Introduction
Medicines manufacturing is a complex and expensive process at scale,
requiring multiple unit operations to produce and purify a product of
interest to required standards. Recent advances in emergent modalities,
for example lipid enveloped particles, present major therapeutic
advantages but also challenges during bioprocessing when compared to
conventional products such as monoclonal antibodies . In order to
maximize bioprocess efficiency then effective unit operations must be
selected and optimized, often using a chain of the most suitable filters
and chromatography columns for purification .
Chromatographic unit operations rely on chemical and physical
characteristics to perform bioseparation of valuable products .
Structure relates directly to function and performance, which for
chromatography columns, spans a hierarchical structure consisting of i)
the space within the packed bed and ii) within individual beads. Both
length scales exhibit variability and often lack definitive control over
physical characteristics.
Additive manufacturing provides an approach whereby the geometry of a
material can be precisely designed and fabricated as specified by CAD
models . This enables physical characteristics such as channel size and
morphology to be designed that meets the intended function and optimized
for performance . The ability to 3D printing porous materials through
polymerization-induced phase-separation enables the formation of a
porous network at the nano-scale, essential to increase the surface area
to volume ratio for adsorption of biomolecules .
Additive manufacturing of porous materials enables the fabrication of
hierarchically porous media, with control over the microscale morphology
through CAD design, and control of the nanoscale through chemical
composition. This enables intelligent design of novel structures that
can be specifically tailored to the product of interest and rapidly
prototyped, including chemical and physical properties that influence
diffusive and permeable flow to improve bioseparations performance. 3D
printing materials for bioprocessing has been demonstrated in multiple
studies .
Computational fluid dynamics has been applied in examining flow behavior
through repeating gyroid structures . This has included a study that
focuses on the chromatographic performance and capabilities of repeating
geometries as comparative media to conventional packed bed resins . The
authors commented on a key advantage being the ability to precisely
specify a desired porosity at a scale analogous to the space between
chromatography beads. Another study has applied magnetic resonance
imaging in conjunction with computational fluid simulations to further
compare flow properties between repeating structures to randomly packed
beds .
High resolution X-ray imaging techniques have become increasingly
capable and popular for viewing and analyzing internal geometries for a
wide range of materials. X-ray Computed Tomography (CT) has been
successfully used to enhance the design of battery materials, whereby
physical characteristics including porosity and pore size can be
evaluated before, during and after use .
Bioprocess media including chromatography resins and nanospun structures
for adherent cell growth have previously been imaged using X-ray CT at
micro- and nanoresolutions . Here we combine the capabilities of 3D
printed hierarchically porous media with that of X-ray CT to control and
assess the resulting morphology across multiple length scales.