularly Specific Studies of the Frictional
Properties of Monolayer Films: A Systematic Comparison of CF3--,
(CH3)2CH--, and CH3-Terminated Films," Langmuir, 1999, Vol. 15, pp.
3179-3185. [0110] Krim, J. "Atomic-Scale Origins of Friction,"
Langmuir, 1996, Vol. 12, pp. 4564-4566. [0111] Laibinis, P.,
Palmer, B., Lee, S., and Jennings, G. K., "The Synthesis of
Organothiols and Their Assembly into Monolayers on Gold," Thin
Films Vol. 24, 1998. [0112] Laibinis, P., Fox, M., Folkers, J., and
Whitesides, G., "Comparisons of Self-Assembled Monolayers on Silver
and Gold," Langmuir, 1991, Vol. 7, pp. 3167-3173. [0113] Lee, S.,
Shon, Y., Colorado, R., Guenard, R., Lee, T., and Perry, S., "The
Influence of Packing Densities and Surface Order on the Frictional
Properties of Alkanethiol Self-Assembled Monolayers (SAMs) on Gold,
Langmuir, 2000, Vol. 16, pp. 2220-2224. [0114] Liu, Y. and Evans,
D., "Structure and Frictional Properties of Self-assembled
Surfactant Monolayers," Langmuir, 1996, Vol. 12, pp. 1235-1244.
[0115] Patel, N., Davies, M., Hartshorne, M., Heaton, R., Roberts,
C., Tendler, S., and Williams, P., "Immobilization of Protein
Molecules onto Homogenous and Mixed Carboxylate-Terminated
Self-Assembled Monolayers," Langmuir, 1997, Vol. 13, pp. 6485-6490.
[0116] Pfahler, J, Harley, J., and Ban, H., "Liquid Transport in
Micron and Submicron Channels," Sensors and Actuators, A21-23,
1990, pp. 431-434. [0117] Tsukruk, V., and Bliznyuk, V., "Adhesive
and Friction Forces Between Chemically Modified Silicon and Silicon
Nitride Surfaces," Langmuir, 1998, Vol. 14, pp. 446-455. [0118]
Xiao, X., Hu, J., Charych, D., and Salmeron, M., "Chain Length
Dependence of the Frictional Properties of Alkylsilane Molecules
Self-Assembled on Mica Studied by Atomic Force Microscopy,"
Langmuir, 1996, Vol. 12, pp. 235-237. [0119] Xu, S., Miller, S.,
Laibinis, P, and Liu, G., "Fabrication of Nanometer Scale Patterns
within Self-Assembled Monolayers by Nanografting," Langmuir, 1999,
Vol. 15, pp. 7244-7251. [0120] U.S. Pat. No. 6,235,340 [0121] U.S.
Pat. No. 5,512,131 [0122] U.S. Pat. No. 5,776,748 [0123] U.S. Pat.
No. 4,690,715 [0124] U.S. Pat. No. 5,620,850 [0125] U.S. Pat. No.
5,079,600
[0126] All US patents and applications and all other published
documents mentioned anywhere in this application are incorporated
herein by reference in their entirety.
* * * * *