Downstream process

Nur Istianah,ST,MT,M.Eng

Definition

• The downstream process is an

additional or complementary process

that is used to improve(polish up) the

results of processing on bioprocess or

fermentation

• In general, the downstream process is

a separation, both primary and

secondary separation

Role of downstream process

• the downstream process has the function

of handling semi-finished products to

become the final product. The downstream

process sometimes functions as an

additional process just before heading to

the final process, or it can also function as

a final process at once.

RIPP

Removal

Isolation

Purification

Polishing

Mechanism

Downstream processing - Operation sequence

1. Removal of particulates (insolubles): common operations are

filtration, centrifugation, also sometimes settling/decanting, also

new absorbents developed

2. Primary isolation: solvent extraction, precipitation, ultrafiltration

desired product concentration increases significantly

3. Purification: Fractional precipitation, several types chromatography-

bulk impurity removal as well as further product concentration

4. Final product isolation (Formulation): final centrifugation, freeze

drying, stability considerations, regulatory approvals, toxin and

pyrogen free etc.

Methods

Separation

Solid-liquid

centrifugation

Filtration

Clarification

Flotation

Drying

Chromatography

crystalization

Liquid-liquid

Missible

Distilation

Membran sep

extraction

Immissible Centrifugation

decanting

Methods

Others

Milling

Mixing

Sieveing

Cell disruption

Cell separation High resolution techniques

flocculation chromatography

centrifugation electrophoresis

filtration dialysis

Cell disruption Finishing/packaging

homogenizers crystallization

hydrolytic enzymes filtration

gel chromatography

drying

Clarification

centrifugation

filtration

Concentration

precipitation

chromatography

ultrafiltration

partitioning

distillation

Unit operations in downstream processing

Stages in downstream processing

Bioreactor

Cell separation Cell disruption

Clarified culture

medium

Cell debries

removal

Product recovery

and concentration

Chromatography

Polishing &

formulation

Capture

Interm-

ediate

Purific.

Final

Chromatography

Do

wn

str

eam

pro

cessin

g

Downstream processing

Generalized flow chart for purification of a protein from a culture broth

Consideration

Mass transfer

Definisi

• Transfer massa: perpindahan molekul

(massa) dari satu titik ke titik lain

• Terjadi pada proses pemisahan

• Driving force utama: perbedaan

konsentrasi

• Dapat terjadi secara natural atau paksaan

Mekanisme

Difusi - flux

• Difusi: perpindahan massa dari

konsentrasi tinggi ke konsentrasi rendah

• Flux: laju perpindahan per satuan luas

• berpindahnya sejumlah massa sat

setiap detiknya per 1 m2 cross area

• Cross area: area (luas penampang) yang

dilewati fluida dan berarah tegal lurus

dengan arah aliran

Flux

Cross area,

A= πr2

Flux

Cross area,

A= ab

b

a

Persamaan Flux

dx

dcDN A

ABA

NA = fluks dari A ke B (mol ∕ m2 s)

DAB = difusivitas dari A ke B (m2∕s)

cA = Konsentrasi A (mol∕ m3)

x = panjang lintasan difusi, ketebalan (m)

Laminar

Persamaan Flux

NA = fluks A (mol ∕ m2s)

kA = koefisien transfer massa A (m∕s)

∆cA = perbedaan konsentrasi A pada ona A dan

B (mol∕ m3)

Turbulent

AAA ckN .

Difusivitas

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