This month we have another big interview, this time with Christophe Stove, a giant literally, but also in the field of micro-sampling and pharmacology/toxicology. This interview was also recorded at last years’ congress (pool side, where Christophe was peer reviewing a piece of research work. Apparently some three quarters of all micro-sampling papers go through Christophe’s hands as a peer reviewer; not a bad way to stay on top of the field!). The bit about his love of the word serendipity, and some longer sections, came more recently by email – all very good, so do read on. Christophe updates us on where his group is with their micro-sampling work, and we also hear about some more recent novel work, including activity-based bioassays.
Apologies for the delays with our blog interviews, shelved since last October with the civil unrest in Chile; these should continue as normal with a backlog of some great interviews to come in the following months.
A typical day for me is difficult to describe. It depends on whether it is during the academic year. There are three kinds of activities that I might be involved in. The first is a laboratory service, so a forensic toxicology service for the department of justice and reference lab activities, for example thyroid hormone activities and other hormones. The second is teaching duties; I have several courses I teach at the Faculty of Pharmaceutical Sciences. The third takes most of my time and it is research.
We try to focus on niche applications. We don’t want to be good at everything, we want to be good at some specific things. During the last few years we’ve focused on two main research lines. The first is micro-sampling and dried blood spot sampling, where we try to tackle some of the logistical issues and limitations that are involved. The other research line, which is quite recent, involves setting-up activity-based bioassays which is allow universal activity-based monitoring of drugs, such as opioids or cannabinoids in biological fluids.
The idea for a bioassay actually came a little bit from my background: my PhD was in cell biology and my post-doc involved molecular biology (Ed’s note: more on this later). Working with new psychoactive substances I wondered ‘rather than looking at the presence of these structures in fluids, wouldn’t it be possible to monitor their activity?’ It’s relatively easy and straightforward. Many people have told me afterwards ‘it’s such a simple idea, so why didn’t anyone else think of it?’ One way is to just set up a culture and modify it to express targets, for example opioid or cannabinoid receptors, and in some way generate a readout to indicate activity.
It is actually quite sensitive: we are competitive with big Mass instruments. We are almost at a point where we shouldn’t become more sensitive because otherwise there may be issues where traditional analysis cannot confirm our results. As it is a screening strategy, it still requires confirmation. We have had instances where we are convinced that something is present, but it couldn’t be confirmed analytically, so we have to consider that and name it as a false positive.
In the field I work in – and I’m obviously biased – it is obviously the introduction of highly sensitive mass spectrometric instrumentation, allowing the quantitative determination of virtually any therapeutic drug (also the ones for which we wish to detect ng/ml concentrations) in a microsample, corresponding to just a few µl of blood. This means that the amount of starting material is just a few pg, the current instrumentarium allows us to detect these pico-quantities.
I consider serendipity as a key word in my scientific career. As a matter of fact, when reflecting about it, this is likely my favourite English word, not just because it reflects my career paths, with many tiny things being decisive for my current position, but also because of the mere sound of the word – like the wind gently blowing through the trees. After becoming a pharmacist, I embarked upon fundamental cancer research during my PhD and first postdoc, before getting a phone call from my antecessor Willy Lambert, to ask whether I was interested to apply for a position as a postdoc with him, back at the Faculty of Pharmaceutical Sciences, to work in the field of bioanalysis. At that point I actually only knew that field from my studies, which I had finished eight years earlier, and I must admit there was a LOT that I didn’t know anymore. Willy still remembered me as a student, and coincidentally a technician I had worked with during my PhD, was in close contact with him. Unbeknown to me, I had been somewhat ‘followed’ at a distance. To make a long story short, I was selected for the postdoc, also liked the field of bioanalysis and eventually succeeded in getting a tenure-track position at the Faculty.
As the Lab was already doing research in the field of TDM and (Forensic) Toxicology, I continued along that line, although (somewhat coincidentally) starting to focus micro-sampling, which has become a key area of expertise throughout the last decade. The selection for my tenure-track also included the start-up of a cell biological research line: for this, I combined my cell biology and molecular biology expertise with my newly acquired knowledge about the issue of detecting new psychoactive substances in forensic toxicology: the concept of activity-based detection of new psychoactive substances was born. It is the aim to keep both research lines – bioanalytical and cell biological – running during the upcoming years.
That’s a difficult question. We do try to focus on ourselves, and on what we are good at. Typically, if we can’t do something, we try to collaborate with other centres rather than trying to integrate it into our lab. I would prefer to work with the specialists in the field rather than trying to be a semi-specialist in a particular area.
We are not involved in clinical services. We have several on-going collaborations with clinics, but there’s no clinical services per se. So, the only service activities that we are doing is for forensics, for the department of justice for forensic toxicology. Nothing like high throughput, for instance.
This is quite difficult to say. As an academic lab, we primarily aim at developing new concepts, tackle existing challenges, or demonstrate proof-of-concepts. This isn’t always an easy route: once proof-of-concept is demonstrated, in many instances we do not necessarily continue along that line, as the ‘challenge’ is no longer there. This is somewhat distinct from e.g. a clinical laboratory environment, where most often a newly developed method is specifically set up with the aim to be run in that lab environment. I am fortunate to have been able to establish good contacts with many collaborators (both in companies, clinical and academic labs), in Belgium, Europe and globally. This combined with a great team of collaborators (current and past), some luck and some out-of-the-box thinking, have allowed several research lines to yield ‘deliverables’ that might have some (clinical) practice in future. Besides ‘conventional’ micro-sampling methods we’ve developed, and the beta-testing of several micro-sampling technologies, I’m thinking more about methodologies to predict the haematocrit of dried blood microsamples (one of which resulted in a patent), and activity-based screening approaches allowing ‘universal screening’ of biofluids (for every past, current and future cannabinoid or opioid). There is some commercial interest in these technologies, but whether they will effectively be brought to use only the future will tell. Although future applicability is virtually always on the top of my mind when developing something new, I’m too much of an academic to effectively dive into that ‘future aspect’. I do admire entrepreneurs that effectively combine both fields, converting lab-developed proof-of-concept work into a real product.
I’m quite biased in that perspective for future in TDM. I consider micro-sampling a field that has some potential, but people must be aware of the limitations and that things need to be done appropriately. We recently wrote a guideline, which was also addressed in a Compass issue: we aim to overcome the issue for many publications in the field that report successes in micro-sampling that to me do not represent successes. In some instances, there are even wrong interpretations. I’m a very strong proponent of micro-sampling but we should also look critically at the data, because if we don’t do so, we will damage the field.
There are several challenges that we need to overcome with micro-sampling, related to haematocrit, contamination and really being sure that the result is the same as what you would obtain with conventional venous sampling. That remains one challenge to really demonstrate, including convincing clinicians that you can get trustworthy results. Obviously, that requires good control of quality, and requires that you really know what micro-sampling is about, rather than performing it just to get a result. Anyone can get a result from a dry bloodspot, but the issue is being sure that the correct result is obtained.
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