A silicon chip for attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy in combination with a modular PDMS herringbone mixer and a microreactor has been successfully fabricated and tested. The modular design allows the chip to be used for a variety of reactions. A model synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine has been performed on chip. When plotting the natural logarithm of the peak area corresponding to the ketone stretch vibration at 1710cm-1, against the residence time, a linear curve can be fitted, suggesting this step to be a first order reaction

Bomer, Johan G.

de Boer, Hans L.

Lozeman, Jasper J.A.

Odijk, Mathieu

van den Berg, Albert

Vollenbroek, Jeroen C.

English

NARCIS 

Modular ATR FT-IR microreactor chip for optimizing reaction conditions

University of Twente Research Information

MODULAR ATR FT-IR MICROREACTOR CHIP FOR OPTIMIZING REACTION CONDITIONSJasper J.A. Lozeman, Jeroen C. Vollenbroek, Johan G. Bomer, Hans L. de Boer, Albert van den Berg, Mathieu OdijkBIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, Technical Medical Centre, Max Planck Center for Complex Fluid Dynamics, University of Twente, Enschede, The Netherlands.A silicon chip for attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy in combination with a modular herringbonemixer1 and a microreactor has been successfully fabricated and tested. The modular design allows the chip to be used for a variety of reactions. Amodel synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine has been performed on chip. When plotting thenatural logarithm of the peak area corresponding to the ketone stretch vibration at 1710cm-1 against the residence time, a linear curve can befitted, suggesting this step to be a first order reaction.Chip Design0.00.10.20.30.40.5100011001200130014001500160017001800Absorbance [a.u.]Wavenumber [cm-1]Fingerprint region3.5min10.5min21.0miny = -0.2029x + 2.7719R² = 0.995-2-1.5-1-0.500.511.522.50 5 10 15 20 25ln(peak area [a.u.])Residence time [min]Ketone peak area over timeReaction MonitoringSynthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione and 1-butylamine. The reactants are mixed by theherringbone mixer, flow is stopped once the reaction chamberis filled. Next, every 3.5min a IR spectrum is generated.FT-IR spectra over time. The broad peak at 3200cm-1,corresponding to the formation of water, increasesover time.FT-IR spectra at 1800-1000cm-1. The ketone peak at1710cm-1 decreases over time, while the peaks at1525cm-1 (skeleton vibration) and 1300cm-1 (C-Nstretch) increase overtime5,6.Reaction chamber Mixing channel30mmTop ViewBottom ViewThe ATR crystal, an adaptation ofearlier designs3,4, is made ofsilicon. This crystal, the bottomlayer of the device, is used for IR-ATR sensing. To couple light intothe silicon, facets are fabricatedusing KOH etching. The reactionchamber and mixing channel,fabricated from PDMS, PMMA,Teflon or COC, are modular in thesense that they can be stacked.The mixing channels mix by usingherringbone mixers1. Channeldimensions: H=100µm W=200µm.References[1] A.D. Stroock, et al. Science. 5555 (2002) 647–651.[2] K.F. Jensen, Chem. Eng. Sci. 2 (2001) 293–303.[3] A. Susarrey-Arce, et al. Sensors Actuators B Chem.(2015) 13-21.[4] E. Karabudak, et al. Anal. Chem. 7 (2012) 3132-3137.[5] E. Pretsch et al. Structure Determination of OrganicCompound, 2009.[6] D.L. Howard, et al. J. Phys. Chem. A. 29 (2015) 7980–7990.The current setup is lacking inanalysis speed. Therefore a newIR spectrometer, using a tunablequantum cascade laser has beenpurchased from IRSweep. Thelaser, which not only has a timeresolution in the microsecondrange, also has an higher poweroutput, increasing signal to noise.Modular DesignABCBCEDFAGModular design of the chip allows for a variety of reactions to be monitored.The simplest combination (left) has been used to obtain the results presentedin this poster. A more complex design (right), can currently use up to 3 layers.Parallelization with multiple chips, could also increase the amount of reactioncomponents.ConventionalIR spectrometerTemperatureRatios of reactantsConcentrationsMixing speedMeasure productsChange variablesA setup is proposed, using microfluidicflow chemistry (MFC), in which thereactions conditions can be changedin real-time, while measuring theformed products online. MFC allowsfor better control over temperature,concentrations and mass transportthan conventional laboratory setups2.Additional benefit of online analysis isfurther insight in reaction kinetics andintermediate products.0.00.10.20.30.40.51000150020002500300035004000Absorbance [a.u.]Wavenumber [cm-1]IR spectra over time3.5min10.5min21.0minThe natural logarithm of the peak area at 1710cm-1, plottedagainst the residence time. The linear fit suggests a first orderreaction.Run reactionIR spectrometerSyringe pumpResistor (heating)AcknowledgementWe would like to thank Max Krakers for thedesign of the herringbone mixer mask.We would like to thank Tobias Elsbecker forfabricating the PMMA, Teflon and COCreaction chamber and mixer channels, andhis to continuing contribution to the project.OutlookProposed ConceptFacetsThis work was supported by the Netherlands Center forMultiscale Catalytic Energy Conversion (MCEC), and NWOGravitation programme funded by the Ministry of Education,Culture and Science of the government of the Netherlands.

 MODULAR ATR FT-IR MICROREACTOR CHIP FOR OPTIMIZING REACTION CONDITIONS Jasper J.A. Lozeman*, Jeroen C. Vollenbroek, Johan G. Bomer, Hans L. de Boer,  Albert van den Berg and Mathieu Odijk BIOS - Lab on a Chip group, MESA+ institute for nanotechnology and Max Planck Center for  complex fluid dynamics, University of Twente, THE NETHERLANDS  ABSTRACT A silicon chip for attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy in combination with a modular PDMS herringbone mixer and a microreactor has been successfully fabricated and tested. The modular design allows the chip to be used for a variety of reactions. A model synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine has been performed on chip. When plotting the natural logarithm of the peak area corresponding to the ketone stretch vibration at 1710cm-1, against the residence time, a linear curve can be fitted, suggesting this step to be a first order reaction.  KEYWORDS: Infrared spectroscopy, attenuated total reflection, online reaction monitoring   INTRODUCTION  Optimizing chemical reaction parameters can be an expensive and time consuming process. Microfluidic flow chemistry is an established method to obtain better control over temperature, concentrations and mass transport [1]. Integrating such a microfluidic-chip with an analytical method allows for direct characterization of the (intermediate) products. ATR FT-IR is chosen as analytical technique since it can be used online, is not destructive and generates both quantitative and qualitative information about the sample. Combinations of microfluidic-chips with ATR FT-IR spectroscopy have been proposed in the past [2,3], but these are often limited to a specific application and can be difficult to fabricate.  We propose a modular, easy-to-fabricate design, consisting of a silicon ATR crystal that can be combined with one or several stacks of PDMS microreactor and herringbone mixer layers [4]. On the side of the chip, two resistors are placed that can be used to heat up the chip, allowing control over the reaction temperature. With this modular design several parameters of the reaction can easily be adjusted, allowing one to optimize a large variety of multi-step reactions.  A schematic representation of two possible combinations of PDMS layers for the microfluidic-chip are shown in Figure 1. In Figure 1A, a silicon ATR crystal in combination with a single PDMS layer, consisting of both a mixer and reaction chamber, is shown. A simple reaction where reactant A plus reactant B becomes product C, can be performed on this chip. In Figure 1B the same ATR crystal is shown, but now with 3 PDMS layers. The top two layers consist of only mixers, and the bottom layer consist of a mixer and a reaction chamber. By selectively punching holes in the PDMS chips and carefully planning where the tubing’s connect to, several reactants can be introduced and mixed in the chip. In the top mixer layer, reactant A and B are mixed, forming product C. Product C will flow into the middle mixer layer, where it is mixed with reactant D to form product E. Product E is introduced to the final, bottom layer where it is mixed with reactant F, to form the end product G.   Figure 1: schematic representation of the chip. (A) ATR crystal with single PDMS layer. (B) ATR crystal with three layers of PDMS, capable of handling a larger number of reactants 978-0-578-40530-8/µTAS 2018/$20©18CBMS-0001 2117 22nd International Conference on MiniaturizedSystems for Chemistry and Life SciencesNovember 11-15, 2018, Kaohsiung, Taiwan EXPERIMENTAL  The silicon ATR crystal is partly based on the design of Karabudak et al. [3]. A 525µm thick silicon wafer with a {100} crystal orientation is anisotropically etched with KOH, creating facets with an angle of 54.7o. Etching is stopped when 75µm of silicon remains, creating increased structural support for the addition of the PDMS microfluidic chip. The created facets are used to couple IR light into the crystal, as schematically represented in Figure 1. The PDMS microfluidic-chips are bonded with oxygen plasma on top of the silicon ATR crystal.  As a proof of concept, a model reaction is performed using a chip with a single PDMS layer configuration, as shown in Figure 1A. For this design, the mixing channel is 70mm long, 200µm wide and 85µm high. The herringbone mixer on top of the channel has grooves with a depth of 15µm [4]. The reaction chamber is approximately 13mm long, 10mm wide and 85µm high, corresponding with a total volume of 12.25µL.  A Paal-Knorr synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine is chosen as model reaction, of which the mechanism is shown in Figure 2. A custom build aligner with integrated mirrors is used to put the ATR-chip in the beam path of a commercially available FT-IR spectrometer (Bruker Vertex 70). Tubing is connected to the PDMS chip and a syringe pump (neMESYS) is used to introduce both reactants into the chip, each with a flow of 5µl/min (total flow of 10µl/min.). After mixing, the solution is introduced to the reaction chamber and the flow is stopped. The reaction chamber is directly above the sensing area of the ATR crystal. IR spectra is recorded every 3.5 minutes over a period of 21 minutes. The reaction is performed at room temperature so the integrated heaters are not used for this experiment.  RESULTS AND DISCUSSION Fabrication results of the chip are shown in Figure 3. On the bottom part of the chip the silicon ATR crystal with dimensions of 30mm by 15mm is clearly visible. Highlighted is the mixing chamber and the reaction chamber. The dots in the reaction chamber are pillars for increased structural support.  The results of the IR spectra are shown in Figure 4A and Figure 4B. On the x-axis the wavenumber is shown which is plotted against the absorbance on the y-axis. Spectra at t=3.5 min (red), t=10.5min (blue) and at 21.0min (yellow) after the start of the reaction are shown. In Figure 4A the spectra from 4000cm-1 to 2500cm-1 are shown. One can clearly see the broad peak around 3400cm-1 increasing, this corresponds to the O-H bond stretching vibration, suggesting either the formation of water (side-product), alcohol (intermediate-product), or a combination of both [5]. The peaks around 3000cm-1, associated with the alkyl-stretches, are decreasing and changing in ratio. This could correspond to the pyrrole formation [5]. Figure 4B shows the spectra from 1800cm-1 to 1000cm-1. Notable peaks that increase in signal are the peak at 1525cm-1, assigned to the skeleton vibration of the pyrrole, the peak at 1410cm-1, likely to be an CH2-C=O deformation vibration and the peak at 1300cm-1, which could be assigned to the C-N stretch vibration [5]. Interesting peaks with decreasing intensities are the initially strong peak at 1710cm-1, which can be assigned with certainty to the ketone stretch vibration, the peak at 1360cm-1, which is a decrease in the CH3 symmetrical deformation and the peak at 1160cm-1, which can be assigned to the OH bending vibration from the isomeric form of hexane-2,5-dione [5,6]. In Figure 4C the natural logarithm of the peak-area of the ketone stretch vibration at 1710cm-1 is plotted against the residence time in the chip. The peak area is decreasing in time at a logarithmic rate, indicating a first order reaction. The same trend is not obtained when integrating the O-H peak at 3400cm-1 or the peak at 1525cm-1. This suggests that different intermediate products are formed with different reaction orders.   Figure 2: Synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine  Figure 3: fabrication result of one of the PDMS chips bonded on the silicon ATR crystal.  2118 CONCLUSION We have demonstrated that it is feasible to fabri-cate a modular, cheap and user friendly chip that can be used for optimizing reaction conditions while monitoring chemical species with IR spectroscopy. The combination of integrated heaters and modular PDMS mixers, allow the chip to be used for a wide range of reactions. A model synthesis of 1-butyl-2,5-dimethyl-1H-pyrrole from hexane-2,5-dione with 1-butylamine proves that reactions can be monitored with the device, and that it can be used to get insight in the reaction order.  Future plans include adding confocal mirrors to the setup to increase light coupling into the ATR crystal, creating a grating coupler to improve the cou-pling efficiency of specific wavelengths, and improv-ing the limit-of-detection by adding structures for surface enhanced infrared spectroscopy.  ACKNOWLEDGEMENTS This work was supported by the Netherlands Center for Multiscale Catalytic Energy Conversion (MCEC), an NWO Gravitation programme funded by the Ministry of Education, Culture and Science of the government of the Netherlands. The authors thank the Photocatalytic Synthesis (PCS) group, Uni-versity of Twente, the Netherlands, headed by Prof. Dr. Guido Mul for the use of their FT-IR instrument. The authors like to thank Dr. Sonia García Blanco and Pablo Muñoz Galindo MSc from the Optical Sci-ences (OS) group, University of Twente, the Nether-lands, for their assistance with optics simulation soft-ware.          Figure 4: (A) FT-IR spectra at 4000-2500cm-1, red line after 3.5min, blue line after 10.5min and yellow line after 21.0min. (B) FT-IR spectra at 1800-1000cm-1, red line after 3.5min, blue line after 10.5min and yellow line after 21.0min. (C) The natu-ral logarithm of the peak area at 1710cm-1, corresponding with the ketone stretch vibration, against the residence time.   0.000.050.100.150.200.252500300035004000Absorbance [a.u.]Wavenumber cm-1Group region3.5min10.5min21.0min0.000.100.200.300.400.50100011001200130014001500160017001800Absorbance [a.u.]Wavenumber cm-1Fingerprint region3.5min10.5min21.0miny = -0.2029x + 2.7719R² = 0.995-2-101230 5 10 15 20 25ln(peak area [a.u.])residence time (min)1710cm-1 peak area over timeC) B) A) 2119REFERENCES [1] K.F. Jensen, Microreaction engineering — is small better?, Chem. Eng. Sci. 56 (2001) 293–303. doi:10.1016/S0009-2509(00)00230-X. [2] A. Susarrey-Arce, R.M. Tiggelaar, M. Morassutto, J. Geerlings, R.G.P. Sanders, B. Geerdink, S. Schlautmann, L. Lefferts, A. van Houselt, J.G.E. Gardeniers, A new ATR-IR microreactor to study electric field-driven processes, Sensors Actuators B Chem. 220 (2015) 13–21. doi:10.1016/j.snb.2015.05.025. [3] E. Karabudak, B.L. Mojet, S. Schlautmann, G. Mul, H.J.G.E. Gardeniers, Attenuated Total Reflection-Infrared Nanofluidic Chip with 71 nL Detection Volume for in Situ Spectroscopic Analysis of Chemical Reaction Intermediates, Anal. Chem. 84 (2012) 3132–3137. doi:10.1021/ac300024m. [4] A.D. Stroock, S.K.W. Dertinger, A. Ajdari, I. Mezić, H.A. Stone, G.M. Whiteside, Chaotic Mixer for Microchannels, Science (80-. ). 295 (2002) 647–651. doi:10.1126/science.1066238. [5] E. Pretsch, P. (Philippe) Bühlmann, M. Badertscher, Structure determination of organic compounds : tables of spectral data., Springer, 2009. [6] D.L. Howard, H.G. Kjaergaard, J. Huang, M. Meuwly, Infrared and Near-Infrared Spectroscopy of Acetylacetone and Hexafluoroacetylacetone, J. Phys. Chem. A. 119 (2015) 7980–7990. doi:10.1021/acs.jpca.5b01863.  CONTACT * J.J.A. Lozeman phone: +31534896065; j.j.a.lozeman@utwente.nl  2120

Modular ATR FT-IR microreactor chip for optimizing reaction conditions

Abstract

Similar works

Full text

Available Versions

NARCIS

University of Twente Research Information

University of Twente Research Information