Dried blood spot (DBS) testing is used for the analysis of many molecules associated with human health and disease, with major applications in newborn screening and patient monitoring programmes all over the world, e.g., for phenylketonuria and other metabolic disorders.
Despite its vast applications, however, the composition of whole blood is highly complex, which limits the use of whole blood samples and microsamples in certain clinical laboratory analyses. For instance, the presence of blood cells can interfere with the optical detection methods used in clinical laboratories as well as point-of-care settings. Interference from haemoglobin in particular is also a major source of variability. The release of nucleic acids and other cellular components from lysed haemocytes and leukocytes has emerged as a new concern for the detection and quantification of circulating extracellular markers within diagnostics, requiring a cell-free blood matrix.
Blood plasma or serum is still the most widely used sample matrix in clinical laboratory investigations, but as of yet standardised methods for plasma microsampling are not available. In this blog post, we look at the potential of blood plasma microsampling within diagnostics.
The diagnostic power of blood plasma
Human blood plasma is arguably the most important and one of the most convenient sources of circulating biomarkers for health and disease. In simple terms, plasma is the liquid component of whole blood, and the plasma fraction is the cell-free matrix that remains when blood cells have been removed, typically through centrifugation of venous blood.
Plasma harbours many clinically-relevant analytes, including proteins, metabolites and nucleic acids, and it is widely used in clinical laboratories for the diagnosis or exclusion of many diseases, e.g., inflammatory diseases, autoimmune diseases, bone marrow diseases, liver disease, and many others. In addition, plasma is used to measure free drug concentrations in many therapeutic drug monitoring applications.
Plasma is also used to monitor the concentrations of experimental drugs and their metabolites during clinical trials for new candidate drugs, since it harbours the drug fraction most relevant for studying the pharmacokinetic and pharmacodynamic effects of the experimental drug. For quantitative analysis of certain analytes, e.g., potassium, plasma is the only suitable sampling matrix since sampling in whole blood does not yield reliable results.
The call for microfluidic blood plasma separation
The ever-increasing demand for patient-centric home-sampling solutions is driving the development of microsamplig methods for plasma. Such technologies could allow for blood plasma microsampling via a sampling device that would separate plasma directly from a drop of finger prick whole blood, as a highly convenient, fast, and non-invasive alternative to the current workflow of venous blood draw followed by plasma separation by centrifugation.
In addition to diagnostic benefits, blood plasma microsampling would offer the same advantages as DBS microsampling, including:
- The possibility to perform remote and home sampling, also for analytes that cannot be measured in whole blood, without the need for a trained phlebotomist.
- Elimination of geographical barriers to accessing a medical care facility, since dried samples can easily be shipped as non-hazardous material to labs or testing centres.
- Microsampling is minimally invasive, which makes it highly suitable for repeated testing/monitoring as well as testing in children or vulnerable individuals.
Plasma microsampling at home – soon available
Before plasma microsampling devices can become a reality, several requirements must be met:
- The plasma sample must be large enough to permit reliable detection of analytes present in trace amounts within the limited blood volume of a finger prick sample. In practice, this means that a plasma microsampling device must have a very high extraction yield to maximise plasma volume from whole blood.
- The device or method must be capable of yielding pure plasma that is completely devoid of interfering haemolytic blood cells or other impurities.
- The plasma separation technology must leave the target analyte(s) structurally intact without altering their concentration.
- The method must offer consistent and reproducible results.
- The device must be suitable for home sampling, i.e., it must be user-friendly such that a layperson can take a high-quality sample at home without any extensive training.
A truly patient-centric solution
The possibility to microsample plasma and whole blood at home or remotely opens up for a truly person-centric diagnostic solution since some disease markers need to be analysed in whole blood while others are detected in plasma. One application that calls for testing on whole blood and plasma samples is monitoring of patients receiving immunosuppressive drugs. In this group, the concentrations of immunosuppressive drugs need to be analysed in whole blood while some biomarkers for organ functionality require plasma as a matrix.
The volumetric microsampling solutions on the market today mainly offer whole blood sampling, which means that patients requiring whole blood and plasma testing currently still need to go to a health care facility for some of their tests.
Capitainer’s qDBS technology has already overcome many of the challenges associated with conventional DBS testing, and we are now working to fill the gap within plasma testing, by using our extensive knowledge and demonstrated experience in microfluidics to develop our first microsampling device for cell-free blood. Stay tuned for updates!
Relevant literature
1. Hauser, J., Lenk, G., Hansson, J., Beck, O., Stemme, G., Roxhed, N. (2018). High Yield Passive Plasma Filtration from Human Finger Prick Blood. Anal. Chem. 2018, 90, 22, 13393–13399, https://doi.org/10.1021/acs.analchem.8b03175.
2. Mielczarek, W. S., Obaje, E. A., Bachmann, T. T., Kersaudy-Kerhoas, K. (2016). Microfluidic blood plasma separation for medical diagnostics: is it worth it? Lab Chip,16, 3441-3448, https://pubs.rsc.org/en/content/articlelanding/2016/lc/c6lc00833j.
3. Asirvatham, J. R., Moses, V., Bjornson, L. (2013). Errors in Potassium Measurement: A Laboratory Perspective for the Clinician. N Am J Med Sci. 2013 Apr; 5(4): 255–259, https://pubmed.ncbi.nlm.nih.gov/23724399/.
Relevant Capitainer Blog Post
Global CRO Altasciences Evaluates Capitainer®qDBS Microsampling