Special Report

Special Focus: Microfluidics

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Surface patterning strategies for

microfluidic applications based on
functionalized poly-p-xylylenes

Microfluidic systems require precise surface modification in order to tailor the interfacial properties. For instance,
in lab-on-a-chip research, defined surface chemistry is key to minimizing contamination and to increasing signal-
to-noise ratios for bioconjugation schemes. Device efficiency and analytical output can also be maximized with
devices that have defined surfaces. Similarly, minimizing biofouling is also crucial to suppress background noise and
ensure device functions. Once defined, surface properties have been engineered, microstructuring of surfaces can
provide defined microenvironments for cell-based culture systems. In this report, we highlight the use of functionalized
poly-p-xylylenes for surface modification with a specific focus on microfluidic systems. Functionalized poly-p-
xylylenes constitute a versatile group of reactive coatings that can provide a defined chemical makeup of substrate
surfaces irrespective of underlying bulk material properties. Recent advances using reactive coatings for surface
modification of microfluidics are introduced, including use as nonfouling coatings, fabrication of patterned surfaces,
functionalization of previously assembled devices, as well as device-bonding applications.

Miniaturized analytical systems have drawn injection molding or rapid prototyping, are Hsien-Yeh Chen1
attention in a broad range of scientific areas, available and have been extensively reviewed in & Joerg Lahann†2
such as chemistry, biology, material science the past [13–15] . The use of polymers, however, 1
Institute of Functional Interfaces,
and life science [1–4] . Microfluidic devices were does not eliminate the need for surface modi- Karlsruhe Institute of Technology,
Eggenstein-Leopoldshafen, Germany
initially made of glass, silicon or quartz, using fication; even more so, because microfluidic 2
Departments of Chemical
conventional microfabrication processes, such applications have meanwhile been expanded Engineering, Materials Science &
as thin-film deposition, lithography, etching from relatively simple ana­lysis of single types of Engineering, Macromolecular Science
& Engineering, University of Michigan,
and bonding techniques [5–9] . However, these biomolecules into more sophisticated bioanayti- Ann Arbor, MI 48109, USA
traditional materials have often been found cal activities that may include live cells [16–19] . †
Author for correspondence:
Tel.: +1 734 763 7543
to be incompatible with the requirements of Here, the flexible nature of polymers and cer- Fax: +1 734 764 7453
biomedical and biotech­nological applications. tain physicochemical properties, such as high E-mail: lahann@[Link]
They are often associated with unfavorable oxygen and carbon dioxide permeability, which
properties, such as relatively high cost (espe- can be favorable for cell biology, may constitute
cially when used in disposables) fragility and further arguments for the use of polymers over
stiffness, harmful and complicated fabrication glass or silicon [15] .
procedures and incompatibility with rapid-pro- The introduction of novel materials and
totyping. For instance, incorporation of valves the increasing availability of polymer micro­
into early microfluidic devices posed a substan- fabrication technologies has led to a number of
tial challenge [10,11] . Alternatively, researchers recent breakthroughs, including a highly inte-
pursued the use of polymers as device mate- grated microdevice containing a temperature
rial; a trend that was supported by the fact sensor, fluorescence detector and heater [20] .
that a variety of polymer materials were readily This device was able to perform nanoliter-scale
available for device fabrication. Today, poly- DNA sampling that enabled the possibility of
mers such as poly­d imethylsiloxane (PDMS), rapid medical diagnosis portability and low-
poly(methyl methacrylate) (PMMA), poly- cost [20] . In addition, studies on cells [21–23] ,
carbonate (PC), polystyrene (PS), and cyclic proteins [24] , DNA [25,26] , as well as the physi-
olefin polymers (COP) are widely used in the cochemical investigation of detailed biological
microfluidic field [9,12,13] . A range of methods processes within synthetic microenvironments
for manufacturing polymeric microdevices, were demonstrated [27–29] . Accordingly, self-
such as soft-lithography, hot or cold embossing, responsive devices [30] can be used for targeted

10.4155/BIO.10.124 © 2010 Future Science Ltd Bioanalysis (2010) 2(10), 1717–1728 ISSN 1757-6180 1717
Special Report | Chen & Lahann

Key term diagnosis [31] , protein adsorption/desorption [32] , The continuously increasing complex-
Reactive coating:
particle manipulation [33,34] , self-assembly [35,36] ity of microfluidic systems will require the
Functionalized poly-p-xylylenes and controlled drug delivery [6,37,38] . development of methods for the precise and
with defined chemical anchoring It is clear that the intrinsic surface properties stable fabrication of additional features, such
groups to be used as coatings of such microfabricated devices, such as hydro- as surface patterns, within microfabricated
for tailoring surface properties.
phobicity/hydrophilicity, cationic/anionic sur- devices [47–53] . If these patterned substrates can
face charges, surface morphology, or the chemi- be easily integrated into microfluidic systems,
cal makeup of the surface, will critically affect the surface modification approach can address
bioanalytical performance. Due to the high the need for chemically and spatially defined
surface-to-volume ratio typically encountered micro-/nano-domains. Patterned microf lu-
in microfluidics, even slight inhomogeneities of idic systems may be of benefit to a number of
the surface make-up can result in poor opera- applications in biotechnology, such as capillary
tional performance or, in the worst case, cause electrophoresis, micro-/nano-assays, separa-
device malfunction [39] . A precise engineering tion devices and targeted diagnostic devices.
strategy for producing well-controlled syn- Currently employed methods for creating pat-
thetic surfaces is increasingly important and terns in microfluidic channels either rely on pat-
the development of sophisticated surface modi- terning of a flat substrate, which is subsequently
fication protocols has become a proliferative sealed to a microstructure, or the use of fluid
subfield of microfluidics (Table 1) . Currently patterning. Specific processes include micro-
available methods on modifying microf lu- fluidic patterning [54] , stencil masking [55,56] ,
idic surfaces include, but are not limited to, laminar flow patterning [57–59] , robotic spot-
polymer grafting, plasma treatment, UV/ ting [60–62] jet printing [63,64] , photolithog-
ozone treatment, salinization, phospholipid raphy [65–69] , microcontact printing [70] and
polymers, adsorption of detergents, proteins, selective plasma etching [71] . Although these
layer-by-layer assembly (LBL), sol-gel and sol- patterning methods have been used to pattern
vent extraction. Recent review articles provide cells [70,72] , proteins [57] and hydrogels [68,69,73]
a comprehensive overview of these techniques. within microfluidic systems, they often are asso-
Interested readers should refer to the follow- ciated with several shortcomings. For example,
ing articles [10,11,40–46] . Table 1 compares CVD- laminar flow-patterning techniques can only
based reactive coatings with other methods achieve continuous patterns. Photolithographic
that are currently employed for the surface processes usually change surface properties and
modification of microfluidics. topology of the device simultaneously. Other

Table 1. Comparison of surface modification techniques for microfluidics.

Technique Stability Chemical Substrate Process Cost Scalability Comments Ref.
versatility dependency time

Chemical vapor Long-term High Low Medium Medium– Medium Requires vacuum equipment [10,36]
deposition high
Polymer Long-term High High Slow Low Good Requires pretreatment or [10,39,40]
grafting coating of substrate
Plasma Short-term Medium Low Medium Medium– Medium Requires vacuum equipment, [10,38]
treatment high poor chemical control
Corona Short-term Limited Low Slow Low Low Poor chemical control [10]
Silanization Long-term Good High Fast Low Good Defined chemistry, [10,38,39,40]
applicable to a limited
number of substrates only
Phospholipid Short-term Good High Slow High Low Requires pretreatment or [10,41]
polymer coating of substrate
Adsorption of Short-term Medium Medium Fast Low Good Dynamic exchange on [36]
surfactants surface, risk of
contaminations
Adsorption of Short-term Poor Medium Fast High Low Dynamic exchange on [36,40]
proteins surface, risk of
contaminations

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 Surface patterning strategies for microfluidic applications | Special Report
methods, such as microcontact printing, spot- excessive deformation or channel clogging,
ting, jet printing and plasma etching, need to and usually optimized bonding conditions are
be conducted prior to device assembly. needed according to different materials or appli-
Regardless of the fabrication methods cations employed [74,75] . For instance, excessive
employed, sealing of the open microchannels heating associated with the bonding process for
and joining device parts together is another thermoplastic can cause melting and deforma-
important aspect necessary to produce the final tion of the channel structure, and high surface
enclosed microdevices. Bonding methods for wettability favors surface bonding [74] . Often,
enclosing micrometer-scale or submicrometer- surface modification procedures are applied
scale devices are challenging in order to avoid in order to improve wettability or to generate
A

Pyrolysis Deposition

Substituted-[2,2]paracyclophanes Reactive Coatings

B Pressure transducer –
system pressure 0.5 mbar

600~800°C
Pyrolysis zone
Starting material

Sample holder Pump

Carrier gas
Deposition -30~40°C

Sublimation zone
90~120°C
Furnace

Sublimation zone Pyrolysis zone Deposition

Figure 1. Instrumentation used for chemical vapor deposition polymerization of

functionalized [2.2]paracyclophanes. (A) Chemical vapor deposition (CVD) polymerization
process used to prepare functionalized poly-p-xylylenes from substituted-[2.2]paracyclophanes.
(B) CVD installation. (C) Custom-built CVD equipment.

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Special Report | Chen & Lahann

Endothelial cell

PDMS µ-device
Antibody

Streptavidin
PPX-PPF

CVD coating

Sealing against Biotinylated surface Layer-by-layer

glass cover self-assembly

Figure 2. Surface modification of a microdevice using reactive chemical vapor deposition

coatings to prepare a biologically active surface. An example shows polydimethylsiloxane-
based (PDMS) microdevice modified with poly(p-xylylene carboxylic acid pentafluorophenolester-
co-p-xylylene), which is used to bind biotin ligands and to self-assemble streptavidin. Biotin-labeled
antibody is then bound to the modified PDMS surface for subsequent cell-receptor acitivity [96] .
CVD: Chemical vapor deposition; PDMS: Polydimethylsiloxane; PPX-PPF: Poly(pxylylene
carboxylic acid pentafluorophenolester-co-p-xylylene).
Reproduced with permission from [96] © American Chemical Society (2003).

functional moieties for enhanced bonding topics including adhesive bonding, welding,
strength. For the case of PDMS, it is a siloxane solvent bonding, thermocompression bond-
elastomer that lacks functional groups to affili- ing and other methods for silicon/glass-based
Key terms ate with adhesives and usually requires oxida- wafer bonding [11,15,74,75,77,78] .
tive environments, such as plasma treatment or Over the past few years, we [79,80] and oth-
Chemical vapor deposition
polymerization: Chemical UV/ozone treatment to induce silanol groups ers [81–88] have explored the use of chemical
process that uses a reactive for bonding purpose [76] . However, hydropho- vapor deposition (CVD) polymerization to
vapor to coat high-purity bic recovery tends to remove silanol groups develop surface modification protocols for a
high-performance polymer films within minutes to hours from the surface, and wide range of different substrate materials [89] .
on a wide range of biologically
relevant substrates. the bonding procedure is usually required to The CVD polymerization process shows prom-
proceed immediately [10] , which limits the ising features, such as conformance to substrate
Lab-on-a-chip: Integration of
several laboratory functions into long-term usability of these methods. Similarly, topology, pinhole-free coverage even in very
a miniaturized chip. thermoplasts can result in hydrophobic sur- thin films and the ability to penetrate [90] and
Nonfouling coating: faces with poor wettability and weak bonding coat complex geometries [91] . CVD polymer-
Prevention of nonspecific strength. In addition, bonding methods asso- ization often does not require solvents, plas-
adsorption or adhesion of ciated with excessive heating and melting are ticizers, catalysts or accelerants, minimizing
biomolecules through also not favored for thermoplasts [74] . A number cytotoxic effects by excluding potential leach-
deposition of coatings.
of review articles have covered a diverse set of ing of low-molecular-weight additives [92,93] .

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 Surface patterning strategies for microfluidic applications | Special Report
In particular, functionalized poly-p-xylylenes polysaccharides or polynucleotides, which
(F igure 1) establish interfaces equipped with were shown to undergo biotinylation. This
chemically reactive groups that can be selected example represents a simple procedure for
from a variety of different chemical species, protein immobilization within polymer-based
including amines, alcohols, aldehydes, acti- lab-on-a-chip devices, such as PDMS-based
vated carboxylic acids, alkynes and anhy- microf luidic devices. This work illustrates
drides [85,94] , which can be selected depending the usefulness of these devices for screening
on the specific needs of a given application. The of pharmacologically relevant compounds in
stability of the polymer films has been exam- cell-based assays.
ined by immersing the coating in a range of
different solvents, including methanol, etha-
nol, acetone and chloroform. In addition, adhe-
Reactive polymer
sion of the polymer coatings on substrates such coatings O
as gold, silicon and metals has been analyzed
by a tape test in conjunction with inspections *

using optical microscopy and infrared spectros- n

copy and has shown mechanical and chemical Substrate
integrity [92,95] . UV radiation
In this progress report, we highlight surface
patterning approaches for microfluidic sys-
tems that are based on functionalized poly-p- Photo mask PEO PEO
xylylenes. The potential of this technology is
demonstrated on the basis of a range of exam-
ples. In addition, current issues in obtaining
O
precisely controlled surface properties for lab-
on-a-chip research, such as nonfouling modi- *

fication, strategies for surface modification of n

preassembled devices, accessibility of the inner Substrate
lumens of microchannels by vapor-borne coat-
ings, as well as adhesive bonding applications,
are discussed in this report.
PEO
Technical discussions
OH
„„Lab-on-a-chip assays
To address above-mentioned challenges with *

respect to defined surface modification of n

Substrate
microfluidic systems, we have recently devel-
oped a series of surface modification approaches
for microfluidic devices based on functionalized Spatially controlled
poly-p-xylylenes. Specifically, poly(p-xylylene protein adsorption
carboxylic acid pentafluorophenolester-co-p-
xylylene) was applied to PDMS microchan-
nels [96] . As shown in F igure 2 , without the
need for further activation, active ester groups
presented through the poly(p-xylylene carbox-
ylic acid pentafluorophenolester-co-p-xylylene)
coating readily reacted with biological ligands
or proteins. To examine the immobilization of
biotin ligands within the microchannels, fluo-
Figure 3. Spatially controlled nonfouling modification via photopatterning
rescein-conjugated streptavidin was bound to of poly(4-benzoyl-p-xylylene-co-p-xylylene) deposited on open
biotin-modified surfaces. In this case, one pair microchannels. PEO molecules are selectively immobilized onto photodefinable
of binding sites is used to link the protein to polymer-modified devices during photopatterning process, and result in the
the surface, leaving two binding sites on the subsequent protein adsorption on the areas that show no presence of PEO.
opposite face for further assembly of relevant PEO: Poly(ethylene oxide).
Reproduced with permission [98] © American Chemical Society (2005).
biomolecules, such as enzymes, antibodies,

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Special Report | Chen & Lahann
confinement of nonfouling molecules and PEO,
and the selective adsorption of proteins including
albumin and fibrinogen within microchannels
were demonstrated.
Furthermore, poly(p-xylylene-4-methyl-2-
bromoisobutyrate-co-p-xylylene) was synthesized
by CVD polymerization [100] and, subsequently,
poly[oligo(ethylene glycol) methyl ether methac-
rylate] hydrogels were prepared via atom transfer
radical polymerization (ATRP) on a CVD-based
initiator coating. Although the focus of this
work is on a flat substrate made of PMMA, this
surface modification technique can be applied
to microfluidic systems fabricated from glass,
quartz, metal or other polymers [91] . The result-
ing poly[oligo(ethylene glycol) methyl ether
methacrylate] hydrogels have shown remarkable
nonfouling properties and can be used for pro-
tein and cell adhesion patterning, as shown in
Figure 4. With respect to the quantitative ana­lysis
of protein adsorption on ������������������������
poly[oligo(ethylene gly-
col) methyl ether methacrylate] surfaces, a recent
Figure 4. Fluorescence (A & B), and phase contrast (C & D) micrographs study has shown an ultra-low protein coverage
show nonfouling property of controlled protein- and cell-resistance on using a microtubule–kinesin model. Kinesin
patterned poly[oligo(ethylene glycol) methyl ether methacrylate] molecules first adsorb to the tested surfaces,
surfaces synthesized via atom transfer radical polymerization on chemical
vapor deposition polymerization approach to prepare vapor-based
followed by microtubules binding to the active
initiator coatings. kinesin on the surface [101] . The landing rate
Reproduced with permission from [100] © Wiley-VCH Verlag GmbH & Co. KGaA of microtubules is determined and correlated
(2008). to the adsorption density [101] . A significantly
decreased kinesin density of 0.16 ± 0.02 µm-2 –
„„Controlled nonfouling modification a 20-fold reduction compared with (EG)3OH-
& microfluidic channels terminated self-assembled monolayer (SAM)
One of the major challenges in microfluidic surfaces – was observed.
devices is the prevention of nonspecific interac-
tions of the analyte with the large surface area „„Surface modification within
available in microchanels. To reduce nonspecific microchannels
interactions, a photodefinable polymer, poly(4- The important question of whether the concept
benzoyl-p-xylylene-co-p-xylylene) [97] , prepared of CVD polymerization is applicable to micro-
by CVD polymerization was used for fabrication channels was addressed only recently [47,102] . A
of hydrogel elements with dimensions smaller series of functionalized poly-p-xylylenes were
than 5 µm. Results from infrared reflection prepared using CVD polymerization within
absorption spectroscopy (IRR AS) and x-ray microfluidic devices, which were comprised
photoelectron (XPS) spectroscopy were found of straight and meandering microchannels
to be in accordance with the predicted polymer (Figure 5) [90] . Silicon substrates were used as
structure of poly(4-benzoyl-p-xylylene-co-p- test fixtures, as they can be reversibly sealed onto
xylylene). The photoactivated carbonyl groups PDMS molds, then coated via CVD polymeri-
of the polymer have the potential to enable light- zation and removed for final examination. XPS
induced crosslinking of molecules and can rap- imaging confirmed that the entire microchannel
idly react via insertion into CH- or NH-bonds footprint was devoid of any detectable amounts
upon photoillumination at 340 nm [98,99] . In of silicon due to an homogeneous polymer film,
F igure 3, the example shows a microchannel which was thicker than 10 nm [103] . Atomic force
consisting of deep and shallow areas that was microscopy (AFM) height profiling and imag-
incubated with fluorescently-labeled fibrinogen ing ellipsometry further verified the presence of
after poly(ethylene oxide) (PEO) modifica- polymer deposition on entire microchannels,
tion. Based on this method, spatially controlled and aspect ratios as high as 37 were found [90] .

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 Surface patterning strategies for microfluidic applications | Special Report
The thickness of the deposited functionalized technological limitations we have recently devel- Key term
poly-p-xylylenes in the microchannels is actu- oped a solventless adhesive bonding (SAB) Solventless adhesive
ally less crucial, as long as the deposition of the approach [106] , which is applicable to a wide bonding: Fabrication
polymer film occurs homogeneously throughout range of materials, including, but not limited procedure to join two or more
the microchannel and the resulting coatings still to, PDMS. As shown in Figure 6, the SAB pro- surfaces together by means of
chemical or physical interactions
provide sufficient amounts of functional groups cess uses two different vapor-deposited polymer between surfaces.
for further modification [90,104] . Assessment of coatings with complementary functional groups.
the chemical reactivity of the CVD coatings Functionalized poly-p-xylylenes������������
are
�����������
confor-
after deposition in complex microgeometries mally applied to substrates of choice via CVD
was therefore pursued. While poly(4-amino-p- polymerization process with thickness between
xylylene-co-p-xylylene) allowed for coupling to 50–100 nm. CVD-based polymer films form
activated carboxyl groups (amide formation), well-adherent coatings on a range of different
poly(4-trifluoroacetyl-p-xylylene-co-p-xylylene) substrate materials, including polymers, glass,
was successfully reacted with hydrazides, and silicon, metals or paper; in addition, the coat-
the resulting anchoring group showed homog- ings are stable under ambient conditions. Thus,
enous distribution throughout the entire micro­
channels, based on the chemical reactivity stud- 100 µm
A
ies [90] . In order to further investigate the limits 1600 µm
* X *

of the CVD technology for microfludics, we sys-

75 µm
tematically conducted CVD polymerization on m n

microchannels with various geometries [104] , and z

used poly(4-pentafluoropropionyl-p-xylylene-co- CH2
y
*
CH2
*

p-xylylene) as an example for this study. PDMS X

+ x
devices comprising regularly structured posts
were reversibly sealed with silicon substrates, CH2
*
CH2
*

coated by CVD, and the resulting polymer

footprints were subjected to a series of surface B
characterizations. The study confirmed that Functionalized
1 2 3 4 5 6 7
poly-p-xylylenes
CVD process parameters could greatly impact
the resulting deposition behavior. While this
x=
study identified void spaces of approximately
25 µm as the lower limit [104] , which can be
coated reproducibly, optimization of the CVD
process should enable deposition in smaller C
dimensions. Chemical reactivity of the deposited
coatings was also verified by covalent binding
of a biotin hydrazide followed by self-assembled
TRITC-strepdavidin or CdSe quantum dots
conjugated streptavidin [104] .

„„Solventless adhesive bonding based on

CVD technology
In many biotechnological applications, the
integration of different materials via adhesive
bonding has posed a continuous challenge. The
bonding requirements are even more stringent
when considering micro- and nano-scale devices.
For instance, methods for PDMS substrates
require oxygen plasma [13,53,76] or UV/ozone
Figure 5. Chemical vapor deposition polymerization to deposit a variety
treatment [105] . In these cases, activation must of nonreactive and reactive polymers within confined geometries.
occur within minutes before bonding to avoid Fluorescence micrographs show the proof-of-concept study of immobilizing
hydrophobic recovery [10] . In addition, these biotins and self-assembled tetramethyl rhodamine isothiocyanate-streptavidins on
bonding techniques are limited to PDMS, the inner surface of microchannels that are modified via reactive polymers after
silicon and glass and, therefore, are not appli- device assembly.
Reproduced with permission from [90] © American Chemical Society (2006).
cable to hybrid devices [76] . To address these

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Special Report | Chen & Lahann
A X
X = CHO
PDMS microchannel

Glass substrate
X = CH2NH2

CVD SAB process

polymerization

m
n Biotin–hydrazide/streptavidin
immobilization onto CHO groups

Reactive groups used Reactive groups used

for conjugation for SAB process
B

Method Material Bonding strength (MPa)

PDMS–PDMS > 2.44 ± 0.15

PDMS–PTFE 1.21 ± 0.35
CVD coatings PDMA–Stainless steel > 2.44 ± 0.15
PDMA–Silicon wafer > 2.44 ± 0.15
PDMS–Glass > 2.44 ± 0.15
PDMS–Gold > 2.44 ± 0.15

CVD coatings PDMS–gold > 2.44 ± 0.15

Physical contact
Heat (140°C) 0.02 ± 0.11
OV/Ozone 0.19 ± 0.09
Oxygen plasma PDMS–PDMS 0.78 ± 0.08
(cured at 120°C) 2.34 ± 0.27
Oxygen plasma 1.15 ± 0.18
(cured at 60°C)

Figure 6. Solventless adhesive bonding process. The fluorescence micrograph shows reactivity
of chemical vapor deposition polymers on sealed microchannels after solventless adhesive bonding
process. A table compares tensile stress of SAB process with current available methods [105] .
CVD: Chemical vapor deposition; PDMS: Polydimethylsiloxane; SAB: Solventless adhesive bonding.
Reproduced with permission from [105] © American Chemical Society (2008).

the resulting films can be stored for extended were brought into conformal contact. The con-
periods prior to bonding without compromis- tacting samples were then allowed to undergo
ing their bonding capability. In one example, covalent bonding at elevated temperatures. For
a substrate coated with poly(4-aminomethyl-p- a diverse range of substrate combinations, bond-
xylylene-co-p-xylylene) and a substrate coated ing strengths were comparable or even higher
with poly(4-formyl-p-xylylene-co-p-xylylene) than those obtained by conventional bonding

1724 Bioanalysis (2010) 2(10) future science group

 Surface patterning strategies for microfluidic applications | Special Report
methods, as shown in Figure 6B. In addition, substrate materials and geometries and, maybe
functional groups that were not used during most importantly, are compatible with a range
the bonding process remained active (i.e., func- of patterning methods.
tional groups at the lumenal surface of micro- As integrated microfluidic systems become
channels), and allowed for subsequent modifica- increasingly complex, surface coating strategies
tion and bioconjugation. As the SAB process is will need to provide access to a wide range of
independent of the chemical composition of the functional groups, so that the actual selection
substrate, relies on well-defined bonding chem- can be driven by the specification of the appli-
istries and can be activated on demand, it may cation of interest, and not by materials’ limita-
have important biotechnological applications tions. In addition, integration of chemical and
in the areas of microfluidics and miniaturized physical surface modification concepts (e.g.,
biomedical devices. micro- and nano-texturing) will result in more
precise mimicry of biological systems, control
Future perspective of cell–cell, cell–protein and protein–surface
So far, there exists no ‘universal’ surface modi- interactions, and may enable future biomedical
fication approach that can work for all types research directions. Future advances in these
of surfaces for microfludics, and the optimal areas will not only contribute to the advance-
approach has to be identified in a case-by-case ment of the field of microfluidics, but also stimu-
fashion with selected methods [42–44] . Within late further scientific and technological progress
the next decade, innovative materials concepts, in modern biology.
such as vapor-based coatings, will provide
generically applicable surface platforms that Financial & competing interests disclosure
can fully integrate a number of device interfaces The authors gratefully acknowledge support from the NSF
with the surrounding biological milieu. Ideally, in form of a CAREER grant (DMR-0449462) and fund-
potentially harmful additives, solvent, initiator ing from the NSF under MRI program (DMR 0420785).
or plasticizers will have to be eliminated from The authors have no other relevant affiliations or financial
the coating process to avoid potential sources of involvement with any organization or entity with a finan-
contamination. CVD-based processes are excel- cial interest in or financial conflict with the subject matter
lent candidates in this respect, as they do not or materials discussed in the manuscript apart from
use solvent initiators or plasticizers. In addition, those disclosed.
vapor-based polymer coatings can offer exquisite No writing assistance was utilized in the production of
coating conformality on a variety of different this manuscript.

Executive summary
„„ Microfluidic systems play a crucial role in many contemporary areas of research, such as genomics, proteomics and cell diagnostics.
„„ Tailoring the surface properties of microfluidic devices to this broad range of applications has become an important research focus and is
often essential for accurate device performance.
„„ Reactive coatings based on functionalized poly-p-xylylenes enable precise surface engineering of otherwise difficult to coat surfaces.
„„ Using chemical vapor deposition polymerization, ultrathin reactive coatings have been deposited on a wide range of different substrates.
„„ Chemical vapor deposition coatings can enable surface patterning and functionalization of previously assembled devices, as well as
device bonding.

2 Berg A, Olthius W, Bergveld P. Micro Total 5 Verpoorte E, De Rooij NF. Microfluidics

Bibliography Ana­lysis Systems 2000 (1st Edition). Kluwer meets mems. Proc. IEEE 91(6), 930–953
Papers of special note have been highlighted as: Academic. Dordrecht, The Netherlands (2003).
n of interest (2000). 6 Ziaie B, Baldi A, Lei M, Gu YD, Siegel RA.
nn of considerable interest
3 Auroux PA, Iossifidis D, Reyes DR, Manz A. Hard and soft micromachining for biomems:
1 Manz A, Graber N, Widmer HM. Micro total ana­lysis systems. 2. Analytical review of techniques and examples of
Miniaturized total chemical ana­lysis systems: standard operations and applications. Anal. applications in microfluidics and drug
a novel concept for chemical sensing. Sens Chem. 74(12), 2637–2652 (2002). delivery. Adv. Drug Deliv. Rev. 56(2),
Actuators B Chem. 1(1–6), 244–248 (1990). 4 Reyes DR, Iossifidis D, Auroux PA, Manz A. 145–172 (2004).
nn Pioneering paper reporting the concept of Micro total ana­lysis systems. 1. Introduction, 7 Huang Y, Mather EL, Bell JL, Madou M.
using miniaturized analytical systems for theory, and technology. Anal. Chem. 74(12), Mems-based sample preparation for molecular
chemical sensing. 2623–2636 (2002). diagnostics. Anal. Bioanal. Chem. 372(1),
49–65 (2002).

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Special Report | Chen & Lahann
8 Liu C. Recent developments in polymer 22 Fu AY, Spence C, Scherer A, Arnold FH, 36 Park JI, Nie Z, Kumachev A et al.
mems. Adv. Mater. 19(22), 3783–3790 Quake SR. A microfabricated fluorescence- A microfluidic approach to chemically driven
(2007). activated cell sorter. Nat. Biotechnol. 17(11), assembly of colloidal particles at gas–liquid
9 Abgrall P, Gue AM. Lab-on-chip 1109–1111 (1999). interfaces. Angew. Chem. Int. Ed. 48(29),
technologies: making a microfluidic network 23 Lucchetta EM, Lee JH, Fu LA, Patel NH, 5300–5304 (2009).
and coupling it into a complete microsystem Ismagilov RF. Dynamics of drosophila 37 Oh JK, Drumright R, Siegwart DJ,
– a review. J. Micromech. Microeng. 17(5), embryonic patterning network perturbed in Matyjaszewski K. The development of
R15–R49 (2007). space and time using microfluidics. Nature microgels/nanogels for drug delivery
n Excellent review to report the development, 434(7037), 1134–1138 (2005). applications. Prog. Polym. Sci. 33(4), 448–477
24 Figeys D, Pinto D. Proteomics on a chip: (2008).
fabrications and applications of
lab-on-chip microsystems. promising developments. Electrophoresis 38 Caldorera-Moore M, Peppas NA. Micro- and
22(2), 208–216 (2001). nanotechnologies for intelligent and responsive
10 Makamba H, Kim JH, Lim K, Park N,
25 Tian JD, Gong H, Sheng NJ et al. Accurate biomaterial-based medical systems. Adv. Drug
Hahn JH. Surface modification of
multiplex gene synthesis from programmable Deliv. Rev. 61(15), 1391–1401 (2009).
poly(dimethylsiloxane) microchannels.
Electrophoresis 24(21), 3607–3619 (2003). DNA microchips. Nature 432(7020), 39 Li Y, Pfohl T, Kim JH et al. Selective surface
1050–1054 (2004). modification in silicon microfluidic channels
n Excellent review of surface
26 Sanders GHW, Manz A. Chip-based for micromanipulation of biological
modification techniques for
microsystems for genomic and proteomic macromolecules. Biomedical Microdevices 3(3),
poly(dimethylsiloxane)‑based microdevices. 239–244 (2001).
ana­lysis. Trends Analyt. Chem. 19(6),
11 Chen Y, Zhang LY, Chen G. Fabrication, 364–378 (2000). 40 Gomez FA. Biological Applications of
modification, and application of department Microfluidics. Wiley-Interscience, Hoboken,
of analytical poly(methyl methacrylate) 27 Beebe DJ, Mensing GA, Walker GM. Physics
and applications of microfluidics in biology. NJ, USA (2008).
microfluidic chips. Electrophoresis 29(9),
1801–1814 (2008). Annu. Rev. Biomed Eng. 4, 261–286 (2002). 41 Zhou JW, Ellis AV, Voelcker NH. Recent
n Insightful report on the importance of developments in pdms surface modification for
12 Becker H, Locascio LE. Polymer microfluidic microfluidic devices. Electrophoresis 31(1), 2–16
devices. Talanta 56(2), 267–287 (2002). physical properties for microfluidics.
(2010).
13 Mcdonald JC, Duffy DC, Anderson JR et al. 28 Regehr KJ, Domenech M, Koepsel JT et al.
42 Belder D, Ludwig M. Surface modification in
Fabrication of microfluidic systems in Biological implications of
microchip electrophoresis. Electrophoresis
poly(dimethylsiloxane). Electrophoresis 21(1), polydimethylsiloxane-based microfluidic cell
24(21), 3595–3606 (2003).
27–40 (2000). culture. Lab Chip 9(15), 2132–2139 (2009).
43 Prakash S, Karacor MB, Banerjee S.
14 Xia YN, Whitesides GM. Soft lithography. 29 Bilitewski U, Genrich M, Kadow S, Mersal G.
Surface modification in microsystems and
Ann. Rev. Mat. Sci. 28, 153–184 (1998). Biochemical ana­lysis with microfluidic
nanosystems. Surf. Sci. Rep. 64(7), 233–254
systems. Anal. Bioanal. Chem. 377(3),
15 Becker H, Gartner C. Polymer (2009).
556–569 (2003).
microfabrication technologies for microfluidic 44 Pallandre A, De Lambert B, Attia R, JonasAM,
systems. Anal. Bioanal. Chem. 390(1), 89–111 30 Domachuk P, Tsioris K, Omenetto FG,
Viovy JL. Surface treatment and
(2008). Kaplan DL. Bio-microfluidics: biomaterials
characterization: perspectives to electrophoresis
and biomimetic designs. Adv. Mater. 22(2),
n Review to focus on fabrication technologies and lab-on-chips. Electrophoresis 27(3),
249–260 (2010).
for various materials. 584–610 (2006).
31 Lai JJ, Hoffman JM, Ebara M et al. Dual
16 Quake SR, Scherer A. From micro- to magnetic-/temperature-responsive
n Review of recent surface modification
nanofabrication with soft materials. Science nanoparticles for microfluidic separations and technology for microdevices.
290(5496), 1536–1540 (2000). assays. Langmuir 23(13), 7385–7391 (2007). 45 Wong I, Ho CM. Surface molecular property
17 El-Ali J, Sorger PK, Jensen KF. Cells on chips. 32 Huber DL, Manginell RP, Samara MA, Kim modifications for poly(dimethylsiloxane)
Nature 442(7101), 403–411 (2006). BI, Bunker BC. Programmed adsorption and (PDMS) based microfluidic devices.
18 Khademhosseini A, Langer R, Borenstein J, release of proteins in a microfluidic device. Microfluid. Nanofluidics 7(3), 291–306 (2009).
Vacanti JP. Microscale technologies for tissue Science 301(5631), 352–354 (2003). 46 Xu Y, Takai M, Ishihara K. Phospholipid
engineering and biology. Proc. Natl Acad. Sci. 33 Sung KE, Vanapalli SA, Mukhija D et al. polymer biointerfaces for lab-on-a-chip devices.
USA 103(8), 2480–2487 (2006). Programmable fluidic production of Ann. Biomed. Eng. 38(6), 1938–1953 (2010).
19 Meyvantsson I, Beebe DJ. Cell culture models microparticles with configurable anisotropy. nn Excellent review of using phospholipid
in microfluidic systems. Annu. Rev. Anal. J. Am. Chem. Soc. 130(4), 1335–1340 (2008). polymer for microfludic applications.
Chem. 1, 423–449 (2008). 34 Dendukuri D, Doyle PS. The synthesis and 47 Hu S, Ren X, Bachman M, Sims CE, Li GP,
20 Burns MA, Johnson BN, Brahmasandra SN assembly of polymeric microparticles using Allbritton NL. Surface-directed, graft
et al. An integrated nanoliter DNA ana­lysis microfluidics. Adv. Mater. 21(41), 4071–4086 polymerization within microfluidic channels.
device. Science 282(5388), 484–487 (1998). (2009). Anal. Chem. 76(7), 1865–1870 (2004).
21 Takayama S, Mcdonald JC, Ostuni E et al. 35 Sing CE, Schmid L, Schneider MF, Franke T, 48 Grzybowski BA, Haag R, Bowden N,
Patterning cells and their environments using Alexander-Katz A. Controlled surface- Whitesides GM. Generation of micrometer-
multiple laminar fluid flows in capillary induced flows from the motion of self- sized patterns for microanalytical applications
networks. Proc. Natl Acad. Sci. USA 96(10), assembled colloidal walkers. Proc. Natl Acad. using a laser direct-write method and
5545–5548 (1999). Sci. USA 107(2), 535–540 (2010). microcontact printing. Anal. Chem. 70(22),
4645–4652 (1998).

1726 Bioanalysis (2010) 2(10) future science group

 Surface patterning strategies for microfluidic applications | Special Report
49 Barker SLR, Tarlov MJ, Canavan H, 61 Heller RA, Schena M, Chai A et al. 74 Tsao CW, Devoe DL. Bonding of
Hickman JJ, Locascio LE. Plastic Discovery and ana­lysis of inflammatory thermoplastic polymer microfluidics.
microfluidic devices modified with disease-related genes using cdna microarrays. Microfluid. Nanofluidics. 6(1), 1–16 (2009).
polyelectrolyte multilayers. Anal. Chem. Proc. Natl Acad. Sci. USA 94(6), 2150–2155 n Comprehensive review of current bonding
72(20), 4899–4903 (2000). (1997).
technologies for microfluidic applications.
50 Ocvirk G, Munroe M, Tang T, Oleschuk R, 62 Shalon D, Smith SJ, Brown PO. A DNA
75 Becker H, Gartner C. Polymer microfabrication
Westra K, Harrison DJ. Electrokinetic microarray system for analyzing complex
methods for microfluidic analytical applications.
control of fluid flow in native DNA samples using two-color fluorescent
Electrophoresis 21(1), 12–26 (2000).
poly(dimethylsiloxane) capillary probe hybridization. Genome Res. 6(7),
electrophoresis devices. Electrophoresis 21(1), 639–645 (1996). 76 Bhattacharya S, Datta A, Berg JM,
107–115 (2000). Gangopadhyay S. Studies on surface wettability
63 Lopez MF, Pluskal MG. Protein micro- and
of poly(dimethyl) siloxane (PDMS) and glass
51 Yang TL, Jung SY, Mao HB, Cremer PS. macroarrays: digitizing the proteome.
under oxygen-plasma treatment and correlation
Fabrication of phospholipid bilayer-coated J. Chromatogr. B Analyt. Technol. Biomed.
with bond strength. J. Microelectromech. Syst.
microchannels for on-chip immunoassays. Life Sci. 787(1), 19–27 (2003).
14(3), 590–597 (2005).
Anal. Chem. 73(2), 165–169 (2001). 64 Roda A, Guardigli M, Russo C, Pasini P,
77 Brown HR. Adhesion between polymers. IBM
52 Berdichevsky Y, Khandurina J, Guttman A, Baraldini M. Protein microdeposition using a
Journal of Research and Development 38(4),
Lo YH. UV/ozone modification of conventional ink-jet printer. BioTechniques
379–389 (1994).
poly(dimethylsiloxane) microfluidic channels. 28(3), 492–496 (2000).
Sens Actuators B Chem. 97(2–3), 402–408 78 Niklaus F, Stemme G, Lu JQ, Gutmann RJ.
65 Holden MA, Jung S-Y, Cremer PS.
(2004). Adhesive wafer bonding. J. Appl. Phys 99(3),
Patterning enzymes inside microfluidic
031101–031128 (2006).
53 Duffy DC, Mcdonald JC, Schueller OJA, channels via photoattachment chemistry.
Whitesides GM. Rapid prototyping of Anal. Chem. 76(7), 1838–1843 (2004). 79 Lahann J. Vapor-based polymer coatings for
microfluidic systems in poly(dimethyl­ potential biomedical applications. Polym. Int.
66 Koh W-G, Revzin A, Pishko MV.
siloxane). Anal. Chem. 70(23), 4974–4984 55(12), 1361–1370 (2006).
Poly(ethylene glycol) hydrogel
(1998). microstructures encapsulating living cells. 80 Lahann J. Reactive polymer coatings for
54 Delamarche E, Bernard A, Schmid H, Langmuir 18(7), 2459–2462 (2002). biomimetic surface engineering. Chemical
Bietsch A, Michel B, Biebuyck H. Engineering Communications 193(11),
67 Koh W-G, Itle LJ, Pishko MV. Molding of
Microfluidic networks for chemical 1457–1468 (2006).
hydrogel microstructures to create
patterning of substrates: Design and multiphenotype cell microarrays. Anal. 81 Senkevich JJ, Desu SB. Poly(chloro-p-xylylene)/
application to bioassays. J. Am. Chem. Soc Chem. 75(21), 5783–5789 (2003). SiO2 multilayer thin films deposited near room
120(3), 500–508 (1998). temperature by thermal cvd. Thin Solid Films
68 Zhan W, Seong GH, Crooks RM. Hydrogel-
nn Seminal work on patterned 322(1–2), 148–157 (1998).
based microreactors as a functional
microfluidic networks. component of microfluidic systems. Anal. 82 Martin TP, Kooi SE, Chang SH, Sedransk KL,
Chem. 74(18), 4647–4652 (2002). Gleason KK. Initiated chemical vapor
55 Graff M, Mohanty SK, Moss E, Frazier AB.
deposition of antimicrobial polymer coatings.
Microstenciling: a generic technology for 69 Heo J, Thomas KJ, Seong GH, Crooks RM.
Biomaterials 28(6), 909–915 (2007).
microscale patterning of vapor deposited A microfluidic bioreactor based on hydrogel-
materials. J. Microelectromech. Syst. 13(6), entrapped E. coli: cell viability, lysis, and 83 Limb SJ, Labelle CB, Gleason KK, Edell DJ,
956–962 (2004). intracellular enzyme reactions. Anal. Chem. Gleason EF. Growth of fluorocarbon polymer
75(1), 22–26 (2003). thin films with high cf2 fractions and low
56 Frimat JP, Menne H, Michels A et al. Plasma
dangling bond concentrations by thermal
stencilling methods for cell patterning. Anal. 70 Mrksich M, Dike LE, Tien J, Ingber DE,
chemical vapor deposition. Appl. Phys Lett.
Bioanal. Chem. 395(3), 601–609 (2009). Whitesides GM. Using microcontact
68(20), 2810–2812 (1996).
57 Takayama S, Mcdonald JC, Ostuni E et al. printing to pattern the attachment of
mammalian cells to self-assembled 84 Lee NH, Frank CW. Surface-initiated vapor
Patterning cells and their environments using
monolayers of alkanethiolates on transparent polymerization of various a-amino acids.
multiple laminar fluid flows in capillary
films of gold and silver. Exp. Cell Res. 235(2), Langmuir 19(4), 1295–1303 (2003).
networks. Proc. Natl Acad. Sci. USA 96(10),
5545–5548 (1999). 305–313 (1997). 85 Kusumo A, Bombalski L, Lin Q,
71 Khademhosseini A, Suh KY, Jon S et al. Matyjaszewski K, Schneider JW, Tilton RD.
58 Regenberg B, Kruehne U, Beyer M et al.
A soft lithographic approach to fabricate High capacity, charge-selective protein uptake
Use of laminar flow patterning for
patterned microfluidic channels. Anal. Chem. by polyelectrolyte brushes. Langmuir 23(8),
miniaturised biochemical assays. Lab Chip
76(13), 3675–3681 (2004). 4448–4454 (2007).
4(6), 654–657 (2004).
72 Rhee SW, Taylor AM, Tu CH, Cribbs DH, 86 Hanefeld P, Westedt U, Wombacher R et al.
59 Takayama S, Ostuni E, Leduc P, Naruse K,
Cotman CW, Jeon NL. Patterned cell culture Coating of poly(p-xylylene) by pla-peo-pla
Ingber DE, Whitesides GM. Subcellular
inside microfluidic devices. Lab Chip 5(1), triblock copolymers with excellent polymer-
positioning of small molecules. Nature
102–107 (2005). polymer adhesion for stent applications.
411(6841), 1016. (2001).
Biomacromolecules 7(7), 2086–2090 (2006).
60 Schena M, Shalon D, Davis RW, Brown PO. 73 Beebe DJ, Moore JS, Bauer JM et al.
Functional hydrogel structures for 87 Gu HW, Xu CJ, Weng LT, Xu B. Solventless
Quantitative monitoring of gene expression
autonomous flow control inside microfluidic polymerization: spatial migration of a catalyst
patterns with a complementary DNA
channels. Nature 404(6778), 588–590 to form polymeric thin films in microchannels.
microarray. Science 270(5235), 467–470
(2000). J. Am. Chem. Soc. 125(31), 9256–9257 (2003).
(1995).

future science group [Link] 1727

Special Report | Chen & Lahann
88 Chang YC, Frank CW. Vapor deposition- 94 Duan HW, Kuang M, Wang DY, Kurth DG, 100 Jiang X, Chen H-Y, Galvan G, Yoshida M,
polymerization of a-amino acid n-carboxy Mohwald H. Colloidally stable amphibious Lahann J. Vapor-based initiator coatings for
anhydride on the silicon(100) native oxide nanocrystals derived from poly atom transfer radical polymerization. Adv.
surface. Langmuir 14(2), 326–334 (1998). {[2-(dimethylamino)ethyl] methaerylatel [Link]. 18(1), 27–35 (2008).
89 Alf ME, Asatekin A, Barr MC et al. capping. Angew. Chem. Int. Ed.44(11), 101 Katira P, Agarwal A, Fischer T et al.
Chemical vapor deposition of 1717–1720 (2005). Quantifying the performance of protein-
conformal, functional, and responsive 95 Nandivada H, Chen HY, Lahann J. resisting surfaces at ultra-low protein
polymer films. Adv. Mater. 22(18), Vapor-based synthesis of poly [(4-formyl-p- coverages using kinesin motor proteins as
1993–2027 (2010). xylylene)-co-(p-xylylene)] and its use for probes. Adv. Mater. 19, 3171–3176 (2007).
n Comprehensive review of current biomimetic surface modifications. Macromol. 102 Gupta M, Gleason KK. Surface modification
Rapid Commun. 26(22), 1794–1799 (2005). of high aspect ratio structures with
technology of chemical vapor deposition to
prepare functional polymers. 96 Lahann J, Balcells M, Lu H, Rodon T, fluoropolymer coatings using chemical vapor
Jensen KF, Langer R. Reactive polymer deposition. Thin Solid Films 517(12),
90 Chen HY, Elkasabi Y, Lahann J. Surface
coatings: a first step toward surface 3547–3550 (2009).
modification of confined microgeometries
engineering of microfluidic devices. Anal. 103 Briggs D. Surface Ana­lysis of Polymers by Xps
via vapor-deposited polymer coatings. J. Am.
Chem. 75(9), 2117–2122 (2003). and Static Sims. Cambridge University Press,
Chem. Soc. 128(1), 374–380 (2006).
97 Suh KY, Langer R, Lahann J. A novel Cambridge, UK (1998).
91 Lahann J, Klee D, Hocker H. Chemical
photodefinable reactive polymer coating and 104 Chen H-Y, Lahann J. Vapor-assisted
vapour deposition polymerization of
its use for microfabrication of hydrogel micropatterning in replica structures: a
substituted [2.2]paracyclophanes.
elements. Adv. Mater. 16(16), 1401–1405 solventless approach towards topologically
Macromol. Rapid Commun. 19(9), 441–444
(2004). and chemically designable surfaces. Adv.
(1998).
98 Chen H-Y, Lahann J. Fabrication of Mater. 19(22), 3801–3808 (2007).
92 Schurmann K, Lahann J, Niggemann P et
discontinuous surface patterns within 105 Mcdonald JC, Whitesides GM.
al. Biologic response to polymer-coated
microfluidic channels using photodefinable Poly(dimethylsiloxane) as a material for
stents: in vitro ana­lysis and results in an iliac
vapor-based polymer coatings. Anal. Chem. fabricating microfluidic devices. Acc. Chem.
artery sheep model. Radiology 230(1),
77(21), 6909–6914 (2005). Res. 35(7), 491–499 (2002).
151–162 (2004).
99 Shen WW, Boxer SG, Knoll W, Frank CW. 106 Chen H-Y, McClelland AA, Chen Z,
93 Lahann J, Klee D, Pluester W, Hoecker H.
Polymer-supported lipid bilayers on Lahann J. Solventless adhesive bonding using
Bioactive immobilization of r-hirudin on
benzophenone-modified substrates. reactive polymer coatings. Anal. Chem.
cvd-coated metallic implant devices.
Biomacromolecules 2(1), 70–79 (2001). 80(11), 4119–4124 (2008).
Biomaterials 22(8), 817–826 (2001).

1728 Bioanalysis (2010) 2(10) future science group