U.S. patent application number 13/495075 was filed with the patent office on 2012-10-11 for microfabricated devices with coated or modified surface and method of making same.
This patent application is currently assigned to P2i Ltd.. Invention is credited to Stephen Coulson.
Application Number | 20120258025 13/495075 |
Document ID | / |
Family ID | 37546174 |
Filed Date | 2012-10-11 |
United States Patent
Application |
20120258025 |
Kind Code |
A1 |
Coulson; Stephen |
October 11, 2012 |
MICROFABRICATED DEVICES WITH COATED OR MODIFIED SURFACE AND METHOD
OF MAKING SAME
Abstract
A microfabricated device or component thereof, such as
microfluidics or nanofluidics device having a uniform non-wetting
or non-absorbing polymeric coating or surface modification formed
on a surface thereof by ionisation or activation technology such as
plasma processing, to produce a surface energy of less than 15
mNm.sup.-l. The treatment enhances the free-flowing properties of a
liquid through the device during use.
Inventors: |
Coulson; Stephen; (Abingdon,
GB) |
Assignee: |
P2i Ltd.
Abingdon
GB
|
Family ID: |
37546174 |
Appl. No.: |
13/495075 |
Filed: |
June 13, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12446999 |
Apr 28, 2009 |
|
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PCT/GB2007/003969 |
Oct 24, 2007 |
|
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13495075 |
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Current U.S.
Class: |
422/502 ;
427/488; 977/700 |
Current CPC
Class: |
C08F 220/24 20130101;
B01L 2200/12 20130101; B05D 1/62 20130101; C09D 4/00 20130101; B05D
5/083 20130101; B01L 2300/165 20130101; B01L 3/502707 20130101 |
Class at
Publication: |
422/502 ;
427/488; 977/700 |
International
Class: |
C08F 2/46 20060101
C08F002/46; B01L 3/00 20060101 B01L003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 28, 2006 |
GB |
0621520.6 |
Claims
1. A method for enhancing the free-flowing properties of liquid
through a microfluidic device with chambers and tunnels for the
containment and flow of fluid, said method comprising using
microfluidic device wherein at least a liquid contacting surface
thereof has a surface energy value of less than 15 mNm.sup.-1 as a
result of the presence of a uniform non-wetting or non-absorbing
coating or surface modification formed thereon by plasma
processing, wherein to produce the coating or surface modification
the device or an element, component or sub-assembly thereof is
exposed to a preliminary continuous plasma to pre-treat the liquid
contacting surface so a monomer or monomers can attach to the
surface, followed by a plasma to allow polymerization of the
monomer(s) to proceed so the coating grows on the surface as a
uniform coating.
2. The method according to claim 1, wherein the plasma to allow the
polymerization of the monomer(s) is a pulsed plasma.
3. The method according to claim 1, wherein the said liquid
contacting surface has deposited thereon a polymeric coating formed
by exposing said surface to a pulsed plasma comprising a compound
of formula (I) ##STR00009## where R.sup.1, R.sup.2 and R.sup.3 are
independently selected from hydrogen, alkyl, haloalkyl or aryl
optionally substituted by halo; and R.sup.4 is a group --X--R.sup.5
where R.sup.5 is an alkyl or haloalkyl group and X is a bond; a
group of formula --C(O)O--, a group of formula
--C(O)O(CH.sub.2).sub.nY-- where n is an integer of from 1 to 10
and Y is a sulphonamide group; or a group
--(O).sub.pR.sup.6(O).sub.q(CH.sub.2).sub.t-- where R.sup.6 is aryl
optionally substituted by halo, p is 0 or 1, q is 0 or 1 and t is 0
or an integer of from 1 to 10, provided that where q is 1, t is
other than 0, in a gaseous state for a sufficient period of time to
allow a polymeric layer to form on the surface.
4. The method according to claim 1, wherein the device or an
element, component or sub-assembly thereof is placed in a plasma
deposition chamber, a glow discharge is ignited within said
chamber, and a voltage applied as a pulsed field.
5. The method according to claim 4, wherein applied voltage is at a
power of from 5 to 500 W.
6. The method according to claim 4, wherein the voltage is pulsed
in a sequence in which the ratio of the time on:time off is in the
range of from 1:500 to 1:1500.
7. The method according to claim 6 wherein the voltage is pulsed in
a sequence where power is on for 20-50 .mu.s, and off for from 1000
.mu.s to 30000 .mu.s.
8. The method according to claim 4 wherein the voltage is applied
as a pulsed field at for a period of from 30 seconds to 90
minutes.
9. The method according to claim 8 wherein the voltage is applied
as a pulsed field for from 5 to 60 minutes.
10. The method according to claim 1, wherein in a preliminary step,
a continuous power plasma is applied to the microfluidic device or
an element, component or sub-assembly thereof.
11. The method according to claim 10, wherein the preliminary step
is conducted in the presence of an inert gas.
12. The method according to claim 3, wherein the compound of
formula (I) in gaseous form is fed into the plasma at a rate of
from 80-300 mg/minute, while the pulsed voltage is applied.
13. The method according to claim 3, wherein the plasma is created
with a voltage at an average power of from 0.001 to
500w/m.sup.3.
14. The method according to claim 13, wherein the plasma is created
with a voltage at an average power of from 0.001 to
100w/m.sup.3.
15. The method according to claim 14, wherein the plasma is created
with a voltage at an average power of from 0.005 to
0.5w/m.sup.3.
16. The method according to claim 3, wherein the compound of
formula (I) is a compound of formula (II) CH.sub.2.dbd.CH--R.sup.5
(II) where R.sup.5 is as defined in claim 5, or a compound of
formula (III) CH.sub.2.dbd.CR.sup.7C(O)O(CH.sub.2).sub.nR.sup.5
(III) where n and R.sup.5 as defined in claim 5 and R.sup.7 is
hydrogen, C.sub.1-10 alkyl, or C.sub.1-10haloalkyl.
17. The method according to claim 16, wherein the compound of
formula (I) is a compound of formula (III).
18. The method according to claim 17, wherein the compound of
formula (III) is a compound of formula (IV) ##STR00010## where
R.sup.7 is as defined in claim 16, and x is an integer of from 1 to
9.
19. The method according to claim 18, wherein the compound of
formula (IV) is 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate.
20. A method for enhancing the free-flowing properties of liquid
through a nanofluidic device with chambers and tunnels for the
containment and flow of fluid, said method comprising using
nanofluidic device wherein at least a liquid contacting surface
thereof has a surface energy value of less than 15 mNm.sup.-1 as a
result of the presence of a uniform non-wetting or non-absorbing
coating or surface modification formed thereon by plasma
processing, wherein to produce the coating or surface modification
the device or an element, component or sub-assembly thereof is
exposed to a preliminary continuous plasma to pre-treat the liquid
contacting surface so a monomer or monomers can attach to the
surface, followed by a plasma to allow polymerization of the
monomer(s) to proceed so the coating grows on the surface as a
uniform coating.
21. The method according to claim 20, wherein the plasma to allow
the polymerization of the monomer(s) is a pulsed plasma.
22. The method according to claim 20, wherein the said liquid
contacting surface has deposited thereon a polymeric coating formed
by exposing said surface to a pulsed plasma comprising a compound
of formula (I) ##STR00011## where R.sup.1, R.sup.2 and R.sup.3 are
independently selected from hydrogen, alkyl, haloalkyl or aryl
optionally substituted by halo; and R.sup.4 is a group --X--R.sup.5
where R.sup.5 is an alkyl or haloalkyl group and X is a bond; a
group of formula --C(O)O--, a group of formula
--C(O)O(CH.sub.2).sub.nY-- where n is an integer of from 1 to 10
and Y is a sulphonamide group; or a group
--(O).sub.pR.sup.6(O).sub.q(CH.sub.2).sub.t-- where R.sup.6 is aryl
optionally substituted by halo, p is 0 or 1, q is 0 or 1 and t is 0
or an integer of from 1 to 10, provided that where q is 1, t is
other than 0, in a gaseous state for a sufficient period of time to
allow a polymeric layer to form on the surface.
23. The method according to claim 20, wherein the device or an
element, component or sub-assembly thereof is placed in a plasma
deposition chamber, a glow discharge is ignited within said
chamber, and a voltage applied as a pulsed field.
24. The method according to claim 23, wherein applied voltage is at
a power of from 5 to 500 W.
25. The method according to claim 23, wherein the voltage is pulsed
in a sequence in which the ratio of the time on:time off is in the
range of from 1:500 to 1:1500.
26. The method according to claim 25, wherein the voltage is pulsed
in a sequence where power is on for 20-50 .mu.s, and off for from
1000 .mu.s to 30000 .mu.s.
27. The method according to claim 23, wherein the voltage is
applied as a pulsed field at for a period of from 30 seconds to 90
minutes.
28. The method according to claim 27, wherein the voltage is
applied as a pulsed field for from 5 to 60 minutes.
29. The method according to claim 20, wherein in a preliminary
step, a continuous power plasma is applied to the nanofluidic
device or an element, component or sub-assembly thereof.
30. The method according to claim 29, wherein the preliminary step
is conducted in the presence of an inert gas.
31. The method according to claim 22, wherein the compound of
formula (I) in gaseous form is fed into the plasma at a rate of
from 80-300 mg/minute, while the pulsed voltage is applied.
32. The method according to claim 22, wherein the plasma is created
with a voltage at an average power of from 0.001 to
500w/m.sup.3.
33. The method according to claim 32, wherein the plasma is created
with a voltage at an average power of from 0.001 to
100w/m.sup.3.
34. The method according to claim 33, wherein the plasma is created
with a voltage at an average power of from 0.005 to
0.5w/m.sup.3.
35. The method according to claim 22, wherein the compound of
formula (I) is a compound of formula (II) CH.sub.2.dbd.CH--R.sup.5
(II) where R.sup.5 is as defined in claim 5, or a compound of
formula (III) CH.sub.2.dbd.CR.sup.7C(O)O(CH.sub.2).sub.nR.sup.5
(III) where n and R.sup.5 as defined in claim 5 and R.sup.7 is
hydrogen, C.sub.1-10 alkyl, or C.sub.1-10haloalkyl.
36. The method according to claim 35, wherein the compound of
formula (I) is a compound of formula (III).
37. The method according to claim 36, wherein the compound of
formula (III) is a compound of formula (IV) ##STR00012## where
R.sup.7 is as defined in claim 35, and x is an integer of from 1 to
9.
38. The method according to claim 37, wherein the compound of
formula (IV) is 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate.
39. A microfluidic device with a uniform coating on an element,
component or sub-assembly thereof made by the method of claim
1.
40. A nanofluidic device with a uniform coating on an element,
component or sub-assembly thereof made by the method of claim 20.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Ser. No.
12/446,999, filed Apr. 28, 2009, which was a national stage
application (under 35 USC .sctn.371) of PCT/GB2007/003969, filed
Oct. 24, 2007, which claims benefit of British application
0621520.6, filed Oct. 28, 2006.
BACKGROUND
[0002] The present invention relates to microfabricated devices, in
particular microfluidics or nanofluidics devices which are treated
to provide a non-wetting, non-absorbing coating thereon, as well as
to processes for their production.
[0003] Microfabrication techniques have long been used in the
electronics industries to produce items such as integrated circuit
boards or printed circuit boards (PCBs) for increasingly
miniaturised electronic devices. These techniques are finding
application in other areas of technology.
[0004] Nanotechnology is a fast growing area of technology in which
materials and devices are designed, synthesised and characterised
on a nanoscale for a wide variety of applications, for example in
microelectronics, semiconductors, optoelectronics,
medicine/pharmaceutical, diagnostics, catalysis, filtration, energy
storage, within the chemical or nuclear industries etc.
[0005] Materials and devices classified as nanotechnology devices
are usually less than 100 nanometers in size. They are generally
produced in one of two basic ways, the first of which involves the
careful construction of the device, molecule by molecule to achieve
the desired structure. The second method involves the gradual
stripping or etching of material from pre-existing structures, and
is largely based upon pre-existing microfabrication technology,
such as that used in conventional semiconductor art.
[0006] Microfluidic or nanofluidic devices are miniaturized devices
with chambers and tunnels for the containment and flow of
fluids.
[0007] Microfluidic devices may be defined as having one or more
channels with at least one dimension less than 1 mm, whilst
nanofluidic devices will have generally smaller channels. With
devices measured at the micrometer level and fluids measured in
nanoliters and picoliters, microfluidics devices are widely used
for example in biotechnology or biochemistry.
[0008] These devices can be used to handle a wide variety of
liquids sample types. However, they are particularly useful in
biochemical research or diagnostics in particular clinical
diagnostics, where they may be used to handle liquids such as blood
samples (including whole blood or fractions such as blood plasma),
bacterial cell suspensions, protein or antibody solutions and other
reagents including organic solvents, buffers and salts. Depending
upon the nature and arrangement of the microfluidic device, it can
be used in a wide range of analytical techniques and methods
including for example, the measurement of molecular diffusion
coefficients, fluid viscosity, pH, chemical binding coefficients
and enzyme reaction kinetics. Other applications for microfluidic
devices include capillary electrophoresis, isoelectric focusing,
immunoassays, flow cytometry, sample injection of proteins for
analysis via mass spectrometry, amplification of nucleic acids for
example using amplification reactions such as the polymerase chain
reaction (PCR), DNA and protein analysis, cell manipulation, cell
separation, cell patterning and chemical gradient formation, high
through-put screening, micro checmical manufacture, cell based
testing of drug candidates, patient monitoring, proteomics and
genomics, chemical microreactions, protein crystallisation, drug
delivery, scale-up to manufacturing of drugs, security and
defence.
[0009] The use of microfluidic devices in carrying out biomedical
research and analysis has a number of significant advantages.
First, because the volume of fluids within these channels is very
small, usually several nanoliters, the amount of reagents and
analytes used is quite small. This is especially significant for
expensive reagents or where reagents are scarce, for example in
some diagnostic applications or forensic DNA analysis.
[0010] The fabrications techniques used to construct microfluidic
devices can be relatively inexpensive and are very amenable both to
highly elaborate, multiplexed devices and also to mass production.
In a manner similar to that for microelectronics, microfluidic
technologies enable the fabrication of highly integrated devices
for performing several different functions on the same substrate
chip. These devices can therefore give rise to the so-called
"lab-on-a-chip" devices, which can be used as portable clinical
diagnostic devices for use for example in doctors' surgeries or
hospitals or even at home as a point-of-care device, reducing the
need for laboratory analysis procedures.
[0011] Microfluidic devices can be fabricated from a variety of
materials, such as silicon, glass, metals or polymers or mixtures
of these using a variety of microfabrication techniques. The
selection of the particular technique depends to a large extent
upon the nature of the substrate material. Depending upon the
intended use, the substrate may be required to be quite rigid or
stiff, or have a particular resistance to chemicals or temperature
cycling to ensure any necessary dimensional stability.
[0012] For example, the manufacture may be carried out by laying
down a photoresist (positive or negative) onto a substrate and in
particular a silicon substrate. The photoresist is exposed to UV
light through a high-resolution mask with the desired device
patterns, so as to allow polymerisation to occur in the exposed
areas. Then excess unpolymerized photoresist is washed off and the
substrate is placed in a wet chemical etching bath that
anisotropically etches it in locations not protected by
photoresist. The result is a substrate such as a silicon wafer in
which microchannels are etched. A coverslip such as a glass
coverslip for instance, is used to fully enclose the channels and
holes are drilled in the glass to allow access to the microchannels
for the sample.
[0013] Deep reactive ion etching (DRIE) may be used as an
alternative to this type of wet chemical etching which is
particularly useful when straighter edges and a deeper etch depth
is required.
[0014] Thermosetting or other curable polymers may also be used to
prepare microfluidic devices, by moulding methods. A particular
example of such a polymer is the silicone polymer,
polydimethylsiloxane (PDMS) but others as are conventional in the
art may be employed. The polymer in liquid form is poured over or
into a mould (usually silicon or photoresist) and cured to
cross-link the polymer. PDMA produces an optically clear,
relatively flexible material that can be stacked onto other cured
polymer slabs to form complex three-dimensional geometries.
[0015] Alternatively, polymers or plastics can be subject to hot
embossing techniques so as to imprint suitable patterns into the
surface of the plastics. Injection moulding may be used to create
complex structures.
[0016] Some microfluidic devices are prepared from layered
polymeric sheets. Outlines of the microfluidic device are cut in
thin sheets of optically transparent plastics such as Mylar.TM.
with a laser cutting tool such as a carbon dioxide laser. The
layers are bonded together with a thin adhesive layer to produce
three-dimensional structures.
[0017] All these techniques are useful and so microfluidics is
showing great promise in a variety of applications as outlined
above.
[0018] However the small volumes involved mean that the liquids are
prone to surface effects, and in particular wetting or adsorption
within the channels. The devices are generally less sensitive than
bulk tests, and are prone to failure if insufficient liquid is able
to pass along the channels. However the varying nature of the
substrates used in these devices means that it is difficult to
ensure that this does not happen.
[0019] Techniques which have been used to address this problem
include sputtering Teflon like coatings onto the devices or using
fluorinated silanes in their construction. However these techniques
present further complications such as poor adhesion quality, lack
of durability and ineffective control of film thickness.
[0020] Ionisation techniques or activation techniques, where
reactive atoms or molecules such as ions or free radicals are
generated and contacted with surface have been used to modify
surfaces. Examples of such techniques include plasma processing
(including plasma deposition and plasma activation), neutron
activation, e-beam or thermal ionisation techniques. They have been
quite widely used for the deposition of polymeric coatings onto a
range of surfaces, and in particular onto fabric surfaces.
[0021] Plasma polymerisation in particular is recognised as being a
clean, dry techniques that generates little waste compared to
conventional wet chemical methods. Using this method, plasmas are
generally generated from organic molecules, which are subjected to
an electrical field. When this is done in the presence of a
substrate, the radicals of the compound in the plasma react on the
substrate to form a polymer film.
[0022] Conventional polymer synthesis tends to produce structures
containing repeat units that bear a strong resemblance to the
monomer species, whereas a polymer network generated using a plasma
can be extremely complex due to extensive monomer fragmentation.
The properties of the resultant coating can depend upon the nature
of the substrate as well as the nature of the monomer used and
conditions under which it is deposited.
[0023] WO03/082483 describes the deposition of non-uniform plasma
polymeric surfaces onto devices so as to achieve certain specific
technical effects such as the control of local wettability,
adhesion and frictional/wear characteristics.
[0024] Plasma deposition of a uniform polymeric coating onto
microfabricated devices and in particular microfluidic or
nanofluidic devices in order to reduce wetting generally and
increase reliability has not previously been described. It is not
clear therefore whether coatings applied in this way would be
effective at eliminating adsorption problems at this level.
[0025] The present inventors have found that by subjecting at least
the surfaces of a microfabricated device which come into contact
with a liquid during use to a ionisation or activation means such
as a plasma which causes modification of the surface to impart
non-wetting properties, the reliability and robustness of the
microfabricated device may be significantly enhanced.
SUMMARY OF THE INVENTION
[0026] According to one aspect, the invention provides apparatus
selected from a microfabricated device or a component thereof
wherein at least one surface thereof has a uniform non-wetting or
non-absorbing coating or surface modification formed thereon by
ionisation or activation technology, so as to produce surface
energy value of less than 15 mNm.sup.-1.
[0027] The ultra low surface energies achievable using these
techniques can be less that 12 mNm.sup.-1, for example from 8-10
mNm.sup.-1 (where mNm.sup.-1 is milliNewtons per metre).
[0028] In one embodiment, the ionisation or activation technology
used is plasma processing. In particular the said surface of the
microfabricated device or component has a uniform non-wetting or
non-absorbing polymeric coating formed thereon by plasma
deposition.
[0029] As used herein, the expression "microfabricated device"
refers to any miniaturised device, or nanotechnological device, in
particular microfluidic or nanofluidic devices, which have channels
etc of less than 1 mm or 100 nanometers respectively. Suitably the
surface of the microfabricated device or component, which has been
treated so as to assume non-wetting or non-absorbing properties, is
that which would, in use, come into contact with liquids. However,
if convenient or required, additional surfaces or even the entire
device may be so treated.
[0030] Treatment using the ionisation or activation techniques may
be effected at any convenient stage of the preparation of the
microfabricated device, so that either the device as a whole or
individual components, elements or sub-assemblies of the device may
be treated. For example, where channels have been etched into or
otherwise formed in a substrate, the substrate may be subjected to
the treatment, which produces a uniform coating over the entire
substrate, and this ensures that the entire surface of the channels
are suitably non-wetting or non-absorbing. Similarly, any cover
plates or laminar materials used in the construction of the device
may be treated before assembly. It will be appreciated that the
formation of the polymeric layer on the surface of an element,
component or sub-assembly of the microfabricated device may occur
before or after the element, component or sub-assembly is formed
from a blank, and that therefore the term "element" as used herein
includes blanks from which components may be produced. The
applicants have found however that even when fully fabricated,
exposure of the device to ionisation or activation techniques and
in particular to plasma will allow monomer molecules and activated
species to penetrate preformed channels and other complex three
dimensional structures and become polymerised in situ on the
surface of the channel.
[0031] Plasma processing to achieve non-wetting or non-absorbing
properties may be achieved, for example, by exposing the surface to
plasma comprising small molecules such as CF.sub.4 and a variety of
saturated and unsaturated hydrocarbon and fluorocarbon compounds
(see, for example, "Plasma Polymerisation", Academic Press Inc.
(London) Ltd. 1985). Longer chain semi and fully fluorinated
compounds may also be used to impart non-wetting or non-absorbing
properties.
[0032] Any monomeric compound or gas which undergoes plasma
polymerisation or modification of the surface to form a non-wetting
or non-absorbing, water-repellent polymeric coating layer or
surface modification on the surface of the microfabricated device
may suitably be used. Suitable monomers which may be used include
those known in the art to be capable of producing water-repellent
polymeric coatings on substrates by plasma polymerisation
including, for example, carbonaceous compounds having reactive
functional groups, particularly substantially --CF.sub.3 dominated
perfluoro compounds (see WO 97/38801), perfluorinated alkenes (Wang
et al., Chem Mater 1996, 2212-2214), hydrogen containing
unsaturated compounds optionally containing halogen atoms or
perhalogenated organic compounds of at least 10 carbon atoms (see
WO 98/58117), organic compounds comprising two double bonds (WO
99/64662), saturated organic compounds having an optionally
substituted alky chain of at least 5 carbon atoms optionally
interposed with a heteroatom (WO 00/05000), optionally substituted
alkynes (WO 00/20130), polyether substituted alkenes (U.S. Pat. No.
6,482,531B) and macrocycles containing at least one heteroatom
(U.S. Pat. No. 6,329,024B), the contents of all of which are herein
incorporated by reference.
[0033] According to one embodiment, the invention provides a
microfabricated device or component thereof having a polymeric
coating, formed by exposing at least one surface of the device to
plasma comprising a compound of formula (I)
##STR00001##
where R.sup.4, R.sup.2 and R.sup.3 are independently selected from
hydrogen, alkyl, haloalkyl or aryl optionally substituted by halo;
and R.sup.4 is a group --X--R.sup.5 where R.sup.5 is an alkyl or
haloalkyl group and X is a bond; a group of formula --C(O)O--, a
group of formula --C(O)O(CH.sub.2).sub.nY-- where n is an integer
of from 1 to 10 and Y is a sulphonamide group; or a group
--(O).sub.pR.sup.6(O).sub.q(CH.sub.2).sub.t-- where R.sup.6 is aryl
optionally substituted by halo, p is 0 or 1, q is 0 or 1 and t is 0
or an integer of from 1 to 10, provided that where q is 1, t is
other than 0, for a sufficient period of time to allow a polymeric
layer to form on the surface.
[0034] As used therein the term "halo" or "halogen" refers to
fluorine, chlorine, bromine and iodine. Particularly preferred halo
groups are fluoro. The term "aryl" refers to aromatic cyclic groups
such as phenyl or naphthyl, in particular phenyl. The term "alkyl"
refers to straight or branched chains of carbon atoms, suitably of
up to 20 carbon atoms in length. The term "alkenyl" refers to
straight or branched unsaturated chains suitably having from 2 to
20 carbon atoms. "Haloalkyl" refers to alkyl chains as defined
above which include at least one halo substituent.
[0035] Suitable haloalkyl groups for R.sup.1, R.sup.2, R.sup.3 and
R.sup.5 are fluoroalkyl groups. The alkyl chains may be straight or
branched and may include cyclic moieties.
[0036] For R.sup.5, the alkyl chains suitably comprise 2 or more
carbon atoms, suitably from 2-20 carbon atoms and preferably from 4
to 12 carbon atoms.
[0037] For R.sup.1, R.sup.2 and R.sup.3, alkyl chains are generally
preferred to have from 1 to 6 carbon atoms.
[0038] Preferably R.sup.5 is a haloalkyl, and more preferably a
perhaloalkyl group, particularly a perfluoroalkyl group of formula
C.sub.mF.sub.2m+1 where m is an integer of 1 or more, suitably from
1-20, and preferably from 4-12 such as 4, 6 or 8.
[0039] Suitable alkyl groups for R.sup.1, R.sup.2 and R.sup.3 have
from 1 to 6 carbon atoms.
[0040] In one embodiment, at least one of R.sup.1, R.sup.2 and
R.sup.3 is hydrogen. In a particular embodiment R.sup.1, R.sup.2,
R.sup.3 are all hydrogen. In yet a further embodiment however
R.sup.3 is an alkyl group such as methyl or propyl.
[0041] Where X is a group --C(O)O(CH.sub.2).sub.nY--, n is an
integer which provides a suitable spacer group. In particular, n is
from 1 to 5, preferably about 2.
[0042] Suitable sulphonamide groups for Y include those of formula
--N(R.sup.7)SO.sub.2-- where R.sup.7 is hydrogen or alkyl such as
C.sub.1-4alkyl, in particular methyl or ethyl.
[0043] In one embodiment, the compound of formula (I) is a compound
of formula (II)
CH.sub.2.dbd.CH--R.sup.5 (II)
where R.sup.5 is as defined above in relation to formula (I).
[0044] In compounds of formula (II), X in formula (I) is a
bond.
[0045] However in a preferred embodiment, the compound of formula
(I) is an acrylate of formula (III)
CH.sub.2.dbd.CR.sup.7C(O)O(CH.sub.2).sub.nR.sup.5 (III)
where n and R.sup.5 as defined above in relation to formula (I) and
R.sup.7 is hydrogen, C.sub.1-10 alkyl, or C.sub.1-10haloalkyl. In
particular R.sup.7 is hydrogen or C.sub.1-6alkyl such as methyl. A
particular example of a compound of formula (III) is a compound of
formula (IV)
##STR00002##
where R.sup.7 is as defined above, and in particular is hydrogen
and x is an integer of from 1 to 9, for instance from 4 to 9, and
preferably 7. In that case, the compound of formula (IV) is 1H, 1H,
2H, 2H-heptadecafluorodecylacylate.
[0046] According to another aspect, the polymeric coating is formed
by exposing at least a surface of the microfabricated device to
plasma comprising one or more organic monomeric compounds, at least
one of which comprises two carbon-carbon double bonds for a
sufficient period of time to allow a polymeric layer to form on the
surface.
[0047] Suitably the compound with more than one double bond
comprises a compound of formula (V)
##STR00003##
where R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13
are all independently selected from hydrogen, halo, alkyl,
haloalkyl or aryl optionally substituted by halo; and Z is a
bridging group.
[0048] Examples of suitable bridging groups Z for use in the
compound of formula (V) are those known in the polymer art. In
particular they include optionally substituted alkyl groups which
may be interposed with oxygen atoms. Suitable optional substituents
for bridging groups Z include perhaloalkyl groups, in particular
perfluoroalkyl groups.
[0049] In a particularly preferred embodiment, the bridging group Z
includes one or more acyloxy or ester groups. In particular, the
bridging group of formula Z is a group of sub-formula (VI)
##STR00004##
where n is an integer of from 1 to 10, suitably from 1 to 3, each
R.sup.14 and R.sup.15 is independently selected from hydrogen,
alkyl or haloalkyl.
[0050] Suitably R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, and
R.sup.13 are haloalkyl such as fluoroalkyl, or hydrogen. In
particular they are all hydrogen.
[0051] Suitably the compound of formula (V) contains at least one
haloalkyl group, preferably a perhaloalkyl group.
[0052] Particular examples of compounds of formula (V) include the
following:
##STR00005##
where R.sup.14 and R.sup.15 are as defined above provided that at
least one is other than hydrogen. A particular example is a
compound of formula B.
##STR00006##
[0053] In a further aspect, the polymeric coating is formed by
exposing at least a surface of the microfabricated device to plasma
comprising a compound of comprising a monomeric saturated organic
compound, said compound comprising an optionally substituted alkyl
chain of at least 5 carbon atoms optionally interposed with a
heteroatom for a sufficient period of time to allow a polymeric
layer to form on the surface.
[0054] The term "saturated" as used herein means that the monomer
does not contain multiple bonds (i.e. double or triple bonds)
between two carbon atoms which are not part of an aromatic ring.
The term "heteroatom" includes oxygen, sulphur, silicon or nitrogen
atoms. Where the alkyl chain is interposed by a nitrogen atom, it
will be substituted so as to form a secondary or tertiary amine.
Similarly, silicons will be substituted appropriately, for example
with two alkoxy groups.
[0055] Particularly suitable monomeric organic compounds are those
of formula (VII)
##STR00007##
where R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are
independently selected from hydrogen, halogen, alkyl, haloalkyl or
aryl optionally substituted by halo; and R.sup.21 is a group
X--R.sup.22 where R.sup.22 is an alkyl or haloalkyl group and X is
a bond; a group of formula --C(O)O(CH.sub.2).sub.xY-- where x is an
integer of from 1 to 10 and Y is a bond or a sulphonamide group; or
a group --(O).sub.pR.sup.23(O).sub.s(CH.sub.2).sub.t-- where
R.sup.23 is aryl optionally substituted by halo, p is 0 or 1, s is
0 or 1 and t is 0 or an integer of from 1 to 10, provided that
where s is 1, t is other than 0.
[0056] Suitable haloalkyl groups for R.sup.16, R.sup.17, R.sup.18,
R.sup.19, and R.sup.20 are fluoroalkyl groups. The alkyl chains may
be straight or branched and may include cyclic moieties and have,
for example from 1 to 6 carbon atoms.
[0057] For R.sup.22, the alkyl chains suitably comprise 1 or more
carbon atoms, suitably from 1-20 carbon atoms and preferably from 6
to 12 carbon atoms.
[0058] Preferably R.sup.22 is a haloalkyl, and more preferably a
perhaloalkyl group, particularly a perfluoroalkyl group of formula
C.sub.zF.sub.2z+1 where z is an integer of 1 or more, suitably from
1-20, and preferably from 6-12 such as 8 or 10.
[0059] Where X is a group --C(O)O(CH.sub.2).sub.yY--, y is an
integer which provides a suitable spacer group. In particular, y is
from 1 to 5, preferably about 2.
[0060] Suitable sulphonamide groups for Y include those of formula
--N(R.sup.23)SO.sub.2.sup.- where R.sup.23 is hydrogen, alkyl or
haloalkyl such as C.sub.1-4alkyl, in particular methyl or
ethyl.
[0061] The monomeric compounds used in the method of the invention
preferably comprises a C.sub.6-25 alkane optionally substituted by
halogen, in particular a perhaloalkane, and especially a
perfluoroalkane.
[0062] According to another aspect, the polymeric coating is formed
by exposing at least one surface of the microfabricated device to
plasma comprising an optionally substituted alkyne for a sufficient
period of time to allow a polymeric layer to form on the
surface.
[0063] Suitably the alkyne compounds used in the method of the
invention comprise chains of carbon atoms, including one or more
carbon-carbon triple bonds. The chains may be optionally interposed
with a heteroatom and may carry substituents including rings and
other functional groups. Suitable chains, which may be straight or
branched, have from 2 to 50 carbon atoms, more suitably from 6 to
18 carbon atoms. They may be present either in the monomer used as
a starting material, or may be created in the monomer on
application of the plasma, for example by the ring opening
[0064] Particularly suitable monomeric organic compounds are those
of formula (VIII)
R.sup.24--C.ident.C--X.sup.1--R.sup.25 (VIII)
where R.sup.24 is hydrogen, alkyl, cycloalkyl, haloalkyl or aryl
optionally substituted by halo; X.sup.1 is a bond or a bridging
group; and R.sup.25 is an alkyl, cycloalkyl or aryl group
optionally substituted by halogen.
[0065] Suitable bridging groups X.sup.1 include groups of formulae
--(CH.sub.2).sub.s--, --CO.sub.2(CH.sub.2).sub.p--,
--(CH.sub.2).sub.pO(CH.sub.2).sub.q--,
--(CH.sub.2).sub.pN(R.sup.26)CH.sub.2).sub.q--,
--(CH.sub.2).sub.pN(R.sup.26)SO.sub.2--, where s is 0 or an integer
of from 1 to 20, p and q are independently selected from integers
of from 1 to 20; and R.sup.26 is hydrogen, alkyl, cycloalkyl or
aryl. Particular alkyl groups for R.sup.26 include C.sub.1-6 alkyl,
in particular, methyl or ethyl.
[0066] Where R.sup.24 is alkyl or haloalkyl, it is generally
preferred to have from 1 to 6 carbon atoms.
[0067] Suitable haloalkyl groups for R.sup.24 include fluoroalkyl
groups. The alkyl chains may be straight or branched and may
include cyclic moieties. Preferably however R.sup.24 is
hydrogen.
[0068] Preferably R.sup.25 is a haloalkyl, and more preferably a
perhaloalkyl group, particularly a perfluoroalkyl group of formula
C.sub.rF.sub.2r+1 where r is an integer of 1 or more, suitably from
1-20, and preferably from 6-12 such as 8 or 10.
[0069] In a preferred embodiment, the compound of formula (VIII) is
a compound of formula (IX)
CH.ident.C(CH.sub.2).sub.s--R.sup.27 (IX)
where s is as defined above and R.sup.27 is haloalkyl, in
particular a perhaloalkyl such as a C.sub.6-12 perfluoro group like
C.sub.6F.sub.13.
[0070] In an alternative preferred embodiment, the compound of
formula (VIII) is a compound of formula (X)
CH.ident.C(O)O(CH.sub.2).sub.pR.sup.27 (X)
where p is an integer of from 1 to 20, and R.sup.27 is as defined
above in relation to formula (IX) above, in particular, a group
C.sub.8F.sub.17. Preferably in this case, p is an integer of from 1
to 6, most preferably about 2.
[0071] Other examples of compounds of formula (I) are compounds of
formula (XI)
CH.ident.C(CH.sub.2).sub.pO(CH.sub.2).sub.qR.sup.27, (XI)
where p is as defined above, but in particular is 1, q is as
defined above but in particular is 1, and R.sup.27 is as defined in
relation to formula (IX), in particular a group C.sub.6F.sub.13; or
compounds of formula (XII)
CH.ident.C(CH.sub.2).sub.pN(R.sup.26)(CH.sub.2).sub.qR.sup.27
(XII)
where p is as defined above, but in particular is 1, q is as
defined above but in particular is 1, R.sup.26 is as defined above
an in particular is hydrogen, and R.sup.27 is as defined in
relation to formula (IX), in particular a group C.sub.7F.sub.15; or
compounds of formula (XIII)
CH.ident.C(CH.sub.2).sub.pN(R.sup.26)SO.sub.2R.sup.27 (XIII)
where p is as defined above, but in particular is 1, R.sup.26 is as
defined above an in particular is ethyl, and R.sup.27 is as defined
in relation to formula (IX), in particular a group
C.sub.8F.sub.17.
[0072] In an alternative embodiment, the alkyne monomer used in the
process is a compound of formula (XIV)
R.sup.28C.ident.C(CH.sub.2).sub.nSiR.sup.29R.sup.30R.sup.31
(XIV)
where R.sup.28 is hydrogen, alkyl, cycloalkyl, haloalkyl or aryl
optionally substituted by halo, R.sup.29, R.sup.30 and R.sup.31 are
independently selected from alkyl or alkoxy, in particular
C.sub.1-6 alkyl or alkoxy.
[0073] Preferred groups R.sup.28 are hydrogen or alkyl, in
particular alkyl.
[0074] Preferred groups R.sup.29, R.sup.30 and R.sup.31 are
C.sub.1-6 alkoxy in particular ethoxy.
[0075] In general, the item to be treated is placed within a plasma
chamber together with the material to be deposited in gaseous
state, a glow discharge is ignited within the chamber and a
suitable voltage is applied, which may be pulsed.
[0076] The non-wetting or non-absorbing polymeric coating may be
produced under both pulsed and continuous-wave plasma deposition
conditions but pulsed plasma is preferred.
[0077] As used herein, the expression "in a gaseous state" refers
to gases or vapours, either alone or in mixture, as well as
aerosols.
[0078] Microfabricated devices treated in this way exhibit enhanced
non-wetting or non-absorbing properties and may advantageously be
used in procedures such as microfluidic procedures to minimise
problems associated with adsorption such as reduced sensitivity or
even failure.
[0079] Precise conditions under which the plasma polymerization
takes place in an effective manner will vary depending upon factors
such as the nature of the polymer, the microfabricated device or
element, component or sub-assembly thereof etc. and will be
determined using routine methods and/or the techniques.
[0080] Suitable plasmas for use in the method of the invention
include non-equilibrium plasmas such as those generated by
radiofrequencies (Rf), microwaves or direct current (DC). They may
operate at atmospheric or sub-atmospheric pressures as are known in
the art. In particular however, they are generated by
radiofrequencies (Rf).
[0081] Various forms of equipment may be used to generate gaseous
plasmas. Generally these comprise containers or plasma chambers in
which plasmas may be generated. Particular examples of such
equipment are described for instance in WO2005/089961 and
WO02/28548, but many other conventional plasma generating apparatus
are available.
[0082] The gas present within the plasma chamber may comprise a
vapour of the monomeric compound alone, but it may be combined with
a carrier gas, in particular, an inert gas such as helium or argon,
if required. In particular helium is a preferred carrier gas as
this can minimise fragmentation of the monomer.
[0083] When used as a mixture, the relative amounts of the monomer
vapour to carrier gas is suitably determined in accordance with
procedures which are conventional in the art. The amount of monomer
added will depend to some extent on the nature of the particular
monomer being used, the nature of the substrate being treated, the
size of the plasma chamber etc. Generally, in the case of
conventional chambers, monomer is delivered in an amount of from
50-250 mg/min, for example at a rate of from 100-150 mg/min. It
will be appreciated however, that the rate will vary depending on
the reactor size chosen and the number of substrates required to be
processed at once; this in turn depends on considerations such as
the annual through-put required and the capital outlay.
[0084] Carrier gas such as helium is suitably administered at a
constant rate for example at a rate of from 5-90, for example from
15-30 sccm. In some instances, the ratio of monomer to carrier gas
will be in the range of from 100:0 to 1:100, for instance in the
range of from 10:0 to 1:100, and in particular about 1:0 to 1:10.
The precise ratio selected will be so as to ensure that the flow
rate required by the process is achieved.
[0085] In some cases, a preliminary continuous power plasma may be
struck for example for from 15 seconds to 10 minutes, for example
from 2-10 minutes within the chamber. This may act as a surface
pre-treatment step, ensuring that the monomer attaches itself
readily to the surface, so that as polymerisation occurs, the
coating "grows" on the surface. The pre-treatment step may be
conducted before monomer is introduced into the chamber, in the
presence of only an inert gas.
[0086] The plasma is then suitably switched to a pulsed plasma to
allow polymerisation to proceed, at least when the monomer is
present.
[0087] In all cases, a glow discharge is suitably ignited by
applying a high frequency voltage, for example at 13.56 MHz. This
is applied using electrodes, which may be internal or external to
the chamber, but in the case of larger chambers are generally
internal.
[0088] Suitably the gas, vapour or gas mixture is supplied at a
rate of at least 1 standard cubic centimetre per minute (sccm) and
preferably in the range of from 1 to 100 sccm.
[0089] In the case of the monomer vapour, this is suitably supplied
at a rate of from 80-300 mg/minute, for example at about 120 mg per
minute depending upon the nature of the monomer, whilst the pulsed
voltage is applied. It may however, be more appropriate for
industrial scale use to have a fixed total monomer delivery that
will vary with respect to the defined process time and will also
depend on the nature of the monomer and the technical effect
required.
[0090] Gases or vapours may be delivered into the plasma chamber
using any conventional method. For example, they may be drawn,
injected or pumped into the plasma region. In particular, where a
plasma chamber is used, gases or vapours may be drawn into the
chamber as a result of a reduction in the pressure within the
chamber, caused by use of an evacuating pump, or they may be
pumped, sprayed, dripped, electrostatically ionised or injected
into the chamber as is common in liquid handling.
[0091] Polymerisation is suitably effected using vapours of
compounds for example of formula (I), which are maintained at
pressures of from 0.1 to 400 mtorr, suitably at about 10-100
mtorr.
[0092] The applied fields are suitably of power of from 5 to 500 W
for example from 20 to 500 W, suitably at about 100W peak power,
applied as a continuous or pulsed field. Where used, pulses are
suitably applied in a sequence which yields very low average
powers, for example in a sequence in which the ratio of the time
on:time off is in the range of from 1:500 to 1:1500. Particular
examples of such sequence are sequences where power is on for 20-50
.mu.s, for example about 30 .mu.s, and off for from 1000 .mu.s to
300001As, in particular about 20000 .mu.s. Typical average powers
obtained in this way are 0.01 W.
[0093] The fields are suitably applied from 30 seconds to 90
minutes, preferably from 5 to 60 minutes, depending upon the nature
of the compound of formula (I) and the substrate such as the
microfabricated device or element, component or sub-assembly
thereof.
[0094] Suitably a plasma chamber used is of sufficient volume to
accommodate multiple microfabricated devices or element, component
or sub-assemblies thereof.
[0095] A particularly suitable apparatus and method for producing
microfabricated devices in accordance with the invention is
described in WO2005/089961, the content of which is hereby
incorporated by reference.
[0096] In particular, when using high volume chambers of this type,
the plasma is created with a voltage as a pulsed field, at an
average power of from 0.001 to 500w/m.sup.3, for example at from
0.001 to 100w/m.sup.3 and suitably at from 0.005 to
0.5w/m.sup.3.
[0097] These conditions are particularly suitable for depositing
good quality uniform coatings, in large chambers, for example in
chambers where the plasma zone has a volume of greater than 500
cm.sup.3, for instance 0.1 m.sup.3 or more, such as from 0.5
m.sup.3-10 m.sup.3 and suitably at about 1 m.sup.3. The layers
formed in this way have good mechanical strength.
[0098] The dimensions of the chamber will be selected so as to
accommodate the particular microfabricated device or element,
component or sub-assembly being treated. For instance, generally
cuboid chambers may be suitable for a wide range of applications,
but if necessary, elongate or rectangular chambers may be
constructed or indeed cylindrical, or of any other suitable
shape.
[0099] The chamber may be a sealable container, to allow for batch
processes, or it may comprise inlets and outlets for the
microfabricated device or element, component or sub-assembly, to
allow it to be utilised in a continuous process as an in-line
system. In particular in the latter case, the pressure conditions
necessary for creating a plasma discharge within the chamber are
maintained using high volume pumps, as is conventional for example
in a device with a "whistling leak". However it will also be
possible to process microfabricated devices or elements, components
or sub-assemblies at atmospheric pressure, or close to, negating
the need for "whistling leaks".
[0100] In a further aspect, the invention provides a method for
enhancing the free-flowing properties of liquid through a
microfluidics or nanofluidics device, said method comprising using
a microfluidics or nanofluidics device wherein at least the
surfaces which contact a liquid, such as the internal surfaces of
the channels or wells, comprise a non-wetting or non-absorbing
polymeric coating or surface modification formed by ionisation or
activation techniques such as plasma processing and have a surface
energy of less than 15mNm.sup.-1.
[0101] Suitably, the microfluidics or nanofluidics device or
sub-assembly is placed in a plasma deposition chamber, a glow
discharge is ignited within said chamber, and a voltage applied as
a pulsed field.
[0102] Suitable monomers and reaction conditions for use in this
method are as described above.
EXAMPLE 1
[0103] A fully constructed microfluidics device comprising a series
of wells interconnected by a range of channels on a transparent
substrate is placed into a plasma chamber with a processing volume
of .about.300 litres. The chamber is connected to supplies of the
required gases and or vapours, via a mass flow controller and/or
liquid mass flow meter and a mixing injector or monomer reservoir
as appropriate.
[0104] The chamber is evacuated to between 3-10 mtorr base pressure
before allowing helium into the chamber at 20 sccm until a pressure
of 80 mtorr is reached. A continuous power plasma was then struck
for 4 minutes using RF at 13.56 MHz at 300 W.
[0105] After this period, 1H, 1H, 2H,
2H-heptadecafluorodecylacylate (CAS #27905-45-9) of formula
##STR00008##
is brought into the chamber at a rate of 120 milli grams per minute
and the plasma switched to a pulsed plasma at 30 micro seconds
on-time and 20 milli seconds off-time at a peak power of 100 W for
40 minutes. On completion of the 40 minutes the plasma power is
turned off along with the processing gases and vapours and the
chamber is evacuated back down to base pressure. The chamber is
then vented to atmospheric pressure and the device is removed.
[0106] The device including the channels and wells is covered with
a non-wetting or non-absorbing polymer layer which prevents liquid
being adsorbed onto the surface, thereby enhancing the free-flowing
properties of liquid sample through the device.
[0107] Devices obtained in this way are used in a kinetic assay of
enzyme activity using a fluorescent signaling system as is
conventional in the art. A similar assay is carried out on a bulk
sample, using similar methodology. The results of multiple assays
show comparable performance. Interfacial and evaporation problems
are avoided in the miniaturized version.
[0108] A fluorescent enzyme inhibition assay is also conducted in
both bulk procedures and miniaturized devices prepared as described
above. Again comparable results are obtained in both the bulk and
miniaturized devices.
[0109] It is clear that the results obtained using microfluidics
devices prepared as described above will provide reliable and
accurate results.
* * * * *