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**Bioreactor design via spreadsheet––a study on the monosodium glutamate (MSG) process
**

Jolius Gimbun, A.B. Dayang Radiah, T.G. Chuah

*

Department of Chemical and Environmental Engineering, Faculty of Engineering, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia Received 25 June 2003; received in revised form 6 October 2003; accepted 20 October 2003

Abstract Preliminary design calculation of a unit operation is always necessary to determine an order of magnitude of the proposed chemical plant. This paper describes an application of a spreadsheet in preliminary design of a bioreactor. There are a few steps in bioreactor design which are mass/mole balances and energy balances calculations before carrying out the bioreactor sizing. A spreadsheet was used as a tool to make a quick and accurate calculation. Glutamic acid fermentation is used to describe the overall method in this bioreactor design via spreadsheet. The method presented here is easy to learn and easy for the designer to scale up and to simulate diﬀerent operating conditions to meet an optimum design from time to time by changing only a few variable such as ﬂow rate and substrate concentration of the feed in the previously constructed spreadsheet. Ó 2003 Elsevier Ltd. All rights reserved.

Keywords: Bioreactor; Spreadsheet; Glutamic acid; Fermentation; Monosodium glutamate

1. Introduction It is often necessary to develop data for a range of operating conditions, so that the optimum conﬁguration of a bioreactor can be found. There are two conventional methods to perform such a task, either by hand calculation (which is somewhat inaccurate and time consuming) or by any of a number of commercial simulations that are faster but costly to licence. A third alternative is presented here: Insert all the manual calculation equations into any spreadsheet program such as Microsoft Excel. This will eliminate the need for employing expensive simulation software and labouring over hand calculations. Further, the time involved from the programmer’s point of view is no more (or considerably less) than that required to learn how to use a commercial simulation package. Microsoft Excel is a commercial spreadsheet software developed by Microsoftâ Corporation, which is widely used today. Microsoft Excel is part of the package Microsoft Oﬃce and it is fully developed with statistics, mathematical and engineering applications (Bloch,

Corresponding author. Tel.: +60-3-894-662-88; fax: +60-3-865670-99. E-mail address: chuah@eng.upm.edu.my (T.G. Chuah). 0260-8774/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.jfoodeng.2003.10.009

*

2000; Liengme, 1997). One of the engineering applications that is available in Microsoft Excel is a root-ﬁnding function such as Ôsolver’ and Ôgoal seek’ which play an important role in process engineering to ﬁnd a correspondence input with a ﬁxed output. Normally in design, the target output is a ﬁxed variable but the input variable is always very diﬃcult to determine via hand calculation because it requires the designer to run a reversed calculation and work with more than one equation and unknown variable. The method presented here is easy to learn, and oﬀers a quick way to make preliminary estimates of the bioreactor diameter and height, cooling coil required, diameter of baﬄe, impeller, and sparger ring. Fig. 1 shows a basic conﬁguration of a typical bioreactor.

2. Spreadsheet calculation procedure Monosodium glutamate (MSG) is widely used not only by housewives to enhance the taste of dishes but also by professional chefs in restaurants all over the world including Malaysia. It is also added into a variety of processed foods, frozen foods, soups, snacks, instant noodles, etc. The process for producing MSG is a typical bioreaction by applying an enzyme. The ﬁrst step in

W power resultant by micro-organism activity. Typical bioreactor conﬁguration (James & David. °C log mean temperature diﬀerence overall heat transfer coeﬃcient. W heat ﬂow into system work done by system gas constant m3 Pa/mole K temperature. kg/s bioreactor bottom pressure. W/m2 °C density. molarity and molecular weight) and the yield of glutamic acid over glucose. . W net power generated in fermentation. The calculation presented here is based on a glutamic acid fermentation process (Fig. Yx=s into the spreadsheet. Subsequently the reaction spreadsheet was developed based on the stoichiometry of glutamic acid fermentation. °C inlet cooling water temperature. W QB Qq Qw R T T1 T2 Tp TLMTD U q power absorbed by broth.e. density. °C Broth temperature. atm atmospheric pressure. W power absorbed by ammonia. 2. related information on the chemicals utilised (i. kg/m3 bioreactor design calculation is a mass/mole and energy balance on the bioreactor. kJ/kg °C energy mass ﬂow rate. Bioreactor design calculation procedure. 2. / Journal of Food Engineering 64 (2004) 277–283 Nomenclature CP E _ m Pb Patm Pair PAmmonia PF Pe QGen QA QF heat capacity. Mass/mole balance First of all.1. The full mole/mass balance spreadsheet is Fig. °C outlet cooling water temperature.278 J. Fig. W energy produced within the system total power generated in fermentation. W power result by agitation heat. 1986). 2). Gimbun et al. atm power absorbed by air ﬂow. 1.

8 2 3 1–1. The stoichiometric equation of L -glutamic acid fermentation is as follow (Murray.55 kg kg kg kg kg Total inlet 346103.2 2. and air (oxygen supply) required can be calculated. which is equal to the bioreactor working volume. & Whitaker. is estimated as: m ð4Þ V ¼ q Table 1 Bioreactor design criteria (Hall. 1999) Dimension Working volume/bioreactor vessel volume Height/vessel diameter ðH =DÞ Vessel diameter/impeller diameter ðD=Di Þ Sparger ring diameter/impeller diameter ðDs =Di Þ Baﬄe/vessel diameter ðDb =DÞ Foam breaker diameter/vessel diameter ðDFB =DÞ L=Di E=W W =Di Ratio 0.68 MW Fermentation Tank Water 3.in À vout CA.79 m /min Fig. From this mole/mass balance the amount of substrate (glucose).J. constructed by linking each cell from the reaction spreadsheet to the equation and chemical or physical properties.22 kg NH3 3506.4 44044.64 kg 3 3 5. The ideal gas law is applied in the spreadsheet for the automatic calculation of air and ammonia ﬂow rate.09 kg CO2 19217. 3.3 7000 kg L 279 Bacteria Corynebacterium glutamicium Pre Seed Seed Feed C6H12O6 O2 NH3 H2O 339427. Summary of mass and heat transfer from MS Excel spreadsheet.7 m /min Broth 346103.1 0.18 m3/min NH3 Air (O2) 39. 3. ammonia.2 0.8 kg C5H9NO4 30322.00 17276. The summary of the mass/mole balance calculated by the Excel spreadsheet is shown in Fig. Gimbun et al.out þ rA V dt ð1Þ Broth ﬁnal volume.6 0.3 kg L Feed Glucose 6674.8 E1 1.out þ rA V ð2Þ dt The ideal gas law applied to estimates the volume ﬂow rate of gases given as: V _ _ P V ¼ nRT ð3Þ Table 2 Bioreactor sizing spreadsheet .3 277769. 1985): C6 H12 O6 þ 2:21O2 þ 0:84NH3 ! 0:84C5 H9 O4 N þ 1:78H2 O þ 3:74H2 O The mass balance for the component A in a bioreactor vessel as stated in Biotol (1992) is: V dCA _ _ ¼ vin CA.in À vout nA.2 The mole balance of component A of a bioreactor from Biotol (1992) is written as: _ dnA _ _ _ _ ¼ vin nA.99 7013.87 kg H2O 293057. Stanbury.25 1 0. / Journal of Food Engineering 64 (2004) 277–283 Feed Glucose 2. The ideal gas law is considered applicable since the air pressure is not more than 2 atm.

the working volume of the bioreactor can be calculated.280 J. Based on this information the total volume of a bioreactor can be calculated. Table 2 is an example of the constructed spreadsheet for bioreactor sizing (Fig. Bioreactor sizing After performing the mass/mole balance. A typical working volume of a bioreactor is 80% of the total volume as shown in Table 1 (Hall et al. .. / Journal of Food Engineering 64 (2004) 277–283 2. Bioreactor mass/mole balance spreadsheet. 4). Gimbun et al.2. Fig. A spreadsheet for the bioreactor sizing is constructed by linking the cells of working volume in the mass/mole balance spreadsheet to the bioreactor design criteria as shown in Table 1. 1999). 4.

/ Journal of Food Engineering 64 (2004) 277–283 281 The general energy balance equation around the tank is given by Biotol (1992) as: _ dE _ _ ¼ min Ein À mout Eout þ Qq þ Qw þ Pe dt ð5Þ V ¼ pD3 pD3 þ 6 4 ð6Þ 2.J. we estimate it based on the typical For both hemispherical end and H ¼ 2D shape factor. 4 (continued) . bioreactor volume is deﬁned as: Fig. Gimbun et al.3. Energy balance and cooling coil design Since the heat generated by microorganism activity is very hard to predict.

/ Journal of Food Engineering 64 (2004) 277–283 Table 3 Data for typical glutamic acid fermentation from Atkinson and Mavituna (1992) Agitator power required Heat of fermentation Agitation heat Broth temperature Inlet cooling water 15 hp (1000 gal)À1 100 Btu (h)(gal)À1 38 Btu (h)(gal)À1 37–38 °C 10 °C operation data for fermentation as shown in Table 3 (Atkinson & Mavituna. which is equal to the cooling coil duty that is yet. air and ammonia ﬂow rate and the substrate ﬂow rate.282 J. 1992). Gimbun et al. to be designed. The energy balance spreadsheet constructed by linking this design data to the cells of the bioreactor working volume. This spreadsheet will calculate the net fermentation heat generated per unit time (power). Water is chosen as the coolant Table 4 Energy balance and cooling coil design spreadsheet .

Liengme. James.5 m 3 2. (1997). (1992). Sinnott. 3. (7)–(10). carried out MS Excel. B. P. Oxford: Butterworth–Heinemann. E. C. London: Pergamon Press. vol. (1986). & Mavituna. A guide to microsoft excel for scientist and engineers. Conclusions A bioreactor design spreadsheet is easy to learn. Oxford: Butterworth–Heinemann. D. London: M Stockton Press. New York: McGraw-Hill. M. Oxford: Butterworth–Heinemann.64 atm 36. B.1 m2 73 mm 63 mm 4. of turbine Impeller diameter Impeller di =dt ratio Motor power required Heat load U Coolant inlet temperature (water) Coolant ﬂow Coil side velocity Coil area required Coil pipe diameter OD Coil pipe diameter ID Coil diameter Coil spacing No. Comprehensive biotechnology. Biotol (1992). (1985). F. Stanbury. A. New York: McGraw-Hill. & David.22 m 6 mm 0. (1999). F..J.1 m3 /min 7. & Whitaker. Process heat transfer. B.12 m 0. A larger coolant inlet will reduce the ﬂow rate of coolant without reducing the total heat transfer area so that the tendency will be to reduce the coolant side velocity into the correct operating range. The energy contained in the liquid is given by Kern (1965) as: _ P ¼ mCP DT ð7Þ References Atkinson. Tey Beng Ti and Ajinomoto (Malaysia) Berhad for their guidance and support. . The heat transfer area. of coil Area provided Value 290 m3 231 m3 6m 2 80 1 atm 1. Excel for engineers and scientists. and oﬀers a quicker way for preliminary calculation of the bioreactor design. By using this method the designer also escapes the costly simulation software license. The purpose of coolant side velocity or coil inner velocity calculation is to check whether the design is applicable or not. New York: John Wiley. Bioprocess technology: modelling and transport phenomena. This method also oﬀers an easy way for the designer to scale up and optimise the process.. because it is cheap and available. Bloch. vol.2 m3 /min 1. F.3 9.). Y. (1965). (1996). which is commonly used in design calculation. A spreadsheet also eliminates human error in doing the iteration calculation. Acknowledgements The authors would like to thank very much to Dr. Biochemical engineering and biotechnology handbook (2nd ed. Gimbun et al. S. Biochemical engineering fundamentals (2nd ed.6 m3 /min 5. Principle of fermentation technology (2nd ed.8 m3 /min 2. The way to overcome such a problem is to design a larger coolant. / Journal of Food Engineering 64 (2004) 277–283 Table 5 Summary of calculated results Parameter Total volume Liquid volume (working volume) Tank OD Total height/diameter Percentage ﬁll Pressure (liquid surface) Pressure (bottom) Air ﬂow rate Oxygen ﬂow rate Ammonia ﬂow rate Sparger diameter Sparger hole diameter Sparger pipe diameter Oﬀ segmented baﬄe (total) db Baﬄe ratio db =dt 0 Baﬄe plate db No. 6 (2nd ed.). O.. Q. Murray. V.53 m 0. Kern.7 MW 550 W/m2 °C 10 °C 3. (2000).). J. S.. A spreadsheet to calculate heat transfer area required is then constructed by linking Eqs. Table 4 shows an example of the constructed spreadsheet for the energy balance and design of the cooling coil. K.06 m 64 209.6 m 1/10 0. The design parameter such as cooling pipe diameter and size of coolant inlet are ﬁxed by the designer. Hall.). TLMTD is deﬁned as: TLMTD ¼ ðT1 À T1 Þ ln½ðTP À T2 Þ=ðTP À T1 Þ ð9Þ Duty of a cooling coil with heat transfer coeﬃcient U is given by Sinnott (1996) as: P ¼ UATLMTD ð10Þ Table 5 shows the summary results of the bioreactor design.1 m 0. If the coolant side velocity is larger than 2 m/s mean then the designed cooling coil is not applicable because of lack in heat transfer. The spreadsheet method also provides a cheaper alternative to the designer compared to costly commercial software.62 m/s 206. Coulson and Richardson’s chemical engineering. 4.4 m2 283 _ By substituting m ¼ vq the energy contained in the gasses phase is written as: _ ð8Þ P ¼ vqCP DT the log mean temperature diﬀerence.8 MW 1. pipe diameter and size of inlet value are used to determine the coolant side velocity. London: Arnold. R.

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