The FUNDABAC® SU Filter
Common technologies employed in upstream cell harvesting include
centrifugation, tangential-flow filtration, and depth filtration, often times
coupled together in larger scale operations. This new concept in single-use
filtration separates solids from suspension using dead-end filtration to
deposit a cake. Flat filter elements are packed close together inside a
multi-layered plastic bag enclosure to provide room for solid depositions up to
8 mm thick and to maximize surface area. The plastic bag is designed with
multiple layers to be able to withstand chemical environments, undergo high
pressures, and reduce gas permeation
cell
harvesting. The plastic filter bag is installed in a
pressure vessel to allow the bag to be compressed via gas to dewater the cake.
This enables filtration of the liquid heel so that there is virtually no
hold-up left in the filter chamber. The filter elements are constructed in HDPE
with an average pore size between 0.8 – 1 μm. These elements are flexible and
conform to the shape of the bag when external pressure is applied. These
elements are also back-washable via a back- flush tank which uses pressurized
filtrate to discharge the deposited solids from the filter media and let them
settle to the bottom of the filter bag. This enables the filter to perform
multiple filtration cycles prior to disposal since solids can accumulate from
cycle to cycle until the bag is full. Once full, the bag can be compressed to
recover the hold-up volume, and the bag containing the solid waste can be
removed and disposed of safely. In-situ filtration, cake washing, dewatering,
and discharging provide a simple operation that reduces equipment costs and
increases overall throughput
Single use bioreactor.
FUNDABAC® SU flowsheet
Advantages of the multi-cycle SU filter
This compact design significantly reduces disposal volume per weight
of waste generated. For cell harvesting in extracellular protein expression,
the volume of the containment under the filter elements can be increased to
handle very high cell loads. Due to the shape and size of cells, filtration
normally takes place with the addition of diatomaceous earth and/or cellulose
to improve flow rates. Under this normal cake filtration, cells undergo
relatively lower shear stress versus other filtration technologies, ensuring
the integrity of the cells are maintained and that intracellular impurities are
not released into the product
contained
filter.
The CONTIBAC® SU Filter – enhancement to the new SU design
In some processes, the filtered cells need to be discharged as
thickened suspensions to pump downstream. In intracellular protein expression,
the spent media must be replaced with a buffer solution to remove undesired
impurities before undergoing cell lysis. An enhancement to the new SU design under
consideration here incorporates an opening at the bottom for slurry discharge.
This significantly extends the lifetime of the filter bag and increases
filtration capacity. After cells are harvested and washed with a buffer
solution, the filter elements can be back-flushed to transfer the concentrated
cells downstream to be lysed
single-use filtration. Disrupting
the cells releases the desired proteins into the buffer solution and the lysed
broth is re-filtered to remove the cell debris, isolating the lysate containing
the desired product to send downstream to purification
single use systems.
CONTIBAC® SU flowsheet
In continuous bioprocessing of cells, the cultures require continual
supply of media to optimize growing conditions, as well as continuous removal
of metabolites and product to prevent a toxic environment. This process allows
for high-density cultures that maximize productivity in small bioreactors and
increase titer levels. This SU design offers a solution to retain the cells in
a recirculating loop off the bioreactor, while separating and replacing the
supernatant. Perfusion bioreactors can sustain cell cultures for several weeks,
which requires a robust, continuous filtration technology to be able to handle
the high cell loads while maintaining continuous high product output
disposable
mixer.
