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Development of a Continuous Microchannel CrystallizerNabeel Kadhim Abbod Alghaffari1, Lau Phei Li1 and David Hassell21: Department of Chemical Engineering, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih, Malaysia 2: Petroleum and Chemical Engineering Programme, Institut Teknologi Brunei, Gadong, Brunei

David.Hassell@itb.edu.bn

Proceeding for "Moving towards the New Chapter in Chemical Engineering amongst ASEAN Region ", the 5th Regional Conference on Chemical Engineering, 7 8 February 2013, PATTAYA, THAILAND

AbstractThis work outlines studies performed to evaluate the performance of a microchannel crystallizer, using paracetamol as the test system. Areas scrutinized include; techniques for rapid microchannel fabrication; identifying a suitable crystallization parameter space with respect to time and temperature; evaluating microchannel mixing performance using computational fluid dynamics. Initial results are presented along with the challenges faced and plans for future work.Keywords; crystallization, microchannel, computational fluid dynamics Introduction Crystal quality plays an important role in the fine chemical and pharmaceutical industries [1], and is generally occurs in two phenomenon steps known as nucleation and growth. Within the modern chemical industries, it is important to control these two phenomenon steps in order to produce a high degree of quality chemicals or pharmaceutical products. Current industrial scale crystallisation takes place in both batch and continuous unit operations and result in numerous issues in the resulting crystal morphology including size distribution [2] and the presence of inclusion [3].

This work presents initial studies aimed at developing a microchannel device suitable for crystallisation, which by providing more controlled hydrodynamics during the crystallisation process would reduce or eliminate the above issues. Microfluidic devices are characterised by their sub-millimeter scale features, and have been widely used in variety of scientific disciplines [2,4-7]. Previous work has shown that microchannels can be suitable for generating narrow crystal size distributions [8-10] with another possible advantage being increased productivity per unit volume [11]. However, there are also challenges to be overcome including channel blockage, issues surround scale out from micro to production scales and the scarcity of suitable downstream process equipment for these devices [1].MICROCHANNEL FABRICATIONThere are many techniques to fabricate a microfluidic device, which include ultraprecision milling, class etching, laser ablation, ultraviolet and X-ray lithography, etc. Micro-scale open channels were fabricated in PDMS which is an inexpensive, nontoxic, chemically stable and optically transparent polymer [12]. This was done by casting it on to a mould containing a positive micro-scale structure. In this work, both soft lithography [13] and xerography [14] were used to fabricate the positive moulds onto which PDMS was applied to create the microfluidic devices.For the technique pioneered by [13] a microchannel design was sketched using computer aided drafting (CAD) software and then a negative image of the sketch printed out on a clear transparent film. A cleaned silicon wafer was spin coated with SU-8 series photoresist (MicroChem, NANO SU-8 50) using a programmable spin coater (Specialty Coating Systems, 6800 Spin Coater Series), where the microchannel height is determined by the spinning speed. Once applied to the substrate, a soft baking step is used to evaporate the SU-8s solvent and stabilise the SU-8 layer. The photo resist spin-coated silicon wafer was then exposed to UV light through the pre-printed photomask to cross-link the SU-8 epoxy so that it will resist the dissolution process at the subsequent developing stage. After a post baking stage at between 65 90 C and development stage using an appropriate developer, the unexposed SU-8 is dissolved leaving the UV exposed SU-8 bonded to the silicon wafer surface. The other technique evaluated in this work in based on that presented by [14], who reported creating a technique to fabricate a positive image mould by means of cutting a two-dimensional-polygon paths representing a microchannel perimeter into an adhesive polymeric sheet. They reported that it was simple, cheap, required no chemicals, and required only 10 to 15 minutes to produce the desired mould compared with three hours in the case of soft lithography. After the microchannel design is drafted using CAD software, a 100 micron Vinyl adhesive sheet is cut using a plotter/cutter machine optimised at maximum addressable resolution and minimum cutting speed and acceleration [15]. After the cut is preformed, a clear pressure sensitive application tape is applied on top of the cut plastic sticker to prevent any unnecessary displacement of the cut parts. The adhesive sheet is then smoothly applied to a chemically cleaned soda-lime glass substrate and the application tape removed. The unwanted Vinyl sticker is then removed leaving the required microchannel structure. One disadvantage of using the xurography technique is the low cutting resolution of 100 microns currently obtained, while the microchannel depth which can be only controlled by the cut plastic sticker thickness. In the case of the work presented here neither of these two limitations are currently relevant, and as such xurography provides a viable alternative to the soft lithography technique. Once the positive microchannel mould was generated, PDMS was mixed with its cross-linker at the recommended ratio (10:1) and then degassed by means of centrifugal or vacuumed desiccator. It was then applied over the mould and baked as recommended by the manufacturer, typically for one hour at 70C. After baking, the casted PDMS was peeled off from the mould before being bonded to a glass substrate. The channels were then attached to teflon tubes at the inlet and outlet to the channel. An extra layer of premixed and degassed PDMS was cast over the interface between the channel and tefron tube to provide an adequate seal between the Teflon tubes and the interfacing ports.Microchannels fabricated by both soft lithography and xurography techniques were subjected to wall profile evaluation, highlighted in Fig 1. The soft lithograph technique produced a trapezoidal wall profile, resulting from Fresnel diffraction [16], while the microchannels produced from the xurography positive mould were seen to have a sharp rectangular wall profile. This, along with the time and cost advantages of the Xurography approach make it the more suitable technique in the proposed application. (a) (b) Figure 1: Wall profiles for channels made using (a) Soft lithography and (b) Xurography The microchannels fabricated using the above methods raptured at the bounding interface at a Reynolds number of order 10-100 due to the higher pressures required. In order to overcome this issue, bounded microchannels were supported in form of sandwich by two 5mm thick sold and transparent sheets of Poly(methyl methacrylate) (PMMA). An array-oriented screws and nets were used in this arrangement to apply a uniformly distributed pressure on the bounded microchannel. crystallizationCrystallisation can be achieved through a number of techniques such as: cooling down a saturated solution, precipitation of a chemical reaction product, removal of solvent, adding an antisolvent agent, or a combination of these techniques [2]. Most of the continuous crystallisation experiments reported in micro-scale devices were done using precipitation [8,10,17,18] or adding an antisolvent [9,19-21] and due to the relative lack of research adopting cooling as a crystallisation mode, work was undertaken to understand the challenges faced in adopting this approach. Paracetamol (Acetaminophen) in water was chosen as the model system, and the solubility at laboratory conditions for various temperatures was characterised using the isothermal method reported by [22]. Initial paracetamol crystallisation experiments were conducted using a microcrystalliser of dimensions 250 micrometer in width, 100 micrometer in height and 50 cm in length, with channel temperature controlled using a piezoelectric device. The supersaturated solution was kept in a pumping chamber submerged in a water bath at the appropriate temperature. One side of the chamber was filled with the solution, whilst the other was filled with water and attached to a syringe pump, both separated by a sliding wall. Additional fluid was pumped into the water filled side, displacing the saturated solution and forcing it into the microchannel. Initial experiments found a range of operating conditions in which crystalisation was not observed, alongside conditions during which channel blockage occurred. A parameter map was designed to estimate a workable operation window for experiments. By assuming: a plug flow regime inside the microcrystalliser, induction time equal to 25 per cent of the total residence time of the microcrystalliser, and ignoring the external tubing residence time, a parameter space for successful crystallisation is possible. This was used to determine the conditions required to observe crystallisation.

Figure 2: Image showing the microchannel geometry used, consisting of 32 parallel-microchannels with a predefined dimension of 350W100H5cmL.Subsequent experiments used the geometry outlined in Fig 3, which consisted of 32 parallel channels with dimensions 350 m width, 100 m height and 5000 m length. The microcrystalliser was cast in PDMS and hydrophilically bounded to a Silicon wafer to allow for accurate temperature control on the microchannel. A solution with a supersaturated degree of 2.7-2.89 produced average nucleated particle diameters of approx 10 nm as measured by an in-line particle size analyzer (Zetasizer Nano ZS90, Malvern Instruments) placed directly after the outlet to the microchannel. However in future to improve the accuracy of the experiments and allow for larger run times to ensure steady state has been reached in the system, the syringe pump system will be replaced with a miniaturized centrifugal submersible pump (MCSP) fitted inside a large vessel containing supersaturated solution.

MIXING MECHANISM MODELLINGIt is possible that crystallisation within a micro scale domain could be further enhanced by introducing of an oscillatory flow within a baffled microchannel. This has previously been shown to enhance and homogenize mass transfer in larger systems [23-25] and to enhance crystal quality [3]. Before experiments were performed, initial computational fluid dynamics modelling was undertaken using COMSOL multiphysics finite element software. The effect of oscillatory flow function shape on the flow inside a smoothed and periodically baffled microchannel was evaluated using a two-dimensional geometry for a single cavity with a 13% baffled area [26]. Simulations were performed using the time dependant incompressible Navier-Stokes equations with no slip boundary conditions at the wall and periodic oscillatory flow at the inlet and outlet of the channel. Initial mesh independence studies were performed to ensure that the flow fields obtained were independent of the mesh used, with a final mesh resolution chosen as 1100 mesh element per mm2. Three types of oscillatory profile were evaluated; sinusoidal; squared shaped and triangular.The dynamical nature of OFR is normally characterised using the following dimensionless groups, Reynolds number, , oscillatory Reynolds number, , and the Strouhal number, . Only and are presented in this work, and are based on the average net velocity and maximum oscillatory velocity respectively. Preliminary simulation results highlighted the cross channel flow created by this type of device, and Fig 3 indicates the ratio of the average axial to tangential flow in the channel over a range of frequencies for all three oscillatory wave types. It can be seen that using a square wave oscillatory function provides greater cross channel flow, and subsequent work will apply convection-diffusion equations for a two phase fluid to this system evaluate mixing performance within this type of device.

Figure 3: Comparison of surface average y-axis absolute velocity component || to the surface average x-axis absolute velocity component || ratio at different oscillatory frequencies and wave profiles. and were 0 and 10 respectively. and were 0 and 10 respectively.conclusionThis work outlines studies performed to evaluate the performance of a microchannel crystallizer, using paracetamol as the test system. After a suitable fabrication technique was identified, initial studies obtained crystals within a microchannel geometry using temperature drop as the crystallisation driving force. However, to ensure repeatable results over longer time periods, modifications to experimental equipment have been identified for further improvement. Initial CFD studies found promising methodologies for the promotion of cross channel mixing within the device, although Areas scrutinised include; techniques for rapid microchannel fabrication; identifying a suitable crystallization parameter space with respect to time and temperature; evaluating microchannel mixing performance using computational fluid dynamics. Initial results are presented along with the challenges faced and plans for future work.References

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