Joint gathering of NL GUTS & PIN-NL, 9 April 2014

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Mark Olde Riekerink

Chemical processes and separation technology on a microscale

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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

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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)

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We serve

leading brands in

analytic instrumentation and

diagnostics globally

Our people serve

world’s top 10 technical universities

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International Customer Base

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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 m2 cleanroom

2012 High Tech Factory (HTF)

• Production facility for micro- and nanotech-based

companies/products

• 13 cleanrooms, 20 laboratories, 46 offices

Enschede – Nanotechnology

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Micronit Cleanroom Facilities (HTF)

• Photolithography processing and

Microstructuring of glass wafers

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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

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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

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Broad Range of Microfluidic Solutions

Droplet Generator Chips

Micromixers

CE Chips

Micro Reactor Chips

Flow Cells

Chip holders and connectors

Fluidic PRO Prototyping

Electrical connections

Macro-to-Micro interfacing

System integration and packaging

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Parallel droplet generation

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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

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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

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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

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Development of continuous flow systems

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Partnership

Access2Flow:

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Chemical processes down to microscale

Laboratory Production Plant

Nano-Microliter

• fast and cost effective

screening

1-10 ml

• optimization via

modular approach

10-100 ml

• production in

parallel reactors

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Multistack reactor (DSM)

• 22 glass layers, of which 10 x 10 ml reaction channels

• 11 cooling layers

Developed for and in

cooperation with DSM

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Mesoreactor

• Reactor volume 3 ml

• 4 bonded glass layers

• Highly efficient mixing structures

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FLOWID Plug & Produce Flow Chemistry

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Switch from batch to continuous flow

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Microreactor Platform - Fluidic Connect Pro

Standard fluidic devices: (75x25mm)

mixers, reactors, droplet generators, CE

Reactor volume ~10 µl

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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

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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

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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

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CE for Point-of-Care Applications (Lab-on-a-Chip)

Features Point-of-Care Lithium Chip

• Glass chip with etched channels

• Powderblasted access holes and reservoirs

• Sputtered metal electrodes

• Dry dicing technique

• 1 cm2 surface area

• CE marked

• On-chip reagents

• Plastic packaging

• Manufacturability in high volume

• Quality assured

• Economic pricing (one-time used chip)

• > 100.000 devices/year

Source: www.medimate.com

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CE for Automated DNA Separation (Fingerprinting)

Sources:

www.chem.agilent.com

www.bio-rad.com

www.perkinelmer.com

www.shimadzu.com

Chip-based capillary gel electrophoresis is

a proven technology for e.g. DNA analysis

Forensics

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CE System for DNA Fingerprinting (conceptual)

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CE Lab-on-a-Chip Prototypes

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Cartridge format

USB stick format

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Dielectrophoresis (DEP) for cell manipulation/sorting

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Acoustophoresis for separation/concentration

• Ultrasonic standing waves allow high-performance separation/

concentration of cells or particles

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Source: www.cellcare.lth.se

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Microfluidic chip for cell separation/concentration

Yeast separation Blood cell separation from plasma