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Integration of functional materials and surface modification for polymeric microfluidic systems
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2013 J. Micromech. Microeng. 23 033001
(http://iopscience.iop.org/0960-1317/23/3/033001)
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IOP PUBLISHING
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
doi:10.1088/0960-1317/23/3/033001
J. Micromech. Microeng. 23 (2013) 033001 (19pp)
TOPICAL REVIEW
Integration of functional materials and
surface modification for polymeric
microfluidic systems
Maria Kitsara and Jens Ducrée
Biomedical Diagnostics Institute, National Centre for Sensor Research, School of Physical Sciences,
Glasnevin, Dublin 9, Ireland
E-mail: [email protected], [email protected] and [email protected]
Received 10 August 2012, in final form 7 January 2013
Published 6 February 2013
Online at stacks.iop.org/JMM/23/033001
Abstract
The opportunity for the commercialization of microfluidic systems has surged over the recent
decade, primarily for medical and the life science applications. This positive development has
been spurred by an increasing number of integrated, highly functional lab-on-a-chip
technologies from the research community. Toward commercialization, there is a dire need for
economic manufacture which involves optimized cost for materials and structuring on the
front-end as well as for a range of back-end processing steps such as surface modification,
integration of functional elements, assembly and packaging. Front-end processing can readily
resort to very well established polymer mass fabrication schemes, e.g. injection molding. Also
assembly and packaging can often be adopted from commercially available processes. In this
review, we survey the back-end processes of hybrid material integration and surface
modification which often need to be tailored to the specifics of miniaturized polymeric
microfluidic systems. On the one hand, the accurate control of these back-end processes
proves to be the key to the technical function of the system and thus the value creation. On the
other hand, the integration of functional materials constitutes a major cost factor.
(Some figures may appear in colour only in the online journal)
1. Introduction
feature a wide range of (customizable) material characteristics.
Furthermore, their thermally induced castability makes
polymers amenable to commercially very well-established,
high-fidelity replication schemes such as hot embossing and
injection molding, thus covering the full scope for upscale
from small-series to mass production [2].
However, there are a few drawbacks intrinsic to polymers
that needed to be overcome: first, most polymers are
intrinsically hydrophobic which is usually challenging for
the operation of microfluidic devices as external pumping is
necessary for priming. As a result of this hydrophobicity, also
biofouling becomes an issue, leading to unspecific binding,
in particular of biomolecules. Strong surface adsorption
may deplete or denature reagents and target molecules,
In the earliest reports, microfluidic chips have been mostly
fabricated by standard photolithographic techniques in silicon,
glass or directly into photoresists such as SU-8 [1]. While
silicon has been very popular due to the wealth of sophisticated
microfabrication processes adapted from the far more
developed microelectronics and the MEMS (micro electro
mechanical systems) industries, glass was the traditional
material of wet chemistry so researchers could resort to a
profound base of well documented know-how, in particular
regarding surface functionalization.
Yet, over time, polymers have been increasingly drawing
attention of the microfluidic community. This is because the
class of polymers exhibit comparatively low material cost and
0960-1317/13/033001+19$33.00
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© 2013 IOP Publishing Ltd
Printed in the UK & the USA
J. Micromech. Microeng. 23 (2013) 033001
Topical Review
thus compromising the functionality of assays and their
(quantitative) results.
Second, more care must be taken to control their
surface chemistry than with glass or silicon. Polymers are
poorly compatible with organic solvents (except for cyclic
olefin materials (COP/COC)). At elevated temperatures, as
for instance present in autoclaves, polymers melt, which
might distort previously defined microstructures. In addition,
polymers have been found to display slower, potentially
unstable electroosmotic flow (EOF) than glass or silicon chips
(exhibiting a natural oxide layer). Also the choice of the
fabrication method may substantially affect the magnitude
of EOF. Appropriate functionalization of the surface of the
polymer microchannels has proven to improve flow control
and suppress biofouling, thus greatly enhancing the reliability
of these polymer-based microchips [3, 4].
In this review, functional materials are reviewed that have
been utilized to bestow specific, non-intrinsic properties upon
common polymeric microfluidic substrates. These materials
include hydrogels, porous monoliths, membranes, organic
electronics as well as paper-based microfluidics. Moreover,
various types of functional coatings applied to polymer
microfluidic systems are outlined, including methods such
as plasma activation, chemical vapor deposition (CVD),
UV (ultraviolet) irradiation, sol–gel chemistry and dynamic
coating as well as local deposition techniques.
While most of the early work was done using polymers
such as PMMA or PC for more temperature-demanding
applications, in recent years there has been a growing interest
in two specific cyclic olefin materials: cyclic olefin polymer
(COP) and cyclic olefin copolymer (COC). These engineering
plastics possess high optical clarity, even into the deep-UV
range [11], low water absorption and, compared to other
polymers, an exceptionally high resistance to organic solvents
[12].
SU-8 is a UV-sensitive epoxy-based negative photoresist
known from surface micromachining which can be
obtained with range of viscosities for forming highthickness films (∼100 μm) by spin coating. The i-line
of common mercury vapor lamps [13, 14] is commonly
employed to photolithographically micropattern high-aspectratio structures. It has also been shown that the SU-8 native
resin itself or through suitable functionalization procedures
is compatible with a range of chemical and biological assays
[15].
As an alternative, PDMS, an elastomeric material, has
been widely used for the fabrication of microfluidic devices
by ‘soft lithography’ [16, 17]. Features on the micron scale
can be replicated with high fidelity in PDMS using replica
molding from a microstructured, e.g. SU-8, master. The replica
can be sealed reversibly or irreversibly without disfeaturing of
the microchannels. PDMS substrates have been utilized with
biological samples because of their low toxicity and their rather
high optical transparency down to 280 nm, making PDMS
compatible to a number of detection methods [18, 19].
2. Polymers in microfluidics
A wide variety of polymer materials have been evaluated
for fabricating microfluidic systems in lieu of silicon or
glass common in conventional microfabrication and wet
chemistry. The most frequently used polymers include
poly(methyl methacrylate) (PMMA), polycarbonate (PC),
cyclic olefin materials, SU-8 and poly(dimethylsiloxane)
(PDMS) [5, 6] which is commonly processed by the so-called
‘soft lithography’ fabrication scheme. Commercial suppliers
mix the native polymers with various additives, e.g. to optimize
their flow properties as a hot melt during injection molding.
These multi-component commercial materials use trade names
and are commonly referred to as plastics.
PMMA has been one of the most widely used polymers
for microfluidics. It is particularly useful for microfluidic chips
due to its comparatively low cost, high optical transparency,
and well definable electric and mechanical properties [7].
Compared with the commonly used polymeric materials,
PMMA is the least hydrophobic polymer, and can directly
generate stable EOF in the microchannels [8]. Owing to
its unique absorption characteristics in the infrared regime,
PMMA is also amenable to direct-write microstructuring by
common CO2 laser ablation systems. These favorable physicochemical properties frequently make PMMA the material of
choice for the fabrication of microfluidic devices.
PC is a widely used thermoplastic polymer which is,
for instance, used for the fabrication of optical data storage
media such as compact disks. Its high durability, strength,
temperature resistance, low density and good optical properties
have also made PC a popular material for the fabrication of
microfluidic devices [9, 10].
3. Polymer processing
There is a variety of machining techniques used for
the fabrication of polymeric microfluidic devices, which
can be coarsely categorized into direct/serial writing and
replication schemes [5, 6, 20–26]. Often used direct structuring
methods comprise (ultra-)precision milling, laser ablation and
photolithography. Replication schemes require a sturdy, lowwear tool featuring the inverse of the replicated structure which
is typically the cost critical step as imperfections such as
(unwanted) surface textures or roughness resulting from the
tool making would fully reproduce in the replicate.
In principle techniques similar to the direct structuring
methods can be used to create the mold. However, the typically
very harsh, physico-thermal conditions during replication and
demolding impose challenges on the resistance to abrasion
and high tolerance to vigorous mechanical stresses on the
tool; as a rule of thumb, the shorter the cycle time (or,
more specifically, the higher the shear stresses) of the
process, the more challenging the demands on the tool.
So robust metal tools displaying high-quality surface finish
normally made by time-consuming and costly precision
milling, electro-discharge machining and/or electroplating
(shims) are virtually imperative for high-throughput injection
molding. Hot embossing is somewhat less challenging to the
sturdiness of the tool as the polymer already resides in the
cavity at the beginning of the process and is only locally
displaced rather than being exposed to the high shear forces
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
in the high-pressure injection of the hot melt into the cavity
during injection molding.
Moreover, it has to be noted that the master would
be the inverse of the replicate, which typically consists
of a channel network in the case of microfluidic systems.
Generating the inverse thus requires the machining of a
large surface area (e.g. of microscope slide, credit card or
disk-size format) at very high surface finish. Even more,
common tool making techniques bear intrinsic limitations on
the minimum feature size and shapes. For instance, while
being rather flexible in three-dimensional structuring, the
tool diameter (practically about 100 μm) sets the minimum
channel width in the milled masters. On the other hand,
while able to pattern very precisely even in the sub-micron
regime, lithography constitutes an essentially two-dimensional
technique which brings about severe limitations in terms of
creating multi-depth structures. So in particular for creating
three-dimensional, multi-scale structures required for many
real-world microfluidic applications, hybrid tooling methods,
e.g. combining precision milling and lithography, have been
developed [27]. These hybrid masters may then be converted
into a more robust replication tool by electroplating (typically
for injection molding) or elastomer casting (typically hot
embossing).
elastomer-based replica molding technique using low-cost
‘soft lithography’ masters has become the work horse for
generating microfluidic chips in many microfluidic research
labs [16, 18, 19, 37–41]. The casting-based replication
proceeds at low temperatures and shear stresses and demolding
is substantially facilitated by virtue of the flexibility of the
PDMS elastomer (and proper surface pretreatment). However,
note that it restricts the choice of the substrate material
exclusively to PDMS which might not be the optimum material
from a functional microfluidics point of view.
3.4. Precision milling of polymers
Precision milling is a common scheme for master/tool making
in polymer replication. It offers high flexibility in terms
of multi-level/multi-scale structuring, and top-of-the-range
machines claim even micron-scale resolution and opticalgrade surface finish. However, these benefits come at the
expense of extended cycle times, sometimes even on a scale
of hours to days. Nevertheless, it is frequently used on a
research-lab scale for direct patterning of polymeric lab-on-achip substrates. Note that direct milling of polymeric substrates
may also deviate from procedures established for metals, e.g.
owing to heat build-up in the thermal insulator material and
chemical compatibility issues of coolants.
3.1. Hot embossing
3.5. Laser ablation of polymers
Hot embossing is a fairly straightforward method with rather
short set-up times of hydraulic press equipment [28]. Typical
cycle times range on the 10 min scale, making hot embossing
efficient for providing the small lot number typically required
during product development. As an alternative to common,
but time-consuming fabrication of metal hot embossing
tools, Fiorini et al [29–33] utilized thermoset polyester
masters that withstand moderate amounts of pressure and
elevated temperatures. Demolding of the rigid, possibly
surface textured tool might be cumbersome, though. Therefore
elastomer tools, e.g. made of hard PDMS, are often used for
the embossing of polymeric devices as they provide the ease of
tool making (by casting), high-fidelity replication and facile
demolding through the flexibility of the material (see also
section 3.3).
Laser ablation is a direct writing technique for polymers which
involves the use of a high-powered pulsed laser to remove
material from a sheet of thermoplastic substrate. Excimer UV
lasers at pulse rates on the order of 10 to 104 Hz are very
common as most plastics absorb UV light. ArF excimer lasers
(λ = 193 nm) have been used to ablate polystyrene (PS), PC,
cellulose acetate and polyethylene terephthalate (PET). KrF
excimer lasers (λ = 248 nm) are employed for PMMA, PET–
glycol modified, PVC, PC and polyimide [42]. CO2 lasers,
with wavelengths in the infrared region (λ = 10.6 μm), can
directly write into PMMA and PET. While it offers rather facile
operation, laser ablation significantly restricts the choice of
materials and lacks the structural definition, surface finish as
well as the three-dimensional patterning capability offered by
precision milling.
3.2. Injection molding
4. Functional materials
The mainstream of industrial polymer processing is carried
out by injection molding. Cycle times are often on the secondscale, only, thus making it possible to fabricate thousands of
replicates in a single shift. However, due to the very complex
and expensive procedures for tooling, process optimization
and set-up times, injection molding is rarely used during
early-stage product development in research laboratories
[24, 34–36].
This section will survey various schemes that have been
developed for the hybrid integration of functional materials
into polymer microfluidic devices. Apart from the specific
characteristics which add hydrodynamic and/or (bio-)
chemical function, important aspects are the amenability
to structuring and assembly schemes which are compatible
with the underlying (polymeric) microfluidic lab-on-a-chip
systems.
3.3. Elastomer-based replica molding
4.1. Hydrogels
Due to the tremendous techno-economic challenges of tool
making and polymer processing infrastructure, and also
through the availability of a robust bonding scheme, an
Hydrogels respond to external stimuli such as temperature,
pH, solvent, electric fields and ionic strength, e.g. by altering
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
a
b
c
d
e
(a)
(b) Golden et al 2007
(b)
(c) Luo et al 2003
(a) Beebe et al 2000
Figure 1. Characteristic hydrogel structures used in microfluidics: (a) reprinted with permission from [44], (b) reprinted with permission
from [50), (c) reprinted with permission from [52].
to biopolymers such as polyethyene glycol (PEG) in protein
conjugation. Poly-N-isopropylacrylamide (pNIPAm) and
copolymers derived from N-isopropylacrylamide (NIPAm)
and acrylamide (Am) polymerization (pNIPAm-co-Am) were
conjugated to avidin and featured improved properties for
in vivo and in vitro applications as a result of polymer
modification of the bio-physicochemical properties of avidin
[49].
Golden and Tien suggested a method for the formation of
microfluidic gels, with an emphasis on formulations containing
native extracellular matrix (ECM) proteins, such as type I
collagen and fibrin. The method is based on the encapsulation
of micromolded meshes of gelatin in a second gel and
the removal of gelatin by heating and flushing to leave
interconnected channels in the remaining gel (figure 1(b))
[50]. Stoeber et al utilized gel formation by dilute aqueous
solutions of triblock copolymers at elevated temperatures in
order to demonstrate active and passive microflow control.
Solutions of a poly(ethylene oxide)–poly(propylene oxide)–
R
poly(ethylene oxide) polymer (trade name Pluronic
F-127)
have been used as a sample system [51].
Luo et al prepared valves from thermoresponsive
monolithic copolymers by photo-patterning of a liquid phase
consisting of an aqueous solution of N-isopropylacrylamide,
N-ethylacrylamide, N,N -methylenebisacrylamide and 4,4 azobis(4-cyanovaleric acid) [52, 53]. The volume change
associated with the polymer phase transition at its LCST leads
to the rapid swelling and the shrinkage of the 2.5% crosslinked
monolithic gel, thus enabling a thermally actuated valve
(figure 1(c)). The LCST at which the valve switches was easily
adjusted within a range of 35–74 ◦ C by varying the proportions
of the monovinyl monomers in the polymerization mixture.
Ikami et al reported an ‘immunopillar chip’ platform which
includes functionalized hydrogel pillars, fabricated inside a
microchannel, with many antibody molecules immobilized
their volume and/or wetting characteristics. In microfluidic
systems, hydrogels have been mostly used as stimulusresponsive actuators for flow control. An attractive option for
microfluidic systems is the class of heat-sensitive hydrogels
which possesses a lower critical solution temperature (LCST).
At lower temperatures, these hydrogels assume a hydrophilic
state with soft and transparent character. However, as the
temperature rises above the LCST threshold, a reversible
transition to collapsed hydrophobic coils leads to the
precipitation of water. The LCST depends on the molecular
(N-weight as well as the polymer and the salt concentration.
Poly(N-isopropylacrylamide) (PNIPAm) is one of the most
widely investigated thermoresponsive hydrogels as it exhibits
a dramatic volume change upon heat stimulation. In the
context of microfluidic systems, it has been implemented as a
temperature actuated valve [43].
Beebe et al have controlled flow on a chip with pHsensitive hydrogel sensors/actuators that contain a photopolymerizing agent, thus allowing for lithographic in situ
patterning [44, 45]. Figure 1(a) shows a device with a hydrogel
element that acts as a chemical sensor, which includes a flexible
membrane that can deform to block the flow in a lateral
channel. Due to change in the pH, the hydrogel polymerized
in the channel above the membrane expands or contracts.
Moreover, they have demonstrated hydrogel/PDMS two- and
three-dimensional hybrid valves that physically separates the
sensing and regulated streams [46].
Kuckling et al have developed a photo-crosslinked,
thermally responsive hydrogel which was utilized in a
macro-scale valve [47]. A fully opening and closing cycle
completed within 8 min. Albrecht et al demonstrated the
fabrication of living cell arrays encapsulated within 3D
hydrogel elements by two methods: photo-patterning and
dielectrophoretic force electro-patterning [48]. Salmaso et al
utilized thermoresponsive polymers as functional alternatives
4
J. Micromech. Microeng. 23 (2013) 033001
(a)
(a)
Topical Review
(b)
(c)
(b)
Figure 2. Characteristic polymer porous monoliths used in microfluidics: (a) reprinted with permission from [58], (b) reprinted with
permission from [60], (c) reprinted with permission from [64].
onto an ensemble of 1 mm diameter PS beads. For the
fabrication of hydrogel pillars, a polyethylene glycol (PEG)based photo-crosslinkable prepolymer solution (MI-1) and a
photo-initiator solution (PIR-1) have been used [54].
Hydrogels’ main advantage is that they can provide
autonomous flow control within microfluidic channels as there
is no requirement for external control due to their ability to
undergo drastic changes in the volume in response to their
surrounding environment. However, it is not always easy
to integrate hydrogel materials into microfluidics and the
preparation of large amount of samples is time-consuming
as the hydrogels are processed individually.
methacrylate-co-ethylene dimethacrylate) and poly(styreneco-divinylbenzene) stationary phases in monolithic format
by thermally initiated, free radical polymerization within
polyimide chips [59]. These chips were then used for the
separation of a mixture of proteins which was monitored by
UV adsorption.
Yang et al combined two technologies, digital
microfluidics (DMF) and PPMs [60]. PPM disks were formed
in situ on DMF devices by dispensing droplets of monomer
solutions onto an array of electrodes followed by UVinitiated polymerization (figure 2(b)). The PPM disks were
used for preparative SPE with all fluidic handling steps
carried out by DMF. Yu et al developed porous polymers
by photo-initiated polymerization of acrylate monomers—
butyl methacrylate and ethylene glycol dimethacrylate—
in porogenic solvent of methanol [61]. It was found that
the pore size of the polymers is greatly affected by UV
intensity, fraction of initiator, fraction of crosslinking agent
and porogen concentration. Satterfield et al developed UVinitiated methacrylate-based PPMs for microfluidic trapping
and concentration of eukaryotic mRNA [62]. Their PPMs are
cast-to-shape and are tunable for functionalization using a
variety of amine-terminated molecules.
He et al demonstrated a highly reproducible way to prepare poly(2-hydroxyethyl methacrylate–ethylene dimethacrylate) monolithic beds within microchannels by photo-initiated
polymerization [63]. Kang et al established the in situ synthesis and use of PPM columns in an integrated multilayer
PDMS/glass microchip for microvalve-assisted on-line microextraction and microchip electrophoresis (figure 2(c)) [64].
Under the control of PDMS microvalves, the grafting of
the microchannel surface and in situ photo-polymerization
of poly(methacrylic acid-co-ethylene glycol dimethacrylate)
monolith in a defined zone were achieved.
Monoliths have also been successfully integrated to
microfluidics for the extraction and analysis of DNA from
biological samples. Polymer monoliths’ main advantage is
the ease of fabrication in microfluidic systems by in situ
polymerization. However, polymer monoliths do not have a
4.2. Porous monoliths
Porous monoliths are traditionally used in chromatography for
analytical or preparative purposes, e.g. solid-phase extraction
(SPE). While they have already been integrated into capillaries
far before the advent of microfluidics, the integration of porous
monoliths, in particular into polymeric microfluidic systems,
poses a number of additional challenges. Apart from the
synthesis procedure itself, common issues are the crosslinking
and reagent compatibility with the (polymeric) channel walls
as well as post-synthesis washing strategies suitable for
branched capillary networks typical for microfluidic lab-ona-chip devices.
Svec has comprehensively reviewed the history of
porous polymer monoliths (PPMs), their functionalities and
applications in microfluidic devices [55]. The specific research
field is widely extended with a great variety of applications
as sorbent materials [56, 57]. Stachowiak et al proposed a
simple method that features UV-initiated reactions mediated
by benzophenone [58]. First, the surface of COC channel walls
is photo-grafted with a thin interlayer polymer and then the
monolith is prepared in situ via UV-initiated polymerization.
Using this method, significant improvement in adhesion of
the monoliths to the plastic devices is achieved (figure 2(a)).
Levkin et al has reported the preparation of poly(lauryl
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
(a)
(b)
(a)
(c)
(b)
(c)
Figure 3. Characteristic membranes used in microfluidics: (a) reprinted with permission from [67], (b) reprinted with permission from [69],
(c) reprinted with permission from [70].
Cancer marker proteins have been electrophoretically
concentrated and then separated in a microfluidic device
by Nge et al by using an ion-permeable membrane
[67]. On-chip preconcentration was achieved using this
membrane which consists of acrylamide, N,N -methylenebisacrylamide and 2-(acrylamido)-2-methylpropanesulfonate.
This negatively charged membrane was in situ photopolymerized near the injection intersection (figure 3(a)).
Baxamusa and Gleasondemonstrated that copolymerization
of hydrophilic and hydrophobic polymers (HEMA and PFA,
respectively) results in a dynamic surface composition in
which the hydration state of the surface determines the
surface reconstruction [68]. Nearingburg and Eliasmade use
of photo-polymerizable proton exchange membranes for
microfluidic fuel cell applications [69]. Membranes are formed
from blending poly(ethylene glycol) diacrylate (PEGDA)
and sulfonated poly(ethylene glycol) phenyl ether acrylate
(sPEGPEA). These PEGDA–sPEGPEA blends were produced
through free radical photo-polymerization within PDMS
microchannels as well as on plain glass slide and were shown
to be easily processed into thin membranes using techniques
which are compatible with the fabrication of microfluidic fuel
cell devices (figure 3(b)).
Finally, micro-capillary film (MCF) membranes were
proposed for separations by Bonyadi and Mackley [70]. These
high surface area compared to many sorbent materials, but they
can be used at very high flow rates. Vázquez and Paull reviewed
the state of the art in this area in the application of monolithic
materials and related porous polymer gels in microfluidic
devices for the period 2005–2010 [65]. This review has focused
on monolithic materials prepared in channels of microfluidic
devices used in advanced applications.
4.3. Membranes
Membrane separations are popular due to the low cost of
their manufacture. Common membrane separation processes
include gas separation, pervaporation, electrolysis, dialysis,
reverse osmosis and micro-, ultra- and nanofiltration.
Separation is achieved by differentially permeable membranes
as a result of applied pressure head, electric field or
concentration gradient. The required membrane properties
depend on particle size (distribution) and/or the separation
mechanism. Based on their structure, the most common types
of membranes are thin-film composite membranes (for gas
separation or reverse osmosis) and porous membranes (for
filtration of larger molecules). Jong et al reviewed a broad
scope of fabrication methods for the integration of membranes
in microfluidic devices. In this review paper the membrane
properties have been specially reported [66].
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
(a)
(A)
(C)
(c)
(b)
a
(B)
b
(D)
(a)
c
(b)
Figure 4. Characteristic paper microfluidic devices: (a) reprinted with permission from [72], (b) reprinted with permission from [75], (c)
reprinted with permission from [80].
MCFs display a number of embedded hollow capillaries and
can be considered as hybrid geometry between flat sheet
and hollow fibers (figure 3(c)). They were produced using
ethylene vinyl alcohol copolymer through a solution-phase
extrusion followed by nonsolvent induced phase separation.
Compared to the conventional membrane geometries, MCFs
provide a higher surface area per unit volume, greater
mechanical strength, ease of handling and more efficient
module fabrication.
Summarizing, the great advantages are the simplicity in
their integration to microfluidic systems and the variety of
the available membrane materials and morphologies, making
them appropriate for very specific applications. Except from
separation applications, membranes can also be utilized for
reagent transport into a reaction chamber in a controllable
manner.
of microfluidic devices in paper (figure 4(a)). This method,
called FLASH (Fast Lithographic Activation of Sheets),
utilizes photolithography which only requires a UV lamp
and a hotplate [72]. Li et al introduced a new method for
making microfluidic patterns on a paper surface using plasma
treatment. The technique employed specific agents to locally
hydrophobize the sheet, which is then exposed to plasma
through a mask to form a variety of wicking patterns on highly
flexible paper substrates [73, 74]. The same group extended
their research in combining this paper sizing chemistry with
digital ink jet printing to produce low-cost, membrane-based
sensors (figure 4(b)) [75].
Klasner et al fabricated paper-based microfluidic devices
from a novel polymer blend using photolithography for the
monitoring of urinary ketones, glucose and salivary nitrite
[76]. Fu et al reported the capabilities of 2D paper networks
with multiple inlets per outlet [77]. They demonstrated the
controlled transport of reagents within paper devices and,
more specifically, methods of flow control by tuning the
geometry of the network and embedding dissolvable barriers.
Weigl et al fabricated a hydrostatic pressure-driven, disposable
microfluidic detector card based on the T-sensor (diffusionbased detection). This device combines the ease of use of a
paper test strip with the versatility of a microfluidic system
[78].
Hwang et al reported the active control of the capillarydriven flow in paper using a centrifugal device. They managed
to integrate a paper strip into a disk-shaped centrifugal
microfluidic platform and rotated it with various spin speeds
to characterize the flow in the paper under different strength
of the centrifugal force [79]. Godino et al improved capillary
flow control by integrating paper sectors in lab-on-a-disk to
4.4. Paper microfluidics
There has been a decade-long tradition of paper membranes
as substrates of commercially very successful (immunochromatographic) lateral flow assays (test strips). These
mostly wicking-based devices are of interest due to
their comparatively low cost of material, fabrication and
instrumentation as well as their ease of use, making them
amenable to patient self-testing. Nevertheless, paper-based
devices exhibiting miniaturized features have only rather
recently been introduced into the microfluidics community.
In 2007, Martinez et al reported a paper-based
microfluidic device performing the simultaneous detection
of glucose and protein in urine [71]. The same research
group introduced a rapid method for laboratory prototyping
7
J. Micromech. Microeng. 23 (2013) 033001
a
Topical Review
(a)
b
(b)
(a)
(c)
Figure 5. Organic electronic devices used in microfluidics: (a) reprinted with permission from [87], (b) reprinted with permission from [88],
(c) reprinted with permission from [90].
leverage advanced functionality such as blood separation,
liquid recirculation, liquid routing and valving (figure 4(c))
[80]. Recently, the same research group presented lowresource fabrication and assembly methods for creating
disposable amperometric detectors in hybrid, paper–polymer
devices [81].
Colorimetric assays for ketones and nitrite were adapted
from the dipstick format to this paper microfluidic chip for
the quantification of acetoacetate in artificial urine, as well as
nitrite in artificial saliva. Leung et al succeeded in detecting the
presence of adsorbed polyvinylamine or potassium polyvinyl
sulfate in paper-based microfluidic devices via the streaming
potential relating to the surface charge density and the flow
rate [82]. Delaney et al combined paper microfluidics with
electrochemiluminescent detection. Inkjet printing is used to
produce paper microfluidic substrates which are combined
with screen-printed electrodes to provide disposable sensors
which can be read without a traditional photodetector or a
mobile camera phone [83].
integrated, highly sensitive, low-cost and compact lab-on-achip devices. Their main applications include monolithically
integrated fluorescence detection schemes.
Someya et al combined microfluidic flow channels,
defined by surface energy differences, with thin-film organic
field-effect transistors [84]. For a specific choice of
semiconductors, the device performance turned out to be
stable with water flowing over the channel region and the
contacts protected by hydrophobic surface films. This provides
evidence that organic semiconductors are not necessarily
degraded by water even when carrying current. Goud et al
demonstrated an organic substrate compatible microneedle
integration technology for biosystem-on-package applications
R
[85]. This
based on two-photon polymerization of Ormocer
hybrid, organic–inorganic material has attracted great interest
in the medical device community because it is nontoxic and
biologically inert. Vannahme et al presented a fabrication
scheme to integrate multiple organic semiconductor laser light
sources into a PMMA chip intended for the excitation of
fluorescent markers of biological samples. In this parallel
process, the topology of both photonic and fluidic structures is
defined by thermal nanoimprinting (figure 5(a)) [86, 87]. Lee
et al introduced a polymer optical backplane for luminescence
detection within microfluidic PDMS chips using large core
polymer waveguides from polyurethane and vertical couplers
(figure 5(b)). The waveguide fabrication realized through a
4.5. Organic electronics
Another category of functional materials are organic (semi-)
conductors to transduce ambient chemical information to
electronic signals. Introduction of organic electronic materials
in polymer microfluidics bears the promise for highly
8
J. Micromech. Microeng. 23 (2013) 033001
Topical Review
new process combining mechanical machining and vapor
polishing with elastomer microtransfer molding. Using this
platform fluorescein detection via fluorescence intensity and
phosphorescence lifetime-based oxygen detection in water
in an oxygen controllable microbial cell culture chip is
demonstrated [88].
Pais et al demonstrated a high-sensitivity, disposable
lab-on-a-chip with a thin-film organic light-emitting diode
(OLED) excitation source and an organic photodiode (OPD)
detector for on-chip fluorescence analysis. Detection of
Rhodamine 6G and fluorescein dyes at concentrations of
100 nM and 10 μM, respectively, has been achieved by using
an NPB/Alq3 thin-film green OLED as the excitation source
and a copper phthalocyanine–fullerene (CuPc/C60) thin-film
OPD as a photodetector [89].
Moreover, Hofmann et al used CuPc/C60 photodiodes to
monitor a peroxyoxalate-based chemiluminescence reaction
within a PDMS microfluidic device [91]. The same research
group developed high-quality integrated microchip filters by
incorporating lysochrome dyes directly into the microfluidic
chip substrate, thereby providing a fully integrated system
that obviates the common need for off-chip optical filters
(figure 4(c)) [90].
Figure 6. Schematic of the presented surface modification
techniques.
Also direct patterning, e.g. by droplet deposition (spotting),
laser writing/local crosslinking through illumination or simple
application by plasma or felt pen, has been applied. In figure 6,
a schematic of the set of the techniques presented in the current
review paper is shown.
5.1. Global deposition techniques
5. Surface modification of polymeric substrates
5.1.1. Plasma activation. Plasma processing and nanotexturing allows control of both surface chemistry and
topography/texture [93–95]. During the plasma treatment, the
physico-chemical nature of the polymer surface is changed
due to oxidation, degradation and crosslinking. These fast and
homogeneous processes induce structural changes within a
depth of a few molecular layers, while maintaining the properties of the bulk. The efficiency of plasma activation processes
depends on several factors such as type/composition of the
substrate material and the gas(es), (partial) pressure, power
and exposure time in the plasma chamber [96, 97].
Common oxygen (O2) gas induces the formation of
hydrophilic groups on the surface. However, the hydrophilic
nature of these surfaces is transient as they quickly revert back
to their native hydrophobic state. While such surfaces display
hydrophobic recovery, Tsougeni et al have demonstrated that
plasma nanotextured surfaces may withstand such recovery
for a period of more than a month [98]. The researchers
have found that the surface morphology and wettability of
PDMS, an example of Si-containing polymers, can be tailored
on demand [99]. Specifically, the surface topography can be
tuned to acquire the desired magnitude of surface roughness
and periodicity in the nanometer and sub-micrometer regime,
respectively.
Vourdas et al proposed a plasma-based technology for
microfluidic fabrication and surface modification [100]. They
utilized anisotropic O2 plasma to etch PMMA in situ via
a highly etch resistant photoresist which contains silicon.
O2 plasma alters the character of the processed polymer
surface, making it rough and very hydrophilic. He et al
proposed a technology which is based in incorporating a
superhydrophobic coating in nanostructured capillary valves
[101]. To this end they employed polyaniline nanofibers
Several coating methods have been developed so far to
engineer the wettability of polymeric microfluidic devices.
Common techniques include vapor-, plasma- and liquid-phase
techniques. These techniques result in different levels of
process control, layer thickness uniformities, and bring about
certain restrains about the topology of surfaces to be coated.
Surface treatments can lead to deposition of new and/or
conversion of native surface layers. Pre-made coating might
dry after deposition or may be dynamically applied during
priming with the process liquids. Coatings might also be in situ
synthesized and physisorb or chemically link to the underlying
surface. Solution-phase deposition techniques often spread the
liquid across the substrate surface by spin coating, spraying
or pumping through channels. Various classes of materials
may be deposited; amongst them are organic materials (e.g.
Teflon, silanes, sol–gels and various surfactants), bio-layers
(e.g. proteins and nucleic acids) and even thin glassy layers
[92]. Typical functions of the surface layers are the definition
of contact angle, provision of functional groups for surface
immobilization (of molecular capture probes), suppression of
non-specific absorption/biofouling, establishment of barrier
properties to prevent swelling/dissolution, gas permeability,
tuning of optical and thermal properties, dirt protection and
scratch resistance.
We will commence this section with techniques
to induce the formation of uniform layers across the
substrate. Depending on the required resolution, local
deposition techniques may either be derived from the
global functionalization schemes such as spray coating or
plasma treatment through shadow or contact masks, or
designated pattern transfer techniques such as screen printing,
microcontact printing or photolithographically guided lift-off.
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J. Micromech. Microeng. 23 (2013) 033001
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5.1.2. Chemical vapor deposition. CVD represents a
versatile technique for the formation of thin-film coatings from
a diversity of materials. Solvent-free, vapor-phase deposition
enables the integration of thin films or nanostructures into
micro- and nanodevices for improved performance [106].
Among CVD techniques, plasma-enhanced CVD (PECVD)
attracts the greatest interest toward polymeric microfluidic
modification. In PECVD of polymers, the plasma gas, which
may or may not be reactive, is used as the process initiator.
Films generated by PECVD offer several advantages over films
produced by conventional polymerization. These thin layers
are highly coherent and adherent to a variety of substrate
films and may be prepared from monomers, which cannot
be polymerized by conventional means.
Yoshida et al surveyed a range of surface modification
methods based on CVD [107]. For instance, Chen
and Lahannreported a surface modification method for
the fabrication of discontinuous surface patterns within
microfluidic systems [108]. The method is based on CVD
of a photo-definable coating, poly-(4-benzoyl-p-xylyleneco-p-xylylene), onto the luminal surface of a microfluidic
device followed by a photo-patterning step to initiate spatially
controlled surface binding.
Riche et al modified the inner surfaces of several preassembled PDMS microfluidic devices with thin layers of
fluoropolymer coatings via initiated CVD. The fluorinated
coating consists of 1H,1H,2H,2H-perfluorodecyl acrylate
(PFDA) crosslinked with ethylene glycol diacrylate (EGDA),
resulting in a poly(PFDA-co-EGDA) coating that features
low surface energy [109]. They studied the ability of using
the aforementioned coatings to prevent absorption of small
molecules and to resist swelling in the presence of organic
solvents such as hexane droplets. Dudek et al reported the
evaluation of a repertoire of surface modifications, including
PECVD of silicon dioxide (SiO2) for the formation of
a hydrophilic surface on COP-based microfluidic devices
[110]. The oxygen/argon PECVD of SiO2 was found to
yield a relatively stable, uniform and reproducible surface
modification with low hydrophobicity and was shown to
give highly reproducible lateral flow characteristics of the
micropillar device.
Moreover, Gandhiraman et al reported the functionalization of COP through PECVD plasma by depositing reactive amine coatings (APTES and ethylenediamine
(EDA)), diethylene glycol dimethyl ether (DEGDME),
3-mercaptopropyltrimethoxysilane (MPTMS) [111, 112].
Eichler et al used microplasma-activated CVD to selectively
deposit hydrophobic and hydrophilic coatings on a Y-shaped
fluidic mixer. By using tetramethyl-silane (TMS) (hydrophobic) and tetraethoxysilane (TEOS) or SiH4 (hydrophilic) coatings in the branching zone, a lateral gradient in surface free
energies is provided and the Y-shaped fluidic mixer can be
turned into a separator for multiphase fluids (figure 8) [113].
Another commonly utilized technique for the deposition
of thin amorphous, polycrystalline and epitaxial films is hotwire CVD (HWCVD) [115]. Joshi et al demonstrated a novel
dry method of surface modification of SU-8 using HWCVD
which is compatible with standard microfabrication techniques
(a)
(b)
Figure 7. Aqueous droplets in (a) pristine and (b) fluorinated
PMMA microchannels with different advancing (dotted square) and
receding (dotted circle) menisci. Reprinted with permission from
[102].
along with an essentially amorphous fluorine coating.
More specifically, they first used O2 plasma in order to
activate the inert PMMA followed by polyethyleneimine
(PEI) coating, an amine-containing functional polymer.
Subramanian et al reported a simple surface modification
procedure for polymeric droplet microfluidic devices that
leads to the generation of stable aqueous droplet trains in
a continuous liquid–liquid segmented flow system (figure 7)
[102]. The general strategy involved an O2 plasma treatment
that introduced hydroxyl groups onto the polymer surface,
used as a functional scaffold to which silanizing reagents were
covalently attached to. Using this two-step procedure, they
hydrophobized PMMA, COC and PC surfaces.
Maheshwari et al studied the functionalization of PDMS
surfaces after plasma oxidation and subsequent reaction with
branched-PEI [103]. The thin films of branched-PEI formed
on the surface exhibit high resistance to hydrophobic recovery
in air. Roy and Yuestudied how argon (Ar), nitrogen (N2)
and O2 plasma treatments modify COC surfaces [104]. They
realized platelet-adhesion experiments which revealed that the
plasma-modified surfaces are more hemocompatible. Among
the Ar, O2 and N2 treatments investigated, the N2 plasma
process rendered the modified COC surface to be the most
hydrophilic and hemocompatible. With respect to Ar, the
O2 plasma process turned out to be superior in conferring
greater wettability, higher roughness, higher thermal bond
strength and improved hemocompatibility. Wang et al
combined air-plasma treatment with subsequent silanization
by 3-aminopropyltriethoxysilane (APTES) and o-[(Nsuccinimdyl)succiny]-omethyl-poly(ethylene glycol) (NSSmPEG) grafting onto a PDMS microchip surface [105].
The modification procedure was carried out in aqueous
solution in absence of organic solvent. The NSS-mPEG side
chains displayed extended structure and created a non-ionic,
hydrophilic layer of polymer brushes on the PDMS surface,
which can effectively prevent the adsorption of biomolecules.
Table 1 summarizes the characteristics of the aforementioned
plasma treatment-based technologies.
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Table 1. Characteristics of plasma treatment techniques in polymer microfluidics.
Research group
Polymeric substrate
Type of gas and contact angle
◦
O2, 5
C4F8, 153◦
Tserepi et al [99]
PDMS
O2, 5◦ Teflon-like coating + O2, ∼140◦
Vourdas et al [100]
PMMA + Si-containing O2, 5◦
photoresist
He et al [101]
PMMA
O2 + CYTOP, 120◦
O2 + CYTOP-polyaniline, 170◦
Subramanian et al [102] PMMA, COC, PC
O2 + heptadecafluoro-1,1,2,2tetrahydrodecyl trichlorosilane
(HFTTCS), 145◦
Maheshwari et al [103] PDMS
O2, ∼8◦
O2 + bPEI, 32◦
Roy and Yue [104]
COC
O2, 7◦ Ar, 10◦ N2, 3◦
Wang et al [105]
PDMS
Air + APTES, 106◦ Air + APTES + mPEG, 64◦
Tsougeni et al [98]
PMMA, PEEK
Stability of the coating
20 days (PMMA), 60 days (PEEK)
Months to years
Not evaluated
Not evaluated
Not evaluated
Not evaluated
85% recovery after 5 days
Stable for ∼5 days
Not evaluated
4 weeks
Table 2. Characteristics of CVD techniques in polymer microfluidics.
Research group
Polymeric substrate Deposited material
Stability of the coating
Chen and Lahann [108]
Riche et al [109]
Dudek et al [110]
Gandhiraman et al [111, 112]
Eichler et al [113]
Joshi et al [114]
PDMS
PDMS
COP
COP
PC, COC
SU-8
Not evaluated
Not evaluated
27 weeks
Not evaluated
20 days
Not evaluated
Poly-(4-benzoyl-p-xylylene-co-p-xylylene)
Poly(PFDA-co-EGDA)
SiO2
APTES, APTES + EDA, DEGDME, MPTMS
HMDSO, TMS, TEOS, SiH4
Amine groups due to the pyrolytic dissociation of ammonia
Short-wavelength radiation in this range can be applied to
the surface modification of fluorocarbon polymers, which
are faintly sensitive to the UV light used in conventional
photochemistries.
Because the photon energy is sufficient to excite and
dissociate various chemical bonds, including C–F bonds,
free radicals form on VUV-irradiated polymer surfaces. Such
radicals successively react with activated oxygen species
which are simultaneously generated through the photoexcitation of atmospheric oxygen molecules. Consequently,
oxidation and etching of polymer surfaces proceed efficiently
under VUV exposure, even on inert fluorocarbon polymers
[118]. Fluorocarbon polymer modification has been conducted
until now by employing UV excimer lasers. Alternatively,
low-intensity sources including mercury lamps at 185 nm,
Xe (147 nm) and Kr (123.6 nm) resonance lamps, and excimer
lamps at 126 nm (Ar2), 146 nm (Kr2), 172 nm (Xe2), 222 nm
(KrCl) and 308 nm (XeCl) can be used.
Schütte et al developed a method for long-term stable
chemical biofunctionalization of COC surfaces in microfluidic
devices by means of mask-patterned UV irradiation [119]. This
method is compatible with upscale to production techniques
such as injection molding and bonding (figure 9). It solves the
problem of the inherently poor compatibility of biomolecules
with common microfabrication procedures as it allows for
the biofunctionalization step to be performed after complete
assembly of the microsystem. Specifically, injection molded
COC microfluidic chips were modified by irradiating the
surface with UV light at low wavelengths (180–190 nm). In
this spectral range, acidic groups are created on the polymer
surfaces that are available for patterned protein binding and
cell adhesion. Pfleging et al modified PS substrates performing
Figure 8. Image of the Y-shaped mixer; the hydrophobically coated
area (lower branch) is not wetted by colored water. Reprinted with
permission from [113].
[114]. As the process relies on the modification of surface
epoxy groups, essentially all polymers containing such groups
may be treated in the same fashion with similar results. In
table 2, the deposited materials by CVD methods as well as
the polymeric substrates used are synoptically presented.
5.1.3. UV irradiation. Modifications of polymer surfaces
can also be induced by laser irradiation. However, commercial
applications are often hindered by the high cost of suitable
lasers. In many cases, low-intensity UV and VUV (vacuum
UV) lamps can modify large areas at considerably lower
costs. Among the various light sources available, VUV light,
whose wavelength is much shorter than 200 nm, is of
particular interest for polymer surface processing [116, 117].
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
(a)
(b)
Figure 10. SEM images of (a) cross-sections of (i) uncoated and (ii)
glass-coated PDMS channels, (b) comparison of diffusion of
Rhodamine B for (i) and (ii) PDMS channels respectively. Reprinted
with permission from [125].
[124]. Such sol–gel coatings, for instance, provide good
protection against aggressive solvents and invigorate the
corrosion resistance of industrial parts. Unlike glass, they can
be deposited and cured at room temperature.
Yang et al demonstrated a micro-free-flow isoelectric
focusing with a TEOS coating in a PDMS microchannel [126].
They used dynamic coating of SiO2 on a PDMS microchannel
and an electrode surface with minimum EOF and electrode
degradation. The glass coating on the electrodes and PDMS
surface improves the bonding strength, chemical resistance
and durability for reuse. Also, Abate et al used sol–gel
chemistry in order to coat PDMS channels (figure 10(a))
to greatly increase the chemical resistance of the channels.
Figure 10(b) shows that the coated PDMS channel blocks the
diffusion of Rhodamine B, only leaving a light residual layer
of dye on the surface of the coating. This method combines
the ease of fabrication afforded by soft lithography with the
chemical robustness and surface modification afforded by
glass. For the sol–gel chemistry, they resorted to TEOS and
methyltriethoxysilane (MTES) as precursors [125].
Roman and Culbertson developed several coatings of
PDMS microchannels using transition metal sol–gel chemistry
[127]. The channels were created using soft lithography and
three metal alkoxide sol–gel precursors were investigated:
titanium isopropoxide, zirconium isopropoxide and vanadium
triisobutoxide oxide. The metal alkoxides diffused into the
sidewalls of a PDMS channel and subsequently hydrolyzed
in the presence of water vapor. This procedure resulted in the
formation of durable metal oxide surfaces: titania, zirconia
or vanadia. In table 4 the deposited materials using sol–gel
chemistry are briefed.
Figure 9. Process scheme applied for patterned surface
biofunctionalization in microfluidic devices by UV irradiation and
subsequent binding of ECM proteins and Pluronic F-127. Reprinted
with permission from [119].
excimer laser irradiation at 193 nm with respect to applications
in microfluidics and cell culture [120].
Nagai et al presented the application of photo-induced
superhydrophilicity of titanium dioxide (TiO2) to microfluidic
manipulation [121]. Moreover, they found a new phenomenon
for reversibly converting the surface wettability using a PDMS
matrix and the photo-catalytic properties of TiO2. A UVirradiated PDMS polymer induced an immediate increase in
the water contact angle on a closely placed TiO2 surface. This
photo-induced wettability conversion, named opto-switching
valve, was demonstrated on a centrifugal disk and continuously
changed the flow direction in a PDMS multi-branched
microchannel network.
Hozumi et al used a 172 nm Xe2 VUV excimer lamp to
hydrophilize a PMMA surface [122]. This study has focused
on the effects of atmospheric pressure during VUV irradiation.
Each of the substrates was exposed to VUV light under a
pressure of 10 Pa, 10 kPa or 100 kPa. The same research group
has also studied the photochemical surface modification of PS
substrates using 172 nm VUV light [123]. The group reported
a very hydrophilic PS surface compared to conventional UV
light sources with wavelengths longer than 200 nm, making it a
powerful technique for polymer surface modification. Table 3
sums up the above UV irradiation techniques.
5.1.4. Sol–gel chemistry. By virtue of their low reaction
temperature and easy control of porosity to allow ion transport,
sol–gel chemistries are widely used as thin-film coatings
5.1.5. Dynamic coatings. Dynamic coating represents a
rather convenient way of surface modification in microfluidic
12
J. Micromech. Microeng. 23 (2013) 033001
Topical Review
Table 3. Characteristics of UV irradiation techniques in polymer microfluidics.
Research group
Polymeric substrate
Wavelength (nm)
Stability of the coating
Schütte et al [119]
COC
185
Pfleging et al [120]
PS
Nagai et al [121]
Hozumi et al [122, 123]
PDMS
PMMA, PS
Laser: 193 Mercury
lamp: 185
248
172
Acid groups’ density decrease
to 25% within 19 weeks
Not evaluated
Not evaluated
PMMA: not evaluated
PS: only 100 kPa remains stable after 30 days
Table 4. Characteristics of sol–gel techniques in polymer microfluidics.
Research group
Polymeric substrate
Deposited material
Stability of the coating
Yang et al [126]
Abate et al [125]
Roman and Culbertson [127]
PDMS
PDMS
PDMS
Glass layer from TEOS
Glass layer from TEOS and MTES
Glass layer from isopropoxide, zirconium
isopropoxide and vanadium triisobutoxide oxide
No available data
devices [128]. In a typical dynamic coating process, surfactant
solutions are pumped at a certain constant speed through
the channel and physisorb to the channel surface. However,
dynamic surface modification is not preferred because
of eventual desorption from the polymer surface which
necessitates that they have to be added to the running buffer
and/or sample. In addition, caution must be taken to avoid
structure alternation or damage to protein analytes by the
surface modifiers.
Lin et al modified PMMA microchannels by using
PEO and PVP dynamic coatings in order to prevent DNA
adsorption on the channel wall of PMMA chips [129]. In
this work, it was found that dynamic PEO and PVP coating
of PMMA microchannels is acceptable when conducting the
separation using PEO solutions containing gold nanoparticles
(GNPs). This is partially because GNPs are more stable in
the two polymer solutions when compared to others such as
cellulose derivatives and linear poly(acrylamide). By using a 2(PEO–PVP)–PEO(GNP) PMMA chip, the separation of DNA
markers V and VI by capillary electrophoresis using 0.75%
PEO(GNP) was accomplished on a short time scale (3 min).
Luo et al presented a method for improving the EOF in a PDMS
separation channel by combining prepolymer additives with a
dynamic coating [130]. They observed that the addition of a
carboxylic acid to the prepolymer prior to curing does not
significantly change the hydrophobicity of the PDMS surface.
However, it is possible to combine the modified PDMS with
a dynamic coating of n-dodecyl β-D-maltoside (DDM), which
prevents protein sticking.
Sikanen et al developed a rapid and simple dynamic
coating method for the immobilization of PEG stabilized
phosphatidylcholine lipid aggregates for microfluidic chips
made from SU-8, PDMS and glass [131]. The biofouling
resistance provided by the PEGylated phospholipid coating
was evaluated by monitoring the interactions between BSA
and the coated surfaces. Jankowski et al presented a scheme
which prevents both static and dynamic wetting of PC by
aqueous solutions including viscous, non-Newtonian solutions
of polymers such as alginate [132]. The procedure uses
(a)
(b)
Figure 11. Pictures of the air–water interface in COC channels:
(a) untreated channel; (b) HEC-treated channel. Reprinted with
permission from [133].
dodecylamine, which is a 12-carbon long primary amine.
The amine group reacts with the carbonate group to create a
urethane bond. The dodecylamine modified channels allow for
stable droplet formation, even of viscous and non-Newtonian
aqueous solutions of polymers. Zhang et al used hydroxyethyl
cellulose (HEC) as dynamic coating for protein separation in
COC microfluidic devices. The coating significantly enhances
the hydrophilicity of the COC surface and also induces a 72%
drop in electroosmotic mobility and a significant reduction
in protein adsorption on the channel wall (figure 11) [133]. In
table 5 the above surfactants applied in polymeric microfluidic
devices are resumed.
5.2. Local deposition techniques
Local deposition techniques have been used mostly for the
introduction of hydrophobic patches into polymeric channels.
This field can be divided into serial writing techniques (felt
pen, laser printing) on the one hand and mask-based on the
other.
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J. Micromech. Microeng. 23 (2013) 033001
Topical Review
Table 5. Characteristics of dynamic coating techniques in polymer microfluidics.
Research group
Polymeric substrate
Surfactant
Stability of the coating
Lin and Chang [129]
Luo et al [130]
Sikanen et al [131]
Jankowski et al [132]
Zhang et al [133]
PMMA
PDMS
PDMS, SU-8
PC
COC
PEO, PVP
n-dodecyl β-D-maltoside (DDM)
PEG stabilized phosphatidylcholine lipid
Dodecylamine
HEC
Not evaluated
Excellent reproducibility of EOF
SU-8: reproducibility of EOF after 3 days
Excellent reproducibility after 4 days
Not evaluated
5.2.1. Serial writing. Among serial writing approaches,
wetting the tip of a felt pen with a hydrophobic solution
and ‘writing’ the coating into the channels yielded the
most satisfying results for prototyping. Steigert et al
applied hydrophobic fluoropolymer-based solutions at specific
positions in a given channel. An accurate positioning of these
patches is often decisive for the hydrophobic flow control in
the channel network, in particular in centrifugal microfluidics
[27]. Do Lago et al proposed a dry process using a laser
printer to selectively deposit toner on a polyester film, which
is subsequently laminated against another polyester film. The
toner layer binds the two polyester films and allows the blank
regions to become channels for microfluidics [134]. Riegger
et al presented a method for the hydrophobic patterning of
microfluidic chips with fluoropolymers (Teflon-carbon black)
which is demonstrated by the fabrication of hydrophobic
valves via dispensing. This coating created superhydrophobic
surfaces on COC substrates and increased the burst pressures
of hydrophobic passive valves [135].
5.2.2. Mask-based techniques. Patrito et al presented a
method for the surface modification of PDMS to promote
localized cell adhesion and proliferation. Thin metal films
are deposited onto PDMS through a physical mask in the
presence of gaseous plasma which generated topographical
and chemical modifications of the polymer surface. Removal
of the deposited metal exposes roughened PDMS regions
enriched with hydrophilic oxygen-containing species [136].
Oliveira et al proposed a method to produce a potential open
microfluidic polymeric device. They fabricated biomimetic
superhydrophobic surfaces on PS using phase separation
substrates by exposing the surface to plasma or UV–ozone
radiation. The ability of superhydrophilic paths to drive liquid
flows in a horizontal position was found to be significantly
higher than for the case of hydrophilic paths patterned onto
smooth surfaces [137].
Tsougeni et al combined photolithography, deep
anisotropic O2 plasma etching to pattern microchannels with
very rough bottom walls on PMMA and PEEK substrates.
Where desirable, the rough surfaces were hydrophobized
by means of C4F8 fluorocarbon plasma deposition step
through a stencil mask creating superhydrophobic patches
and hydrophilic stripes (figure 12) [138]. Selective protein
adsorption on rough hydrophilic stripes has been obtained by
this method [139].
Lai et al proposed a resin gas injection technique
for bonding and surface modification of polymer-based
microfluidic platforms. By applying the masking technique,
local modification of the channel surface can be achieved
through sequential resin gas injection. This approach also lends
(a)
(b)
(c)
(d)
(e)
(f )
(g)
(h)
(i)
(j)
Figure 12. (a)–(h) Snapshots of a red dye–water solution in a
PMMA microchannel with integrated superhydrophobic,
hydrophobic and superhydrophilic stripes, (i) optical microscope
image of the microchannel with the variable wetting characteristics
and ( j) the respective water contact angles. Reprinted with
permission from [138].
14
J. Micromech. Microeng. 23 (2013) 033001
Topical Review
Figure 13. Comparison between traditional masking method for achieving hydrophilic surface patterning and PCT methods to induce
hydrophobic recovery. Reprinted with permission from [141].
Concluding, the eventual choice of the integrated
materials needs to be viewed in the light of the specific target
application, the fabrication and assembly technology as well
as cost issues.
Regarding the modification methods applied in polymeric
microfluidics for wettability control, we specifically analyzed
a range of schemes for uniform modification of substrates
in view of their prospective applications. The choice of the
modification method which can be applied mainly depends on
the requirements on long-term stability as well as cost issues
and equipment availability.
itself to form a layer of crosslinked polyacrylamide gel on
the walls of the microchannel, serving as a sieving material
for DNA separation by electrophoresis [140]. Alternatively,
Guckenberger et al proposed a method to induce controlled
hydrophobic recovery by applying repeatable physical contact
treatment (PCT) with common laboratory applicators such
as brushing with wipers or peeling with tapes [141]. PCT
was shown to be robust for three different sample materials,
inducing hydrophobic recovery in both PS and COP, and
accelerating hydrophobic recovery in PDMS before natural
hydrophobic recovery occurred. Figure 13 depicts the PCT
method in comparison with the conventional mask-based
method.
• Amongst various plasma treatment techniques, oxygen
plasma is most extensively used for the formation of
hydrophilic surface groups. Even though the plasmainduced hydrophilic nature of these surfaces is of transient
character, studies toward improving the stability of plasma
treated surfaces are very promising, as presented in
section 5.1.1.
• PECVD provides highly homogeneous thin films and
may be prepared from monomers, which cannot be
polymerized by conventional means. PECVD coatings
are stable and can be applied to a variety of substrates
but special equipment is needed.
• UV and VUV irradiation can modify large areas at
considerably lower costs. However, these techniques
require designated equipment, especially at short
wavelengths.
• The main advantage of sol–gel technologies is that they
provide chemical resistance to microfluidic devices, even
if they have not been used extensively and mainly on
PDMS devices.
• A major drawback of the conceptually rather simple
dynamic surface coating is the eventual desorption from
the polymer surface, which necessitates that surfactants
are added to the running buffer.
6. Conclusions
In this paper we have outlined the most common materials and
associated processes to enhance the functionality of polymeric
microfluidic systems. Typical materials are hydrogels, porous
monoliths, membranes, paper and organic electronics.
• Hydrogels represent a promising class of materials for
passive valving based on designated physico-chemical
stimuli such as heat, radiation and pH change.
• Porous monoliths and membranes are the dominant
materials for separation technologies.
• Paper represents a relatively new material for integration
into microfluidic systems, offering strong application
potential when cost-efficiency paired with low demands
on lab infrastructure are paramount.
• Organic electronics have so far been rarely explored in
the context of microfluidics and their main advantage is
that the high quality of the integrated components can
lead to the development of high-sensitivity disposable
microfluidic devices.
15
J. Micromech. Microeng. 23 (2013) 033001
Topical Review
Regarding the local deposition techniques, the majority
of them derive from the global/homogeneous modification
methods such as plasma treatment, UV irradiation, CVD or
spin coating by using masks, so they can be considered as
a sub-category of global deposition techniques. A few direct
patterning techniques such as felt pen are mainly utilized on
prototyping purposes.
In conclusion, the field of modifying the surface
properties is of outstanding relevance to establish flow
control in polymeric microfluidic devices. The field has
significantly evolved and extensive research is still underway.
In particular the transition from prototyping to cost-efficient
mass manufacturing schemes is critical for commercialization.
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Acknowledgments
This work was funded in part by the ENIAC project
CAJAL4EU (120215-Cajal4EU Project), Enterprise Ireland
under contract number IR/2010/0002, the ERDF and the
Science Foundation Ireland under grant no 10/CE/B1821.
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