biotechflow martin hofmann 22sep2015 berlin plus installed 600
TRANSCRIPT
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A client case studyovercoming the design challenges of expanded bed adsorption columns
Martin Hofmann
Managing Director Biotechflow Ltd Mobile +44(0) 7980 74 77 30 Website biotechflow.com Email [email protected]
Copyright Biotechflow 2015
mailto:[email protected]
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2Martin Hofmann. Copyright Biotechflow 2015
Expanded Bed Adsorption
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3Martin Hofmann. Copyright Biotechflow 2015
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4Martin Hofmann Copyright Biotechflow 2015
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5Martin Hofmann Copyright Biotechflow 2015
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6Martin Hofmann. Copyright Biotechflow 2015
Expanded Bed Adsorption
Crude, unclarified high cell density, highly-viscous feedWhole cell mixture; homogenized cell broth; foods; plasma
Rhobust MabDirect Protein ACaptures MAb
Velocity450-500 cm/hr
24 L/min1414 L/hr
Cells, cell debris, host cell proteins (HCPs) and DNA
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Challenges from the URSreceived and ordered 21st Dec 2013
Maximum overall height 2 metre
1 metre piston adjustment
Anti-vortex outlet media must not leave, air must leave
Cleanable zero dead-space piston seals
Ultrasound adjustable position
Disposable rotating multiport inlet and outlet
7Martin Hofmann. Copyright Biotechflow 2015
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Height Challenge
Martin Hofmann. Copyright Biotechflow 2015 8
2600
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0
mm
DoorwayHeight
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Martin Hofmann. Copyright Biotechflow 2015 9
Piston Design Criteria
There are no meshes, and the process is always upflow
Design has to prevent of the formation of vortices in the expanded bed
Air must freely leave freely
Move at ca. 2.5 mm sec-1 1000 mm immediately in response to control
Fail-safe
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Martin Hofmann. Copyright Biotechflow 2015 10
Piston Design
Slope angle critical For air removal and resin retention
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Martin Hofmann. Copyright Biotechflow 2015 11
Piston Seal Functions
Piston seal to perform 4 main functions:
Provide efficient sealing
Hold the piston securely in place at 4.5 bar test pressure
Provide a mechanism to form a gap for cleaning between seal and tube wall
Afford zero dead space between piston and tube wall during process
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Martin Hofmann. Copyright Biotechflow 2015 12
Piston seals - final
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Martin Hofmann. Copyright Biotechflow 2015 13
Piston seal mechanisms
Deflated seal, reduces by 2mm for cleaning
Access to this gap is via a hatch
Steel rings carry the seal
No unswept areas
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Martin Hofmann. Copyright Biotechflow 2015 14
Anti-jet Top MP outlet
The critical parameters were:-
Veins (Kiviniemi, 2009 and Rindels, 1983)
Outlet holes
Anti-jet rod
Cone
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Martin Hofmann. Copyright Biotechflow 2015 15
Anti-vortex device type A
These designs failed to prevent a vortex
Resin beads swirled up and left the column
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Martin Hofmann. Copyright Biotechflow 2015 16
Anti-vortex device final design
120-degree angle
Three veins
Anti-jet rod extends beyond cone
Sacrificial and disposable
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Martin Hofmann. Copyright Biotechflow 2015 17
Successful anti-vortex device B
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Martin Hofmann. Copyright Biotechflow 2015 18
Use of Ultrasound
6 or 8 ultrasound transceivers monitor:
Monitor the position of piston
Feedback to the skid flow meter and pump
New Functions on latest column REAL TIME PAT.
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19Martin Hofmann Copyright Biotechflow 2015
Inclinometer within 0.01-degrees.
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Martin Hofmann. Copyright Biotechflow 2015 20
Ultrasound Beam
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21Martin Hofmann Copyright Biotechflow 2015
Sepharose Compression In 2m Steel Column (model by 2 m
tank)
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15:50:24 16:04:48 16:19:12 16:33:36 16:48:00 17:02:24 17:16:48 17:31:12 17:45:36 18:00:00
Time, hr:min:sec
Ultr
asou
nd R
esp.
10 ml / kg
8 ml / kg
6 ml / kg4 ml / kg 2 ml / kg
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23Martin Hofmann Copyright Biotechflow 2015
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0 2 4 6 8 10 12Acetone Conc., millilitre acetone / kg water
Ultr
asou
nd R
esp
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8000 8500 9000 9500 10000 10500 11000 11500 12000Time (secs)
-0.5
0
0.5
1
1.5
2
2.5
3
3.50
10
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8000 8500 9000 9500 10000 10500 11000 11500 12000Time (secs)
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
Bed Relax after off-line buffer change step.
Bed Compression on going back on-line
Buffer driving IgG off
IgG peak with shoulderBuffer Exchange from
pH 8.4 to pH 3.5
Blank ultrasndUVProduct ultrasnd
Graph 1 Run 1 US + UV
890.0025
880.0041
870.0036
870.0035
880.0034
880.0033
870.0033
880.0032
880.0032
880.0032
870.0032
880.0032
890
880
880
880
880
870
890
890
880.0002
880.0076
870.0317
880.041
870.0496
870.0582
870.0686
870.0813
870.0984
870.1193
870.1433
870.1711
860.2035
860.2456
870.3224
870.4652
870.7121
851.0358
861.3616
861.6545
861.8906
862.0689
852.1968
862.2893
852.3529
852.4005
862.4375
852.4663
852.4876
852.5005
852.5153
852.5297
842.5349
852.542
842.5479
842.552
842.5654
842.5587
832.5574
842.561
842.5674
842.5685
842.5688
832.5694
832.5719
832.5694
832.5734
842.5758
842.5745
832.5747
822.5734
842.5751
832.5759
832.5724
832.5796
842.5742
832.5767
832.5794
832.5737
832.5763
822.5818
832.579
822.5743
832.573
822.5693
822.5809
832.5755
832.5798
832.5807
822.5776
832.5794
822.578
822.5752
822.5827
822.5808
822.5763
822.5798
832.581
822.5764
822.582
822.5732
832.5746
822.5775
822.5808
822.5753
822.5795
822.5791
822.5777
822.5777
822.5788
822.5806
822.581
822.5759
822.5735
822.5775
822.5792
822.5777
822.5824
822.5775
822.5806
822.5832
812.5787
822.579
822.5755
812.5818
822.5784
812.5843
812.5852
812.5794
822.5832
822.5867
812.5738
822.5733
812.5822
822.577
812.5789
812.58
822.5761
812.5782
812.5786
812.5841
822.5754
812.5784
812.5822
812.584
812.5859
812.5775
812.5787
812.5857
812.5831
812.5812
812.5792
812.5821
812.5806
812.5799
812.5812
812.5822
812.5782
822.5814
822.5822
822.5838
812.5842
822.5769
822.5816
812.583
812.5866
812.5812
822.5802
822.5856
812.5782
822.583
812.5835
812.5782
812.5833
812.5779
822.5817
822.585
812.583
802.5873
812.5832
812.5832
812.5806
812.5847
812.5806
812.5825
812.5847
812.5862
812.5836
812.5819
812.5862
802.5859
812.5833
822.5898
812.5881
812.5838
802.583
812.5857
812.5826
812.5866
822.5884
812.5852
802.587
812.5819
802.5856
812.5901
812.5881
812.5838
812.5896
812.5872
812.5857
812.5918
812.5848
812.5841
802.5824
812.5838
802.5774
802.5872
802.5856
802.5805
802.5879
802.5781
802.5794
802.586
812.5821
802.5815
812.5868
812.5817
812.5819
812.5838
802.5853
802.5882
812.5836
802.5794
812.5886
812.5843
812.5844
812.5831
812.5847
812.5835
812.5844
802.5836
812.5843
802.5831
802.5876
812.5862
812.5808
812.5888
812.5852
812.5944
802.5851
812.584
812.5828
812.5918
812.5837
812.5877
812.5816
812.5859
812.5839
812.5868
812.5863
812.5812
812.5849
802.588
812.5877
812.5853
812.583
812.5882
802.5862
822.5869
812.5874
812.5849
812.5866
822.5803
822.5834
832.5891
822.5871
832.5798
822.5807
822.5787
822.5876
832.5785
832.5839
832.5819
842.5846
842.5858
842.5832
832.5815
842.5889
842.5839
852.5849
862.5869
842.5861
862.5862
862.5865
862.5878
862.5818
862.5839
872.5857
862.5853
862.5904
872.5849
872.5848
872.5854
862.5835
862.5845
872.5902
862.5849
862.589
852.5836
862.5824
852.5866
852.5878
852.5889
852.5818
842.5807
832.5865
842.588
842.59
832.5855
842.5878
832.5832
822.5858
832.5838
822.5875
822.588
822.5847
822.591
822.5885
812.5841
822.584
812.5913
812.5872
812.5872
802.5862
802.5869
802.5818
802.5929
802.5895
792.5859
802.5841
802.5824
792.5803
802.5799
792.5835
792.5883
802.5836
792.5817
802.5838
802.5869
792.5908
802.582
792.5865
792.589
802.5875
792.581
802.5855
792.5812
792.5824
802.5875
792.5861
792.5848
802.5845
802.5884
792.5882
792.5873
792.581
792.5871
792.5877
792.5829
792.5825
792.5915
792.5861
792.5811
792.5844
792.5863
782.5856
782.5877
792.5848
792.5821
792.5825
792.5857
792.5878
792.5859
782.5897
782.5878
782.5858
772.5897
782.5852
782.5844
782.5856
792.5868
782.5865
782.5893
782.5854
782.5839
792.5866
782.59
782.5827
782.5843
782.5881
772.5905
782.5838
772.5866
782.5874
782.5875
772.585
772.5876
782.5884
782.5836
772.5853
772.5894
782.5862
782.5879
782.5811
782.5862
782.5883
782.5862
782.5883
782.5867
782.5834
772.5837
772.5921
782.5876
792.5881
782.5841
782.5862
782.5828
782.5904
792.551
792.5416
792.5384
792.5267
802.526
792.5245
800.2092
800.0115
810.0069
820.059
810.0601
820.012
810.0013
830.0003
830.0002
830.0002
840.0002
840.0002
840.0002
842.52
842.5283
842.5029
852.4777
852.4565
852.4235
852.3661
842.269
842.0982
841.8603
841.5795
831.2659
820.9276
830.6456
830.441
820.3157
820.2423
810.1925
810.1527
800.1131
790.0748
780.0457
790.0275
770.0171
780.0125
770.0101
770.0091
760.0079
740.0078
750.0067
750.0063
730.0058
740.0061
730.0054
730.0052
720.0052
720.0047
730.0047
720.0042
720.0042
710.0042
710.0038
710.0038
710.0037
700.0036
700.0034
700.0035
700.0033
700.0032
700.0032
700.0032
690.0031
700.003
690.003
680.0029
680.0028
680.0028
680.0027
680.0026
670.0026
670.0026
670.0026
660.0026
660.0025
660.0025
650.0025
650.0024
650.0024
630.0024
630.0023
630.0023
620.0022
620.0023
610.0022
610.0022
600.0022
590.0022
590.0022
590.0022
580.0022
570.0021
570.0021
560.0021
560.0021
550.002
550.002
540.002
550.002
540.002
530.0019
530.002
530.002
530.0019
520.0019
520.0019
520.0019
510.0019
510.0019
520.0019
510.0019
500.0019
500.0019
490.0018
510.0019
500.0019
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510.0018
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560.0017
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560.0017
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570.0018
560.0017
570.0017
570.0017
560.0017
570.0017
580.0018
570.0017
570.0017
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580.0017
590.0017
580.0017
570.0017
580.0017
590.0019
590.0017
590.0017
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590.0017
590.0017
590.0017
590.0017
600.0017
590.0017
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600.0017
590.0017
590.0017
600.0017
600.0017
600.0017
610.0017
600.0017
610.0018
610.0018
600.0017
610.0094
610
61-0.0004
620
610.0001
610.0002
620.0002
620.0003
610.0003
620.0003
620.0003
620.0002
630.0002
620.0018
620.0024
620.0022
620.002
630.0018
630.002
630.0019
620.0016
630.0012
630.0011
620.001
640.001
630.001
630.001
640.001
640.001
630.0011
630.0013
640.0015
640.0017
640.0022
640.0032
640.0053
640.0089
640.014
640.0207
640.0292
650.0395
640.0505
640.0623
650.0761
640.0921
640.1119
650.1314
650.1559
650.1714
650.1845
650.2096
650.2672
640.378
650.5495
640.7694
661.0608
651.4204
651.8099
652.1773
652.373
652.4516
652.5063
652.5704
662.6467
672.7318
662.8284
662.9048
662.9782
663.0739
663.1151
663.0582
652.7906
672.2328
661.481
660.9067
660.5684
670.3709
660.2415
670.1595
670.1065
660.0749
660.0567
670.0444
660.0365
670.0309
660.0266
660.0232
670.0207
670.0186
660.0169
660.0157
660.0149
670.014
660.0133
670.0125
670.0118
670.011
680.0106
660.0107
680.0105
680.0097
680.0091
680.0091
670.0089
670.0086
670.0082
680.0084
670.0079
670.0077
680.0073
670.0071
670.0072
670.0069
670.007
670.0066
670.0067
670.0073
670.0091
670.0119
670.0166
670.0214
670.027
670.0324
670.0378
670.0427
670.0473
670.0511
670.0541
670.0563
670.0567
670.0561
680.0551
680.0522
680.044
670.0366
680.031
680.0259
680.0221
670.0191
680.0168
680.0148
680.0133
680.012
680.011
680.0102
670.0094
680.0087
680.0008
680.0012
67-0.001
68-0.0014
69-0.0005
68-0.0002
68-0.0003
68-0.0005
68-0.0003
68-0.0004
68-0.0004
68-0.0004
68-0.0003
680.0153
680.0136
680.0113
680.0095
680.0082
680.0073
680.0069
680.0066
680.0059
680.0053
680.0054
680.0063
680.0075
680.0089
680.0105
680.0119
690.0132
680.0147
680.0159
680.0171
680.018
680.0186
680.0191
680.0193
680.0185
680.0169
680.0145
680.0125
680.0109
680.0093
680.0076
680.006
680.0046
680.0035
690.0027
680.0021
680.0016
680.0013
690.0011
680.0009
690.0008
690.0007
680.0006
690.0006
680.0006
680.0005
680.0005
680.0005
680.0005
690.0006
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690.0004
680.0004
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680.0004
700.0003
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680.0004
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690.0008
690.0009
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700.0013
690.0016
690.0017
690.0015
690.0011
690.0007
690.0006
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690.0005
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