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High Throughput Methodology for Continuous Preparation of Hydroxyapatite Nanoparticles in a Microporous Tube-in-Tube Microchannel Reactor Qing Yang,†,‡ Jie-Xin Wang,*,† Lei Shao,‡ Qi-An Wang,† Fen Guo,‡ Jian-Feng Chen,*,‡ Lin Gu, and Yong-Tao An§ Key Lab for Nanomaterials, Ministry of Education, Beijing UniVersity of Chemical Technology, Beijing, 100029, PR China, Research Center of the Ministry of Education for High GraVity Engineering and Technology, Beijing UniVersity of Chemical Technology, Beijing, 100029, PR China, and AdVanced Technology & Materials Co., Ltd., Beijing, 100081, PR China

A microporous tube-in-tube microchannel reactor (MTMCR) was successfully adopted to prepare hydroxyapatite (HAP) nanoparticles. The rodlike HAP nanoparticles with a mean size of 58 nm, a specific surface area of 49.32 m2/g, and a narrow size distribution were obtained in an MTMCR under a high throughput of 3 L/min. The mean particle size sharply decreased with increasing the continuous phase flow rate, while first decreased and subsequently increased with increasing the dispersed phase flow rate and the reactant concentration. The extension of the mixing distance led to the initial rapid and following slight decrease of the mean particle size. The size of HAP nanoparticles was also strongly dependent on the micropore size on the surface of inner tube. Small micropore size was beneficial for producing small particles. For comparison, HAP nanoparticles were also prepared in a stirred tank reactor (STR) and a T-junction microchannel reactor (TMCR), clearly exhibiting the advantages of the MTMCR over the STR and TMCR due to the achievement of uniformly smaller HAP nanoparticles and a high throughput for industrial production. 1. Introduction A microreactor or microchannel reactor is a continuous flowtype reactor with the characteristic dimensions of channels under a millimeter in size.1 Owing to its inherent property of large area-to-volume ratio, the microreactor presents many advantages including optimum temperature control, minimal substance consumption, a short reaction period, low environment impact, and high operation safety.2-7 Hence the microreactor has extended many valuable applications in the chemistry, chemical engineering, and biotechnology fields such as production of toxic and hazardous chemicals,8,9 waste treatment,10 drug screening,11 biomolecule analysis,12 and so forth. Recently, microreactor technology has received vast scientific and industrial interests in the preparation of nanomaterials because the highly efficient heat and mass transfer in the microreactor provides the possibility of realizing a homogeneous reaction environment within a small volume, which is essential for the formation of fine nanoparticles. Many researchers have experimentally studied the application of the microreactor to the synthesis of nanoparticles of metals,13,14 semiconductors,15,16 inorganic salt,17,18 organic compounds,19 drugs,20 and others, proving that process intensification advantages offered by microreactor technology were suitable for nanoparticle production in a continuous mode. It is obvious that a continuous synthesis method would have the ability to perform large-scale industrial production of nanoparticles. However, owing to the small volume, the maximum throughput of a single microreactor is usually on the order of a few tons per annum while the desired * To whom correspondence should be addressed. Tel.: +86-1064447274. Fax: +86-10-64423474. E-mail: [email protected] (J.-X.W.). Tel.: +86-10-64446466. Fax: +86-10-64434784. E-mail: [email protected] (J.-F.C.). † Key Lab for Nanomaterials, Ministry of Education, Beijing University of Chemical Technology. ‡ Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology. § Advanced Technology & Materials Co., Ltd.

plant capacity requires tens to hundreds of tons of product annually. Thus, increasing the throughput of the microreactor is of necessity to the transition of microreactor technology from lab-scale to industrial-scale chemical processes. Aiming to obtain a high throughput, a so-called numberingup method is employed to scale up the microreactor.21,22 In theory, numbering-up is highly advantageous to the preservation of reaction physics and channel flow hydrodynamics; however, in reality, some problems have also emerged when this method is put into service. The most important challenge is how to ensure flow equidistribution with minimal pressure loss in each microchannel.23 In order to help all the microchannels to work under identical conditions, besides utilizing a control system to monitor flow distribution precisely, it is also necessary to design a device that can split the inlet feed stream into a multitude of small ones with the same flow velocity.24,25 Hence, manifold structures are usually introduced into the design of a microreactor system containing a lot of parallel microchannels.26-28 The employment of manifolds together with the precise control and monitoring system could smooth away the problem of flow maldistribution to a great extent, but the use of these devices would inevitably increase cost and inflexibility of fabrication and operation. Therefore, to solve all these technical or economic problems associated with scaling-up, developing a simpleconstruction microreactor that can achieve high plant capacity, even flow distribution, and easy operation seems to be an alternative approach required for the widely commercial application of microreactor technology. In our laboratory, a pilot-plant microdevice, designated as a microporous tube-in-tube microchannel reactor (MTMCR), has been recently developed.29,30 In the MTMCR, two coaxial tubes form annular cross-sectional microchannel, and micropores on the annular surface of one end of the inner tube are applied as the dispersion medium. The liquid in the inner tube through the annular micropore belt is dispersed into plenty of small separate streams, followed by the high-speed impinging with the laminar flow in the chamber between inner and outer tubes

10.1021/ie9005436  2010 American Chemical Society Published on Web 11/17/2009

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within a very short time. Previous works demonstrate that an MTMCR has the characteristics of high micromixing efficiency, large capacity, and good controllability and has also been used in the preparation of BaSO4 nanoparticles as a model compound.29,30 However, it is still very necessary to examine the possibility of producing more various and valuable nanoparticles in this platform. Hydroxyapatite (HAP, Ca10(PO4)6(OH)2) is the principal inorganic constituent of vertebrate skeletal systems.31 HAP has extensively been employed as a bioceramic material in various biomedical fields such as implant materials and protein chromatography applications because of its excellent bioactive, biocompatibility, osteoconductivity, and affinity.32-34 Besides biomedical applications, HAP has also exhibited its applicability as industrial material, e.g. ion exchange material or catalyst carrier.35-37 In particular, new developments in the preparation of nanosized HAP particles have helped HAP exploit a great deal of new uses. For instance, HAP nanoparticles could surprisingly retard the multiplication of cancer cells and be efficiently employed as a drug carrier.38,39 In this paper, an MTMCR was employed to prepare HAP nanoparticles. The effects of the operation parameters such as flow rate, mixing distance, reactant concentration, and micropore size were explored. A T-junction microchannel reactor and a stirred tank reactor were also used for comparison. 2. Experimental Section 2.1. Materials and Setup. Analytical reagent (AR) grade calcium nitrate tetrahydrate (Ca(NO3)2 · 4H2O), ammonium hydrogen phosphate ((NH4)2HPO4), ammonium hydroxide, and absolute ethyl alcohol were purchased from Sinopharm Chemical Reagent Beijing Co. Ltd., China. Deionized water was obtained from a Hitech-Kflow water purification system (Shanghai Hogon Scientific Instrument Co. Ltd., China). Figure 1 illustrates a schematic diagram of the experimental setup (a) and photographs of the MTMCR (b). There are two main parts in the microreactor, i.e. the inner tube and the outer tube. A lot of micropores are distributed around the wall at one end of the inner tube (micropore zone: porosity of 46%; length of 1 cm). The inner tubes with micropore sizes of 5, 10, 20, and 40 µm were employed in this study. The width of the microchannel, namely the distance between the inner and outer tubes, is 500 µm. Besides one outlet, several sampling points are designed along the axial position of the outer tube to explore the effect of the mixing distance on the particle size. More details about MTMCR can be found in refs 29 and 30. 2.2. Preparation of HAP Nanoparticles. Ca(NO3)2 · 4H2O and (NH4)2HPO4 were respectively dissolved in deionized water to form the reactant solutions. By adding ammonium hydroxide, the pH values of the two solutions were adjusted to 9.5. Subsequently, the as-obtained (NH4)2HPO4 solution (dispersed phase) and Ca(NO3)2 solution (continuous phase) were respectively pumped into the inner and outer tubes with two feed pumps at room temperature (25 °C). After passing through the micropores of the inner tube, (NH4)2HPO4 solution was dispersed into microstreams and reacted with Ca(NO3)2 solution in the microchannel to form HAP precursor, which was collected at different sampling points for further treatment. For comparison, HAP nanoparticles were also prepared in a T-junction microchannel reactor (TMCR) and a stirred tank reactor (STR). The configuration of the TMCR is schematically shown in Figure 2. Two feed channels and one reaction channel converge at the T-type junction, where the reactants impinge and then flow through the reaction channel as the reaction

Figure 1. (a) Schematic diagram of experimental setup and the structure of the reactor: (A) tank; (B) feed pump; (C) flowmeter; (D) inlet of inner tube; (E) inlet of outer tube; (F) outlet; (G) micropores; (H) microchannel; (I) sample points. (b) Photographs of microporous tube-in-tube microreactor: (left) inner tube (J) and outer tube (K); (right) micropore zone.

Figure 2. Schematic diagram of T-junction microchannel reactor: (A) horizontal feed channel; (B) vertical feed channel; (C) reaction channel.

proceeds. Ca(NO3)2 solution and (NH4)2HPO4 solution were separately pumped into the horizontal feed channel and the vertical feed channel. The channel width (x) and depth (y) are 400 and 500 µm for all the three channels, respectively. For the preparation of HAP nanoparticles in the STR, (NH4)2HPO4 solution was dropwise added into Ca(NO3)2 solution under highspeed stirring condition (1000 rpm). After completing the input of (NH4)2HPO4 solution, the HAP precursor was continually stirred for another 2 h. After they were obtained in the three different reactors, HAP precursors were immediately transferred to a Teflon autoclave, which was enclosed firmly in a stainless steel pressure vessel and placed in a heater filled with glycerol, and then hydrothermally treated at 220 °C for 4 h. After hydrothermal crystallization, the products were separated from the mother liquor by filtration. After being washed five times with deionized water and once more with absolute ethyl alcohol, the products were dried in a drying cabinet at 80 °C for 12 h to obtain HAP nanoparticles. 2.3. Characterization. The morphology of HAP samples and HAP precursors was observed by transmission electron microscopy (TEM) (H-800, Hitachi, Japan) and field-emission scanning electron microscopy (FE-SEM) (JSM-6701F, JEOL, Japan), respectively. The mean particle size and the corresponding size distribution were estimated by measuring the sizes of at least

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Figure 3. TEM images of HAP nanoparticles prepared at the continuous phase flow rate of (a) 500, (b) 833, (c) 1667, and (d) 2500 mL/min. The dispersed phase flow rates were all 500 mL/min.

Figure 4. Effect of continuous phase flow rate on (a) particle length-width ratio distribution and (b) the corresponding Reynolds number and mean particle size.

300 particles in the TEM images with the aid of professional image analysis and processing software (Image-Pro Plus 5.1, Media Cybernetics Inc., USA). The length and width of a particle were both determined, and the length-width ratio was also calculated. The length was prescribed as the specific particle size. The specific surface area of HAP samples was detected by a BET surface area analyzer (ASAP-2010, Micromeritics Instrument Corp., USA) via the nitrogen-adsorption method. The crystal form of HAP samples was examined by X-ray diffraction analysis (XRD) (XRD-6000, Shimadzu, Japan), and the chemical composition was analyzed by Fourier transmission infrared spectroscopy (FT-IR) (8700, Nicolet, USA). 3. Results and Discussion 3.1. Influence of Continuous Phase Flow Rate. TEM images of HAP nanoparticles prepared at different continuous

phase flow rates are shown in Figure 3. It can be clearly observed that at a high flow rate of 1667 or 2500 mL/min, the as-prepared nanoparticles had a more uniform rodlike morphology with smaller size and the narrower size distribution compared to those at a low flow rate of 500 or 833 mL/min. The length-width ratio distribution in Figure 4a also indicates that the length-width ratio of HAP nanoparticles was inversely proportional to the continuous phase flow rate and had an obvious narrowing distribution owing to the increase of the continuous phase flow rate. The evolution of the mean particle sizes vs the continuous phase flow rates is presented in Figure 4b. The corresponding Reynolds numbers are also indicated in this figure. Clearly, increasing the continuous phase flow rate from 500 to 2500 mL/min systematically decreased the particle size from 498 to 72 nm. The possible reason is that increasing the continuous phase flow rate can induce the increase of


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Figure 5. Effect of dispersed phase flow rate on (a) the corresponding Reynolds number and mean particle size and (b) particle length-width ratio distribution.

Figure 6. Effect of mixing distance on (a) mean particle size and (b) particle length-width ratio distribution.

Reynolds number and the enhancement of mixing effectiveness. This is favorable for convection and interdiffusion of reactants, thereby resulting in an even nucleation and growth environment and leading to small particle size and narrow size distribution.40 In addition, when passing through the micropores and going into the microchannel, the dispersed phase is transformed to small droplets by a cross-flow shearing force. The cross-flow shearing force is also enhanced with the increase of the continuous phase flow rate, thereby reducing the geometric scale of the dispersed phase, shortening the diffusion distance and providing a large contact area.41 As a result, an excellent reaction environment for the formation of small particles with uniform size distribution is obtained. 3.2. Influence of Dispersed Phase Flow Rate. The effect of the dispersed phase flow rate on the mean particle size of HAP nanoparticles is exhibited in Figure 5a. It is worth mentioning that a rapid size decrease from 102 to 72 nm was observed when the dispersed phase flow rate was increased from 125 to 500 mL/min. Further increasing the flow rate reversely created a size increase effect. Similarly, the particle length-width ratio distribution first became narrower and then turned wider with the continuous increase of the dispersed phase flow rate, as shown in Figure 5b. There are two probable reasons for this complex phenomenon. On one hand, the increased Reynolds number from the increase of the dispersed phase flow rate contributes to an even distribution of supersaturation in the reaction environment, thereby leading to uniform distribution of the driving force for the nucleation and growth processes and giving rise to narrow particle size distribution, as stated earlier. On the other hand, the cross-flow shearing force inevitably becomes smaller with an increasing dispersed phase flow rate due to the dispersion of the more dispersed phase in

the continuous phase. Therefore, the weakened flow splitting effect would cause uneven micromixing of the two phases and result in the formation of nonuniform particles. This negative influence would prevail against the positive contribution of the increase of the dispersed phase flow rate itself with further raising the dispersed phase flow rate to a high value. 3.3. Influence of Mixing Distance. The influence of the mixing distance, namely the distance from micropore zone to each sampling point, on the mean particle size and the corresponding length-width ratio distribution of HAP nanoparticles is given in Figure 6a and b, respectively. The mean particle size sharply decreased from 112 to 80 nm with the increase of the mixing distance from 10 to 55 mm, and then slightly decreased to 72 nm with the further increased mixing distance to 110 mm. When the mixing distance was changed from 10 to 55 mm, the particle length-width ratio had an obvious narrowing distribution trend and a decrease of the mean ratio from 4.8 to 3.6. However, no significant change was observed when the mixing distance was beyond 55 mm. From a practical point of view, it is convenient for getting better micromixing homogeneity with a relatively short mixing distance, because it allows performing the entire experiment flexibly according to different needs.42 3.4. Influence of Reactant Concentration. The influence of the reactant concentration on the mean particle size of HAP nanoparticles is shown in Figure 7. The results indicated that the mean particle size first decreased and then increased with increasing the concentrations of Ca(NO3)2 and (NH4)2HPO4 solutions. This could be attributed to the fact that the increases of the concentrations of Ca(NO3)2 and (NH4)2HPO4 solutions led to a high supersaturation level. This made nucleation and

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Figure 7. Effect of reactant concentration on mean particle size.

Figure 8. Effect of micropore size on mean particle size.

growth proceed very fast, thereby resulting in the generation of small particles.43 However, a large amount of HAP primary nuclei were spontaneously formed when the concentration reached a rather high value. In this case, the aggregation of HAP primary nuclei was greatly intensified during the reaction, causing the polydispersity of HAP nanoparticles. 3.5. Influence of Micropore Size. The influence of the micropore size on the mean particle size of HAP nanoparticles is exhibited in Figure 8. Obviously, the mean particle size decreased from 94 to 72 nm with the decrease of the micropore size from 40 to 5 µm. The size of the dispersed phase is mainly determined by the pore size of micropores on the annular surface of the inner tube.44 The micromixing between Ca(NO3)2 solution and (NH4)2HPO4 solution was strongly improved by decreasing the micropore size, thereby resulting in improved morphology, particle size, and size distribution of HAP nanoparticles. 3.6. Comparison of HAP Nanoparticles Prepared in Different Reactors. Figure 9a and b display XRD patterns and

IR spectra of HAP precursors and nanoparticles prepared under the optimized experimental runs of the three different reactors, respectively. XRD patterns indicated that the HAP precursor prepared in the STR was a single phase HAP with low crystallinity degree compared with the JCPDS 74-0566 file data for HAP since the HAP precursor was continually stirred for 2 h after the addition of (NH4)2HPO4 solution into Ca(NO3)2 solution. However, HAP precursors obtained in the TMCR and MTMCR were amorphous calcium phosphate (termed as ACP) due to the absence of a long-time stirring process. IR spectra showed that more absorption bands assigned to HAP could be detected in the HAP precursor prepared in the STR than in the TMCR and MTMCR, which is consistent with the results from XRD patterns. Furthermore, it is obviously found in XRD patterns and IR spectra that, after hydrothermal crystallization, HAP nanoparticles prepared in the three different reactors had the same characteristic HAP crystal form and chemical component.45,46 Figure 10a, c, and e present SEM images of HAP precursors prepared in the three different reactors. Spherelike particles with a size of about 30 nm corresponded to ACP or low-crystallized HAP. As shown in the insets of Figure 10a, c, and e, the aggregates of the particles revealed the characteristic morphology of HAP precursors prepared in the three different reactors. Among them, HAP precursor obtained in MTMCR had the most uniform aggregates with the smallest size and the best dispersion. TEM images of HAP nanoparticles prepared in the three different reactors and the corresponding particle size distributions are also shown in Figure 10b, d, f, and g. It could be clearly observed that HAP nanoparticles appeared typical rodlike shape. However, the nanoparticles obtained in MTMCR had the most uniform morphology and the narrowest size distribution. There were no distinct differences in the shape and size distribution between the nanoparticles produced in STR and TMCR. As seen in Table 1, the special surface area of HAP precursors prepared in the MTMCR was larger than that of HAP precursors prepared in the STR and TMCR, mainly attributed to the low aggregation of spherelike ACP particles in the HAP precursor. After hydrothermal treatment of HAP precursors, the special surface area of as-prepared HAP nanoparticles was greatly decreased, but the nanoparticles prepared in the MTMCR still had the largest specific surface area of 49.32 m2/g owing to the smallest size of 58 nm. From the aforementioned results, it is deduced that the reactor type had an obvious effect on the aggregation degree of HAP precursors and further markedly affected the morphology and size distribution of as-prepared HAP nanoparticles. In a batch

Figure 9. (a) XRD patterns and (b) IR spectra of (1-3) HAP precursors and (4-6) HAP nanoparticles prepared in different reactors: (1, 4) STR (Cc ) 0.267 mol/L, Cd ) 0.8 mol/L); (2, 5) TMCR (Cc ) 0.067 mol/L, Cd ) 0.2 mol/L, Fc ) 61.5 mL/min, Fd ) 12.3 mL/min); (3, 6) MTMCR (Cc ) 0.167 mol/L, Cd ) 0.5 mol/L, Fc ) 2500 mL/min, Fd ) 500 mL/min, L ) 110 mm, S ) 5 µm).


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Figure 10. (a, c, e) SEM images of HAP precursors and (b, d, f) TEM images and (g) the corresponding particle size distributions of HAP nanoparticles prepared in the (a, b) STR, (c, d) TMCR, and (e, f) MTMCR. The operation parameters of the three different reactors were identical with those in Figure 9.

reactor like the STR, it is hard to obtain uniform small particles because of the poor micromixing. In a conventional microre-

actor, e.g. TMCR, mixing is mainly adjusted by molecule diffusion. The mixing process is relatively slow for the absence

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Table 1. Mean Particle Size of HAP Nanoparticles and Specific Surface Area of HAP Precursors and Nanoparticles Prepared in Different Reactors Ap (m2/g) reactor

Dp (nm)

precursor

nanoparticle

STR TMCR MTMCR

102 92 58

81.19 83.20 87.63

45.21 46.79 49.32

of turbulence, leading to lacking chemical homogeneity and then inducing the polydispersity of the obtained particles.47 In the proposed MTMCR, (NH4)2HPO4 solution is dispersed through micropores on the annular surface of the inner tube, as illustrated in the axial cross-sectional profile of micropore zone of MTMCR in Figure 11. Since the annular micropore belt is analogous to lots of distributive T-junctions, the microchannel can be regarded as a multi-T-junction microchannel, where (NH4)2HPO4 solution is split into a series of separate multichannel streams and fed into Ca(NO3)2 solution. Obviously, such a special multibranch cross-flow mixing method can increase the contact area and shorten the diffusion distance, thereby intensifying the micromixing and promoting the formation of small and uniform nanoparticles. As shown in the radial cross-sectional profile of micropore zone of MTMCR in Figure 11, the annular crosssectional microchannel of the MTMCR can be referred to as a multichannel reactor, namely the aggregate of numerous multiT-junction microchannels having trapezoid cross-section, which is of great benefit to achieving a high throughout. In fact, the throughput of an MTMCR can reach up to 9 L/min or even larger with an excellent micromixing performance maintained.29,30 More importantly, it is worth noting that thanks to the special symmetrical structure of an MTMCR, in situ self-equi-distribution of two separate ingoing streams can effectively be achieved in an MTMCR with no help from any additional devices, which is favorable for reducing cost and simplifying operation. 4. Conclusion The rodlike HAP nanoparticles with tunable size of 55-95 nm and narrow size distribution can be successfully prepared in an MTMCR under a high throughput of 3 L/min. The mean particle size of HAP nanoparticles quickly decreased with the increase of the continuous phase flow rate, while it first decreased and then increased with the increases of the dispersed phase flow rate and the reactant concentration. Increasing the mixing distance resulted in a decrease of the mean particle size, but the change was not obvious when the mixing distance exceeded 55 mm. The micropore size had an important positive effect on the mean particle size. Furthermore, the comparison

experiment results in three reactors proved that HAP nanoparticles synthesized in the MTMCR had the smallest mean particle size of 58 nm, the narrowest size distribution, and the largest specific surface area of 49.32 m2/g as compared with those obtained in the STR and TMCR. Therefore, it is expected that an MTMCR would become a promising and cost-effective platform for the continuous and high-throughput production of valuable and high-quality nanoparticles. Acknowledgment This work was financially supported by the National “863” Program of China (Nos. 2007AA030207 and 2008AA03A332), National Natural Science Foundation of China (Nos. 20806004 and 20821004), and National “973” Program of China (No. 2009CB219903). Nomenclature Cc ) concentration of continuous phase (mol/L) Cd ) concentration of dispersion phase (mol/L) Fc ) flow rate of continuous phase (mL/min) Fd ) flow rate of dispersion phase (mL/min) L ) mixing distance (mm) S ) micropore size (µm) dp ) particle size in length dimension (nm) Dp ) mean particle size in length dimension (nm) Ap ) special surface area of HAP nanoparticles (m2/g) N ) number fraction of particle size (%) rp ) particle length-width ratio Re ) Reynolds number

Literature Cited (1) Lo¨we, H.; Ehrfeld, W. State-of-the-art in microreaction technology: concepts, manufacturing and applications. Electrochim. Acta 1999, 44, 3679. (2) Ja¨hnishch, K.; Hessel, V.; Lo¨we, H.; Baerns, M. Chemistry in microstructured reactors. Angew. Chem., Int. Ed. 2004, 43, 406. (3) Pennemann, H.; Hessel, V.; Lo¨we, H. Chemical microprocess technology s from laboratory-scale to production. Chem. Eng. Sci. 2004, 59, 4789. (4) Kralisch, D.; Kreisel, G. Assessment of the ecological potential of microreaction technology. Chem. Eng. Sci. 2007, 62, 1094. (5) Tonkovich, A. L. Y.; Yang, B.; Perry, S. T.; Fitzgerald, S. P.; Wang, Y. From seconds to milliseconds to microseconds through tailored microchannel reactor design of a steam reformer. Catal. Today 2007, 120, 21. (6) Cao, C. S.; Palo, D. R.; Tonkovich, A. L. Y.; Wang, Y. Catalyst screening and kinetic studies using microchannel reactors. Catal. Today 2007, 125, 29. (7) Cao, C. S.; Hu, J. L.; Li, S. R.; Wilcox, W.; Wang, Y. Intensified Fischer-Tropsch synthesis process with microchannel catalytic reactors. Catal. Today 2009, 140, 149.

Figure 11. Detailed illustration of structural analogy between the MTMCR and a multi-T-junction microchannel reactor.

Ind. Eng. Chem. Res., Vol. 49, No. 1, 2010 (8) Ajmera, S. K.; Losey, M. W.; Jensen, K. F.; Schmidt, M. A. Microfabricated packed-bed reactor for phosgene synthesis. AIChE J. 2001, 47, 1639. (9) Tonkovich, A. L.; Jarosch, K.; Arora, R.; Silva, L.; Perry, S.; McDaniel, J.; Daly, F.; Litt, B. Methanol production FPSO plant concept using multiple microchannel unit operations. Chem. Eng. J. 2008, 135S, S2. (10) Sichler, P.; Bu¨ttgenbach, S.; Baars-Hibbe, L.; Schrader, C.; Gericke, K. H. A micro plasma reactor for fluorinated waste gas treatment. Chem. Eng. J. 2004, 101, 465. (11) Watts, P.; Haswell, S. J. Continuous flow reactors for drug discover. Drug Disc. Today 2003, 8, 586. (12) Zhao, C.; Jiang, H. H.; Smith, D. R.; Bruckenstein, S.; Wood, T. D. Intergration of an on-line protein digestion microreactor to a nanoelectrospray emitter for peptide mapping. Anal. Biochem. 2006, 359, 167. (13) Wagner, J.; Ko¨hler, J. M. Continuous synthesis of gold nanoparticles in a microreactor. Nano Lett. 2005, 5, 685. (14) Huang, J. L.; Lin, L. Q.; Li, Q. B.; Sun, D. H.; Wang, Y. P.; Lu, Y. H.; He, N.; Yang, K.; Yang, X.; Wang, H. X.; Wang., W. T.; Lin, W. S. Continuous-flow biosynthesis of silver nanoparticles by lixivium of sundried cinnamomum camphora leaf in tubular microreactors. Ind. Eng. Chem. Res. 2008, 47, 6081. (15) Takagi, M.; Maki, T; Miyahara, M; Mae, K. Production of titania nanoparticles by using a new microreactor assembled with same axle dual pipe. Chem. Eng. J. 2004, 101, 269. (16) Shestopalov, I.; Tice, J. D.; Ismagilov, R. F. Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system. Lab. Chip 2004, 4, 316. (17) Wang, K.; Wang., Y. J.; Chen, G. G.; Luo, G. S.; Wang, J. D. Enhancement of mixing and mass transfer performance with a microstructure minireactor for controllable preparation of CaCO3 nanoparticles. Ind. Eng. Chem. Res. 2007, 46, 6092. (18) Ying, Y.; Chen, G. W.; Zhao, Y. C.; Li, S. L.; Yuan, Q. A high throughput methodology for continuous preparation of monodispersed nanocrystals in microfluidic reactors. Chem. Eng. J. 2008, 135, 209. (19) Zhang, S. H.; Shen, S. C.; Chen, Z.; Yun, J. X; Yao, K. J; Chen, B. B.; Chen, J. Z. Preparation of solid lipid nanoparticles in co-flowing microchannels. Chem. Eng. J. 2008, 144, 324. (20) Zhao, H.; Wang, J. X.; Wang, Q. A.; Chen, J. F.; Yun, J. Controlled liquid antisolvent precipitation of hydrophobic pharmaceutical nanoparticls in a microchannel reactor. Ind. Eng. Chem. Res. 2007, 46, 8229. (21) Jongen, N.; Donnet, M.; Bowen, P.; Lemaıˆtre, J.; Hofmann, H.; Schenk, R.; Hofmann, C.; Aoun-Habbache, M.; Guillemet-Fritsch, S.; Sarrias, J.; Rousset, A.; Viviani, M.; Buscaglia, M. T.; Buscaglia, V.; Nanni, P.; Testino, A.; Herguijuela, J. R. Development of a continuous segmented flow tubular reactor and the “Scale-out” concept s in search of perfect powders. Chem. Eng. Technol. 2003, 26, 303. (22) Tonkovich, A.; Kuhlmann, D.; Rogers, A.; McDaniel, J.; Fitzgerald, S.; Arora, R.; Yuschak, T. Microchannel technology scale-up to commercial capacity. Chem. Eng. Res. Des. 2005, 83, 634. (23) Commenge, J. M.; Falk, L.; Corriou, J. P.; Matlosz, M. Optimal design for flow uniformity in microchannel reactors. AIChE J. 2002, 48, 345. (24) Jensen, K. F. Microreaction engineering s is small better. Chem. Eng. Sci. 2001, 56, 293. (25) Mills, P. L.; Quiram, D. J.; Ryley, J. F. Microreactor technology and process miniaturization for catalytic reactions s A perspective on recent developments and emerging technologies. Chem. Eng. Sci. 2007, 62, 6992. (26) Chen, Y. P.; Cheng, P. Heat transfer and pressure drop in fractal tree-like microchannel nets. Int. J. Heat Mass Transfer 2002, 45, 2643. (27) Schenk, R.; Hessel, V.; Hofmann, C.; Lo¨we, H.; Scho¨nfeld, F. Novel liquid-flow splitting unit specifically made for numbering-up of liquid/liquid chemical microprocessing. Chem. Eng. Technol. 2003, 26, 1271. (28) Tonomura, O.; Tanaka, S.; Noda, M.; Kano, M.; Hasebe, S.; Hashimoto, I. CFD-based optimal design of manifold in plate-fin microedevices. Chem. Eng. J. 2004, 101, 397.

147

(29) Wang, Q. A.; Wang, J. X.; Yu, W.; Shao, L.; Chen, G. Z.; Chen, J. F. Investigation of micromixing efficiency in a novel high throughput microporous tube-in-tube microchannel reactor. Ind. Eng. Chem. Res. 2009, 48, 5004. (30) Wang, Q. A.; Wang, J. X.; Li, M.; Shao, L.; Chen, J. F.; Gu, L.; An, Y. T. Large-scale preparation of barium sulphate nanoparticles in a high throughput tube-in-tube microchannel reactor. Chem. Eng. J. 2009, 149, 473. (31) Dorozhkin, S. V.; Epple, M. Biological and medical significance of calcium phosphates. Angew. Chem., Int. Ed. 2002, 41, 3130. (32) Mohamed, K. R.; Mostafa, A. A. Preparation and bioactivity evaluation of hydroxyapatite-titania/chitosan-gelatin polymeric biocomposites. Mater. Sci. Eng., C 2008, 28, 1087. (33) Qiu, H. J.; Yang, J.; Kodali, P.; Koh, J.; Ameer, G. A. A citric acid-based hydroxyapatite composite for orthopedic implants. Biomaterials 2006, 27, 5845. (34) Suen, R. B.; Lin, S. C.; Hsu, W. H. Hydroxyapatite-based immobilized metal affinity adsorbents for protein purification. J. Chromatogr. A. 2004, 1048, 31. (35) Vega, E. D.; Pedregosa, J. C.; Narda, G. E.; Morando, P. J. Removal of oxovanadium (IV) from aqueous solutions by using commercial crystalline calcium hydroxyapatite. Water Res. 2003, 37, 1776. (36) Zhu, R. H.; Yu, R. B.; Yao, J. X.; Mao, D.; Xing, C. J.; Wang, D. Removal of Cd2+ from aqueous solutions by hydroxyapatite. Catal. Today 2008, 139, 94. (37) Cheikhi, N.; Kacini, M.; Rouimi, M.; Ziyad, M.; Liotta, L. F.; Pantaleo, G.; Deganello, G. Direct synthesis of methyl isobutyl ketone in gas-phase reaction over palladium-loaded hydroxyapatite. J. Catal. 2005, 232, 257. (38) Liu, Z. S.; Tang, S. L.; Ai, Z. L.; Hu, J. Growth inhibition of human hepatoma and colon carcinoma cell line treated with hydroxyapatite nanoparticles. Chin. J. Exp. Surg. 2006, 23, 266. (39) Liu, T. Y.; Chen, S. Y.; Liu, D. M.; Liou, S. C. On the study of BSA-loaded calcium-dificient hydroxyapatite nano-carriers for controlled drug delivery. J. Controlled Release 2005, 107, 112. (40) Trippa, G.; Jachuck, R. J. J. Process intensification: precipitation of calcium carbonate using narrow channel reactors. Chem. Eng. Res. Des. 2003, 81, 766. (41) Xu, J. H.; Luo, G. S.; Chen, G. G.; Wang, J. D. Experimental and theoretical approaches on droplet formation from a micrometer screen hole. J. Membr. Sci. 2005, 266, 121. (42) Paniæ, S.; Loebbecke, S.; Tuercke, T.; Antes, J.; Bosˇkoviæ, D. Experimental approaches to a better understanding of microfluidic devices. Chem. Eng. J. 2004, 101, 409. (43) Kucher, M.; Babic, D.; Kind, M. Precipitation of barium sulfate: experimental investigation about the influence of supersaturation and free lattice ion ratio on particle formation. Chem. Eng. Process. 2006, 45, 900. (44) Vladisavljeviæ, G. T.; Lambrich, U.; Nakajima, M.; Schubert, H. Production of O/W emulsions using SPG membranes, ceramic R-aluminium oxide membranes, microfluidizer and a silicon microchannel plate s a comparative study. Colloids Surf. A 2004, 232, 199. (45) Chen, F.; Wang, Z. C.; Lin, C. J. Preparation and characterization of nano-sized hydroxyapatite particles and hydroxyapatite/chitosan nanocomposite for use in biomedical materials. Mater. Lett. 2002, 57, 858. (46) Antonakos, A.; Liarokapis, E.; Leventouri, T. Micro-Raman and FTIR studies of synthetic and natural apatites. Biomaterials 2007, 28, 3043. (47) Edel, J. B.; Fortt, R.; deMello, J. C.; deMello, A. J. Microfluidic routes to the controlled production of nanoparticles. Chem. Commun. 2002, 1136.

ReceiVed for reView April 3, 2009 ReVised manuscript receiVed October 21, 2009 Accepted November 2, 2009 IE9005436

High Throughput Methodology for Continuous Preparation of

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