In our last article, we explored the economics of decentralized blood sampling and how at-home self-sampling may reduce healthcare costs by reducing the number of clinic visits, simplifying sample transport, and making testing more accessible. However, these advantages depend on one critical factor: sample stability.

For blood testing to move beyond traditional clinical workflows, blood samples must remain suitable for analysis while being collected, stored, and transported under less controlled conditions. This is where dried blood sampling differs fundamentally from conventional venous whole blood collection.

Why liquid blood is operationally demanding

Once venous blood is collected, it does not become biologically inactive. Cells remain active and enzymes continue to function. This means that metabolic processes can alter blood composition after collection, making whole blood samples inherently time-sensitive. For example, in unprocessed whole blood, glucose concentrations are reported to decline by approximately 5-7% per hour because blood cells continue to consume glucose through glycolysis (1, and references therein). This is why conventional glucose testing often relies on rapid plasma separation, short collection to analysis time, or specialized collection tubes containing glycolysis inhibitors (2).

In contrast, the use of dried filter paper blood spots, or simply dried blood spots (DBS), for glucose measurement is well established. Early studies showed that glucose remains stable in DBS for at least seven days under room conditions and that filter paper-based measurements can be precise, reproducible, and closely correlated with conventional whole blood glucose analysis (3, 4).

Glucose is just one example, however. Depending on the analyte, liquid blood samples may need to be centrifuged, refrigerated, frozen, treated with stabilizing additives, or transported quickly to preserve sample quality. These handling requirements make testing workflows more complex and can make it difficult to move blood collection out of the clinical setting. In a conventional clinical testing workflow, these demands are often manageable because collection occurs in close proximity to trained staff and laboratory infrastructure. In home-based or remote sampling, however, the same requirements can become limiting. A blood sample that must be chilled immediately, transported rapidly, or processed within a narrow time window is much harder to integrate into postal return or self-sampling programs.

What changes when blood is dried

When blood is dried, the specimen changes from a liquid to a solid matrix, while the analytes of interest remain available for analysis. Removing the liquid environment reduces the conditions that support ongoing biological processes, including enzymatic activity. As a result, many analytes become less vulnerable to changes during transport and storage.

This does not mean that pre-analytical handling no longer matters. Temperature, humidity, drying conditions, storage duration, and packaging can all still matter. However, for suitable applications, drying can create a sample format that is far less demanding to transport and store than liquid blood.

This is what makes dried microsampling so relevant to decentralized diagnostics. Samples that remain acceptable at ambient temperature for days, or sometimes longer, can be returned by post rather than refrigerated courier, collected at home rather than in a clinic, and handled with less dependence on immediate laboratory processing.

Clinically relevant analytes with established stability in dried blood

The value of dried blood samples becomes clearer when looking at analytes with established use or promising stability in dried formats. In addition to glucose, discussed above, the examples below illustrate how dried blood can support clinically important testing across metabolic health, newborn disease screening and therapeutic drug monitoring.

– Endocrine and metabolic biomarkers

In liquid blood, certain peptide hormones are highly sensitive to proteolytic degradation. Two such examples are insulin and C-peptide, whose stability can depend strongly on sample type, storage temperature, and the time between collection and processing. However, once dried onto a filter paper, the lack of moisture inhibits proteolysis, making stability less dependent on rigorous pre-analytical handling.

Researchers have demonstrated that C-peptide, a marker of beta-cell function used to distinguish between Type 1 and Type 2 diabetes, remains stable in DBS for up to six months at room temperature, with good correlation and agreement with venous samples (5, 6). More recent work has also shown that home DBS C-peptide sampling can be used to monitor β-cell function in newly diagnosed Type 1 diabetes, enabling more frequent assessment without repeated clinical site visits (7). Similarly, thyroid-stimulating hormone (TSH) shows excellent correlation between venous samples and DBS. TSH values have been reported to remain stable for up to 30 days at 22°C, though storage conditions, particularly humidity, can influence how well TSH is preserved in DBS over time (8, 9). Beyond its established role in newborn screening for congenital hypothyroidism, its ambient-temperature stability makes TSH a good candidate for remote monitoring of thyroid health.

– Newborn screening markers

Dried blood spot (DBS) microsampling has long been central to newborn screening, including the measurement of phenylalanine (Phe) for phenylketonuria. This established use shows how analyte stability in the dried format can make large-scale, decentralized testing practical. For example, phenylalanine in DBS has been reported to decrease by only about 5.7% per year when stored at room temperature in a dry environment, although elevated heat and humidity can accelerate degradation (10).

– Therapeutic drugs including immunosuppressants

Stability also matters for therapeutics. Some drug substances can undergo post-collection transformation in liquid blood, which can affect the reliability of therapeutic drug monitoring if samples are not stabilized appropriately. Azathioprine, an immunosuppressive prodrug, is a notable example; it has been shown to undergo spontaneous conversion to 6-mercaptopurine in fresh human blood in vitro through reaction with glutathione (11). This poses problems for assays that aim to measure azathioprine itself, since spontaneous post-collection conversion to 6-mercaptopurine can reduce the amount of parent drug present in the sample before analysis.

DBS has attracted significant interest for therapeutic drug monitoring, particularly where patients require repeated measurements over time. Tacrolimus, an immunosuppressant used after transplantation, has been studied extensively in dried blood formats. One validated LC-MS/MS method reported stability in DBS for at least one week at room temperature and 4°C, while a more recent clinical study showed that volumetric finger-prick sampling could be used to monitor tacrolimus in kidney transplant recipients, supporting its potential for self-sampling-based follow-up (12, 13). Several antibiotics have also been investigated in dried blood formats, with published data showing useful stability under defined storage conditions for drugs such as linezolid, ceftazidime, and meropenem (14). These selected examples indicate that dried microsampling may support selected forms of remote treatment monitoring as well as diagnostics.

From sample stability to scalable testing

The practical value of dried blood sampling depends on more than convenience. These stability advantages help explain why DBS can support the simpler logistics and lower-burden workflows discussed in our previous article on the cost of blood collection in healthcare. For suitable analytes, stability in the dried format can enable simpler transport, remote collection, and reduced reliance on immediate laboratory processing.

Not every biomarker or drug substance will be suitable for dried blood analysis. But where analyte stability and analytical performance are well established, dried microsampling can help support more scalable, patient-centered approaches to screening, diagnostics and therapeutic drug monitoring. For organizations considering dried blood sampling, the next step is therefore not only to ask whether the analyte is stable in the dried format, but also whether the sampling technology can deliver the accuracy and precision required for the intended use.

As described in an earlier article on Capitainer’s technology, volumetric dried blood microsampling is designed to build on the sample stability benefits demonstrated by DBS while addressing the variability associated with conventional DBS cards. By combining dried-sample stability with accurate and precise volumetric collection, Capitainer helps make dried blood testing possible in application areas where reliable high-precision quantification is essential.

Interested in exploring whether dried microsampling could support your application? Contact us to discuss suitable sampling formats and workflows.

References:

1. Bruns DE, Knowler WC. Stabilization of glucose in blood samples: why it matters. Clin Chem. 2009 May;55(5):850-2.

2. Sacks DB, Arnold M, Bakris GL, et al.; National Academy of Clinical Biochemistry; Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011 Jun;34(6):e61-99.

3. Winocour PH, McKinnon GA, McMurray JR, Anderson DC. Evaluation of the measurement of blood glucose levels on dried filter paper blood spots. Diabet Med. 1985 Jul;2(4):269-71.

4. Abyholm AS. Determination of glucose in dried filter paper blood spots. Scand J Clin Lab Invest. 1981 May;41(3):269-74.

5. Willemsen RH, Burling K, Barker P, et al. Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3350-3358.

6. Johansson J, Becker C, Persson NG, Fex M, Törn C. C-peptide in dried blood spots. Scand J Clin Lab Invest. 2010 Oct;70(6):404-9.

7. Hendriks AEJ, Marcovecchio ML, Evans ML, et al; INNODIA Consortium. Early Detection of β-Cell Decline Using Home Dried Blood Spot C-Peptide Levels in New-Onset Type 1 Diabetes. Diabetes Care. 2025 Sep 1;48(9):1484-1492.

8. Magalhães PKR, Miranda CH, Vilar FC, et al. Effects of drying and storage conditions on the stability of TSH in blood spots. Arch Endocrinol Metab. 2018 Apr 5;62(2):201-204.

9. Adam BW, Hall EM, Sternberg M, et al. The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States. Clin Biochem. 2011 Dec;44(17-18):1445-50.

10. Moat SJ, George RS, Carling RS. Use of dried blood spot specimens to monitor patients with inherited metabolic disorders. Int J Neonatal Screen. 2020 Mar 26;6(2):26.

11. Chrzanowska M, Hermann T, Gapińska M. Kinetics of azathioprine metabolism in fresh human blood. Pol J Pharmacol Pharm. 1985;37(5):641-8.

12. Shokati T, Bodenberger N, Gadpaille H, et al. Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS. J Vis Exp. 2015 Nov 8;(105):e52424.

13. Vethe NT, Åsberg A, Andersen AM,  et al. Clinical performance of volumetric finger-prick sampling for the monitoring of tacrolimus, creatinine and haemoglobin in kidney transplant recipients. Br J Clin Pharmacol. 2023 Dec;89(12):3690-3701.

14. Dalla Zuanna P, Curci D, Lucafò M, et al. Preanalytical Stability of 13 Antibiotics in Biological Samples: A Crucial Factor for Therapeutic Drug Monitoring. Antibiotics (Basel). 2024 Jul 20;13(7):675.