We have investigated the bonding stability of various silane treatments for the integration of track-etched membranes with poly(dimethylsiloxane) (PDMS) microfluidic devices. We compare various treatments using trialkoxysilanes or dipodal silanes to determine the effect of the organofunctional group, cross-link density, reaction solvent, and catalyst on the bond stability. We find that devices made using existing silane methods delaminated after one day when immersed in cell culture medium at 37 °C. In contrast, the dipodal silane, bis[3-(trimethoxysilyl)propyl]amine, is shown to yield stable and functional integration of membranes with PDMS that is suitable for long-term cell culture. To demonstrate application of the technique, we fabricated an open-surface device in which cells cultured on a track-etched membrane can be stimulated at their basal side via embedded microfluidic channels. C2C12 mouse myoblasts were differentiated into myotubes over the course of two weeks on these devices to demonstrate biocompatibility. Finally, devices were imaged during the basal-side delivery of a fluorescent stain to validate the membrane operation and long-term stability of the bonding technique.

1.
Y.
Torisawa
,
B.
Chueh
,
D.
Huh
,
P.
Ramamurthy
,
T. M.
Roth
,
K. F.
Barald
, and
S.
Takayama
, “
Efficient formation of uniform-sized embryoid bodies using a compartmentalized microchannel device
,”
Lab Chip
7
(
6
),
770
776
(
2007
).
2.
T.
Kim
,
M.
Pinelis
, and
M. M.
Maharbiz
, “
Generating steep, shear-free gradients of small molecules for cell culture
,”
Biomed. Microdevices
11
(
1
),
65
73
(
2009
).
3.
D. M.
Cate
,
C. G.
Sip
, and
A.
Folch
, “
A microfluidic platform for generation of sharp gradients in open-access culture
,”
Biomicrofluidics
4
(
4
),
044105
(
2010
).
4.
V. V.
Abhyankar
,
M. A.
Lokuta
,
A.
Huttenlocher
, and
D. J.
Beebe
, “
Characterization of a membrane-based gradient generator for use in cell-signaling studies
,”
Lab Chip
6
(
3
),
389
(
2006
).
5.
C. G.
Sip
,
N.
Bhattacharjee
, and
A.
Folch
, “
Microfluidic transwell inserts for generation of tissue culture-friendly gradients in well plates
,”
Lab Chip
14
(
2
),
302
314
(
2014
).
6.
J.
Kawada
,
H.
Kimura
,
H.
Akutsu
,
Y.
Sakai
, and
T.
Fujii
, “
Spatiotemporally controlled delivery of soluble factors for stem cell differentiation
,”
Lab Chip
12
(
21
),
4508
4515
(
2012
).
7.
C.
Kim
,
K.
Kreppenhofer
,
J.
Kashef
,
D.
Gradl
,
D.
Herrmann
,
M.
Schneider
,
R.
Ahrens
,
A.
Guber
, and
D.
Wedlich
, “
Diffusion- and convection-based activation of Wnt/β-catenin signaling in a gradient generating microfluidic chip
,”
Lab Chip
12
(
24
),
5186
5194
(
2012
).
8.
A. A.
Epshteyn
,
S.
Maher
,
A. J.
Taylor
,
A. B.
Holton
,
J. T.
Borenstein
, and
J. D.
Cuiffi
, “
Membrane-integrated microfluidic device for high-resolution live cell imaging
,”
Biomicrofluidics
5
(
4
),
046501
(
2011
).
9.
A. K. H.
Achyuta
,
A. J.
Conway
,
R. B.
Crouse
,
E. C.
Bannister
,
R. N.
Lee
,
C. P.
Katnik
,
A. A.
Behensky
,
J.
Cuevas
, and
S. S.
Sundaram
, “
A modular approach to create a neurovascular unit-on-a-chip
,”
Lab Chip
13
(
4
),
542
553
(
2013
).
10.
D.
Huh
,
B. D.
Matthews
,
A.
Mammoto
,
M.
Montoya-Zavala
,
H. Y.
Hsin
, and
D. E.
Ingber
, “
Reconstituting organ-level lung functions on a chip
,”
Science
328
(
5986
),
1662
1668
(
2010
).
11.
R. F.
Ismagilov
,
J. M. K.
Ng
,
P. J. A.
Kenis
, and
G. M.
Whitesides
, “
Microfluidic arrays of fluid−fluid diffusional contacts as detection elements and combinatorial tools
,”
Anal. Chem.
73
(
21
),
5207
5213
(
2001
).
12.
T.-C.
Kuo
,
D. M.
Cannon
,
Y.
Chen
,
J. J.
Tulock
,
M. A.
Shannon
,
J. V.
Sweedler
, and
P. W.
Bohn
, “
Gateable nanofluidic interconnects for multilayered microfluidic separation systems
,”
Anal. Chem.
75
(
8
),
1861
1867
(
2003
).
13.
Y.
Zhang
and
A. T.
Timperman
, “
Integration of nanocapillary arrays into microfluidic devices for use as analyte concentrators
,”
Analyst
128
(
6
),
537
542
(
2003
).
14.
B. R.
Flachsbart
,
K.
Wong
,
J. M.
Iannacone
,
E. N.
Abante
,
R. L.
Vlach
,
P. A.
Rauchfuss
,
P. W.
Bohn
,
J. V.
Sweedler
, and
M. A.
Shannon
, “
Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing
,”
Lab Chip
6
(
5
),
667
674
(
2006
).
15.
S. N.
Masand
,
L.
Mignone
,
J. D.
Zahn
, and
D. I.
Shreiber
, “
Nanoporous membrane-sealed microfluidic devices for improved cell viability
,”
Biomed. Microdevices
13
(
6
),
955
961
(
2011
).
16.
M.
Morel
,
J.-C.
Galas
,
M.
Dahan
, and
V.
Studer
, “
Concentration landscape generators for shear free dynamic chemical stimulation
,”
Lab Chip
12
(
7
),
1340
(
2012
).
17.
B.
Chueh
,
D.
Huh
,
C. R.
Kyrtsos
,
T.
Houssin
,
N.
Futai
, and
S.
Takayama
, “
Leakage-free bonding of porous membranes into layered microfluidic array systems
,”
Anal. Chem.
79
(
9
),
3504
3508
(
2007
).
18.
J. J.
VanDersarl
,
A. M.
Xu
, and
N. A.
Melosh
, “
Rapid spatial and temporal controlled signal delivery over large cell culture areas
,”
Lab Chip
11
(
18
),
3057
(
2011
).
19.
H.
Kimura
,
T.
Yamamoto
,
H.
Sakai
,
Y.
Sakai
, and
T.
Fujii
, “
An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models
,”
Lab Chip
8
(
5
),
741
746
(
2008
).
20.
K.
Aran
,
L. A.
Sasso
,
N.
Kamdar
, and
J. D.
Zahn
, “
Irreversible, direct bonding of nanoporous polymer membranes to PDMS or glass microdevices
,”
Lab Chip
10
(
5
),
548
(
2010
).
21.
E. P.
Plueddemann
,
Silane Coupling Agents
(
Springer
,
1982
).
22.
M. E.
Vlachopoulou
,
A.
Tserepi
,
P.
Pavli
,
P.
Argitis
,
M.
Sanopoulou
, and
K. A.
Misiakos
, “
A low temperature surface modification assisted method for bonding plastic substrates
,”
J. Micromech. Microeng.
19
,
015007
(
2009
).
23.
Z.
Zhang
,
P.
Zhao
, and
G.
Xiao
, “
The fabrication of polymer microfluidic devices using a solid-to-solid interfacial polyaddition
,”
Polymer
50
(
23
),
5358
5361
(
2009
).
24.
L.
Tang
and
N. Y.
Lee
, “
A facile route for irreversible bonding of plastic-PDMS hybrid microdevices at room temperature
,”
Lab Chip
10
(
10
),
1274
(
2010
).
25.
K. S.
Lee
and
R. J.
Ram
, “
Plastic–PDMS bonding for high pressure hydrolytically stable active microfluidics
,”
Lab Chip
9
(
11
),
1618
(
2009
).
26.
See http://www.gelest.com/goods/pdf/faq/question%208.pdf for Gelest, Inc., Difficult Substrates.
27.
C.-H.
Hsu
,
C.
Chen
, and
A.
Folch
, “
Microcanals for micropipette access to single cells in microfluidic environments
,”
Lab Chip
4
(
5
),
420
(
2004
).
28.
D.
Yaffe
and
O.
Saxel
, “
Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle
,”
Nature
270
(
5639
),
725
727
(
1977
).
29.
See supplementary material at http://dx.doi.org/10.1063/1.4883075 for example XPS spectra and elemental composition data.
30.
V.
Sunkara
,
D.-K.
Park
,
H.
Hwang
,
R.
Chantiwas
,
S. A.
Soper
, and
Y.-K.
Cho
, “
Simple room temperature bonding of thermoplastics and poly(dimethylsiloxane)
,”
Lab Chip
11
(
5
),
962
(
2011
).
31.
D.
Zhu
and
W. J.
van Ooij
, “
Enhanced corrosion resistance of AA 2024-T3 and hot-dip galvanized steel using a mixture of bis-[triethoxysilylpropyl]tetrasulfide and bis-[trimethoxysilylpropyl]amine
,”
Electrochim. Acta
49
(
7
),
1113
1125
(
2004
).
32.
Y. S.
Shin
,
K.
Cho
,
S. H.
Lim
,
S.
Chung
,
S.-J.
Park
,
C.
Chung
,
D.-C.
Han
, and
J. K.
Chang
, “
PDMS-based micro PCR chip with Parylene coating
,”.
J. Micromech. Microeng.
13
(
5
),
768
(
2003
).
33.
T. Y.
Chang
,
V. G.
Yadav
,
S.
De Leo
,
A.
Mohedas
,
B.
Rajalingam
,
C.-L.
Chen
,
S.
Selvarasah
,
M. R.
Dokmeci
, and
A.
Khademhosseini
, “
Cell and protein compatibility of parylene-C surfaces
,”
Langmuir
23
(
23
),
11718
11725
(
2007
).

Supplementary Material

You do not currently have access to this content.