A Drop is All it Takes: Automated Mitra® for Volumetric Microsampling
As scientists, we all have different motivations which drew us into pursuing a scientific career. For some it might have been the love for knowledge (a concept which is literally embodied in the etymology of Ph. D); for others, it might be the lure of pushing the boundaries of innovation, and for some the opportunity to omniscience by harnessing the power of a multidisciplinary team and collaborations with knowledgeable partners. Would you be surprised if I told you this is the story of a serendipitous combination of all the above?
In our applications laboratory, projects occur for two reasons: an opportunity to develop a dedicated customer’s solution or a route to innovation in analytical science. The two approaches can be linked, and fruitful collaborations with a customer can indeed lead further than the initially agreed plan.
Watch the Webcast – Automated VAMS® Technology: The story behind it
And that is exactly what happened with our work using automated Volumetric Absorptive Microsampling via Mitra® devices with VAMS® technology.
Let me start from the beginning.
Whilst I had heard about Mitra® devices with VAMS® technology before, I never had the chance to test the volumetric microsampling concept directly.
That was until 2018, when one of our customers was looking into automating the extraction of steroids as performance-enhancing compounds from whole blood in anti-doping analysis. They were keen to explore the newly introduced VAMS® approach for that purpose. Beforehand, I had only really come across the legacy blood microsampling techniques, i.e. Dried Blood Spots (DBSs), which I knew had been widely adopted in clinical and forensic laboratories since the 1960s1.
The new Mitra® devices certainly intrigued me, offering an innovative alternative approach not only to microsampling for blood , but also potentially for other biofluids as well (e.g. saliva, urine, sweat).
Introduced back in 2014 and later patented by Neoteryx2, VAMS® technology was developed to overcome the uneven analyte distribution challenges associated with DBS samples due to the Haematocrit (Hct) effect, i.e. the proportion of red cells within blood, which has a significant impact on its viscosity and consequently on blood distribution on DBS spotting paper3. On the other hand, Mitra® devices absorb a fixed volume of blood (10 μL, 20 μL or 30 μL), eliminating both spot migration and spot punch location biases which were previously observed with DBS.
At the time, the focus of the project using Mitra devices with VAMS was very much on the automation of the sample preparation only, specifically applied to our customer’s application. For that purpose, we translated the manual method onto our instrument top X-Y robotic platform, applied Design of Experiment (DoE) to optimise the automated extraction methodology for the target analytes in whole blood using the Mitra devices, and then proved comparability between the manual and the automated approach. Job done.
However, the beauty and facile nature of Mitra® as a microsampling device stuck with us. As an automation company, we were driven by the possibilities to fully explore the complete automation of the Mitra® sample preparation workflow.
The major question which remained unanswered was the handling of the Mitra® microsamplers and their VAMS tips before extraction. Could we automate the delivery of the VAMS tips from the dedicated 96-Autorack™ for the Mitra® devices directly into the vial to proceed with the automated extraction as a fully automated workflow?
Needless to say, we accepted this challenge and began to investigate the options available. This work could not have succeeded if it wasn’t for the ongoing support from our invaluable collaborators, our friends at Neoteryx and at Integrated Liner Technology (ILT) caps and septa, which helped us address the major practical hurdles we encountered during development.
In 2020 we were ready to test the automated Mitra® solution. We wanted to make sure it was going to fulfil the requirements of a real-case scenario in terms of robustness and reliability. If we also produced analytically relevant data, well, so much the better!
We needed a partner. Enquiries were brought forward, introductions were made and in 2020 a fantastic opportunity to work together with Dr Rachel Carling and her team at Synnovis (formerly Viapath) arose.
Rachel is Consultant Scientist and Director of Biochemical Sciences at St Thomas’ Hospital, London, and her team is heavily involved with therapeutic drug monitoring (TDM) testing to provide patients with frequent monitoring and dose adjustment.
For our collaboration, we chose to focus on the measurement of immunosuppressants in whole blood which is central to the monitoring of patients with solid organ transplants.
Two years later, the paper capturing all our efforts to develop and optimise a fully automated workflow for Mitra® handling and extraction for TDM has now been published and is available by following the app note link below.
Furthermore, should automated volumetric microsampling with Mitra® have intrigued you as much as it intrigued us, do reach out and let’s explore the automation advantage for your workflow. As you might have guessed, here at Element Cambridge, we love a collaborative challenge.
To realise your fully Automated Mitra® with VAMS workflows then – a drop is all it takes.
Camilla Liscio – Principal Scientist
Camilla Liscio is the Principal Scientist at Element Laboratory Solutions-Cambridge, passionate about helping scientists implement automation, and its synergy with data analytics, within their laboratories. After a master’s degree in Chemistry at the University of Genoa, Italy, she continued her academic education path with a PhD in Analytical Sciences, followed by a Marie Curie postdoctoral fellowship which brought her to the UK. Once her postdoctoral experience was complete, she moved to industry spending three years as a Researcher in the Organic Analysis team at the National Measurement Laboratory (NML), LGC, Teddington. In 2016 she started her journey with automation when she joined Element (formerly Anatune) as an Application Chemist. In 2021 she accepted the Principal Scientist role and now looks after the operational and R&D side of the Applications team. When she is not in the lab developing new automated applications, she can be found in the kitchen cooking, walking her Japanese Spitz Scintilla or crafting.
1. R. Guthrie et al., A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants, Pediatrics, 1963, 32:338–343.
2. N. Spooner et al. A device for dried blood microsampling in quantitative bioanalysis. Overcoming the issues associated with blood haematocrit, Bioanalysis, 2014, 7: 653–659.
3. A.J. Wilhelm et al.Therapeutic Drug Monitoring by Dried Blood Spot: Progress to Date and Future Directions, Clinical Pharmacokinetics, 2014, 53:961–973.