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AALTO UNIVERSITY SCHOOL OF CHEMICAL TECHNOLOGY

Master’s Programme in Chemical, Biochemical and Materials Engineering
CHEM-E3140 - Bioprocess technology II

Downstream Processing - Crystallization

Anna Nuotio, 370837

Katri Hukkanen, 348225
Sanna Virtanen, 357203
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Table of contents
1. Abstract ..................................................................................................................................................... 3
2. Background ................................................................................................................................................ 3
3. Mechanism and processes ........................................................................................................................ 4
4. Case study from bioprocess technology.................................................................................................... 6
5. Conclusions ................................................................................................................................................ 6
References ......................................................................................................................................................... 7
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1. Abstract
Crystallization is a separation and purification method widely used for final purification of
components. Crystallization consists of two stages: formation of nuclei and growth of crystals. For
crystallization to occur the solution should be first supersaturated. The first step of crystallization is
formation of nucleation where crystals are formed when particles gather into clusters. There are
two different nucleation formations – primary and secondary. The second step of crystallization is
crystal growth where nucleus size increases after the critical cluster size is achieved. Crystallization
is widely used in chemical industry due to rather low operation temperatures and energy
consumptions. Main crystallization processes are cooling and evaporative crystallization.

2. Background
Crystallization, one of the oldest of unit operations in the portfolio of industrial separations, is a
separation and purification method widely used for final purification of components. Crystallization
is especially used for high quality products, which have high purity grade. The oldest crystallization
techniques are applied in salt and sugar production (Myerson, 2001).

Many organic liquids are purified by crystallization rather than by distillation, because enthalpies of
crystallization are usually lower than enthalpies of vaporization. Crystallization is also an important
technique in the desalination of seawater, the freeze-concentration of fruit juices, the recovery of
valuable materials such as metal salts from electroplating processes, the production of materials for
the electronic industries and in biotechnological operations such as the processing of proteins.
(Coulson & Richardson, 2002)

The industrial applications of crystallization are not necessarily confined to the production of pure
solids substances. Lately large-scale purification techniques have been developed for substances
that are normally liquid at room temperature. E.g. low-temperature crystallisation can be used as
purification method for liquid hydrocarbon mixtures in petroleum industry. (Mullin, 2001)
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3. Mechanism and processes

Crystallization consists of two stages: formation of nuclei and growth of crystals. For crystallization
to happen the solution should be first supersaturated thus the solution must contain more dissolved
material than it would under normal conditions. Several methods can be used to obtain
supersaturation such as solvent evaporation, cooling, chemical reaction and addition of a second
solvent to reduce the solubility of the solute, solvent layering and sublimation along with other
methods. (Coulson & Richardson, 2002)

Figure 1. Mechanisms of crystallization nucleation (Unknown 2016).

The first step of crystallization is formation of nucleation where crystals are formed when particles
gather into clusters. The clusters become stable nuclei after achieving the critical cluster size. There
are two different nucleation formations – primary and secondary as seen figure 1. Primary
nucleation is spontaneous and homogeneous in the absence of foreign particles. (Pokki 2016) Thus,
in the presence of foreign particles nucleation formation is heterogeneous and then the formation
is induced by foreign particles and occurs lower supersaturation concentration compared to
homogeneous primary nucleation as shown in figure 2. Secondary nucleation appears when
crystals already exist in the solution and it is caused by collision of crystals. This type of nucleation
formation is typical mechanism in industrial crystallization because of low supersaturation
concentration as shown in figure 2. (Unknown 2016)
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Figure 2. Concentration and temperature for formations of nucleation (Unknown 2016).

The next step of crystallization is crystal growth where nucleus size increases after the critical cluster
size is achieved. Crystal growth increases its own dimension in thin layers. Crystal growth rate is
affected by various physical factors, such as surface tension of solution, pressure, temperature,
relative crystal velocity in the solution, Reynolds number and other factors. (Coulson & Richardson,
2002)

Chemical industry produces 70% of all solid materials by crystallization and precipitation. The wide
use is due to rather low temperatures and energy consumptions in operations. In addition high
purity level can be achieved with single step. Crystallization is also a critical phase designating
product quality as purity and handling features such as wetting or caking. (Giulietti et al. 2001) Main
crystallization processes are cooling and evaporative crystallization though other methods exist as
well. In cooling crystallization crystals are formed by cooling the solution. In evaporative
crystallization the solvent is removed by evaporation to form crystals and thus requires a lot more
energy than cooling crystallization. In industrial scale the crystallization reactors may be either batch
or continuous reactors e.g. crystallizers. (Stanbury et al. 2013)
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4. Case study from bioprocess technology

Crystallization is typical downstream processing method for high quality products with high purity
requirements. The method is widely used for example in organic acid production. (Stanbury et al.
2013) One of the most common organic acids is citric acid which is used in several industries such
as pharmaceutical, food and beverage industries (Teixeira et al. 2012). This chapter presents the
principle of citric acid production utilizing crystallization.

After fermentation the broth is filtered and precipitated with Ca(OH)2 at pH of 7.2 and temperature
of 70-90 °C. Calcium citrate crystals are formed in the reaction. After filtration the calcium citrate is
reacted with sulfuric acid to precipitate the calcium in the form of calcium sulfate. Anhydrous citric
acid is released (when reaction occurs above 40 °C) and then clarified with active carbon and
crystallized with evaporation. The resulted product has very high purity level due to crystallization
and therefore is suitable for foodstuffs or pharmaceuticals. (Max et al. 2010, Stanbury et al. 2013)
The schematic block diagram of the production process is presented in figure 3.

Figure 3. Production of Citric acid.

5. Conclusions
Crystallization is an important downstream processing method in bioprocess technology and in all
chemical industry. Downstream processing can contribute to a large portion of end product price.
Therefore crystallization has an advantage compared to other solid liquid separation operations
such as distillation since crystallization is a rather energy efficient unit operation. In addition the
yielded product has very high purity level and therefore wide scale of end use opportunities.
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Even though crystallization is an old and effective method, new modelling and controlling
techniques can develop the operation to even more effective with higher purity and yield with
smaller cost in the future.

References
Coulson, J. M., and J. F. Richardson. 2002 Chemical Engineering–Particle Technology and Separation
Process, vol. 2

Giulietti, M., Seckler, M.M., Derenzo, S., Ré, M.I., & Cekinski, E. (2001). Industrial crystallization
and precipitation from solutions: state of the technique. Brazilian Journal of Chemical Engineering,
18(4), 423-440. https://dx.doi.org/10.1590/S0104-66322001000400007

Max, B., Salgado, J.M., Rodríguez, N., Cortés, S., Converti, A., & Domínguez, J.M. (2010).
Biotechnological production of citric acid. Brazilian Journal of Microbiology, 41(4), 862-875.
https://dx.doi.org/10.1590/S1517-83822010000400005

Mullin, J. W. (2001). Crystallization. Butterworth-Heinemann.

Myerson, A.S., (2001), Handbook of Industrial Crystallization, 2nd Ed, Elsevier Science and
Technology Books

Pokki, J-P. Engineering Thermodynamics, Separation Processes, part 2 Crystallization lecture notes,
Aalto University.

Seader, J.D., Henley, E.J., (2006), Separation Process Principles, John Wiley & Sons Inc, USA

Stanbury, P. F., Whitaker, A., & Hall, S. J. (2013). Principles of fermentation technology. Elsevier.

Teixeira, G.A., Vieira, W.F., Finzer, J.R.D. & Malagoni, R.A. (2012). Citric acid crystallization process
in dense phase using vibrated bed. Journal of Food Engineering. vol. 111, no. 2, pp. 458-465.

Unknown, http://sundoc.bibliothek.uni-halle.de/diss-online/05/06H049/t3.pdf , 30.11.2016