Note: Descriptions are shown in the official language in which they were submitted.
CA 02681897 2009-10-08
MICROFLUIDIC DEVICE, COMPOSITION AND METHOD OF FORMING
Field of the Invention
[0001] The present invention relates in general to compositions of matter for
forming
microfluidic devices, and, in particular, to solid thermoplastic elastomers
(TPEs), including
TPEs incorporating soft and hard blocks, for this use.
Background of the Invention
[0002] There are many microfluidic devices that could be produced, for
example,
using the structure presented described by Unger, et al. (Science, 288, 113
(2000)), in
which one or more polymer layers with embedded channels are assembled and
bonded
to a substrate. Such devices permit the pattern on a surface of the polymer
layers to be
covered and thereby enclose the channels to produce a closed device.
[0003] There are two major roadblocks to mass-production of plastic-based lab
on
chip (LOC) and other microfluidic devices, such as those used for biological,
chemical
and gas detection applications. The first one is related to the availability
of high-
throughput fabrication technologies that can be used to pattern materials with
features
having micron to nanometer scales with high through-put, very good critical
dimension
(CD) control, and low cost. Standard microfabrication processes like those
imported from
microelectronics, have severe limitations in that they do not apply for
materials other than
standard processing resists.
[0004] The second limitation is related to the nature of the materials that
can be
processed. For the above mentioned applications, the materials need to be
easily
shaped while presenting good chemical, optical and mechanical properties.
Traditionally
silicon substrates were used with various etching techniques on such materials
as quartz.
Over the last 10 years several micro and nano structuration methods have been
developed that promise solutions for mass production of patterned materials at
affordable
costs. Nanoimprint lithography, nano-embossing, hot embossing and lithography
are the
most widely used, and the materials most widely used are quartz, galls,
silicon, silicone or
hard thermoplastic materials (e.g. polycarbonates, PMMA, etc.).
[0005] Processing conditions required for the embossing of the commonly used
hard
thermoplastic materials require significant applied pressure. High quality
replication has
been achieved with PMMA materials at 180 C and a pressure of 100 bar (Studer,
et al.
1
CA 02681897 2009-10-08
Chen, Appl. Phys. Lett., 2002, 80, 3614-3616) while Cameron et at. (Lab Chip,
2006, 6,
936-941) have reported optimized conditions for PCO materials with an
embossing
temperature of 40-70 C above Tg and applied forces of 10-20 bar.
[0006] However two major issues are impeding the adaptation of those
fabrication
methods for the LOC and many other applications. Firstly, low cost, hard
thermoplastics
materials (polycarbonate, polystyrene...) can be easily shaped and patterned,
but the
assembly (bonding) of thermoplastic parts to form functional and complex
devices or
systems with adequate sealing is very difficult and limited by the plastic
bonding
technologies. Hard thermoplastics need pressure and high temperature
processing
conditions for bonding constitutive elements. Seals around microfluidic
channels are
required, and this generally requires very good quality mating surfaces, as
the channels
are typically defined at interfaces between two parts (usually layers).
Additionally non-
permanent sealing of hard thermoplastics parts, and resealable bonds are not
currently
possible.
[0007] To avoid these difficulties, elastomer silicone materials have been
used
instead of hard thermoplastics. There are many advantages to using these
materials in
terms of less brittleness, and better bonding. Furthermore, they provide for
flexibility that
may be useful for controlling flow of liquids through the channels. The known
methods for
patterning (replicating micro- or nano-scale features) silicone elastomers
such as PDMS
have not been successfully produced in high throughput fabrication processes.
So while
silicone elastomers have significant advantages in terms of producing bonds
for layered
structures, silicone elastomer-based microfluidic devices remain costly.
Furthermore it is
difficult to produce multi-layer PDMS (and expensive to bond multiple layers
of PDMS
and like silicone elastomer) structures.
[0008] Two main options for bonding can be used to bond microstructured layers
of
PDMS: partial thermal curing process of separate patterned layers, which are
subsequently
brought in contact together for cure completion; and plasma treatment, in
which cured
PDMS layers are oxidized in 02 plasma, then finally aligned and permanently
bonded. Both
approaches need an accurate control of first curing and patterning step in
order to preserve
a sufficient reactivity for the subsequent bonding step. Thus, successive
bonding of several
layers becomes difficult, given the time and conditions under which the layers
must be
assembled. While this is possible in a lab, it is difficult or impossible to
produce in a high
through-put facility. Thermal bonding is made more expensive by the time it
takes and
power consumed. Plasma treatment requires expensive controls for material
manipulation
because once a sample is removed from the plasma chamber (which is a costly
treatment)
2
CA 02681897 2009-10-08
the modified surface properties are un-stable, meaning that the bonding
procedure needs to
be completed rapidly.
[0009] In a paper entitled Thermoplastic Elastomer Gels: An Advanced Substrate
for
Microfluidic Chemical Analysis Systems to Sudarsan et al. (Anal. Chem. 2005,
77, 5167-
5173), a novel class of compounds, namely thermoplastic elastomer gels, are
disclosed
and tested for properties desired of substrates for microfluidic devices. The
TPE gels
Sudarsan teaches and uses are highly dilute TPE gels having from 9 to 33 wt.%
of TPE
(SEBS copolymer resin (CP-9000)) and 67-91 wt.% of mineral oil. The TPE gels
were
produced using vacuum and heating, which is time consuming and expensive.
[0010] Sudarsan et al. teaches a straightforward method for fabrication of
microchannel structures using SEBS gels, essentially involving a sequence of
steps to
create one or more impressions of a negative relief structure in the heated
elastomer
substrate. For example, according to Sudarsan et al., impressions in a gel (33
wt % TPE,
67 wt. % mineral oil) are made by placing a slab of the gel on top of a master
mold that
has been preheated to -110 C on a hot plate. Within seconds, Sudarsan et al.
reports,
the elastomer begins to soften and can be gently pressed down by hand for
several
seconds to make uniform contact with the structures on the mold. After cooling
and
release, the solidified gel precisely replicates the shape of the structures
on the master.
[0011] As will be appreciated by those of skill in the art, the oil content
and unique
structure of gels make them significantly easier to mold. For example, it is
well known in
the injection molding field that oil added to TPE improves processability of
the material.
The gel structure is a scaffold of cross-linked molecules having a lower
polymer density
and therefore requiring less energy to reorganize, than solid polymers.
[0012] According to Sudarsan et al., "the gel material inherently adheres to
smooth
elastomer, glass, or plastic surfaces, allowing static or low-pressure fluidic
networks to be
easily constructed. In addition, stronger bonds can be achieved either with
elastomer or
glass surfaces by briefly heating the material at the bond interface to a
temperature just
below its softening point using a hot plate or handheld heat gun. Bonds to
glass surfaces
are removable, while bonds between elastomer layers can be made seamless and
essentially permanent."
[0013] Sudarsan et al. teaches heating the gel to an intermediate temperature
regime
(-60 C < T < -90-120 C), in which structural rearrangements associated with
an order-
disorder transition permits limited rearrangement of the structure. The upper
limit of the
3
CA 02681897 2009-10-08
intermediate temperature regime varies with the amount of mineral oil, and the
oil
composition.
[0014] At least 2/3 of the material in the gel is mineral oil, and this oil
imparts the
properties of the gel required for the facile molding technique to be
effective. There are
nonetheless some drawbacks to the use of these oils in microfluidic
applications, and to
the gel structure more generally. Firstly, the requirement for producing the
gels increases
the costs and labour of producing the material, as gels generally are formed
by mixing
over a significant period of time, under heat and in a vacuum. Secondly
certain
mechanical properties of the gels, such as rigidity and integrity of the gel,
are generally
lower than that of solid polymers, which can limit the range of operating
temperatures and
pressures of devices made of TPE gels. Thirdly, and most importantly for some
applications, the permeability of liquids into and out of the gel may limit
the kinds of fluids
that the microfluidic device can treat. If there is risk of contamination of
the sample by the
introduction of mineral oil or any impurity contained within the gel, or
inversely from
absorption of components of a stored fluid into the gel, for example in a
given thermal,
chemical or mechanical state, or a change therein, the microfluidic device
formed of a gel
may not be suitable. Also the swelling of gels when in contact with other
fluids may
further limit the applications of microfluidic devices fabricated from TPE
gels, as swelling
applies a mechanical pressure that may cause undesired changes fluid dynamics
of the
overall device.
[0015] The surface quality of patterned TPE gels taught by Sudarsan et al. are
of
concern for many applications. The presence of oil introduces uncertainty and
difficulty
controlling the surface properties. For example, it is not known how the
surface,
especially in the neighbourhood of patterned microchannels, is composed. There
does
not appear to be a patterning technique that can control these surfaces so
that they are
characterized by a high level of styrene blocks (or EB groups), at the expense
of oil. If
the surface has high polymer content, it is not known whether the blocks of
the copolymer
are homogeneous. These parameters are crucial, especially for microfluidic
systems,
and most especially for systems that require surface modification or
treatment. In other
areas of research, Applicant has found that oil reduces the surface quality of
TPEs
leading to highly inhomogeneous surfaces. It does not appear to Applicant that
TPE gels
are viable alternatives for producing microfluidic devices for a wide range of
applications,
especially to a majority of applications where introduction of oil into the
microfluidic
channels is proscribed.
4
CA 02681897 2009-10-08
[0016] In three works by I. Stoyanov: a thesis (Karlsruhe University) entitled
Development of modular microfluidic devices for bioanalytical sensors, and
papers
entitled "Microfluidic devices with integrated active valves based on
thermoplastic
elastomers" (Microelectronic Engineering 83 (2006) 1681-1683), and "Low-cost
and
chemical resistant microfluidic devices based on thermoplastic elastomers for
a novel
biosensor system" (Mater. Res. Soc. Symp. Proc. Vol. 872 J 11.4 pp.169-174):
thermoplastic elastomers are considered for microfluidic applications.
[0017] Stoyanov proposes TPU as a reasonable compromise between performance,
technological complexity and price for some microfluidic applications, and
notes: that
some of the thermoplastics reported to be used for production of microfluidic
components
(poly(methylmetacrylate) PMMA, polycarbonate, polystyrene) do not have
sufficient
chemical resistance; that thermoplastic polyolefins (polyethylene,
polypropylene) possess
a very high chemical resistance and can be easily formed by hot embossing, but
have
poor sealing characteristics due to their non-elastic properties; and that
other classes of
materials with extraordinary chemical resistance like fluorpolymers
(polytetrafluoroethylene (PTFE) or excellent sealing properties like silicones
(PDMS) are
difficult to be reliably connected with macrofluidic components, because of
their chemical
inertness (PTFE) or lack of sufficient mechanical strength (PDMS).
[0018] These works use thermoplastic polyurethane elastomer foils TPU (a
specific
grade of TPE) having a Shore A surface hardness of 85-93. Clearly TPUs were
chosen
in part because of their surface hardness being only sufficiently less than
those of
polyethylene, and polypropylene to overcome their sealing problems, because
softer
materials such as PDMS are stated to lack required mechanical strength.
[0019] Because of the relative inelasticity of TPUs, Stoyanov must work with
thin foils
(100-600 pm thickness) to obtain a required flexibility. Consequently they can
not impart
features of certain depths. Because of the thin foil structure, Stoyanov was
further unable to
bond two microstructured foils due to major deformations. Thin foils bend too
much,
inducing leakage.
[0020] It is further noted that Stoyanov required high pressure and
temperature (50-120
bars and 140-160 C) to thermoform the foils, which induces more shrinkage,
higher friction
and longer cycle time than lower pressure and temperature methods. The
thermoforming
requires use of metallic molds, and cannot be performed with low-cost molds.
5
CA 02681897 2009-10-08
(0021] Further still, TPU are not capable of room temperature, atmospheric
pressure or
low pressure bonding (either permanent or reversible). To bond together TPU
parts (or TPU
and others plastic substrates), Stoyanov applied pressure to contacting
surfaces and they
also needed to use treatment involving solvent exposure, or thermal bonding to
achieve
satisfactory bonds. These treatments, and the pressure needed for bonding, can
be
detrimental to the preservation of (bio or chemical) surface treatments and/or
to the quality of
the features patterned on the surface. Delicate features may deform or
collapse under the
pressure, changing microfludic behavior of the devices (flow time, capillary
effects, etc.)...)
of the device, especially if a multi-layered device is desired.
[0022] Accordingly it is noted that viable elastomeric materials used in
microfluidics
have all had Shore A hardnesses above about 85 (i.e the top end of Shore A -
Shore D
hardness). The only known exception to this is Sudarsan et al., who teaches a
gel having
potential problems with integrity. Gels used according to the teachings of
Sudarsan et al.
have Shore hardnesses in the mid to lower range of the Shore 00 scale.
[0023] At Nanotech Montreux 2007, applicant submitted a title for a poster
presentation but did not present any poster there. The title was:
Thermoplastics
Elastomeric (TPE) Blocks Copolymers, a New Material Platform for
Microfluidics: Proof of
Concept for Complex Siphon Valving on CD, and this title was published.
[0024] Accordingly there is a need in the art for new materials for use in
microfluidic
devices that are as easily patterned and bonded as the TPE gels, but not
subject to the
drawbacks of the TPE gels. In general there is a need for compositions that
can be
patterned, and bonded to like compositions as well as a variety of other
compositions,
while providing seals required for very fine channels such as microfluidic
channels, and
remaining relatively inert and non-reactive to a wide variety of fluids.
Summary of the Invention
[0025] Applicant has discovered, unexpectedly, that solid soft (Shore A
hardness that
is < -50, more preferably 1 .. 45, 1 .. 40, 5 .. 38, and most preferably 10 ..
35) TPEs, have
many of the advantages of (non-solid) TPE gels in terms of patterning and
bonding, while
providing inert, non-reactive, and higher integrity materials for producing
microfluidic
channels. There are various advantages over different prior art microfluidic
substrate
types. Herein the prefix "micro" refers to smaller than 0.1 mm, and includes
nano-scale
channels, fluidics, etc.
6
CA 02681897 2009-10-08
[0026] Gels are highly dispersed polymer chains whereas soft solid TPEs are
polymer dense. TPE gels have Shore 0, and Shore 00 hardnesses, with Young's
Moduli ranging from about 0.01-10 MPa. These gels can be formed into slabs as
shown
by Sudarsan et al. that are quite thick, but it may not be trivial to produce,
manipulate and
pattern thin, uniform webs of this material. These slabs can be patterned with
only gentle
manual pressure on a hotplate, as taught by Sudarsan et al. Sudarsan then
teaches the
possibility of pressure free bonding to produce low pressure or static
pressure microfluidic
networks, but that if higher pressure is required, thermal bonding is
possible.
[0027] TPE gels have problems retaining the mineral oil or other
extender/solvent
through relatively permeable surfaces. It is well known in the art that the
mineral oil in
such gels escape over time resulting in shrinkage of the slab, and potentially
diluting,
tainting, or otherwise interfering with fluids in a microfluidic device. Over
a wide range of
temperatures and pressures, and throughout changes within the range, soft
solid TPEs
do not bleed or interact with a contacting liquid.
[0028] The differences in structures and polymer densities between TPE gels
and
soft solid TPEs would not suggest that soft solid TPEs are equally disposed to
provide the
patterning advantages of TPE gels. Surprisingly applicant has found that soft
solid TPEs
can be patterned as solid films without any pressure (except atmospheric
pressure), for
example, if the web is 0.5 mm thick (or more), the feature density is 40% (or
less) and the
features are 50 pm deep (or less). In general a nominal pressure form 0.01 to
0.5 MPa
can be used to assist pattern formation in other conditions. Furthermore
Applicant has
found that soft solid TPEs can be spin cast or solvent cast using appropriate
solvents
(benzene, chlorobenzene, toluene,...). These methods permit relatively low
cost, high
quality photoresist molds to be used for the patterning.
[0029] It is known to use hard thermoplastics in microfluidics. Such materials
generally have a Young's modulus of 1,000-10,000 MPa (i.e. having a Shore
hardness on
the D scale, -40-85). While they can be formed into films or webs relatively
easily,
patterning generally requires 10 MPa or more of pressure, and therefore high
pressure
molds must be used, such as those made of metal, or silicon. Hard plastics
have some
perennial demolding issues. Demolding of hard plastic parts remains
problematic due to
the stiffness of the material. Demolding induces stresses on the patterned
surface that
damage edges of the patterned parts, and friction between the mold and part
are another
source of damage. Soft, solid TPEs due their mechanical properties, are not
subject to
such behaviour. The microchannels produced are free of defects. Furthermore,
because
demolding is improved, we have been able to use low cost molds such as epoxy
and SU8
7
CA 02681897 2009-10-08
ones, and even we have been able to mold TPE parts with high aspect ratios,
and even
negative profiles.
[0030] Furthermore there are difficulties bonding hard thermoplastic layers to
provide
seals, generally requiring bonding agents, solvents, etc. and/or high
temperature and
pressure to produce a stack of the materials, all of which may make surface
chemistry or
desired coatings more difficult to maintain, and risk micro-patterned
structures collapsing
or deforming, leading to changes in microfluidic behavior (flow time control
and capillary
effects which are both critical in term of dimension). Hard thermoplastics
generally have
poor gas permeability even at elevated temperatures, which can lead to
entrapment of
bubbles, and are inflexible resulting in defects when demolding. Some softer
TPEs are
also known but have limitations discussed above.
[0031] It is also known to use non-TPE materials, such as PDMS, but patterned
layers of PDMS are not readily mass produced. The speed and cost with which
PDMS
can be patterned have made it suitable to special purpose, prototype, and
other limited-
run devices, where the necessary equipment exists. There are also problems
with PDMS
in that it may be difficult or impossible to bond many layers without damaging
the
patterned structure of intermediate layers, and it is increasingly desirable
to provide multi-
layered microfluidic devices. The materials are also relatively expensive.
[0032] A variety of solid soft (Shore A = 1..50) TPEs may be used in
accordance with
the present invention. Soft solid TPEs diverse in composition, chemistry and
morphology,
have permeability coefficients for nitrogen and oxygen gas that are 20 to 400
times lower
than that of PDMS at room temperature. Exemplified soft solid TPEs (styrenic-
TPE and
ethylene vinyl acetate polymers) have N2, C02, and 02 gas permeabilities
ranging from
5*10-3 to 7*10-10 cm3 (STP) cm/cm2 s cmHg), which is believed to significantly
reduce
entrapment of air bubbles between a mold and the soft solid TPEs, facilitating
high
fidelity, low temperature, and low pressure-time patterning and allowing
thermoforming
without vacuum assistance (Vacuum chamber for forming). The softness of TPEs
also
generally facilitates bonding as the material conforms intimately to a wide
variety of
smooth surfaces. Specific gas permeabilities, elastic, compressibility and
zero shear rate
properties of a variety of soft solid TPEs make a high-throughput thermal
replication
method possible, and permit simple, low pressure bonding (permanent or
reversible) of
patterened parts to a variety of substrates.
[0033] In some aspects of the invention, the soft solid TPEs are block
copolymer
(BCP) TPEs, which typically have mechanical modulii 2-3 orders of magnitude
lower than
8
CA 02681897 2009-10-08
those of hard thermoplastics. BCP-TPEs exhibit zero shear viscosity values 3
to 6 orders
of magnitude lower than those of hard TP, offering a partial explanation as to
why BCP
TPEs such as styrenic block polymers (e.g. SBS, SEPS, SIS, SIBS, and SEBS,
especially those containing about 85-90% soft blocks), can be patterned with
high fidelity
using low temperature (down to atmospheric pressure), and low pressure-time
molding.
[0034] Accordingly a composition is provided, the composition made of at least
60
wt. % of a thermoplastic elastomer (TPE) resin and additives that are solid at
least from
0-30 C (preferably at least from 0-50 C), the composition having a Shore A
hardness that
is less than 50, and bearing a patterned surface, the pattern comprising at
least one
microfluidic channel having a cross-sectional dimension smaller than 100
microns.
[0035] The composition preferably comprises at least 80 wt. %, 90 wt. %, 95
wt. %,
98 wt. %, 99 wt. %, and 99.5 wt. % of the TPE resin.
[0036] The microfluidic channel preferably: extends between two ends, each end
being one of the following: an input, an output, a junction or a chamber, is a
closed
chamber, has an aspect ratio between 1:10 and 10:1, or has a negative profile.
[0037] The patterned surface is preferably adapted to provide: a reversible
seal when
applied to a smooth surface at ambient temperature and pressure; an
irreversible seal
when applied to a smooth surface at temperature below 150 C, under a pressure
less
than 0.5 bars (or more preferably 0.3 and 0.2 bars), for less than 1 hr; is
irreversible and
applied with a ambient temperature and pressure, for example over a period of
4 days.
[0038] The TPE resin preferably has a viscoelastic phase that exhibits liquid-
like flow
at temperatures below 20 C, more preferably below 0 C. The TPE resin may have
soft
and hard blocks, the soft blocks having a glass transition temperature below
20 C, more
preferably below 0 C, more preferably between -60 and -100 C. The TPE resin
may be:
a styrenic block polymer, an olefin vinyl polymer, a thermoplastic rubber, a
copolyester, a
polyurethane, a polyolefin blend, a polyolefin alloy, or a polyamide; or a
styrenic block
polymer, or an olefin vinyl polymer; or a styrenic block polymer; or SBS,
SEBS, SEPS,
SIS, SIBS, EVA, COPE, TPU, TPO, TPV, PEBA, or TPE based acrylic, or SBS, SEES,
SEPS, SIS, SIBS, or EVA, or SBS, SEBS, SEPS, SIS, SIBS, or SEBS; or oil free
SEBS
and the composition has a thermal resistance greater than about 95 C.
[0039] Accordingly a microfluidic device comprising the composition is
provided. The
microfluidic device may further comprising a second part having a first
meeting surface,
the first meeting surface covering enough of the patterned surface to enclose
at least part
9
CA 02681897 2009-10-08
of the microfluidic channel. The second part may be: composed of a same,
similar or
dissimilar thermoplastic elastomer as the first part; in the form of a film;
composed of a
less flexible material than the first part, to support the microfluidic
device; composed of a
material chosen for thermal resistance, to support the microfluidic device at
an elevated
temperature. The second part may have a second meeting surface bearing a
pattern
comprising at least one microfluidic channel having a cross-sectional
dimension smaller
than 100 microns. The second part may be composed of a similar thermoplastic
elastomer, and having a second meeting surface bearing a pattern comprising a
groove
defining at least one microfluidic channel having a cross-sectional dimension
smaller than
100 microns, and be irreversibly bonded to the composition.
[0040] Also in accordance with the invention, there is provided a method for
forming a
microfluidic device, the method comprising: providing the composition onto a
relief mold
having at least one ridge defined thereon for forming a microfluidic channel
on the
surface; heating the composition adjacent the relief mold above a highest
glass transition
temperature of the thermoplastic elastomer, for a pressure-time of less than 5
bars
seconds per micron of depth of the relief mold; and cooling the composition
and removing
it from the mold as a part, whereby the substantially smooth surface is
patterned.
[0041] The ridge of the relief mold may extend between two of the following:
junctions
with one or more other ridges, raised structural features of the mold, and a
mold limit
aligned with an edge of the part.
[0042] The method may further comprise bonding the part to a second part as
per the
structure of the microfluidic device.
[0043] Further features of the invention will be described or will become
apparent in
the course of the following detailed description.
Brief Description of the Drawings
[0044] In order that the invention may be more clearly understood, embodiments
thereof will now be described in detail by way of example, with reference to
the
accompanying drawings, in which:
FIG. 1 is a schematic flow chart of a high throughput method for forming
(thermoforming)
a part of a microfluidic device in accordance with an embodiment of the
invention;
CA 02681897 2009-10-08
FIG. 2 is a graph showing DMTA measurements (E', E" and tan 6) for SEBS and
rigid
polystyrene;
FIG. 3 is a graph of Eas a function of temperature for 3 different SEBS soft
solid TPE
films;
FIG. 4 is a mosaic of SEM images showing microstructure patterning of soft
solid TPEs
using hot embossing and soft lithography;
FIG. 5 includes three SEM images showing patterns that are dense, have high
aspect
ratios, and have micrometric features having a negative profile;
FIG. 6 is a mosaic of 6 panels showing various embodiments of bonded
microfluidic
devices; and
FIG. 7 is a mosaic of 4 images showing film patterning by spin coating; and
FIG. 8 are results of a profilometric study of TPE microchannel stability
before and after a
thermal treatment.
Description of Preferred Embodiments
[0045] Solid soft thermoplastic elastomers (TPEs) are formed from at least 60
wt. %
of a TPE resin and other additives that are solid over a wide range of
temperatures, (e.g.
0-50 C) form a new class of materials for forming microfluidic devices.
Additives well
known in the art include inert additives such as filler, as well as or may be
used to affect
one or more property of the soft solid TPE (such as additives to improve
optical
properties, thermal properties, adhesiveness (e.g. tackifiers), plasticizers),
or additives to
facilitate curing or processing of the material. The soft solid TPEs
preferably contain 80,
83.33, 90, 95, 98, 99, or 99.5 wt. % of the resin and solid additives. They
have
advantages not previously recognized in these applications. The 40% or less
balance of
the composition may include non polar mineral oil, such as naphtenic and
paraffinic
based ones (among others oils), or other known processing aids, or additives
that affect a
material property of the polymer.
[0046] Herein a TPE is said to be "soft" if it has a shore A hardness that is
less than
50. More preferably soft TPEs have Shore A hardnesses of 1-45, 1-40, 5-38, and
most
preferably they have Shore A hardnesses from 10-35. A TPE is said to be solid
if it is a
non-gelatinous, non-liquid material that has substantial material integrity in
operation as a
microfluidic device. TPE's typically have a network that consists in large
part of non-
11
CA 02681897 2009-10-08
covalent, hence reversible cross-links (e.g., hydrogen bonding, van der Waals
interaction
or electrostatic interplay). Upon heating, non-covalent bonds can be broken,
which
makes the material deformable. Under cooling, the crosslinks are restored,
thereby
preserving shape and form induced during thermal treatment. Moreover, this
feature
makes it possible to recycle material in case thermoforming processes have
failed, or if it
is desirable to repattern the material for a different use.There are six
classes of
commercial TPEs presently used: styrenic block copolymers, polyolefin blends,
elastomeric alloys (TPE-v or TPV), thermoplastic polyurethanes, thermoplastic
copolyester and thermoplastic polyamides. Some examples of these would not be
suitable because the Shore A hardness would be greater than about 50, for
example, but
in general there are examples from each class that are amenable to application
in
microfluidic devices, especially given the varieties of materials that can be
produced with
different molecular weight polymers, and different amounts of plasticizers and
other
additives.
[0047] A styrenic block polymer, an olefin vinyl polymer, a thermoplastic
rubber, a
copolyester, a polyurethane, a polyolefin blend, a polyolefin alloy, or a
polyamide TPE,
are classes of preferred TPEs. The following compounds are preferred TPEs:
SBS,
SEBS, SEPS, SIS, SIBS, EVA, COPE, TPU, TPO, TPV, TPE based Acrylic, or PEBA.
More preferably, the TPEs are: SBS, SEBS, SEPS, SIS, SIBS, or EVA. More
preferably
still, are SBS, SEBS, SEPS, SIS, SIBS. Examples of an ethylene vinyl acetate
polymer
compound and several styrenic block polymer compounds, are described herein
below.
Preferably the TPE has a viscoelastic phase that exhibits liquid flow at
temperatures
below 200 C, more preferably 180 C, more preferably below 150 C are preferred.
[0048] A wide variety of soft solid TPEs have similar viscoelastic and polymer
flow
conditions at (respective) processing temperatures that promote intimate
surface
contacting with a die, and result in surfaces that are able to bond to a
variety of surfaces
with minimal temperature, pressure and time. If the elastic modulus and zero
shear rate
properties are satisfactory, at specific soft solid TPE formulation will be
satisfactory. Most
TPEs are block copolymers (BCPs), comprising different monomer sequences being
distributed either randomly, statistically and even in larger domains through
diblock or
triblock architectures. BCP-TPEs exhibit two glass transition temperatures
corresponding
respectively to soft blocks providing softness and bonding properties and hard
blocks
acting as junction points that stabilize the polymer matrix which provide the
desired
rigidity. Generally BCP-TPEs are amenable to the present invention. Preferably
the soft
blocks have a viscoelastic phase that is exhibits liquid flow at temperatures
below 200 C.
12
CA 02681897 2009-10-08
[0049] In a first approach and for one part, TPE replication takes advantage
of
mechanical modulii that are typically 2-3 orders of magnitude lower than those
of hard
thermoplastics. More rigorously, according to Stephan's equation, the force
required for
polymer micro-displacement is linearly proportional to the zero shear
viscosity parameter
(qo). (Alternative Lithography: Unleashing the Potentials of Nanotechnology,
ed. C. M.
Sotomayor Torres, Kluwer Academic/Plenum Publishers, New York (2003), the
contents
of which are incorporated herein by reference). For PMMA, PS and PC materials,
through typical embossing temperature ranges, with several hundreds of
thousands
molecular weight polymers and at typical low shear rate values of 10 4 -10.1 s
-1, ijo ranges
from 105 to 1010 Pa s at their respective embossing temperatures. Such
viscosity values
result in a need for several tens of bars of pressure to be applied, to induce
polymer
displacement rates in the range of 1 pm/s (see Yao, et al. Polym. Eng, Sci.,
2007, 47,
530-539, and Juang et al. Polym. Eng. Sci., 2002, 42, 539-550, the content of
both of
which is incorporated herein by reference).
[0050] In contrast, soft solid BCP-TPE materials (especially those with a
percentage
of hard blocks inferior to 15%) show values of 170 in between 102 and 104 Pa
s, as
reported by Sebastian et al. (see Sebastian, et al., Macromol., 2002, 35, 2700-
2706 and
Macromol., 2002, 35, 2707-2713, the content of both of which is incorporated
herein by
reference) using steady-shear low-stress rheology experiments with styrene-
isoprene-
styrene block copolymers, which are largely comparable to the SEBS material
selected
for this study. Based on these reports, we can assume that BCP-TPE zero shear
viscosities values can be 3 to 6 orders of magnitude lower than those of hard
TP, thus
explaining the attractive processing conditions, such as short embossing time
and low
pressure needed for high quality pattern replication.
[00511 Furthermore, soft solid TPEs are particularly suitable for forming
because of
their gas permeabilities. During heating of the material without any external
pressure (i.e.
under only atmospheric pressure), we observed that the air bubbles trapped
between the
mold and the polymer disappear, which indicates a relatively high gas
permeability of the
TPE material at elevated temperatures. In fact, for stryrenic TPE based
material,
crystallized PS nanodomains interrupt the gas flow and retard permeation in
comparison
to the soft and more permeable soft blocks (EB, I, EP,...).
[0052] Although soft solid TPEs are diverse in composition, chemistry and
morphology, the literature suggests that permeability coefficients for
nitrogen and oxygen
gas can be 20 to 400 times lower than that of PDMS at room temperature (for
N2, C02,
and 02, gases permeability values for styrenic-TPE and ethylene vinyl acetate
polymers
13
CA 02681897 2009-10-08
range form 0,005 to 7.10-10 cm3 (STP) cm/cm2.s cmHg) (see Csernica et al.,
MacromoL,
1987, 20, 2468-2471, Yang et at. J. Appl. Polym. Sci., 1990, 41, 1141-1150,
Odani et al.
Polym. Eng. Sci., 1977, 17, 527-534, Kim et al., J. Appl. Polym. Sci., 1997,
66, 1117-
1122, Ferdinand et al., Colloid Polym. Sci., 1989, 267, 1057-1063, Senuma,
Macromol.
Chem. Phys., 2000, 201, 568-576, Schauer, et al. J. Appl. Polym. Sci., 1966,
61, 1333-
1337, and Barnabeo et al., J. Polym. Sci., 1975, 13, 1979-1986).
Methods of patterning
[0053] The mechanical and flow properties (such as viscoelasticity) of the
soft solid
TPE materials outlined above permit very simple and low-cost methods for
microstructure
patterning that obviates the need for high pressure presses and molds,
chemical
solvents, etc. and is amenable to mass production. Furthermore expensive
vacuum
equipment can be avoided for atmospheric pressure molding of relatively low
depth
features.
[0054] FIG. 1 is a schematic flow chart illustrating the chief steps of a high
throughput
method of forming a patterned piece for use in a microfluidic or nanofluidic
device, and
FIG. 1 a is a schematic illustration of an apparatus for forming a patterned
piece for use in
a microfluidic or nanofluidic device, in accordance with an embodiment of the
invention.
[0055] In step 10 a soft solid TPE as described above is provided. Applicant
has
demonstrated a number of methods of producing patterned parts, including such
techniques as spin casting and solvent casting using appropriate solvents
(benzene,
chlorobenzene, toluene,...), however, advantageously, the polymer can be
provided in a
substantially neat form, obviating the need for high quality exhaust,
purification, and/or
solvent reclamation equipment.
[0056] There are three states in which the polymer can be provided: solid,
liquid, or
solution. If solid, the part can have substantially any form having a
relatively smooth
surface for placement on the mold. The part may be joined to one or more other
parts as
well. The preferred solid form in which to supply the part, for mass
production, is a film.
Films of high purity, and controlled thickness, can be provided with film
extrusion
techniques known in the art. If the material is supplied as a liquid, such as
in an injection
molding system, high speed patterning and forming can be provided. As a
solution, spin
coating can be performed, although this technique is believed not equally
susceptible to
high throughput production. Spin coating may be preferred for high quality
parts having
high feature density or very small dimensions.
14
CA 02681897 2009-10-08
[0057] In step 12, the material is placed on a microstructure relief mold,
either by
injection of the soft solid TPE as molten material, or as a solid part. In
FIG. 1a the soft
solid TPE material 20 is shown making intimate contact with a mold 22, which
the
material 20 will do once the material is at or above the mold temperature and
pressure
conditions. In accordance with the invention, the mold can be an inexpensive,
relatively
low pressure mold, such as SU8 molds formed by well known lithographic
techniques.
While the mold shown in FIG. 1 a is a plate-type mold, it could have a variety
of shapes.
The mold may be part of an enclosed space, as used for injection molding. In
practice,
substantially any mold that can survive the heat cycling, provides modest
strength, and
supports a relief will serve to mold a wide variety of the solid soft TPE
films.
[0058] It will be noted that the mold 22 of FIG. 1a can include a variety of
features,
including high aspect ratio molds, and even negative profile features. A
variety of
features produced are shown in FIG. 4, and are discussed below. Demolding is
greatly
facilitated by the flexibility of the soft solid TPE, and high aspect ratio
(AR) features can
be reproduced with high fidelity. The rigid nature of hard thermoplastics
makes demolding
difficult or even impossible when high aspect ratio features are required. Due
to the low
elastic modulus and low melt viscosity of TPE, it is possible to easily
pattern high aspect in
TPE by thermoforming methods (e.g. hot embossing, as well as by injection
molding)
without the complications that are typically encountered with TP.
[0059] Applicant has patterned features having dimensions as small as 10 pm in
a 100
pm thick TPE slab (with an aspect ratio up to 10:1). Soft solid TPEs are so
forgiving
because of their compressibility; they can be molded flawlessly with higher
aspect ratios
and even negative profiles. Features having negative profile, such as features
that have
a higher cross-sectional area further from a plane of the mold have been
reproduced.
Top cross-section area might be in the range of 5x5 mm2 to 0.01x0.01 mm2,
while bottom
cross-section deals with areas which can be from 99% to 25% of the top one.
Soft solid
TPEs have demonstrated very low pressure patterning and bonding, and avoid the
previously noted problems with the quality of replication of edges of hard
thermoplastics.
[0060] In step 14 the temperature and pressure of the material is controlled
to permit
molding. The surface of the soft solid TPE part adjacent the mold is heated to
a
temperature above the glass transition temperature of the hard domain
materials, but
below the glass transition temperature of the soft blocks (for diblock polymer
materials)
otherwise above a glass transition temperature of the polymer system in order
to mold.
CA 02681897 2009-10-08
[00611 If the material is provided in a liquid form, it is initially at a
temperature higher
than needed for molding, and controlling the temperature involves controlling
the cooling
rate. If the material is provided at a temperature and pressure below the
molding
conditions, the material will be heated to a temperature, and/or subjected to
a pressure to
match or exceed the molding conditions, for example by heating the material 20
directly
(conductively, convectively, or radiatively), or by heating the mold or other
element in
contact with, or adjacent the material 20.
[0062] In some embodiments, no external pressure (i.e. other than atmospheric
pressure) is required, for example if the surfaces are substantially smooth
and surface
roughness is fully compensated by surface elasticity of the film. If the
material was
inserted as a cold part (film or otherwise), heating is applied to the
material while it is on
the mold. While this heating and/or cooling could be controlled in any number
of ways
known in the art, in FIG. 1 a, a hot plate 24 is provided for this task, which
heats the
mold 22, which in turn, imparts the heat to the material 20. Applicant has
demonstrated
patterning of a SEBS foil with only atmospheric pressure, at a temperature of
170 C, with
a cycle time of 150 s, as is described below. Applicant has demonstrated
patterning of a
Evatane foil with only atmospheric pressure, at a temperature of 100 C, with a
cycle time
of 150 s, as is described below.
[0063] Other embodiments use some pressure 26 to expedite patterning.
Depending
on a thickness of the part, a desired time, and a relief depth of the mold,
some pressure,
such as less than 5 bar, preferably less than 4 bar, 3 bar, 2 bar or 1.5 bar,
may be
applied. The reduced pressure and temperature requirements for patterning of
soft solid
TPEs opens the door to very low cost, reliable, high-throughput patterning
techniques.
Pressure required for patterning TPEs is 1-2 orders of magnitude smaller than
the
pressure required for embossing commonly used TPs (i.e. -1 bar instead of -10s-
100s of
bars).
[0064] In terms of quality, soft solid TPE molded structures show well-defined
shapes
and excellent surface quality, additionally, any defects related to the
influence of the
shear force resulting from the difference of thermal expansion coefficient of
the polymer
and the mold has been observed. Defects perennially encountered when
patterning hard
thermoplastics (Y. He, J.-Z. Fu and Z.-C. Chen, Microsy. Technol., 14, 325
(2008) and M.
Worgull and M. Heckele, Microsy. Technol., 10, 432 (2004) such as edge damage
and
asymmetric pull-off of plastics part due to interfacial friction are absent.
This is mainly
attributed to the capabilities of TPE materials to sustain deformation through
their
compression set characteristics (i. e. 11 % at 23 C for CL30 TPE styrenic
material).
16
CA 02681897 2009-10-08
[0065] In step 16, the material 20 is cooled and the patterned piece is
removed from
the mold 22. This cooling can be performed quickly, for example by immersion
into a
water bath, with no damage to the materials or the patterned structure.
[0066] In optional step 18, the cooled part is bonded patterned-surface down,
onto a
second part to form a microfluidic device having at least one microchannel.
The
microchannel may extend between two ends, each of the ends being an input, an
output,
a junction or a chamber. The second part may be of a similar composition, or a
dissimilar
composition. It may be preferable for one layer in a multi-layer device to
have substantial
rigidity.
[0067] A patterned part (either made by thermoforming methods or spin coated
method) of soft solid TPE can be assembled by placing the patterned surface on
a
smooth substrate (plastic, glass, ceramic, etc.), or an already patterned TPE
part.
Minimal force is required for bonding (in general no force other than
atmospheric
pressure is required once contact is made), and as most soft solid TPEs adhere
to itself
readily, stacks of these patterned parts may be successively assembled without
risk of
deforming microchannels between other layers. In some cases, layers can be
reversibly
bonded at ambient temperatures, and bonding can be made irreversible with
thermal
treatment. In other cases at room temperature, after a bonding period, the
bonding is
irreversible. However other materials require thermal treatment to provide
liquid-tight
bonds to like layers, but do not require pressure above about 1.5 bars, more
preferably
1.3 bars, more preferably 1.2 bars, to fully bond.
[0068] It is believed that for the broad class of soft solid TPEs, that
bonding to like
layers can be performed with moderate thermal conditions (lower than the
melting point of
the soft solid TPE) and with low pressure (i.e. total pressure (atmospheric +
applied) less
than 1.5 bars, more preferably less than 1.3 bars, more preferably less than
about 1.2
bars), and further that soft solid TPEs may be bonded to dissimilar surfaces
to provide a
liquid-tight seal, under similar temperatures and pressures. Because of the
softness of
soft solid TPEs, they form intimate contact with surfaces composed of a wide
variety of
materials. If soft enough (e.g. E' below 5 MPa) TPEs may conform at the
molecular level,
hence promoting a perfect, watertight seal with a number of substrates (e.g.,
plastics,
glass, and silicon). It is believed that several soft-solid TPEs formulations
that
incorporate tackifiers can be adequately bonded at room temperature to like
materials
and different materials to provide a seal, as desirable for microfluidic
devices.
17
CA 02681897 2009-10-08
[0069] Soft solid block copolymer TPEs that contain 15% or less of the hard
block
component are particularly advantageous with respect to bonding. Without
wanting to be
limited by the foregoing theory in all aspects of the present invention,
Applicant explains
the ability for soft solid BCP TPEs to locally reconfigure with the properties
of the soft
polymer chains (such as ethylene-butylene EB blocks) contained in a coblock
polymer.
Soft solid BCP TPEs are formed with two types of segments (one soft, one hard)
which
are (bonded along each polymer chain. The soft segments exhibit
viscoelasticity to a
high degree, and can flow at moderate temperatures, permitting very close
forming of the
copolymer at moderate temperatures, and further providing for very high
elasticity of the
material. This flow of the soft blocks is believed to permit bonding to a wide
variety of
surfaces having the various compositions.
[0070] In particular, for styrenics BCP with low styrene content (i.e hard
block
content) (10-12%), thermodynamic incompatibly between blocks induces nanophase
separation and self-assembly of polystyrene (PS) domains into nanometric
clusters (10-
30 nm in diameter) which are distributed in a three-dimensional fashion with
hexagonal
symmetry in the rubbery matrix of ethylene-butylene (EB) (fig 8). This
morphological
structure provides the basis of the material's performance: rigid PS domains
act as
junction points that stabilize the polymer matrix, while the EB dominant phase
offers
elastomeric properties at room temperature and previously discussed bonding
properties.
[0071] Moreover, such size and cluster distribution allow us to consider TPE
surface
properties to be uniform and homogenous at the microfluidic scale for devices
that are
fabricated from this material (see Roy Thermoplastic Elastomers (TPE) Block
Copolymers, a New Material Platform for Microfluidics: Proof-of-Concept for
Complex
Siphon Valving on CD, in: Proceedings of the 12th International Conference on
Miniaturized Systems for Chemistry and Life Sciences, San Diego (2008), the
content of
which is incorporated herein by reference. For further reading the interested
reader is
referred to a comprehensive overview published by Holden. G. Holden, N. R.
Legge, R.
Quirk and H. E. Schroeder, Thermoplastic Elastomers, 2nd edition, Hanser-
Gardner
Publications, Cincinnati (1996).
[0072] The styrenics BCP (SEBS, SIBS) materials, without any tackifier, was
found to
adhere spontaneously with planar surfaces, and the contact line propagated
across the
entire substrate without the need of applying any external pressure.
[0073] Soft solid TPEs may be chosen to operate in a variety of thermal
regimes. For
example, widely used PCR (polymerase chain reaction) devices operate at
temperatures
18
CA 02681897 2009-10-08
around 95 C. While this would be impossible with TPE gels, oil-free soft solid
TPEs can
operate within this temperature range. Demonstrated of soft solid TPEs that
can sustain
service temperatures of 95 C for 60 minutes without microchannel damages or
leakage is
provided herein below (fig 5)
[0074] While the foregoing embodiments provided one route to fabricating a
part for a
microfluidic device, it will be appreciated that other forming and patterning
techniques
could equally be used. Most soft solid TPE materials can be dissolved in
solvents
(benzene, chlorobenzene, toluene, etc. the selection of which is well within
the abilities of
on of ordinary skill in the art) permitting spin coating and solvent casting
forming
technologies to be used for TPE film microstructuration. Spin casting has
known value
for producing thin membranes with highly uniform depth and excellent feature
reproduction. Applicant has patterned microstructures as small as 10 pm by
spin casting,
and smaller features can be produced as easily, given suitable molds.
19
CA 02681897 2009-10-08
Examples
[0075] Applicant has demonstrated that solid soft TPE films, such as those
formed of
styrenic block copolymers including styrene-ethylene-butylene-styrene (SEBS)
and SIBS
(styrene)/(isobutylene)/(styrene)) for one part and non blocks polymers such
as ethylene
vinyl acetate (EVA) polymer, can be patterned with high fidelity microfluidic
channels
using low temperature and low pressure-time thermoforming, and further that
solid soft
TPEs have advantageous properties in terms of bonding. Styrenic block
copolymer
elastomer is composed of diblock, triblock, star block, other multi-block
structures, or
blends of these structures.
Soft solid TPE materials and characterizations
[0076] The experiments focused mainly on soft solid styrenic block copolymer
TPEs.
Three commercially available grades of styrene/ethylene/butylene/styrene
(SEBS) block
copolymers (Versaflex SEBS CL30 from GLS Corp, McHenry, IL, USA; and SEBS
MD6945 and G1657 from Kraton Polymers, Houston, TX, USA) and one
styrene/isobutylene/styrene SIBS compound (SIBSTAR 072T from Kaneka, Houston,
TX,
USA) were purchased. These SEBS compositions have 10-12% PS blocks. For the
ethylene vinyl acetate (EVA) TPE material, EVATANE 62-40 was purchased from
Arkema
Inc. Philadelphia, PA, USA. Additionally, we have used a recently introduced
solid soft
TPE (Mediprene Oil Free series) developed by VTC TPE Group, Inc Sweden.
[0077] As delivered soft solid TPE pellets of each kind were used to form
films by
extrusion using a Killion KL100 single screw extruder (Killion Laboratories,
Inc., Houston,
TX, USA). The opening of the flat die was set between 0.2-3.0 mm for different
film
thicknesses and a customized calendar (Metaplast, Inc., Chassieu, France) was
used to
collect the film on a roll. Extrusion was performed at a temperature of 140-
270 C, a
screw revolution of 10-1000 rpm and a roller casting speed of 10-65 cm/min.
The films
had thicknesses according to the flat die opening, but in all cases the width
of the film
was 15.0 cm and the length of the film was greater than 10 m. For patterning,
4" TPE
films were cut from the roll and successively rinsed with deionized (DI) water
(18.2 MOhm
cm), isopropanol and methanol (both from Fisher Scientific, Ottawa, ON,
Canada),
followed by drying in a stream of nitrogen gas.
Softness characterization
[0078] TPE mechanical and thermal characterizations were carried out with a
dynamic mechanical thermal analyzer (DMTA, ARES LS2 rheometer, Rheometric
CA 02681897 2009-10-08
Scientific, Piscataway, NJ, USA), at temperatures ranging from -130 to 200 C.
Storage
(E') and loss (E") modulii were determined at 1 Hz with a strain of 0.02% and
a heating
rate of 2 C/min. FIG. 2 shows the storage (E') and loss (E") modulii as
function of
temperature for CL30 SEBS (as well as for polystyrene PS). In essence, E' and
E" are a
measure of the stored and dissipated energy related to the elastic and viscous
responses
of the material. The ratio of these modulii, E"/E, is the tangent of the phase
angle shift 8
between stress and strain vectors, which characterizes the damping behavior of
a
material. These parameters help determine phase transitions, which are
detected as
changes in the elastic modulii as well as peaks in the temperature curve of
tan 8 which
was used to determine a suitable molding temperature for the material. The
curves also
reveal differences in morphological and mechanical properties for the two
polymers and
help explain bonding behavior of the SEBS material.
[0079] As shown in FIG. 2, the peak at -54.8 C corresponds to the glass
transition
temperature of the ethylene-butylene soft blocks that are distributed
throughout the
material. The fact that this glass transition is far below an operating
temperature of 0-
100 C is advantageous for achieving conformal contact and bonding at moderate
temperatures, as it indicates liquid-like behavior of the soft block material,
while the hard
blocks provide support and retention of the soft block material.
[0080] FIG. 3 shows graphs of E' storage modulii of the three SEBS film
materials.
Clearly shown is a so-called rubber plateau which extends from about 0-10 C to
75-85 C
for each of the three materials. Modulii of 1.1, 1.6 and 3.4 MPa at 25 C are
obtained for
CL30, MD6945 and G1657, respectively. These mechanical properties indicate
that the
thermoplastic materials that are soft like PDMS (i. e. 0.5-5 MPa), while with
only 10-15%
styrene content, are 1000 times softer than polystyrene (i.e. 1-5 GPa). On the
other
hand, its block-copolymer structure provides thermal resistance along with
mechanical
robustness superior to standard PDMS formulations, as exemplified by a
relatively large
elongation at break (e.g. 300-1200%) that can be achieved for the selected
materials.
Unlike PDMS, the soft blocks provide bonding capabilities above their glass
transition, i.e.
above --80 20 C. So at room temperature, the polymer chains can
reorganize/reorient
according to the contact surface properties, inducing conformal bonding
without any
heating and applied pressure. SEBS (like other solid soft TPEs) exhibit
effective polymer-
polymer interactions at ambient conditions. For this reason, styrenic TPE
materials and
some of its derivates are included in pressure sensitive adhesives (PSA), such
as the
famous post-it sticker, which can be glued to a broad range of supports, such
as metal,
glass or wood without mediation by heat, pressure or solvents. Similar to
other
21
CA 02681897 2009-10-08
adhesives, styrenic TPE materials possess solid and liquid properties alike,
which enable
it to wet another surface at the microscopic scale, while maintaining rigidity
at the
macroscopic level (see Creton Block Copolymers for Adhesive Applications, in:
Macromolecular Engineering: Precise Synthesis, Materials Properties,
Applications, eds.
K. Matyjaszewski, Y. Gnanou and L. Leibler, Wiley-VCH, Weinheim (2007), 1731-
1752).
Optical characterization
(0081] A number of lab-on-chip applications involve optical reading, which
demands
for materials providing transparency, primarily in the UV-visible range.
Optical
transmission spectra were collected from one 1-mm-thick films of SEBS (CL30,
MD6945,
G1657 and SIBSTAR 072T) using a Beckman DU-640 spectrometer from 200 up to
1000
nm wavelenght. Defining 50% transmittance as an acceptable limit in
transparency,
PDMS provides a transparency window that is the widest of the 3 materials
(i.e. from 280
to 1000 nm). On the other side, for Zeonor and SEBS polymers, 50%
transmittance is
reached at 340 nm and 295nm, respectively. This is sufficient for most
commonly used
fluorescent dyes, including Cy3 ()ex = 550 nm; Aem = 570 nm) and Cy5 (Aex =
650 nm;
Aem = 670 nm), for which SEBS transparency reaches 90-92%. Styrenic TPE
polymers
are typically clear, because styrene domains are too small (e.g., 10-30 nm) to
scatter
light. Another attractive feature of these materials is that they show a
relatively low auto-
fluorescence background over a wide spectral range.
[0082] These materials offer a similar optical transparency and flexibility to
PDMS
while providing the possibility for structuration using known, industrially
scalable,
thermoforming processes such as injection molding and hot embossing.
Biocompatibility
[0083] In terms of bio-compatibility, with the Versaflex CL30 material, we
succeeded
in handling DNA and protein solutions for microfluidic spotting and we
performed human
cells cultures including smooth muscle cells, corneal and dermal fibroblasts
on
microstructured surfaces (M. D. Guillemette, B. Cui, E. Roy, R. Gauvin, C. J.
Giasson, M.
B. Esch, P. Carrier, A. Deschambeault, M. Dumoulin, M. Toner, L. Germain, T.
Veres and
F. A. Auger, Integr. Biol., 1, 196 (2009)
Thermoforming and characterization
[0084] The devices used in this work were fabricated using two variants of
thermal
forming: i) standard vacuum-assisted hot embossing and ii) soft thermoplastic
22
CA 02681897 2009-10-08
lithography. For either process, TPE films were cut with scissors from the
extruded roll,
cleaned with methanol and isoproponal and finally dried with nitrogen gas
prior to
microstructure patterning. Extruded films can be stored over long periods of
time (e.g.,
two years) without any notable degradation, making it possible to use the
material on
demand and without any time consuming pre-compounding steps.
Hot embossing
[0085] Hot embossing was carried out using an EVG 520 HE system (EV Group)
equipped with heating and cooling modules on both upper and lower embossing
plates.
All embossing experiments were done under a primary vacuum of 0.1 mbar. In
order to
select an optimal embossing temperature for high-quality replication, the
temperature
variation of tan 6SEBS (FIG. 2) is useful. A barely visible shoulder (blocked
by the PS
curve) is observed at 89.9 C and is associated with the glass transition of
the PS phase
(while the glass transition for neat PS is observed at 104.3 C). The
difference in
amplitude between those two PS glass transitions is related to the ultra-
minority fraction
of styrene content in SEBS. Most importantly, for embossing parameter
determination
and temperature service in use, the difference of 14.4 C between those two
transitions is
related to a "lowering effect" and was interpreted as a consequence of
premature
molecular motions in polystyrene domains induced by the poly(ethylene-
butylene)
segmental mobility. For a more complete explanation, see Munteanua et al, J.
Optoelectron. Adv. Mater., 2005, 7, 3135-3148, and Mortise-Seguela et al.,
Macromol.,
1980, 13, 100-107.
[0086] Most work on the embossing of hard TPs (i.e., PMMA, PC, and PS)
recommends embossing temperatures ranging from 140-220 C (i.e. about 40-90 C
above
the glass transition), in order to have a good compromise between temperature
and
pressure. For styrenic BCPs, determination of optimized embossing temperature
diverges from those guidelines. In fact, hard styrene nanodomains will not
spontaneously
dissociate at the lower glass transition, but gradually deform while retaining
quasi-integrity
in the poly(ethylene-butylene) matrix, as long as the temperature does not
exceed the
broad and large peak observed for the present materials at 141 C.
Consequently in order
to avoid any thermal history effect and to improve polymer flow behaviour, we
need to fix
an embossing temperature above that temperature, called by several authors
"domain
disruption temperature". For example, see C. Wang, Macromol., 2001, 34, 9006-
9014,
and N. Nakajima, Rubber Chem. Technol., 1996, 69, 73-81. Above this
temperature, E'
reaches a plateau region (attained at -160-165 C) with a stable value of 0.1
MPa,
23
CA 02681897 2009-10-08
suggesting that an embossing temperature of 170 C should be well suitable for
high-
quality motif replication.
[0087] Once top and bottom plates of the embossing machine reached 170 C, a
force
of 1.0 kN (1.3 bar) was applied for 2 min. With the force still applied, the
system is cooled
to 75 C, followed by a release of the pressure. Upon removal of the stack from
the
instrument, the embossed TPE film is peeled-off the mold.
[0088] FIG. 4 is a mosaic of 9 magnified images of microfluidic structures
produced in
accordance with the present invention. Patterned films shown in FIGs. 4(a)-(f)
were
formed by hot embossing of SEBS films. SEBS films were embossed under
different
temperature and pressure conditions (from 0.5 to 5 bars and 100 C to 170 C)
for G1657,
MD6945, SIBSTAR 072T, or Mediprene OF 400M. The motifs replicated varied as
well.
The replicated motifs are well-defined, indicating a high level of fidelity
that can be
achieved with this approach. Moreover, the surface is smooth and free of
defects,
showing a root mean squared (rms) roughness of 1.5 and 3.0 nm for areas that
were in
contact with silicon and SU-8 portions of the mold, respectively. Good
uniformity of
replication over 4" areas was noted. Herein roughness measurements were
performed
using a multi-mode Nanoscope IV atomic force microscope (Veeco Metrology
Group,
Santa Barbara, CA, USA), operated at ambient conditions and in contact mode
using
silicon nitride cantilevers (NP-S20, Veeco) with a spring constant of 0.58
N/m.
Soft lithography
[0089] Soft thermoplastic lithography uses little or no pressure beyond
ambient
atmospheric pressure and an elevated temperature to replicate a pattern on a
film. This
kind of replication is possible because of the mechanical and viscoelastic
properties of
the soft solid TPE materials. A film was first placed on the Si/SU-8 mold. An
almost
perfect contact was achieved if the depth of relief features is less than a
few microns and
the thickness of the film is greater than about 2.5 mm, thanks to the
viscoelastic
properties of the polymer. In the present examples, a 3 mm SEBS film (CL30)
was used.
The SEBS film is placed on a hot plate and heated to 170 C for 2.5 min at
atmospheric
pressure. At this temperature, the solid soft TPE material turned opaque due
to
coalescence of the styrene nanodomains, accompanied by a considerable decrease
in
viscosity. At this point, the film generates sufficient pressure (-50 Pa) to
ensure polymer
displacement over micrometer scale relief distances. At the same time, the few
remaining air bubbles trapped between the mold and the SEBS disappeared, which
is
attributed to the relatively high gas permeability of the soft solid TPE
materials at elevated
24
CA 02681897 2009-10-08
temperatures. Crystallized PS nanodomains interrupt the gas flow and retard
permeation
in comparison to the soft and more permeable EB polymer blocks. Upon
completion of
the thermoforming process, the stack is immersed in water for rapid cooling
and
hardening of the patterned SEBS film. The SEBS film becomes transparent as a
result of
nanophase separation, once the material is cooled.
[0090] For Ethylene Vinyl Acetate (EVA) films were patterned by soft
lithography
under ambient pressure, and the patterned film is shown in FIG. 4(h). The EVA
film was
2.5 mm-thick, the temperature was raised to 100 C for 3 min, and then the film
was flash
cooled by immersion in water.
[0091] FIGs. 4(g),(h) are SEM images revealed that fluidic structures were
replicated
with excellent fidelity. No perceptible difference is found comparing patterns
replicated by
hot embossing with soft lithography. Inspection of the patterned surface by
AFM
indicated a rms roughness of 2.2 and 3.1 nm for areas that were in contact
with silicon
and SU-8 portions of the mold, respectively. As was the case for hot
embossing, the
same mold was used for a large number of replication cycles (e.g., >50) while
retaining
consistent quality of resultant replicas. Scanning electron microscope (SEM)
images
were taken using an S-4800 scanning electron microscope (Hitachi, Mississauga,
ON)
operated at an acceleration voltage of 1.0 to 1.5 kV.
High aspect ratio and negative profile examples
[0092] Demolding is greatly facilitated by the flexibility of the solid soft
TPE and high
aspect ratio (AR) features can be reproduced with high fidelity. Due to the
low elastic
modulus and low melt viscosity of soft solid TPEs, we were able to show that
it is possible to
pattern high aspect features by thermoforming methods without the
complications that are
typically encountered with TP. Some examples of CL30 SEBS films patterned by
hot
embossing with low cost photoresist-based (SU-8) moulds are imaged in FIG. 5.
FIG. 5a is
an image showing two negative profile or undercut patterned features, i.e.
features that
have a higher cross-sectional area further from a plane of the mold, or the
surface of the
part. FIGs. 5b,c show high-density, high aspect ratio features that have been
produced with
excellent accuracy. Thin SEBS films patterned with structures having diameters
as small as
10 pm in a 100 urn thick TPE slab (aspect ratio up to 10:1) are shown in FIG.
5c. All
samples shown in FIG. 5, were prepared with the EVG 520 hot embossing system,
under
a primary vacuum of 0.1 mbar, at a processing temperature variation of of 140
C within a
10 min period embossing time.
CA 02681897 2009-10-08
[0093] Applicant has demonstrated that a variety of channels and features can
be
formed in microfluidic devices composed of soft solid TPEs, making them useful
for the
full array of microfluidic devices. Applicant has shown that low pressure and
temperature
forming regimes are possible, including film forming techniques.
Spin coating
[0094] Applicant melted MD 6945 (an oil free SEBS) and the EVA polymer and
diluted the polymer in different batches with TPE/chlorobenzene, or
TPE/toluene dilutions
in ratios ranging from of 1:2 to 1:1000. A prescribed volume of the polymer
was
dispensed into a center of a SU-8 photoresist mold that was spinning at
between 0 and
6500 rpm. Thin films with thicknesses from 10 to 400 pm were produced.
Naturally,
thicker layers can be achieved by iterative depositions. Microstructures as
small as 10
pm have been made, and smaller features should be possible.
[0095] During the spin coating, if the solvent did not fully evaporate, a post
forming
thermal treatment (at 100 C for 4 min.) was used to complete evaporation. Like
thermoformed TPE parts, spin coated parts can be easily separated from the
mold, and
the same advantages in terms of quality, aspect ratio, negative profile and
bonding are
noted.
[0096] Applicant has found that oil impacts strongly on the quality of SEBS
films when
formed by spin casting, which is attributed to the fact that inclusion of oil
in as-sold
polymers seems to prevent homogenous dilution of the soft solid TPE. Additives
might
be used to cure this. The spin coated films that contain oil have an abundance
of defects.
[0097] FIG. 7 is a mosaic of images relating to the spin coating examples.
FIG. 7(a)
shows a soft solid TPE (CL30 TPE material, which contains 5-25 % of oil) spin
coated
using chlorobenzene solvent. It will be noted that the discontinuities are
apparent and the
film produced is replete with defects. FIG. 7(b) is neat MD6945 spin coated
with
chlorobenzene over a microstructured SU-8 photoresist mold. FIG. 7(c-d) are
SEM
images showing a square microfluidic chamber array (200x200pm2) and linear
channel
array (100pm) composed of MD6945.
Bonding
[0098] A chief advantage of patterned films of solid soft TPE is that these
can be
assembled by simply placing the patterned surface on a smooth substrate
(plastics,
glass, ceramics...) or a like film (already patterned or not) with minimal
pressure and
26
CA 02681897 2009-10-08
temperature. Furthermore as no solvent or surface treatment is required,
various surface
modifications (like hydrophilic treatment) can be selectively performed on
parts of the
patterned film with less risk of damage. Because the bonding can be
irreversible or
reversible with or without thermal treatment (depending on a compatibility of
the
substrate) it is possible to treat the patterned films or parts with very
sensitive materials
and still provide sealed, functioning microfluidic devices. Furthermore there
is no time
sensitivity. Such patterned films can be stored for extended periods and then
subsequently bonded. These facts make it much easier to assemble multi-layer
devices.
[0099] As minimal force is required for bonding (in some cases no force is
required at
all once contact is made), and as the solid soft TPE adheres to itself
readily, stacks of
these patterned parts may be successively assembled without risk of deforming
microchannels between other layers (as would follow from high pressure bonding
strategies). Layers can be bonded first without applied pressure or increased
temperature and bonding can be made irreversible with thermal treatment (with
or without
carefully selected pressure) depending on the selected grades of materials.
[0100] Some styrenic block copolymers like (MD6945, SIBSTAR072 or Mediprene
OF 400M grades) produce permanent bonds to like materials without any applied
pressure or heat, these soft solid TPEs therefore offer major advantages
compared to
PDMS, hard plastics and gel TPEs. Mediprene OF 400M is oil free. Every soft
solid TPE
attempted by the applicant produced a liquid-tight seal.
[0101] FIG. 6 is a mosaic of 6 images showing bonding and loading efficiency
of soft
solid TPEs in microfluidic devices. FIG. 6a is a photograph showing an inlet
part of a
microfluidic device consisting of a SEBS CL30 patterned film bonded (non-
permanently)
to a polystyrene (hard thermoplastic) substrate. This bonding was performed at
room
temperature under ambient pressure by simply making contact between the film
and the
substrate. The bond line grew with no assistance until the whole material was
covered. It
will be noted that the device provides a seal sufficient to produce a useful
device and the
dyed liquid was retained in the channels as well as the inlet ports.
[0102] FIG. 6b is a photograph showing the same bonding features of a
microfluidic
device consisting of a SEBS CL30 patterned film bonded (non-permanently) to a
polyclyclo(olefin) (hard thermoplastic) substrate. The bonding was achieved in
the same
manner as in FIG. 6a.
27
CA 02681897 2009-10-08
[0103] FIG. 6c is a fluorescence microscope image of DNA patterns realized
with
TPE microfluidic network temporarily bonded on an activated Zeonor 1060R
substrate.
The bonding was produced in the same manner, however, prior to bonding, the
Zeonor
substrate was treated in order to be compatible with the DNA immobilization
protocol by:
1 hr ozonation treatment using an 03 zomax OZO-2VTT ozone generator; followed
by
treatment with a solution of 8 mg 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide and 2
mg N-hydroxysuccinimide (NHS) in phosphate buffer saline (pH=7.4). This image
was
taken of the Zeonor surface after the removal of the patterned film. The lines
show
clearly that the bonding was fluid tight. While no defect is apparent in the
depicted array,
the number of spots showing signs of cross-contamination (e.g., Cy3 and Cy5
fluoresce
signal being present in the same area) was -4% on average. Fluorescence
emission
was largely uniform among spots in the array, although fluorescence intensity
decreased
from left to right for both sections (e.g., -20% for P1 and -30% for P2). This
finding was
systematic for arrays produced with the particular design pattern, and results
from
depletion effects occurring along the corresponding trajectories. However,
fluorescence
intensities within the modified areas were uniform for both Cy3 and Cy5-labeld
oligonucleotides, irrespective of the length of connected microchannels. One
example of
a microfluidic device is a spotter.
[0104] FIG. 6d is a CD-like microfluidic device consisting of a Mediprene OF
400M
SEBS patterned film permanently bonded to a polyclyclo(olefin) disc. The
bonding was
performed at 100 C for 10 min. At the bottom of this image one can observe
some
microchannels loaded with colored solutions.
[0105] FIG. 6e schematically illustrates two MD6945 SEBS films (one patterned)
permanently bonded together at room temperature, with no applied pressure,
proving that
multilayered devices are readily produced.
[0106] Mediprene OF 400M, MD6945 and SISBSTAR 072T also bond permanently to
like layers at room temperature with no applied pressure within 2-3 days.
Three and four
layer microfluidic devices have been produced by iteratively applying
Mediprene OF
400M SEBS patterned film on top of a polystyrene substrate.
[0107] FIG. 6f is a cross-sectional view of 5x5 pmz embedded microchannels
obtained by non permanent bonding of CL30 TPE part on a Zeonor substrate at
ambient
temperature and pressure. The absence of any transition zone between the two
materials indicates a high degree of conformity. Moreover, the microchannels
are fully
open and do not show any signs of deformation. The material therefore seems
suitable
28
CA 02681897 2009-10-08
for assembly and bonding of full thermoplastic microfluidic devices without
the need of
sophisticated equipment, or for surface treatments that may be detrimental to
biological
applications of microfluidic systems.
[0108] An optical profilometric investigation of microchannel stability
throughout a
thermal treatment (95 C for 30 min.) of a microfluidic device consisting of a
2 mm thick
Mediprene OF 400M SEBS film on a polyclyclo(olefin) substrate. While the
majority of
soft solid TPEs are not suitable for operation in temperatures as high as 95 ,
such
temperatures are desired for PCR and other operations. Applicant has
demonstrated that
some soft solid TPEs are useful for this purpose. FIG. 7 shows 3 examples of
before and
after profiles at three locations. SEM image of three microchannels (15pm
wide/25 pm
deep) after same thermal treatment. The channels did not collapse, and flow
through
them is expected to be substantially unaltered by the treatment.
29
