A recent study carried out in a Swedish clinical testing laboratory aimed to evaluate the suitability of Capitainer’s quantitative DBS collection device, Captainer®B, for at-home sampling of HbA1c. Analysis of routine blood samples from diabetes patients revealed excellent agreement and almost identical results between qDBS and liquid blood, when HbA1c was detected immunologically on a Roche cobas® 6000 instrument. In addition, dried blood on Captainer®B cards was stable at room temperature for at least one month without any impactful change in measured HbAc1 levels.

HbA1c is a crucial biomarker for long-term glucose control and is widely used in the diagnosis of Type 2 diabetes as well as monitoring of blood glucose control in Type 1 and Type 2 diabetes. HbA1c (glycated haemoglobin or haemoglobin A1c) refers to the fraction of haemoglobin in the blood that is biochemically joined to glucose. The more glucose present in the blood, the higher the percentage of glycated red blood cells, and the higher the HbA1c result will be.

Current HbA1c testing methods mainly rely on EDTA-blood collected in a hospital or clinic by qualified personnel, either by venepuncture or capillary sampling. These samples are analysed for HbA1c content using various methods, including chromatography, electrophoresis, enzymatic assays, and immunoassays. One of the most widely used analytical platforms in clinical chemistry laboratories is the cobas 6000 analyzer from Roche. The presence of EDTA prevents the blood from coagulating so that HbA1c and other proteins present in the plasma can be analysed. In addition, HbA1c testing requires that red blood cells are lysed, and this is typically carried out in the testing lab manually or within the analyzer.

Dried blood spots emerging as an alternative sample type for HbA1c testing

Testing laboratories are increasingly recommending that blood samples are dried or lysed before sending into the lab. Interest in using dried blood samples is growing, as a more convenient approach that allows samples to be transported via regular mail.

Previous patient satisfaction studies have found that diabetes patients were happy with dried blood spot (DBS) sampling and prefer home sampling over traditional venous sampling at a medical centre (1, and references therein). A quantitative dried blood spot (qDBS) collection device that meters a known volume of blood in a pre-cut disc is therefore expected to facilitate at-home sampling for HbA1c, allow samples to be sent to a testing lab by regular postage, as well as greatly improve the overall patient experience.

Evaluating qDBS vs. venous blood samples in a clinical lab setting

To explore the potential of qDBS for at-home HbA1c sampling, researchers at Uppsala University’s Department of Medical Science in Sweden evaluated Capitainer’s qDBS device as a pre-step for HbA1c testing in a Swedish hospital laboratory setting.

When they measured HbA1c levels immunologically on a cobas 6000 instrument, they found excellent agreement between HbA1c levels measured in regular venous blood samples and in dried blood samples extracted from Capitainer’s qDBS device. Importantly, the study also resulted in a sample extraction protocol from Capitainer’s device that includes a red blood cell lysis step, thus simplifying the pre-analytical sample preparation workflow.

The study findings were published recently in The Scandinavian Journal of Clinical & Laboratory Investigation (2).

Excellent correlation between qDBS samples and fresh blood from diabetes patients, when analysed on cobas 6000

This study evaluated more than 100 venous blood samples over a broad range of HbA1c levels that had been collected in EDTA-containing tubes as part of routine testing of diabetes patients in Uppsala University Hospital in Sweden. The workflow was as follows:

1. Samples of 25 μL of blood, mimicking a drop of finger-prick blood, from each of the EDTA-tubes were applied to a microfluidic channel within Capitainer’s qDBS device (marketed as Capitainer®B). This device is designed to meter an exact volume of 10 μL to a pre-cut disc through the microfluidic channel.
2. The blood was left to dry into the disc overnight at room temperature.
3. HbA1c was then eluted from the qDBS disc using an extensively optimised protocol that incorporates a red blood cell lysis step, which is described in (2).
4. The extracted HbA1c samples were analysed on a cobas 6000 instrument in duplicate using Tina-Quant reagent; this workflow detects HbA1c via a specific antibody.
5. All samples were also analysed for HbA1c using capillary zone electrophoresis on a CAPILLARYS 3 TERA, which is the instrument used for routine testing of patient samples at Uppsala University Hospital, and which served as the reference method in this study.

The study found that analytical performance specifications using Captainer®B in comparison with standard clinical laboratory methods were in agreement for HbA1c concentrations up to 75 mmol/mol. The Swedish Medicines Agency’s treatment recommendation for glucose control in type 2 diabetes specifies a target value of 42–52 mmol/mol. Importantly, all samples in this interval were inside the national accuracy goal for HbA1c for hospital laboratory equipment in Sweden.

In addition, the study revealed that qDBS samples were stable at room temperature for at least one month, which further supports the feasibility of the approach for at-home sampling of HbA1c and regular shipping back to a clinical testing lab.

Transforming the patient experience with at-home sampling of HbA1c

The current study demonstrates that Captainer®B is an ideal sampling solution for at-home monitoring of long-term glucose control and echoes the results of other recent studies exploring the suitability of qDBS for routine at-home sampling. For instance, researchers in Norway investigating self-sampling for routine monitoring of kidney transplant patients recently found that the sampling success rate was consistent for Captainer®B (92-96%) regardless of whether sampling was performed by healthcare staff or the patients themselves, with or without supervision (3).

Implementation of at-home HbA1c sampling is expected to completely change disease management, by reducing the demand on diabetes patients to attend regular appointments to monitor long-term glucose control; many of these patients have already indicated satisfaction with at-home sampling and a preference for microsampling over venepuncture.

In addition to excellent performance in determining target analyte levels, in this case HbAc1, this study and others highlight other major advantages of using qDBS over venous blood sampling, including increased accessed to diagnostics in remote/sparsely populated areas. In addition, the introduction of at-home qDBS sampling to reduce the number check-ups needed at medical centres may also contribute to better treatment compliance, e.g., for patients with bipolar disorder treated with lithium, who need regular therapeutic drug monitoring.

References

1. Verougstraete N, Stove V, Stove CP. Remote HbA1c testing via microsampling: fit for purpose? Clin Chem Lab Med. 2023 Jul 10;62(1):3-17.
2. Rollborn N, Larsson A, Kultima K.  Analysis of HbA1c using microfluidic card (Capitainer qDBS card) as a pre-step before determination of the HbA1c value with an immunological method, Scandinavian Journal of Clinical and Laboratory Investigation, 2024.
3. Vethe NT, Åsberg A, Andersen AM, Skauby RH, Bergan S, Midtvedt K. Clinical performance of volumetric finger-prick sampling for the monitoring of tacrolimus, creatinine and hemoglobin in kidney transplant recipients. Br J Clin Pharmacol. 2023 Aug 3.