The research, published in Annals of Clinical and Translational Neurology, evaluated two FDA-cleared capillary blood collection devices, TAPII and Tasso+, for measuring four key Alzheimer’s plasma biomarkers: the amyloid-beta 42/40 ratio, phosphorylated tau 217 (pTau217), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). These analytes tell complementary stories about the disease. The Aβ42/40 ratio reflects amyloid deposition, pTau217 is currently the strongest single plasma marker for discriminating autopsy-confirmed Alzheimer’s disease from other neurodegenerative conditions, NfL signals neuroaxonal injury, and GFAP marks astrocyte activation associated with the onset of amyloid pathology. The team, led by researchers at the Johns Hopkins Center for CSF Disorders, compared capillary plasma measurements to simultaneously collected venous plasma and cerebrospinal fluid from the same individuals.

The cohort comprised 192 patients examined between October 2021 and April 2024, with a mean age of 61 years and a clinically diverse mix of diagnoses. The group included 25 patients with Alzheimer’s disease, 42 with idiopathic normal pressure hydrocephalus, 28 with vascular dementia, 61 with other neurological conditions such as dementia with Lewy bodies, frontotemporal dementia, Parkinson’s disease and idiopathic intracranial hypertension, and 36 cognitively normal participants split into younger and older normal groups. Each patient who could provide samples underwent venipuncture on one arm and capillary collection on the other using either TAPII or Tasso+, both containing EDTA as an anticoagulant. Twenty patients provided samples with both devices. Cerebrospinal fluid was obtained by diagnostic large-volume lumbar puncture under sterile conditions.

The devices themselves are compact, single-use tools designed to collect small amounts of capillary whole blood painlessly from capillaries in the skin. TAPII, approved in 2019, uses an array of 16 microneedles, each 500 micrometers in length, and gentle vacuum to draw blood. Tasso+, cleared in 2022, uses a single lancet 5 millimeters long. Both are described by their manufacturers as suitable for use by a caregiver or the patient themselves, if able, from the comfort of home. In this study, Tasso+ collected a mean volume of 294.1 microliters and TAPII 266.94 microliters, with Tasso+ succeeding in collecting more than 50 microliters of whole blood in 90.3 percent of attempts and TAPII in 86 percent, differences that were not statistically significant. Both devices yielded sufficient blood for multi-biomarker immunoassays in more than 85 percent of collections.

All biomarker levels were measured in singlicate on a Simoa HD-X analyzer using commercially available kits, with inter-assay coefficients of variation below 12 percent for all analytes. The results for three of the four biomarkers were strikingly positive. Capillary concentrations of NfL, GFAP and Aβ42/40 from both devices correlated strongly with their venous plasma counterparts. TAPII-derived NfL showed a correlation coefficient of 0.86 with venous NfL, GFAP 0.84 and Aβ42/40 0.74, all highly significant. Tasso+ performed similarly, with NfL at 0.91, GFAP at 0.80 and Aβ42/40 at 0.75. Pairwise comparisons found no significant differences between TAPII, Tasso+ and venous measurements for these three analytes, and Bland-Altman analysis revealed minimal bias and tight agreement for Aβ42/40 across the range of values, with wider limits of agreement for NfL and particularly GFAP, which showed substantial variability and multiple outliers for both devices.

Then came the surprise. pTau217, the biomarker that has consistently outperformed other phosphorylated tau isoforms in distinguishing Alzheimer’s disease from other dementias and in predicting PET positivity, failed to replicate between capillary and venous samples. Tasso+ capillary pTau217 correlated only weakly with venous pTau217 (r = 0.23, p = 0.04), and TAPII pTau217 did not correlate significantly at all (p = 0.12). Bland-Altman analysis demonstrated a consistent positive bias for both devices, with mean biases of approximately 7 picograms per milliliter for TAPII and 3 picograms per milliliter for Tasso+, and this overestimation became more pronounced at higher pTau217 concentrations. Passing-Bablok regression confirmed substantial proportional bias, with slope estimates markedly deviating from one for both devices. The practical consequence was dramatic: over 95 percent of capillary pTau217 concentrations across all patient groups, even cognitively normal controls, exceeded the preliminary cutoff of 0.42 picograms per milliliter used in established literature to indicate significant brain amyloid pathology. In venous plasma, only the Alzheimer’s disease group and the mixed neurodegenerative Other group exceeded that threshold on average. The study reports a nearly 30-fold difference between TAPII and venous measurements, a 10-fold difference between Tasso+ and venous, and a 3-fold difference between the two capillary devices themselves.

The authors propose several hypotheses for this pTau217 anomaly. Phosphorylated tau species, including pTau217, as well as alpha-synuclein aggregates, have been shown to exist in peripheral nerve terminals of the skin, raising the plausible hypothesis that capillary collection devices may release peripheral pTau217 into the whole blood sample collected, thereby inflating the overall concentration. Matrix effects unique to the pTau217 assay may also be involved, since all the other analytes were run on a different assay kit. Differences in the dimensions and number of needles utilized by the two devices may explain variation in pTau217 concentration as well as hemolysis, which was significantly higher in capillary samples (TAPII 2.08 out of 4, Tasso+ 1.37 out of 4) compared with venous. Notably, hemolysis did not significantly alter the strong relationship between capillary and venous measurements of Aβ42/40, NfL and GFAP, suggesting the pTau217 problem is specific rather than a general quality issue with capillary specimens.

When the researchers compared capillary and venous plasma to cerebrospinal fluid, venous NfL, GFAP and pTau217 all correlated significantly with CSF analytes (NfL r = 0.73, GFAP r = 0.59, pTau217 r = 0.33), consistent with previous CSF-plasma studies. Capillary NfL and GFAP also correlated modestly with CSF measures, whereas capillary Aβ42/40 and pTau217 did not correlate significantly with CSF. Age-adjusted logistic regression models constructed separately for each sample type found comparable discrimination of Alzheimer’s disease status across venous and capillary measurements for all four biomarkers, with no statistically significant differences in AUC. Venous pTau217 demonstrated the highest individual biomarker performance (AUC 0.88, 95 percent CI 0.82-0.94), while GFAP and Aβ42/40 showed similar diagnostic performance across capillary and venous sample types.

Lasso-regularized logistic regression, used to account for the small number of clinically diagnosed Alzheimer’s cases (n = 25) and reduce overfitting, identified age and plasma GFAP as the most consistent predictors of Alzheimer’s disease across all sample types. Models incorporating these two variables yielded AUC values of 0.75 for TAPII-derived capillary plasma, 0.87 for Tasso+-derived capillary plasma and 0.83 for venous plasma. Remarkably, the Tasso+ model, built from just age and GFAP, exceeded both the TAPII and venous models and fell close to AUC values generated by plasma Alzheimer’s biomarker testing in larger studies. The authors suggest that capillary GFAP, particularly in combination with age or APOE genotype, could serve as a scalable screening tool for Alzheimer’s disease in primary care or decentralized research settings. NfL, while elevated in Alzheimer’s disease, is also elevated in many other neurodegenerative conditions present in the cohort, explaining its weak discriminatory power between Alzheimer’s and non-Alzheimer’s participants. The reduced predictive utility of capillary Aβ42/40 concurs with previous studies citing the plasma amyloid ratio’s greatest diagnostic power in preclinical and mild cognitive impairment stages, whereas this cohort primarily comprised clinical Alzheimer’s dementia.

Pain scores, measured on a Numeric Rating Scale from 0 to 10, were dramatically lower for capillary collections than for traditional venipuncture. Tasso+ scored a mean of 0.2 out of 10, TAPII 0.73 out of 10, and venous collection 2.24 out of 10, with all pairwise comparisons highly significant. The authors note that lower pain associated with capillary collection may improve patient compliance for blood draws, a finding consistent with other studies using capillary collection devices. The study was conducted in a supervised clinical setting, and the authors caution that findings may differ in unsupervised or at-home collection environments. The cohort was also not randomized between devices, which may introduce bias but reflects real-world clinical conditions, and the number of clinically diagnosed Alzheimer’s cases was relatively small, limiting statistical power.

The overall conclusion is a nuanced one. The findings support the feasibility of capillary biomarker testing and the use of capillary collection devices in decentralized Alzheimer’s clinical trials and studies, with minimal loss of diagnostic signal for NfL, GFAP and Aβ42/40 compared with venous plasma. But a clear need exists for specific guidelines and assay optimization for capillary biomarkers, particularly pTau217, due to significant technical or biological differences between TAPII, Tasso+ and venous plasma samples. The authors envision a future in which patients or caregivers could provide a small capillary sample at home or in a clinic, and clinicians could triage them for confirmatory CSF or PET testing based on algorithmic risk. Before that vision becomes reality, capillary blood biomarker tests will need to be thoroughly evaluated as CSF and venous plasma assays have been over the past decade, potentially necessitating separate cutoffs and guidelines for different plasma sample types to account for the measurement gap that this study has now exposed.

Subject of Research: Validation of two capillary blood collection devices for measuring Alzheimer's disease plasma biomarkers against venous plasma and cerebrospinal fluid

Article Title: Alzheimer's Disease Biomarkers Measured by Capillary Blood Collection Versus Venous Plasma and Cerebrospinal Fluid

Article References: Ho, S., Shen, Z., Lewis, A., Patel, M., Zheng, A., Proscino, G., Ho, T., Wang, J., Albert, M., & Moghekar, A. (2026). Alzheimer's Disease Biomarkers Measured by Capillary Blood Collection Versus Venous Plasma and Cerebrospinal Fluid. Annals of Clinical and Translational Neurology, Article acn3.70524. https://doi.org/10.1002/acn3.70524

Image Credits: AI Generated

DOI: 10.1002/acn3.70524

Keywords: Alzheimer's disease, blood biomarkers, capillary blood collection, pTau217, GFAP, neurofilament light chain, amyloid beta 42/40, cerebrospinal fluid, Tasso+, TAPII, decentralized clinical trials, plasma biomarkers

The study, led by Mohammed Limbada of the research organisation Zambart together with colleagues at the London School of Hygiene and Tropical Medicine, the Institute of Tropical Medicine in Antwerp and the University of Oxford, set out to answer a deceptively simple question: can adults living with HIV, without any medical training, successfully collect enough capillary blood on their own using commercially available self-collection devices, and would they find the experience acceptable compared with a standard needle draw? The researchers enrolled 70 adults who were already taking antiretroviral therapy and attending routine monitoring visits at a clinic in Lusaka, running the trial between October and December 2024. The work formed part of the AMPHEUS project, funded by the Gates Foundation, an initiative exploring decentralised approaches to viral load monitoring.

The trial’s design was a randomized crossover, one of the most statistically efficient ways to compare two interventions when the outcome of interest is a binary success or failure. Each participant used both devices, Tasso+ manufactured by Tasso, Inc. of Seattle, and Collect2Know version 1.0, or C2K, supplied by the Institute of Tropical Medicine in Antwerp, but in an order determined by random allocation. This crossover structure matters because each participant serves as their own control: differences in dexterity, pain tolerance, anxiety about needles or familiarity with medical procedures are distributed evenly across both devices rather than confounding the comparison. The first use of each device took place under supervision at the clinic, and a week later each participant performed a second, entirely unsupervised collection at home, replicating the real-world conditions under which such devices would actually be deployed.

The technical bar for success was deliberately pragmatic. A collection was counted as successful only if the participant, working alone and unsupervised, managed to obtain at least 0.5 millilitres of capillary blood, the volume the investigators prespecified as necessary for downstream viral load processing. Half a millilitre is a small quantity by clinical standards, roughly ten drops, but collecting it reliably from capillary vessels rather than a vein is far from trivial. Capillary blood devices typically work either by lancing the fingertip and wicking droplets into an absorbent tip, as C2K does, or by pressing a small cartridge against the upper arm, where a vacuum and a shallow blade combination draw blood into a sealed tube, as the Tasso+ device does. Each approach carries its own engineering challenges: sufficient blood flow, user-applied pressure, clotting, and the geometry of the collection chamber all influence whether the target volume is reached.

The results were strikingly one-sided. Of the 63 participants who completed the study, 85.7 percent, or 54 of 63, successfully collected at least 0.5 millilitres with Tasso+ during unsupervised use, compared with just 38.1 percent, or 24 of 63, with C2K v1.0. The difference was highly statistically significant, with a McNemar test yielding a p-value below 0.001 and an odds ratio of 10.99 with a 95 percent confidence interval spanning 3.45 to 56.06. In practical terms, a participant who succeeded with Tasso+ had roughly an elevenfold higher odds of success than with C2K. The paired nature of the data makes the failure pattern even more telling: among the 54 participants who achieved a successful collection with Tasso+, 33, or 61.1 percent, nonetheless failed to collect a usable sample with C2K. The participants, who ranged in age from 18 to over 50 and were 64.5 percent female, thus demonstrated that the gap was not a matter of user capability but of device design.

Usability questionnaires administered after each collection added a layer of subjective evidence that aligned with the objective success rates. Participants rated the Tasso+ device as easier to use, and their experiences relative to standard venepuncture were revealing. Where the conventional needle draw was associated with pain, fear and the discomfort of exposing a limb in a busy clinic, the self-collection devices were reported to hurt less, provoke less anxiety and offer greater privacy. These are not trivial considerations in the context of HIV care. Stigma remains a powerful deterrent to engagement with health services in many settings, and anything that reduces the visibility and invasiveness of routine monitoring has the potential to improve retention in care, which is itself one of the strongest predictors of long-term treatment success.

The perspectives of healthcare workers, gathered through the qualitative component of the study and its formative phase, pointed to a different but complementary benefit. Nurses and clinicians highlighted reduced clinic congestion as a key advantage of self-sampling. In facilities where a single phlebotomist may process dozens of patients each morning, decoupling the collection of blood from the clinic visit would free staff time, shorten queues and potentially allow viral load samples to be collected before appointments even begin. Combined with the possibility of returning samples by courier or postal systems, pre-appointment collection could compress the turnaround time between a scheduled monitoring visit and a actionable result, giving clinicians the information they need while the patient is still in front of them.

The investigators are careful, and rightly so, about the limits of what their trial demonstrates. Success in this study was defined by volume alone. The researchers explicitly note that their findings do not establish whether the capillary specimens collected by these devices are suitable for HIV viral load testing. Capillary blood differs from venous blood in several analytically relevant ways: it is generally more prone to haemolysis, its collection into dried or stabilised matrices can affect RNA integrity, and the plasma volume recoverable from half a millilitre of whole blood is small. Viral load assays are validated against venous plasma, and any deviation in sample type must be shown to produce equivalent results across clinically relevant viral load ranges, from fully suppressed samples below the detection threshold to high-level viraemia above 100,000 copies per millilitre. The authors call for further studies directly comparing device-collected capillary blood with standard venous plasma to establish this analytical performance, and that work will be the true gatekeeper determining whether self-collection can enter routine care.

Even with that caveat, the trial carries considerable weight for the field. It was prospectively registered with the Pan African Clinical Trial Registry, approved by ethics committees in Zambia, Belgium and the United Kingdom, and conducted under Good Clinical Practice guidelines, giving its findings a methodological rigour that many usability studies lack. The crossover design, the prespecified volume threshold and the inclusion of both supervised and unsupervised use together provide a realistic picture of how the devices would perform outside a research setting. The magnitude of the difference between the two devices also carries a practical message for programme implementers: device choice is not a detail but a determinant of success, and a device that fails in nearly two out of three paired attempts would impose unacceptable retesting burdens at scale.

The broader context makes the Zambian findings timely. Global health authorities have set ambitious targets for viral load monitoring coverage, and the laboratory networks that process millions of samples annually across eastern and southern Africa are under constant pressure to expand. Decentralising the first step of the testing cascade, the collection itself, would not eliminate the need for laboratories, but it would remove one of the most labour-intensive and visit-dependent links in the chain. If subsequent analytical validation confirms that capillary samples from devices such as Tasso+ can yield viral load results equivalent to venous plasma, the model tested in Lusaka, a patient collecting a few drops of blood at home a week before a routine appointment, could become a standard component of HIV care, not only in Zambia but across the many settings where the burden of disease and the scarcity of phlebotomy services intersect.

Subject of Research: Usability and acceptability of capillary blood self-collection devices for HIV viral load monitoring in Zambia

Article Title: Usability and acceptability of capillary blood self-collection devices among adults living with HIV in Zambia: a randomized crossover trial

Article References: Limbada, M., Phiri, C., Schaap, A., Simuyamba, M., Hensen, B., Baetselier, I. D., den Bossche, D. V., Maluzi, K., Kawambwa, B., Chiyanta, B., Ruperez, M., Platteau, T., Kosloff, B., Simwinga, M., Fraser, C., Bonsall, D., & Ayles, H. M. (2026). Usability and acceptability of capillary blood self-collection devices among adults living with HIV in Zambia: a randomized crossover trial. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14530-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14530-w

Keywords: HIV, viral load monitoring, capillary blood self-collection, Tasso+, Collect2Know, Zambia, randomized crossover trial, antiretroviral therapy, medical devices, decentralised testing, usability, patient acceptability