Chemical emical proces cesses ses an and separ arat atio ion n te techno hnology logy on a a micros croscale cale Mark Olde Riekerink Joint gathering of NL GUTS & PIN-NL, 9 April 2014 - Confidential -
Outline • Company introduction • Chemical processes on a microscale • Continuous flow • Multistack reactor • Mesoreactor • Microreactor • Separation technologies on a microscale • Capillary electrophoresis (CE) • Dielectrophoresis (DEP) • Acoustophoresis • Passive microfluidics confidential 2
Micronit Microfluidics – Key Facts Started in 1999 by Ronny van’t Oever & Micha Mulder (Founders) Location : Enschede, The Netherlands University of Twente: Hot spot of micro- & nanotechnology Annual turnover growth > 40% > 700 customers in > 50 countries worldwide About 50 employees and growing Highly educated multi-disciplinary team ISO 9001 certified, ISO 13485 (in 2014) 3 - Confidential -
International Customer Base Our people serve world’s top 10 We serve leading brands in technical universities analytic instrumentation and diagnostics globally 4 - Confidential -
Enschede – Nanotechnology MESA+, University of Twente • One of the largest micro-/nanotech groups worldwide • 500 people, 275 PhD’s and postdocs 2010 Nanolab • Infrastructure : >60 million euros • 1250 m 2 cleanroom 2012 High Tech Factory (HTF) • Production facility for micro- and nanotech-based companies/products • 13 cleanrooms, 20 laboratories, 46 offices 5
Micronit Cleanroom Facilities (HTF) • Photolithography processing and Microstructuring of glass wafers 6 - Confidential -
Micronit – What We Can Offer • Developing, prototyping and high-volume manufacturing of standard & custom Lab-on-a-Chip products • Microfluidic solutions for Life Sciences, Chemistry and Industrial applications • Unique combination of microfluidics know-how, semi-conductor, MEMS & micromachining capabilities • Market innovator powered by R&D department, cleanroom facilities and intellectual property 7 - Confidential -
Core Business MANUFACTURING • High-accuracy micromachining • Rapid prototyping • High-volume manufacturing capabilities DEVELOPMENT PARTNER • Co-engineering • Design for manufacturing • Microfluidics know-how RESEARCH TOOLS • Easy-to-use microfluidic kits to get started • Off-the-shelf standard microfluidic chip modules • Custom prototyping & low-volume manufacturing 8 - Confidential -
Broad Range of Microfluidic Solutions Droplet Generator Chips Chip holders and connectors Micromixers Fluidic PRO Prototyping CE Chips Electrical connections Micro Reactor Chips Macro-to-Micro interfacing Flow Cells System integration and packaging 9
Parallel droplet generation 10 10 - Confidential -
Advantages of Glass (I) CHEMICAL INERTNESS • Solvents and water do not dissolve glass • Minimum interference with reaction or analysis THERMAL STABILITY • Very well defined flat surface and mechanically stable • Glass is stable in time and has a very long shelf life OPTICALLY CLEAR • Glass is optically superior, special types even in UV-range • Glass has a low (auto) fluorescence 11 11
Advantages of Glass (II) KNOWN MATERIAL • Glass is relatively easy to coat using traditional procedures • Easier to comply with regulations NON-POROUS • Small molecules won’t diffuse into glass • No materials can diffuse out of the glass SUITABLE FOR LOW- AND HIGH-VOLUME MANUFACTURING • Micromachining in glass in volume is very economical • Prototyping processes identical to manufacturing processes 12 12
Outline • Company introduction • Chemical processes on a microscale • Continuous flow • Multistack reactor • Mesoreactor • Microreactor • Separation technologies on a microscale • Capillary electrophoresis (CE) • Dielectrophoresis (DEP) • Acoustophoresis • Passive microfluidics confidential 13 13
Development of continuous flow systems Partnership Access2Flow: confidential 14 14
Chemical processes down to microscale Laboratory Production Plant 1-10 ml 10-100 ml Nano-Microliter • optimization via • production in • fast and cost effective modular approach parallel reactors screening 15 15
Multistack reactor (DSM) • 22 glass layers, of which 10 x 10 ml reaction channels • 11 cooling layers Developed for and in cooperation with DSM 16 16
Mesoreactor • Reactor volume 3 ml • 4 bonded glass layers • Highly efficient mixing structures 17 17 - Confidential -
FLOWID Plug & Produce Flow Chemistry Switch from batch to continuous flow 18 18 - Confidential -
Microreactor Platform - Fluidic Connect Pro Reactor volume ~10 µl Standard fluidic devices: (75x25mm) mixers, reactors, droplet generators, CE 19 19
FlowStart Microreactor System • Smart, safe and clean chemistry • Accelerates the optimization of chemical processes by automated microreactor technology • Batch-to-flow translations The FlowStart microreactor system, developed in cooperation with Micronit Microfluidics 20 20
Outline • Company introduction • Chemical processes on a microscale • Continuous flow • Multistack reactor • Mesoreactor • Microreactor • Separation technologies on a microscale • Capillary electrophoresis (CE) • Dielectrophoresis (DEP) • Acoustophoresis • Passive microfluidics confidential 21 21
Capillary electrophoresis (CE) • Separation of charged molecules (e.g. ions, DNA fragments) based on their charge and mobility • Separation accuracy (resolution) dependent on channel length • Microfluidic applications: • DNA analysis • Blood analysis • Water analysis confidential 22 22
CE for Point-of-Care Applications (Lab-on-a-Chip) Features Point-of-Care Lithium Chip • On-chip reagents • Glass chip with etched channels • Plastic packaging • Powderblasted access holes and • Manufacturability in high reservoirs volume • Sputtered metal electrodes • Quality assured • Dry dicing technique • Economic pricing (one- • 1 cm 2 surface area time used chip) • CE marked • > 100.000 devices/year Source: www.medimate.com 23 23 - Confidential -
CE for Automated DNA Separation (Fingerprinting) Chip-based capillary gel electrophoresis is a proven technology for e.g. DNA analysis Forensics Sources: www.chem.agilent.com www.bio-rad.com www.perkinelmer.com www.shimadzu.com 24 24
CE System for DNA Fingerprinting (conceptual) 25 25 - Confidential -
CE Lab-on-a-Chip Prototypes Cartridge format USB stick format 26 26 - Confidential -
Dielectrophoresis (DEP) for cell manipulation/sorting 27 27 - Confidential -
Acoustophoresis for separation/concentration • Ultrasonic standing waves allow high-performance separation/ concentration of cells or particles Source: www.cellcare.lth.se confidential 28 28
Microfluidic chip for cell separation/concentration Yeast separation Blood cell separation from plasma 29 29
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