Knauer AZURA SMB Pilot User manual

SMB systems
Instructions
Document no. V6675

AZURA® SMB system instructions V6775
2
Note: For your own safety, read the instructions and observe the
warnings and safety information on the device and in the instructions.
Keep the instructions for future reference.
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KNAUER Wissenschaftliche Geräte GmbH
Hegauer Weg 38
14163 Berlin
Germany
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Internet: www.knauer.net
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Article number: V6775
Version number: 1.1
Last update: 2019/01/15
This document contains confidential information and may not be
reproduced without written content of KNAUER Wissenschaftliche
Geräte GmbH.
© KNAUER Wissenschaftliche Geräte GmbH 2019
All rights reserved.
AZURA® is a registered trademark of
KNAUER Wissenschaftliche Geräte GmbH.
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Publisher:
Version information:
The information in this document is subject
to change without prior notice.
For latest version of the siinstructions, check our website:
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Table of contents
AZURA® SMB system instructions, V6775
Table of contents
1. Product information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Intended use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 AZURA® SMB system variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2.1 AZURA® SMB Lab. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2.2 AZURA® SMB Pilot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 System configuration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3.1 AZURA® SMB Lab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3.2 AZURA® SMB Pilot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2. Simulated Moving Bed principle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2 Elution chromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.3 True counter-current process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.4 Simulated counter-current process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.5 Eciency and economic aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3. Scope of delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.1 AZURA SMB Lab System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.2 AZURA SMB Pilot System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4. Basic safety instructions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.1 Target group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.2 Safety equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.3 What must the user take into account? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.4 Warning notifications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.5 Decontamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
5. Symbols and signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
6. Unpacking and setup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.1 Operating environment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.1.1 Space requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.1.2 General requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.1.3 Earthquake areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.2 Storing unopened shipping boxes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.3 Unpacking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.4 Power supply. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
6.5 Connecting the capillaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
6.6 Flow charts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
6.7 Connecting system to computer via LAN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
6.7.1 Connecting the single devices to the computer . . . . . . . . . . . . . . . . . . . . . . . 20
6.7.2 Configuring the LAN settings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
6.7.3 Connecting the cables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
6.7.4 Configuring the router. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
6.7.5 Integrating the LAN into a company network . . . . . . . . . . . . . . . . . . . . . . . . . 21
6.7.6 Controlling several systems separately in a LAN. . . . . . . . . . . . . . . . . . . . . . . 22
6.7.7 Remote control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Table of contents
AZURA® SMB system instructions, V6775
7. Star t-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24
7.1 Initial start-up checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
7.2 SOP: SMB power-up and shut-down . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
7.2.1 Power-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
7.2.2 Shut down . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7.3 SOP: SMB start-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7.3.1 Removing air, flushing/cleaning the SMB and cleaning columns . . . . . . . . . 26
7.3.2 Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
7.3.3 Flushing the system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
7.3.4 Washing one single column . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
7.3.5 Flushing all columns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
7.3.6 Washing all columns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
8. Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
8.1 Software operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
8.2 Meaning of the LEDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
8.3 SOP: AZURA® SMB separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
8.3.1 Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
8.3.2 Starting the system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
8.3.3 Pausing the separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
8.3.4 Stopping the separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
8.4 Change Zone configurations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
8.4.1 From 2:2:2:2 to 1:3:3:1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
8.4.2 From 2:2:2:2 to 1:1:1:1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
9. Functionality tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38
9.1 Installation Qualification (IQ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
9.2 Operation Qualification (OQ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
10. Troubleshooting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39
10.1 First measures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
10.2 LAN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
10.3 Possible problems and solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
11. Maintenance and care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
11.1 SOP: Cleaning procedure for pressure release valves and connected tubings for
AZURA® Lab SMB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
11.1.1 Zone 1 pump & zone 2 pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
11.1.2 Feed pump & zone 4 pump. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
11.2 SOP: Cleaning procedure for pressure release valves and connected tubings for
AZURA® Pilot SMB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
11.3 Maintaining the AZURA® Lab System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.3.1 P um ps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.3.2 VICI valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.4 Maintaining the AZURA® Pilot system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.4 .1 Pump s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.4.2 VICI valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
11.5 Decommissioning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
11.6 Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
11.7 Storage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
11.7.1 Disconnecting the power supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Table of contents
AZURA® SMB system instructions, V6775
12. Technical data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46
12.1 General system parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
12.2 Technical parameters. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
12.3 Wetted materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
13. Chemical compatibility of wetted materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .48
13.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
13.2 Plastics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
13.3 Non-metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
13.4 Metals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
14. Legal information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
14.1 Transport damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
14.2 Warranty conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
14.3 Warranty seal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
14.4 Declaration of Conformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
14.5 Disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
15. Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53
16. Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54

1Product information
AZURA® SMB system instructions, V6775
1. Product information
1.1 Intended use
Note: Only use the system for applications that fall within the range of
the intended use. Otherwise, the protective and safety equipment of the
system could fail.
Application Separation and extraction
Pharmaceutical chemistry Chiral compound (cis-trans phytol, stero-
ids, peptides, antibiotics, etc.)
Food chemistry Fatty acids, carbohydrate mixtures
(sucrose/molasses, fructose/glucose, etc.)
Biochemistry Phenylalanine, fermentation/cell culture
products (citric acid, sugars, antibodies,
enzymes, etc.)
Petrochemistry C8-Hydrocarbon (xylene/toluene, etc.)
1.2 AZURA® SMB system variants
1.2 .1 AZURA® SMB Lab
This SMB system is optimized for separation tasks on a scale of several
hundred grams. The standard configuration consists of four AZURA®
assistants ASM 2.1L with seven multi-position valves and four AZURA®
pumps P 4.1S as well as our user-friendly software PurityChrom® MCC
including required IT hardware.
Depending on the special requirements of every separation the SMB
system can be freely configured via valve switch (e.g. closed-loop, open-
loop) and is upgradable with detectors and flow meters.
Individual configuration is available on request.
Fig.1 System layout AZURA® SMB Lab (example)

2 Product information
AZURA® SMB system instructions, V6775
1.2.2 AZURA® SMB Pilot
The AZURA® SMB Pilot is designed for the separation of binary mixtures
on a hundred gram to kilogram scale and is typically used with columns
up to 50 or 100 mm ID. Its special emphasis is put on the continuous ope-
ration mode and highest productivity.
The SMB standard configuration consists of four AZURA® pumps P 2.1L
and seven 8-port multiposition valves integrated into four AZURA® assis-
tants ASM 2.1L. Our user-friendly software PurityChrom® MCC and the
required IT hardware are also included.
We oer several variations of the standard system configuration.
Fig.2 System layout AZURA® SMB Pilot (example)
1.3 System configuration
The standard AZURA® SMB systems consists of four pumps and seven
multi-position valves.
The devices are arranged as follows:
Three pumps (Extract, Ranate, Eluent) are placed inside the SMB
cycle.
The feed pump is placed outside the SMB cycle.
Four valves are placed at the pump outlets.
Three valves are placed at the pump inlets. The feed pump inlet is not
connected to a multiposition valve.

3Product information
AZURA® SMB system instructions, V6775
Fig.3 SMB design scheme
1. 3.1 AZURA® SMB Lab
Number of
columns
Max. flow
rate
Max. pres-
sure
Description Article no.
8 50 ml/min 130 bar Stainless steel A29000
Biocompatible (PAEK, ceramic) A29001
1.3.2 AZURA® SMB Pilot
Number of
columns
Max. flow
rate
Max. pres-
sure
Description Article no.
8500 ml/min 100 bar Stainless steel A29501
How AZURA® SMB works
System confi guration
The standard AZURA® SMB systems consists of
four pumps and seven multi-position valves.
The devices are arranged as follows:
•
Three pumps (Extract, Ra nate, Eluent) are
placed inside the SMB cycle.
•
The feed pump is placed outside the SMB cycle.
•Four valves are placed at the pump outlets.
•
Three valves are placed at the pump inlets. The
feed pump inlet is not connected to a multi-
position valve.
Due to this confi guration the SMB system can be
used very fl exible for many di erent separation
modes. Additionally to the process stability
AZURA® SMB systems are outperforming every
other SMB system on the market regarding ma-
terial and confi guration fl exibility as well usable
pressure range.
Schematic AZURA® SMB design
Feed Raffi nate
EluentExtract
Zone 3
Zone 2 Zone 4
Zone 1
Column
switching
direction
14
AZURA® SMB systems
KNAUER_Brosch_SMB_12do.indd 14 28.08.17 10:51

AZURA® SMB system instructions V6775
4 Simulated Moving Bed principle
2.1 Introduction
Due to the fast development of new compounds and the more preci-
se knowledge about them, there is an increasing demand for purified
products. In most cases, chemical syntheses produce a lot of side com-
ponents. Therefore, dierent separation steps have to be involved into
production processes.
The most established and theoretically described thermal separation pro-
cesses (e.g. distillation, extraction, crystallization etc.) can not be applied
to all separation tasks. Among new separation methods, the adsorption
chromatography is a very eective but expensive process. The principle
of adsorption chromatography was discovered in the last century. The
separation is caused by dierent anities of the compounds (dissolved in
a liquid) to a useful solid phase.
Applications of adsorption chromatography were limited to analytical
scale for a long time. In the analytical scale, the mixtures are very diluted
and the distribution of a component between liquid and the solid phase
can be described by linear relations.
In the last few decades, adsorption chromatography is more and more
applied to the preparative process scale, where higher concentrations are
used and the liquid-solid distribution of a component becomes non-line-
ar and concentrationdependent. The peak profile and the retention times
are changing, so that modeling is more complicated.
The most established chromatographic process mode is elution chroma-
tography. Due to the theoretical understanding of this mode, it is possib-
le to use it in a very large scale. The regime of elution chromatography is
a discontinuous one, i.e. only discrete amounts of a mixture can be sepa-
rated. For higher amounts, a continuous mode should be favored. For a
binary (or pseudo-binary) mixture, the SMB process (Simulated Moving
Bed) with conventional chromatographic columns is successful.
Only the general principles of SMB will be explained in these instructions.
2.2 Elution chromatography
Among the established industrial scale separation processes preparative
adsorption chromatography is more and more used. Some separation
task (e.g. the separation of enantiomers) can be solved only by chromato-
graphy. The basic principle of elution chromatography is shown in Fig.4.
Fig.4 Principle of elution chromatography
The chromatographic column packed with a solid phase (adsorbent) will
be permanently penetrated by a fluid phase (eluent) with a well defined
2. Simulated Moving Bed principle

AZURA® SMB system instructions V6775
5Simulated Moving Bed principle
interstitial velocity. At the time t0a well defined amount of the sample
mixture is injected into the column. Due to dierent interaction forces
of the mixture components and the adsorbent (dierent migration ve-
locities), a separation of the mixture into the pure components will take
place. At the column outlet the purified components can be detected and
collected. This is the general principle of chromatography.
In preparative chromatography, the column is highly overloaded and is
not sucient to completely separate the mixture into the pure compo-
nents. The peaks are overlapping. This is shown in Fig.5. An unspecific
detector would show only the sum of both components, while the single
components are detectable in combination with a specific detector.
Fig.5 Overlapping of peaks in preparative-scale chromatography
The reason for overloading the column is, that there are time sections (t1,
t2), where the components elute in the required purity with a high concen-
tration. Because of the higher concentrations smaller liquid volumes are
necessary to separate equal amounts of the sample, such that the sepa-
ration of the value added components from the eluent (e.g. in vacuum
evaporators) is much simpler and cheaper.
The overlapping part of the concentration profile shown in Fig.5 with a
lower purity than required can be recycled to the column inlet.
In elution chromatography pulses are injected into the column, which are
separated in time (left side of Fig.6).
Fig.6 Process mode of elution chromatography
While migrating through the column, these pulses are broadened, due to
axial dispersion and dierent migration velocities and they are separated

AZURA® SMB system instructions V6775
6 Simulated Moving Bed principle
into the pure components due to dierent interaction forces to the adsor-
bent.
The time between two pulses i and i+1 have to be chosen in such a case,
that the slowest component of pulse i elutes before the fastest compo-
nent of pulse i+1 or just before they overlap too much, where pulse i is
injected before pulse i+1 (Fig.6).
If you would separate the column into small sections, there are parts
with two or more components within. Here and only here, the separation
process takes place. In other sections there is only pure eluent and the
separation capacity of the solid is not used. At the transients between the-
se and the sections containing the components dilution and mixing are
taking place. If two peaks are overlapping, because of dierent migration
velocities, there is also mixing.
In the last described sections no separation takes place. These parts
causes a lower use of the adsorbent capacity, but can not be avoided in
elution chromatography. This is because of the discontinuous or batch
regime of the process, i.e. only discrete amounts of the mixture can be
injected. Increasing the scale of the column, increases the total amount,
but it does not change the discontinuous character, connected with the
lower use of the adsorbent capacity and dilution eects.
To separate larger amounts with smaller columns, other process modes
than elution have to be used either a true counter-current process or a
simulated one.
2.3 True counter-current process
By contacting an up-flowing liquid with a down-flowing solid in a separa-
tion column, a true counter-current chromatographic process is realized,
called True Moving Bed (TMB). The TMB was first commercialized in the
hypersorption process of the Union Oil Company of California in the early
1950th.
Fig.7 Principle of a True Moving Bed (left) and typical concentration profile
(right)

AZURA® SMB system instructions V6775
7Simulated Moving Bed principle
Unloaded solid (adsorbent) is continuously filled into the upper end of
the column, while liquid (eluent) is pumped into the lower one. The bina-
ry (or pseudo-binary) feed-mixture is continuously injected in the middle
of the column. To separate the components of the mixture, they have to
be dierently adsorbed on the solid.
The two feed components are called A and B, where A is the less and B
the more adsorbed component, respectively. If there is a suitable ratio
between the volumetric flow rates of the solid and the liquid phase,
component B is adsorbed on the solid and is flowing downwards, while
component A is displaced from the solid and is transported upward by
the liquid. Pure component B can be withdrawn in the lower and pure
A in the upper part of the column. The TMB process is able to separate
binary or pseudo-binary mixtures into the two parts, where one part con-
tains the less adsorbed compound, while the more adsorbed compound
is in the other one. To achieve more than two fractions, dicult changes
are necessary.
The separation column can be divided into four zones or sections shown
in Fig.7. These zone are fulfilling dierent functions.
Injecting a well defined volumetric flow rate with a well defined concen-
tration of feed into an initially unloaded column at time t0all species are
transported into zone III. Following the laws of adsorption, the compo-
nents of the mixture will be distributed between the liquid and the so-
lid phase. The more adsorbed component will be enriched in the solid
phase.
Since a high purity of component A is required in the ranate stream,
component B has to be adsorbed in section III in the volume between
feed inlet and ranate outlet. Therefore, the function of zone III is to
adsorb component B or to separate it from A, respectively. The inverse
problem exists in section II, where component A has to be desorbed from
the solid phase and to be pushed back into zone III. Section II has the
function to separate component A from B.
Zone I has to clean the solid. All components flowing into this section
have to be desorbed, so that only the unloaded solid reaches the lower
end of the column and is recycled to the upper end. In zone IV, vice versa,
the liquid has to be cleaned. Recycling the pure liquid to the lower end
of the column, decreases the desorbent or eluent consumption. Conden-
sed, there are two separation sections (zone II and III) and two cleaning
sections (zone I and IV).
If you realize a suitable ratio of the volumetric flow rates of the liquid and
the solid phase in each zone, a concentration profile like that sketched on
the right side in Fig.7 is created. The ranate stream contains nearly no
B and the extract stream nearly no A. The most important parameters for
properly designing a TMB unit are the volumetric flow rates of the liquid
and the solid phase.
The true counter-current chromatographic process has the main draw-
back that the solid transport is dicult to realize due to back-mixing of
the adsorbent particles. Another important point is, that only small flow
rates are possible, since otherwise the solid would be pushed back by the
liquid. So the separation performance of the process is decreased.
To avoid these problems, dierent attempts have been made, however
they shall not be explained in detail here. The probably best possibility to
avoid the TMB drawbacks is explained now.

AZURA® SMB system instructions V6775
8 Simulated Moving Bed principle
2.4 Simulated counter-current process
The simulated counter-current process (Simulated Moving Bed - SMB) was
developed in the early 60th by the Universal Oil Products Company. It was
mainly applied to industrial-scale separations, like the xylene separation or
the fructose-glucose separation. The process scheme is shown in Fig.8.
Fig.8 Principle of a simulated counter-current process according to UOP
There is a strong analogy between the SMB and the TMB process. Under
the use of a suitable system of adsorbent and eluent, a feed stream is se-
parated into two withdrawal streams containing the pure components of a
binary or pseudo-binary mixture.
C
o
l
u
m
n
S
w
i
t
c
h
i
n
g
Eluent
Extract
Ranate
Feed
ZONE 1
ZONE 2
ZONE 3
ZONE 4
Fig.9 SMB process scheme

AZURA® SMB system instructions V6775
9Simulated Moving Bed principle
For SMB applications the large column in Fig.8 can also be substituted by
a number of chromatographic columns. This is sketched for 8 columns in
Fig.9. Like in the TMB process there are feed, eluent, extract and ranate
inlets and outlets, dividing the circle of columns into four sections. In Fig.9
the columns are distributed symmetrically, i.e. there are equal numbers of
columns in each section.
Special valves allow the liquid to flow in only one direction. The inlets and
outlets are arranged in a pre-defined manner and are switched in the same
direction as the fluid flows.
The switching time TShift can be achieved from the volumetric flow rate of
the solid and the solid volume.
Where VSolid is the solid volume and Vsthe volumetric flow rate of the phase
respectively. The counter-current stream is only realized at the switching.
Otherwise the columns are only a serial connection of conventional fixed
beds. The necessary switches of a column to reach its initial position is cal-
led a cycle. Due to the discrete switching mode, there is no stationary but
only a cyclic steady state in SMB technology.
The four sections of the SMB fulfil the same functions as in the TMB pro-
cess, i.e. in the zones II and III the binary mixture is separated, and in the
zones I and IV the solid and the liquid are cleaned, respectively. There are
the same requirements in length or number of columns as in TMB.
Because of the desorption the extract-concentration is decreased and the
breakthrough causes an increasing concentration in the ranate at each
switching interval. Typical concentration profiles of both outlets for a 4- co-
lumn SMB configuration are shown in Fig.10.
Fig.10 Concentration profiles at extract and ranate outlet (dashed lines: im-
purities)
.

AZURA® SMB system instructions V6775
10 Simulated Moving Bed principle
In Fig.10 the concentrations are normalized on the feed concentration of
each component. These normalized concentrations are plotted versus the
time coordinate. There are typical zigzag profiles, where a triangle sym-
bolizes one switching interval or tact. After 12 of these intervals (i.e. 3 full
cycles for a four column SMB process) the cyclic steady state is reached
(two proceeding triangles are almost identical). By integrating the profiles
over the time range, the averaged concentration can be calculated, i.e. the
concentration measured in a vessel.
Since only four columns (minimal number) are supposed in simulating-
Fig.10 the separation performance is low, i.e. there are impurities of the
other component in each outlet. Increasing the number or the length of the
columns would increase the separation performance.
2.5 Eciency and economic aspects
Chromatographic separation processes belong to the expensive ones,
compared with other thermal separation processes (distillation, crys-
tallization, etc.). This is caused by high prices for the adsorbents (e.g.
spherical silica gel in a high quality, chemically modified) and by the pure
solvents needed.
Nevertheless, chromatographic processes are very eective. They are
suitable for dicult separation problems, where the mixture compounds
have very similar physico-chemical properties as well as for the separa-
tion of very expensive products. This is fulfilled for many products of the
pharmaceutical and fine chemical industry or the food and drug industry.
In these industries some compounds are produced, which can only be
separated by chromatography.
In the previous chapters, three chromatographic modes were described
(elution, TMB, SMB). Out of these modes preparative elution chromato-
graphy is theoretically as well as practically the best known one. It has
been applied for a long time and creates the standard, at that new met-
hods are measured.
The modes are suitable for preparative scale processes. These scales can
be very dierent ones: While in petrol-chemistry 100,000 metric tons per
annum are produced, in the pharmaceutical industry only a few kilograms
are produced. From an industrial point of view only elution chromatogra-
phy and the SMB process are attractive out of the three modes, due to
the diculties connected with the solid movement in TMB.
To compare the two important modes (elution, SMB) in a fair way, the
plant scale has to be considered. After optimization of the two modes
dierent optimal points in the multidimensional space of process relevant
parameters are reached.
Such parameters are in the elution mode the volumetric flow rate of
the eluent, the injected amount of the mixture per pulse, the time gap
between two pulses, the produced amounts of purified compound, the
column geometry, the properties of the column packing, the required
purity, the temperature, etc. In SMB the volumetric flow rates (solid and
liquid) in each zone, the number of columns and the column geometry,
the produced amounts of purified compounds, the feed and withdrawal
concentrations, the properties of the column packing, the required purity,
the temperature etc. are relevant. Both modes are suitable for various
separation tasks. The specific problem, hence, has to been known for a
fair comparison.

AZURA® SMB system instructions V6775
11Scope of delivery
The SMB process enables the separation of binary mixtures by means of
a simulated countercurrent between the solid and liquid phases. This is
accomplished with a series of chromatography columns arranged in a ring.
An eluent flow circulates through this ring. Two inlets (for feed and eluent)
and two outlets (extract/red and ranate/blue) define four separation
zones. By continuously feeding sample and synchronously switching the
columns against the eluent flow direction, a countercurrent is achieved
between the solid and liquid phases, leading to high purity of both target
fractions. The movement of the solid phase is realized by simultaneously
switching seven multi-position valves (AZURA® SMB).
The SMB saves up to 90% of the eluent in comparison to a batch process.
Due to the simulated countercurrent, the stationary phase is significantly
better utilized with the SMB technique as compared to the batch process
technique. The number of theoretical plates might be also less important,
making it possible to use cost-eective larger particle size for the stationary
phases.
3. Scope of delivery
Note: Only use original parts and accessories made by KNAUER or a
company authorized by KNAUER.
3.1 AZURA SMB Lab System
1 x AZURA® Assistant ASM 2.1 L with 1 x AZURA® Pump P4.1S (10 ml
pump head) and 1 x 8-Multiposition-valve
3 x AZURA® Assistant ASM 2.1 L with 1 x AZURA® Pump P4.1S (50 ml
pump head) and 2 x 8-Multiposition-valve
SMB-Set with 1/16‘‘ capillaries, screw connections, T-pieces and con-
nections for the assembly of the system
Open/Closed Loop Kit
PurityChrom® MCC control software
Eluent tray AZURA® E2.1 L
Chromatography Work station with Mini-PC and 24“ monitor
WLAN Router
Stainless Steel version:
Pump heads (stainless steel)
Multiposition-valve-head (stainless steel)
Capillaries (stainless steel)
Biocompatible version:
Pump heads (ceramic)
Multiposition valve head (PAEK)
Capillaries (PEEK)
Optional:
Flowmeter
Oven
Detectors
Valid documents:
Instructions for AZURA SMB system (document no. V6775)
Declarations of conformity for single devices

AZURA® SMB system instructions V6775
12 Scope of delivery
4.1 Target group
4.2 Safety equipment
4.3 What must the user take into account?
This document address persons who are qualified as chemical laboratory
technicians or have completed comparable vocational training.
The following knowledge is required:
Fundamental knowledge of liquid chromatography
Knowledge regarding substances that are suitable only to a limited
extent for use in liquid chromatography
Knowledge regarding the health risks of chemicals
Participation during an installation of a device or a training by the com-
pany KNAUER or an authorized company.
If you do not belong to this or a comparable professional group, you may
not perform the work described in these instructions under any circum-
stances. In this case, please contact your superior.
When working with the device, take measures according to lab regula-
tions and wear protective clothing:
Safety glasses with side protection
Protective gloves
Lab coat
All safety instructions in this document
The environmental, installation, and connection specifications in this
document
National and international regulations pertaining to laboratory work
Original spare parts, tools, and solvents made or recommended by
KNAUER
Good Laboratory Practice (GLP)
Accident prevention regulations published by the accident insurance
companies for laboratory work
Filtration of substances under analysis
Use of inline filters
Once the capillaries have been used, never re-use them in other areas
of the HPLC system.
Only use a given PEEK fitting for one specific port and never re-use it
for other ports. Always install new PEEK fittings on each separate port.
Follow KNAUER or manufacturer’s instructions on caring for the co-
lums.
3.2 AZURA SMB Pilot System
1 x AZURA® Assistant ASM 2.1 L with 1 x 8-Multiposition-valve
3 x AZURA® Assistant ASM 2.1 L with 2 x 8-Multiposition-valves
4 x AZURA® Pump P 2.1 L
SMB-set with 1/8‘‘ capillaries, screw connections, T-pieces and connec-
tions for the assembly of the system
Open/Closed Loop Kit
PurityChrom® MCC control software
Chromatography Work station with Mini-PC and 24“ monitor
WLAN Router
Stainless Steel version:
Pump heads (stainless steel)
Multiposition-valve-head (stainless steel)
Capillaries (stainless steel)
Optional:
Flowmeter
Oven
Detectors
Valid documents:
Instructions for AZURA SMB system (document no. V6775)
Declarations of conformity for single devices

AZURA® SMB system instructions V6775
13Basic safety instructions
4. Basic safety instructions
4.1 Target group
4.2 Safety equipment
4.3 What must the user take into account?
This document address persons who are qualified as chemical laboratory
technicians or have completed comparable vocational training.
The following knowledge is required:
Fundamental knowledge of liquid chromatography
Knowledge regarding substances that are suitable only to a limited
extent for use in liquid chromatography
Knowledge regarding the health risks of chemicals
Participation during an installation of a device or a training by the com-
pany KNAUER or an authorized company.
If you do not belong to this or a comparable professional group, you may
not perform the work described in these instructions under any circum-
stances. In this case, please contact your superior.
When working with the device, take measures according to lab regula-
tions and wear protective clothing:
Safety glasses with side protection
Protective gloves
Lab coat
All safety instructions in this document
The environmental, installation, and connection specifications in this
document
National and international regulations pertaining to laboratory work
Original spare parts, tools, and solvents made or recommended by
KNAUER
Good Laboratory Practice (GLP)
Accident prevention regulations published by the accident insurance
companies for laboratory work
Filtration of substances under analysis
Use of inline filters
Once the capillaries have been used, never re-use them in other areas
of the HPLC system.
Only use a given PEEK fitting for one specific port and never re-use it
for other ports. Always install new PEEK fittings on each separate port.
Follow KNAUER or manufacturer’s instructions on caring for the co-
lums.

AZURA® SMB system instructions V6775
14 Basic safety instructions
4.5 Decontamination
1
Gerätename Betriebsanleitung, V-Nummer
Contamination of devices with toxic, infectious or radioactive substances
poses a hazard for all persons during operation, repair, sale, and disposal
of a device.
All contaminated devices must be properly decontaminated by a specia-
list company or the operating company before they can be recommissi-
oned, repaired, sold, or disposed of. All materials or fluids used for
decontamination must be collected separately and disposed of properly.
Decontamination Report
Devices without a completed Decontamination Report will not be repai-
red. If you would like to return a device to KNAUER, make sure to enclose
a completed Decontamination Report with the device:
https://www.knauer.net/decontamination-report.
Life-threatening injuries
Health danger if getting in contact with toxic, infectious or radio-active
substances.
Before disposing of the device or sending it away for repair, you are
required to decontaminate the device in a technically correct manner.
4.4 Warning notifications
More safety-relevant information is listed below:
flammability: Organic solvents are highly flammable. Since capillaries
can detach from their screw fittings and allow solvent to escape, it is
prohibited to have any open flames near the analytical system.
solvent tray: Risk of electrical shock or short circuit if liquids get into
the device‘s interior. For this reason, place all bottles in a solvent tray.
solvent lines: Install capillaries and tubing in such a way that liquids
cannot get into the interior in case of a leak.
leaks: Regularly check if any system components are leaking.
power cable: Defective power cables are not to be used to connect
the device and the power supply system.
self-ignition point: Only use eluents that have a self-ignition point hig-
her than 150 °C under normal ambient conditions.
power strip: If several devices are connected to one power strip, al-
ways consider the maximum power consumption of each device.
power supply: Only connect devices to voltage sources, whose voltage
equals the device‘s voltage.
toxicity: Organic eluents are toxic above a certain concentration.
Ensure that work areas are always well-ventilated! Wear protective
gloves and safety glasses when working on the device!
Where is use of the device prohibited?
Never use the system in potentially explosive atmospheres without
appropriate protective equipment. For further information, contact the
Technical Support of KNAUER.
Secure decommissioning
Take the device completely out of operation by disconnecting the power
plug from the power supply (wall socket or power strip).
Opening the device
The device may be opened by the KNAUER Technical Support or any
company authorized by KNAUER only.
Possible dangers related to the device are divided into personal and
material damage in these instructions.
Sign Meaning
DANGER (red) indicates a hazardous situation
which, if not avoided, will result in death or
serious injury.
WARNING (orange) indicates a hazardous
situation which, if not avoided, could result in
death or serious injury.
CAUTION (yellow) indicates a hazardous
situation which, if not avoided, could result in
minor or moderate injury.
NOTICE (blue) is used to address practices
not related to physical injury.

AZURA® SMB system instructions V6775
15Symbols and signs
4.5 Decontamination
5. Symbols and signs
The following symbols and signs can be found on the devices:
Symbol Meaning
Electric shock hazard
Electrostatic discharge hazard, damages to sys-
tem, device, or components can occur.
Obey maximum load for leak tray during transpor-
tation, installation and operation.
A device or system marked with CE fulfills the pro-
duct specific requirements of European directives.
This is confirmed in a Declaration of Conformity.
Testing seals in Canada and the USA at nationally
recognized testing centers (NRTL). The certified
device or system has successfully passed the qua-
lity and security tests.
On some devices, a warranty seal is attached. For
more information see paragraph 14.3 on page 52.
1
Gerätename Betriebsanleitung, V-Nummer
Contamination of devices with toxic, infectious or radioactive substances
poses a hazard for all persons during operation, repair, sale, and disposal
of a device.
All contaminated devices must be properly decontaminated by a specia-
list company or the operating company before they can be recommissi-
oned, repaired, sold, or disposed of. All materials or fluids used for
decontamination must be collected separately and disposed of properly.
Decontamination Report
Devices without a completed Decontamination Report will not be repai-
red. If you would like to return a device to KNAUER, make sure to enclose
a completed Decontamination Report with the device:
https://www.knauer.net/decontamination-report.
Life-threatening injuries
Health danger if getting in contact with toxic, infectious or radio-active
substances.
Before disposing of the device or sending it away for repair, you are
required to decontaminate the device in a technically correct manner.