Concept of Microfluidics for Chemical Production
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II Workshop on Translational Nanomedicine Donostia-San Sebastian Sep 18-19, 2017 Concept of Microfluidics for Chemical Production Dr. Thomas R. Dietrich IVAM Microtechnology Network Dortmund, Germany www.ivam.de AGENDA - Introduction to IVAM Microtechnology Network esp. its microfluidic activities - concept of micro reaction technology - manufacturing of microfluidic components - examples This is who we are Type of member personal member network partner 2% 10% International institute 25% Microtechnology company 63% Business of companies and institutes § micro technology § nano technology § MEMS Network § advanced materials § photonics Business regions of IVAM members 22% 30% 35% 100% 78% 48% 40% 40% 27% 40% percentage of 9% IVAM members doing business in these regions Source: IVAM Survey 2016 4 free world map template: www.presentationmagazine.com 26.09.17 Technologies in Member Companies Microtechnology MEMS Nanotechnology Photonics Advanced Materials • micro chemical engineering • biotechnology • medical applications 5 26.09.17 Major target markets 6 26.09.17 IVAM activities in Micro Fluidics Experts and Focus Groups Companies and Research Institutions, working on the commercialization of microfluidics Chair: Dominique Bouwes, Micronit Microfluidics Research Advisory Board Member Prof. Roland Zengerle IMTEK, Hahn-Schickard Executive Microfluidics Board Entrepreneurship Member Dr. Hans van den Vlekkert LioniX BV Micro Fluidics in Chemistry Micro Fluidic Applications Chemistry Biotechnology Medical technology Product development Analytics Mobile Diagnostics Production Lab-on-a-Chip Lab applications § Wording micro reaction technology micro chemical engineering micro process engineering micro reactor micro structured reactor (micro shaped flows) Microreactors for Nanomedicine AAPS PharmSciTech. 2014 Dec; 15(6): 1527–1534. Published online 2014 Jul 22. Nanomedicine Scale-up Technologies: Feasibilities and Challenges Rishi Paliwal, R. Jayachandra Babu, and Srinath Palakurthicorresponding author Europe and USA are leading in MRT Internationalization: Formation of Micro Process Engineering Center in Mexiko April 2008 El Norte (April 2008) Internationalization: Introduction of Micro Chemical Engineering in Brazil MICROREACTION TECHNOLOGY: A TOOL FOR SUSTAINABLE CHEMISTRY Signing of cooperation contract between CTGAS-ER (research institute funded by SENAI and PETROBRAS) and mikroglas in Natal 2012 International Activities in Asia Japan: public funding since 2000 60 Mio € first 13 production plants installed in 2013 China: Research Institutes e.g. in Dalian, Beijing, Shanghai, Hongzhou IMRET 14 2016 in Beijing, China Ehrfeld Mikrotechnik BTS: MIPROWA production reactor for Shaoxing Eastlake Biochemical (China) production capacity of up to 10,000 t/a Batch vs. “Micro” Main differences: batch-reactor micro-reactor dimensions cm – m µm regime batch continuous control by time by geometry driving force thermodynamics kinetics à Better control of chemistry Motivation: Enhance SAFETY glyoxylic acid from dimethyl maleate Ozonolysis § fast reaction § strongly exothermal reaction § highly explosive reaction conditions § in batch: very low temperatures (-20°C to -70°C) Austrian newspaper, Why should this be done in microstructured reactors? August 10th, 2004: § high specific interfacial area § isothermal operation possible § low hold up § exact defined reaction conditions (e.g. T, flow) § continuous process at higher temperatures Motivation: SUSTAINABILITY SUSTAINABLE CHEMISTRY stoichiometric mixtures reactions at = less sideproducts higher concentrations and waste or even without solvents enhanced safety energy supply controlled by geometry WHERE and WHEN necessary BATCH vs. MICRO reactor batch reactor micro reactor effect diameter cm to m several µm to several mm volume several ml to several 1000 l < 1 ml to several 10 ml --> higher safety flow -- several µl/min to several ml/min residence time = production time (min - hrs) ms to a few minutes --> only for fast reactions Reynold's numbers > 2.300 very low --> laminar flow surface to volume ratio < 100 m²/m³ 10,000 - 300.000 m²/m³ --> surface is very important Source: Paul Watts Mixing in a Micro Reactor laminar flow à by diffusion Diffusion time ∝ (diffusion path)2 § 0.0005 sec 1 µm (bacteria) § 0.05 sec 10 µm (cell) § 5 sec 100 µm § 500 sec 1000 µm (1 mm) T. Motokawa Cells: Molecules are transported everywhere in the cell within a second by molecular diffusion. The living cell is still by far the most efficient and versatile microreactor. No stirring is needed. Source: Jun-ichi Yoshida, Uni Kyoto SuperFocus Mixer for fast mixing - mixing of two liquids or gases - 124 channel inlets in a mixing chamber - flowrates up to 10 l/h possible - length of reaction channel 70 mm typical flow: f = 10 ml/min typical residence time: tr = 0.1 - 1 s 2 Mixing only by diffusion: td ~ dl / D short diffusion time by multi - lamellae reaction channel: w = 500 µm width of lamellae: dl = 4 µm diffusion time: td = several ms td < tr (Micro) structure by structurized media Encased flow, Free flow, Free droplet flow Free gas bubble Free falling droplets, Channel with encased by encased by flow, e.g. spray, solid walls liquid sheets liquid encased by liquid encased by gas Fluid streams are pre-shaped à microreactors without microstructured channels Advantages because of large surface to volume ratio 55 A =f(R) 50 S 45 40 35 3 - 30 m dR 2 25 / m S 20 A 15 AS 10 L=10mm 5 0 0 500 1000 1500 2000 2500 3000 R / µm 2 -3 dR / µm AS / m m 100 400 A decrease of channel diameter enhances 250 160 heat- and mass transfer by diffusion 500 80 1000 40 Surface to volume ratio is significantly increased 5000 8 Heat Transfer § In a batch reaction heat is removed from the reaction mixture at the surface of the reaction vessel § As the flask gets bigger its harder to remove heat § Use large cooling baths as a heat sink § Often cool to a much lower temperature than needed (e.g. -78 oC) § At an industrial scale this is difficult! § Expensive Chemists slow down chemistry just to control the heat management! Task: heat management narrow temperature distribution in microreactors No parallel reaction because of good temperature control ! counterflow channel width: 1.0 mm channel depth: 0.5 mm channel length: 280 mm Inlet liquid 1 wall thickness: 0.2 mm Inlet liquid 2 Outlet liquid 2 Outlet liquid 1 New Approach with µ-Reaction Technology conventional technology new technology with µ-reactors Becht Degussa May 2007 chemistry is forced into a given plant chemistry influences CHEMISTRY the design of the reactor Glass-Microreactor for Photochemistry with small channels designed according the absorption length The synthesis of bioactive compounds by photodecarboxylative addition of carboxylates to phthalimides S. Gallagher, F. Hatoum, M. Oelgemöller and A. G. Griesbeck, Book of Abstracts, Central Europ. Conf. on Photochemistry (CECP 2008), Bad Hofgastein,Austria, February 2008, p. 69. Results: - significant reduction of reaction time - yield 97% - channel length: 1.4 m - f = 0.08 ml/min - residence time: 21 min - exposure at 300 nm (Luzchem UV Panel) Choice of Material e.g. for a nitration reaction properties resistantChemically resistant temperatures pressure up optical resistantagainst against up to 150°C to 10 bar transparent HNO3/H2SO4 organic solvents material metal ceramic glass polymers silicon Choice of Material • ceramics, especially because of: • high temperature stability IMVT, KIT • stainless steel, especially because of: • resistance against high pressure • good heat conductivity Ehrfeld • glass, especially because of • chemical stability • optical transparency • electrical insulation mikroglas mikroglas – Interdigital Mixer different functions in different layers exit component 1 component 2 3D-printing technologies inkjet fused deposition modelling 2-photon polymerization stereo lithography Advantages: Issues: rapid manufacturing material mostly polymer specific designs in each reactor chemically not very stable Microsystems & Nanoengineering 2, Article number: 16063 (2016) doi:10.1038/micronano.2016.63 SCALE-UP for large volume production Scale-Up by - parallelization - numbering-up - equaling-up Reaction Classification & Advantages § Type A reactions § Very fast (< 1s) § Controlled by the mixing processes § Increase Yield through better mixing/heat exchange § Type B reactions § Rapid reaction (10s to 20min) § Predominantly kinetically controlled § Avoid overcooking and increase Yield § Type C reactions § Slow reaction (> 10min) § Batch processes with thermal hazard § Enhance safety § Need intensification Source: Lonza – Microreactor Technology (2009) Reaction Classification & Advantages D.M. Roberge et al. CE&T 2005: Reactions at Lonza Type A reactions 21% Type B reactions 50% 23% Type C reaction 6% Remaining Sigma Aldrich / Merck : Explorer Kit Borosilicate glass reactors with different mixing regimes and different sizes manufactured by Little Things Factory Sigma-Aldrich Microreactor Explorer Kit 19979 prototype http://www.sigmaaldrich.com/technical- documents/articles/chemfiles/microreactor-technology.html Syrris, UK: Microreactors for R&D Africa Microreactors Asia Microreactors Ehrfeld Mikrotechnik: Modular MR System INVITE und F³-factory - Modular Production future chemical production: - smaller and more flexible - modular construction - on-site/in-time production Research still necessary! Downstream processes Missing steps for processes in continuous separation ofside products (serveral steps reactions, change of solvents,