Microcontact printing (microCP) is a versatile tool for the chemical surface modification of substrates based on a mechanical concept. It makes use of an elastomeric stamp with a relief pattern. The stamp is inked with the chemical and the pattern of this chemical is transferred onto the substrate surface by contact. So far this technique has been in general performed manually or with modified expensive microelectronic aligners. We present here a new instrument, called Microcontact Printer, to pattern organic molecules as well as proteins and DNAs with a fully automated process. The mechanical design of this low cost and compact instrument is reviewed. Potential applications are discussed in the field of biochips and MEMS with emphasize on two exemples recently developed in our laboratory: (1) wet etching of glass microfluidic channels patterned by microCP and (2) grafting of biomolecules inside microfluidic channel

BOU CHAKRA, Elie

CABRERA, Michel

HANNES, Benjamin

I-Revues

18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
1 
A new instrument for automated microcontact printing. 
Applications to MEMS and biochips fabrication. 
 
Elie Bou Chakra, Benjamin Hannes & Michel Cabrera 
 
Institut des Nanotechnologies de Lyon   UMR CNRS ECL-INSA-UCBL n°5270 
Ecole Centrale de Lyon  - 36, avenue Guy de Collongue  69131 Ecully Cedex 
Michel.cabrera@ec-lyon.fr  
 
 
 
Abstract: 
 
Microcontact printing (CP) is a versatile tool for the chemical surface modification of substrates based 
on a mechanical concept. It makes use of an elastomeric stamp with a relief pattern. The stamp is inked 
with the chemical and the pattern of this chemical is transferred onto the substrate surface by contact. So 
far this technique has been in general performed manually or with modified expensive microelectronic 
aligners. We present here a new instrument, called Microcontact Printer, to pattern organic molecules as 
well as proteins and DNAs with a fully automated process. The mechanical design of this low cost and 
compact instrument is reviewed. Potential applications are discussed in the field of biochips and MEMS 
with emphasize on two exemples recently developed in our laboratory: (1) wet etching of glass 
microfluidic channels patterned by CP and (2) grafting of biomolecules inside microfluidic channel. 
 
Résumé : 
 
Le microtamponnage (TP) est un procédé flexible pour la chimie de surface de substrats basé sur un 
principe mécanique. L’outil de base est un tampon en élastomère comportant des motifs en relief. Le 
tampon est encré avec un produit chimique, qui est transféré à la surface du substrat par contact. Jusqu’à 
présent cette technique était mise en œuvre manuellement ou à l’aide d’aligneurs microélectroniques 
coûteux. Nous présentons un nouvel instrument complètement automatisé, un Microtamponneur, qui 
permet de créer des motifs de molécules organiques, de protéines et d’ADN. La conception mécanique de 
cet instrument compact et à bas coût est détaillée. Les applications potentielles pour les biopuces et les 
MEMS sont passées en revue avec deux exemples récemment développés dans notre laboratoire : (1) la 
gravure de circuits microfluidiques en verre avec des motifs crées par TP et (2) le greffage de 
biomolécules à l’intérieur d’un canal microfluidique. 
 
Key-words: microcontact printing ; MEMS ; biochip 
 
1 Introduction 
 
Microcontact printing (µCP) is a versatile tool for the surface modification of substrates 
(Xia & Whitesides 1998). It makes use of an elastomeric stamp of PDMS with a relief pattern. 
As shown in Figure 1, the stamp is inked with the chemical to deposit, so that a pattern of 
chemical is transferred onto the surface of the substrate by direct contact of the stamp with the 
substrate. Microcontact printing is in general additive (transfer of material form stamp to 
substrate), but it can be also subtractive (removal of material form substrate to stamp). 
In the case of chemicals like silanes or alkanethiols, it is well known that organic 
monolayers can be directly formed on silicon or glass substrates (Schreiber 2000). Specifically 
in the case of alkanethiols, patterns with a thickness of only 2-3 nanometers are good protecting 
masks for the etching of the substrate, which is under consideration for applications in micro 
and nanoelectronics (Kumar & Whitesides 1993). Lateral resolution in the 40 nm range has 
been recently demonstrated (Kang et al 2006). 
 
18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
2 
 
FIG. 1 – The Principle of Microcontact Printing 
 
Microcontact printing is not limited to microelectronics. To our knowledge, µCP is one the 
most promising way to address organic molecules and chemical on a substrate with such an 
extreme resolution. This point is illustrated in Figure 2 in the case of DNA and protein chips. 
This figure shows a comparison between key addressing technologies as regards the lateral 
resolution of the feature on the chip and the chip integration. The chip integration is defined as 
the number of different biomolecules probes on the chip (that is to say of different chemical 
compositions). Potentially, the degree of integration of biochips made by CP is two orders of 
magnitude better than the one obtained by photochemistry, which is the actual standard for 
DNA (Affymetrix technology). This is of course extremely important for biochip sensitivity. 
Unlike DPN, µCP can pattern large surfaces, so mass production is possible by collective 
fabrication. As a consequence, different research teams are exploring the potential of µCP for 
the grafting of DNA or proteins (Delamarche 2005), as well as the direct synthesis of DNA onto 
biochips (Xiao et al 2002).  
 
FIG. 2 – Comparison of different technologies for the manufacturing of biochips 
Fabrication of the master 
Molding of the PDMS stamp 
Demolding of the stamp 
Si master 
PDMS
Si master 
PDMS
PDMS
Chemical or 
biological “ink” 
Inking of the stamp 
Substrate 
Mechanical contact for ink transfer 
PDMS
Substrate 
Patterned substrate after stamp removal 
Preparation of the PDMS stamp Transfer of “ink” pattern by CP 
Fabrication of the silicon master 
18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
3 
 
To take full advantage of µCP potential, it is essential to perform the stamping with great 
repeatiblity and accuracy. But so far, µCP has been in general performed manually (Delamarche 
2005) or with modified expensive aligners derived from the microelectronic industry 
(http://www.evgroupcom/). We present here a new instrument, that we call Microcontact 
Printer, to pattern by µCP organic molecules (silanes, thiols, phosphoramidites for DNA 
synthesis, Fmoc for peptide synthesis, etc.), as well as proteins and DNAs on silicon or glass 
substrates with a micrometric resolution. We have developed a low cost and very compact 
instrument with a process simple and for the first time fully automatic. The mechanical design 
of the machine is reviewed in the next section. By varying the nature of the chemical and the 
substrate, it is possible to use this machine in a wide range of applications. To illustrate this 
point in the second part of this paper, two practical applications recently developed in our 
laboratory are also discussed: (1) the grafting of biomolecules by CP inside microfluidic 
channels and (2) the wet etching of glass microfluidic channels patterned by CP. 
 
2 Overview of the Microcontact Printer 
 
Our Microcontact Printer aims at patterning microscope slides or small silicon substrates 
with 50 x 15 cm pattern. For many applications, like the fabrication of protein or DNA chips by 
grafting of biomolecules, it is absolutely necessary to deposit different chemicals on the same 
substrate with different stamps. For more demanding applications, like the production of DNA 
chips by in situ chemical synthesis of oligonucleotides (Xiao et al 2002), it is necessary to 
sequentially deposit a series of different chemicals exactly at the same place on the substrates 
So the mechanical repeatability of the movement of the stamp and the possibility to change 
stamps and substrates are important points. We are looking also for the production of a small 
series of substrates. 
Therefore the Microcontact Printer has been designed to stamp a series of substrates after 
the initial calibration of the machine with the first substrate and keeping the set up of the 
machine for all other substrates. The instrument allows full monitoring of the process 
parameters to carefully control the load on the stamp (see section 4.), use different inks without 
cross contamination and change easily substrates and the stamps without re-alignment. Process 
reproducibility, full automation, quality control and use of minute quantity of reactants are also 
required. 
The design of the machine (Figure 3) is based on a pneumatic actuator which pushes the 
stamp back and forwards. As the movement of this actuator is not accurate enough, the 
movement of the stamp is guided by a high accuracy miniaturized linear slide. The machine 
incorporates features allowing the alignments of the stamp with the substrate, the change of 
substrate and/or stamp. It incorporates a miniaturized and automated inking system by 
pulverization and also CCD camera for quality control during the inking and the stamp/substrate 
contact (the inking and the quality systems have been described in a separate paper about the 
previous generation of machine: Hannes et al. 2005). (Hannes et al 2005). 
The parallelism of the stamp with the substrate during the contact is extremely important to 
avoid pattern distortion. Therefore the stamp holder is suspended with the two spherical 
bearings and hold by means of spring. This gives the freedom to align the parallelism with 
micrometric screws. 
The overall mechanical repeatability of the movement of the stamp is in the +/ 0.5 m 
range.This machine allows patterning of substrates by CP with results comparable with 
conventional mask aligners and UV illuminator for photolithography. The advantages are as 
follows: (i) the Microcontact Printer is much compact and less expensive than a mask aligner 
and that CP, (ii) it allows transferring a greater variety of products than a UV illuminator, 
which is limited to photopolymers or photochemical products. 
18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
4 
 
FIG. 3 – Overview of the Microcontact Printer 
 
3 First application for the etching of glass devices for microfluidics 
 
We present here a new process for the fabrication of glass lab-on-chips and plant-on-chips 
without any photolithographic steps. The etching of glass microfluidic devices, with deep 
channels is a complex process, which requires so far expensive microelectronic equipment and 
skilled personal for the etching itself (wet or dry etching) and for the preparation of the masks. 
These masks made of thick photopolymer, metals, or combination of both, have to withstand the 
harsh conditions necessary for the glass etching. We report here a flexible, quick and easy 
process which could be standardized and which could be also of great help for chemists or 
biologists willing to prepare glass microfluidic devices in their own laboratory. The innovative 
core of this process (CP followed by chemical etching) can be performed in a standard 
chemical fume hood. As a matter of fact, a clean room environment is not needed.  
Starting with substrates ready to use, 3”x1” microscope glass slides coated with a 
50 nm silver - 150 nm chromium bilayer, this process consists in stamping the pattern of the 
microfluidic device (e.g. channels, reservoirs, connections, etc.) with the Microcontact Printer. 
The chemical deposited on top of the silver layer is an alkanethiol, which serves as the first 
protecting mask. Then the substrate is simply dipped successively in four different beckers (i) to 
open the silver and chromium layers with acidic solutions, (ii) to remove the silver layer, (iii) to 
etch the glass through the chromium with fluorhydric acid and (iv) lastly to remove the 
remaining chromium with aquia regia. This leads to bare glass with 10-70 µm deep channels. 
Then the substrates can be sealed or covered with glass or other materials (simply by gluing or 
with an “easy” anodic bonding process under development). 
Figure 3 shows an example of a reservoir (diameter 300 µm) and a channel (width 50 µm) 
etched in a low cost soda-lime glass slide (20 m etch depth). The overall process is quick: a 
few seconds for stamping and the different etching steps, except for the etching of the glass 
which is performed at a rate of ~ 1 µm / minute. For industrial purpose, the process throughput 
is extremely high, so mass production is conceivable. 
Pneumatic actuator Flexible coupler 
YZX alignments  
Linear slide 
LEDs 
Lighting 
Substrate 
holder 
Substrate 
Inking head  
X 
Y 
Z 
Red PDMS stamp Removable stamp holder  
Micrometric screws for the stamp/substrate parallelism  
18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
5 
 
 
FIG. 4 – View of a reservoir and a channel etched in a microscope slide. 
 
In the field of research, the fabrication of the PDMS stamps can be performed by a rapid 
prototyping technique (under development) based on ink jet printing. By principle, µCP allows 
introducing a great flexibility in the design of microfluidic devices, so that modular fabrication 
is possible. Thanks to the design of the stamp holder of the Microcontact Printer allowing the 
exchange of stamps, multiple patterning of the same substrate with different stamps are 
possible. It is thus possible to make a complex microfluidic device by addition (stamping) of 
different elemental units. The principle is to design a stamp for every elemental chemical 
function: reservoir, channel, mixer, divider, heat exchanger,… and to dedicate one stamp per 
elemental function. The modular fabrication and optimization of plant-on-chips is possible with 
a way of “thinking” close to Chemical Engineering. 
 
4 Second application for the grafting of biomolecules inside microfluidic channels 
 
The Microcontact Printer allows also the grafting of biomolecules not only on top of plane 
substrates, but also inside (at the bottom) of microfluidic channels. Today, the integration of 
biochips in lab-on-chips is seen has a powerful solution to perform automatically all the 
complex and time consuming pre-processing or post-processing steps necessary for the use of 
biochips. Thanks to the features of our Microcontact Printer, µCP can be used for that purpose. 
 
This is illustrated in Figure 5, which shows on the left side, the principle of the grafting of 
fluorescent antibodies inside a microfluidic channel without damaging the fragile borders of the 
glass channel. Key dimensions are listed in the figure. The whole stamp is inked with the 
antibodies but the PDMS has a raised feature, which is very carefully applied at the bottom of 
the channel. As a consequence the transfer of antibodies from the stamp to the substrate is 
limited to the surface contact. This is proven by the scanned fluorescence image of the substrate 
which shows no significant fluorescence signal outside the channel. A high resolution scanning 
(not shown) proves that the width of the fluorescence is equal to the width of the PDMS raised 
feature. 
 The raised feature is an isolated piece of elastomeric material, a few cm long, with a 30 m 
width. The mechanical resolution of the Microcontact Printer allows fine alignment of the 
feature with the channel. But from the mechanical point of view, the issue was to finely regulate 
the load of the stamp during the contact, in order to avoid the collapse of the whole stamp. To 
do so, the solution was not to apply directly the pressure of the pneumatic actuator on the stamp. 
As show in Fig 5, two micrometric screws with micrometric resolution were used to limit the 
compression of the stamp (L-L’ ~ 2 ). So the load in excess is applied to the screws and not to 
the PDMS feature. It was possible to finely regulate the load on the stamp along the 5 cm long 
raised feature. To the best of our knowledge this is the first time that such a regulation is 
described for CP.  
18ème Congrès Français de Mécanique Grenoble, 27-31 août 2007 
6 
 
FIG. 5 – Grafting of antibodies inside microfluidic channels by µCP 
(d = 20 m; d’=70 m; L=1 mm; s’= 30 m h=25 m; h’~ 22,5+/-1 m). 
 
4 Conclusions 
 
In this paper, the design of an advanced instrument for automated CP is reported. This 
compact and low cost machine is only made of mechanical part available on the shelves. Its 
resolution is in the micrometric range and it incorporates many features which should make it 
useful for chemist and biologist willing to perform specific surface chemistry by µCP. This is 
illustrated with two applications for the fabrication of microfluidic glass devices and for the 
integration of biochips in lab-on-chips. It is known also that the stamp deformation during the 
contact is one of the limiting issue of µCP at very high resolution (Huang et al 2005). We have 
reported here a new solution to control the load on the stamp with fine regulation. The potential 
of this solution to reduce stamp deformation at submicrometic resolution is under investigation. 
 
References 
 
Delamarche E. 2005. Microcontact Printing of Proteins. In Nanobiotechnology, ed. CMNaCA 
Mirkin, pp. 31-52. Weinheim: Wiley-Vch Verlag GmbH 
Hannes B, Dilosquer G, Bou Chakra E, Bessueille F, Martin J, Cabrera M. 2005. New method 
for repeatable patterning of substrates for biodevices by automated microcontact 
printing. Eurosensors XIX. 11th-14th September 2005, Barcelona, Spain 
Huang YY, Zhou W, Hsia KJ, Menard E, Park JU, et al. 2005. Stamp Collapse in Soft 
Lithography. Langmuir 21:8058-68 
Kang H, Lee J, Park J, Lee HH. 2006. An improved method of preparing composite 
poly(dimethylsiloxane) moulds. Nanotechnology 17:197-200 
Kumar A, Whitesides GM. 1993. Features of gold having micrometer to centimeter dimensions 
can be formed through a combination of stamping with an elastomeric stamp and an 
alkanethiol ``ink' followed by chemical etching. Applied Physics Letters 63:2002-4 
Schreiber F. 2000. Structure and growth of self-assembling monolayers. Progress in Surface 
Science 65:151-257 
Xia Y, Whitesides GM. 1998. Soft Lithography. Angewandte Chemie International Edition 
37:550-75 
Xiao PF, He NY, Liu ZC, He QG, Sun X, Lu ZH. 2002. In situ synthesis of oligonucleotide 
arrays by using soft lithography. Nanotechnology:756-62 


A new instrument for automated microcontact printing with applications to mems and biochips fabrication

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A new instrument for automated microcontact printing with applications to mems and biochips fabrication

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