Minimalist Monitoring

We are all well aware that patients in developing countries urgently need access to medications for chronic illnesses. But a discussion we have far less frequently is what happens once those patients receive the treatments they need.

“Monitoring drug concentration in patient blood is an important aspect of medical treatment to improve the efficiency of the drugs and decrease the side effects,” says Lin Xue, a postdoctoral scholar at École Polytechnique Fédérale de Lausanne. But it’s easier said than done; most monitoring calls for expensive equipment and complex facilities that may not be available in resource-poor areas. Often, patients have to stay close to the lab or hospital, infringing on their quality of life – and that’s if they’re able to access monitoring at all. Xue and his colleagues recognized the need for affordable point-of-care detection of drug concentrations in blood and developed a biosensor molecule made up of three components (1):

1. An antibody fragment that can bind the drug to be monitored,
2. The light-producing enzyme luciferase, and
3. A “tagging” molecule called SNAP-tag, which carries a fluorescent ligand that the antibody binds only when no drug is present.

In the absence of the drug, the antibody and SNAP-tag bind, causing a reaction called “bioluminescent resonance energy transfer” that produces a red light. But as drug concentrations increase, the antibody preferentially binds to the drug, displacing the fluorescent ligand and causing the emission of a blue light instead. The result? A simple, measurable visual that indicates the amount of drug present in a patient’s blood.

“The biosensors can be incorporated into paper-based point-of-care devices, which are cheap, portable, time-saving and easy to use. They could even be used by the non-experts, such as the patients themselves,” says Xue and emphasizes that the system works with any antibody: “We can theoretically design antibody-based sensors towards an unlimited number of synthetic drugs.” And the sensor’s performance was independent of the antibody used – meaning that there’s no costly, time-consuming optimization process needed to create a sensor for a new type of drug.

What would such a sensor look like in the clinic? Ideally, as simple as modern blood glucose meters, allowing patients to take a fingerprick sample and use a handheld reader, perhaps in conjunction with a smartphone. In fact, Xue’s colleagues have already developed working prototypes of test strips and a reader, so the researchers are optimistic that their device should be available in the next few years. Ultimately, they’d also like to expand it; after all, says Xue, the need for monitoring doesn’t stop at drug levels – he anticipates tests for pathogens, hormones, vitamins, and even biomarkers.