flow chemistry and micro process engineering … institute for chemical technology ict flow...

F r a U n h o F e r I n s T I T U T e F o r C h e m I C a l T e C h n o l o g y I C T

Flow Chemistry and miCro ProCess engineeringDesign anD optimization of chemical processes

F l o w C h e m I s T r y a n d m I C r o P r o C e s s e n g I n e e r I n g

D E s I g n a n D o P t I m I z a t I o n o f c h E m I c a l P r o c E s s E s –

f r o m l a B o r a t o r y t o P r o D u c t I o n s c a l E

Cover P ICTUre

Set-up of microreaction

processes at technical scale.

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Passive mixing structures

in microreactors intensify

mass transport.

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Micro process engineering:

Continuous chemical

processing in microstruc-

tured channels (left) and

assembling microreactors

into a production plant

(right).

over the past few years microstructured reactors have found increasing application in chemical

laboratories. Both academic and industrial research has clearly demonstrated that the application

of micro-structured reactors, mixers and other microfluidic components offers numerous

technical advantages for chemical processes, ranging from process safety to process efficiency.

microstructured reactors are characterized in particular by a high surface-to-volume ratio and

channel dimensions in the sub-millimeter range, which offer a significant increase in heat and

mass transfer within the reactor. the continuous processing of microreactors (“flow chemistry”)

also permits short residence times and narrow residence time distributions, which can be

precisely adjusted.

compared with conventional chemical processes, microreactor processes therefore offer

sub-stantial improvements in yield, selectivity, product quality and safety for chemical reactions

that involve a high heat of reaction or are sensitive to dosing and mixing. moreover, micro-

reaction technology opens up opportunities for new process windows and synthetic routes.

the fraunhofer Ict has been developing microreaction processes for more than 15 years for

process optimization and production.

customers and project partners from the chemical, pharmaceutical and process technology

industries can now access a wide range of products, processes and services in the area of

micro process engineering and microreaction technology, extending from analysis, design and

optimization of chemical processes to the synthesis of speciality and fine chemicals, and the

development of tailored microreaction systems for use in laboratories and production plants.

miCro ProCess engineering miCro-sCale ContinUoUs ChemiCal ProCesses

From ProCess oPtimiZation to ProdUCtion

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Plant for continuous

synthesis and downstream

processing in micro-

structured reactors.

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Alternative processing:

photo chemistry in

microreactors.

We identify and develop economically and ecologically attractive synthesis routes for our

customers. high yields and selectivities are important here, but are not the only factors we

consider. reducing the number of reaction steps, minimizing hazard potential and improving

resource and energy efficiency are equally important goals. With this in view, micro process

engineering has become a key tool for process optimization. We target the benefits of micro

effects and simultaneously test alternative process conditions that are not accessible using

classical batch processes, for example by running processes at higher temperature, pressure and

reagent concentrations or at significantly reduced contact times. We also replace stoichiometric

reaction steps with catalytic processes or realize alternative process strategies, for example

photochemical processes in microreactors.

the tools of micro process engineering must be integrated into high-performance laboratory

equipment in order to be able to use its advantages effectively in the r&D laboratory. for this

purpose we have developed modular laboratory systems which allow fast reaction and para-

meter screenings. using these laboratory systems, almost any microfluidic process for liquid,

liquid/liquid and gas/liquid reactions can quickly be set up, and the configuration can easily be

adjusted. a wide selection of microstructured reactors, mostly made of glass, is available for

these tasks. the process control units of our laboratory systems fully automate the processing

and data logging of individually designed experimental plans. this permits systematic parame-

ter screenings and the generation of sample libraries for subsequent investigations. moreover,

our laboratory systems have additional ports for online and offline analysis, integrated safety

features as well as optional remote control and surveillance systems for reactions with an

increased hazard potential.

In our pilot plants, we transfer the insights we gain into process optimizations to production

tasks, realizing customer-specific processes with a high throughput using tailored microreactors.

In addition to synthesis, we also make successful use of continuous micro processes in

downstream process operations for purification purposes and subsequent work-up.

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Microstructured glass

reactors are the most

important element of

continuous reaction

processes.

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Production of hazardous

substances in remotely

controlled microreactor

processes.

Potentially haZardoUs ProCesses

a special field of research at the fraunhofer Ict is the development of microreactor processes

for the safe management of reaction systems that are potentially explosive or otherwise

hazardous. We have more than 50 years of expertise in the area of explosives synthesis as

well as the associated infrastructure and safety equipment.

the advantages offered by micro process engineering make it particularly suited for use in

processes with an increased hazard potential – such as removing strong reaction heat, preven-

ting unwanted side or decomposition reactions or processing safely toxic, explosive and other

unstable products and intermediates in small hold-ups under short residence times at the point

of use.

alongside its various laboratory processes, the fraunhofer Ict has also developed special

multipurpose plants at technical scale, which permit both the continuous synthesis of liquid,

explosive materials and their subsequent, continuous processing in the relevant production

quantities. at the heart of these plants are microreactors, which have been specially developed

for high-throughput applications for both synthesis and downstream processing. Due to their

modular design, these components can be quickly exchanged for the specific production

campaign. the appropriate microreactors are integrated into the production plants to match

the synthesis product and throughput required. all plants have a wide range of safety features

and every aspect is controlled and monitored remotely.

the multipurpose microreactor plants are used for the production of a variety of explosive

substances and made up to customers’ specifications. typical throughputs are in the range of

several hundred grams per minute. compared to classical production processes, the plants offer

increased process safety with sometimes dramatic reductions in processing time, improvements

in product purity and stability as well as significant savings in capital and operational expenditures.

micro-structured reactors can be used for the high-precision processing of multi-phase fluid

systems (e. g. liquid/liquid or gas/liquid) in the form of segmented flows and unimodal

emulsions, opening up new application opportunities.

at the fraunhofer Ict specially-developed microfluidic structures are used to generate fluid

segments in the form of droplets and bubbles by continuously shearing them off or constricting

them into a second liquid phase. the size of the formed droplets or bubbles and the frequency

of the segmentation can be controlled very precisely through the selected flow conditions,

reactor geometries and other process parameters.

the droplets or fluid segments function as closed reaction vessels, having no chemical

interaction with the transport phase. Within the fluid segments – each with a volume of just

a few nanoliters – the syntheses of high value products can be performed by suppressing cross-

contamination, dilution and dispersion effects caused by convection and diffusion. reaction

and substance screenings can thus be conducted with a high degree of efficiency. moreover,

mixing of the reagents in the nanoliter segment is strongly intensified by advection, without the

need for complex static mixing structures which are usually required in microreactors.

at the fraunhofer Ict segmented flow processes in microreactors are used for the production

of single and multiple emulsions, continuous micro encapsulation processes and the production

of nano and micro particles. the precise control of the droplet size is used to synthesize mono-

modal spherical polymer particles and microcapsules which can be filled with a wide range of

active ingredients during the process. the size of the polymer particles is infinitely adjustable

over a broad range, e.g. between a few micrometers and several hundred micrometers; typical

wall thicknesses of polymer microcapsules lie in the range of approx. 100 nm.

on the other hand, segmented flow processing can also be used to deliberately intensify inter-

actions between two-phase systems, for example in nano particle syntheses or in phase transfer

catalysis. By providing large interfacial areas, we can significantly accelerate the mass transport

over the phase boundary layers compared to macroscopic processes.

mUltiPhase ProCessing in miCroreaCtors the droPlet as a reaCtor

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Microreactor for manu-

facturing spherical polymer

particles.

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Segmented flow in micro-

channels (top: gas/liquid;

below: liquid/liquid) (left)

and continuous production

of multiple emulsions for

manufacturing of micro-

capsules (right).

sPeCtrosCoPiC and CalorimetriC ProCess analysis in miCroreaCtors

at the fraunhofer Ict process analysis is an invaluable tool for the design and optimization of

chemical processes. By adapting spectroscopic and calorimetric techniques to microreaction

processes we conduct process diagnostics with a high degree of temporal and spatial resolution.

spectroscopic process analysis in the form of uV/Vis, nIr, Ir and raman spectroscopy is adap-

ted to microreaction processes as inline, online or at-line measurement technology – depending

on the specific problem. tailor-made optical cells commonly form the interface to the chemical

process. In addition, high-speed microscopy and the very latest imaging techniques are applied

to gather visual and spectral information simultaneously in a certain area of a microreactor

with high spatial and temporal resolution. this kind of process tomography gives us a direct

insight into the process as it is taking place, and thus provides kinetic and mechanistic data

which is extremely valuable when designing process components and selecting suitable process

conditions. With the help of fiber optics, we can also apply spectroscopy in a microreaction

process at many discrete positions simultaneously, to monitor the progress of reactions over a

longer distance in real-time (multiplex spectroscopy). In combination with screening procedures,

statistically planned experiments and chemometric analysis it is possible to identify suitable

process windows and optimum process conditions with a high degree of efficiency.

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Spectroscopic process

analysis in microreactors

using fiber optics.

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Time and spatially resol-

ved reaction calorimetry

in microreactors using

heat flow sensor arrays.

another powerful method of process analysis that has been developed at the fraunhofer Ict

is a calorimetric measuring system that can be adapted to continuous microreaction processes.

It permits calorimetric monitoring of chemical processes in real-time.

at the heart of the µl reaction calorimeter are sensor arrays based on miniaturized thermo-

electric elements (seebeck elements) for the localized, quantitative measurement of heat

flows. the sensor arrays consist of up to 40 individual sensors, which can detect the reaction

heat generated in a microreactor with a correspondingly high degree of temporal and spatial

resolution. this measurement data can be used to obtain thermokinetic information about the

observed chemical reaction. In addition, the µl reaction calorimeter can be used to determine

reaction enthalpies and other key safety data for chemical reactions depending on the selected

process conditions. as the reactor volume is very small, even targeted investigations of critical

process conditions (worst case scenarios) can be safely carried out, which would be difficult or

even impossible using conventional calorimetry.

as well as being used for the analysis of strongly exothermic reactions, the highly sensitive

sensors also permit calorimetric investigations of continuous processes with low reaction heat

as well as endothermic processes. In addition, the modular design of the measurement system

makes it possible to adapt the sensor arrays to different reactor types and reactor sizes. With

fast calibration and user-friendly measurement software, the µl reaction calorimeter is

particularly suitable for the calorimetric screening of reaction and process conditions.

design and FaBriCation oF miCrostrUCtUred reaCtors

one important element in the development of microreaction processes is the design of

tailored microfluidic components. Both mathematical methods and numerical simulation tools

(e.g. computational fluid Dynamics, cfD) as well as standardized experimental measurement

methods are applied. these generate quantitative and qualitative data concerning important

performance characteristics, for example the mixing efficiency and residence time behavior of

microstructured reactors.

to characterize the residence time behavior of microfluidic components we have developed

special spectroscopic measurement techniques and the corresponding mathematical modelling

tools, which demonstrate the relationship between the fluid channel design and the residence

time characteristics.

With cfD we can make predictions of performance and effects within chemical processes,

either in advance or accompanying the process development, using approximate calculations

of the flow conditions, heat and mass transfer characteristics as well as related factors such as

mixing efficiency, residence time and pressure drop. simulations provide information on process

conditions, not just for selected points but with a virtually unlimited scope in terms of time and

space. moreover, cfD tools provide extensive options for visualization of the calculated process

conditions.

In order to take account of the special effects that occur at the micro-scale, such as boundary

layer phenomena and the large surface-to-volume ratio, special cfD tools suited for the micro-

scopic region are used. furthermore, micro-effects are considered by software modifications or

by integrating supplements like user defined subroutines.




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Visualization of the

fluid dynamics in three-

dimensional microchan-

nel structures using CFD

(sample simulation) (left)

and 3D characterization

of laser-structured micro-

fluidic structures (right).

In micro process engineering glass in particular is used as a transparent, chemical inert and

biological compatible substrate. the design of tailor-made microreactors and other microfluidic

components requires flexible micro-structuring techniques allowing the fast development and

testing of microfluidic prototypes and a rapid re-designing of microfluidic components.

at the fraunhofer Ict laser structuring techniques based on ultrashort pulse laser ablation are

applied for this purpose. focused picosecond laser pulses allow controlled and well-defined

material removal on a micro-scale. Due to minimal thermal stress, no strain or micro-cracks

occur during the micro-structuring process. moreover, the micro-structures exhibit an excellent

geometric precision and can be obtained with high aspect ratios. laser ablation is therefore a

powerful technique for the rapid generation of microfluidic structures in various substrates such

as glass, ceramics, metals and polymers. In contrast to conventional processes for generating

microfluidic structures such as wet etching or sandblasting, no masks are required saving time

and resources in the development of microreaction processes. In laser ablation microfluidic

structures are written directly into the substrate. the re-design of a microfluidic structure can

be quickly executed by simply adjusting the corresponding 3D-caD data. this allows a fast,

iterative optimization of various microfluidic structures and a tailor-made microreactor design.

oUr ProdUCts and serViCes

We provide our customers and project partners with rapid and comprehensive access to the

diverse applications of flow chemistry and micro process engineering.

the fraunhofer Ict offers a broad variety of microreaction systems as solutions in the fields

of chemical synthesis and process development, process optimization and process analysis. as

r&D services, we also offer feasibility studies, rapid parameter screenings and targeted analysis

of individual process steps as well as detailed safety investigations.

Based on more than 15 years of experience, we develop tailored microreactor processes for

customer-specific tasks in all areas from the laboratory to production scale.

to enable our customers to perform their own research, we supply complete laboratory systems

for synthesis and process analysis.

finally, we develop products together with our customers in the areas of fine and speciality

chemicals including the continuous manufacturing of microcapsules and nano/micro particles.

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Micro-structuring of glass

reactors by ultrashort pulse

laser ablation.

Fraunhofer Institute for

Chemical Technology ICT

Joseph-von-Fraunhofer-Strasse 7

76327 Pfinztal (Berghausen)

Germany

Director:

Prof. Dr.-Ing. Peter Elsner

Contact

Dr. Stefan Löbbecke

Phone +49 7 21 46 40-230

[email protected]

www.ict.fraunhofer.de

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flow chemistry and micro process engineering … institute for chemical technology ict flow...

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