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Can Fingerstick Sampling Support Longitudinal Proteomics?

Alamar’s dried blood spot workflow highlights the analytical demands behind remote sampling and decentralized study design
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Written byAimee Cichocki
InterviewingStephen Williams
Dried blood spot sampling for home-collected samples
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Dried blood spot sampling offers a practical route to biological sample collection outside the clinic. A few drops of blood can dry on a collection device, ship at ambient temperature, and reach participants who may live far from major research centers. For proteomics, however, small-volume sampling raises a more difficult question: can dried microsamples still support reliable, multiplex protein measurement?

Alamar Biosciences’ launch of the NULISA Dried Blood Spot Extraction Kit brings that question into focus. The kit is designed to recover proteins from dried blood spot and dried plasma spot microsamples collected on third-party remote sampling devices, extending Alamar’s NULISA platform into home-collected samples for longitudinal, decentralized, and population-scale research.

For Dr. Stephen Williams, Chief Scientific Officer at Alamar, the opportunity starts with better sampling.

“The old way of collecting blood was to slash the end of a finger with a stylet and squeeze it until you had enough blood,” Williams recalls. “You were squeezing out tissue fluid and all kinds of things, so the lack of standardization in the collection process was a real problem.”

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Newer collection devices have helped address that issue. “Over the past few years, better collection devices with more standardized collections have evolved,” he continues. “That standardization enables people to start asking the question: what can you measure?”

Why Dried Microsamples Have Been Difficult

Even with improved devices, dried blood spot and dried plasma spot samples still provide much less starting material than a venous blood draw. That creates an immediate analytical challenge.

Alamar typically uses about 30 microliters of plasma for its assays, which Williams describes as small compared to most platforms. Remote collection devices can provide less, forcing researchers to work with smaller samples and greater dilution.

“When you do that, you’re lowering the concentration of all the proteins at once,” Williams explains. “The key demand it places on a platform is sensitivity.”

For multiplex proteomics, that sensitivity requirement can determine whether low-abundance targets remain measurable after extraction, dilution, drying, and reconstitution.

What Ultra-Sensitive Measurement Changes

According to Alamar, validation work showed 85–95 percent target detectability across its NULISA CNS and Inflammation panels on most supported microsampling platforms. Williams describes the result as stronger than expected.

“The surprise to me was how good the detectability was,” he reflects. “We still detect somewhere above 85 percent of proteins on our panels, even in dried blood spots. I actually would have expected us to lose more.”

He links that performance to the platform’s dynamic range. Some proteomics workflows extend dynamic range by running analytes at different dilutions, but dried microsamples complicate that strategy because the sample has already been pushed into a lower concentration range.

“What we’re capitalizing on is that the dynamic range was already big enough,” Williams explains. “Now you’ve pushed all of the concentrations down, but you can still measure those proteins.”

Not every target survives the process. “You’re going to lose some proteins,” Williams cautions. “The very low-abundance ones that were only just detectable may be lost when you dilute them further. And some proteins are affected by drying and reconstituting. Some will just get denatured.”

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Why Neurology Is a Strong Early Application

Neurology offers a compelling use case because several blood-based biomarkers now show strong alignment with harder-to-access clinical standards.

“The exciting thing about neuro is just how good blood-based markers actually are,” Williams explains. “Some of them are extraordinarily good.”

He points to the field’s progression from positron emission tomography (PET) imaging to cerebrospinal fluid and then plasma. PET imaging helped establish reference standards for amyloid burden, tau burden, and other features of neurodegeneration. Cerebrospinal fluid (CSF) biomarkers then emerged as a more accessible approximation. More recently, researchers have looked for plasma markers that reflect the same biology.

Williams highlights brain-derived phosphorylated tau 217 as one example. Tau contributes to the tangles associated with Alzheimer’s pathology, and phosphorylation forms part of the disease process. The brain-derived modified version, he explains, can be “especially good at predicting what the brain amyloid burden will be.”

A plasma marker that reflects a difficult or expensive imaging measure could help researchers identify disease earlier, support trial enrollment, and monitor biological change over time.

How Home Collection Could Change Study Design

The value of fingerstick or microneedle sampling becomes clearer when researchers move from one-time measurements to repeat sampling. In large clinical studies, participants often need to visit a site for blood collection, with samples then routed through central laboratory logistics. That model works, but it can limit frequency and participation, especially in older or cognitively impaired populations.

“If you’d really like to do more of a real-world study and measure changes in the blood over time, it becomes a practicality argument,” Williams explains. “It improves adherence, makes it more practical, and lets you measure things more frequently.”

Remote microsampling could also pair with digital cognitive testing. “Now you can test cognitive function on the phone or on the computer,” Williams continues, “and measure the important blood-based biomarkers in parallel. That makes some large-scale trials more attractive.”

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The same logic applies to screening and recruitment. Researchers could use more practical collection models to identify people who may qualify for trials before moving them into more intensive clinical workflows.

The Case for Repeat Measurements

Longitudinal sampling could help researchers track progression, monitor treatment response, and refine eligibility decisions. “One way is if you have a measure that reflects progression of disease or response to treatment,” Williams explains. “Then you can see if someone is actually responding.” That could prove useful before a clinical outcome becomes visible.

Williams also gives the example of a person with borderline test results. “If you screen me today and I’m just below the threshold for amyloid positivity, I’d like you to test me again next year,” he explains. “You can see whether I crossed the threshold for eligibility.”

That type of repeat testing becomes more practical when sample collection does not depend on repeated clinic visits or venous blood draws.

What Researchers Still Need to Watch

Dried microsamples still require careful validation. Lower starting volume, extra dilution, protein loss, hemoglobin contamination, cell lysis, and collection-related tissue effects can all influence results.

“You get some contamination, there’s hemoglobin, you get some cell lysis,” Williams explains. “If there was interference between those released proteins and others, that would be a problem.”

Specificity can help address some of those risks. In neurology, Williams notes that total tau can be affected by tissue trauma, platelet activation, and peripheral signals. Brain-derived tau may avoid some of that interference because it is more specific to the biology of interest.

“That specificity of the platform helps overcome some of the things that are innate to the collection process,” he explains.

From Collection Convenience to Research Scale

The broader significance of dried blood spot and dried plasma spot proteomics lies in study design. Home-collected micro samples could reduce reliance on scheduled phlebotomy, expand access to participants outside major research centers, and support more frequent sampling across larger populations.

Those gains depend on analytical performance. The sample must preserve enough usable biology, the assay must detect low-abundance proteins after dilution, and the workflow must control preanalytical variability.

For Williams, improved collection devices and ultra-sensitive multiplex platforms have shifted the conversation. The field can now move beyond whether dried microsamples can be collected with enough consistency and ask what longitudinal biology they can reveal.

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Meet the Author(s):

  • Aimee Cichocki is the Editorial Director at Separation Science and Chromatography Forum. Aimee brings a broad range of experience in creating, editing, and formatting scientific content. With a degree in medicinal chemistry, a 10-year background in formulation chemistry, an MBA, and a diverse background in publishing, Aimee guides editorial initiatives at Separation Science and Chromatography Forum. Aimee is dedicated to ensuring the delivery of informative, reliable, and practical content to our audience of analytical scientists.

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