Dried Blood Spot

Volume controlled Dried Blood Spot (DBS): A key player in personalized medicine

Dried blood spot sampling and subsequent analysis is an area that is of particular interest in relation to medicine, scientific research and the pharmaceutical industries collectively. It is a field that is growing rapidly and technological advancements are made.

What is DBS?

DBS is an alternative strategy for blood sampling that appears to be gaining momentum. It consists of applying a few drops of blood on an absorptive material and letting it dry before being used for appropriate downstream analysis. It was first introduced in 1963 by Robert Guthrie to facilitate the neonatal screening of phenylketonuria. This technique can be used for quantitative and qualitative applications; therefore, it rapidly spread to other applications such as virology, toxicology, therapeutic drug monitoring and genetics. 

DBS sampling showed excellent results when compared to conventional blood sampling methods. A recent review counted more than 2000 different parameters for which an analytical method was described in the literature, covering a wide range of medical applications [1]. This demonstrates the versatility and interest of the scientific community for this approach.

How is DBS performed?

DBS sampling is fast, cost-effective and conveniently requires only a finger or heel prick to draw capillary blood which is then collected on a filter paper card. This method is much less invasive in comparison to conventional venipuncture and patients of hospitals and labs too could benefit as it is less time consuming than conventional blood sampling (ie.venipuncture).

DBS and therapeutic drug monitoring

Tacrolimus is an immunosuppressant drug used for the treatment of graft recipients. Dose monitoring is required to ensure the patient’s exposure to the therapeutic drug is appropriate. DBS analysis was shown to be comparable to whole blood. It is consequently a suitable method for determining the overexposure or underexposure to tacrolimus, enabling the dose to be adjusted accordingly [2]. This application has a large potential in clinical applications such as the monitoring of antipsychotic drugs and antidepressants, enabling real-time analysis of plasma drug concentration levels, ensuring they are kept within the required range for an individual [3]. This personalized medicine approach to drug applications can be applied to many conditions

DBS and toxicology

Micro-sampling using DBS, in both animal and human studies has been widely used in the context of toxicology – including toxicokinetics and environmental and forensic toxicology {Reviewed in [4]. It is considered that in such applications, these can be widely used for analyte identification – such as markers to identify substance abuse [5]. 

In pre-clinical trial animal studies, pharmaceutical companies have employed DBS to monitor drug exposure in animals (toxicokinetics), this has been useful in rapidly establishing the suitable number of animals required with appropriate doses to adhere to the 3Rs in animal research [6].

Benefits of DBS

Less blood is taken from an individual in comparison to conventional methods. Samples are easily transported to analytical laboratories without the requirements for freezing or dry ice. [6] Importantly, the blood components appear to be more stable with preservation of the material of interest, this is of particular interest as RNA material has been shown to be preserved [7], considering RNA is particularly susceptible to degradation by endogenous factors.

Challenges of DBS

The low sample volume may not be suitable in some cases to reach the required sensitivity for specific molecules of interest. Concerns have been raised in relation to the effect of plasma/serum concentrations and haematocrit on spot size however, ongoing development continues to overcome this [8].

Personalized medicine

Personalized medicine can be defined as a medicine or therapy that has been specifically designed or tailored to suit the needs and requirements of the individual. We are each unique in our genetic makeup, this impacts our health in addition to lifestyle and environmental factors. The combination of information regarding our genome, along with additional clinical and/or diagnostic data, can elucidate patterns that will enable disease risk factors to be identified (earlier in principle). This will facilitate educated decisions, moving forward in relation to personalised medicines and even changes in dietary habits. DBS Systems is one of the leading organizations which provides the HemaXis DB10 devices for Labs and Hospitals across the world that can enable a bigger patient reach.

Benefits of personalized medicine

There are many benefits to personalised medicine and it can be applied across most fields of medicine. As an example, neurodegenerative conditions are on the rise as the population lives longer however, there are presently no cures for diseases such as Alzheimer’s. Advancements in metabolomic, proteomic and genomic approaches have been made [9] and research is striving to find appropriate biomarkers to help diagnose such disease conditions. The use of a test such as HemaXis DB10 in correlation with these biomarkers may provide clinicians with early diagnostic criteria to slow the progression or halt the disease. The key is early intervention.

Genomics and personalized medicine – what everyone needs to know

Fundamentally, almost all areas of medicine are affected by genetic disease and the clarification of the role of genetics in human disease combined with improvements in sequencing technologies can provide rapid diagnosis. Two interconnected and advanced methods of biological analyses are the sequencings of the human genome and new technologies that analyze DNA. 

In the clinic, whole-exome sequencing is increasingly being used for diagnostic purposes and detection of gene variants, in particular for genetically heterogeneous diseases [10]. With the emergence and continuing advancement of bio-analytical techniques, the use of DBS is of interest as a primary test. Globally, the interest in the advantages from a retrospective and prospective stance is being explored with DBS samples being used in conjunction with newborn screening programs in conjunction with high-throughput next-generation sequencing [11] [12]. Identification of disease-related gene mutations or modifications can provide the space for the development of specific and in many cases, personalized therapeutics.

Normalizing genetic testing into routine medical practices along with plans to entrench whole-genome sequencing within the NHS has brought to the forefront the importance of genomics to clinicians [13]. In this regard, the use of DBS has huge potential for genomics and personalized medicine to work hand in hand. Genomic medicine could transform healthcare.

Pharmacogenomics and personalized medicine 

New technologies have led to the transformation of different fields of medicine; including medicinal therapeutics, now encompassing personalized medicine using a pharmacogenetic approach. Pharmacogenetics is a relatively new area of pharmacology – investigating the relationship between an individual’s genetic makeup and the ability for the individual to metabolize specific drugs [14]. DBS will enable rapid detection of levels of drugs in capillary samples at a given time point.

The future for DBS 

The advancements in technological advancements and our greater understanding now mean that there will be more focus on personalized medicine companies and any new personalized medicine initiatives. These new applications will have the ability to present greater choices in relation to healthcare management for both the population and clinicians as a whole. Volumetric DBS offers many advantages, including the ability to control the volume of blood drawn. This can improve not only the accuracy of DBS analysis but uses minimal exploitable blood volume. Furthermore, the increase in volumetric DBS precision enables repeatability, important for consecutive and subsequent analyses.


References

  1. Freeman, J. D., et al., State of the Science in Dried Blood Spots, Clinical Chemistry, 2018. 64(4).
  2. Zwart, T..C., et al., Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device. British Journal of Clinical Pharmacology, 2018. 84(12): p. 2889-2902. 
  3. Geers, L.M., et al., Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Clozapine. J Clin Psychiatry, 2017. 78(9): p. e1211-e1218.
  4. Stove, C.P., et al., Dried blood spots in toxicology: from the cradle to the grave? Crit Rev Toxicol, 2012. 42(3): p. 230-43.
  5. Velghe, S., R. De Troyer, and C. Stove, Dried blood spots in therapeutic drug monitoring and toxicology. Expert Opinion on Drug Metabolism & Toxicology, 2018. 14(1): p. 1-3.
  6. Spooner, N., R. Lad, and M. Barfield, Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method. Anal Chem, 2009. 81(4): p. 1557-63.
  7. Aitken, S.C., et al., Stability of HIV-1 Nucleic Acids in Dried Blood Spot Samples for HIV-1 Drug Resistance Genotyping. PLoS One, 2015. 10(7): p. e0131541.
  8. Wilhelm, A.J., J.C.G. den Burger, and E.L. Swart, Therapeutic drug monitoring by dried blood spot: progress to date and future directions. Clinical pharmacokinetics, 2014. 53(11): p. 961-973.
  9. Gotovac, K., et al., Personalized Medicine in Neurodegenerative Diseases: How Far Away? Molecular Diagnosis & Therapy, 2014. 18(1): p. 17-24.
  10. Yang, Y., et al., Molecular findings among patients referred for clinical whole-exome sequencing. JAMA, 2014. 312(18): p. 1870-1879.
  11. Boemer, F., et al., A next-generation newborn screening pilot study: NGS on dried blood spots detects causal mutations in patients with inherited metabolic diseases. Scientific Reports, 2017. 7(1): p. 17641.
  12. Poulsen, J.B., et al., High-Quality Exome Sequencing of Whole-Genome Amplified Neonatal Dried Blood Spot DNA. PLoS One, 2016. 11(4): p. e0153253.
  13. Brittain, H.K., R. Scott, and E. Thomas, The rise of the genome and personalised medicine. Clin Med (Lond), 2017. 17(6): p. 545-551.
  14. Topić, E., 5. Pharmacogenomics and Personalized Medicine. EJIFCC, 2008. 19(1): p. 31-41.