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Consecutive microcontact printing — ligands for asymmetric catalysis in silicon channels
Sensors and Actuators B 79 (2001) 78±84
Consecutive microcontact printing Ð ligands for asymmetric catalysis in silicon channels Helene Anderssona,*, Christina JoÈnssonb, Christina Mobergb, GoÈran Stemmea a
Department of Signals, Sensors and Systems, Royal Institute of Technology, S-10044 Stockholm, Sweden Department of Chemistry, Organic Chemistry, Royal Institute of Technology, S-10044 Stockholm, Sweden
b
Accepted 6 April 2001
Abstract Consecutive microcontact printing (mCP) has been developed to enable multiple functionalization of silicon surfaces, such as the immobilization of chiral ligands. The technique involves two subsequent printing steps using unstructured poly(methylsiloxane) stamps. The pattern is already de®ned on the substrate, consisting of etched channels. Hence, no precise alignment is needed between the two printing steps. A carboxylic acid group containing reagent was initially printed onto the silicon oxide surface and transformed to an anhydride. In the second printing step an ester bond was formed with the hydroxy-functionalized ligand. The formed molecular layers were evaluated by contact angle measurements, scanning electron microscopy (SEM) and electron spectroscopy for chemical analysis (ESCA), indicating that the consecutive mCP was successful. Initially, printing was performed on planar silicon surfaces but to realize a ¯ow-through micro¯uidic device for high throughput screening a mCP technique was developed for etched channels. To verify the technique, hydrophobic valves consisting of octadecyltrichlorosilane were formed using mCP in deep reactive ion etched channels (50 mm wide and 50 mm deep). The printed hydrophobic patches were visualized by SEM and functioned well. Finally, the consecutive mCP technique was applied to immobilize the ligand in the channels. The channels were then sealed with a low-temperature bonding technique using an adhesive PDMS ®lm, which does not destroy the printed ligand. In this study mCP is used in a novel manner. It enables a convenient method for performing complex surface modi®cation of etched structures, which is a frequently appearing problem in biochemical micro¯uidic systems. # 2001 Elsevier Science B.V. All rights reserved. Keywords: Microcontact printing; Chiral ligand; Catalysis; Solid phase screening; Hydrophobic valve
1. Introduction High throughput screening for the discovery of new chemical compounds and processes is currently attracting much attention. The purpose of the screening is either to optimize the selectivity and/or reactivity of a chemical reaction or to optimize the properties of a product. Miniaturized systems offer many advantages in the ®eld of high throughput screening. The efforts to combine organic chemistry and micromachining are increasing but, although potentially very useful, catalysis-on-a-chip is not yet very well explored. A micro¯uidic device for high throughput screening would reduce the catalyst and reagent consumption and facilitate the separation and control of the end product since the catalyst or reagent is immobilized on the chip surface. Miniaturized catalytic devices can also be used * Corresponding author. Tel.: 46-8-790-92-36; fax: 46-8-10-08-58. E-mail address: [email protected] (H. Andersson).
to conveniently gain kinetic and thermodynamic data for reactions. In addition, such devices are suitable for recycling and are therefore environmentally friendly. A possible chip design for performing combinatorial assays with immobilized catalysts would be an array of channels or reaction chambers with common or separate inlets and outlets, as illustrated in Fig. 1, where the catalysts are attached on the internal walls. To enable screening of several catalysts on the same chip a convenient and effective technique for applying different catalysts in the different elements constituting the array is needed. To seal the device, a low-temperature bonding technique must be applied to avoid destruction of the immobilized catalysts. Microcontact printing (mCP) is a widely applicable technique to generate patterns, with submicron feature size, by area-selective printing of reagents or molecules with desired functions using a poly(methylsiloxane) (PDMS) stamp. It provides a more direct and ¯exible method for surface modi®cation and reduces the number of chemical steps
0925-4005/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved. PII: S 0 9 2 5 - 4 0 0 5 ( 0 1 ) 0 0 8 3 8 - 3
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Fig. 1. A conceptual drawing of an array of flow-through serpentine channels for combinatorial assays.
associated with traditional photolithographic methods [1]. The mCP is a cost-effective strategy for forming small, highquality structures and it requires very little capital investment. The procedure is remarkable in its simplicity and speed [2]. It has been used to pattern alkanethiolates on gold, silver and copper substrates [2], alkylamines on reactive self assembled monolayers (SAM) of alkanethiolates [3], alkyltrichlorosilanes on metal oxides [4], colloids on polymers [5] and proteins on glass, plastics and silicon [6]. Instead of mCP a lift-off method can be used in order to create a pattern. In this technique, the substrate must have a patterned mask of metal, for example, and it is then immersed in a solution of the compound of interest. The metal mask is removed after the molecular layer has been formed leaving a pattern on the substrate [7]. Advantages of the lift-off technique are that it enables precision alignment and smaller feature size than mCP. Some of the drawbacks with this technique are that it requires clean room facilities, and that it includes a higher number of process steps than mCP. In addition, this technique consumes more time and reagents, is less ¯exible in terms of the choice of molecules since the formed layer must withstand the metal etching solution, and it involves metal processing that might interfere with other processes. Another alternative for generating lithographically de®ned patterns is the use of plasma polymerization. The pattern can be de®ned by a standard photoresist mask if this technique is used. Some of the advantages with this technique are that it is a dry chemical process, and that it is fast and simple and gives high precision. However, it is only possible to deposit a limited number of compounds by plasma polymerization. Therefore, this technique is not suitable for applications where a large variety of compounds are to be deposited (i.e. in screening assays). Hence, mCP seems to be the most suitable method to generate a pattern of a large number of different compounds on planar surfaces. The mCP on non-planar surfaces has so far only been shown on curved surfaces, i.e. on the outside of a capillary with a radius curvature of 500 or 50 mm [8]. Inregistry mCP in large (3:5 mm 3:6 mm) KOH etched structures has also been shown [9]. However, mCP has not previously been used to generate patterns in channels. Therefore, a model molecule, Octadecyltrichlorosilane
79
(OTS) has been used in this study to establish a technique for mCP in channels. In order to immobilize more complex molecules, such as ligands for asymmetric metal catalysis a technique, consecutive mCP, has also been developed. Here, one molecular layer is ®rst printed in order to transform the surface functionality to enable printing of the next layer on top of the ®rst. Finally, consecutive mCP of ligands for asymmetric catalysis in deep reactive ion etched channels was investigated. In this study ¯at stamps without patterns are used since the pattern is present on the substrate, i.e. the etched channels. This is a great advantage when performing consecutive mCP since no precise alignment of the two stamping steps is required. 2. Chemistry design Asymmetric catalysis is a powerful technique used, e.g. by the pharmaceutical industry in the search for new active compounds for pharmaceuticals. We have chosen to attach a chiral ligand capable of performing this type of catalysis on the silicon surface. A versatile ligand containing a suitable reactive attachment point was desired. For this purpose a pybox (2,6-bis(oxazolyl)pyridine) derivative, capable of catalyzing a variety of reactions, was selected. For the attachment of the alcohol to the surface, ester formation was considered to be appropriate. Esters can be formed via the reaction between an alcohol and a carboxylic acid in the presence of a suitable coupling reagent or from an alcohol and a carboxylic acid derivative. The latter method was chosen for the functionalization of the surface in order to avoid three-component reactions, believed not to be suitable for the present application. Initial functionalization of the surface via mCP with a carboxylic acid group-containing reagent enabling ester formation with the hydroxy group on the ligand was therefore performed. The mCP procedure has been performed in a consecutive manner where no precise alignment is necessary because the pattern, consisting of etched channels, is already generated on the substrate (Fig. 2).
Fig. 2. A schematic showing the principle consecutive mCP in channels, where `a' and `b' represent different reagents.
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3. Experimental 3.1. Microchannel fabrication The 300 mm thick p-type silicon wafers (10 cm in diameter) were used as the starting material. The channels were deep reactive ion etched using an ICP (Surface Technology Systems Multiplex) and standard photoresist masking. The channels were 40±100 mm wide and were etched 50 mm deep. The photoresist was stripped in acetone and the wafers were carefully rinsed with water and dried. The channels were reversibly sealed with a PDMS ®lm which was applied like an adhesive tape on the structured wafer [10]. 3.2. Microcontact printing The elastomeric stamps were fabricated of PDMS (Sylgard 184, Dow Corning). The elastomer and curing agent were mixed in a 10:1 ratio. The mixture was poured onto an unstructured, ¯at, silicon wafer coated with a thin ®lm of plasma polymerized C4F8. After degassing for 5 min in vacuum, curing for 15 min at 1408C, and cooling, the elastomer stamp was peeled off the master. Before use, the stamp was cut into suitable pieces (sizes of approximately 1 cm 1 cm). All PDMS stamps were carefully washed in ethanol before inking. All silicon surfaces to be used as substrates for mCP were treated with concentrated sulfuric acid and 30% hydrogen peroxide (in a ratio of 2.5:1) in order to oxidize the surface to obtain free hydroxy groups for further functionalizations. 3.2.1. Octadecyltrichlorosilane (OTS) printing The method for mCP of OTS was adapted from John et al. [11]. The unpatterned stamp was coated with a solution of 0.4% (v/v) OTS in hexadecane for approximately 5 min, dried in a stream of nitrogen gas and placed on top of the substrate. A 200 g weight was placed on top of the stamp to establish and maintain direct contact between the silicon surface and the stamp. The stamp was applied for 15 min, during which time the OTS was transferred onto the silicon surface. The substrate was separated from the stamp and sequentially rinsed and sonicated in toluene, isopropyl alcohol and water, and then dried. 3.2.2. Consecutive printing of 4-(chlorosulfonyl)benzoic acid and pybox 4-(Chlorosulfonyl)benzoic acid was dissolved in ethanol (1 mg/0.1 ml) and then applied on the PDMS-stamp. The time for the inking procedure was about 5±15 min. Then the stamp was applied to the oxidized silicon chip and the printing was performed for 15 min using a 500 g weight. The chip was sonicated for 5 min in ethanol, washed with methanol and dichloromethane and put in an oven-dried round-bottomed ¯ask under vacuum for 10 min to dry completely.
The ¯ask was charged with 2 ml of dimethylformamide (DMF), 150 ml of triethylamine and 30 ml of tri¯uoroacetic acid anhydride under N2 purging [12]. Acetic acid was then added drop wise until pH 5. The reaction mixture and the chip were incubated for 30 min. The chip was then washed carefully with dichloromethane and dried. The ligand was directly printed on the activated surface, forming ester bonds. First the chiral 2,6-bis(oxazolyl)pyridine (the compound was prepared from 4-chloro-2,6bis[40 (R)-phenyloxazolin-20 -yl]pyridine by a procedure that will be published later) [13] was dissolved in dimethylsulfoxide or DMF (note that the solvent must be compatible with the PDMS stamp and at the same time dissolve the substance used for printing). The solution was then applied to a clean stamp and inked for 30 min. Excess solution was removed and the stamp was dried in a stream of nitrogen. Printing was performed for 45 min using a 500 g weight. The chip was then washed and sonicated for 5 min in dichloromethane and acetone. The chip was kept under vacuum or in dichloromethane for 1±7 days before ESCA analysis was performed. 3.3. Electron spectroscopy for chemical analysis (ESCA) ESCA spectra were recorded using a Kratos AXIS HS Xray photoelectron spectrometer (Kratos Analytical, Manchester, UK). The samples were analyzed using a monochromator (Al X-ray source). The pressure during the analysis was below 1 10 7 Torr. The analysis area was <1 mm2. 3.4. Contact angle measurements The contact angle of water was measured with a Rame Hart goniometer for the different molecular layers. The contact angle data were collected by using water with a droplet size of 5 ml. 4. Results and discussion The consecutive mCP technique was ®rst evaluated on unstructured silicon surfaces. The cleaning of the substrate in sulfuric acid and hydrogen peroxide (2.5:1) proved to be a very important ®rst step in the printing procedure to generate a thin silicon oxide ®lm. To generate a good-quality molecular layer it is important to sonicate the chip in an appropriate solvent after the mCP step to remove unbound molecules from the surface. The synthetic procedure involved the transformation of the surface via mCP of 4-(chlorosulfonyl)benzoic acid, anhydride formation (in solution) and ®nally mCP of the ligand, (2,6-bis(oxazolyl)pyridine) (Scheme 1). Contact angle measurements were performed on each molecular layer to verify the mCP. Four measurements were performed on each layer resulting in the following averaged values, silicon oxide 228, anhydride 338, pybox 96.58. The
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Scheme 1. Synthetic scheme of consecutive mCP of 4-(chlorosulfonyl)benzoic acid and 2,6-bis(oxazolyl)pyridine.
ligand. In addition, measurements of the anhydride layer clearly show a peak at the shift expected for the carbon atom in the anhydride-bond. Measurements were performed both on and beside the printed area in order to investigate the spreading of the pattern. This demonstrated that the ligand was present at the stamped area but not at the negative control spot. The samples were kept in air or in an organic solvent (dichloromethane) during the time between mCP and ESCA. The surfaces were analyzed both directly after mCP and after 2 weeks. The formed molecular layer seems to be rather stable, as there were no noticeable differences in the ESCA spectra. In addition, mCP performed in the clean room and in a normal laboratory resulted in identical ESCA results. In mCP the elastomeric stamp is soaked with the target molecule, which diffuses into the rubbery bulk, the latter providing a reservoir of reactant. Conformal contact between the stamp and the substrate causes local delivery of these molecules, allowing their reaction with the surface [14]. Therefore, when applying mCP on a structured
results show that the surface characteristics changed after each surface treatment and the values correspond well with the hydrophobicity of the outermost atom layers. Negative control mCP of only the solvents used in the different steps was also performed. No change in the contact angle of the silicon oxide surface was detected after the control stamping of solvents. The chemical composition of the surface layer (about 2± 10 nm) was studied with ESCA, also known as X-ray photoelectron spectroscopy (XPS). Here, information is obtained about the oxidation state of the elements as well as their chemical environment. In the analysis, wide spectra were ®rst run to detect elements present in the surface layer. This was followed by detailed spectra for each element, and then the relative surface composition was obtained from the quanti®cation of C, O, Si and N. All other elements were at noise level (which is about 0.5±1 at.%). The ESCA results of the different molecular layers are listed in Table 1. The table shows that the carbon content increases with the number of layers and the presence of nitrogen from the immobilized
Table 1 The table shows the results from ESCA analysis of the different molecular layers on the substrate formed via mCPa Sample type Silicon oxide Carboxylic acid Anhydride Pybox (ligand) a
Nitrogen (1s) b
NV NVb NVb 1, 2
Carbon (1s) C=C, C±C b
NV <2 4, 9 7.5±10.5
Carbon (1s) O±C=O,±C(=O)±O±C(=O)± NVb NVb 1, 1 NVb
All values are in atomic percent calculated from raw areas in the ESCA spectra and normal background noise/contamination has been substracted from the noted values. b NV: no value.
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substrate (i.e. with etched channels) it is important to ®rst con®rm that the stamp comes into contact with the internal walls of the channels. This was determined by pressing a PDMS stamp onto a 50 mm wide and deep channel and simultaneously observing the process from the side through a microscope. The stamp was ¯exible enough to form contact with the internal walls of the channel. In developing a technique for mCP in etched channels a model molecule, OTS, was used to generate hydrophobic valves in deep reactive ion etched channels since this provides a means of evaluating the printed area. Hydrophobic valves of OTS have previously been formed by lift-off methods and proved to function [7]. The mCP procedure for OTS described for the unstructured substrates was applied without any modi®cations. The OTS pattern was easily imaged in the scanning electron microscope (SEM) and its contact angle with water differed signi®cantly from that of silicon oxide (110 and 228, respectively). In Fig. 3, an array of channels, 100 mm wide and 50 mm deep is shown where a patch of OTS has successfully been printed in the channels. OTS is present on the bottom of the channel as well as on the side of the walls. To verify the function of the hydrophobic valves, a drop of water was applied at one end of the open channels. The water ®lled the channels automatically by capillary forces until the beginning of the OTS patch, as shown in Fig. 4. To determine if the whole patch is intact a drop of water was applied in the middle of the patch, Fig. 5. The water did not ®ll the channels in any direction showing that the OTS coverage is homogeneous, in accordance with the SEM pictures. The water tests were performed on untreated channels as well. Here, the whole channels were immediately ®lled by
Fig. 4. A light microscopy image showing the function of the hydrophobic valves. Water was added to the open channels from the left in the picture and was stopped by the microcontacted printed OTS patch shown in Fig. 3.
capillary forces. An OTS patch was also printed into a 50 mm deep channel with different widths, ranging from 40 to 100 mm. The patch was tested by applying water. The water ®lled the channel until the beginning of the patch demonstrating that the mCP into the channel was successful even at the part where the channel is only 40 mm wide, as shown in Fig. 6. The one-step mCP of OTS in the channels clearly shows that it is possible to achieve speci®c application of a molecular layer with good edge coverage onto etched
Fig. 3. A SEM image of an array of channels, 100 mm wide and 50 mm deep, which have partly been coated with OTS by mCP. The photo shows that the OTS-layer covers both the side walls and the bottom of the channel.
H. Andersson et al. / Sensors and Actuators B 79 (2001) 78±84
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Fig. 7. A photo showing a wetting test. Methanol was added from the left in the picture and was stopped by the printed pybox indicating successful immobilization of pybox in the channels.
Fig. 5. A drop of water was put in the channels in the middle of the printed area. The water does not fill the channels in any directions indicating that the OTS patch is intact and homogeneous.
channels. Therefore, the next step was to immobilize the catalytic molecule, pybox, in the channels via the consecutive mCP-technique established on the unstructured substrates. SEM images were taken on each molecular layer in the channels, but unfortunately the ligand was dif®cult to visualize. However, it was possible to detect the presence of the ligand in the channels by looking at the borders of the printed area. The printing was also evaluated by wetting tests since the pybox contact angle (96.58) differs signi®cantly from that of the under-laying anhydride (338). In Fig. 7, a photo shows that methanol ®lls the array of channels until the beginning of the printed patch of pybox indicating that the pybox has been immobilized successfully. Finally, the device was sealed with a PDMS ®lm. This is a roomtemperature bonding technique, which is required to avoid destruction of the printed ligand. The mCP in this study has been performed using ¯at PDMS stamps with no topographic pattern, i.e. the edge of the PDMS stamp de®ned the edge of the stamped surface. This was possible because the pattern, i.e. the etched channel, was already present on the substrate and had been generated by conventional lithography. When printing
molecules using consecutive mCP it is important that the pattern is present on the substrate to avoid the need for precise alignment of the two printing steps. In addition, when printing ligands for catalytically active metals organic solvents are used and PDMS is known to swell in organic solvents distorting the pattern on the stamp (to different extent depending on the solvent) [15]. Since the ®nal pattern is de®ned by photolithography and etching the swelling of the stamp does not effect the outcome of the mCP in this study. In developing micro¯uidic chips for screening and analysis it is important to make them user-friendly. The user must be able to easily change the functional groups of the internal surface of the micro¯uidic chip. Therefore, it was important to develop a technique for performing mCP in etched structures since application of molecules by mCP can be performed by the user outside the clean room and by using consecutive mCP a large variety of compounds can be immobilized. Chiral ligands for asymmetric catalysis other than pybox are also currently immobilized using consecutive mCP. 5. Conclusions This study shows that consecutive mCP facilitates surface modi®cations. In the ®rst printing step, suitable functional
Fig. 6. A light microscopy image showing a functional hydrophobic valve of OTS generated by mCP in a channel, which is only 40 mm wide.
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groups are attached to the surface. A ligand or a reagent can then be immobilized in the second printing step. In the attempt to realize a micro¯uidic device for catalyst screening, a consecutive mCP technique has successfully been applied in deep reactive ion etched channels. Acknowledgements The authors would like to thank Lubica Macakova at the Royal Institute of Technology, Department of Chemistry, Surface Chemistry, for the contact angle measurements and Linda Sundberg at the Royal Institute of Technology, Department of Polymer Technology for help with the PDMS stamps. Finally, we would like to thank the Foundation for Strategic Research (SSF) for funding this study performed within the Nanochemistry Program at the Royal Institute of Technology. References [1] A. Kumar, H. Biebuyck, G. Whitesides, Patterning self-assembled monolayers: applications in material science, Langmuir 10 (1994) 1498±1511. [2] Y. Xia, G. Whitesides, Soft Lithography, Angew. Chem. Int. Ed. 37 (1998) 550±575. [3] L. Yan, X. Zhao, G. Whitesides, Patterning a preformed reactive SAM using microcontact printing, J. Am. Chem. Soc. 120 (1998) 6179±6180. [4] N. Jeon, R. Nuzzo, Patterned self-assembled monolayers formed by microcontact printing direct selective metalization by chemical vapor deposition on planar and nonplanar substrates, Langmuir 11 (1995) 3024±3026. [5] P. Hidber, W. Helbig, E. Kim, G. Whitesides, Microcontact printing of palladium colloids: micron-scale patterning by electroless deposition of copper, Langmuir 12 (1996) 1375±1380. [6] A. Bernard, E. Delamarche, H. Schmid, B. Michel, H. Bosshard, H. Biebuyck, Printing patterns of proteins, Langmuir 14 (1998) 2225±2229. [7] K. Handique, B. Gogoi, D. Burke, C. Mastrangelo, M. Burns, Microfluidic flow control using selective hydrophobic patterning, SPIE 3224 (1997) 185±195. [8] R. Jackman, S. Brittain, A. Adams, M. Prentiss, G. Whitesides, Design and fabrication of topologically complex, three-dimensional microstructures, Science 280 (1998) 2089±2091. [9] A. Folch, M. Schmidt, Wafer-level in-registry microstamping, J. Microelectromechanical Syst. 8 (1999) 85±89. [10] J. McDonald, D. Duffy, J. Andersson, D. Chiu, H. Wu, O. Schueller, G. Whitesides, Fabrication of microfluidic systems in poly(dimethylsiloxane), Electrophoresis 21 (2000) 27±40.
[11] P.St. John, L. Kam, S. Turner, H. Craighead, M. Issacson, J. Turner, W. Shain, Preferential glial cell attachment to microcontact printed surfaces, J. Neurosci. 75 (1997) 171±177. [12] L. Yan, W.T.S. Huck, X.M. Zhao, G.M. Whitesides, Patterning thin films of poly(ethylene imine) on a reactive SAM using microcontact printing, Langmuir 15 (1999) 1208±1214. [13] H. Nishiyama, S. Yamaguchi, M. Kondo, K. Itoh, Electronic substituents effect of nitrogen ligands in catalytic asymmetric hydrosilylation of ketones: chiral 4-substituted bis(oxazolinyl)pyridines, J. Org. Chem. 57 (1992) 4306±4309. [14] N. Larsen, H. Biebuyck, E. Delamarche, B. Michel, Order in microcontact printed self-assembled monolayers, J. Am. Chem. Soc. 119 (1997) 3017±3026. [15] K.F. Jensen, The Impact of MEMS on the Chemical and Pharmaceutical Industries, Solid-State Sensors and Actuator Workshop, Hilton Head Island, South Carolina, June 2000, 105±110.
Biographies Helene Andersson was born in 1974 in Hudiksvall, Sweden. She received her MSc degree in Molecular Biotechnology in 1998 from Uppsala University, Sweden. In the beginning of 1999, she started her PhD studies at the Department of Signals, Sensors and Systems at the Royal Institute of Technology, Stockholm, Sweden. Her main research areas are microfluidics, micro total analysis systems, micropumps and nanochemistry. Christina JoÈnsson was born in 1972 in NorrkoÈping, Sweden. She received her MSc degree in Chemistry in 1997 from LinkoÈping University. In June 1999, she started her PhD studies at the Department of Organic Chemistry at the Royal Institute of Technology, Stockholm, Sweden. Her main research area is synthesis of chiral ligands for asymmetric catalysis and their immobilization on solid support in order to perform nanochemistry. Christina Moberg was born in GaÈvle, Sweden, in 1947. She received her BSc degree in 1970 at the Stockholm University and the PhD degree in organic chemistry in 1975 from the Royal Institute of Technology, Stockholm, Sweden. She became Associate Professor in 1989 and was appointed Full Professor in 1997. Her research is devoted to the development of new selective organic synthetic methods employing asymmetric metal catalysts. GoÈran Stemme was born in Stockholm, Sweden, on 4 February 1958. He received the MSc degree in Electrical Engineering in 1981 and the PhD degree in Solid State Electronics in 1987, both from the Chalmers University of Technology, Gothenburg, Sweden. In 1981, he joined the Department of Solid State Electronics, Chalmers University of Technology, Gothenburg, Sweden. There, in 1990, he became an Associate Professor (Docent) heading the silicon sensor research group. In 1991, Dr Stemme was appointed Professor at the Royal Institute of Technology, Stockholm, Sweden. He heads the Instrumentation Laboratory at the department of Signals, Sensors & Systems. His research is devoted to sensors and actuators based on micromachining of silicon. Dr Stemme is a subject editor for the IEEE/ASME J. Microelectromechanical Systems.
Consecutive microcontact printing Ð ligands for asymmetric catalysis in silicon channels Helene Anderssona,*, Christina JoÈnssonb, Christina Mobergb, GoÈran Stemmea a
Department of Signals, Sensors and Systems, Royal Institute of Technology, S-10044 Stockholm, Sweden Department of Chemistry, Organic Chemistry, Royal Institute of Technology, S-10044 Stockholm, Sweden
b
Accepted 6 April 2001
Abstract Consecutive microcontact printing (mCP) has been developed to enable multiple functionalization of silicon surfaces, such as the immobilization of chiral ligands. The technique involves two subsequent printing steps using unstructured poly(methylsiloxane) stamps. The pattern is already de®ned on the substrate, consisting of etched channels. Hence, no precise alignment is needed between the two printing steps. A carboxylic acid group containing reagent was initially printed onto the silicon oxide surface and transformed to an anhydride. In the second printing step an ester bond was formed with the hydroxy-functionalized ligand. The formed molecular layers were evaluated by contact angle measurements, scanning electron microscopy (SEM) and electron spectroscopy for chemical analysis (ESCA), indicating that the consecutive mCP was successful. Initially, printing was performed on planar silicon surfaces but to realize a ¯ow-through micro¯uidic device for high throughput screening a mCP technique was developed for etched channels. To verify the technique, hydrophobic valves consisting of octadecyltrichlorosilane were formed using mCP in deep reactive ion etched channels (50 mm wide and 50 mm deep). The printed hydrophobic patches were visualized by SEM and functioned well. Finally, the consecutive mCP technique was applied to immobilize the ligand in the channels. The channels were then sealed with a low-temperature bonding technique using an adhesive PDMS ®lm, which does not destroy the printed ligand. In this study mCP is used in a novel manner. It enables a convenient method for performing complex surface modi®cation of etched structures, which is a frequently appearing problem in biochemical micro¯uidic systems. # 2001 Elsevier Science B.V. All rights reserved. Keywords: Microcontact printing; Chiral ligand; Catalysis; Solid phase screening; Hydrophobic valve
1. Introduction High throughput screening for the discovery of new chemical compounds and processes is currently attracting much attention. The purpose of the screening is either to optimize the selectivity and/or reactivity of a chemical reaction or to optimize the properties of a product. Miniaturized systems offer many advantages in the ®eld of high throughput screening. The efforts to combine organic chemistry and micromachining are increasing but, although potentially very useful, catalysis-on-a-chip is not yet very well explored. A micro¯uidic device for high throughput screening would reduce the catalyst and reagent consumption and facilitate the separation and control of the end product since the catalyst or reagent is immobilized on the chip surface. Miniaturized catalytic devices can also be used * Corresponding author. Tel.: 46-8-790-92-36; fax: 46-8-10-08-58. E-mail address: [email protected] (H. Andersson).
to conveniently gain kinetic and thermodynamic data for reactions. In addition, such devices are suitable for recycling and are therefore environmentally friendly. A possible chip design for performing combinatorial assays with immobilized catalysts would be an array of channels or reaction chambers with common or separate inlets and outlets, as illustrated in Fig. 1, where the catalysts are attached on the internal walls. To enable screening of several catalysts on the same chip a convenient and effective technique for applying different catalysts in the different elements constituting the array is needed. To seal the device, a low-temperature bonding technique must be applied to avoid destruction of the immobilized catalysts. Microcontact printing (mCP) is a widely applicable technique to generate patterns, with submicron feature size, by area-selective printing of reagents or molecules with desired functions using a poly(methylsiloxane) (PDMS) stamp. It provides a more direct and ¯exible method for surface modi®cation and reduces the number of chemical steps
0925-4005/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved. PII: S 0 9 2 5 - 4 0 0 5 ( 0 1 ) 0 0 8 3 8 - 3
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Fig. 1. A conceptual drawing of an array of flow-through serpentine channels for combinatorial assays.
associated with traditional photolithographic methods [1]. The mCP is a cost-effective strategy for forming small, highquality structures and it requires very little capital investment. The procedure is remarkable in its simplicity and speed [2]. It has been used to pattern alkanethiolates on gold, silver and copper substrates [2], alkylamines on reactive self assembled monolayers (SAM) of alkanethiolates [3], alkyltrichlorosilanes on metal oxides [4], colloids on polymers [5] and proteins on glass, plastics and silicon [6]. Instead of mCP a lift-off method can be used in order to create a pattern. In this technique, the substrate must have a patterned mask of metal, for example, and it is then immersed in a solution of the compound of interest. The metal mask is removed after the molecular layer has been formed leaving a pattern on the substrate [7]. Advantages of the lift-off technique are that it enables precision alignment and smaller feature size than mCP. Some of the drawbacks with this technique are that it requires clean room facilities, and that it includes a higher number of process steps than mCP. In addition, this technique consumes more time and reagents, is less ¯exible in terms of the choice of molecules since the formed layer must withstand the metal etching solution, and it involves metal processing that might interfere with other processes. Another alternative for generating lithographically de®ned patterns is the use of plasma polymerization. The pattern can be de®ned by a standard photoresist mask if this technique is used. Some of the advantages with this technique are that it is a dry chemical process, and that it is fast and simple and gives high precision. However, it is only possible to deposit a limited number of compounds by plasma polymerization. Therefore, this technique is not suitable for applications where a large variety of compounds are to be deposited (i.e. in screening assays). Hence, mCP seems to be the most suitable method to generate a pattern of a large number of different compounds on planar surfaces. The mCP on non-planar surfaces has so far only been shown on curved surfaces, i.e. on the outside of a capillary with a radius curvature of 500 or 50 mm [8]. Inregistry mCP in large (3:5 mm 3:6 mm) KOH etched structures has also been shown [9]. However, mCP has not previously been used to generate patterns in channels. Therefore, a model molecule, Octadecyltrichlorosilane
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(OTS) has been used in this study to establish a technique for mCP in channels. In order to immobilize more complex molecules, such as ligands for asymmetric metal catalysis a technique, consecutive mCP, has also been developed. Here, one molecular layer is ®rst printed in order to transform the surface functionality to enable printing of the next layer on top of the ®rst. Finally, consecutive mCP of ligands for asymmetric catalysis in deep reactive ion etched channels was investigated. In this study ¯at stamps without patterns are used since the pattern is present on the substrate, i.e. the etched channels. This is a great advantage when performing consecutive mCP since no precise alignment of the two stamping steps is required. 2. Chemistry design Asymmetric catalysis is a powerful technique used, e.g. by the pharmaceutical industry in the search for new active compounds for pharmaceuticals. We have chosen to attach a chiral ligand capable of performing this type of catalysis on the silicon surface. A versatile ligand containing a suitable reactive attachment point was desired. For this purpose a pybox (2,6-bis(oxazolyl)pyridine) derivative, capable of catalyzing a variety of reactions, was selected. For the attachment of the alcohol to the surface, ester formation was considered to be appropriate. Esters can be formed via the reaction between an alcohol and a carboxylic acid in the presence of a suitable coupling reagent or from an alcohol and a carboxylic acid derivative. The latter method was chosen for the functionalization of the surface in order to avoid three-component reactions, believed not to be suitable for the present application. Initial functionalization of the surface via mCP with a carboxylic acid group-containing reagent enabling ester formation with the hydroxy group on the ligand was therefore performed. The mCP procedure has been performed in a consecutive manner where no precise alignment is necessary because the pattern, consisting of etched channels, is already generated on the substrate (Fig. 2).
Fig. 2. A schematic showing the principle consecutive mCP in channels, where `a' and `b' represent different reagents.
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3. Experimental 3.1. Microchannel fabrication The 300 mm thick p-type silicon wafers (10 cm in diameter) were used as the starting material. The channels were deep reactive ion etched using an ICP (Surface Technology Systems Multiplex) and standard photoresist masking. The channels were 40±100 mm wide and were etched 50 mm deep. The photoresist was stripped in acetone and the wafers were carefully rinsed with water and dried. The channels were reversibly sealed with a PDMS ®lm which was applied like an adhesive tape on the structured wafer [10]. 3.2. Microcontact printing The elastomeric stamps were fabricated of PDMS (Sylgard 184, Dow Corning). The elastomer and curing agent were mixed in a 10:1 ratio. The mixture was poured onto an unstructured, ¯at, silicon wafer coated with a thin ®lm of plasma polymerized C4F8. After degassing for 5 min in vacuum, curing for 15 min at 1408C, and cooling, the elastomer stamp was peeled off the master. Before use, the stamp was cut into suitable pieces (sizes of approximately 1 cm 1 cm). All PDMS stamps were carefully washed in ethanol before inking. All silicon surfaces to be used as substrates for mCP were treated with concentrated sulfuric acid and 30% hydrogen peroxide (in a ratio of 2.5:1) in order to oxidize the surface to obtain free hydroxy groups for further functionalizations. 3.2.1. Octadecyltrichlorosilane (OTS) printing The method for mCP of OTS was adapted from John et al. [11]. The unpatterned stamp was coated with a solution of 0.4% (v/v) OTS in hexadecane for approximately 5 min, dried in a stream of nitrogen gas and placed on top of the substrate. A 200 g weight was placed on top of the stamp to establish and maintain direct contact between the silicon surface and the stamp. The stamp was applied for 15 min, during which time the OTS was transferred onto the silicon surface. The substrate was separated from the stamp and sequentially rinsed and sonicated in toluene, isopropyl alcohol and water, and then dried. 3.2.2. Consecutive printing of 4-(chlorosulfonyl)benzoic acid and pybox 4-(Chlorosulfonyl)benzoic acid was dissolved in ethanol (1 mg/0.1 ml) and then applied on the PDMS-stamp. The time for the inking procedure was about 5±15 min. Then the stamp was applied to the oxidized silicon chip and the printing was performed for 15 min using a 500 g weight. The chip was sonicated for 5 min in ethanol, washed with methanol and dichloromethane and put in an oven-dried round-bottomed ¯ask under vacuum for 10 min to dry completely.
The ¯ask was charged with 2 ml of dimethylformamide (DMF), 150 ml of triethylamine and 30 ml of tri¯uoroacetic acid anhydride under N2 purging [12]. Acetic acid was then added drop wise until pH 5. The reaction mixture and the chip were incubated for 30 min. The chip was then washed carefully with dichloromethane and dried. The ligand was directly printed on the activated surface, forming ester bonds. First the chiral 2,6-bis(oxazolyl)pyridine (the compound was prepared from 4-chloro-2,6bis[40 (R)-phenyloxazolin-20 -yl]pyridine by a procedure that will be published later) [13] was dissolved in dimethylsulfoxide or DMF (note that the solvent must be compatible with the PDMS stamp and at the same time dissolve the substance used for printing). The solution was then applied to a clean stamp and inked for 30 min. Excess solution was removed and the stamp was dried in a stream of nitrogen. Printing was performed for 45 min using a 500 g weight. The chip was then washed and sonicated for 5 min in dichloromethane and acetone. The chip was kept under vacuum or in dichloromethane for 1±7 days before ESCA analysis was performed. 3.3. Electron spectroscopy for chemical analysis (ESCA) ESCA spectra were recorded using a Kratos AXIS HS Xray photoelectron spectrometer (Kratos Analytical, Manchester, UK). The samples were analyzed using a monochromator (Al X-ray source). The pressure during the analysis was below 1 10 7 Torr. The analysis area was <1 mm2. 3.4. Contact angle measurements The contact angle of water was measured with a Rame Hart goniometer for the different molecular layers. The contact angle data were collected by using water with a droplet size of 5 ml. 4. Results and discussion The consecutive mCP technique was ®rst evaluated on unstructured silicon surfaces. The cleaning of the substrate in sulfuric acid and hydrogen peroxide (2.5:1) proved to be a very important ®rst step in the printing procedure to generate a thin silicon oxide ®lm. To generate a good-quality molecular layer it is important to sonicate the chip in an appropriate solvent after the mCP step to remove unbound molecules from the surface. The synthetic procedure involved the transformation of the surface via mCP of 4-(chlorosulfonyl)benzoic acid, anhydride formation (in solution) and ®nally mCP of the ligand, (2,6-bis(oxazolyl)pyridine) (Scheme 1). Contact angle measurements were performed on each molecular layer to verify the mCP. Four measurements were performed on each layer resulting in the following averaged values, silicon oxide 228, anhydride 338, pybox 96.58. The
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Scheme 1. Synthetic scheme of consecutive mCP of 4-(chlorosulfonyl)benzoic acid and 2,6-bis(oxazolyl)pyridine.
ligand. In addition, measurements of the anhydride layer clearly show a peak at the shift expected for the carbon atom in the anhydride-bond. Measurements were performed both on and beside the printed area in order to investigate the spreading of the pattern. This demonstrated that the ligand was present at the stamped area but not at the negative control spot. The samples were kept in air or in an organic solvent (dichloromethane) during the time between mCP and ESCA. The surfaces were analyzed both directly after mCP and after 2 weeks. The formed molecular layer seems to be rather stable, as there were no noticeable differences in the ESCA spectra. In addition, mCP performed in the clean room and in a normal laboratory resulted in identical ESCA results. In mCP the elastomeric stamp is soaked with the target molecule, which diffuses into the rubbery bulk, the latter providing a reservoir of reactant. Conformal contact between the stamp and the substrate causes local delivery of these molecules, allowing their reaction with the surface [14]. Therefore, when applying mCP on a structured
results show that the surface characteristics changed after each surface treatment and the values correspond well with the hydrophobicity of the outermost atom layers. Negative control mCP of only the solvents used in the different steps was also performed. No change in the contact angle of the silicon oxide surface was detected after the control stamping of solvents. The chemical composition of the surface layer (about 2± 10 nm) was studied with ESCA, also known as X-ray photoelectron spectroscopy (XPS). Here, information is obtained about the oxidation state of the elements as well as their chemical environment. In the analysis, wide spectra were ®rst run to detect elements present in the surface layer. This was followed by detailed spectra for each element, and then the relative surface composition was obtained from the quanti®cation of C, O, Si and N. All other elements were at noise level (which is about 0.5±1 at.%). The ESCA results of the different molecular layers are listed in Table 1. The table shows that the carbon content increases with the number of layers and the presence of nitrogen from the immobilized
Table 1 The table shows the results from ESCA analysis of the different molecular layers on the substrate formed via mCPa Sample type Silicon oxide Carboxylic acid Anhydride Pybox (ligand) a
Nitrogen (1s) b
NV NVb NVb 1, 2
Carbon (1s) C=C, C±C b
NV <2 4, 9 7.5±10.5
Carbon (1s) O±C=O,±C(=O)±O±C(=O)± NVb NVb 1, 1 NVb
All values are in atomic percent calculated from raw areas in the ESCA spectra and normal background noise/contamination has been substracted from the noted values. b NV: no value.
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substrate (i.e. with etched channels) it is important to ®rst con®rm that the stamp comes into contact with the internal walls of the channels. This was determined by pressing a PDMS stamp onto a 50 mm wide and deep channel and simultaneously observing the process from the side through a microscope. The stamp was ¯exible enough to form contact with the internal walls of the channel. In developing a technique for mCP in etched channels a model molecule, OTS, was used to generate hydrophobic valves in deep reactive ion etched channels since this provides a means of evaluating the printed area. Hydrophobic valves of OTS have previously been formed by lift-off methods and proved to function [7]. The mCP procedure for OTS described for the unstructured substrates was applied without any modi®cations. The OTS pattern was easily imaged in the scanning electron microscope (SEM) and its contact angle with water differed signi®cantly from that of silicon oxide (110 and 228, respectively). In Fig. 3, an array of channels, 100 mm wide and 50 mm deep is shown where a patch of OTS has successfully been printed in the channels. OTS is present on the bottom of the channel as well as on the side of the walls. To verify the function of the hydrophobic valves, a drop of water was applied at one end of the open channels. The water ®lled the channels automatically by capillary forces until the beginning of the OTS patch, as shown in Fig. 4. To determine if the whole patch is intact a drop of water was applied in the middle of the patch, Fig. 5. The water did not ®ll the channels in any direction showing that the OTS coverage is homogeneous, in accordance with the SEM pictures. The water tests were performed on untreated channels as well. Here, the whole channels were immediately ®lled by
Fig. 4. A light microscopy image showing the function of the hydrophobic valves. Water was added to the open channels from the left in the picture and was stopped by the microcontacted printed OTS patch shown in Fig. 3.
capillary forces. An OTS patch was also printed into a 50 mm deep channel with different widths, ranging from 40 to 100 mm. The patch was tested by applying water. The water ®lled the channel until the beginning of the patch demonstrating that the mCP into the channel was successful even at the part where the channel is only 40 mm wide, as shown in Fig. 6. The one-step mCP of OTS in the channels clearly shows that it is possible to achieve speci®c application of a molecular layer with good edge coverage onto etched
Fig. 3. A SEM image of an array of channels, 100 mm wide and 50 mm deep, which have partly been coated with OTS by mCP. The photo shows that the OTS-layer covers both the side walls and the bottom of the channel.
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Fig. 7. A photo showing a wetting test. Methanol was added from the left in the picture and was stopped by the printed pybox indicating successful immobilization of pybox in the channels.
Fig. 5. A drop of water was put in the channels in the middle of the printed area. The water does not fill the channels in any directions indicating that the OTS patch is intact and homogeneous.
channels. Therefore, the next step was to immobilize the catalytic molecule, pybox, in the channels via the consecutive mCP-technique established on the unstructured substrates. SEM images were taken on each molecular layer in the channels, but unfortunately the ligand was dif®cult to visualize. However, it was possible to detect the presence of the ligand in the channels by looking at the borders of the printed area. The printing was also evaluated by wetting tests since the pybox contact angle (96.58) differs signi®cantly from that of the under-laying anhydride (338). In Fig. 7, a photo shows that methanol ®lls the array of channels until the beginning of the printed patch of pybox indicating that the pybox has been immobilized successfully. Finally, the device was sealed with a PDMS ®lm. This is a roomtemperature bonding technique, which is required to avoid destruction of the printed ligand. The mCP in this study has been performed using ¯at PDMS stamps with no topographic pattern, i.e. the edge of the PDMS stamp de®ned the edge of the stamped surface. This was possible because the pattern, i.e. the etched channel, was already present on the substrate and had been generated by conventional lithography. When printing
molecules using consecutive mCP it is important that the pattern is present on the substrate to avoid the need for precise alignment of the two printing steps. In addition, when printing ligands for catalytically active metals organic solvents are used and PDMS is known to swell in organic solvents distorting the pattern on the stamp (to different extent depending on the solvent) [15]. Since the ®nal pattern is de®ned by photolithography and etching the swelling of the stamp does not effect the outcome of the mCP in this study. In developing micro¯uidic chips for screening and analysis it is important to make them user-friendly. The user must be able to easily change the functional groups of the internal surface of the micro¯uidic chip. Therefore, it was important to develop a technique for performing mCP in etched structures since application of molecules by mCP can be performed by the user outside the clean room and by using consecutive mCP a large variety of compounds can be immobilized. Chiral ligands for asymmetric catalysis other than pybox are also currently immobilized using consecutive mCP. 5. Conclusions This study shows that consecutive mCP facilitates surface modi®cations. In the ®rst printing step, suitable functional
Fig. 6. A light microscopy image showing a functional hydrophobic valve of OTS generated by mCP in a channel, which is only 40 mm wide.
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groups are attached to the surface. A ligand or a reagent can then be immobilized in the second printing step. In the attempt to realize a micro¯uidic device for catalyst screening, a consecutive mCP technique has successfully been applied in deep reactive ion etched channels. Acknowledgements The authors would like to thank Lubica Macakova at the Royal Institute of Technology, Department of Chemistry, Surface Chemistry, for the contact angle measurements and Linda Sundberg at the Royal Institute of Technology, Department of Polymer Technology for help with the PDMS stamps. Finally, we would like to thank the Foundation for Strategic Research (SSF) for funding this study performed within the Nanochemistry Program at the Royal Institute of Technology. References [1] A. Kumar, H. Biebuyck, G. Whitesides, Patterning self-assembled monolayers: applications in material science, Langmuir 10 (1994) 1498±1511. [2] Y. Xia, G. Whitesides, Soft Lithography, Angew. Chem. Int. Ed. 37 (1998) 550±575. [3] L. Yan, X. Zhao, G. Whitesides, Patterning a preformed reactive SAM using microcontact printing, J. Am. Chem. Soc. 120 (1998) 6179±6180. [4] N. Jeon, R. Nuzzo, Patterned self-assembled monolayers formed by microcontact printing direct selective metalization by chemical vapor deposition on planar and nonplanar substrates, Langmuir 11 (1995) 3024±3026. [5] P. Hidber, W. Helbig, E. Kim, G. Whitesides, Microcontact printing of palladium colloids: micron-scale patterning by electroless deposition of copper, Langmuir 12 (1996) 1375±1380. [6] A. Bernard, E. Delamarche, H. Schmid, B. Michel, H. Bosshard, H. Biebuyck, Printing patterns of proteins, Langmuir 14 (1998) 2225±2229. [7] K. Handique, B. Gogoi, D. Burke, C. Mastrangelo, M. Burns, Microfluidic flow control using selective hydrophobic patterning, SPIE 3224 (1997) 185±195. [8] R. Jackman, S. Brittain, A. Adams, M. Prentiss, G. Whitesides, Design and fabrication of topologically complex, three-dimensional microstructures, Science 280 (1998) 2089±2091. [9] A. Folch, M. Schmidt, Wafer-level in-registry microstamping, J. Microelectromechanical Syst. 8 (1999) 85±89. [10] J. McDonald, D. Duffy, J. Andersson, D. Chiu, H. Wu, O. Schueller, G. Whitesides, Fabrication of microfluidic systems in poly(dimethylsiloxane), Electrophoresis 21 (2000) 27±40.
[11] P.St. John, L. Kam, S. Turner, H. Craighead, M. Issacson, J. Turner, W. Shain, Preferential glial cell attachment to microcontact printed surfaces, J. Neurosci. 75 (1997) 171±177. [12] L. Yan, W.T.S. Huck, X.M. Zhao, G.M. Whitesides, Patterning thin films of poly(ethylene imine) on a reactive SAM using microcontact printing, Langmuir 15 (1999) 1208±1214. [13] H. Nishiyama, S. Yamaguchi, M. Kondo, K. Itoh, Electronic substituents effect of nitrogen ligands in catalytic asymmetric hydrosilylation of ketones: chiral 4-substituted bis(oxazolinyl)pyridines, J. Org. Chem. 57 (1992) 4306±4309. [14] N. Larsen, H. Biebuyck, E. Delamarche, B. Michel, Order in microcontact printed self-assembled monolayers, J. Am. Chem. Soc. 119 (1997) 3017±3026. [15] K.F. Jensen, The Impact of MEMS on the Chemical and Pharmaceutical Industries, Solid-State Sensors and Actuator Workshop, Hilton Head Island, South Carolina, June 2000, 105±110.
Biographies Helene Andersson was born in 1974 in Hudiksvall, Sweden. She received her MSc degree in Molecular Biotechnology in 1998 from Uppsala University, Sweden. In the beginning of 1999, she started her PhD studies at the Department of Signals, Sensors and Systems at the Royal Institute of Technology, Stockholm, Sweden. Her main research areas are microfluidics, micro total analysis systems, micropumps and nanochemistry. Christina JoÈnsson was born in 1972 in NorrkoÈping, Sweden. She received her MSc degree in Chemistry in 1997 from LinkoÈping University. In June 1999, she started her PhD studies at the Department of Organic Chemistry at the Royal Institute of Technology, Stockholm, Sweden. Her main research area is synthesis of chiral ligands for asymmetric catalysis and their immobilization on solid support in order to perform nanochemistry. Christina Moberg was born in GaÈvle, Sweden, in 1947. She received her BSc degree in 1970 at the Stockholm University and the PhD degree in organic chemistry in 1975 from the Royal Institute of Technology, Stockholm, Sweden. She became Associate Professor in 1989 and was appointed Full Professor in 1997. Her research is devoted to the development of new selective organic synthetic methods employing asymmetric metal catalysts. GoÈran Stemme was born in Stockholm, Sweden, on 4 February 1958. He received the MSc degree in Electrical Engineering in 1981 and the PhD degree in Solid State Electronics in 1987, both from the Chalmers University of Technology, Gothenburg, Sweden. In 1981, he joined the Department of Solid State Electronics, Chalmers University of Technology, Gothenburg, Sweden. There, in 1990, he became an Associate Professor (Docent) heading the silicon sensor research group. In 1991, Dr Stemme was appointed Professor at the Royal Institute of Technology, Stockholm, Sweden. He heads the Instrumentation Laboratory at the department of Signals, Sensors & Systems. His research is devoted to sensors and actuators based on micromachining of silicon. Dr Stemme is a subject editor for the IEEE/ASME J. Microelectromechanical Systems.