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Analytical & Pharmaceutical Research

Research Article Volume 7 Issue 5

Comparison of particle swarm optimization and genetic algorithm for multiproduct batch plant design of protein production

Youness El Hamzaoui, Juan Antonio Alvarez Arellano

Correspondence: Youness El Hamzaoui, Facultad de Ingenier, Tel 00521(999)9601138

Received: January 15, 2018 | Published: September 20, 2018

Citation: El Hamzaoui Y, Alvarez Arellano JA. Comparison of particle swarm optimization and genetic algorithm for multiproduct batch plant design of protein production. J Anal Pharm Res. 2018;7(5):553-563. DOI: 10.15406/japlr.2018.07.00282

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Abstract

This work deals with the problem of the optimization of multiproduct batch plant design (MBPD) found in a chemical engineering process. The aim of this work is to minimize the investment cost and find out the number and size of parallel equipment units in each stage. For this purpose, it is proposed to solve the problem in two different ways: the first way is by using particle swarm algorithms (PSA) and the second way is by genetic algorithms (GAs). This paper presents the effectiveness and performance comparison of PSA and GAs for optimal design of multiproduct batch plant. The calculation results (investment cost, number and size of equipment, computational time, CPU time and idle times in plant) obtained by GAs are better than PSA. This methodology can help the decision makers and constitutes a very promising framework for finding asset of good solutions.

Keywords: mathematical modeling, chemical engineering optimization, particle swarm algorithms, genetic algorithms, batch plant design

Introduction

Pharmaceutical researchers and biotechnology companies are devoted to developing medicines, such as: therapeutic proteins, human insulin, vaccines for hepatitis, food grade protein, chymosin detergent enzyme, and cryophilic protease. This allows patients to live longer, heathier, and more productive. However, in recent years, there has been an increased interest development of systematic method for the design of batch process in chemicals, food products, and pharmaceutical industries. Basically, batch plants are composed of items operating in a discontinuous way, where each batch then visits a fixed number of equipment items, as required by a given synthesis sequence so called production recipe. Many works in the literature on batch process design are based on expressions that relate the batch sizes linearly with the equipment sizes.1–10 The number required of volume and size of parallel equipment units in each stage is to be determined. Nevertheless, the design of batch plants requires involving how equipment may be utilized. However you look at it the optimal design of a multiproduct batch chemical process involves the production requirement of each product and the total production time available for all products has been considered. The number and size of parallel equipment units in each stage as well as the location and size of intermediate storage are to be determined in order to minimize the investment cost.

The aim of this work was to solve the multiproduct batch plant design problem using (PSA) and (GAs), respectively. The model presented is general, it takes into account all the available options to increase the efficiency of the batch plant design: unit duplication in-phase and out-phase and intermediate storage tanks.

We have found out that PSA performed effectively and gave a solution, but we would like to solve the problem more effectively, that’s why we proposed to apply GAs, an intelligent problem-solving method that has demonstrated its effectiveness in solving combinatorial optimization problem, and satisfactory results have been obtained.

Materials and methods

System description and experimental data

The case study, taken from the literature, is a multiproduct batch plant for the production of proteins.11 This example is used as a test bench since it provides models describing the unit operations involved in the process. The batch plant involves eight stages for producing four recombinant proteins, on one hand, two therapeutic proteins, human insulin (A) and vaccine for hepatitis (B) and, on the other hand, a food grade protein, chymosin (C), and a detergent enzyme, cryophilic protease (D). Figure 1 is the flowsheet of the multiproduct batch plant considered in this study. All the proteins are produced as cells grow in the fermenter. It is hardly necessary to say that the number of intermediate storage tanks is an important constituent of our process: Three tanks have been selected: the first after the fermenter, the second after the first ultrafilter, and the third after the second ultrafilter.

Figure 1 Multiproduct batch plant for protein production.

Vaccines and protease are considered to be intracellular. The first microfilter is used to concentrate the cell suspension, which is then sent to the homogenizer for the second microfilter, which is used to remove the cell debris from the solution proteins. The first ultrafiltration step is designed to concentrate the solution in order to minimize the extractor volume. In the liquid–liquid extractor, salt concentration (NaCl) is used as solution in order to minimize the extractor volume. In the liquid–liquid extractor, salt concentration (NaCl) is used to first drive the product to a poly-ethylene-glycol (PEG) phase and again into an aqueous saline solution in the back extraction. The second ultrafiltration is used again to concentrate the solution. The last stage is chromatography, during which selective binding is used to better separate the product of interest from the other proteins.

Insulin and chymosin are extracellular products. Proteins are separated from the cells in the first microfilter, where cells and some of the supernatant liquid stay behind to reduce the amount of valuable products lost in the retentate, extra water is added to the cell suspension. The homogenizer and the second microfilter for cell debris removal are not used when the product is extracellular. Nevertheless, the first ultrafilter is necessary to concentrate the dilute solution prior to extraction. The final step of extraction, second ultrafiltration, and chromatography are common to both the extracellular and intracellular products. In Table 1 we make an estimation of production targets and product prices.12–14

Problem statement

The model formulation for DMBP’s problem approach adopted in this section is based on Montagna el al.15 It considers not only treatment in batch steps, which usually appear in all types of formulation, but also represents semi continuous units that are part of the whole process (pumps, heat exchangers, etc). A semi-continuous unit is defined as a continuous unit alternating idle times and normal activity periods. Besides, this formulation takes into account mid-term intermediate storage tanks, the obligatory mass balance at the intermediate storage stage, which is one of the most efficient strategies to decouple bottlenecks in batch plant design. They are just used to divide the whole process into subprocesses in order to store an amount of materials corresponding to the difference of each sub-process productivity. In this section we describe the unit models from a conceptual standpoint and also the procedure to derive the data needed for solving the mathematical model. These data are summarized in Table 2 & Table 3.

Most of the separation processes information are taken from Asenjo and Patrick.,16 the posynomial modeling approach is taken from Salomone and Iribarren.,17 The general batch process literature as reported in,18 describes batch stages j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ through a sizing equation and a cycle time that are applied for a product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@  as follows:

V j S ij B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=zfa juaGdaWgaaWcbaqcLbmacaWFQbaaleqaaKqzGeGaa8xzIiaa=nfaju aGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaa=jeajuaG daWgaaWcbaqcLbmacaWFPbaaleqaaaaa@5055@   (1)

Where V j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFwbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A43@  is the size of stage , e.g., m 3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=1ga juaGdaahaaWcbeqaaKqzadGaa83maaaaaaa@45C9@ of the vessel, B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFcbqcfa4aaSbaaSqaaKqzadGaa8xAaaWcbeaaaaa@3A2E@  is the batch size for product , e.g., kg MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFRbGaa83zaaaa@3862@  of product exiting from the last stage, S ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFtbqcfa4aaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3B2A@  is the size factor of stage  product , i.e., the size needed at stage to produce 1kg MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=fda caaMc8Uaa83Aaiaa=Dgaaaa@464F@ of final product  and T ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFubqcfa4aaSbaaKqaGfaajugWaiaa=LgacaWFQbaajeaybeaaaaa@3BE9@  is the time required to process a batch of product  in stage  considering the fermentor and the insulin product as an example. If we estimate a final concentration of dry biomass/ m 3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jga caWFPbGaa83Baiaa=1gacaWFHbGaa83Caiaa=nhacaWFVaGaa8xBaK qbaoaaCaaaleqabaqcLbmacaWFZaaaaaaa@4CEE@ , that 0.4 of this biomass is proteins and 0.05 of these proteins is insulin, and an overall yield estimate of the process of 0.8 (0.8 of the insulin produced in the fermenter exits the chromatographic column), then the size factor for the fermenter for producing insulin can be estimate as

S ij = m 3 50kg×0.4×0.05×0.8 =1.25 m 3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=nfa juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaaykW7ca WF9aGaaGPaVNqbaoaalaaakeaajugibiaa=1gajuaGdaahaaWcbeqa aKqzadGaa83maaaaaOqaaKqzGeGaa8xnaiaa=bdacaWFRbGaa83zai aa=DnacaWFWaGaa8Nlaiaa=rdacaWFxdGaa8hmaiaa=5cacaWFWaGa a8xnaiaa=DnacaWFWaGaa8Nlaiaa=HdaaaGaaGPaVlaa=1dacaaMc8 Uaa8xmaiaa=5cacaWFYaGaa8xnaiaa=1gajuaGdaahaaWcbeqaaKqz adGaa83maaaaaaa@68F9@ (2)

Similarly, vaccine, chymosine, and cryophilic protease were estimated to be 0.1, 0.15, and 0.2 of total proteins of the biomass, respectively. The batch stage description is completed by estimating a processing time  for stage when producing product . For the fermenter, we estimate T ij =24h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaaykW7ca WF9aGaaGPaVlaa=jdacaWF0aGaaGPaVlaa=Hgaaaa@4F1A@  for all products, which includes time for charging, cell growth, and discharging.

This model of batch stages given by constraint (1a) is the simplest one. Its level of detail suffices for the fermenter and the extractor. These units are truly batch items chat hold the load to be processed and whose operations are governed by kinetics, and hence, the operating time does not depend on the batch size. The first approximation for the extractor, we take a phase ratio of (1b) for all products. Therefore, the required extractor volume is twice the inlet batch volume, while the inlet and outlet aqueous saline batches are of the same volume. It is also assumed, as a result of preliminary balances, that this operation reduces the total amount of proteins to about twice the amount of the target protein. with respect to the kinetic effects we take as first estimates19 the following times: 15 min stirring to approach phase equilibrium, 30 min settling to get almost complete disengaging of the phases, and 20 min for charging and discharging. A special consideration must be done in the case of the microfiltration, homogenization, and ultrafiltration stages. Although the mathematical model considers them batch stages, their corresponding equipment consists of holding vessels and semicontinous units that operate on the material that is recirculated into the holding vessel. The batch items are sized as described before. For example, for the homogenizer processing cryophilic protease, we estimated that the fermentor broth is concentrated 4 times up to 200kg/ m 3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jda caWFWaGaa8hmaiaaykW7caWFRbGaa83zaiaa=9cacaWFTbqcfa4aaW baaSqabeaajugWaiaa=ndaaaaaaa@4BED@  at microfilter 1 and considered a yield of 1 because the intracellular protease is fully retained at the microfilter. Then the size factor of the homogenizer vessel is 4 times smaller than the fermenters, i.e., S ij =0.08 m 3 /kg MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=nfa juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaa=1daca aMc8Uaa8hmaiaa=5cacaWFWaGaa8hoaiaa=1gajuaGdaahaaWcbeqa aKqzadGaa83maaaajugibiaaygW7caWFVaGaa83Aaiaa=Dgaaaa@54A4@ protease. The sizing equation for semicontinuous items can also be found in the general batch processes literature:20

R j = D ij B i θ ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jfa juaGdaWgaaWcbaqcLbmacaWFQbaaleqaaKqzGeGaaGPaVlaa=1daca aMc8Uaa8hraKqbaoaaBaaaleaajugWaiaa=LgacaWFQbaaleqaaKqb aoaalaaakeaajugibiaa=jeajuaGdaWgaaWcbaqcLbmacaWFPbaale qaaaGcbaqcLbsacaWF4oqcfa4aaSbaaSqaaKqzadGaa8xAaiaa=Pga aSqabaaaaaaa@5953@ (3)

Where R j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiGaa8Nuam aaBaaaleaajugWaiaa=PgaaSqabaaaaa@3922@  is the size of the semicontinuous item k MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFRbaaaa@377A@ , usually a rate of processing. For example, in the case of the homogenizer, it is the capacity in cubic meters of suspension per hour, but in the case of the filters  is their area of filtration A j ( m 2 ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=fea juaGdaWgaaWcbaqcLbmacaWFQbaaleqaaKqbaoaabmaakeaajugibi aa=1gajuaGdaahaaWcbeqaaKqzadGaa8NmaaaaaOGaayjkaiaawMca aaaa@4C22@ . B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFcbqcfa4aaSbaaSqaaKqzadGaa8xAaaWcbeaaaaa@3A2E@  is again the batch size, θ ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=H7a juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaaaaa@4742@ is the operating time that the semicontinuous itemneeds to process a batch of product, and D ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFebqcfa4aaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3B1B@ is the duty factor (a size factor for semicontinuous items), i.e., the size needed at stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ to process 1kg of product  in 1h. For example, if we adopt three passes through the homogenizer, its duty factor is the vessel size factor 0.08 m 3 /kg×3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=bda caWFUaGaa8hmaiaa=HdacaaMc8Uaa8xBaKqbaoaaCaaaleqabaqcLb macaWFZaaaaKqzGeGaa83laiaa=TgacaWFNbGaaGPaVlaa=DnacaWF Zaaaaa@50C8@ , i.e., D ij =0.24 m 3 /kg. MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rea juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaaykW7ca WF9aGaaGPaVlaa=bdacaWFUaGaa8Nmaiaa=rdacaaMc8Uaa8xBaKqb aoaaCaaaleqabaqcLbmacaWFZaaaaKqzGeGaa83laiaa=TgacaWFNb Gaa8Nlaaaa@56CE@  The meaning of a capacity of 0.24 m 3 /h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=bda caWFUaGaa8Nmaiaa=rdacaaMc8Uaa8xBaKqbaoaaCaaaleqabaqcLb macaWFZaaaaKqzGeGaa83laiaa=Hgaaaa@4C44@  is that it allows 1kg MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=fda caaMc8Uaa83Aaiaa=Dgaaaa@464F@  of final product cryophilic protease to be processed in 1h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=fda caWFObaaaa@43D9@ .

The general batch processes literature considers semicontinuous units to work in series with batch units so that their operating time are the times for filling or emptying the batch units. However, in the process considered, pumps are the only semicontinuous units, which transfer batches between the units. As the pumps cost does not have a relevant impact on the plant design, they were not explicitly modeled. The times for filling and emptying batch items were estimated and included in the batch cycle times. On the other hand, the process does have special semicontinuous units with an important economic impact on the cost. They are the homogenizer and ultrafilters, but their operating time is the batch processing time of the respective stage. The mathematical model depends on both the batch size and the size of the semicontinuous item are as follows:

V j S ij B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=zfa juaGdaWgaaWcbaqcLbmacaWFQbaaleqaaKqzGeGaa8xzIiaa=nfaju aGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaa=jeajuaG daWgaaWcbaqcLbmacaWFPbaaleqaaaaa@5055@ (4a)

            

T ij = T ij 0 + T ij 1 B i R j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa juaGdaWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaaykW7ca WF9aGaaGPaVlaa=rfajuaGdaqhaaWcbaqcLbmacaWFPbGaa8NAaaWc baqcLbmacaWFWaaaaKqzGeGaaGPaVlaa=TcacaaMc8Uaa8hvaKqbao aaDaaaleaajugWaiaa=LgacaWFQbaaleaajugibiaa=fdaaaGaaGPa VNqbaoaalaaakeaajugibiaa=jeajuaGdaWgaaWcbaqcLbmacaWFPb aaleqaaaGcbaqcLbsacaWFsbqcfa4aaSbaaSqaaKqzadGaa8NAaaWc beaaaaaaaa@6697@ (4b)

   

Where R j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFsbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A3F@ refers to the size of the semicontinuous item that operates on the batch size at stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ . T ij 0 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa juaGdaqhaaWcbaqcLbmacaWFPbGaa8NAaaWcbaqcLbmacaWFWaaaaa aa@48BB@  and T ij 1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa lmaaDaaabaqcLbmacaWFPbGaa8NAaaWcbaqcLbmacaWFXaaaaaaa@482E@  are appropriate time factors that take into account contributions to the total cycle time of the stage that are either fixed amounts of time or proportional to the batch size and inversely proportional to the size of the semicontinuous item. For the homogenizer, R j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFsbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A3F@  is its capacity, T ij 1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa lmaaDaaabaqcLbmacaWFPbGaa8NAaaWcbaqcLbmacaWFXaaaaaaa@482E@  the duty factor of the homogenizer itself, and T ij 0 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa juaGdaqhaaWcbaqcLbmacaWFPbGaa8NAaaWcbaqcLbmacaWFWaaaaa aa@48BB@ includes the estimated times for filling and emptying the homogenizer holding vessel. In the case of ultrafilters, a fixed permeate flux model was considered with a rate of 20L/ m 2 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jda caWFWaGaaGPaVlaa=XeacaWFVaGaa8xBaKqbaoaaCaaaleqabaqcLb macaWFYaaaaaaa@4A34@ of membrane area/h. In this case, the size of the semicontinuous item R j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFsbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A3F@  is the filtration area. T ij 0 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=rfa juaGdaqhaaWcbaqcLbmacaWFPbGaa8NAaaWcbaqcLbmacaWFWaaaaa aa@48BB@ is again the time for filling and emptying the retentate holding vessel, and is the inverse of the permeate flux times the ratio ( m 3 permeate/kg ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaqcfa4aaeWaaO qaamXvP5wqSX2qVrwzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbac fiqcLbsacaWFTbqcfa4aaWbaaSqabeaajugWaiaa=ndaaaqcLbsaca aMc8Uaa8hCaiaa=vgacaWFYbGaa8xBaiaa=vgacaWFHbGaa8hDaiaa =vgacaaMc8Uaa83laiaa=TgacaWFNbaakiaawIcacaGLPaaaaaa@5578@ . This ratio is estimated from a mass balance taking into account that the ultrafilters are used for a water removal from solutions up to 50g/L MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=vda caWFWaGaaGjbVlaa=DgacaWFVaGaa8htaaaa@4797@  of total proteins. Ultrafilters are used to reduce the volume required at the liquid extractor and the chromatographic column. The upper bound on concentration is a constraint that avoids protein precipitation. The microfilter model is quite similar to that of the ultrafilter, but there are two batch items associated to them instead of one, the retentate and the permeate vessels, plus the semicontinuous item area of filtration. For microfilter 1 a fixed permeate flux of 200L/ m 2 h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jda caWFWaGaa8hmaiaaykW7caWFmbGaa83laiaa=1gajuaGdaahaaWcbe qaaKqzadGaa8Nmaaaajugibiaa=Hgaaaa@4C5D@  is adopted. For extracellular insulin and chymosin, we estimate a total permeate (feedwater plus make up water) twice the feed, while for intracellular protease and vaccine we estimate it in 75% of the feed (the retentate is concentrated four times). For microfilter 2 a fixed permeate flux model is also used. In this case, the flux is smaller than the one in microfilter 1 because the pore size to retain cell debris is smaller than the one for whole cells. As a first estimation we take 100L/ m 2 h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=fda caWFWaGaa8hmaiaaykW7caWFmbGaa83laiaa=1gajuaGdaahaaWcbe qaaKqzadGaa8Nmaaaajugibiaa=Hgaaaa@4C5C@  and a total permeate (feed plus make up water) twice the feed. With respect to the chromatographic column, an adsorptive type chromatography is considered, with a binding capacity of 20kg/ m 3 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=jda caWFWaGaa83Aaiaa=DgacaWFVaGaa8xBaKqbaoaaCaaaleqabaqcLb macaWFZaaaaaaa@49B1@  of column packing. The size factor of this unit is the inverse of that binding capacity. As a first approximation, a fixed total operating time of 0.5h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=bda caWFUaGaa8xnaiaa=Hgaaaa@453D@  was estimated for loading, eluting, and washing regeneration. Finally, the stage model is completed with a cost model that expresses the cost of each unit as a function of its size, in the form of a power law. These expressions are summarized in Table 4, with most of the cost data.20

Model equations The mathematical optimization model for designing the multiproduct batch plant is described in this section. The model includes the stage models described in the previous section plus additional constraints that are explained in this section. The plant consists of M MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFnbaaaa@375C@  batch stages (in our case 8 batch stages). Each stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@  has a size V j ( m 3 ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=zfa juaGdaWgaaWcbaqcLbmacaWFQbaaleqaaKqbaoaabmaakeaajugibi aa=1gajuaGdaahaaWcbeqaaKqzadGaa83maaaaaOGaayjkaiaawMca aaaa@4C38@ , and more than one unit can be installed in parallel. They can work either in-phase (starting operation simultaneously) or out of phase (starting times are distributed equally spaced between them). The duplication in phase is adopted in case the required stage size exceeds the specific upper bound. In this case G j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFhbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A34@ units are selected, splitting the incoming batch into G j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFhbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A34@  smaller batches, which are processed simultaneously by the G j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFhbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A34@ units. After processing, the batches are added again into a unique outgoing batch. Otherwise, duplication out-of-phase is used for time-limiting stages, if a stage has the largest processing time, then it is a bottleneck for the production rate. Assigning M j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFnbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A3A@  units at this stage, working in out of phase mode, reduces the limiting processing time and thus increases the production rate of the train. For this case, the batches coming from the upstream stages are not split. Instead, successive batches produced by the upstream stage are received by different units of stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ , which in turn pass them at equally spaced times onto the downstream batch stage. The allocation and sizing of intermediate storage has been included in the model to get a more efficient plant design. The goal is to increase unit utilization. The insertion of a storage tank decouples the process into two subprocesses: one upstream from the tank, and the other downstream. This allows the adoption of independent batch sizes and limiting cycle times for each subprocess.
Therefore, the previously unique B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFcbqcfa4aaSbaaSqaaKqzadGaa8xAaaWcbeaaaaa@3A2E@ is changed to batch sizes B ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFcbqcfa4aaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3B19@ defined for product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@ in stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ . Appropriate constraints adjust the batch sizes among different units. The objective is to minimize the capital cost of the plant. The decision variables in the model are as follows:

At each batch stage the number of parallel units in phase and out of phase and their size, and the installation or absence of intermediate storage between the batch stages and their size. The plant is designed to satisfy a demand of Q i ( kg ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFrbqcfa4aaSbaaSqaaKqzadGaa8xAaaWcbeaajuaGdaqadaGcbaqc LbsacaWFRbGaa83zaaGccaGLOaGaayzkaaaaaa@3ECB@  of each product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@ , for the P MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFqbaaaa@375F@ product considered, within a time horizon H( h ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFibqcfa4aaeWaaOqaaKqzGeGaa8hAaaGccaGLOaGaayzkaaaaaa@3AFA@ . In summary, the objective function to be optimized is

MinCost= j=1 M M j G j a j V j α j + j=1 M V T j η j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaWexLMBbXgBd9 gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugibiaa=1ea caWFPbGaa8NBaiaa=neacaWFVbGaa83Caiaa=rhacaaMc8Uaa8xpai aaykW7juaGdaaeWbGcbaqcLbsacaWFnbqcfa4aaSbaaSqaaKqzadGa a8NAaaWcbeaajugibiaa=DeajuaGdaWgaaWcbaqcLbmacaWFQbaale qaaKqzGeGaa8xyaKqbaoaaBaaaleaajugWaiaa=PgaaSqabaqcLbsa caWFwbqcfa4aa0baaSqaaKqzadGaa8NAaaWcbaqcLbmacaWFXoWcda WgaaadbaqcLbmacaWFQbaameqaaaaajugibiaa=TcajuaGdaaeWbGc baqcLbsacaWFwbGaa8hvaKqbaoaaDaaaleaajugWaiaa=PgaaSqaaK qzadGaa83TdSWaaSbaaWqaaKqzadGaa8NAaaadbeaaaaaaleaajugW aiaa=PgacaWF9aGaa8xmaaWcbaqcLbmacaWFnbaajugibiabggHiLd aaleaajugWaiaa=PgacaWF9aGaa8xmaaWcbaqcLbmacaWFnbaajugi biabggHiLdaaaa@7F0D@ (5)

              

Where α j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqySde McdaWgaaWcbaacbiqcLbmacaWFQbaaleqaaaaa@3BC1@  and α j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqySde McdaWgaaWcbaacbiqcLbmacaWFQbaaleqaaaaa@3BC1@ , c j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 3yaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B06@ and η j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaceaaqrqcLbsacq aH3oaAkmaaBaaaleaaieGajugWaiaa=PgaaSqabaaaaa@3C25@  are appropriate cost coefficients that depend on the type of equipment being considered. V T j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 Nvaiaa=rfakmaaBaaaleaajugWaiaa=PgaaSqabaaaaa@3BCE@ is the size of the storage tank allocated after stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ . The size of each unit has to be large enough to be able to process every product:

V j S ij B ij G j i=1,...,P;j=1,...,M MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbGc daWgaaWcbaqcLbmacaWFQbaaleqaaKqzGeGaa8xzIOWaaSaaaeaaju gibiaa=nfakmaaBaaaleaajugWaiaa=LgacaWFQbaaleqaaKqzGeGa a8NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaakeaajugibi aa=DeakmaaBaaaleaajugWaiaa=PgaaSqabaaaaKqzGeGaaGPaVlaa =bGicaWFPbGaa8xpaiaa=fdacaWFSaGaa8Nlaiaa=5cacaWFUaGaa8 hlaiaa=bfacaWF7aGaa8haIiaa=PgacaWF9aGaa8xmaiaa=XcacaWF UaGaa8Nlaiaa=5cacaWFSaGaa8xtaaaa@6690@ (6)

    Where S ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 3uaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3BE0@ is the size factor for product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@  in stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ . In case of parallel units working in phase, the division of B ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFcbqcfa4aaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3B19@ by the number of units G j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFhbqcfa4aaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3A34@  takes into account the reduction in the batch size to be processed by these units. The operation time T ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hvaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3BE1@  to process product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@ at stage j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ has the general following form:

T ij = T ij 0 + T ij 1 B ij R j i=1,...,P;j=1,...,M MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFubGc daWgaaWcbaqcLbmacaWFPbGaa8NAaaWcbeaajugibiaaykW7caWF9a GaaGPaVlaa=rfakmaaDaaaleaajugWaiaa=LgacaWFQbaaleaajugW aiaa=bdaaaqcLbsacaWFRaGaa8hvaOWaa0baaSqaaKqzadGaa8xAai aa=PgaaSqaaKqzadGaa8xmaaaakmaalaaabaqcLbsacaWFcbGcdaWg aaWcbaqcLbmacaWFPbGaa8NAaaWcbeaaaOqaaKqzGeGaa8NuaOWaaS baaSqaaKqzadGaa8NAaaWcbeaaaaqcLbsacaaMc8UaaGPaVlaaykW7 caaMc8UaaGPaVlaa=bGicaWFPbGaaGPaVlaa=1dacaaMc8Uaa8xmai aa=XcacaWFUaGaa8Nlaiaa=5cacaWFSaGaa8huaiaa=TdacaWFaiIa a8NAaiaa=1dacaWFXaGaa8hlaiaa=5cacaWFUaGaa8Nlaiaa=Xcaca WFnbaaaa@7C18@ (7)

             Where j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ and j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ are appropriate constants that depend on both the product and the stage. Expression 7 accounts for a fixed and variable contribution to the total operating time. The last term in Eq 7 depends on both the batch size and the size of the semicontinuous item associated to this batch stage, as was already discussed previousely.

The limiting cycle time for product h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hAaaaa@38B1@  in the subprocess T L h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hvaiaa=XeakmaaCaaaleqabaqcLbmacaWFObaaaaaa@3BB8@ , , is the largest processing time in this production train:

T L i h T ij M j i=1,...,P;j J j ;h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFubGa a8htaKqbaoaaDaaaleaajugWaiaa=LgaaSqaaKqzadGaa8hAaaaaju gibiaa=vMikmaalaaabaqcLbsacaWFubGcdaWgaaWcbaqcLbmacaWF PbGaa8NAaaWcbeaaaOqaaKqzGeGaa8xtaOWaaSbaaSqaaKqzadGaa8 NAaaWcbeaaaaqcLbsacaaMc8UaaGPaVlaaykW7caaMc8UaaGPaVlaa =bGicaWFPbGaaGPaVlaa=1dacaaMc8Uaa8xmaiaa=XcacaWFUaGaa8 Nlaiaa=5cacaWFSaGaa8huaiaa=TdacaaMc8Uaa8haIiaa=PgacaWF iiIaa8NsaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaajugibiaa=Tdaca aMc8Uaa8haIiaa=Hgaaaa@72C1@ (8)

        

Where J h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 NsaOWaaSbaaSqaaKqzadGaa8hAaaWcbeaaaaa@3AEB@  is the set of units which conform the subprocess h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hAaaaa@38B1@  the division by the number of units in parallel working out of phase, M j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xtaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3AF0@  takes into account the reduction in the cycle time of this stage due to the operation of M j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xtaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3AF0@ units that alternatively process the consecutive batches. To avoid accumulation of material, the processing rate of both subprocess downstream and upstream of the storage tank must be the same:

( B i d T L i d )=( B i u T L i u )i=1,2,...,P MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaabmaabaWaaS aaaeaatCvAUfeBSn0BKvguHDwzZbqegauqYLwySbsvUL2yVrwzG00u aGqbcKqzGeGaa8NqaKqbaoaaDaaaleaajugWaiaa=LgaaSqaaKqzad Gaa8hzaaaaaOqaaKqzGeGaa8hvaiaa=XeajuaGdaqhaaWcbaqcLbma caWFPbaaleaajugWaiaa=rgaaaaaaaGccaGLOaGaayzkaaqcLbsaca aMc8Uaa8xpaiaaykW7kmaabmaabaWaaSaaaeaajugibiaa=jeajuaG daqhaaWcbaqcLbmacaWFPbaaleaajugWaiaa=vhaaaaakeaajugibi aa=rfacaWFmbqcfa4aa0baaSqaaKqzadGaa8xAaaWcbaqcLbmacaWF 1baaaaaaaOGaayjkaiaawMcaaKqzGeGaaGPaVlaaykW7caaMc8UaaG PaVlaaykW7caWFaiIaa8xAaiaaykW7caWF9aGaaGPaVlaa=fdacaWF SaGaa8Nmaiaa=XcacaWFUaGaa8Nlaiaa=5cacaWFSaGaa8huaaaa@798D@ (9)

              

The constraints 9 equalizes the production rate upstream and downstream of the storage tank. To express 9 in a simple form, the inverse of the production rate of product i( E i ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xAaOWaaeWaaeaajugibiaa=veakmaaBaaaleaajugWaiaa=LgaaSqa baaakiaawIcacaGLPaaaaaa@3DFD@ , is defined as

E i = T L i h B ij i=1,2,...,P;j J h ;h MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFfbGc daWgaaWcbaqcLbmacaWFPbaaleqaaKqzGeGaaGPaVlaa=1dacaaMc8 UcdaWcaaqaaKqzGeGaa8hvaiaa=XeajuaGdaqhaaWcbaqcLbmacaWF PbaaleaajugWaiaa=Hgaaaaakeaajugibiaa=jeakmaaBaaaleaaju gWaiaa=LgacaWFQbaaleqaaaaajugibiaaykW7caaMc8UaaGPaVlaa ykW7caaMc8Uaa8haIiaa=LgacaaMc8Uaa8xpaiaaykW7caWFXaGaa8 hlaiaa=jdacaWFSaGaa8Nlaiaa=5cacaWFUaGaa8hlaiaa=bfacaWF 7aGaa8haIiaa=PgacaWFiiIaa8NsaOWaaSbaaSqaaKqzadGaa8hAaa Wcbeaajugibiaa=TdacaaMc8Uaa8haIiaa=Hgaaaa@7545@ (10)

     Expression 10 is used to replace T L i n MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaceaaMhacbiqcLb sacaWFubGaa8htaKqbaoaaDaaaleaajugWaiaa=LgaaSqaaKqzadGa a8NBaaaaaaa@3F4F@ in constraint 8, dropping constraint 9. The production constraint is posed as follows: during the time horizon H MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hsaaaa@3891@ the plant must produce the target production quantities Q i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xuaOWaaSbaaSqaaKqzadGaa8xAaaWcbeaaaaa@3AF3@ of each product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@ . The number of batches of each product i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFPbaaaa@3778@  to be produced during time H MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hsaaaa@3891@  is Q i B i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaalaaabaacbi qcLbsacaWFrbGcdaWgaaWcbaqcLbmacaWFPbaaleqaaaGcbaqcLbsa caWFcbGcdaWgaaWcbaqcLbmacaWFPbaaleqaaaaaaaa@3EB8@ , and the production of each batch demands a time T L i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hvaiaa=XeakmaaBaaaleaajugWaiaa=LgaaSqabaaaaa@3BC3@ , The following constraints holds:

i=1 P Q i E i H MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaaqahabaWexL MBbXgBd9gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugi biaa=ffakmaaBaaaleaaieGajugWaiaa+LgaaSqabaqcLbsacaWFfb GcdaWgaaWcbaqcLbmacaGFPbaaleqaaKqzGeGaa8hzIiaa=HeaaSqa aKqzadGaa4xAaiaa=1dacaWFXaaaleaajugWaiaa=bfaaKqzGeGaey yeIuoaaaa@550E@ (11)

          

The size of the storage tank V T j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 Nvaiaa=rfakmaaBaaaleaajugWaiaa=PgaaSqabaaaaa@3BCE@ , allocated after batch stage j MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaamOAaaaa@36E6@ , is given by the following expression:25

V T j S T ij ( B ij + B ij+1 )i=1,...,M;j=1,...,M-1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbGa a8hvaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaajugibiaa=vMicaWFtb Gaa8hvaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaGcdaqadaqa aKqzGeGaa8NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaqcLb sacaWFRaGaa8NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgacaWFRaGa a8xmaaWcbeaaaOGaayjkaiaawMcaaKqzGeGaaGPaVlaaykW7caWFai Iaa8xAaiaa=1dacaWFXaGaa8hlaiaa=5cacaWFUaGaa8Nlaiaa=Xca caWFnbGaa83oaiaaykW7caWFaiIaa8NAaiaa=1dacaWFXaGaa8hlai aa=5cacaWFUaGaa8Nlaiaa=XcacaWFnbGaa8xlaiaa=fdacaaMc8Ua aGPaVlaaykW7aaa@7527@ (12)

          

Where S T ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 3uaiaa=rfakmaaBaaaleaajugWaiaa=LgacaWFQbaaleqaaaaa@3CB5@  is the size factor corresponding to the intermediate storage tank, with identical definition to the batch stages. As no a priori tank allocation is given, binary variables y j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xEaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B1C@  are used to select their allocation. The value of variables y j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xEaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B1C@ is 1 if a tank is placed in position j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeaaciGaaiaabeqaamaabaabaaGcbaacbiqcLbsaca WFQbaaaa@3779@ , or zero otherwise. Constraint 12 is generalized to size the tank only if it exits:

V T j S T ij ( B ij + B ij+1 )- F j ( 1- y j )i=1,...,P;j=1,...,M-1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbGa a8hvaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaajugibiaa=vMicaWFtb Gaa8hvaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaGcdaqadaqa aKqzGeGaa8NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaqcLb sacaWFRaGaa8NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgacaWFRaGa a8xmaaWcbeaaaOGaayjkaiaawMcaaKqzGeGaa8xlaiaa=zeakmaaBa aaleaajugWaiaa=PgaaSqabaGcdaqadaqaaKqzGeGaa8xmaiaa=1ca caWF5bGcdaWgaaWcbaqcLbmacaWFQbaaleqaaaGccaGLOaGaayzkaa qcLbsacaaMc8UaaGPaVlaa=bGicaWFPbGaa8xpaiaa=fdacaWFSaGa a8Nlaiaa=5cacaWFUaGaa8hlaiaa=bfacaWF7aGaa8haIiaa=Pgaca WF9aGaa8xmaiaa=XcacaWFUaGaa8Nlaiaa=5cacaWFSaGaa8xtaiaa =1cacaWFXaaaaa@7A3C@    (13)

    

Where F j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 NraOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3AE9@  is a constant value sufficiently large such that when y j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xEaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B1C@ is 0 ( the tank does not exist), the constraint is trivially satisfied for any value of V T j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 Nvaiaa=rfakmaaBaaaleaajugWaiaa=PgaaSqabaaaaa@3BCE@ . In particular, the cost minimization will drive V T j =0 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbGa a8hvaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaajugibiaaykW7caWF9a GaaGPaVlaa=bdaaaa@4C92@ . When the tank exists ( y j =1 ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaabmaabaWexL MBbXgBd9gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugi biaa=LhakmaaBaaaleaajugWaiaa=PgaaSqabaqcLbsacaaMc8Uaa8 xpaiaaykW7caWFXaaakiaawIcacaGLPaaaaaa@4D74@ the term with F j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 NraOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3AE9@  vanishes, and the original constraint (12) holds. If the storage tank does not exist between two consecutive stages, then their batch sizes are constrained to be equal. Otherwise, this constraint is relaxed. This effect is imposed by the following constraints:

1+( 1 Φ -1 ) y j B ij B ij+1 1+( Φ-1 ) y j i=1,...,P;j=1,...,M-1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFXaGa a83kaOWaaeWaaeaadaWcaaqaaKqzGeGaa8xmaaGcbaqcLbsacaWFMo aaaiaa=1cacaWFXaaakiaawIcacaGLPaaajugibiaa=LhakmaaBaaa leaajugWaiaa=PgaaSqabaqcLbsacaWFKjIcdaWcaaqaaKqzGeGaa8 NqaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaakeaajugibiaa =jeakmaaBaaaleaajugWaiaa=LgacaWFQbGaa83kaiaa=fdaaSqaba aaaKqzGeGaa8hzIiaa=fdacaWFRaGcdaqadaqaaKqzGeGaa8NPdiaa =1cacaWFXaaakiaawIcacaGLPaaajugibiaa=LhakmaaBaaaleaaju gWaiaa=PgaaSqabaqcLbsacaaMc8UaaGPaVlaa=bGicaWFPbGaa8xp aiaa=fdacaWFSaGaa8Nlaiaa=5cacaWFUaGaa8hlaiaa=bfacaWF7a Gaa8haIiaa=PgacaWF9aGaa8xmaiaa=XcacaWFUaGaa8Nlaiaa=5ca caWFSaGaa8xtaiaa=1cacaWFXaaaaa@7AC4@ (14)

       Where Φ MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeuOPdy eaaa@3937@ is a constant value corresponding to the maximum ratio allowed between two consecutive batch sizes.

In summary, the multiproduct plant design model that includes the options of parallel units in-phase and/or out of phase and provision of intermediate storage, consists of the objective function 5 subject to constraints 6, 8, 11, 13, and 14, plus the upper and lower bounds that may apply. An important feature of the model is that both the objective function and the constraints are posynomial expressions that possess a unique local (and thus, global) solution.20 This basic model has been adapted to handle the particular feature of the composite stages (homogenizer, ultrafilters, and microfilters). In this case, constraint 6 is applied not to a general batch stage size but to each of the items that compose it. So in the case of microfilters, constraint 6 applies to both the retentate and the permeate vessels. A new parameter S R ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 3uaiaa=jfakmaaBaaaleaajugWaiaa=LgacaWFQbaaleqaaaaa@3CB3@  was introduced to represent the size factor of the retentate vessel, while S ij MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 3uaOWaaSbaaSqaaKqzadGaa8xAaiaa=PgaaSqabaaaaa@3BE0@ was left for the permeate vessel. Also in this case, the objective function must account for all the stage components. The notation a j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xyaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B04@ and α j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqySde McdaWgaaWcbaacbiqcLbmacaWFQbaaleqaaaaa@3BC1@  were left for the cost coefficients of the permeate vessel, b j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 NyaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B05@ and β j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFYoGc daWgaaWcbaqcLbmacaWFQbaaleqaaaaa@4708@  for the retentate vessel, and d j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hzaOWaaSbaaSqaaKqzadGaa8NAaaWcbeaaaaa@3B07@ and γ j MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeq4SdC McdaWgaaWcbaacbiqcLbmacaWFQbaaleqaaaaa@3BC9@  for the filtration area. A similar approach was implemented for the ultrafilters (retentate vessel and ultrafiltration area) and homogenizer (holding vessel and the homogenizer itself).

Methodology

Between 1960s and 1970s witnessed a tremendous development in the size and complexity of industrial organizations. Administrative decision-making has become very complex and involves large numbers of workers, materials and equipment. A decision is a recommendation for the best design or operation in a given system or process engineering, so as to minimize the costs or maximize the gains.21 Using the term "best" implies that there is a choice or set of alternative strategies of action to make decisions. The term optimal is usually used to denote the maximum or minimum of the objective function and the overall process of maximizing or minimizing is called optimization. The optimization problems are not only in the design of industrial systems and services, but also apply in the manufacturing and operation of these systems once they are designed. Including various methods of optimization, we can mention: MINLP, Particle Swarm Optimization and Genetics Algorithms.

Particle swarm algorithms

The PSA is a population-based optimization algorithm, which was inspired by the social behavior of animals such as fish schooling and birds flocking, it can solve a variety of hard optimization problems. It can handle constrains with mixed variables requiring only a few parameters to be tuned, making it attractive from an implementation viewpoint.22 In PSA, its population is called a swarm and each individual is called a particle. Each particle flies through the problem space to search for optima. Each particle represents a potential solution of solution space, all particles form a swarm. The best position passed through by a flying particle is the optimal solution of this particle and is called pbest, and the best position passed through by a swarm is considered as optimal solution of the global and is called gbest. Each particle updates itself by pbest and gbest. A new generation is produced by this updating. The quality of a particle is evaluated by value the adaptability of an optimal function. In PSA, each particle can be regard as a point of solution space. Assume the number of particles in a group is M, and the dimension of variable of a particle is N. The ith particle at iteration k has the following two attributes:

  1. A current position in an N-dimensional search space which represents a potential solution: X i k =( x i,1 k ,... x i,n k ... x i,N k ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFybqc fa4aa0baaSqaaKqzadGaa8xAaaWcbaqcLbmacaWFRbaaaKqzGeGaaG PaVlaa=1dacaaMc8UcdaqadaqaaKqzGeGaa8hEaKqbaoaaDaaaleaa jugWaiaa=LgacaWFSaGaa8xmaaWcbaqcLbmacaWFRbaaaKqzGeGaa8 hlaiaa=5cacaWFUaGaa8Nlaiaa=HhajuaGdaqhaaWcbaqcLbmacaWF PbGaa8hlaiaa=5gaaSqaaKqzadGaa83Aaaaajugibiaa=5cacaWFUa Gaa8Nlaiaa=HhajuaGdaqhaaWcbaqcLbmacaWFPbGaa8hlaiaa=5ea aSqaaKqzadGaa83AaaaaaOGaayjkaiaawMcaaaaa@6C07@ , where x i,n k [ l n , u n ] MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWF4bqc fa4aa0baaSqaaKqzadGaa8xAaiaa=XcacaWFUbaaleaajugWaiaa=T gaaaqcLbsacaWFiiIcdaWadaqaaKqzGeGaa8hBaOWaaSbaaSqaaKqz adGaa8NBaaWcbeaajugibiaa=XcacaWF1bGcdaWgaaWcbaqcLbmaca WFUbaaleqaaaGccaGLBbGaayzxaaaaaa@56AF@  is the nth dimensional variable, 1nN MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaiaaigdacqGHKj YOieGacaWFUbGaeyizImQaamOtaaaa@3D20@ , l n MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hBaOWaaSbaaSqaaKqzadGaa8NBaaWcbeaaaaa@3B13@ and u n MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xDaOWaaSbaaSqaaKqzadGaa8NBaaWcbeaaaaa@3B1C@ are the lower and upper bounds for the nth dimension, respectively.
  2. A current velocity, V i k =( v i,1 k ,... v i,n k ,... v i,N k ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbqc fa4aa0baaSqaaKqzadGaa8xAaaWcbaqcLbmacaWFRbaaaKqzGeGaaG PaVlaa=1dacaaMc8UcdaqadaqaaKqzGeGaa8NDaKqbaoaaDaaaleaa jugWaiaa=LgacaWFSaGaa8xmaaWcbaqcLbmacaWFRbaaaKqzGeGaa8 hlaiaa=5cacaWFUaGaa8Nlaiaa=zhajuaGdaqhaaWcbaqcLbmacaWF PbGaa8hlaiaa=5gaaSqaaKqzadGaa83Aaaaajugibiaa=XcacaWFUa Gaa8Nlaiaa=5cacaWF2bqcfa4aa0baaSqaaKqzadGaa8xAaiaa=Xca caWFobaaleaajugWaiaa=TgaaaaakiaawIcacaGLPaaaaaa@6CAC@ , which controls its fly speed and direction. V i k MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9 vqaqpepm0xbba9pwe9Q8fs0=yqaqpepae9pg0FirpepeKkFr0xfr=x fr=xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaamOvamaaDa aaleaacaWGPbaabaGaam4Aaaaaaaa@38DD@ is restricted to a maximum velocity V max k =( v max,1 k ,... v max,n k ,... v max,N k ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFwbqc fa4aa0baaSqaaKqzadGaa8xBaiaa=fgacaWF4baaleaajugWaiaa=T gaaaqcLbsacaaMc8Uaa8xpaiaaykW7kmaabmaabaqcLbsacaWF2bqc fa4aa0baaSqaaKqzadGaa8xBaiaa=fgacaWF4bGaa8hlaiaa=fdaaS qaaKqzadGaa83Aaaaajugibiaa=XcacaWFUaGaa8Nlaiaa=5cacaWF 2bqcfa4aa0baaSqaaKqzadGaa8xBaiaa=fgacaWF4bGaa8hlaiaa=5 gaaSqaaKqzadGaa83Aaaaajugibiaa=XcacaWFUaGaa8Nlaiaa=5ca caWF2bqcfa4aa0baaSqaaKqzadGaa8xBaiaa=fgacaWF4bGaa8hlai aa=5eaaSqaaKqzadGaa83AaaaaaOGaayjkaiaawMcaaaaa@7428@ . At each iteration, the swarm is uploaded by the following equations:

V i k+1 = ω V i k +c1r1(   P i k X i k )+c2r2(   P g k X i k ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFwbqcfa4damaaDaaaleaajugWa8qacaWFPbaal8aa baqcLbmapeGaa83AaiabgUcaRiaaigdaaaqcLbsacqGH9aqpcaWFGc Gaa8xYdiaa=zfajuaGpaWaa0baaSqaaKqzadWdbiaa=LgaaSWdaeaa jugWa8qacaWFRbaaaKqzGeGaey4kaSIaa83yaiaaigdacaWFYbGaaG ymaOWaaeWaa8aabaqcLbsapeGaa8hOaiaa=bfajuaGpaWaa0baaSqa aKqzadWdbiaa=LgaaSWdaeaajugWa8qacaWFRbaaaKqzGeGaeyOeI0 Iaa8hwaKqba+aadaqhaaWcbaqcLbmapeGaa8xAaaWcpaqaaKqzadWd biaa=TgaaaaakiaawIcacaGLPaaajugibiabgUcaRiaa=ngacaaIYa Gaa8NCaiaaikdakmaabmaapaqaaKqzGeWdbiaa=bkacaWFqbqcfa4d amaaDaaaleaajugWa8qacaWFNbaal8aabaqcLbmapeGaa83Aaaaaju gibiabgkHiTiaa=HfajuaGpaWaa0baaSqaaKqzadWdbiaa=LgaaSWd aeaajugWa8qacaWFRbaaaaGccaGLOaGaayzkaaaaaa@751A@ (15)

X i k+1 =  X i k +  V i k+1 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFybqcfa4damaaDaaaleaajugWa8qacaWFPbaal8aa baqcLbmapeGaa83AaiabgUcaRiaaigdaaaqcLbsacqGH9aqpcaWFGc Gaa8hwaKqba+aadaqhaaWcbaqcLbmapeGaa8xAaaWcpaqaaKqzadWd biaa=TgaaaqcLbsacqGHRaWkcaWFGcGaa8NvaKqba+aadaqhaaWcba qcLbmapeGaa8xAaaWcpaqaaKqzadWdbiaa=TgacqGHRaWkcaaIXaaa aaaa@5296@ (16)

    Where P i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 huaOWaaSbaaSqaaKqzadGaa8xAaaWcbeaaaaa@3AF2@  is the best previous position of the ith particle (also known as pbest) and P g MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 huaOWaaSbaaSqaaKqzadGaa83zaaWcbeaaaaa@3AF0@ is the global best position among all the particles in the swarm (also known as gbest). They are given by the following equations:

P i =  {    X i : :f( X i )  P i    P i  :f( X i )   P i MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFqbGcpaWaaSbaaSqaaKqzadWdbiaa=LgaaSWdaeqa aKqzGeWdbiabg2da9iaa=bkacaGG7bGcpaWaa0baaSqaaKqzGeWdbi aa=bkacaWFGcGaa8hwaKqba+aadaWgaaadbaqcLbmapeGaa8xAaaad paqabaqcLbsapeGaaiOoaiaa=bkacaGG6aGaa8NzaOWaaeWaaeaaju gibiaadIfakmaaBaaaleaajugWaiaa=LgaaSqabaaakiaawIcacaGL PaaajugibiabgsMiJkaa=bkacaWFqbqcfa4damaaBaaameaajugWa8 qacaWFPbaam8aabeaaaSqaaKqzGeWdbiaa=bkacaWFGcGaa8huaOWd amaaBaaameaajugib8qacaWFPbGaa8hOaiaa=bkacaGG6aGaa8NzaO WaaeWaaeaajugibiaadIfakmaaBaaaleaajugWaiaa=LgaaSqabaaa kiaawIcacaGLPaaajugibiabgwMiZcadpaqabaqcLbsapeGaa8hOai aa=bfak8aadaWgaaadbaqcLbmapeGaa8xAaaadpaqabaaaaaaa@6D39@ (17)               

P g    { P o ,  P 1 ,...,  P M }  f ( P g )=min( f( P o ),  f( P 1 )f( P M ) ) MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFqbGcpaWaaSbaaSqaaKqzadWdbiaa=DgaaSWdaeqa aKqzGeWdbiaabckacqGHiiIZcaqGGcGaaeiOaOWaaiWaa8aabaqcLb sapeGaa8huaOWdamaaBaaaleaajugWa8qacaWFVbaal8aabeaajugi b8qacaGGSaGaaeiOaiaa=bfak8aadaWgaaWcbaqcLbmapeGaaGymaa WcpaqabaqcLbsapeGaaiilaiaac6cacaGGUaGaaiOlaiaacYcacaqG GcGaa8huaOWdamaaBaaaleaajugWa8qacaWFnbaal8aabeaaaOWdbi aawUhacaGL9baajugibiaa=bkacaWFGcGaa8Nzaiaa=bkakmaabmaa paqaaKqzGeWdbiaa=bfak8aadaWgaaWcbaqcLbmapeGaa83zaaWcpa qabaaak8qacaGLOaGaayzkaaqcLbsacqGH9aqpciGGTbGaaiyAaiaa c6gakmaabmaapaqaaKqzGeWdbiaa=zgakmaabmaapaqaaKqzGeWdbi aa=bfak8aadaWgaaWcbaqcLbmapeGaa83BaaWcpaqabaaak8qacaGL OaGaayzkaaqcLbsacaGGSaGaa8hOaiaa=bkacaWFMbGcdaqadaWdae aajugib8qacaWFqbGcpaWaaSbaaSqaaKqzadWdbiaaigdaaSWdaeqa aaGcpeGaayjkaiaawMcaaKqzGeGaeyOjGWRaa8NzaOWaaeWaa8aaba qcLbsapeGaa8huaOWdamaaBaaaleaajugWa8qacaWFnbaal8aabeaa aOWdbiaawIcacaGLPaaaaiaawIcacaGLPaaaaaa@7F94@ (17)

              

Where f MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzadGaa8 Nzaaaa@394E@ is the objective function, M MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 xtaaaa@3896@ is the total number of particles. r 1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFYbGcdaWgaaWcbaqcLbmacaWFXaaaleqaaaaa@3AFC@ and r 2 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFYbGcdaWgaaWcbaqcLbmacaWFYaaaleqaaaaa@3AFD@ are the elements generated from two uniform random sequences on the interval [ 0 , 1 ] MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaadmaabaqcLb sacaaIWaGaaiilaiaaigdaaOGaay5waiaaw2faaaaa@3BDE@ : r 1 U ( 0 , 1 ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFYbGcpaWaaSbaaSqaamXvP5wqSX2qVrwzqf2zLnha ryaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbmacaGFXaaaleqaaKqzGe Gaa4xhIiaaykW7caaMc8Uaa4xvaOWaaeWaaeaajugibiaa+bdacaGF SaGaa4xmaaGccaGLOaGaayzkaaaaaa@5037@ ; r 2 U ( 0 , 1 ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFYbGcpaWaaSbaaSqaamXvP5wqSX2qVrwzqf2zLnha ryaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbmacaGFYaaaleqaaKqzGe Gaa4xhIiaaykW7caaMc8Uaa4xvaOWaaeWaaeaajugibiaa+bdacaGF SaGaa4xmaaGccaGLOaGaayzkaaaaaa@5038@ and ω MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqyYdC haaa@398A@ is an inertia weight30 which is typically chosen in the range of [ 0 , 1 ] MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaadmaabaqcLb sacaaIWaGaaiilaiaaigdaaOGaay5waiaaw2faaaaa@3BDE@ . A larger inertia weight facilitates global exploration and a smaller inertia weight tends to facilitate local exploration to fine tune the current search area. Therefore the inertia weight ω MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqyYdC haaa@398A@ is critical for the PSO’s convergence behavior. A suitable value for the inertia weight ω MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaKqzGeGaeqyYdC haaa@398A@ usually provides balance between global and local exploration abilities and consequently results in a better optimum solution. Initially the inertia weight was kept constant. However, some literatures indicated that it is better to initially set the inertia to a large value, in order to promote global exploration of the search space, and gradually decrease it to get more refined solutions. c 1 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFJbGc daWgaaWcbaqcLbmacaWFXaaaleqaaaaa@467D@ and c 2 MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFJbGc daWgaaWcbaqcLbmacaWFYaaaleqaaaaa@467E@ are acceleration constants which also control how far a particle will move in a single iteration.

Genetic Algorithms

GA, proposed in this paper based on the work of Wang et al.,22 are related to the mechanics of natural selection and natural genetics. They combine the survival of the fittest among string structures with a structured yet randomized information exchange to form search algorithms with some of the innovative flair of human search. In every generation, a new set of individuals (strings) is created using bits and pieces of the fittest of the old individuals; while randomized, a GA are no simple random walk. They efficiently exploit historical information to speculate on new search points with expected improved performance.23 According to Wang et al.,23 the canonical steps of the GA can be described as follows:

  1. The problem to be addressed is defined and captured in an objective function that indicated the fitness of any potential solution.
  2. A population of candidate solutions is initialized subject to certain constraints. Typically, each trial solution is coded as a vector X MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqaciaa=Hfaaa a@3812@ , termed a chromosome, with elements being described as solutions represented by binary strings. The desired degree of precision would indicate the appropriate length of the binary coding.
  3. Each chromosome X i ,i=1,2,...,P MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFybGc daWgaaWcbaqcLbmacaWFPbaaleqaaKqzGeGaaGPaVlaa=XcacaWFPb GaaGPaVlaa=1dacaaMc8Uaa8xmaiaa=XcacaWFYaGaa8hlaiaa=5ca caWFUaGaa8Nlaiaa=XcacaWFqbaaaa@5479@ , in the population is decoded into a form appropriate for evaluation and is then assigned a fitness score, μ( X ) MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaiabeY7aTnaabm aabaacbiGaa8hwaaGaayjkaiaawMcaaaaa@3B51@  according to the objective.
  4. Selection in genetics algorithms is often accomplished via differential reproduction according to fitness. In a typical approach, each chromosome is assigned a probability of reproduction, P i ,i=1,2,...,P MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFqbGc daWgaaWcbaacbiqcLbmacaGFPbaaleqaaKqzGeGaa8hlaiaaykW7ca WFPbGaaGPaVlaa=1dacaWFXaGaa8hlaiaa=jdacaWFSaGaa8Nlaiaa =5cacaWFUaGaa8hlaiaa=bfaaaa@52F0@  , so that its likelihood of being selected is proportional to its fitness relative to the other chromosomes in the population. If the fitness of each chromosome is a strictly positive number to be maximized, this is often accomplished using roulette wheel selection (Goldberg, 1989). Successive trials are conducted in which a chromosome is selected, until all available positions are filled. Those chromosomes with above-average fitness will tend to generate more copies than those with below-average fitness.
  5. According to the assigned probabilities of reproduction, P i ,i=1,2,...,P MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamXvP5wqSX2qVr wzqf2zLnharyaqbjxAHXgiv5wAJ9gzLbsttbacfiqcLbsacaWFqbGc daWgaaWcbaacbiqcLbmacaGFPbaaleqaaKqzGeGaa8hlaiaaykW7ca WFPbGaaGPaVlaa=1dacaWFXaGaa8hlaiaa=jdacaWFSaGaa8Nlaiaa =5cacaWFUaGaa8hlaiaa=bfaaaa@52F0@ , a new population of chromosomes is generated by probabilistically selecting strings from the current population. The selected chromosomes generate “offspring” via the use of specific genetic operators, such as crossover and bit mutation. Crossover is applied to two chromosomes (parents) and creates two new chromosomes (offspring) by selecting a random position along the coding and splicing the section that appears before the selected position in the first string with the section that appears after the selected position in the second string and vice versa. Bit mutation simply offers the chance to flip each bit in the coding of a new solution. According to our experiments, the parameters used for running GA and PSA are showed in Table 5.

Statistical analysis methods

The interest in statistical analysis methods has grown recently in the field of computational intelligence. In this section, I will discuss the basic and give a survey of a complete set of variance analysis procedures developed to perform the comparison between PSA and GA, via the use of describing a test of the null hypothesis, which applies to independent random samples from two normal populations of size n 1 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFUbGcpaWaaSbaaSqaaKqzadWdbiaaigdaaSWdaeqa aaaa@3B30@  and n 2 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFUbGcpaWaaSbaaSqaaKqzadWdbiaaikdaaSWdaeqa aaaa@3B31@ are taken from normal population having the same variance, it follows n 1 1 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFUbGcpaWaaSbaaSqaaKqzadWdbiaaigdaaSWdaeqa aKqzGeGaeyOeI0IaaGymaaaa@3D67@ distribution with n 2 1 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFUbGcpaWaaSbaaSqaaKqzadWdbiaaikdaaSWdaeqa aKqzGeGaeyOeI0IaaGymaaaa@3D68@ and F=  S 1 2 S 2 2 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFgbGaeyypa0Jaa8hOaOWaaSaaa8aabaqcLbsapeGa a83uaKqba+aadaqhaaWcbaqcLbmapeGaaGymaaWcpaqaaKqzadWdbi aaikdaaaaak8aabaqcLbsapeGaa83uaKqba+aadaqhaaWcbaqcLbma peGaaGOmaaWcpaqaaKqzadWdbiaaikdaaaaaaaaa@47AE@ degrees of freedom, according to this equation:

F=  S 1 2 S 2 2 MathType@MTEF@5@5@+= feaagKart1ev2aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeaeaa aaaaaaa8qacaWFgbGaeyypa0Jaa8hOaOWaaSaaa8aabaqcLbsapeGa a83uaKqba+aadaqhaaWcbaqcLbmapeGaaGymaaWcpaqaaKqzadWdbi aaikdaaaaak8aabaqcLbsapeGaa83uaKqba+aadaqhaaWcbaqcLbma peGaaGOmaaWcpaqaaKqzadWdbiaaikdaaaaaaaaa@47AE@

However, The error from the optimal solution is given by:

error%=100 | x exp - x cal | x exp MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaamaaxacabaWexL MBbXgBd9gzLbvyNv2CaeHbafKCPfgBGuLBPn2BKvginnfaiuGajugi biaa=vgacaWFYbGaa8NCaiaa=9gacaWFYbGaaGPaVlaa=vcacaWF9a Gaa8xmaiaa=bdacaWFWaGcdaWcaaqaamaaemaabaacbiqcLbsacaGF 4bqcfa4aaSbaaSqaaKqzadGaa4xzaiaa+HhacaGFWbaaleqaaKqzGe Gaa8xlaiaa+HhakmaaBaaaleaajugWaiaa=ngacaWFHbGaa8hBaaWc beaaaOGaay5bSlaawIa7aaqaaKqzGeGaa4hEaKqbaoaaBaaabaGaa4 xzaiaa+HhacaGFWbaabeaaaaqcLbsacaaMb8UaaGzaVdWcbeqaaaaa aaa@6608@ (19)

  In this research, x e x p MathType@MTEF@5@5@+= feaagKart1ev2aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbGeaGqk0=Mr0xXdbba91rFfpec8Eeeu0xXdbba9frFj0=OqFf ea0dXdd9vqaq=JfrVkFHe9pgea0dXdar=Jb9hs0dXdbPYxe9vr0=vr 0=vqpWqaaeaabaGaciaacaqabeaadaqaaqaaaOqaaGqacKqzGeGaa8 hEaKqbaoaaBaaabaGaa8xzaiaa=HhacaWFWbaabeaaaaa@3C40@  is considered to be the optimal solution founded by Montagna (Plant cost $829,500), where the equation (19) is a criterion to confirm the optimal values.

Results

The problem could be formulated as the minimization of the investment cost for equipment and storage tanks. Given that the problem modeled has non linear objective function. For the purpose of optimization problem, the model developed has been solved with PSA and GAs Matlab Toolbox respectively, which is included in the GNU Octave Scientific Programming Language, using the data shown in Table 1-4. A horizon time of 6000 h has been considered. However, the intermediate storage cost coefficient with size factors is shown in Table 6.

Product

Name

Production (kg/year)

Price (dollar/kg)

1

Insulin

1500

8000

2

Vaccine

1000

7500

3

Chymosin

3000

1000

4

Protease

6000

500

Table 1 Product prices and demands

Stage (j)

 Sij (m3/kg)

 

Unit

Insulin

Vaccine

Chymosin

Protease

1

Fermenter

1.25

0.625

0.415

0.3125

2

Microfilter I

r:1.25

r:0.625

r:0.415

r:0.3125

 

p:2.5

p:no

p:0.830

p:no

3

Homogenizer

No

0.155

No

0.08

4

Microfilter II

No

r:0.155

No

r:0.08

p:0.31

 

p:0.16

5

Ultrafilter I

2.5

0.31

0.83

0.16

6

Extractor

0.4

0.2

0.14

0.1

7

Ultrafilter II

0.4

0.2

0.14

0.1

8

Chromatographer

0.05

0.05

0.05

0.05

Table 2 Size factors Sij (r, retentate; p, permeate)

Stage

 

Tij (h)

j

Unit

Insulin

Vaccine

Chymosine

Protease

1

Fermentor

24

24

24

24

2

Microfilter I

12.5 A-1Bi

2.5 A-1Bi

4.15 A-1Bi

1.25 A-1Bi

3

Homogeneizer

no

0.465 cap-1Bi

 no

0.24 cap-1Bi

4

Microfilter II

no

3.1 A-1Bi

no

1.6 A-1Bi

5

Ultrafilter I

105A-1Bi

5.5 A-1Bi

35 A-1 Bi

3 A-1Bi

6

Extractor

1.5

1.5

1.5

1.5

7

Ultrafilter II

18A-1Bi

8 A-1Bi

4.75 A-1Bi

3 A-1 Bi

8

Chromatographer

0.5

0.5

0.5

0.5

Table 3 Time factors Tij[Bi(kg)]

Unit

Size

Cost

Fermenter

Vj (m3)

63400V0.6

Micro and ultrafilters

Vretentate (m3)

5750Vr0.6

Homogenizer

Vholding (m3)

5750V0.6

Cap (m3/h)

12100cap0.75

Extractor

Vextr (m3)

23100V0.65

Chromatography

Vchrom (m3)

360000V0.995

Table 4 Cost of equipment (U.S. Dollars)

Algorithms

Parameters

Value

GA

Population size

200

Number of generations

1000

Crossover probability

0.6

Mutation probability

0.4

Elitism

1

PSA

Number of particles

200

Number of generations

1000

Inertial weight

1.00

Acceleration constants

2.00

Table 5 The parameters used for running GA and PSA

Unita

STij size factor for product i in stage j

Insulin

Vaccine

Chymosin

Protease

Fermenter

1.25

0.625

0.415

0.3125

Microfilter I

2.50

0.155

0.83

0.08

Homogenizer

2.50

0.155

0.83

0.08

Microfilter II

2.50

0.31

0.83

0.16

Ultrafilter I

0.40

0.20

0.135

0.10

Extractor

0.40

0.20

0.135

0.10

Ultrafilter II

0.05

0.05

0.05

0.05

Chromatography

0

0

0

0

Table 6 Intermediate storage cost coefficients and size factors

On the other hand, the Table 7 shows the comparison of results for 30 runs between PSA and GA.

Values

PSA ($)

GA ($)

Best

912,450

833,674

Average

948,948

850,319.9401

Worst

976,321.5001

865,492.3154

Standart deviation

9.7558

1.5327

Table 7 Amplitude in mill volts of the Lead-1 of electrocardiography in sheep

*Significant (P≤0.05); NSNot significant (P>0.05)

Nevertless, the optimization runs results for the investment cost calculated by PSA and GA during 30 runs is illustrated in Table 8.

Technique

Plant cost ($)

%from optimal solución

CPU time (s)

PSA

912,450

10

800

GA

833,647

0.5

100

Table 8 Amplitude in mill volts of the Lead-1 of electrocardiography in sheep

*Significant (P≤0.05); NSNot significant (P>0.05)

Nonetheless, the equipment structure computed by PSA is showed in Table 9.

Stage

1

2

3

4

5

6

7

8

Vj

24.7456

1.1814

9.922

0.8921

0.6017

0.0825

Rj

NA

A: 16.2041

Cap: 1.0989

A:8.668

A: 109.3301

NA

A: 17.8134

NA

VTj

29.7066

NA

NA

NA

2.2154

NA

0.3795

NA

Mj

3

3

3

3

3

3

3

3

Gj

3

3

3

3

3

3

3

3

Table 9 Amplitude in mill volts of the Lead-1 of electrocardiography in sheep

*Significant (P≤0.05); NSNot significant (P>0.05)

However, Table 10 shows equipment structure calculated by GA.

Stage

1

2

3

4

5

6

7

8

Vj

22.6085

1.0794

9.0651

0.8151

0.5497

0.0754

Rj

NA

A: 14.8047

Cap:1.004

A:7.9194

A: 99.8880

NA

A: 6.2750

NA

VTj

27.1410

NA

NA

NA

2.0241

NA

0.3795

NA

Mj

1

1

1

1

1

1

1

1

Gj

1

1

1

1

1

1

1

1

Table 10 Amplitude in mill volts of the Lead-1 of electrocardiography in sheep

*Significant (P≤0.05); NSNot significant (P>0.05)

The idle times in plant calculated by PSA is provided in Table 11.

Unit

Product

1

2

3

4

5

6

7

8

Insulin

0

0

NA

NA

0

57.7

NA

67.11

Vaccine

0

54

0

0

60.79

57.7

22.9

67.11

Chymosin

0

17

NA

NA

17.54

57.7

27.9

67.11

Protease

0

63

16

15

63.07

57.7

55.03

67.11

Table 11 Idle times in plant calculated by PSA (seconds)

However, the idle times in plant calculated by GA is shown in Table 12.

Unit

Product

1

2

3

4

5

6

7

8

Insulin

0

0

NA

NA

0

0.01

0

0

Vaccine

0

1.93

0.04

0

2.91

0

0.17

0

Chymosin

0

0.01

NA

NA

0

0

0.31

0.17

Protease

0

2.09

0

0

3.07

0

0.5

0

Table 12 Idle times in plant calculated by GA (seconds)

The results of the statistical analysis are illustrated in Table 13 &Table 14.

Algorithm

N

Avg

SD

Standard
error

95% confidence interval of mean

Min

Max

Min

Max

PSA

30

1859.0000

8.48935

2.68743

1833.9205

1845.0795

1828

1857

GA

30

1838.0000

5.49936

2.08701

1828.2733

1837.7201

1828

1845

Table 13 The results of two algorithms solving MBPD problem

 

Quadratic sum

Free degree

Mean
Square

F

Significance

SDB

2339.676

3

779.895

15.455

0.000

SDI

1814.100

36

50.392

-

-

SUM

4154.775

39

-

-

-

Table 14 Variance analysis result of MBPD problem

Discussion

It is clear from the summary of the results shown in Table 7, that the performance of both PSA and GA produce adequate values regarding the cost for equipment and storage tanks. However, GA performs better than the PSA in terms of the average and the worst fitness values and the standard deviation. Table 7, also, shows the best final solution found in the 30 runs of PSA and GA. According to our knowledge, the case study about the optimal design of protein production plant has been taken from Montagna. However, they solved the problem using rigorous mathematical programing (MINLP), their model includes 104 binary variables and has been convexified using the transformation proposed by Kocis and Grossmann. The MINLP model has been solved using DICOPT++, which is included in the GAMS optimization modeling software. The algorithm implemented in DICOPT++ relies on the Outer Approximation/Equality Relaxation/Augmented Penalty (OA/ER/AP) method. The OA/ER/AP solution method consists of the decomposition of the original MINLP problems into a sequence of two subproblems: a non linear programming (NLP) subproblem and a mixed integer linear programming (MILP) subproblem also known as the Master problem, which is solved to global optimality (minimize the caplital cost $829,500). However, in previous work of Montagna and other, their model needed a long computational time (more than 86400 seconds) and require several initial values to the optimization variables, they also showed in their paper that the behavior of the demand was completely deterministic.

Whilst, this assumption does not seem to be always a reliable representation of the reality, since in practice the demand of pharmaceutical products resulting from the batch industry is usually variable. Simulations outcomes were then compared with experimental data in order to check the accuracy of the method. Table 8 presents the results obtained in different optimization runs for multiproduct batch plant design. For each simulator run, the average numerical effort spent on solving the problem on LINUX System, Intel ® D, CPU2.80 GHz, 2.99 of RAM. Table 8 shows plant cost, % from optimal solution and CPU time obtaining during 30 runs. PSA and GA performed effectively and give a solution within 10 and 0.5% of the global optimal $912,450 and $833,647, respectively. Furthermore, the important feedback could be taken from Table 8, is the GA results in a faster convergence than PSA and the MINLP algorithm. In addition, the GA is so close to the global optimal of MBPD (0.5% from optimal solution) and provides also an interesting solution, in terms of quality as well as of computational time as illustrated in Table 8, while Table 9 presents the sizes for the units involving a set of discrete equipment structure given by PSA. The inconvenience of this configuration is just stopped at 6000h with risk of failing to fulfill the potential future demand coming from a fluctuation of the market.
In order to show how the evolution process is going on for both PSA and GAs, respectively, the convergence of the best fitness values. The convergence rate of objective function values as a function of generations for both PSA and GAs where for clarity only 1000 generations are shown. For the optimization problem considered, GAs decrease rapidly and converge at a faster rate (around 500 generations) compared to that for PSA (about 800 generations), from which it is clear that GAs seem to perform better compared to PSA. So, for the present problem the performance of the GAs is better than PSA from an evolutionary point of view.

To compare the computational time, the swarm/population size is fixed to 200 for both PSA and GAs algorithms. Whereas, the generation number is varied. Simulation were carried out and conducted on LINUX System, Intel (R) D, CPU 2.80GHz, 2.99 of RAM Computer, in the GNU Octave environment. Here the result in the form of graph is shown in. It is clear from that the computational time for GAs is very low compared to the PSA optimization algorithm. Further, it can also be observed from hat in case of GAs the computational time increases linearly with the number of generations, whereas for PSA the computational time increases almost exponentially with the number of generations. The higher computational time for PSA is due to the communication between the particles after each generation. Hence as the number of generations increases, the computational time increases almost exponentially.

Table 9 presents the sizes for the units involving a set of discrete equipment structure given by PSA. The inconvenience of this configuration is just stopped at 6000 hours with risk of failing to fulfill the potential future demand coming from a fluctuation changing of the market.

On the other hand, the calculation of the structure of equipment using GA is illustrated in Table 10. The total production time, also, computed by GA is 5491.12 hours to fulfill the eventual increase of future demand caused by market fluctuation. In addition, the GAs results in a faster convergence. However, the equipment structure showed by PSA is very expensive. Furthermore, the PSA approach has the disadvantage of long CPU time.

At the same time as, the GA allow the reduction of the idle time to the stage, in any way, Table 11 & Table 12 show the idle times obtained by PSA and GA respectively.

However, some observations about some important aspects in our implication of GAs and some problems in practice: the most important of all is the method of coding, because the codification is very important issue when a genetic algorithm is designed to dealing with combinatorial problem, also of the characteristics and inner structure of the DMBP.

The commonly adopter concatenated, multi-parameter, mapped, fixed point coding are not effective in searching for the global optimum. According to the inner structure of the design problem of multiproduct batch that gives us some clues for designing the above mixed continuous discrete coding method with a four-point crossover operator. As is evident from the results of application, this coding method is well fit for the proposed problem.

Another aspect that affects the effectiveness of our Genetic Algorithms procedure considerably is crossover.

Corresponding to the proposed coding method, we adopted a four-point crossover. It is commonly believed that multipoint crossover is more effective than the traditional one point crossover method.

It is also important to note that the selection of crossover points as well as the way to carry out the crossover should take in account the bit string structure, as is the case in our codification.

One problem in practice is the premature loss of diversity in the population, which results in premature convergence, because premature convergence is so often the case in the implementation of GA according to our calculation experience.

Our experience makes it clear that the Elitism parameter can solve the premature problem effectively and conveniently.

In order to further explain the effects of these algorithms on solving the MBPD problem, the variance analysis was performed. Each of the PSA and GA algorithms was run 30 times. The Minitab software was used to analyze the results. Therefore, the results are given in Table 13 & Table 14.

Table 14 indicates that, the mean square deviation between groups (SDB) is 779.895. The mean square deviation within groups (SDI) is 50.392. The test statistic F=15.477. If significance level α=0.05, then the critical value 2.92≤ Fα(3.36)≤2.84. Thus, F>Fα(3.36) indicating that the difference between the average is significant, that is, the performance difference of algorithms is significant.

Nevertheless, these techniques are not a panacea, despite their apparent robustness, there are control “parameters” involved in these metaheuristics and appropriate setting of these parameters is a key point for success.

Conclusion

Techniques such as PSA and GA are inspired by nature, and have proved themselves to be effective solutions to optimization problems. We applied Genetic Algorithms with an effective mixed continues discrete coding method with a four crossover point to solve the problem of DMBP. GA perform effectively and give a solution within 0.5% of the global optimum. Whilst, it is observed that, in terms of computational time, the GAs approach is faster. The computational time increases linearly with the number of generations for GA, whereas for PSA the computational time increases almost exponentially with the number of generations, interpreting that, the higher computational time for PSA is due to the communication between the particles after each generation. Furthermore, the results provided by GA are much better with respect to PSA. In this paper, the GA gave us the highest efficiency and justifies its use for solving nonlinear mathematical models. Therefore, this work provides an interesting decision/making approach to improve the design of multiproduct batch plants under conflicting goals.

Acknowledgements

The authors Dr. Youness El Hamzaoui and Dr. Juan Antonio Alvarez Arellano from Facultad de Ingenieria, Universidad Autonoma del Carmen, expresse their gratitude to Dr. Jose Alfredo Hernandez Perez from CIICAP-UAEM for his comments and suggestions in order to improve this research article.

Conflict of interest

The author declares that their is no conflict of interest.

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