what is microsampling? a conversation with james rudge
by Neoteryx | 5 min read
James Rudge has served as our Global Microsampling Specialist since January of 2015. Prior to joining Neoteryx, Dr. Rudge worked for Phenomenex for 14 years and is a co-inventor of the Mitra Microsampling Device and the Volumetric Absorptive Matrix Sampling technology.
This conversation is an excerpt from the e-book Exploring Microsampling by Bioanalysis Zone. In it, James explains the workings and applications of Mitra® devices based on VAMS® technology, and makes some predictions for the next 5-10 years of microsampling.
Could you tell us about the Mitra VAMS technology?
VAMS stands for volumetric absorptive microsampling, and is a technique for obtaining a small amount of a biological fluid. It’s based on the best bits of dried blood spot and low volume pipetting.
The idea behind it is that you’ve got a small, absorptive hydrophilic polymer on the end of what looks like a pipette tip. When you apply the tip at a positive angle at a blood pool, whether that’s a finger prick or taken from an animal’s tail, and then very rapidly the blood (in this case) is absorbed onto the tip, allowed to dry.
It’s quantitative, so it usually takes up 10 or 20 microlitres, which solves one of the fundamental issues of DBS. Then, in very much the same way as dried blood spotting (DBS), the blood on the tips are dried and they can be sent via regular mail to a laboratory, so it allows for remote sampling and analysis at a laboratory many thousands of miles away. Within the laboratory this is where the pipette tip comes into play – having the pipette tip means you have the option to automate a product onto standard lab liquid handling systems.
What are the uses of the technology?
The uses of the technology are quite wide, from drug clinical trials in which the blood of individuals needs monitoring through to research in low-resourced regions, through to analyzing even larger molecules such as proteins and peptides – even RNA and DNA!
What are the limitations of the technology?
The limitations of the technology are based upon what it is the lab really wants to measure and how it’s going to measure it. If one takes, for example, an immunosuppressive like (Tacrolimus), it’s a perfect candidate for volumetric absorptive microsampling because that molecule will partition mainly into the hematocrit, and in actual fact, in the lab it is analyzed from blood and not a portion of blood such as plasma or serum.
On the flip side, if one wanted to measure potassium then it wouldn’t be a good candidate and the reason for that is because plasma-potassium is tested quite a bit in terms of measuring electrolytes. The body will selectively pump potassium into cells so when you collect blood and you let that blood dry onto a surface like a DBS card then the drying action causes a release of cellular potassium into the plasma massively biasing the results and making them interpretable.
If you’ve got compounds which only exist in the plasma fraction, such as vitamin D, then you can measure vitamin D levels using VAMs but then one has to be aware that the plasma concentration. This is because for the same volume is always going to be higher for the blood concentration because the blood cells take up some of that volume so one has to think about different reference ranges or adjusting the data to match the plasma data.
So it really depends on what it is you want to do.
What benefits of microsampling have you seen in your own work?
In the clinical environment, it’s all about the patient experience, so some of the drugs that patients are expected to take have a very narrow therapeutic index, so monitoring is important.
Immunosuppresants are the perfect example. When dosed too high, you get necrosis of an organ. Too low a dosing, and then you risk organ rejection. One of the side effects of these drugs is that some of the people on these drug regimens can become immunocompromised - going to clinic is disruptive for the patient, as hospital could potentially be exposed to pathogens.
So, to be able to offer a microsampling solution where they can test at home, is really good and is less disruptive to their lives, it’s safer, and it means you can potentially take more time points. One could argue for and against why you would want to do that, but it gives the opportunity to do this rather than go back into the clinic for multiple blood draws.
Another great area is drug compliance and there’s been some really interesting statistics out, which show that drug non-compliance can be anywhere between 30 and 80%. One of the ways in which we can try and improve drug compliance is to monitor at home by people testing themselves, and that provides some huge benefits.
To what extent is lack of training and education accountable for the slow transition to microsampling?
The key thing for me is that there has to be a body of good peer-reviewed data out there – both in analytical chemistry, but also in clinical chemistry, so that late adopters oftechnology feel confident that the technology is going to work for them, and that’s what’s really important.
How can we overcome this?
It’s all about education, all about learning, training, reading and being engaged with the technology. Once one feels more comfortable about using the technology, you know what the potential drawbacks and challenges are, you can build upon that and make good, robust methods that can be very relevant for what it is you’re trying to do.
What advice would you give to researchers/labs looking to implement microsampling?
For me, it would be to learn as much as you can – go to conferences, read journals. It’s a new technology – yes, it’s been around for a while but back in the 1960s those blood spots were essentially analysed by semi-quantitative methods. There are a lot more challenges now as we’re really trying to tighten up the quantitation. So don’t give up!
Where do you see the field in the next 5-10 years?
In the next 5-10 years, because of the massive increase in computing power and instrument sensitivity and specificity, I see a whole raft of biomarkers coming out for various clinical reasons, so there’ll be a whole pile of new tests compatible with microsampling that are going to be clinically relevant and clinically available.
Perhaps in the next 20 years I hope that with just one drop of blood we’ll be able to analyze the genome, phenome and metabolome, and then detect and personalize the treatment of a disease based on one blood spot.
Find Exploring Microsampling and other informative documents in our Mitra microsampling resource library.