Without any delay: drug dose adjustment at the point of care

Many therapeutic drugs are very powerful, but they are also very toxic at the same time. Thus, they have to be measured regularly, again and again, so that an adjustment of the individual drug dosage can be made. Until now, the "normal" way was to take the blood sample, send it to a central laboratory and get the results after some days. A new point-of-care test can measure it in 15 minutes.

Prof. Segura, what is the project ISyPeM 2 (Intelligent Integrated Systems for Personalized Medicine)?

Prof. Jean-Manuel Segura; In the ISyPeM 2 project we develop a new kind of point-of-care device, which makes it possible to measure the concentration of therapeutic drugs in the blood – directly from a single drop of blood. Then, the results will be shown in a reasonable time of about 15 minutes. This device would be offered to general practitioners, specialized clinicians or even directly to the patients. Currently, if therapeutic drugs must be monitored, a blood sample must be taken which would be sent to a central laboratory. And it can take some days to get the results of the sample. Also, there is no real help for the practitioner, no suggestion how to adjust the dose of the drug. Now, in the context of the project, we want to bring the analysis close to the patient and the practitioner.

How does this point-of-care test (POCT) work?

Segura: It is a multicomponent system. The project is not finished yet, but what we envision is a cartridge -reader system. The cartridge which is a disposable component can extract plasma from the blood. After that, it mixes the plasma with the reagents and then brings the solution to the measurement cell. For the read-out, the technology we use is a homogeneous assay based on fluorescence which may be relatively standard but was not very often used for compact devices. Basically, it is "mix and measure", no complicated external sample preparation needs to be done. The blood will be extracted, you mix and measure it.

Why is such a device necessary?

Segura: It's probably not absolutely necessary, but it has two main benefits. First, the time for the diagnosis. It is not life-threatening, but it would be much more efficient when the patient would not have to leave the office, but instead get the diagnosis immediately. So, basically, the measurement will be taken and after 15 minutes the practitioner or the specialist can directly make an adjustment to the drug dosage based on the test results. Also, the individual devices are connected to a remote database. This means that beyond the patient’s measurements, the device provides the physician with information of similar cases, giving a suggestion of dosage adjustment.

The second advantage is the amount of blood needed for the test. Currently, for a test 500 microliters are needed. This is especially difficult for children or neonates. For newborns, there are several therapeutic drugs which need to me monitored. We are working with one particular drug, the antibiotic Tobramycin. That one is typically given to a neonate who got bacterial infection for a couple of days. The concentration of the antibiotic needs to be precisely adjusted. If it is too low, the infection is basically not treated. But if it is too high, then it can be nephrotoxic, but also ototoxic, leading to the child’s hearing loss. For the drug dosage adjustment, regular measurements need to be taken. But taking a blood sample of 500 microliter is for a neonate actually quite critical. With our device, it would be enough to take 20 microliters which is just a small drop of blood. That is the clear advantage. It is less risky for the child.

How can it be integrated into daily clinic life?

Segura: It depends a bit on the drug the patient has to take. Which drug requires monitoring and how often it has to be done is defined by clinical practice. For example, for Tobramycin you have a best practice, telling when to measure and how often. What we would change, is, instead of sending it to the central laboratory with the blood sample, we would immediately make an adjustment of the drug dosage. It could be directly integrated into daily clinic life, just as it would be done without the POCT. But the outcome would improve.

Can it be used for any drug?

Segura: In principle, yes. Only the cartridge would be different for the different drugs. For example, if a physician is measuring Tobramycin, he needs the cartridge for Tobramycin. However, not all drugs require monitoring. Right now, there are between 20 and 50 therapeutic drugs that require monitoring, but it is rapidly increasing. The new drugs are more potent, but they are also very often more toxic which means that the dosage should be very well adjusted.

What is the current status of the project? What are the next steps?

Segura: We have shown that we can implement the test into a paper micro chamber. The interesting thing is that paper can help to extract plasma from the blood. We use it then for the mixing in the measurement chamber. So, we have a very compact cartridge made out of paper.

Currently, it is more a proof of principle project. We want to show that it is possible and how it would look like. The project itself ends in October, so currently we are looking for industrial partners who are interested to continue the project, so we can develop it into a product and bring it to the market.

Where are POCT currently developing? Where do you see their future?

Segura: I think there is a lot of potential for POCT, especially if they can be made more compact and easier to handle. Afterwards, this really depends on the disease or the illness. In some cases, there will be a very rapid test that you can do for instance at the side of an accident or at the place where the patient is. Sometimes it can be something like a "real" POCT, but there could be also something in between a rapid test and a clinical analyzer. The one key feature is the quality of analyzing. So how do you ensure that the quality is the same as in the central laboratories? But in term of costs, rapidity and usability, I think there is a potential future for point-of-care diagnostics.