BRIC 2008: Bioprocess intensification by microcapillary separations systems

Lead Research Organisation: University of Cambridge
Department Name: Chemical Engineering and Biotechnology

Abstract

Biotherapeutic manufacturers have a need for new downstream processing techniques that match the purification ability and reliability of current manufacturing methods but which provide significantly higher throughput, ease of use and economy. Comparisons of current techniques (perfusion and monolith-based chromatography, membrane filtration) with earlier methods (ultracentrifugation, precipitation) highlight the central role of developments in materials science. Previous advances in separations technology have exploited microstructured materials and though complex at inception, the manufacturing technology for these materials has evolved so that filtration membranes and perfusion adsorbents can now be made reliably and reproducibly, at reasonable cost, quality and volume. Furthermore, module design and automation have evolved in parallel to enable convenience, speed and disposability. Our concept is to implement high definition micro-channel separations within an extruded flat film, modular format using a novel microstructured material, a MicroCapillary Film (MCF), which has been invented in this laboratory by the co-applicant. MCFs contain any number of uniform, parallel capillaries within a flat polymer film. They can be made reproducibly with capillary diameters down to 100 microns and they can be fabricated from a range of low-cost polymer resins (PMMA, MBS, polystyrene blends) using a high-throughput extrusion process. They can be manufactured precisely, cheaply and in bulk. The surface of capillaries within an MCF can be chemically modified to bind to target biological products within a complex mixture. The bound biological remains held on the MCF whilst other compounds in the mixture can be washed away. In a subsequent step the bound biological can be detached from the surface of the capillary and collected at the outflow from the MCF in a pure state. MCFs can be fabricated into MicroFlow Devices (MFDs) that are suitable for use in biomanufacturing operations. Residence time distributions for flows in MFDs are remarkably narrow, even at high throughput, and this provides the ideal plug-flow behaviour that is needed for sharp chromatography column breakthrough at high liquid flow rates. As a result of this desirable flow behaviour MFDs have been used for a wide range of preparative-scale fine-chemical syntheses and in the present context they represent a clear alternative to current polymer monolith and membrane chromatography systems for bio-separations.

Technical Summary

Our plan is to implement high definition micro-channel separations within an extruded flat film, modular format using a novel microstructured material, a MicroCapillary Film (MCF), which has been invented in this laboratory by the co-applicant. An MCF typically contains 19 parallel capillaries, each of 410 micron diameter, within a flat polymer film (20 mm by 2 mm). Any number of capillaries can be incorporated into a film by simply changing the extruder die. MCFs can be made reproducibly with capillary diameters down to 100 microns and they can be fabricated from a range of low-cost polymer resins (PMMA, MBS, polystyrene blends) using a high-throughput extrusion process. They can be manufactured precisely, cheaply and in bulk. MCFs can be fabricated into MicroFlow Devices (MFDs) that from established theory are expected to display high dynamic binding capacities at high flow rates. Residence time distributions for flows in the MFD are remarkably narrow, even at high throughput; the 8 cm spiral MFD displays a similar number of theoretical plates to a conventional 20 cm Sepharose packed column when operated with a flow velocity of 160 m/h, compared to 100 cm/h for the column. This provides the ideal plug-flow behaviour that is needed for sharp chromatography column breakthrough at high liquid flow rates. As a result of these desirable capacity and flow properties MFDs represent a clear alternative to polymer monolith and membrane chromatography systems for bio-separations. This project will demonstrate the advantages of MFDs over conventional chromatography technologies. We will fabricate a cation-exchange functionalised MCF and use this for the purification of monoclonal antibodies.

Publications

10 25 50
 
Description A novel microcapillary film device has been developed for the fast and efficient isolation of proteins, DNA and viruses.
Exploitation Route Further development is ongoing regarding the use of these devices in the manufacture of biological products.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description The findings of this project are being carried forward for the development of novel chromatographic devices for the analysis and manufactuire of biopharmaceutical products.
First Year Of Impact 2014
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Beacon Project 
Organisation MedImmune
Department MedImmune Cambridge
Country United Kingdom 
Sector Private 
PI Contribution As a result of an RCUK funded CASE project with MedImmune PLC on the topic of microcapillary separations a collaborative research initiative, the Beacon Project, was commenced with industrial funding of £3.5M.
Collaborator Contribution The partners have contributed expertise in biopharmaceuticals manufacture and funding.
Impact Numerous publications as listed on URL
Start Year 2015