Project Details
Description
ACRoBAT was a €1.5m research project, funded under the EU FP7 Marie-Curie IAPP framework, which aimed to manufacture an adsorbent carbon based cartridge within a perfusion system for the removal of strongly, protein bound and macromolecular toxins and inflammatory molecules including hepatic and uremic toxins, exotoxin, endotoxin and cytokines.
Whilst the superior adsorptive capacity of activated carbons had been recognised for many years their use has been predominantly limited to the treatment of poisoning in the West. However, activated carbons with advanced properties and potential had been developed over recent years which could be used for an expanded range of biomedical applications.
These carbons offer a cheap and broad spectrum adsorptive approach to biological toxin removal, addressing a range of current health care challenges in the treatment of life threatening infection, renal failure, liver failure and in organ transplant optimisation. The project will seek to optimise the adsorptive potential of activated carbon technology, incorporating bioligand binding strategies for targeted toxin removal.
The project developed highly porous bead and monolith adsorbent systems for augmented removal of protein bound and high molecular weight toxins through technology transfer between the partners. These systems were tested and an adsorbent cartridge will be designed to sit in-line with and augment current haemodialysis, comparing bead and monolith systems.
A second adaptation of the sorbent system was considered in parallel with the haemoperfusion device to improve the viability of donor organs for transplant.
A third adaptation of the sorbent system considered novel toxin neutralising antibody synthesis and bioligand binding strategies in the development of a bioselective sorbent haemoperfusion cartridge for targeted, systemic biotoxin removal.
ACRoBAT was a four year research project lead by Dr Susan Sandeman at the University of Brighton, working jointly with a consortium of partners with complementary expertise from academic and private sector partners. It also drew on the experience of Eastern European project partner IEPOR in the clinical development of synthetic activated carbons for extracorporeal use.
Whilst the superior adsorptive capacity of activated carbons had been recognised for many years their use has been predominantly limited to the treatment of poisoning in the West. However, activated carbons with advanced properties and potential had been developed over recent years which could be used for an expanded range of biomedical applications.
These carbons offer a cheap and broad spectrum adsorptive approach to biological toxin removal, addressing a range of current health care challenges in the treatment of life threatening infection, renal failure, liver failure and in organ transplant optimisation. The project will seek to optimise the adsorptive potential of activated carbon technology, incorporating bioligand binding strategies for targeted toxin removal.
The project developed highly porous bead and monolith adsorbent systems for augmented removal of protein bound and high molecular weight toxins through technology transfer between the partners. These systems were tested and an adsorbent cartridge will be designed to sit in-line with and augment current haemodialysis, comparing bead and monolith systems.
A second adaptation of the sorbent system was considered in parallel with the haemoperfusion device to improve the viability of donor organs for transplant.
A third adaptation of the sorbent system considered novel toxin neutralising antibody synthesis and bioligand binding strategies in the development of a bioselective sorbent haemoperfusion cartridge for targeted, systemic biotoxin removal.
ACRoBAT was a four year research project lead by Dr Susan Sandeman at the University of Brighton, working jointly with a consortium of partners with complementary expertise from academic and private sector partners. It also drew on the experience of Eastern European project partner IEPOR in the clinical development of synthetic activated carbons for extracorporeal use.
Key findings
Within the project it was possible to:
> optimise carbon bead and monolith synthesis strategies, comparing different precursor formulations, pyrolysis and activation techniques, allowing a more cost effective and efficient synthesis route for scaling up production of this technology
> demonstrate haemocompatibility and the porosity required to adsorb specifically sized marker molecules using in vitro model systems for biotoxins related to kidney and liver failure
> demonstrate that an appropriate porosity profile can be maintained using improved synthesis techniques in scaled up test prototypes
> to develop, clinically relevant,scaled up testing models
> to show for the first time that it is possible to covalently immobilise Bacillus anthracis exotoxin specific antibodies onto cross-linked macroporous polymer monoliths for the removal of anthrax protective antigen. Such technology could be used in the event of future bioterrorism attacks involving anthrax toxin in addition to other smart biomaterial applications related to toxin removal.
Work within the project has allowed exchange of best practice through knowledge transfer visits between international activated carbon specialists from IEPOR (Ukraine) and UK SME MCI allowing the development of cheaper and more efficient processing strategies for economic benefit in the scale up of production routes. It has been possible to adapt standard haemocompatibility profiling to assess activated carbons for blood perfusion applications and to develop improved assessment techniques to allow for toxin rebound into the systemic circulation following removal by adsorption.
Work within the second half of the project focused on the development of ischaemic injury test models to assess adsorbent efficacy in donor organ preservation applications, haemocompatibility profiling of the antibody immobilized macroporous polymer prototypes and in vivo testing of device iterations. The project results support the potential for such adsorbent based medical device technologies to have significant clinical impact through improved removal of inflammatory and infectious molecules which currently drive tissue damage and produce life-threatening clinical complications.
G Ingavle, L Baillie, Y Zheng, E Lis, I Savina, C Howell, S Mikhalovsky, S Sandeman. (2015). Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilised protein A for removal of anthrax toxin protective antigen. Biomaterials. 50:140-153.
> optimise carbon bead and monolith synthesis strategies, comparing different precursor formulations, pyrolysis and activation techniques, allowing a more cost effective and efficient synthesis route for scaling up production of this technology
> demonstrate haemocompatibility and the porosity required to adsorb specifically sized marker molecules using in vitro model systems for biotoxins related to kidney and liver failure
> demonstrate that an appropriate porosity profile can be maintained using improved synthesis techniques in scaled up test prototypes
> to develop, clinically relevant,scaled up testing models
> to show for the first time that it is possible to covalently immobilise Bacillus anthracis exotoxin specific antibodies onto cross-linked macroporous polymer monoliths for the removal of anthrax protective antigen. Such technology could be used in the event of future bioterrorism attacks involving anthrax toxin in addition to other smart biomaterial applications related to toxin removal.
Work within the project has allowed exchange of best practice through knowledge transfer visits between international activated carbon specialists from IEPOR (Ukraine) and UK SME MCI allowing the development of cheaper and more efficient processing strategies for economic benefit in the scale up of production routes. It has been possible to adapt standard haemocompatibility profiling to assess activated carbons for blood perfusion applications and to develop improved assessment techniques to allow for toxin rebound into the systemic circulation following removal by adsorption.
Work within the second half of the project focused on the development of ischaemic injury test models to assess adsorbent efficacy in donor organ preservation applications, haemocompatibility profiling of the antibody immobilized macroporous polymer prototypes and in vivo testing of device iterations. The project results support the potential for such adsorbent based medical device technologies to have significant clinical impact through improved removal of inflammatory and infectious molecules which currently drive tissue damage and produce life-threatening clinical complications.
G Ingavle, L Baillie, Y Zheng, E Lis, I Savina, C Howell, S Mikhalovsky, S Sandeman. (2015). Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilised protein A for removal of anthrax toxin protective antigen. Biomaterials. 50:140-153.
| Acronym | ACRoBAT |
|---|---|
| Status | Finished |
| Effective start/end date | 1/12/12 → 30/11/16 |
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