I'm going to talk to you about mixing orders and buy erections and you know I'm not going to focus specifically on biotechnology going to broaden the scope out a lot of the mixing problems that you incomes they're not any different in one biological system like a bit of fermentation for instance than they are in the biopharmaceutical reactor so I'm going to talk to you about you know things that doesn't relate to farmer but which I still sink to the important moment here already I hope you're all ready to do so I'm not going to spend any time on this what I'd like to say just a few words about our faller tank equipment where I work so we basically sells tank equipment components and that would primarily be tank cleaning equipments then we have a mixing portfolio that consists of agitators what's known as rotate get mixes and magnetic mixes then we sell all instrumentation chain covers and tank accessories but as pillow cholerae to say it my area of expertise is kind of mixing in general so you see the agenda might fall I'm going to start out by talking to you about what kind of mixing duties are actually important when we consider buyer actions then I'm going to tell you about what will happen if you have poor mixing and I'm going to illustrate that by a number of examples drawn from my own work so that's also one of the reasons why I'm not only talking about by industrial rotation and Nutella culture and Bill I'll talk about what you should consider when you design an agitator for a bioreactor and then if we have time then I'll go a little bit into a magnetic mixer this I've also so the reason why mixing is important in by reaction systems is basically it's basically to ensure that we keep the cells in suspension that of course we need to do then it's to ensure that we have adequate blending of substrates that we are introducing during the process adequately fast pH adjustment etc if we're introducing gases we utilize the mixing equipment to enhance the mass transfer if we need to do heat transfer then the mixing will aid conviction and thereby heat transfer and ultimately we use or we basically do this to promote the biological reactions taking place so if we just look at the economic impact of poor mixing in general then it's been estimated around 20 years ago that the impact of poor mixing on industrial applications in the u.s. in general across all industries was around one to ten billion US dollars per year and of course also if she don't have optimal yield then you need to do more downstream processing so but let me start out by giving you one example of what poor mixing tele2 and this is an example of an adequate cell dispersion and is taken from the from the brewing industry so we're considering mixing in fermentation yeah probably the oldest biotechnological the reaction that you can think about so if you look at how lager is manufactured commercially today it's done in in batch reactors you sing vertical cylinder conical fermenters without having any mechanical education in them and we're talking tanks that are maybe 100 to 600 Cuba meets cubic meter scale typically you're using what's called high gravity words so that would be words that you ferment that have a very high sugar content and the typical fermentation temperatures maybe 12 to 20 salty grades you apply cooling by having internal jackets on the tank and the underlying assumption here is that a conviction courage due to temperature differences between the cooling Jets and the beer and the effect this difference of rising co2 bubbles that you'll get when the yeast converts sugar into ethanol and see you to that that will ensure good mixing so you don't need an external agitator that's been the general thinking and it's been assumed that good mixing ensures homogeneity of temperature and the East concentration and then the final assumption has been that when the yeast is exhausted sorry when the sugars exhausted the yeast will sit him in down to the bottom and you can take off the yeast before you transfer the beers the filter line what's her story staying and then to a filter line so some years ago a guy called Chris Bolton from the Brewing Company cause he actually looked into how a yeast was distributed instead of just assuming that it was distributed in a certain way and he presented that to European brewing convention Congress and he used what's called an IVA instrument to measure the concentration of viable yeast cells he put these instruments into waterproof enclosures and he immersed them into tink so here you see his experimental system this was done in full scale he put in a number of these so you can see they're sitting here and just to give you an idea here they are mounting them on a wire and they look like this this is the waterproof enclosure here you have the sensor and then they put them in so that they were sitting here so he can basically measure the yeast concentration at a lot of different positions in this tank here again the probe location the tank was a 1636 actually the working volume tank through us like to work in hectoliters but it's basically 160 3.6 cubic metre what you see in this graph is it's this one shows the sugar content the evolution in the sugar concentration and the medium versus time rulers like to record this in terms of present gravity they missed basically just measure the density they concurrently that was the sugar concentration and what you see here is the viable yeast cell concentration mission of this Papa probe in the tank so this one or the yellow curve here is for the next probe the red one we go further down and now we get into the core now you can see something happening so what you can see here is initially in the fermentation the yeast is actually not very well distributed and that's because the the heav'n started formation of a lot of co2 yet that will provide the mixing needed in this reaction and then when approximately 60% does the sugars been consumed yeast actually starts to settle out in the cone if you have all the east feeling as a compact compact mass down in the Komen it's not going to do you a lot of good because you have all kind of mess transfer issues into that sediment to actually convert the sugar tool to alcohol so one way of actually getting around this would have cost you two to install some kind of mechanical mixing system and you can use educators for that but they've been used very little in the beer industry because of the brewing industry because they are not considered at least by Brewer as very sanitary instead a system called the ISO mix system is currently being installed in the number of major brewing groups and this system is basically based on mixing by rotary death makes us that are modified Alfa Laval rotary jet hits that maybe some of you or most of you know from CIP so the principle behind this system is that you take you take the fermenting beer it recirculated by an external pump and then you re inducted into the vault liquid why I want of these rotary it mixes you can add different things in the loop if you want you they don't do that in the brewing industry if you want to remove heat you can do that in a plate heat exchanger that you introduce in the loop and basically the mixer can be installed either from the top of or the bottom if you install it from the top it can also be used CIP basically because that was the original purpose of the machine so I just want to illustrate the function to you here what you see here is a transparent tank it's filled with water that contains iodine and starch so when you add those two components together they form this black complex because in there a component called thiosulfate by a sulfate will reduce the iodine to Ayodhya and it turns colobus so you can actually use this kind of system to visualize mixing so I'm just going to show you what the system operates like so then the thiosulfate is injected and you can see how the liquid is decolorized but you can also see how the head operates it actually doesn't turn very fast the mixing action is provided by liquid Jets leaving these four nozzles that are pretty high velocity that's what gives you the mixing but because the jet is route that the kids are rotating you're actually covering the entire lism what you see here is the the effect that we've seen in different breweries after installing the system so this is the reduction in process time for different breweries and you can see that we've seen reductions in process time of area where from 15 percent of two modes of more than 40 percent by installing the system so this is basically something where we get a faster process just because we keep the source in suspension instead of just letting them sit at the bottom of the tank for elevated period of time okay the next example that I want to show you is an example of inadequate liquid phase blending and the model system that I'm going to discuss is enzymatic oxidation of lecture beyond I guess it was a system that I work with when I did my PhD and you know I thought I should be doing a lot of enzyme kinetics and I did but it ended up being more of a mixing study also because we saw some really strange effects or at least we couldn't explain them initially anyway like to pay only gas it just to give you some kind of background about that it's actually used in organ transplantation and calcium supplements cosmetics right now it has other applications could be used as a colon detergent as a corrosion protection and food technology it can be used in a city land Phil and cheese production and their functional drink sister to a supplement calcium the reaction of producing lecture beyond gases from leg toes is shown here so you you have an enzyme that you call a lactose oxidase and it oxidizes lactose into a leg tone that's broken down into lecture beyond I guess it the Bible the byproduct is hydrogen peroxide so you need to add cancel AIDS because otherwise the hydrogen peroxide will basically kill your enzyme activity so you need to add the lactose oxidase and you need to add catalase so we started that in pretty small scale all our experiments were done in a 1 liter bioreactor we kept the dissolved oxygen tension constant using feedback regulation of to mass flow controller that dispersed respect to the air and nitrogen so we kept the very same oxygen concentration throughout the reaction pH was kept constant at six point six point four by addition of of two mole of sodium hydroxide base in but we had buffer in there so when you looked at the when you looked at the pH meter every time I drop up base went in the pH would go down to maybe six point boy every time pH dropped to six point three nine it would add a drop it would go up to six point forty you couldn't see any oscillations whatsoever the pH meter but what we saw when we started this reaction was that we had a declining rate in reaction it declined very fast with time to read in reaction and then we started looking at what happened when we increased the oxygen concentration we found out that the rate increased the initial rate increased increase the oxygen concentration but the real is the activation also were not quite a lot so we speculated could this basically be because when the rate goes up by putting more alkali if we don't have perfect mixing that alkali can destroy the enzyme so that gives us faster deactivation and actually that turned out to be exactly the case so if we switch from two molar sodium hydroxide to a weak base ammonia you know that deactivation it just just disappeared completely and that basically proved that mixing was very important in this system so the enzyme deactivated when we used 2 molar sodium hydroxide for neutralization even though we were doing this is really small scale we're talking 1 liter reactor we had two Rostand turbines in there that were revolving at 1,000 rpm I mean it was mixing really really fast every time you put in a drop off of sodium hydroxide you couldn't see any change and the peak meet at whatsoever you didn't have any oscillations or something so this was just because you had a very small song with a higher local pH spell you fought very small amount of time I mean that would be something that you could see another biological system also so is she for instant go to cell culture you can have the same situation if you have gradients in pH due to pure mixing because often it's old culture you don't have a very rigorous mix but you want that Union mix so you can actually in some situations its fluctuations in pH which can lead to a lower lower yield if we go from these two into industrial aerobic Fantasia then I've just have a picture here for typical industrials from you can see you have a lot of internals in here you have some cooling coils here to remove heat then you have an agitator shaft here fill it with to rust and impellers rusted impeller sleeve typically bento they've been used quite a lot in industrial fermentation and then you have baffles entertained to break out of the vortices that would otherwise result if you don't have Bethel's you'll get the vortex so if we look at the typical aerobic fermentation then if we consider yeast as an example east fermentation where the purpose is to produce yeast or to produce a product that's captured and used that could be reasons B insulin if you look at the way in over Dornoch it makes insulin then you really want to keep the sugar concentration homogenius and you want to keep it low because if you don't keep the sugar concentration low these will start to produce alcohol and you don't want to make beer that you want to make east you want to ensure a constant pH you want to ensure sufficient oxygen transfer by adequate air dispersion and when we are talking aerobic fermentation you need a lot of oxygen transfer so in a typical industrial scale bio red kind of maybe where you may be producing east you might be producing some enzyme and filamentous fungi it's be an e.coli fermentation typical aeration rates will be on the order of maybe one volume of gas per volume of fermentation volume per minute so we're talking huge amount of air you need to introduce you need to be able to break that out with the agitator otherwise you're not going to get good mess so you're not going to get the process result that you after also if you have these very aerobic fermentations they will generate a lot of heat so you also need to make sure that you can actually remove that heat so by having good mixing if you have the coils in the tank and you will you will get better heat transfer beating so what I'm going to do now is I'm going to introduce you to how you would actually or what to consider when you actually select an educator for perhaps a an aerobic highly aerobic fermentation so here's just a small schematic of an agitator so you have a motor with a gearbox and then you have an agitator shaft and an impeller at the bottom you could have multiple and pedis also and you can see in this tank you have baffles you can have different entity types you can have top mounted entertainers they would what would be would be what you would normally put into a fermentation tank actually there would be a top mounted educator with bottom support uniform mouths and agitators and you can have side mounted agitators these guys here typically not used in industrial fermentation you would typically need a top mounted educator with bottoms of all we talked about baffles a little bit already but the reason why you actually introducing Bethel's is to prevent the vortex formation that would otherwise resolve if you don't have the baffles and if you are having the impeller placed centrally in the tank if what what would happen is that the liquid will basically just go around like this you'll get a vortex but you won't get good mixing I mean it's just fluid elements traveling around so you need the Bethel's to get really good then if we look at the impeller type that you can use you can use what's called radial flow in pellets you can use what's called actual flow in pillars and then you can use something called clothes clearance and pillows but these ones are in pellets that are typically used for Hibiscus products so we don't want to consider them here because even hibiscus industrial fermentation it's like if you are having an industrial fermentation of filamentous fungi I mean you won't use these ones you'll use these kind of impellers and just to give you an idea about what the difference is then radial flow in pillars they basically produce a radial flow they're primarily used with low viscosity liquids in their battle teams and the disk turbines of them are normally used for gas dispersion so here you see a number of different their rate of flow and pillars the Rostand turbine has been used quite a lot in in industrial fermentation but people tend to move from this type maybe over to this type now I'll come back to why you see a picture where you can actually see the flow pattern made by a radial flow and pillar so it since our flow radial and then part of the fluid I burn it down like this part of the flow goes like this so you have two circulation use the other type of repellers are called the actual fluid pillars so they pump primarily but not exclusively vertic basically either upwards or downwards depending on basically whether or not you put the impeller like that or whether or not you put it upside upside down and take the shaft in the opposite direction they used me mean low to medium viscosity liquids that should say low to medium viscosity yeah activity you so they pump downwards but as I say you can she used them in a pumping motor for instance if she wanted this first guess and they produce a flow pattern like this so a flow is diverted down and then it goes all the way up and down so you only have one circulation when we consider impellers they are basically two numbers that are very important the first one is the Reynolds number it says something about the ratio of inertial forces to viscous forces and whether or not the flow is turbulent transitional or laminar and you need to know that because mixing when when you design an impeller you'll have different functionalities for how long it takes to mix whether or not the flow is actually turbulent or twisted transition another really important number is called the power number so it relates the power input to the stirrer speed and impeller diameter and there are several reasons why it's important but one of them is that if you have an impeller with a high-power number that means that you have a large torque so it means that if you choose such an impeller you also have to size your shaft and gearbox etcetera so it becomes more expensive and here somewhere power numbers for different impellers so you can see that Rostand impeller we talked about before it has a very high power number so that means that if you take a if you take a Rustin turbine it will normally it will revolve a pretty slow speed but it will draw a lot not talk then you can have other in palos like for instance this one here that's called a lightning a 315 that's a hydrofoil impeller like this one it has a very low-power number so it means that to dissipate the same power it needs to revolve faster but it doesn't require as much torque so you can make achiever construction so if we look at our educators in Alfa Laval our entity that's our primarily hydrofoil impellers are based on hydrofoil impellers they have a they're very good at pumping so if you compare something called a pumping number which basically says something about how good is the impeller pumping or making flow compared to the power number so that would be something about how much power as it consuming it has a very high ratio of two point six and common for other types it's maybe zero point six so this basically means that you with such an impeller like this one you can you can make a lot of pumping at low energy consumption compared to other and pillows have the same diameter operated at the same rotational speed so if you have a process where you need a lot of flow I mean you should go for this kind of energy if we look at the mixing time then mixing time can be important as we already discussed because for instance if you are blending in substrate in a reaction where where you need to have a sufficiently low substrate concentration all the time because otherwise your organism might start producing ethanol if we are talking used it might start producing hesitate if we're talking a coli or it could be that if we are having filamentous fungi or enzyme production in filamentous fungi they will just shut down the enzyme production don't have that low substrate concentration all the time to get that low substrate concentration you need to have an adequately low mixing type so therefore it's important to to actually study this mixing time if you look at a system with a single impeller in a tank with the FIM it's R equal to the height that's what this basically says this is the height this is the diameter and we are operating in the turbulent regime then the mixing time can just be written as a constant times the power divided by the unit mass raised to a certain exponent times the tank diameter raised to the power of two first times the impeller diameter divided by the tenth time of the rate to the power of minus one-third this equation basically says that if you put in to impel us that have the same diameter and that they are operated at the same power input it doesn't matter what the impeller looks like it's going to produce exactly the same mixing time so then you might argue why am i standing here talking about this because now I'm coming to the conclusion then you can put in whatever it doesn't matter but it is actually not unimportant because as I told you before if you choose the an impeller with low power number like for instance that in the boiling pillar it will be much cheaper to install than an impeller of the same diameter where you have the same power per unit volume that has a higher power so it's still important to think about not because it'll give you a different process result but because it'll be much much cheaper to anymore also what you can do is that if you say that you want to operate at the same talk what you can do is you can actually install a an impeller like in so foiling pillar that has a low power number but for much larger diameter before you get to the same torque as a impeller with a with the high power number that has a smaller diameter and you can see here that the diameter of the impeller section in the equation so that if you do that you will get faster mixing the equation actually also say that if you scale up at constant power input that is done at least in some industries that you say are now we we transfer from I don't know 10 10 meter cube to 100 meter cube how should we do that scale up are we probably keep the specific power input constant if you actually do that then your mixing time will increase with the type tank diameter raised to the power of 2/3 so mixing problems definitely become worse on scale-up so you have to think about that what you go in and do in the lab or in small pilot scale it's not necessarily the same things that you're going to see on the large scale so you really have to pay attention during the gala now these were just vessels that look a little bit like me so small and bulky aspect ratio around one if you take tall tanks then it does matter quite a lot what kind of a pillar you put in so if you put these a radial flow and peanuts in so cerebrate several radial flow and pillars on top of one another then they will produce something called Sony so so nning it's basically a situation where those loops that I told you that I showed you yeah you may imagine that you have a tall tank and you have another one of these impeller sitting up here so Sony is a situation where that loop that this impeller generates it's not going to get intimate contact the lower loop that impeller that would be sitting up here is providing so it means that if you drop in some feet from the top it will get pretty me pretty fast mixed in at the top and pillar but it will take a long time for it to be exchanged down to this song so that it can be mixed into the lower part of the tank if you take those actual flow and Payless instead and have multiple of those stacked on top of one another so learning is much less severe so if you have tall tanks with more than one impeller and mixing time is self-importance then mixing time will be lower if you use extra flowing pillows like the flinch that's all ends of oil and pillar rather than radial flowing pillars so if you remember that bioreactor I showed you in the very beginning it had to rust and turbines on top of one another it's not going to give you a very good liquid mixing it's actually pretty slow in making an even concentration in whatever substrate you put it on the top if you want faster mixing you need to go in and retrofit on that on that educator then if we look at gas dispersion which is very important also in a robbing industrial fermentation then there are some concepts there also so the first concept is the transition from what is called flooded to loaded so flooding is a situation where you're basically either you're providing too much gas that the impeller can handle or you're operating the impeller too slow so it can't handle the guests so it's a situation where you know the problems pretty much just rise up that are well distributed in the tank this is loaded that's a situation where now they're actually well distributed at least above the impeller and here that they're completely dispersed in the entire volume so the this studying this transition from frauded to loaded it's important because it tells you how much gas can the impeller handle before it kind of runs out of speed because if you get to a situation like this then mass transfer is going to be really bad so you're just putting in a lot of air that's not going to do you any good another important concept is what happens with the power on the on the motor when you start guessing because some impellers some impellers will actually take up less power so that means that unless you're running the the motor on a variable frequency drive you're not actually getting all the power out of that impeller that you want to get out of the impeller so it's best if the power num number remains constant when you start actually adding gas so if we lowered gas dispersion then radial flow and pillars they've traditionally been used and and that's also the reason why you saw those kind of impellers and then industrial bye rekt I showed you before they're very good at this person guess the Ralston was the preferred choice but it has you know it has the disadvantage that the power if you operated at a constant speed and start putting any guest with the power actually decreases upon guessing if you take one like this power doesn't increase when you start getting gas it just stays constant so that means that you can do basically the sizing once and for all and you know how much power it's going to draw and then it can actually handle much more gas also before it floods that situation where the the guess wasn't very well distributed so I would definitely choose an impeller like this for for any guests toss brother and pillow like this you can however also use actual flowing pillows but you need to you need to operate the minimal so they're pumping upwards if you try to take actual flow impeller and start guessing it and it's pumping downwards then I mean you all know guess wants to go upwards the impeller wants to pump downwards so what's going to happen is that you're going to get a lot of instabilities you're going to get a lot of torque fluctuations on the shaft and the gearbox so from a mechanical point of view it's just not good and I've heard stories about I think it was I think it was merge that did some trials where they wanted to test a Down pumping in a town pumping actual flow impeller in their pilot plant and the top fluctuations were so big that the fermentor it actually pulled itself out of its grounding and it kind of started so you don't want to take an actual flow impeller and make it pop downwards so just some recommendations on one until if she should actually choose then first of all if we are talking mixing in those small bulky chains that haven't height equal to the diameter and we don't consider gas dispersion then choose a low power number pillar like for instance the in some oil in pillar if we're talking mixing in town tanks but without gas dispersion then choose actual flowing pillars because they don't give you this Sony you can choose either upon bus or townhome bus it doesn't really matter if we're talking applications where both mixing and gas dispersion is of importance and tall tanks like for instance in industrial fermentation then you should probably use a modern radial flow and the law and pillar forgets dispersion and then some actual flow and pillars as the Obon pillars to provide good liquid mix okay now I just want to talk a little bit about cell culture and the reason why I don't talk about soul culture before now was that I wanted to kind of introduce those concepts for for educators before getting to the soul culture so cell cultures are animal and insect cell culture is basically used in the production of highly valuable valuable biological such as vaccines hormones growth vectors and maybe monoclonal antibodies the cells they leg a cell wall if you look at if you compare it to for instance aerobic fermentation the oxygen transfer requirement is very low compared to if you have aerobic fermentation of same bacteria yeast or filamentous fungi so you don't need to transfer that much air however the de saucé you to concentration has to be controlled because too high values will lead to toxicity to themselves so if you start a cell culture pea you will find out the people are very worried about shear stress because of that legged cell wall so these are systems that were at least originally thought to be very sheer sensitive and that has led to a situation where people in general employ very gentle education however nowadays it's been realized that the bubble liquid cell regions are probably actually more important and then if you take a system where you don't introduce gas into the system and agitate you can actually annotate them it's fairly high power efforts without destroying themselves but this bubble liquid self interface very important and you can you can basically break that up into four parts you'll have bubble for me sittin at its barger then the bubbles they can coalesce they can also break up in the vicinity of the impeller they will rise up the liquid and at the very end they will burst at the surface and it's actually that bubble bursting with is it's a major issue because if you look at how much energy is released when a bubble bursts it might sound totally counterintuitive but nonetheless if you look at bubble bursting out of the surface it releases a very high local energy level it's only local of 0.5 kilowatt per milliliter so if you have a self you know that's rises up in that bubble liquid interface and it reaches the surface then that cell will be exposed to that high anyway so bottle sizes below five millimeters are considered to be the most lethal once and for this very reason you will any difference effect since when you do cell culturing so if you're for instance a if this affection Veronica if 68 that gives a protective effect if you look in the literature there are several suggestions for why it gives a protective effect and they're probably all you know valid and they just give it cumulative in some studies it is predicted to take duty and cooperation in the cell membranes but also the bomb surface properties of those bubbles are altered and less cells actually adhere to the bubble surface so you have less cells transferring to the top where the bubbles burst so another thing that you have to consider in soul culture is that if you utilize if you if you are adjusting pH with alkali then that can actually give you pretty big excursions in pH if you have too little mixing in there and there will probably you're there this has been system with too little mixing because people have thought that the cells were so sensitive to me so if you look for instance that some work done innate constantly the scale using a small diamond to rust and turbine revolving at 60 rpm that's pretty typical energy inputs in itself culture then if you just dipped in pH of 1515 alkali to adjust pH on the surface then that actually gave you pH excursions of 0.8 each minute and that can give you a lower cell viability and a can impede product formation so you can actually get been a liquid blending if you dissipate the same amount of energy by using one of those last I am at the hydrofoil and Palace so you know if you have a situation like this you might want to be thinking about not using a rust and producing a hydrofoil instead the fastest mixing however and therefore the least excursions in pH you will get if you add the feeling point very close to the in pilloried by installing a dip pipe it's often not used because it's considered hard to clean but you can't mean it if you just put in two tanking machines so that you don't have a shadow that they mount handle so it's not impossible and it does give you a very fast mixing so that you don't explosions and if we go over the co2 toxicity then as I already said we need to control the dassault co2 concentration because it's tier two into high concentration can be toxic to the cells the co2 concentration that the soul will depend on what amount of partial pressure of co2 you have in the gas bottles so therefore it's important to have a certain gas flow rate so that you have a sufficiently small partial pressure of co2 in those gas bubbles so one strategy that's probably not really a pipe that much in practice but one strategy 50 actually introduced to Sparta's one introduced fairly big bubbles so that they could help you drive out the co2 and another one that produced small bottles that actually gave you that transfer oxygen into the medium that you need so just to conclude on this I have a suggest the sign here and it's not something that I came up with by habit from a you know a very good reference book in colors mixing in the industrial fermentation that if you're interested in in this topic in itself is a fantastic reference from chaps are called mixing and fermentation and cell culture but what these guys propose and they're too first thought is here they used to work with Merck then they proposed that in all my rectus you should use their modern way the floor a pillar that's the lower pillar against dispersion and then you should combine it with an actual floor hydrofoil that's the of our pillars to provide good liquid mix and you should operate a sufficient intentions intensity to provide that liquid mix I mean you can't operate a too little see either but there will also not be difficult sellers the design should annoy you to pH excursions and that subsurface addition pipes would be most efficient but you need to consider CIP oxygenation requirement should be called to co2 ventilation rage you should try to keep the bubbles above five millimeters and size but practice that can be very difficult to control and then you should use sometimes effective like floor on Ekaterina at least survive master data and I think my time is about to run out I do have a section here about magnetic makes a really short section but if any of you are interested in the magnetic mixes we have one up on display out there and I mean you can just come by and then we can talk magnetic mixes if you want to talk about the differences but they are just to give you three key words they are typically used in bed sizes that are not that big you don't have a mechanical seal through the tank wall like you do with an entertainer they can be used in cell culture but are often used in the downstream processes rather than in actual cell culture so with this I would like to thank you all for your attention and I'm happy to ask any questions you may have maybe a larger thing yeah I mean at least our design is made in such a way that it's actually welded into the bottom of the tank so so there is no way that I can you know introduce one eye up like I would beams with we were talking educators for instance we could have several site intranet potatoes sitting in a tank yeah but it's because of the construction I can't install it like this you know if it's a I can't install it so it's kind of sitting sideways you know what I mean it has to be sitting like this does that answer the question yes but the primary reason why you can't go up in there in science and above a certain size is because it's basically because the the entire device is controlled by magnets right so if I have a very say I have a very large tank 100 meter cube something like that which is not uncommon in an industrial fermentation then I would need a very large impeller to actually handle that and I would have a very hard time actually building a design with suitable bearings and suitable magnets that could actually do this so that where the limitation signs have said but volumes you can handle two magnetic me okay yeah you know I would say if you take the ISO mix system we've used that up to 5,000 centipoise or something like that so you can use that in fairly viscous applications also you know the way we approach is this a little bit that we look at the process that the customer has and then let's say you have a situation where where you want to have really fast mixing which the roto jet mixes will provide but it's also a design where you need to do CIP then often we can design it in such a way that you can use the same device to provide fast mixing and to do use the same device afterwards for the CIP duty then that might be more cost efficient than an impeller solution so the end of the day what we recommend it boils down to looking at the individual application and then finding out what is the most cost efficient yeah and there are areas that we never do with educators like for instance we don't go into a beer fermentation with educators we exclusively use the ISO mix systems there are areas where the ISO my system is too expensive compared to educators for instance if you have milk silo tank now I know that I'm going into applications that are not anywhere related to Farmer but let's say then that you have a very simple storage tank it could be milk whatever then simple silent entry agitator that's pretty cost-effective would be the the choice you don't want to go for something like the rotary jet mixes that can provide you with very fast mixing because you don't really need it you stay in the middle and bottom I mean you are going to have some Sony there is no way around you know I'm not getting any Sony the the point is basically just that it's much less severe than it is with them with actual know sort of radial flowing pillars because there is really severe if you look at studies that's compared them like one to one you will see that if you you will see that that if you're worried one system would say rust and turbines multiple rusted turbines would compare that to multiple multiple actual flow and pillars and you do it at this put in exactly the same amount of power and everything then the mixing time is probably twice in the radial flow and pillar system compared to the actual Florida system you're going to have a certain amount of Sony I would say if you want to if you want to get out of that Sony problem what you really should do is that you should Sidda is taking two deep pipes but a lot of people just don't like the idea about subsurface additions from a sanitary point they like yes to put in substrate on the surface and then keep their fingers crossed that the impellers can you know distribute that fast enough but you would get very fast mixing with for instance radials no impetus if you were just prepared to have to dip pipes one for each each of this moment and then you don't have to consider this only if you use educators for girls depending on the angle are you mean if you have a cylinder conical tank facing you it's a good question because if you look into if you look into the literature then people always use model systems to study them something like this and they always use this bottom because you say that you needed this most bottom to have you know optimal operation nothing in pillar because the disposal will provide you with something where the currents can go down and then go up with sand that's pretty difficult if you have a bottom looking like this so yeah yeah in all our info we tend to have something that was actually there would be a situation where I would personally begin to look at you know maybe maybe a bottom mounted one that was pumping upwards right because then it is pumping off what's it making a little bit the top and then it's going back there but it's not something that's well studied so I can't really back it up a lot of hard facts it's funny if you look in the literature the 99.9% of harrassing has been made with Bethel chains is centrally mounted at potatoes in tanks of an aspect ratio of 1 then if you go out the industry and you look at the industry I mean you do find a few of those but not very many thank you