TEKNIK SEPARASI - istianahnuristianah.lecture.ub.ac.id/files/2017/02/TEKNIK-SEPARASI-1.pdf · TEKNIK SEPARASI NUR ISTIANAH,ST.MT.,M.Eng . OVERVIEW OF BIOSEPARATIONS ... 12 Separation

TEKNIK SEPARASI NUR ISTIANAH,ST.MT.,M.Eng

OVERVIEW OF BIOSEPARATIONS

• Up to 90% of new product cost is in downstream processing.

• More than 60% of the cost of third and fourth generation antibiotics is in purification.

Bioseparations are elaborate and expensive.

For recombinant DNA fermentation products, downstream processing can account for 80 to 90% of the overall processing cost.

BIOSEPARATION COST

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To improve the design of bioseparations, the following

questions should be answered:

(1) What is the value of the product?

(2) What is an acceptable product quality?

(3) Where is the product in each process stream?

(4) Where are the impurities in each process stream?

(5) What are the unusual physicochemical properties of

the product and the principal impurities?

(6) What are the economics of various alternative

separations?

BIOPRODUCTS

BIOPRODUCTS

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Bioproducts can be broadly classified into three categories:

small molecules, large molecules, and particulate products.

There are three corresponding separation procedures for

purifying them.

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(1) Separation of insolubles

* Objectives: remove or collect cells, cell debris, or

other particulates

* Typical operations: filtration, centrifugation

* Relatively little product concentration or

improvement of product quality occurs.

Most bioseparations have four similar steps:

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Most bioseparations have four similar steps (2/3):

(1) Separation of insolubles

(2) Isolation of products

* Objectives: remove materials of widely divergent

properties compared to the desired product

* Typical operations: extraction, adsorption,

ultrafiltration, precipitation

* Appreciable concentration and product quality

increases usually occur.

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Most bioseparations have four similar steps (3/3):

(1) Separation of insolubles

(2) Isolation of products

(3) Purification

* Objectives: remove impurities of similar chemical

functionality and physical properties

* Typical operations: chromatography, affinity

methods, fractional precipitation, electrophoresis

(4) Polishing

* Objectives: remove liquids

* Typical operations: drying, crystallization (not

always possible)

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Processing profile of antibiotics:

Product

Step Typical Process Conc.

(g/L)

Quality

(%)

Harvest broth Fermentation 0.1-5 0.1-1.0

Separation of

insolubles

Filtration 1.0-5 0.2-2.0

Isolation Extraction 5-50 1-10

Purification Chromatography 50-200 50-80

Polishing Crystallization 50-200 90-100

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Separation principles used in various recovery steps:

Size • Filtration

• Membrane

Density

• Sedimentation

• Centrifugation

• Flotation

Diffusivity

• Membrane

Shape • Filtration

• Sedimentation

• Centrifugation

Polarity

• Extraction

• Chromatography

• Adsorption

Solubility

• Extraction

• Precipitation

• cristallisation

Elc. charge

• Adsorption

• Electrophoresis

Volatility

• Distillation

• Pervaporation

Bioseparation Technique

• According to product characteristic

• Considering selectivity and productivity

• Selectivity: main product/byproduct

• Productivity: main product/time

Bioseparation Technique

• Low selectivity-high productivity

• Cell disruption

• Precipitation

• Centrifugation

• Extraction

• Leaching

• Filtration (+micro, ultra)

• Adsorption

• High selectivity-low productivity

• Ultracentrifugation

• Chromatography

• Affinity separation

• electrophoresis

EXAMPLE

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Process for ethanol production from fermentation:

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Manufacture of citric acid:

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Penicillin production:

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Production of an intracellular enzyme:

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Processing scheme for recombinant insulin:

(Inclusion Body)

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Processing scheme for recombinant insulin (2/2):

THANKS FOR YOUR ATTENTION

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