Concept of Microfluidics for Chemical Production

Dr. Thomas R. DietrichIVAM Microtechnology Network

Dortmund, Germanywww.ivam.de

II Workshop on Translational NanomedicineDonostia-San Sebastian Sep 18-19, 2017

AGENDA

- Introduction to IVAM Microtechnology Networkesp. its microfluidic activities

- concept of micro reaction technology

- manufacturing of microfluidic components

- examples

This is who we are

International

Microtechnology

Business

Network

Type of member

company63%

institute25%

network partner10%

personal member

2%

of companies and institutes§ micro technology§ nano technology§ MEMS § advanced materials§ photonics

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Business regions of IVAM members

free world map template: www.presentationmagazine.com

78%100%

48%

35%

40%

40%40%

Source: IVAM Survey 2016

percentage of IVAM members doing business in these regions

22%

27%

9%

30%

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Technologies in Member Companies

MicrotechnologyMEMSNanotechnologyPhotonicsAdvanced Materials

• micro chemical engineering• biotechnology• medical applications

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Major target markets

IVAM activities in Micro Fluidics

Experts and Focus Groups

Prof. Roland Zengerle IMTEK, Hahn-Schickard

Dr. Hans van den VlekkertLioniX BV

Microfluidics Research

MicrofluidicsEntrepreneurship

Companies and Research Institutions, working on the commercialization of microfluidicsChair: Dominique Bouwes, Micronit

Advisory BoardMember

Executive BoardMember

Micro Fluidics in Chemistry

§ Wording micro reaction technologymicro chemical engineeringmicro process engineering

micro reactormicro structured reactor(micro shaped flows)

Micro Fluidic ApplicationsChemistry

Product developmentProduction

BiotechnologyAnalyticsLab-on-a-Chip

Medical technologyMobile DiagnosticsLab applications

Microreactors for Nanomedicine

AAPS PharmSciTech. 2014 Dec; 15(6): 1527–1534.Published online 2014 Jul 22. Nanomedicine Scale-up Technologies: Feasibilities and ChallengesRishi Paliwal, R. Jayachandra Babu, and Srinath Palakurthicorresponding author

Europe and USA are leading in MRT

Internationalization:Formation of Micro Process Engineering Center in MexikoApril 2008

El Norte (April 2008)

MICROREACTION TECHNOLOGY:A TOOL FOR SUSTAINABLE CHEMISTRY

Internationalization:Introduction of Micro Chemical Engineering in Brazil

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 µmregime batch continuouscontrol by time by geometrydriving force thermodynamics kinetics

à Better control of chemistry

Motivation: Enhance SAFETY

Austrian newspaper,August 10th, 2004:

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)

Why should this be done in microstructured reactors?§ high specific interfacial area§ isothermal operation possible§ low hold up§ exact defined reaction conditions (e.g. T, flow)§ continuous process at higher temperatures

SUSTAINABLE CHEMISTRY

reactions at higher concentrations

or even without solvents

stoichiometric mixtures= less sideproducts

and waste

energy supplyWHERE and WHEN necessary

enhanced safetycontrolled by geometry

Motivation: SUSTAINABILITY

BATCH vs. MICRO reactor

Source: Paul Watts

batchreactor microreactor effectdiameter cmtom severalµmtoseveralmmvolume severalmltoseveral1000l <1mltoseveral10ml -->highersafetyflow -- severalµl/mintoseveralml/minresidencetime =productiontime(min-hrs) mstoafewminutes -->onlyforfastreactionsReynold'snumbers >2.300 verylow -->laminarflowsurfacetovolumeratio <100m²/m³ 10,000-300.000m²/m³ -->surfaceisveryimportant

Mixing in a Micro Reactorlaminar 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)

Cells:Molecules are transported everywhere in the cell within a second by molecular diffusion. The living cell is still by far the most efficientand versatile microreactor.

No stirring is needed.

T. Motokawa

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

reaction channel: w = 500 µmwidth of lamellae: dl = 4 µmdiffusion time: td = several ms

td < tr

typical flow: f = 10 ml/mintypical residence time: tr = 0.1 - 1 s

Mixing only by diffusion: td ~ dl2 / D

short diffusion time by multi - lamellae

(Micro) structure by structurized media

Fluid streams are pre-shaped à microreactors without microstructured channels

Encased flow, Channel with

solid walls

Free flow, encased by

liquid sheets

Free droplet flow encased by

liquid

Free gas bubble flow,

encased by liquid

Free falling droplets,e.g. spray,

encased by gas

0 500 1000 1500 2000 2500 30000

5

10

15

20

25

30

35

40

45

50

55 AS=f(R)

AS /

m2 m

-3

R / µm

Advantages because oflarge surface to volume ratio

dR / µm AS / m2m-3

100 400250 160500 80

1000 405000 8

dR

AS

L=10mm

A decrease of channel diameter enhancesheat- and mass transfer by diffusion

Surface to volume ratio is significantly increased

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

No parallel reaction because of good temperature control !

narrow temperature distributionin microreactors

Inlet liquid 1

Outlet liquid 2 Outlet liquid 1Inlet liquid 2

counterflow

channel width: 1.0 mmchannel depth: 0.5 mmchannel length: 280 mmwall thickness: 0.2 mm

New Approach with µ-Reaction Technology

CHEMISTRY chemistry influencesthe design of the reactor

new technology with µ-reactors

chemistry is forcedinto a given plant

conventional technology

Becht Degussa May 2007

Glass-Microreactor for Photochemistrywith small channels designed according the absorption length

The synthesis of bioactive compounds by photodecarboxylative addition ofcarboxylates 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

properties

material

resistant against HNO3/H2SO4

resistant against organic solvents

temperatures up to 150°C

pressure up to 10 bar

optical transparent

metal

ceramic

glass

polymers

silicon

properties

material

Chemicallyresistant

resistant against organic solvents

temperatures up to 150°C

pressure up to 10 bar

optical transparent

e.g. for a nitration reaction

• glass, especially because of• chemical stability• optical transparency• electrical insulation

• ceramics, especially because of:• high temperature stability

• stainless steel, especially because of:• resistance against high pressure• good heat conductivity

Ehrfeld

mikroglas

Choice of Material

IMVT, KIT

different functionsin different layers

exit

component 1

component 2

mikroglas – Interdigital Mixer

inkjet

stereo lithography2-photon polymerization

fuseddepositionmodelling

3D-printing technologies

Advantages: rapid manufacturingspecific designs in each reactor

Issues: material mostly polymerchemically 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

Source: Lonza – Microreactor Technology (2009)

§ 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

21%

23%

6%

50%

D.M. Roberge et al. CE&T 2005:Reactions at Lonza

Type A reactions

Type B reactions

Type C reaction

Remaining

Reaction Classification & Advantages

Sigma Aldrich / Merck : Explorer Kit

Sigma-Aldrich MicroreactorExplorer Kit 19979 prototype

Borosilicate glass reactors with different mixing regimes and different sizes manufactured by Little Things Factory

http://www.sigmaaldrich.com/technical-documents/articles/chemfiles/microreactor-technology.html

Syrris, UK: Microreactors for R&D

Asia Microreactors

Africa Microreactors

Ehrfeld Mikrotechnik: Modular MR System

future chemical production:- smaller and more flexible- modular construction- on-site/in-time production

INVITE und F³-factory - Modular Production

Research still necessary!

Missing steps for processes inmicro chemical engineeing

Downstream processescontinuous separation of side products(serveral steps reactions, change of solvents, solvent recycling, etc.)

Continuous solid handlingmany starting materials / final products are solids !(e.g. in pharma-products)

New Processes, new Products

Novel Process Windowsuse of new possibilities(e.g.: effective energy sources: ultrasound, microwave, (solar-)light, more effective catalysts)

Optimization of Product Porperties(e.g. particles, morphology, emulsions)

Efficient Use of Energy, new Energy sources

Energy for chemical reactionsusing alternative energy sources, e.g. solar energy(Photochemistry, Electrochemistry, etc.)

Energy efficient production processesby controlled conti-production(Online-Sensors, -Analytics, process automation)

Use in otherapplication fields Use in non-chemical industries

e.g. decentralized energy supplyeffective energy management(fuel cells, energy storage)

bio(techno)logical processesuse of enzymatic prozesses(e.g. cleaning of waste water)

Summary

- Micro reactors and plants can help to solve today's problems:§ better control of chemical processes§ sustainable: less resources, waste, energy consumptoin§ research and large scale production is possible§ development of flow chemistry

- Micro reaction technology and automation§ automated process development§ automated process and quality control§ automated safety measures

- Research is still going on:§ some unit operations still missing (e.g. downstream processing)§ good modules still expensive§ incluing into eucation of chemists and engineers

Microfluidic components and equipment should be a standard tool in chemical laboratories!

IVAM Microtechnology NetworkJoseph-von-Fraunhofer-Str. 13D - 44227 Dortmundwww.ivam.cominfo@ivam.de

¡Muchas gracias por su atención!Eskerrik asko zure arreta!

Thank you very much for your attention!

Vielen Dank für Ihre Aufmerksamkeit !

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