Heparin, which prevents blood from clotting, has been used as an active compound in blood thinners for more than a century. “It’s made from pig’s intestines”, tells Aisling Foley. Together with Ilaria Poledri she founded ExCulture that won the Innovator League in the Philips Innovation Award on Monday 15 May 2023. “Epidemics like African Swine Fever and the 80 % global dependency on China for heparin production have caused shortages over the past years, so we have been working with the TU Delft on heparin production by fermentation, without the need to slaughter pigs first.”
The Delft patent for the development of heparin by bacteria is in the name of Professor Mark van Loosdrecht (Faculty of Applied Sciences). In the subjects Turning Technology into Business, master's student Winnifred Noorlander developed the patent into a startup and from there, together with fellow student Mandy van Overeem, into a pilot setup. After Noorlander suffered a double concussion as a result of two accidents, Delft Enterprises started looking for successors and found Foley and Poledri ready to take the case.
You both graduated from Leiden University and you're working with a TU Delft patent. How does that work?
Aisling Foley: "I studied chemistry and also did a masters in Science-based Business. My co-founder Ilaria Poledri did the same master's alongside her biology studies. Delft Enterprises, which focuses on valorising innovations and technology from TU Delft, was looking for people who wanted to run a start-up to further develop a patented technology from the department of environmental biotechnology (Faculty of Applied Sciences, ed.) for which they had identified had biomedical applications. It just went from there basically. Our biopharmaceutical and biomedical backgrounds were complimentary in the group of environmental biotechnology.”
The video clip on your website shows a glass vessel with a bubbling brownish broth. What's going on in there?
“These are naturally occurring micro-organisms; the main species is Candidatus Accumulibacter. We are keeping these in an artificial sea water solution in the bubble column reactor and feeding them with nutrients and carbon feedstock. Meanwhile we subject them to stresses of temperature and pH variations, favouring the selection of glycogen-accumulating and phosphate-accumulating organisms. These have a symbiotic relationship producing the sugars or the polysaccharides which include the heparin we focus on.”
How do you extract this heparin from the mixture?
“For now, we focus on the fermentation process in the bioreactor and the initial extraction. With the help of a postdoc Sergio Tomas Martinez, we've managed to increase the yield to about 10% of the biomass that we remove from the system is 50% pure heparin. He did that in the lab of Yuemei Lin and Mark van Loosdrecht at environmental biotechnology. So, our focus in the coming months is to achieve 99% purity or more to do the various studies to confirm that our product has the same activity as commercially available heparin.”
What's the further planning?
“Within the next eighteen months we aim to confirm the characterisation of the compounds and check their chemical activity. In parallel with that we want to set up our lab outside of the university to be ready for future commercialisation. Our goal is to scale up the production to one kilogram hopefully by the end of 2024. In the further future we might do a pilot scale up to 100 litres. Ultimately, we’d like to sell the process to a heparin manufacturer or pharmaceutical company.”
It sounds like Leiden with its BioScience Park is probably a good place to start?
“We‘re really trying to leverage expertise from both Delft and Leiden. We’re in between the Leiden BioScience Park biopharmaceuticals network and the Delft University departments of environmental biotechnology and process engineering. Leiden is the best place for testing the compound and for some of the purification studies as well. With all the expertise in bioprocessing and fermenters, we're well supported in Delft. Also, we’d like to set up our reactor in Delft.”
Over the phone, Winnifred Noorlander says she is happy that her lecturer Dap Hartman highlighted her role in the story. It also pleases her to see that the startup is successful. "This technology is much more than just heparin. It is a manufacturing platform with huge potential," she explains. She herself is combining rehabilitation with writing her final thesis for the Management of Technology study (Faculty of Engineering, Governance & Management).
- More information on the ExCulture website and the website of the Philips Innovation Award (PhIA).
- Originally, Winnifred Noorlander developed the technique to produce an anti-inflammatory. Read about the development in the first two years.
Update 06-06-2023: Three paragraphs added on Winnifred Noorlander's role. Delta was made aware of the omission by her former lecturer Dap Hartman.