Paving the way for personalised medicine

ChemSci Pick of the Week

Scientists in Germany have come up with an improved system for detecting analytes in blood in real time.

Dr Frank Biedermann is passionate about designing sensors that can analyse a patient’s blood in real time. "I experienced an emergency admission to hospital, where my blood parameters had to be analysed", he says. "I was rather shocked that it took about 30 minutes before the results came back from the lab, which could have been crucial minutes if my conditions had been something serious. I believe that inexpensive sensors are needed that can check the presence and concentration of relevant metabolites in real time, like nowadays pH and cation/anions can be routinely monitored online in the blood flow."

Similarly, sensors that can monitor molecules in a patient's blood in real time are crucial in the development of personalised medicine – whereby drugs and dosages are tailored to a patient’s metabolism. At the moment average doses are devised for 'average' – mostly male – test patients. However factors such as gender, age, weight, lifestyle and background affect how we metabolise a drug, and therefore how large a dose we should receive. If we could follow how drugs are being metabolised in real patients, we could devise more effective drugs and dosages for them.

Dr Frank Biedermann and his team from the Institute of Nanotechnology at the Karlsruhe Institute of Technology in Germany have devised a system that can rapidly detect target molecules. Their system involves large supramolecular compounds that act as 'host' for the target molecules. When the 'host' detects the target 'guest', the two molecules bind together, causing fluorescence, meaning that the presence of the target molecule can be observed.
Unfortunately the 'hosts' can often bind a large number of different 'guests' – meaning they don't always target the correct molecule. Dr Biedermann explains how the team has used the concept of 'artificial guests' to overcome this problem.

"Current artificial hosts behave a bit like a single person that is looking everywhere for a partner – these hosts bind to many things and are not selective. In sensing, one would very much prefer to have molecular binders at hand that only bind their 'true love' (i.e the target analyte) and not interact with everyone that is available. Unfortunately, synthetic chemists are largely unable so far to prepare selectively binding hosts that simultaneously feature a sufficiently high binding strength. Therefore, we were looking for ways to make use of the current unselective, strongly binding hosts and to teach them to be selective – to only respond to their 'true love'.

"We found through experiments and simulations that it is a good strategy to add to the system a known, strong binder – i.e. a temporary partner but not 'true love' that binds much more strongly than other matrix components with the host, but which is not the ideal match yet. This means that the host – that is now 'in a relationship' with the strong binder is not responsive anymore to other matrix components that naturally occur in blood serum at varying concentrations. However, the true love – the target analyte – still can displace the temporary partner from its complex with the host, to form the host–target analyte complex."

The team has applied this system to detect the Alzheimer's drug memantine, under physiological conditions. The system is not only quick but inexpensive, and paves the way to design sensors for a variety of targets.

This article is free to read in our open access, flagship journal Chemical Science: Frank Biedermann et al., Chem. Sci., 2019, Advance Article. DOI: 10.1039/C9SC00705E. You can access our 2019 ChemSci Picks in this article collection.