Blood by Post: How Microsampling Is Changing Where Samples Come From

Most blood tests still depend on a venous draw. That means a trained phlebotomist, a collection centre, a centrifuge and, often, a cold chain to get the sample to the lab intact. In a city that’s routine. In remote and regional Australia, it can mean a long drive, a missed day of work, or a sample that never gets collected.

Microsampling takes a different approach. A small volume of blood, typically tens of microlitres from a finger-prick, is collected onto a card or an absorbent tip, dried, and sent to the laboratory by ordinary post. There’s no centrifuge, no cold chain, and in many cases no clinician present at collection.

Not a new idea, but newly practical

Dried blood has been in routine use for decades. In Australia, newborn screening programmes have relied on heel-prick blood spots on filter card since the late 1960s.

What has changed is the analytics. Modern LC-MS/MS can quantify many drugs, metabolites and biomarkers from a few microlitres of blood, so a small, dried sample now carries enough material for meaningful quantitation. Collection devices have improved alongside it.

The main formats

Dried blood spots (DBS). Blood is dropped onto filter paper and allowed to spread. Simple and cheap, but the volume in any punched disc depends on how the blood spread, which is affected by the sample’s haematocrit.

Volumetric absorptive microsampling (VAMS). An absorbent polymer tip wicks up a fixed volume of blood, regardless of haematocrit. This removes the volume bias of conventional spots.

Volumetric DBS devices. These collect a defined volume through a capillary before depositing it onto the card, combining a known volume with the familiar card format.

What microsampling opens up

The advantages go beyond convenience.

Decentralised research and clinical trials. Participants can collect samples at home on a set schedule, widening who can take part and reducing site visits.

Remote and regional health research. Studies can reach communities where venous collection is impractical, and samples survive the journey without refrigeration.

Repeated or time-critical sampling. Pharmacokinetic studies and therapeutic drug monitoring research often need several samples over a day. A finger-prick at home is far easier than repeated venous draws.

Small-volume populations. Paediatric studies and preclinical work benefit from collecting less blood per sample.

Sample stability and logistics. Many analytes are more stable dried than in liquid blood, and dried samples are simpler and cheaper to ship and store.

What it asks of the laboratory

Microsampling moves complexity from the collection site to the laboratory. A few issues come up consistently.

Haematocrit. In conventional DBS, haematocrit affects how far the blood spreads, how much ends up in a punch, and sometimes extraction recovery. Volumetric devices fix the volume problem, but haematocrit can still influence recovery, so it needs assessing during validation.

Whole blood versus plasma. Most reference ranges and historical data are based on plasma or serum. Dried samples are whole blood, so results are not directly interchangeable. Bridging studies comparing paired microsamples and venous samples are needed before results can be interpreted against existing data.

Extraction and recovery. Analytes must be extracted from a dried, solid matrix. Recovery can depend on the extraction conditions and on the sample’s haematocrit, so each method needs to show consistent recovery across the haematocrit range it will encounter.

Sensitivity at small volumes. With only a few microlitres per sample, the method has to deliver adequate sensitivity after extraction and dilution. This is where modern triple quadrupole LC-MS/MS makes the approach workable.

Sample quality. Samples collected without a trained collector can be over-filled, under-filled, contaminated or poorly dried. Clear collection instructions and acceptance criteria at the laboratory are as important as the analysis itself.

Validation frameworks are catching up

Regulatory guidance now explicitly covers dried samples. ICH M10, the international guideline on bioanalytical method validation adopted in 2022, includes dried matrix methods among its special cases. For therapeutic drug monitoring, the International Association of Therapeutic Drug Monitoring and Clinical Toxicology has published guidance on developing and validating DBS-based methods. Together these give laboratories a clearer path from research use towards routine application.

Where this could be heading

Microsampling won’t replace venous collection, and it doesn’t suit every analyte or every application. But interest is growing in collecting more samples outside traditional settings, particularly for research and studies that need frequent or remote sampling. For Australia, where distance can be a real barrier to collection, microsampling paired with sensitive LC-MS/MS is one option worth watching as validation guidance matures and more laboratories gain experience with it.