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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.
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
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
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
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
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 .