bioreactor designs for solid state fermentation

Biochemical Engineering Journal 13 (2003) 113–125 Bioreactor designs for solid state fermentation A Durand∗ Platform for Development in Biotechnology, UMR-INRA 1082 (IBQ), 17 Rue Sully, Dijon 21065, France Received 17 December 2001; accepted after revision 24 July 2002 Abstract Solid state fermentation has gained renewed attention not only from researchers but also from industry This technique has become a more and more attractive alternative to submerged fermentation for specific applications due to the recent improvements, especially in the design This paper reviews the various reactor designs and focuses on the differences between lab-scale and industrial-scale designs It highlights the main designs that have emerged over the last 10 years and the potential for scaling-up for each category of reactor © 2002 Elsevier Science B.V All rights reserved Keywords: Solid state fermentation; Bioreactor design; Engineering; Scale-up strategies Introduction Is solid state fermentation (SSF) a new challenge for a very ancient technology? The question is worth asking because this “ancient art” is in the process of becoming a modern technology During the last 10 years, many articles have been published, several books have been edited showing a spurt of SSF processes even in western countries The fact that this process is particularly well adapted to the metabolism of fungi, the micro-organisms most commonly in SSF processes, is an important feature because of the characteristics of these micro-organisms (apical growth, enzymatic activities) Moreover, in western countries, recent important problems has emerged such as: pollution of soils and the potential use of bioremediation, BSE epidemic and the necessity to find alternative for animal feeding, to cite only two examples Thus, SSF has gained a new interest from researchers and manufacturers over the past 10 years Many papers have appeared on the use of solid state fermentation, with studies on the effects of different factors on fungus metabolism, and the potential for producing different metabolites [1–3] The great majority of these papers were SSF processes at laboratory-scale Conversely, very few works have been carried out on the engineering aspects and problems of scale-up Compared to submerged fermentation, the solid media used in SSF contain less water but an important gas phase exist between the particles This feature is of great importance ∗ Tel.: +33-3-8069-3061; fax: +33-3-8069-3229 E-mail address: durand@dijon.inra.fr (A Durand) because of the poor thermal conductivity of the air compared to the water Another point is the wide variety of matrices used in SSF which vary in terms of composition, size, mechanical resistance, porosity and water holding capacity All these factors can affect the reactor design and the control strategy for the parameters Indeed in submerged fermentation, we can consider roughly that all the media are made up essentially of water In this environment, the temperature and pH regulations are trivial and pose no problem during the scaling-up of a process In submerged fermentation, only one major difficulty is encountered: the transfer of oxygen to micro-organisms which depends upon the shape, the size of the reactor and the agitation/aeration system used To characterise this transfer, a parameter, KL a (oxygen transfer coefficient), has been defined It can be considered as a “similarity invariant”, i.e its value expresses the capacity of the equipment to transfer oxygen independently of the volume of the reactor and so, constitutes an important parameter used for the scale-up studies in submerged fermentation In SSF, besides the oxygen transfer which can be a limiting factor for some designs, the problems are more complex and affect the control of two important parameters: the temperature and the water content of the solid medium Other factors also affect the bioreactor design: (i) the morphology of the fungus (presence or not of septum in the hyphae) and, related to this, its resistance to mechanical agitation, (ii) the necessity or not to have a sterile process Before analysing the various types of bioreactors, their advantages and drawbacks, it is important to specify that in a general way, many types of reactors are able to run at laboratory-scale with small quantities of medium But, the 1369-703X/02/$ – see front matter © 2002 Elsevier Science B.V All rights reserved PII: S - X ( ) 0 - 114 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 scale-up is complicated mainly by intense heat generation and heterogeneity in the system [4] In this paper, emphasis will be put on the differences between bench-scale bioreactors and pilot or industrial units and also between non-sterile and sterile process Bioreactor classification Two categories of bioreactor exist for the SSF processes: (i) at laboratory-scale, using quantities of dry solid medium from a few grams up to few kilograms, (ii) at pilot and industrial-scale, where several kilograms up to several tons are used The first category comprises many designs, more or less sophisticated, while the second category, which is used mainly at industrial level, is markedly less varied Within each category, some of the bioreactors can operate in aseptic conditions 2.1 Laboratory-scale bioreactors Several types of equipment are used for SSF Petri dishes, jars, wide mouth Erlenmeyer flasks, Roux bottles and roller bottles offer the advantage of simplicity [5,6] Without forced aeration and agitation, only the temperature of the room, where they are incubated, is regulated Easy to use in large numbers, they are particularly well adapted for the screening of substrates or micro-organisms in the first steps of a research and development program One of the interesting lab-scale units is the equipment developed and patented by an ORSTOM team between 1975 and 1980 [7] It is composed of small columns (Ø cm, length 20 cm) filled with a medium previously inoculated and placed in a thermoregulated water-bath (Fig 1) Water saturated air passes through each column This eqiupment is widely used by many researchers and offers the possibility to aerate the culture and also analyse the micro-organism respiration by connecting the columns to a gas chromatograph with an automated sampler that routinely samples each column This equipment is convenient for screening studies, optimisation of the medium composition and measurement of CO2 produced The small quantity of medium (few grams) used and the geometry of the glass column is suitable for maintaining the temperature in the reactors (the heat removal through the wall seems to be sufficient) The design of this reactor, however, does not permit sampling during fermentation and so it is necessary to sacrifice one entire column for each analysis during the process This equipment, with its advantages (forced aeration, cheap, relatively easy to use), can constitute a first step in the research A new generation of small reactors was developed by an INRA-team in France a few years later The first model developed [8] addressed problems concerning the regulation of the water content of the medium A second model built during 2000 has been tested but has not been reported in the literature As shown in the photograph (Fig 2), this reactor has a working volume of about l Compared to the first model, the principal changes were the introduction of a relative humidity probe, a cooling coil on the air circuit and a heating cover for the vessel These changes improved the regulation of the water content during the process As for the ORSTOM columns, the mini-reactors are filled with a medium previously inoculated in a sterile hood Each reactor is automatically controlled by a computer Moreover, samples can be taken by opening the cover in the presence of a flame without problem of contamination In this type of reactor, the temperature and the water amount of the medium can be monitored by means of the regulation of the temperature, relative humidity and flow rate of the air going through the substrate layer Different profiles for the air-inlet temperature and flow rate can be elaborated and generate useful information for the scaling-up studies Fig Typical lab-scale column reactor Several columns detailed on the right part of the figure are located in a water-bath for temperature control A Durand / Biochemical Engineering Journal 13 (2003) 113–125 115 Fig Photography and schematic of a lab-scale sterile reactor (1) Heating cover, (2) medium temperature probe, (3) stainless steel sieve, (4) air-inlet temperature probe, (5) relative humidity probe, (6) resistive heater, (7) water temperature probe, (8) massic flow meter, (9) level probe, (10) insulating jacket Fig Rotating drum bioreactor (1) Air-inlet, (2) rotating joint, (3) coupling, (4) air nozzles, (5) air line, (6) rollers, (7) rotating drum, (8) solid medium, (9) rim 116 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 Fig Perforated drum bioreactor Another concept, based on continuous agitation of the solid medium, was developed by several teams mentioned below The bioreactors can be a rotating drum (Fig 3), a perforated drum (Fig 4) or an horizontal paddle mixer (Fig 5) With or without a water-jacket, this type of reactor is required to be continuously mixed to increase the contact between the reactor wall and the solid medium and also to provide oxygen to the micro-organism For rotating drum bioreactors, as an horizontal cylinder, the mixing is provided by the tumbling motion of the solid medium which may be aided by baffles on the inner wall of the rotating drum (perforated or not) However, in all these reactors, the mixing is less efficient than with a paddle mixer [9] Indeed, agglomeration of substrate particles during the growth of the mycelium can occur which increases the difficulty of regulating the temperature of the solid medium Moreover, the oxygen transfer inside these balls of medium, agglomerated by the fungal hyphae and also very often by the stickiness of the substrate used, may be very low or nil In addition, from an engineering point of view, a water-jacket on a moving body of a reactor causes problems that increase with scale [10] A continuous mixing horizontal paddle mixer (Fig 5) was developed by a Dutch team at Wageningen University This aseptic fermenter was used for different purposes and to improve simultaneous control of temperature and moisture content Although heat transport to the bioreactor wall was improved, this device becomes inefficient for larger volume [11] because heat removal only through the wall becomes increasingly inefficient as the volume increases Generally, a continuous agitation, even if it is gentle, can modify the structure of the solid medium to a pasty texture Depending upon the nature of the particles (clay granules as support for example), this agitation can also be abrasive and so be harmful for the mycelium especially if the hyphae have no septa For processes in which the substrate bed must remain static, a reactor designed by ORSTOM team in France and named Zymotis is an interesting equipment [12,13] It consists of vertical internal heat transfer plates in which cold water circulates (Fig 6) Between each plate the previously inoculated solid medium is loaded Thermostated air is introduced through the bottom of each partition This reactor, which looks like a tray reactor where the layers of substrate would be set vertically, appears difficult to work in aseptic conditions Very often in SSF a shrinkage of the volume of medium occurs during the mycelium growth With this type of device, Fig Photography of an horizontal paddle mixer used in the Wageningen University of Agriculture Schematic of a stirred horizontal bioreactor (1) Air-inlet, (2) temperature probes, (3) water-jacket, (4) paddles, (5) air outlet, (6) agitation motor, (7) reactor, (8) solid medium, (9) agitation shaft A Durand / Biochemical Engineering Journal 13 (2003) 113–125 117 Fig Photography of the Zymotis showing heat exchanger plates for the thermostated water circulation (at left) and during a culture (at right) the risk is that the contacts with the vertical plates will decrease as the fermentation progresses, which would lead to poor heat transfer and air channelling Finally, the scale-up of such a design appears very difficult 2.2 Pilot and industrial-scale bioreactors As mentioned before, the number of reactor types used at pilot scale and in industry is less wide due, at once to some important reasons and necessities which are that: • above some critical quantity of substrate, the heat removal becomes difficult to solve and restricts the design strategies available The solid medium becomes compacted or creates air channelling, shrinkage, etc All these factors affect heat and mass transfer, • the properties of the micro-organism with respect to its resistance to mechanical stirring, its oxygen requirement and temperature range When the mycelium hyphae not have septa, they can be destroyed by a mechanical stirring So, the culture layer will be thin to allow heat Fig Koji-type reactor: (1) Koji room, (2) water valve, (3) UV tube, (4, 8, 13) air blowers, (5, 11) air filters, (6) air outlet, (7) humidifier, (9) heater, (10) air recirculation, (12) air-inlet, (14) trays, (15) tray holders 118 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 removal which automatically orientates to a category of reactor, • the nature of the substrate and the need to pretreat or not it, appropriate procedures for the inoculation, the sterility or the level of contamination acceptable for the process and the application, • the economy of the country where the process is developed especially with respects to the labour cost Indeed some technologies need more manpower than others, • handling poses different problems such as the ease of filling, emptying and cleaning the reactor The heat and mass transfer problems identified above can be attributed to poor aeration This problem can be addressed using the following strategies: (i) the air circulates around the substrate layer or (ii) it goes through it Within the second strategy, three possibilities are available: unmixed, intermittently or continuously mixed beds 2.2.1 SSF bioreactors without forced aeration This category is ancient and the simplest Probably different ancient civilisations have used this technology domestically for fermenting miscellaneous raw agricultural products in baskets The microbial starter culture might be transferred in the form of a “mouldy medium” Although this technology has advanced, it is still based on the same principle Applied on commercial scale, it corresponds to the tray fermenters (Fig 7) as typified by the famous Koji process [14–18] Made of wood, metal or plastic, perforated or not, these trays, containing the solid medium at a maximum depth of 15 cm, are placed in thermostated rooms The trays are stacked in tiers, one above the other with a gap of a few centimetre This technology can be scaled-up easily because only the number of trays is increased Although it has been extensively used in industry (mainly in Asian countries), this technology requires large areas (incubation rooms) and is labour intensive It is difficult to apply this technology to sterile processes except if sterile rooms are built and if procedures and equipment for the employees are provided, which will be prohibitive An alternative could be to use polypropylene semi permeable sterilizable bags to maintain sterility Moreover, some bags have a microporous zone which allows a passive airflow rate from 20 to 2000 cm3 /(cm2 /min) 2.2.2 Unmixed SSF bioreactors with forced aeration The basic design feature of packed-bed bioreactors is the introduction of air through a sieve which supports the substrate In this way, a bioreactor was developed at pre-pilot scale (Fig 8) for defining the control strategy and optimising the air-inlet temperature, the airflow rate, the addition of water and agitation during a SSF process [8] Located in a clean room, the reactor can be pasteurised in situ by steam generated by the water-bath used for the air humidification This reactor is very simple and can process a few kilograms of dry solid medium These reactors constitute an interesting tool that can be used in two ways: (i) to analyse Fig General view and schematic of the unmixed bioreactors with forced aeration (1) Basket conateining the solid medium, (2) valves for airflow adjustment, (3) air temperature probe, (4) relative humidity probe, (5) draincocks, (6) heating box, (7) humidifier, (8) coil for circulation of cold water, (9) resistive heater empirically the global evolution of a process and determine the environmental parameters for regulating the temperature and the moisture of the solid medium, (ii) to study mass and heat transfer phenomena and oxygen diffusion [19] Both the reactor diameter and the height of the substrate layer are around 40 cm, so the quantity of solid medium is sufficient to predict what can happen in a larger volume [20] In the absence of mathematical models for the scale-up, these reactors are very useful No mechanical agitation exists inside these reactors, but the medium can be manually agitated in situ or it can be transferred into a kneading machine and reloaded into the basket However, this type of device without agitation is limited by the metabolic heat production Temperature gradients from the bottom to the top of A Durand / Biochemical Engineering Journal 13 (2003) 113–125 the layer appear unavoidable As the majority of the heat is eliminated by convection and water evaporation [21], the bed dries out and the water additions needed have to be calculated and agitation is required in order to distribute the added water uniformly To reduce the need for a strong aeration, another concept was recently developed It consists of the introduction of heat exchangers directly beneath the perforated plates which support the substrate and/or inside the substrate layers A similar strategy on a lab-scale but with vertical heat exchangers has been demonstrated for the Zymotis bioreactor [12] Based on this principle, a first bioreactor was patented [22] and used by a German company (Prophyta) for producing biopesticides in sterile conditions The fermenter is a tower with perforated plates on which the solid medium is located Sterile air can go through each plate Beneath each plate, heat exchangers are located to remove heat during the cultivation (Fig 9) A similar bioreactor, PlafractorTM , was patented by an Indian company, Biocon, [23] Metabolic heat, as in the previous reactor, is mainly removed by conduction This reactor was constructed by stacking and interconnecting individual modules (Fig 10) Non-communicating channels 119 deliver cooling and heating fluids sandwiched between two sheets Communicating channels can deliver fluids for sterilising (with steam or ethylene oxide for example), for adjusting the moisture and oxygen content and for extracting the compound of interest after the cultivation Moreover, the interior of each module has a mixing arm that revolves about the central axis of the module while rotating This reactor has been used mostly for metabolite production In the patent, a maximum quantity of 20 kg of wheat bran was mentioned with approximately 22,600 cm2 plate area, but the number of modules was not mentioned Finally, no details were given about the disposal of the waste product, the cleaning procedure which seems relatively complicated and generally the possibility to scale-up this device 2.2.3 Continuously mixed SSF bioreactors with air circulation This category is essentially a rotating drum because continuous mixing is necessary to maximize the exposure of each substrate particle to the thermostated air circulating in the headspace Different teams have worked on this design and it is mostly used at lab and pre-pilot scale Although Fig Schematic of the patented industrial bioreactor showing the exchanger plates under each tray [22] 120 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 Fig 10 Scheamtic of the PlafractorTM reactor [23] rotating drums have been described in the past, the largest reactor recently cited in the literature was a 200 l stainless steel rotating drum (Ø 56 cm and 90 cm long) which used 10 kg of steamed wheat bran as substrate [24] for kinetic studies of Rhizopus Researches were carried out at lab-scale to study the efficiency of this design, the role of the baffles and the influence of the filling (amount of substrate per unit volume) on the mass transfer by using tracer or image analysis [25–27] These works introduced the rational design and scale-up of this type of reactor In several cases, the mycelium and the substrate particles, particularly starchy and sticky materials, agglomerate Under these conditions, even with baffles inside the drum, it was very difficult to separate these aggregates, consequently, the heat, mass and oxygen transfers were greatly reduced When the rotation rate of the drum is increased, it can affect the mycelium growth presumably because of shear effects [25] For a discontinuously rotating drum, the design is identical to the reactor described above but between two agitations, it operates like a tray reactor So, it is absolutely necessary to limit the height of the substrate layer, otherwise it will be necessary to continuously agitate due to the heat accumulation and, taking into account the poor thermal conductivity of the air, the medium temperature will inevitably increase Very few studies have been published on this type Using this rotating drum, a strategy for regulating the medium temperature was described in a thesis [28] and in a publication [29] It consists of activating the rotation of the drum in response to the temperature measured by a thermocouple in the medium Efficient for a 4.7 l working A Durand / Biochemical Engineering Journal 13 (2003) 113–125 121 Fig 11 Discontinuously rotating drum [28] volume (Fig 11), on soy beans with Rhizopus, for tempe production, no scale-up studies have been attempted 2.2.4 Intermittently mixed bed bioreactors with forced aeration In general, these bioreactors can be described as packed beds in which conditioned air passes through the bed An agitation device is periodically used to mix the bed and at the same time, water is sprayed if necessary The design of these reactors, the capacity of which varies from a few kilograms to several tons, is influenced the necessity or not to operate in sterile conditions For non-sterile processes, a number of advances have been done in the design and application of such bioreactors One design is represented by the rotary type automatic Koji making equipment marketed by Fujiwara in Japan (Fig 12) The treated substrate is heaped up on a rotary disc Depending on the diameter of this disc, different working volumes are available but always with a layer of maximum thickness 50 cm This non-sterile reactor operates with a Fig 12 Photography and schematic of the Koji making equipment: (1) Koji room, (2) rotating perforated table, (3) turning machine, (4, 11) screw and machine for unloading, (5) air conditioner, (6) fan, (7) air outlet, (S) dampers (9) air filter, (10) machine for filling, (12) control board 122 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 microcomputer which controls all the parameters (temperature of the air-inlet, air flow rate and agitation periods) The main drawback of this equipment is the need to prepare and inoculate the substrate in other equipment before filling the reactor Nevertheless this type of design is widely used in Asian countries Similar to the reactors used in the barley malting process, huge equipment has been built for the first step of the process for making soy sauce A specific building contains the solid state reactor which is generally rectangular with a length of several meters Several tons of pretreated and inoculated substrate are put on a wire mesh and conditioned air is forced through the layer An agitator trolley periodically mixes the solid medium Although this kind of reactor is very simple and basic, it is widely used in many Asian manufacturers of soy sauces An INRA team in Dijon (France) has developed a nonsterile process strategy based on the following principle (Fig 13) The temperature (Tm ) and the moisture (WAm ) of medium are maintained by a regulation of the temperature, relative humidity and flow rate of the air input It is also necessary to spray water (E) and agitate (A) periodically The Fig 13 General schematic of the intermittently packed bed reactor with forced aeration (Tin , HRin and Din ) respectively the temperature, relative humidity and flow rate of the air-inlet, (Tout , HRout and Dout ), respectively, the temperature, relative humidity and flow rate of the air outlet, (Tm ) temperature of the solid medium, (WAm ) water amount of the solid medium, (Mg ) total mass of the solid medium, (A) agitation, (E) water spray Fig 14 Pilot plant reactor [30]: Photography showing a general view of the reactor (left), a detail of the swelling joints A schematic diagram of this pilot plant (1) Carriage motor, (2) screw motor, (3) valves for inoculum and water spraying, (4) temperature probes, (5) weight gauges, (6) relative humidity probe, (7) cooler, (8) humidifier by steam injection, (9) airflow meter, (10) fan, (11) heater, (12) air filter, (13) cooler A Durand / Biochemical Engineering Journal 13 (2003) 113–125 volume of water sprayed is calculated from on line measurements of the total mass of the medium (Mg ) and by estimating the mass losses due to respiration (CO2 ) On this basis, a reactor of 1.6 m3 capacity using t of sugar beet pulp (with 25% of dry matter) per batch was reported [20] This reactor has been successfully used for different applications including protein enrichment of agro-industrial by-products, production of enzymes or biopesticides [30] The system has been since continuously improved Compared to the first reactor, the main changes (Fig 14) were in the equipment itself with some accessories (pump for inoculation and water spraying), the air conditioning and the software for the control and the regulation of the parameters during the process Particularly, a mathematical model has been established for maintaining the moisture of the medium during the process by taking into account the dry matter losses and the evaporation due to the aeration Moreover, this reactor is closed by a cover in three parts allowing the passage of the screw axis during the mixing By this way, it is possible to pasteurise the reactor and/or to treat the substrate in situ, near 80 ◦ C Using the same design, two larger reactors (each with overall dimensions of 17.6 m × 3.6 m × 2.0 m) and a maximum working capacity of 50 t (20% dry matter) were constructed [31] to demonstrate the potential industrial-scale-up of this fermenter For sterile processes, the reactors based on this same principle are smaller and, currently, no industrial application has been published in the literature Such sterile processes are necessary because: 123 Fig 15 Photography of the ribbon mixer developed by Wageningen University of Agriculture [32] Fig 16 Photography and schematic diagram of the sterile reactor developed by the National Institute of Agronomic Research in Dijon [30] (F) Air filter, (HC) humidification chamber, (HB) heating battery, (BP) by-pass, (CB) cooling battery, (HM) probe for air relative humidity measurement, (TP) probe for medium temperature measurement, (WG) weight gauges, (SH) sterile sample handling, (JR) water temperature regulation in the double jacket, (AD) planetary agitation device, (M) motor for agitation, (IS) sterile system for adding inoculum and solutions, (CO) water air condenser 124 A Durand / Biochemical Engineering Journal 13 (2003) 113–125 • the product obtained must be sterile for application and legislative reasons (food and pharmaceutical industries for example), • the micro-organism used has a very slow growth rate and so must be cultivated in clean conditions Indeed, usually, it is considered that beyond days cultivation, it is very difficult to work in non-sterile conditions An original design has been developed by the Wageningen University in Holland and used at pilot scale for studying production of a biopesticide [32] This reactor with a total capacity of 50 l can hold up to 20 kg of wet cereal grains substrate It consists of a conical vessel mixed by a ribbon at the wall (Fig 15) This reactor, developed in co-operation with Hosokawa Micron, is sterilisable in situ by steam Sensors register the temperature at several heights in the bed, also during mixing Another bioreactor with a 50 l bed was patented by Durand et al [33] This reactor, which has a planetary mixing device (Fig 16) is entirely piloted by a micro-computer during the different process steps: sterilisation of the bioreactor while empty, sterilisation of the medium, process control during the fermentation and data acquisition Among others, this reactor was used for the production by fed-batch SSF of gibberellic acid (Bandelier et al., 1997) and for the production (after 15 days cultivation) of conidia for biological control application [34] Up to date, no scale-up of this device was carried out in the industry Conclusions and perspectives Over the last 10 years, significant progress has been made in the design of solid state reactors More and more, studies appear in the literature with promising perspectives Some designs, such as the rocking drum bioreactor, appear more difficult to scale-up than others [13] When we analyse the evolution of the solid state processes in the world, we observe that it is not a matter of chance that the research and the industrial applications are most important in the Asian countries An ancient and important tradition, mainly for the food industries, promoted this evolution But, despite this success, little improvements were carried out from the traditional Koji equipment and, in most cases, the scaling-up has only consisted in mechanising the tray fermenter It can also be observed that if a pilot reactor exists, empirical studies can be conducted for effective process control design and successful industrial-scale-up [2] Up to now, the majority of the scale-up was done using the rules of thumb, but taking into account the great advantages of the SSF process, several research teams are working around the world and significant advances have been made in the development of quantitative approaches for heat and mass transfer ([35,36]; Ashley et al., 1999), mathematical modelling [13], measurement of some process variables [37,38] and for the development of growth models [6] Interesting approaches have been used by several workers not only to characterise the oxygen transfer and the effects of air pressure oscillation amplitude [39], but also to attempt to better understand the behaviour of the micro-organism in such solid state systems [40] However, some aspects of SSF processes still need research: development of probes mainly for moisture measurement, control and regulation of process variables, analytical procedures well adapted to these specific media, measurement of the gaseous environment Finally, and especially if the aim of the studies is not only academic but for industrial applications, it is important to keep in mind that some phenomenon studied at laboratory-scale are not representative of large-scale because the scaling-up is impossible Very often, the problems linked to the increase in the volume (mass compaction, shrinkage, diminution of the heat transfer, etc.) not appear at the bench scale and serious errors can be made in the choice of bioreactor design or process control strategy If an industrial submerged fermentation process is running, it would be unrealistic to imagine its replacement by a SSF process taking into account the level of investment already done by the industry [1] Despite a volumetric productivity, very often greatly higher obtained in SSF (around 10 times more for enzyme production for example), it is difficult on an economical point of view to change the production tool But by improving the reactor and the process control; the industry could consider the solid state fermentation as a very attractive alternative when new investments are decided or when new processes are developed Finally, for some industrial applications (production of spores for cheese making for example), SSF constitutes the sole solution for a production process and now, more viable and optimised tool can be proposed to the industry References [1] P Nigam, D Singh, Solid-state (substrate) fermentation systems and their applications in biotechnology, J Basic Microbiol 34 (6) (1994) 405–423 [2] A Durand, Solid 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