Microgravity:A Tool for Industrial Research

Applied Research on the

International Space Station

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Directorate of Manned Spaceflight and MicrogravityDirection des Vols Habités et de la Microgravité

CONTENTS

Microgravity: a Tool for Industrial Research 1

Microgravity Research Networks 4

Casting of High-Performance Alloys 6

Bearing Alloys for Car Engines 8

Combustion 10

Crystal growth of Cadmium Telluride (CdTe) 12

Enhancement of Oil Recovery 14

Crystal Growth of Biological Macromolecules 16

Atomic Clock Ensemble in Space (ACES) 18

Life Sciences and Biotechnology 20

Biomedicine - Osteoporosis 22

Biomedicine 24

Activities in the USA and Japan 26

National Initiatives in Europe 27

Outlook 28

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Microgravity research has been undertakenin Europe for the past 15 years, boththrough ESA programmes and initiatives atnational level. With the forthcomingInternational Space Station (ISS), there isstrong motivation to expand on theseactivities notably by involving Europeanindustry to achieve the move fromfundamental research towards appliedprojects.

This brochure introduces selected examplesof research where microgravity as a tool isrelevant for application-oriented andindustrial research. Each area demonstratespotential for applications and commercialspin-offs. Past results are mentioned andcurrent and future avenues forexperimentation are presented. ESA’sMicrogravity Applications PromotionProgramme has the mission to addressresearchers from industry and academia andto develop relevant projects.

With the advent of the ISS, an endeavour inwhich Europe is fully participating,microgravity becomes a strategic researchtool for innovative private ventures. Thisbrochure provides a first step in promotingthe view that integrating microgravity as anadditional parameter into terrestrial researchefforts can indeed be beneficial to privateenterprise.

Microgravity: a Tool for Industrial Research

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Microgravity ResearchPossibilities

The International Space Station provides aunique opportunity for research andapplications and a testbed fortechnological development for a period of 10 – 15 years. Disciplines of interestinclude research in the microgravityenvironment, space science (astrophysicsand astronomy), Earth observation,engineering science and spacetechnology.

Past and present research programmeshighlight how microgravity can be auseful, and in some cases unique, tool forthe study of a number of physical,chemical and biological processes that areimportant in science, engineering andtechnology.

Microgravity or near-weightlessnesscorresponds to a free fall situation. This

can be obtained through various meansand for different durations: drop towersand drop shafts (up to 10 seconds),aircraft flying parabolic trajectories (about20 seconds), sounding rockets (up to 15minutes), unmanned satellites (weeks tomonths) and manned orbiting systemssuch as the Shuttle (a few weeks), Mirand finally the International SpaceStation, which will be in operation for adecade at least.

Gravity is a pervasive phenomenon,creating a force that influences virtually allaspects of life on Earth. The impact onphysical and biological processes isobvious. In a number of cases it is used toadvantage, for instance to shape ametallic part by pouring a melt into amould, to separate lighter from heavierconstituents through sedimentation or forthe transport of fluids. However, theeffects of gravity can be undesirable if wewant to study the complex interaction ofdifferent forces involved, for example, influids (liquids and gases).

In microgravity, various phenomena aresignificantly altered, in particularconvection, buoyancy, hydrostaticpressure and sedimentation. Scientificdisciplines affected include fluid physicsand transport phenomena, combustion,crystal growth and solidification,biological processes and biotechnology.Microgravity is instrumental in unmaskingand unravelling processes that areinterwoven or overshadowed in normalgravity. For example, crystal growth from

The Fluid ScienceLaboratory under

development in ESA’sMFC programme (left)

The Material ScienceLaboratory, an element

of the MFCprogramme, shown inColumbus Laboratory

configuration (right)

The MicrogravityFacilities for Columbus

(MFC): a view inside theColumbus Laboratory

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or to give more insight into Earth-basedprocesses so as to enable improvement oroptimisation. For that purpose, specificinstruments will be provided by ESA.

With the availability of the ISS, examiningspecific applied research questions in amicrogravity environment may be, in thelong term, a rewarding undertaking forindustry.

A major aspect of this promotionprogramme is the setting up of Europe-wide teams and networks involvingpartners from academia and industry whowill work jointly on industrially-relevantresearch. The aim is to initiate industrialprojects in which terrestrial research withindustrial objectives will be supported byESA, including ground-based activitiesand flight opportunities, together withthe participation of researchers fromuniversities.

melt and solutions, capillary effects,multiphase flow, diffusive transportprocesses, can under normal gravityconditions be dominated by effects suchas buoyancy, thermal convection andsedimentation. Microgravity may thereforebe regarded as an important tool forincreasing precision in the measurementof thermophysical properties, forimproving models of complexphenomena and hence manufacturingprocesses on Earth. In the fields ofmedicine and life science, theamplification in space of certainphysiological changes motivatesinvestigations of the underlyingmechanisms and the development ofboth innovative treatments andexperimental hardware.

ESA’s Microgravity ApplicationsPromotion Programme

Back in 1995, when deciding Europe’sparticipation in the ISS project, ministersfrom ESA Member States stipulated an ISSUtilisation Preparation Programmeincluding a Microgravity ApplicationsPromotion (MAP) programme element. Itsbroad aim is to prepare for the ‘steady-state’ utilisation phase after assembly ofthe Station is completed in 2003.

The MAP Programme’s objective is todevelop pilot projects demonstrating thatthe ISS is a unique tool for industrialresearch, and to obtain data that wouldeither be needed for numerical simulation

The Biolab; anelement of the MFC(left)

The HumanPhysiology Module; anelement of the MFC(right)

Science operations forthe Multi UserFacilities

Several projects are already supported by ESA’s Microgravity ApplicationsPromotion Programme. These networks,with the participation of industry andresearch institutes, are expecting to derivebenefits from the inclusion of microgravityas an additional parameter into theirapplied research efforts. These projectsare funded by ESA in increments of twoyears, leading up to flight experiments onthe ISS from 2002 onwards.

Indeed, the development of advancedindustrial processes and products isincreasingly based on detailedunderstanding of the underlyingphenomena.

The topics and the corresponding leadcentres are:– Osteoporosis, MEDES, Toulouse, France.– Crystal Growth of Cadmium Telluride

(CdTe) and related Compounds, Crystallographic Institute, Univ. Freiburg,Germany.

– Precision Measurement of DiffusionCoefficients Related to Oil Recovery,Microgravity Research Centre, UniversitéLibre de Bruxelles, Belgium.

– Atomic Clock Ensemble in Space (ACES),Ecole Normale Supérieure, Paris, France.

Furthermore, a study on a facility forcommercial crystallisation of biologicalmacromolecules in space is being initiated.

Additional topics are addressed throughthe activities of ESA Topical Teams. Theseteams seek a dialogue with Europeanindustry to expand successful basicmicrogravity research towards applications.Presently, 12 Topical Teams are active,listed in the table on this page. Proposalsfor new Topical Teams are being solicited,specifically in Biotechnology.

Ground-based research involving gravity-dependent phenomena is also supportedby the European Commission.

ESA is proposing to expand relevant EU-funded projects to includemicrogravity flight experiments. These will be funded by the MicrogravityApplications Promotion Programme.

Typical research areas that are consideredto be promising are described in the tableon the following page.

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There are presently 12 active Topical Teams:– The Influence of Steady and Alternating Magnetic Fields

on Crystal Growth and Alloy Solidification– Convection and Pattern Formation in Morphological

Instability during Directional Solidification– Metastable States and Phases– Equilibrium and Dynamic Properties of Adsorbed Layers– Particle Aggregation and Dispersion– Double Diffusive Instabilities with Soret Effect– Thermophysical Properties of Fluids– Magnetic Fluids: Gravity Dependent Phenomena and

Related Applications– Foams and Capillary Flows– Droplet, Particle, Spray, Cloud Combustion– Flame-Vortex Interaction– Combustion Synthesis

Microgravity ResearchNetworks

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Possible Research Topics for Gravity-related Research with Industrial Objectives

Objectives of microgravity Industrial research objectives Applicationsinvestigations

Casting of High Performance Alloys

Advanced process control Validation of theoretical models Cast products with reproducible and Turbine blades and castunder controlled conditions. predictable properties structural parts with improvedDetermination of thermophysical properties and reliabilitydata with an accuracy notattainable under normal gravity

Particle reinforced Understand particle motion and Homogeneous dispersions in metal Cast parts of light metal withcomposites aggregation mechanisms matrix composites improved stiffness and high

thermal conductivity

Crystal Growth

Crystal growth of electronic Understand the influence of gravity Improve the quality and High sensitivity X-ray detectorsand photonic materials from on the crystal growth process and homogeneity of crystals of for medical diagnosticsa melt or the vapour phase produce benchmark samples compounds such as GaAs, ZnSe,

CdTe etc.

Crystal growth of biological Monitor and control the process in Identify the drug inhibiting an Fast drug design on the basis ofmacromolecules order to grow high quality crystals active molecule the detailed structure of the

suitable for detailed structure target moleculedetermination

Particle Technologies Understand particle nucleation, Production of nanoscale particles Advanced nanomaterialsgrowth, aggregation and dispersionmechanisms

Energy Production and Management

Heat and mass transfer Validation of theoretical models for Understanding of the basic rules of Enhanced oil recovery andmultiphase flows, boiling mechanism, processes energy production techniquesflows in porous media

Combustion Basic understanding of droplet and Accurate models of energy Low consumption, low pollutantspray vaporisation production and propulsion processes emission engines and power plants

Biotechnology and Medicine

Biology and physiology Role of gravity at the molecular level, Molecular and cellular control of Drugs modulating cell activityon cell physiology, and on gene expression, of cell and proliferation for applicationsdevelopmental processes differentiation and proliferation in agronomy and medicine

Tissue engineering Cell-cell relations and tissue Controlled tissue development, Organotypical materials, artificialdifferentiation in stable, controlled intelligent bioreactors, organotypical organs, and implantablefluidic systems conditions intelligent curing devices

Biomedicine and health care Better understanding of gravity effects Undertstanding of mechanisms Therapies for osteoporosis andon metabolism and physiology leading to diseases and validation of would healing, health monitoring

preventative and therapeutic and analytical techniquescountermeasures

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Cross section ofaluminium alloy

showing more regulararrangement of

dendrites, grown in amicrogravityenvironment

New materials for the automotive andaircraft industry are intended to providesubstantial weight saving. The prospect ofhigher efficiency, lower fuel consumptionand lower emissions is at stake. However,these new materials with higher strengthand stiffness should also be produced atlower cost, e.g. by precision castinginstead of machining. Advancedcomputational methods and melt flowcontrol techniques using magnetic fieldsare used in casting processes to improvemechanical properties.

Flow in the melt dominates the transportof heat and the redistribution ofelements and particles. Microgravityconditions provide for well-characterisedtransport conditions of pure diffusion,to help validate theories and models.Furthermore, rotating magnetic fieldswill be provided for achieving

controlled flow in conducting melts atrates not attainable on Earth. This willprovide the means for distinguishingbetween the effects of convective flow atthe solidifying interface and those ofhigh-strength magnetic fields asused on the ground.

Casting of High-PerformanceAlloys

Conventional materials often do notmeet the demands of industry - bettercontrol is necessary of the formation ofthe microstructure during casting, andthereby of the final product properties.

The microgravity environment enablesus to obtain more precise data on themicrostructure formation mechanisms,complementing those derived in thelaboratory.

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Airbus A330

processes and attempt to prevent theminstead of simply reacting a posteriori. To make these tools effective and reliable,accurate data on thermophysicalproperties are needed.

Thermophysical properties of materials athigh temperatures have already beenmeasured in microgravity withunprecedented accuracy. This techniquewill be extended to industrial materialsafter the validation of the data.

Critical knowledge gained frommicrogravity experiments will validatenew, more complex models, acceleratingthe current trend towards predictable andreproducible casting, and enabling thedevelopment of new processes.

With advances in computation techniquesand numerical models, the castingindustry now faces the lack of accuratedata on thermophysical properties such asthermal conductivity, density, diffusivity,specific heat and viscosity. The accuracyof such measurements is frequentlydegraded directly or indirectly by gravity(contamination by contact with acontainer, surface deformation,convection etc.).

In the foreseeable future, advancedcontrol techniques will rely heavily onnumerical codes to predict deviations in

Numerical models are as accurate as the thermophysical datathey use. Microgravity provides unique conditions for measuringthermophysical properties with an unprecedented accuracy.

The advent of a permanent in-orbitcapability will enable the measurementof data from experiments withindustrial materials on a routine basis.

Aluminimum forgedconnecting rod

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Metallographic sectionof an AlSiBi-alloy

rapidly cooled fromabout 1000°C to room

temperature undernormal gravity

Some alloys exhibit two immiscible liquidphases within a certain temperaturerange. The different densities of theseliquid phases leads, on Earth, to theformation of two layers. This prevents thehomogeneous distribution of particles ina matrix using simple and inexpensivecasting processes. Therefore, the industrialexploitation of such alloys has beenlimited so far.

A number of attempts to obtain, inmicrogravity, a homogeneous distributionin various alloys and model materials alsounexpectedly yielded separated phases.This is attributed to a droplet migrationmechanism, called Marangoni migration,which is driven by gradients of interfacialtension along the surfaces of droplets.These gradients relate directly to the localtemperature gradients in the matrixduring cooling and solidification and aretherefore independent of gravity. Thismechanism was studied on a theoreticalbasis and models were developed.Dedicated microgravity experimentsvalidated these numerical models,particularly for multiple droplet migration.The possibility of controlling the directionof migration and the velocity of dropletsthrough mastering the heat flow inmolten alloys has been demonstrated.The next natural step is to transfer thisnew knowledge into productionprocesses.

The ideal would be to minimise thesedimentation caused by gravity bybalancing it with the Marangonimigration effect. If the droplets reach astate of dynamic equilibrium, then a

Bearing Alloys for Car Engines

The casting of immiscible alloys by conventional methodsdoes not yield material with the expected homogeneousparticle distribution.

Tests in microgravity havedemonstrated the contribution of agravity-independent mechanism inthe separation process.

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Bearing half shells

stable dispersion in a solidifying matrixbecomes attainable. This concept hasbeen tested and new materials, forexample an aluminium alloy matrix withevenly-distributed inclusions of lead orbismuth, are being tested as candidatesfor advanced sliding bearings in carengines.

In these materials the hard matrix sustainsthe dynamic loads from the combustionprocess, while the soft inclusions provideself-lubrication. Developing this newfabrication method into an economicallyviable casting process would permit thedevelopment of engines consumingsignificantly less fuel.

Further work will address the optimisationof the process and its application todifferent materials. Further quantitativemeasurements and model validation willbe needed, for which microgravity will bea tool of critical importance.

A new casting process could be devised for the fabricationof bearing alloys consisting of soft particle dispersions in astrong matrix obtained from immiscible alloys.

Schematic of acontinuous process forcasting of monotecticalloys

Combustion processes provide energysources for surface and air transportation,space heating, electrical energyproduction, waste incineration andmaterial synthesis. However, combustioncan also cause undesired effects, likeunwanted explosions, fire hazards andtoxic exhausts. The challenging goal ofcombustion research is to enhance theadvantageous aspects and to diminishundesired effects.

Gravity fundamentally affects manycombustion processes. Reducing itseffects can help to highlightunderlying mechanisms that arenormally overshadowed byconvection, buoyancy or

sedimentation. Thus, microgravity offersunique possibilities for improving thephysical understanding of combustionprocesses, precisely measuring datarelevant to combustion, and developingor validating numerical models.

Droplet cloud combustion and spraycombustion are examples of processeswhere microgravity may contribute tooptimisation. These processes areemployed in piston and turbine engines,and in industrial burners. A detailedunderstanding of the processes isnecessary to maximise efficiency, andminimise fuel consumption, soot

production and thus pollution.

Microgravity facilitates theinvestigation of droplet interactionsin clouds, since an environmentwithout convection and buoyancyallows homogeneous droplet

distribution, and more precisemeasurements of evaporation, ignitionand flame propagation.

Currently in Europe, four major topics arebeing discussed with industrialparticipation:

1. High-Pressure Droplet Cloud Combustion;2. Particle Cloud Combustion;3. Soot Formation in Diffusion Flames;4. Stability and Structure of Lean

Premixed Flames.

Combustion processes often occur veryrapidly, so that detailed studies on dropletvaporisation and spray ignition can be

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Efficiency increases inautomobile and gasturbine engines, powerplants and industrialburners is of great interest.

Combustion

Microgravity investigationswill help to unravel thecomplex mechanismsinvolved in combustionprocesses.

The OH concentration field around amethanol droplet flame in 1g

The OH concentration around a methanol flame under µg

OH plus non-resonant fluorescenceof an n-heptane flame in 1g

OH plus non-resonant fluorescence of an n-heptane flame under µg

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The cylindrical dropcapsule of the ZARMdroptower in Bremen.The cutaway pictureshows an experimentalsetup to observecombustion processes

performed effectively during shortmicrogravity periods, like those providedin drop towers. However, mapping of theparameter space requires long-durationmicrogravity experiments, and severalexperiment modules are presently availablefor use in precursor sounding rocketexperiments. These activities are expectedto expand with the advent of the ISS.

Droplets are fuel-saturatedporous ceramic spheresDiameter: 5 mmPorosity: >80%

OH around an n-heptane flame in1g after subtraction of the non-resonance image

The detailed understanding ofunderlying phenomena will beessential in the advancement of designcodes for industrial combustionprocesses.

OH-LIPF images of 1g and µgdroplet flames

X-ray investigation ofteeth using greatly

reduced radiation dose

Materials for electronics such as CdTe andrelated compounds are used in highlysensitive detectors and photorefractivedevices. To date, these applications arelimited and expensive because of thedifficulties in routinely growing crystals ofsufficient quality.

CdTe-based X-ray and gamma-raydetectors have high potential in real timedental imaging or mammography,including 3-D tomography. This promises

faster and more reliable medicaldiagnosis, while exposing the patient tolower radiation doses. CdTe infrareddetectors enable high-resolution thermalimaging and high data rate opticaltelecommunication. In addition, thephotorefractive properties can beexploited for high-performance devices inoptical ultrasonic non-destructive testing. Today, the commercialisation of suchadvanced detection systems is impededby the difficulty in growing large CdTesingle crystals with the required quality.The melt growth method usuallyemployed for the production of CdTecrystals is the vertical Bridgmantechnique. Crucible contact contributes toincreasing the impurity content andgenerates extensive twinning. In addition,the stress induced by the crucible in amaterial with poor mechanical propertiesresults in very high dislocation densities sothat, eventually, the yield in terms of theusable fraction of the crystal does notexceed 5%.

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Crystal Growth of CadmiumTelluride (CdTe)

The application potential of CdTe has not been exploitedbecause of the difficulty in growing sufficiently large crystalswith the required quality.

Recent results of microgravity experiments have demonstratedthat new techniques can be employed to grow good qualitycrystals

Growth of CadmiumTelluride by the Markov

method

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Recent results of microgravity experimentshave demonstrated that new techniqueswith substantially improved yield can beenvisaged.

One microgravity technique is theprogressive detachment of the melt from the crucible during directionalsolidification. When the material solidifiesfrom a detached melt, its impurity contentis lower and no mechanical stress isinduced by the differential contraction ofthe crucible and the crystal duringcooling. As a result, the density of twinsand dislocations in the crystal is decreasedby several orders of magnitude. Laminarconvective flows can be imposed in themelt by applying a rotating magnetic fieldso as to minimise fluctuations at the solid-liquid interface and, thereby, enhance thehomogeneity of the crystal.

Another technique is growth from vapour.It takes place at significantly lowertemperatures and, in the case of semi-closed configurations, without touchingthe walls of the growth ampoule.Nevertheless, there is compellingevidence that gravity-driven convectiveflow in the vapour phase has salienteffects on the compositional homogeneityof the crystals, particularly those withlarge dimensions. A thoroughunderstanding of the convective flow andof its coupling with the growth processwill permit major advances in optimisingCdTe crystal production.

Microgravity will help to validate and optimise the ‘detachedgrowth’ process. To that end, experiments are already inpreparation.

Space experiments will be instrumental in validating models anddemonstrating the full potential of the vapour growthtechnique for detector materials.

Cd (Te, Ga) crystal grown from vapour without wallcontact (5 cm diameter)

Three typicalampoules shownbefore integration intothe Automatic MirrorFurnace (AMF) flownduring the long-duration EURECAmission.Left: flight ampoule forthe growth of AgGaS2using the TravellingHeater Method (THM)Centre: flight ampoulefor the growth of InPusing THM. The threeparts of the samplebetween the twographite plugs (dark)can be seen. From topto bottom; the sourcematerial, the solventzone and the seed.Right: the gold-platedflight ampouleprovided the thermalgradient suitable forcrystal growth in theBridgmanconfiguration

Oil is one of the Earth’s greatest resources.Oil companies are working continuously toenhance oil recovery methods and todiscover new reservoirs. Moderngeophysical and geological explorationmethods allow detection of hydrocarbonreservoirs at depths of up to 7000 m.

Understanding fluid physics in crude oilreservoirs is a major challenge foroptimising exploitation. Present modellingmethods are based on pressure-temperatureequilibrium diagrams and on gravitydifferentiation. However, rising exploitationcosts are forcing oil companies to developimproved models that more accuratelypredict reservoir production capabilities.Advanced models account for constituentconcentrations, and thus allow thedetermination, from the chemical analysis ofa probe taken from a reservoir, thereservoir’s volume, its vertical extension andthe quality of its oil. However, thedevelopment of such models requiresprecise diffusion coefficients, which so farare not available because convectivemotions and buoyancy affect theirmeasurement on Earth. This results ininaccurate forecasts.

The availability of accurate diffusioncoefficients allows the reliable prediction ofoil prospect specifications by numericalcodes. Such codes simulate laws thatdescribe the kinetics of pressure andtemperature-dependent physicochemicalprocesses that generate hydrocarbonmixtures from organic matter. Theconcentration distribution of constituents inthese hydrocarbon mixtures is driven mainlyby phase separation and diffusion causedby concentration differences andtemperature gradients.

The role of thermodiffusion (the Soret effect)in petroleum reservoirs is not yet fullyunderstood. Numerical modellingneglecting thermodiffusion results in thepredicted vertical extension of a reservoir

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Enhancement of Oil Recovery

The reliable prediction of oil reservoir capacity and oilcomposition enables oil companies to economically optimisetheir exploitation techniques.

Two projects have been initiated dealing with the precisedetermination of mass transport in hydrocarbon mixtures: ‘Diffusion Coefficient for Crude Oil’ and ‘Soret Coefficient forCrude Oil’.

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Getaway Special (GAS)carrying theexperiments

being inaccurate to an order of 100 m,indicating the need to account forthermodiffusion.

As buoyancy and convection affect thedistribution of constituents in fluids undernormal gravity conditions, accuratecoefficients of pure diffusion can bemeasured only in microgravity. Several daysor even weeks are required for suchmeasurements. Consequently, ESA issponsoring two projects on the precisemeasurement of diffusion coefficients incrude oil mixtures. The relevance of theprojects is underlined by the activeparticipation of the European petroleumindustry.

In the first project an experiment aboard theUS Space Shuttle flew during June 1998(STS-91), during which – among others –the diffusion coefficients of various crude oiland hydrocarbon mixtures were measuredaccurately with a specific experimentalsetup. This experiment was housed in a‘Getaway Special’ canister, a low-coststandardised payload container.

The second project aims to measureprecisely Soret diffusion coefficients of crudeoil mixtures, and considers temperaturegradients and pressure conditions as foundin oil reservoirs. Again a Getaway Specialcanister will be used, scheduled to fly inspring 2000.

Diffusion coefficients, measuredprecisely in microgravity, will be usedin numerical codes to predict oilreservoir capacities reliably.

Experimental arrangement of DCCO

Biological macromolecules such asproteins, enzymes and viruses play a keyrole in the complex machinery of life.They possess active sites which makethem bind or interact with othermolecules in a very specific manner thatdetermines their biological function. Theyintervene in the regulation, reproductionand maintenance mechanisms of livingorganisms, and they can be the cause ofdiseases and disorders. Pharmaceuticaldrugs are molecules that inhibit the activesites of macromolecules and, in principle,are intended to affect only the targetedmacromolecule.

The vast majority of current drugs are theresult of systematic testing, first atmolecular level, then at a clinical level.This extensive process significantlyincreases the cost of the product.

With a detailed knowledge of the 3-Dstructure of a macromolecule, biochemistscan restrict the range of drugs to betested. Furthermore, with a rational drugdesign approach, one may attempt tosynthesise a drug targeted exclusively ona specific macromolecule. That means adrug will perfectly bind to themacromolecule and inhibit its biologicalfunction while remaining inert vis-a-visother macromolecules.

The 3-D structure of the macromoleculecan be discovered through the analysis ofcrystals by X-ray diffraction: the diffractionpattern maps the structure of themolecules in the crystal. The better thequality of the crystal, the faster and themore accurate the determination of thestructure and the faster the identificationof a drug.

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Crystal Growth of BiologicalMacromolecules

Crystals of a biological macromolecule enable researchers todetermine the structure of the macromolecule itself andunderstand its function.

Knowing the structure of a macromolecule permits a fasterselection of the appropriate drug, or the design of a new drug.

The lack of good quality crystals precludes the precisedetermination of molecular structures with adequate precision.

This crystal of the membrane protein complex Photosystem I was grown in spacein ESA’s Advanced Protein Crystallisation Facility (APCF). 4 mm in length, 1.5 mm in

diameter, it yielded the best data set ever obtained

Under otherwiseidentical conditions,significant fewer,though larger, crystalsof thaumatin wereobtained in APCFreactors activated inmicrogravity (d,e and f )than in theircounterparts activatedon the ground (a, b andc, respectively). Inaddition, the space-grown crystalsexhibited a markedincrease of structuralquality over theground-grown crystals(higher resolution andlower mosiacity)

tested. It is likely that the growth of manycrystals could be conducted moresuccessfully in space.

Current efforts toward understanding andcontrolling the various mechanismsinvolved in the overall process willcontinue. Well defined and documentedexperiments in microgravity will help uslearn to control and optimise conditions,leading to better crystals. It will alsopermit the prediction of which moleculesof interest to the pharmaceutical industrywill benefit from crystallisation in spaceconditions.

Controlled crystallisation requires a multi-parameter approach. Gravity-dependentparameters that may affect crystallisationinclude sedimentation, convection andconsequently nutrient transport rate andwall contacts.

Research efforts in laboratories aim tocontrol the conditions in order to favourthe nucleation of a small number ofcrystals and, subsequently, steady growthto large sizes and crystallographicperfection.

Crystals of Photosystem I grown in spacehad a 10 to 20 times larger volume thanthose grown on the ground and allowedthe refinement of the structure from 4 Åto 3.4 Å. Space crystals of Collagenasediffracted with a higher intensitycompared with their groundcounterparts, and allowed a furtherrefinement of the structure. Underotherwise identical conditions in space,fewer but larger thaumatin crystals wereobtained with a measurably higherinternal order.

Comparable improvements incrystallisation under microgravity havebeen reported in the scientific literaturefor about 20% of the macromolecules

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Freed from the effects ofgravity, crystallisation inspace has generated somehighly promising results.

The principal of protein structureanalysis

ACES is a programme to test theperformance of a new type of atomicclock that exploits and depends uponmicrogravity conditions. The project hasbeen approved to fly on the InternationalSpace Station as an external payload,starting in 2002 for a period of one and ahalf years.

In its European baseline configuration,ACES consists of the following keyelements:

- A laser-cooled atomic clock ‘PHARAO’ –contributed by France,

- A Hydrogen Maser – contributed bySwitzerland,

- A laser link for optical transfer of timeand frequency – contributed by France

- A microwave link for transfer of timeand frequency – contributed by ESA

The caesium atom clock ‘PHARAO’ useslaser cooling to reduce the velocity ofatoms to a few centimetres per second,which corresponds to a temperature ofabout 1 µK. Under microgravity conditionsthe atoms remain at these low velocities,while on Earth they would increase theirspeed rapidly due to gravitationalacceleration when the lasers wereswitched off for signal interrogation.

The principle of the atomicclock

The principle of an atomic clock is to lockan oscillator to the atomic resonancefrequency ν0. Heisenberg’s uncertaintyprinciple shows that the greater theinteraction time of the atoms with theradiation emitted by the oscillator, thenarrower the resonance.

Two key points determine the ultimateperformance of an atomic clock: a narrowresonance and a high signal-to-noise ratio.

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Atomic Clock Ensemble inSpace (ACES)

Fundamental Physics Experiments with ACES

New experiments testing General Relativity within the solar system.

– Measure the Shapiro effect (the retardation of photons, in the Sun’s gravitational field).

– Measure the Einstein redshift to an accuracy of 10-6 i.e., an improvement by a factor of 100 compared to existing measurements.

– Check the stability of some of the fundamental constants of physics: assessing possible time-dependent drifts and/or spatial effect.

Radio astronomy

– Improving the angular resolution when observing remote stellar objects by Very Long Base Interferometry(VLBI).

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This atomic fountainclock has been inoperation at theObservatoire de Parissince 1995, and has arelative stability of1.3x10-13 τ-1/2 (where τis the measurementtime in seconds). Withan accuracy of 2x10-15,this is currently theworld’s most accurateclock.

‘ACES’– An exemplary model of the synergy between Science and

Technology – A tool for improving knowledge of the interplay between

radiation and matter.– A tool for high-performance synchronisation of ground-

based clocks.– A testbed for a new generation of spaceborne atomic clocks.– A scientific cooperation project involving European and

international laboratories. – A project demonstrating the value of the International

Space Station as a testbed for advanced Research and Technology

Navigation and positioning

– New concepts for higher performance GPS systems.– Geodesy with millimetric precision.– Precise tracking of remote space probes.

Time and frequency metrology

– Comparing and synchronising clocks over intercontinental distances to an accuracy of 10-16.

– Distributing the International Atomic Time with an accuracy of the order of 30 picoseconds, i.e. an improvement by a factor of 100 compared to current GPS and GLONASS systems.

Laser cooling allows an interaction time100 to 1000 times greater than for aconventional aesium clock.

It is expected that the new atomic clockwill reach a frequency stability between10-16 to 10-17 per day with an accuracy of10-16. This is one to two orders ofmagnitude better than can be achievedwith the most advanced clocks on theground.

The Hydrogen Maser will serve as areference clock to verify the performanceof the atomic clock. The microwave andthe optical links will allow laboratories onthe ground to receive the data and tointeract with the space-based systems.

The aims of ACES

- Validate in space the performance ofthis new generation of clocks.

- Provide an ultra-high performanceglobal time-scale.

- Perform fundamental physics tests.

The ultra-precise measurement offrequency and time will enable advancedinvestigations in fundamental physics andwill also have practical applications. It willallow experimental investigation of theproperties of space and time, which arefundamental in all modern, classical,quantum and gravitational physics. Fortime and frequency metrology, theaccuracy and stability of PHARAO,together with high-performancetechniques for comparing Earth-basedand orbiting clocks, will improve the

accuracy of International Atomic Timeand allow new navigation andpositioning applications.

Influence of gravity onliving organisms

Gravity is a fundamental force that has amarked influence on all life on Earth. Lifescientists and biomedical researchersexploit the space environment and inparticular the near-weightlessness in orderto answer fundamental questions in basicbiology relating to humans, plants and

animals. Various investigations on theresponse of microgravity on lungs, brain,nervous system, bones and muscles havealready been performed. This research isnot only of interest for the health andsurvival of astronauts but is also relevantin the understanding of balancedisorders, osteoporosis, andcardiovascular disease.

This research is only at the very beginningof clarifying the role of gravity at themolecular level. Present basic studiesaddress the reaction-diffusion feedbackpattern-forming processes that occur inself-organising systems.

For cell-cell relations or for the respectivecell functions within a differentiatingtissue, the origin of a change is likely toinvolve subtle modifications of theirmechanical and biochemical micro-environment. Experimental investigationof such minute changes and theireventual application would benefit fromthe increased stability of fluid systems inmicrogravity and from reducedmechanical loads.

Fluid dynamic models describingmacroscopic systems are not valid in thesub-micron range. Experiments inmicrogravity are needed to observe andto determine the influence of gravity onthe processing and amplification ofsignals involved in the gravity sensingand response of cells, cell aggregates andtissue or whole organisms. Any advancein the understanding of thesefundamental aspects is important for thefuture of medical science.

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Life Sciences andBiotechnology

Microgravity is a new non-invasive tool to investigate cellularfunctions. It will provide new insight into how cells perceivesignals and react to them. This is essential for the betterunderstanding of biological and physiological processes withpotential applications in molecular medicine, such as woundand tissue repair.

“Regulation of Cell Growth and Differentiation” - Cascade of early cellularresponses to growth factor binding to a membrane receptor; a process that mayamplify microgravity sensitivity

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ESA’s Space Bioreactor for Suspension Culture of Sensitive Cell and MulticellularSystems

Biotechnology - tissueengineering

Millions of people suffer organ or tissueloss from diseases and accidents everyyear. Yet transplantation of tissues andorgans is severely limited by theavailability of donors. Growing tissuesamples outside the body is one of themajor goals of current medical research,and the microgravity environment hasgreat potential for advancing thisresearch.

Experiments in bioreactors are performedto study how cells multiply and interactto form skin, bone and organs, and thesecell and tissue culturing techniques alsoaid the study of cancer cells and tumourformation.

Knowledge gained in microgravity on theregulation of cell growth anddifferentiation will also help improve thecultivation of sensitive and highlydifferentiated cell strains like thoseneeded to obtain artificial organs. Studiesof cells’ ability to migrate in reducedgravity may produce new insights intothe factors that allow cancer to spread.When combined with biomedicalresearch on Earth, these investigationscould contribute to the development ofnew ways to prevent and treat relateddiseases.

Experimental data obtained in microgravity and hypergravitystudies indicate a change in cell functions related to thegravity level. The underlying fundamental mechanismsresponsible for the sensitivity of living systems to gravityremain, however, to be fully understood.

The benefits of low gravity for growing cell cultures derivefrom the absence of convection and sedimentation, whichfor 3-D cell aggregates favour the creation of tissue-likeenvironment.

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Osteoporosis is often called a ‘women’sdisease’, although 15 % of theosteoporotic-related problems reportedconcern men.

In Europe, osteoporotic-related fracturestotal more than one million a year. Thefrequency of osteoporotic fractures isexpected to increase dramatically, partlydue to the increasing percentage ofelderly in the population.

With related health care expenses inEurope amounting to 25 million ECUdaily, osteoporosis attracts considerableattention from the biomedical industry.Microgravity is particularly relevant sincestudies performed on astronauts and onanimals showed an accelerated bone lossand a bone structure impairmentespecially in the weight-bearing bones.

ESA is sponsoring a project onosteoporosis. It aims at developing anaccelerated experimental model toevaluate trabecular bone architecture andbone quality evolution during space flightexposure. The activity includes bonesample and in vivo observations, as wellas in vitro samples (2-D and 3-Dbiomaterials). These will serve as standardbiosamples. They could also be used fordrug screening. The second majorelement of the Osteoporosis project is thedevelopment of a 3-D high resolution

analytical instrument for the quantitativecharacterisation of bone density andbone architecture.

This instrument will first be applicable forin vitro investigations, and ultimately forinvestigations on humans. The in vivoobservation of the microstructure ofbones is today clinically not feasible. This instrument will therefore be a majorcontribution towards the betterunderstanding of bone evolution and fora more accurate prediction of risks. Sincethe risk of bone fracture seems to be

Biomedicine - Osteoporosis

Astronauts and other biological systems experience acceleratedbone loss. Microgravity therefore provides for an acceleratedtestbed for osteoporosis studies.

Bone densitometer

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Normal trabecular bone (left)and osteoporotic bone (right)

- to develop a bone microarchitectureanalyser for the quantitative, highresolution, rapid, non-invasivecharacterisation of the kinetic evolutionof the model. This will also beapplicable to humans in the longerterm. The analytical tool is a 3-DPeripheral Computer Tomograph withan in vivo target resolution of 20 µm.

This project began in spring 1997 andinvolves academic and industry partners.

strongly related to bone microstructure, itcan be assessed quantitatively with thenew instrument.

On the basis of the data obtained withthis instrument an acceleratedphysiological model will be developedand validated. It can be employed for:- the testing of bone reconstruction

matrices, i.e. biomaterials,- the study of osteopenia prevention

based on exercise, mechanicalconstraints, and diet,

- the testing and screening of drugs.

The project has two major objectives:- to develop a 3-D bone artefact

supporting the co-culture of bone cellstogether with the experimental setupfor the simulation and control oforganotypical conditions.

In April 1997 ESA started to supportan application-oriented project withthe objective of exploiting theenhanced bone-loss phenomenonobserved in space.

3D-µCT image of bonesamples exhibiting aconsiderable bone strengthdifference

Unactivated platelets,in a resting state, with

characteristic discshapes (~3µm in

diameter) (left)

Two activated plateletswith characteristic

pseudopodia enablingthem to aggregate and

to adhere to vascularsurfaces. A red bloodcell is present behind

one platelet (~7µm in diameter)

(right)

Blood cell preservation

Simulating microgravity conditions onEarth could increase the preservation timeof blood cells both for therapeutic andresearch applications. To achieve this goalone must first understand how microgravityacts on the cell metabolism and then createthese conditions in blood banks.

The use of stored blood cells is of importancein the treatment of bleeding or thepathological deficiency of certain cell types.

Platelets and red blood cells mustbe stored ready to use in bloodbanks. Improving the preservationconditions would preserve thefunctional state of the cells andtherefore guarantee the efficiencyof the treatment while at the sametime reducing the treatmentcosts.

Other topics of interest

Monitoring the health and body functionof astronauts and related investigationshave led to a variety of new insights intothe influence of space environment onhuman beings. Dedicated instrumentswere developed for medical diagnosticsand validated in space, and are now usedon Earth.

An example is the fluid shift in thehuman body caused by the absence ofhydrostatic pressure observed undermicrogravity conditions. A dedicatedinstrument using ultrasound has beendeveloped to measure fluid accumulationin human tissues resulting from such fluidshift. Analogous forms of oedema occurpreferentially in the facial tissue for kidneydisease for example, whereas cardiacpatients show oedema in the lower part

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Biomedicine

The preservation state ofplatelets in microgravityhas been observed to besignificantly higher thanin ground-stored samplesdue to reduced plateletaggregation.

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of the body. In this way swellings in theforehead or the tibia can serve asdiagnostic or prognostic hints and becontrolled by the new ultrasoundinstrument.

For the measurement of inner eyepressure in space a device, which theuser can operate without help, has beendeveloped that determines the increasedue to microgravity. This ‘self-tonometer’can also be used to control the increaseof the intra-ocular pressure on Earth. Theinstrument registers the pressure by totalreflection of an infrared beam and is nowon the market for regular self-control anddiagnostic of patients with risk ofglaucoma, one of the most frequentreasons for early blindness.

The development of a non-invasivedetection instrument to observe eyemovements in all three dimensions byvideo-oculography is another example.The reaction of the eye to lightstimulation can be registered continuouslyand has been used to investigate thecoordination of information onorientation obtained by the eye and bythe gravity-sensing organ in the inner ear.This method has been successfully testedon Mir and Shuttle missions, and can beused in the detection of disturbances inthe vestibular, neurological or oculomotordomains. This diagnostic instrument isnow commercially available for terrestrialuse.

Monitoring the health of astronauts has led to additionalknowledge of the influence of space flight on human beings.Dedicated instruments were developed, validated in space andare now used for medical diagnostics on Earth.

Formation of bloodclots of fibrin networksand blood platelets(thrombocytes)

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Drop Shaft, Hokkaido(Japan)

NASA began a programme in 1985 topromote the involvement of industry inspace-related activities through theformation of Centers for SpaceCommercialization (CSC). The objective isto motivate industry to invest in space-based R&D. The following centres arejointly supported by industry and NASA:

– University of Alabama-Birmingham: macromolecular crystallography, growthof structurally improved protein crystalsunder microgravity.

– Auburn University: solidification designby measurement of critical thermophysicalproperty data of molten alloys for improvedalloy and process development on Earth.

– Colorado School of Mines: commercial applications of combustion in space: combustors (power plants, aircraft engines), fire safety, ceramic powders, combustion synthesis.

– BioServe Space Technologies: bioprocessing/bioproduct development,using space as a laboratory to address terrestrial health concerns, ‘biocybernetic’materials.

– University of Alabama in Huntsville: Consortium for Materials Development in Space: liquid metal sintering, vapourgrown single crystals, electrodepositionof hydroxyapatite.

– University of Houston, Texas: Space Vacuum Epitaxy Center: use of the ultra- vacuum of space for processing ultra- pure, thin-film materials by epitaxy.

– University of Wisconsin-Madison:Center for Space Automation andRobotics, use of microgravity to enhanceproduction of plant materials forpharmaceutical and agricultural purposes.

– Northeastern University Boston, MA,industrial research on zeolite crystalgrowth.

In Japan, microgravity applications arepromoted by the Japan Space UtilisationPromotion Office, with participation fromNASDA and MITI. The activities areconcentrating on the utilisation of a 750 m drop shaft - JAMIC. By providingan inexpensive and easily accessedmicrogravity environment for experimentdurations of up to about 10 seconds, theinterest of industry in later using theSpace Station is being developed. A high-priority project is focusing on thedetermination of thermophysicalproperties of molten semiconductors withthe goal of developing high-quality siliconsingle crystals for the next generation ofminiaturised electronic devices. This willbe achieved through numericallycontrolled processing using material data(thermal conductivity, diffusivity, etc.) ofhigh precision, measured without thedisturbing influence of convection. Othertopics are the investigation of technicalcombustion processes for which thebetter understanding of basicphenomena, such as droplet evaporationand ignition, is expected to result in thereduction of fuel consumption andexhaust emissions, thus leading toimproved process efficiency of gasturbines, burners and diesel engines.

Activities in the US and Japan

Combustion researchexperiments can easilybe carried out at theDrop Tower in Bremen(Germany)

processes, as well as for the control offluids in fuel cells in space. CNES is alsoinvolved in the development of a newatomic clock, relying on the quiescentstate of ultra-cold atoms that can beachieved in a microgravity environment.This will eventually lead to at least oneorder of magnitude improvement offrequency stability of space-based clocks.

One of the Japanese projects oncombustion is being carried out incooperation with Germany, using the 110 m drop tower of ZARM Bremen. TheGerman Aerospace Research Centre (DLR)has strongly supported applicationoriented and applied research in the past.A typical example is the research anddevelopment of monotectic alloys, whichresulted in a patented casting process forthe production of self-lubricating bearingmaterials. This process uses the knowledgegained through microgravity experimentson interface tension-driven convection tocompensate for separation by sedimentationon the ground. A specific programme forthe promotion of applied research hasbeen initiated, and the programme of‘Research under Space Conditions’emphasises industrial applications. Spaceindustry is starting its own promotionalactivities by contributing to existingresearch networks and by stimulatingnew applied research fields, includingapplications in space. Examples arematerials for sensors and detectorsoperating in harsh environments.

Other national agencies are now shiftingtheir microgravity programme prioritiesfrom fundamental to applied research. Anexample is the French space agencyCNES, which has been supporting theinvestigation of phenomena near thecritical point. Experimental results showedthe existence of a new, so far unknown,mechanism of heat transport, the so-called ‘piston effect’. Efforts are nowunder way to use this effect in industrialapplications, e.g. in supercritical fluids,chemical and nuclear decontamination

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National Initiatives in Europe

Towards commercialutilisation ...

This brochure has presented someexamples on how microgravity as aresearch tool increases the understandingof gravity-related phenomena in processesand products of industrial significance.Microgravity can also help to obtain moreaccurate data needed for theimprovement of certain ground-basedprocesses and products. An importanttask is to include microgravity as a tool inindustrial research and to use the resultsfor increasing the reliability of numericalsimulation and modelling. Recentworkshops have helped to identify topicsof interest to industry and of a highmicrogravity relevance. Another importantaspect is the development of instrumentsfor experimentation in space that are alsoof interest for new commercial terrestrialapplications. This is particularly true in themedical field.

The era of the International Space Stationwill open new opportunities for application-oriented research. The unique feature ofthe ISS is the availability of microgravityfor long periods and the presence ofastronauts for experimentation. This large-scale research facility will allow flexibleaccess for the accommodation ofsophisticated instruments.

The possibilities range from basic toapplied research to the utilisation of theISS as a platform for industrial R&D by theprivate sector on a commercial basis. Forsuch customers, adequate guarantees ofconfidentiality, including intellectualproperty rights, will be secured.

For the early utilisation phase of the ISS, a call for proposals was issued in 1998.New projects will be selected andapproved early in 1999.

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Outlook

This brochure was prepared by:

Dr. R. Binot, ESADr. E. Kufner, ESADr. O. Minster, ESADr. D. Routier, Matra Marconi Space,

formerly Novespace, under ESA contractDr. H. J. Sprenger, Intospace,under ESA contractDr. H. U. Walter, ESA

Published by:

ESA Publications DivisionEditor: Andrew WilsonDesign: Carel HaakmanISBN: 92-9092-605-8© European Space Agency 1998

Images courtesy of:

Cover – ESAPage 1 – ESA/D. DucrosPage 2, 3, 5 – ESAPage 6 – Audi AG and CEN GrenoblePage 7 – Airbus Industrie and Centro Ricerche FiatPage 8, 9 – Deutsches Zentrum für Luft- und Raumfahrt (DLR)Page 10, 11 – ZARM, BremenPage 11 – ESAPage 12 – University of FreiburgPage 13 – DASA and University of FreiburgPage 14, 15 – C-Core, Memorial University of Newfoundland

and MRC, Université Libre BruxellesPage 16,17 – W. Saenger, P. Fromme, Univ. Berlin and R. Giegé,

IBMC StrasbourgPage 19 – CNESPage 20 – University of UtrechtPage 21 – Mechanex B.V.Page 22 – Matra Marconi SpacePage 23 – National Osteoporosis Foundation and

Professor Dr. P. Ruegsegger, IBT-ETH ZurichPage 24 – D. Schmitt, Etablissement de Transfusion Sanguine de

StrasbourgPage 25 – DLRPage 26 – NASA and Japan Space Utilization Promotion CenterPage 27 – ZARMPage 28 – ESA

nn><Contact: ESA Publications Divisionc/o ESTEC, PO Box 299, 2200 AG Noordwijk, The NetherlandsTel. (31) 71 565 3400 - Fax (31) 71 565 5433

Contact Addresses

European Space AgencyDirectorate of Manned Spaceflight and MicrogravityPhysical Sciences Co-ordination and Microgravity Applications Promotion OfficeESTECPostbus 2992200 AG NoordwijkThe Netherlands

Programmatic Aspects: Dr. H. U. Walter

Materials Science: Dr. O. Minster

Fluid Science/Combustion: Dr. E. Kufner

Biotechnology: Dr. ir. R. Binot

Tel: + 31 71 565-3262 (Secretary)Fax: + 31 71 565-3661e-mail: MAP@estec.esa.nl