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the intelligent membrane filtration system - GE Healthcare Life ...

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ÄKTAcrossflow – <strong>the</strong> <strong>intelligent</strong><br />

<strong>membrane</strong> <strong>filtration</strong> <strong>system</strong><br />

ÄKTAcrossflow is a fully automated<br />

<strong>filtration</strong> <strong>system</strong> for cross flow <strong>membrane</strong><br />

screening and process development.<br />

It is also <strong>the</strong> first <strong>system</strong> to enable<br />

automation at small-scale, with capacity<br />

ranging from liters down to 25 ml,<br />

making it useful for research and protein<br />

preparation. The compact design fits<br />

neatly onto a bench top and <strong>the</strong> <strong>system</strong><br />

works with a broad range of applications<br />

from micro<strong>filtration</strong> to ultra<strong>filtration</strong>.<br />

ÄKTAcrossflow, developed toge<strong>the</strong>r with a biopharmaceutical<br />

manufacturer, is <strong>the</strong> latest member of <strong>the</strong> ÄKTAdesign family,<br />

and extends <strong>the</strong> UNICORN controlled platform into <strong>membrane</strong><br />

<strong>filtration</strong>. The <strong>system</strong> comprises a separation unit built with<br />

ÄKTAdesign components for reliability, flexibility and scalability.<br />

UV, pH and conductivity detectors as well as air, pressure, and<br />

temperature sensors are all part of <strong>the</strong> unit. Electronically<br />

actuated diaphragm valves reduce hold-up volumes and prevent<br />

dead volumes. The compact, space-saving, bench top <strong>system</strong><br />

is ideal for a broad range of applications, and has <strong>the</strong> ability to<br />

operate ei<strong>the</strong>r hollow fiber cartridges or cassettes.<br />

6 Downstream • thirty nine<br />

Fast, secure and automated<br />

The UNICORN control software monitors and captures sensor data<br />

and real-time parameter trends; while method wizards provide<br />

easy method generation. This combination of control during cross<br />

flow processing and <strong>the</strong> automatic handling and evaluation of<br />

data ensures complete mastery of cross flow processes.<br />

One of <strong>the</strong> benefits of working with ÄKTAcrossflow is <strong>the</strong> significant<br />

amount of time that can be saved during process development.<br />

Results are delivered by UNICORN in just a few hours compared<br />

to weeks when working with manual <strong>system</strong>s, while human error<br />

is eliminated from <strong>the</strong> task of transferring data to spreadsheets.<br />

Moreover, UNICORN allows efficient data evaluation and<br />

provides full tracking and documentation of processes (Fig 1).<br />

UNICORN complies fully with all applicable regulations, including<br />

21 CFR Part 11.


Protects sample<br />

ÄKTAcrossflow offers <strong>the</strong> highest level of protection for your<br />

sample. The <strong>system</strong> has three high precision metering pumps<br />

that operate over <strong>the</strong> entire flow/viscosity range without <strong>the</strong> need<br />

for flowmeters. The verified pump design minimizes shear forces,<br />

ensuring that sensitive cellular material is not damaged. Moreover,<br />

heat transfer from <strong>the</strong> pump heads to <strong>the</strong> process fluid is so low<br />

that cooling is unnecessary. The feed pump features four pump<br />

heads for gentle and pulsation-free circulation of sensitive process<br />

fluids at rates up to 600 ml/min. The transfer and permeate pumps<br />

allow for 200 ml/min pulsation-free flow.<br />

Sanitary design<br />

The pump heads have a sanitary design with a self-contained<br />

rinsing <strong>system</strong> to prevent contamination and pump damage.<br />

Valve units are also sanitarily designed, with EPDM <strong>membrane</strong>s for<br />

high chemical resistance. The valve blocks include multiple valves<br />

to minimize hold up volumes. The <strong>system</strong> is effectively sanitized<br />

with 1 M sodium hydroxide (NaOH) which has demonstrated<br />

high efficiency in microbial challenge tests, fulfilling <strong>the</strong> USP 27<br />

requirements of log 6 reduction of colony forming units.<br />

A more efficient way of working<br />

The ÄKTAcrossflow <strong>system</strong> with UNICORN control supports <strong>the</strong><br />

process control modes commonly used in ultra<strong>filtration</strong> and<br />

micro<strong>filtration</strong> applications such as TMP control and flux control<br />

(Fig 2). These control modes can be combined with selectable feed<br />

pump instructions, such as feed flow rate, feed pressure, Delta P,<br />

retentate flow rate or shear rate. UNICORN also reports real-time<br />

process parameters such as retentate volume, concentration factor,<br />

dia<strong>filtration</strong> exchange factor, and accumulated permeate volume.<br />

The networking capabilities with UNICORN/OPC allow for flexibility in<br />

process design and total process control. As <strong>the</strong> cross flow process<br />

is scaled up, <strong>the</strong> ÄKTAcrossflow <strong>system</strong> can communicate with <strong>the</strong><br />

UNICORN controlled manufacturing cross flow skid, just as <strong>the</strong><br />

ÄKTApilot <strong>system</strong> can communicate with <strong>the</strong> BioProcess skid.<br />

UNICORN links <strong>the</strong> unit operations to create one fluid process.<br />

ÄKTAcrossflow uniting processes<br />

<strong>GE</strong> <strong>Healthcare</strong>’s long experience and expertise in automated<br />

chromatography procedures can now be transferred to cross flow<br />

<strong>filtration</strong> to provide an integrated process solution with <strong>the</strong> familiar<br />

and proven UNICORN platform. Figure 3 shows an integrated<br />

process for plasmid purification combining ÄKTAcrossflow and<br />

ÄKTAexplorer <strong>system</strong>s.<br />

In summary<br />

ÄKTAcrossflow is providing a small revolution in <strong>filtration</strong>. By<br />

building UNICORN into <strong>the</strong> <strong>system</strong>, <strong>filtration</strong> processes can now<br />

be automated allowing <strong>the</strong> operator to be in full control of <strong>the</strong><br />

process, and get results in a matter of hours.<br />

Fig 1. UNICORN fulfills stringent control and data<br />

handling procedures.<br />

Fig 2. Raw data recorded from process optimization for<br />

BSA concentration/dia<strong>filtration</strong> using TMP scouting with<br />

100g/l and 20g/l BSA solutions.<br />

Fig 3. An integrated plasmid purification workflow<br />

using ÄKTAcrossflow and ÄKTAexplorer. For process<br />

development, <strong>the</strong> PlasmidSelect process can purify over<br />

100 mg of plasmid DNA in a single run on ÄKTAcrossflow<br />

and ÄKTAexplorer <strong>system</strong>s. For production scales, an<br />

integrated process using UniFlux and ÄKTAprocess <br />

<strong>system</strong>s can provide several kilograms of supercoiled<br />

plasmid DNA.<br />

Fur<strong>the</strong>r information<br />

Data File<br />

ÄKTAcrossflow automated cross flow <strong>filtration</strong><br />

for process development, Code No. 11-0032-71<br />

Brochure<br />

ÄKTAcrossflow Putting <strong>the</strong> ”brain” into<br />

<strong>membrane</strong> screening, Code No. 11-0034-87<br />

Downstream • thirty nine 7

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