Paving the way to monitoring drug dosage at home
Everyone’s body reacts to therapeutic drugs slightly differently, not all metabolisms are created equal. Most drugs don’t need to be monitored at individual level, but for those with a narrow therapeutic window, therapeutic drug monitoring (TDM) is vital. “In the case of treatment of children with leukaemia, for example, where a drug called MTX can be used, then TDM is needed. The dose is high, and the drug is toxic, so you can only offer this treatment if you have a lab next door,” says Anja Boisen, lead researcher of the THERA project, hosted by the Technical University of Denmark and funded by the European Research Council. The result is that many who could benefit from the drug can’t access it since the testing facilities needed to use the MTX safely aren’t to hand. “And even when monitoring is carried out by, for example an ELISA, it would still be much better to be able to follow the individual patient more closely,” she adds. This is where the work of the THERA project comes in.
Portable and accurate therapeutic drug monitoring
By using surface-enhanced Raman spectroscopy (SERS), a very sensitive technique that can be integrated in a lab-on-chip solution, THERA has come up with an accurate tool in a small package: a tabletop device, that can perform TDM from a single droplet of blood, in a matter of minutes. “And all this without the need for specialised personnel, at a fraction of the cost currently associated with TDM,” Boisen remarks. SERS uses a nanostructured surface, on which a filtered blood sample is placed, and an optical technique to give a chemical fingerprint of whatever is on our nanostructured surface. “In the future, you could imagine that the patient could monitor drugs at home, allowing patients to leave hospital earlier than they can today. That, I believe, would significantly increase the quality of life and lower costs as well,” she explains. This would be a major contrast to current tools used to monitor therapeutic drugs, such as high-performance liquid chromatography, mass spectrometry and ELISA. All these tools require laboratory equipment and trained technicians. But current systems have the benefit of being well established. Breaking into an existing market with an innovative approach can be hard.
From novel idea to practical alternative
The team has already shown that their system can detect to a limit of 0.1 μM on ‘pure, artificial samples’ – these are lab samples that are always consistent. “When you move to patient samples, all patients are different, and their blood also contains different drug mixtures. So, we need to do more controls. The variability is significantly higher when going to patient samples,” notes Boisen. The work has already begun. The project has tested patient samples provided by Copenhagen University Hospital. Thanks to a BII grant from the BioInnovation Institute in Denmark, the team has the funding it needs to build on the support it received from the EU under THERA. Their success in identifying the target concentration range in blood took more than 10 years of ‘background’ research in SERS and centrifugal microfluidics – and strong teamwork. “I am most proud of the unique team effort and creativity that has brought us to where we are today. It requires a combination of skills and great collaboration across scientific disciplines such as optics, surface chemistry, electrochemistry, mechanical engineering, AI and medicine.” Boisen is optimistic about the way ahead: “We’ll use the BII funding to do more research on this. We are currently developing a second prototype and expanding its usability. The plan is to establish a company in around 18 months from now.”
Keywords
THERA, therapeutic drug monitoring, surface-enhanced Raman spectroscopy, SERS