3. Background
Ions are electrostatically bound to an
insoluble and chemically inert matrix
– Anion exchangers bear positively charged
functional groups that bind negatively charged
particles.
During elution the anion exchanger can be
described by the following chemical
equation:
4. Why an anion exchanger?
Assumptions
•Denatured insulin had a 0% binding efficiency
•Insulin-Ester had a 100% binding efficiency and 90% recovery
•Isoelectric point of Denatured Insulin is higher than Insulin-Ester
Component
Flowrate
(kg/batch)
Mass Percent
(%)
Conc.
(g/L)
Denatured Insulin 0.4359 0.03 0.30
Insulin-Ester 296.38 20.22 202.25
Water 1168.65 79.75 797.46
5. Anion Exchanger Advantages
Capable of handling
large volumes
Efficient, precise
separation
– Accurate separation of
Insulin ester and
denatured Insulin
1
6. Large pressure drop
– Require expensive pumps
High resolution requires small beads
– Small beads decrease flow rate
Each cycle requires several stages
– Charging, sample input, washing, elution,
cleaning
Anion Exchanger Disadvantages
8. Membrane Chromatography
Allows for much larger throughput (about 100
times that of ion exchange) and a higher
efficiency
Uses microporous membrane
Small pressure drop compared to traditional
ion exchangers
Scaling up separation is simplified
9. Exclusion Chromatography
Separates on basis of
Molecular Mass
Column is filled with semi-
solid beads of a polymeric
gel
– The porosity of the gel can
be changed as to exclude
molecules of a set size
Useful for samples
containing many types of
proteins 5
10. Affinity Chromatography
Matrix anchored ligand
– Specifically binds to
protein of interest
Can exploit protein’s
unique biochemical
properties instead of
charge in ion exchange
Requires low flowrates
8
11. Anion Exchanger Design
Ergun Equation for pressure drop in a packed
bed
( ) µε
ρ
⋅−
⋅
⋅
=
1
Re
A
QDp
75.1
Re
150
+=Pf
( )ε
ε
ρ
−
⋅
⋅⋅
=∆
⋅
1
2
P
solutionp
D
A
QLf
P
12. Design Considerations
Property Dimension
Bead Diameter, DP
35μm
Column Lenth, L 3.47m
Column Diameter, D 1.3 m
Pressure Drop, ΔP 1718 kPa
Void Fraction, ε 0.4
Vessel Volume 4604 L
All constants were taken from Perry’s Chemical Engineering Handbook
7
13. Vessel Sizing
Exchanger is very large
– Much larger than needed, however, this will save
on pumping costs
Total flow rate through the anion exhanger is
1.721 x 10-5
m3
/s
– Based on 80h batch time and 826kg/batch
– Scaled up by a factor of 6
16. Resins
Serves as the media for stationary phase
– Polymeric matrix with immobilized charged
functional groups
Quaternary Ammonium functional group
Diethylaminoethane functional group
Can be regenerated in the columns and
used for many production cycles
– anionic resin: 500 - 1,000 cycles
8
17. Estimated Costs for Anion Exchanger
Unit Cost/Unit # of Units Total
Anion Exchanger $261,000 1 $261,000
Resin ~9 $/L 110 $910
Peripheral Equip. $50,000 N/A $50,000
Shipping $2,000 1 $2,000
Installation $100,000 N/A $100,000
Controls/Software $25,000 1 $25,000
Total Equip. Cost $438,910
18. Estimated Operation Costs / Year
Operation Total
Utilities $10,000
Maintenance $5,000
Supplies $1,000
Total Operations $16,000
*Overhead costs,
taxes and insurance
costs have not been
included in this
estimate
The total cost associated with the purchase of an Anion
Exchanger with one year of operation is approximately
$454,910.