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.