In this interview, NewsMedical speaks with Quanterix about blood spot testing for neurological applications.
Please could you introduce yourself and tell me a little about your role at Quanterix?
My career journey has included three phases:
- An education in chemistry, biochemistry, and structural biology
- 15 years of development of biopharmaceutical characterization and quality testing technologies
- A recent transition to biomarkers
The most important practice learned after introducing multiple early technologies into regulated markets has been that interesting technologies create a starting point; developing a complete solution that scales globally requires the addition of standards, controls, sustainable training programs, and well-designed quality specifications.
My role at Quanterix as Vice President of Product Management is to transform customer feedback into a detailed product description that can be developed and manufactured.
Can you give us a quick overview of what dried blood spot (DBS) testing is and how it works?
The familiar blood draw performed during routine testing is considered “wet” and collected in tubes. While a routine process at this point, the resources required are significant: a trained phlebotomist, sterile device, intravenous puncture, cold chain transportation, and storage.
These requirements create cost, logistical, and access barriers that ultimately limit health care access.
DBS or DPS represents an alternative biocollection method where a much smaller volume of blood is extracted by finger or heel prick and blotted on a membrane.
Once adsorbed to the membrane, many analytes are stable at room temperature, removing the logistics and cost of cold chain storage from the collection to analysis site.
In preparation for analysis, the DBS/DPS is resuspended in liquid and extracted, providing the input to an analytical method.
When you combine the reduction of cost and simplification of collection, shipment, storage with access to more patients, DBS/DPS offer tremendous potential advantages and open new opportunities that benefit the clinician, testing laboratory and patient.
DBS testing has been used in clinical testing. What’s unique about DBS for neurodegenerative diseases?
DBS/DPS remains in an early development stage but has made entry into the clinic. One example is the use of a Hepatitis C confirmatory, but not diagnostic testing. For the above reasons, nearly every blood-based test could benefit if converted from wet tube-based to dry spot-based. Neurodegenerative diseases could especially benefit from dry spot biocollection methods due to the large number of samples that may be required over the course of a 10-20 years of disease progression. DBS/DPS may offer a cost-effective means of monitoring patients with at-home collection followed by ambient shipment to a testing laboratory.
Image Credit: Gorodenkoff/Shutterstock.com
Why is there such growing interest in using blood-based biomarkers, especially for neurological diseases, and what limitations still exist in conventional blood testing?
The exponential interest in neurology blood-based biomarkers stems from the technical breakthroughs in testing brought about by ultra-sensitive protein quantitation. The peripheral organs of the body, such as liver, kidney, pancreas and heart have direct and nearly uninhibited access to the blood stream.
Blood-based biomarkers for heart and kidney disease reach sufficiently high concentrations that ultra-sensitive analytical methods are not required. The brain simply isn’t as accessible. The blood-brain barrier provides an important and highly protective environment that limits the availability of biomarker proteins to blood.
In application breakthroughs, ultra-sensitive technologies such as Simoa® have demonstrated the ability to detect and quantitate minute amounts of highly informative neuronal biomarkers in plasma and serum. This, in turn, has created a positive feedback mechanism for biomarker discovery. Example biomarkers such as p-Tau 181 and p-Tau 217 were identified by mass spectrometry and subsequently quantitated by Simoa. With those success stories, the neuronal biomarker community is looking for more examples of early detection biomarkers.
What makes the DBS approach so promising, particularly for neurodegenerative diseases and other challenging areas of biomarker detection?
The magnitude and pace of progress are currently bringing tremendous promise throughout the neurology field.
P-Tau 217 was described as a breakthrough blood-based biomarker for Alzheimer’s as early as 2020. Quanterix announced the release of the first commercial p-Tau 217 assay in 2024. Within one year, in 2025, all four analytes of the Simoa Neurology 4-plex E assay kit( NfL, GFAP, AB40, Ab42) and p-Tau 217 were successfully measured in a dry plasma spot. Improvements in reproducibility, quantifiability, and standardization are still required, but the proof of concept has already been demonstrated. This is an extremely exciting time for the neurology research space.
The Simoa platform is currently recognized for its ultra-sensitive biomarker detection in neurological biomarker blood testing. How does Simoa uniquely fit the DBS testing workflow?
As described earlier, the ultra-sensitivity of Simoa enabled measurement of early detection of Alzheimer’s biomarkers in blood for the first time. With an intravenous wet sample blood draw, sample volume is not typically limiting, and 100 uL is routinely provided as input to the assay.
With dry blood/plasma spot, the challenge to detect a very small number of molecules increases because the sample available after capture and extraction is nearly ten to fifteen-fold less. The ultra-sensitivity of Simoa offers the possibility to extract exciting information on patient health from a single, cost-effective, and highly accessible drop of blood/plasma.
What does the combination of Simoa’s ultra-sensitive detection and DBS sampling enable that was impossible before in neurodegenerative disease research?
In combination, Simoa and DBS/DPS scale neurodegenerative tests in an unmatched fashion. Imaging technologies, such as PET, have provided invaluable metrics for diagnosis and clinical trial enrollment and endpoint criteria. At the same time, the cost and access to imaging-based methods can be inhibiting. The cost of clinical trial enrollment using only a PET scan ($3000 each) compared to a hybrid approach that utilizes a PET scan and a blood test ($50 each) has been estimated to decrease by nearly $7 million for a 1000-patient study.
This enables more therapeutics to access the clinical stage and more diverse communities to be considered. Simoa ultra-sensitivity and DBS enable fundamental advancements to translate into scalable solutions that broadly improve human health.
Advanced ultra-sensitive immunoassay technologies, like the single-molecule array (Simoa) technology, have made DBS testing for neurological disorders possible. What are the remaining challenges in the DBS testing workflow?
As exciting as it has been to witness the early measurement of neurology biomarkers from a DBS/DPS, the field is just getting started with multiple important milestones ahead. First, there is a need for more signal as quantitation of p-tau 217 with DPS is still challenging. This could be done via improved analytical technologies such as Simoa, larger sampling volumes, more efficient plasma separation, or more effective extraction methods.
Multiple controls are also required to monitor key steps in the process, inlcluding loading, plasma separation, extraction, and run controls. After adequate performance and controls are in place, standardization will be required to enable comparability across studies. There is a tremendous amount of work yet to be done.
How does Quanterix’s new extraction kit help researchers and clinicians unlock the full potential of this sampling method?
Multiple DBS/DPC collection devices are currently available. Despite different approaches amongst these devices to collection and separation of blood into plasma, every device requires an extraction step. The proteins once adsorbed to the membrane need to be re-solubilized, collected in a tube and prepared for analysis. The new Simoa dry blood extraction kit, which is based on work done at the University of Gothenberg, provides a simple, off-the-shelf solution for this key step. Early work with the kit has shown effective extraction of p-Tau 217, Nf-l, GFAP, Ab40 and Ab42 in a fashion fully compatible with Simoa analysis.
How do you see dried blood testing evolving in the biomarker research and clinical space, and what role will Quanterix continue playing in advancing DBS testing?
With the clear potential to translate recent biomarker discoveries into scalable health care solutions, multiple groups will work collaboratively to improve the collection device, measure stability, refine extraction methods, improve analytical performance and establish calibrators. Together, we will work toward an RUO solution that iteratively evolves to meet the needs of clinical researchers. Quanterix is committed to partnering closely with researchers to learn how it can help at each step in that process.
Please share some further information or links you would like to share with our audience:
- Quanterix Simoa Dry Blood Extraction Kit: https://www.quanterix.com/simoa-assay-kits/simoa-dry-blood-extraction-kit/
- Karikari, T.K., et al. (2020). Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Molecular Psychiatry, 26(2), pp.429–442. https://doi.org/10.1038/s41380-020-00923-z.
- Kolanko, M.A., et al. (2024). Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood. Brain Communications, (online) 6(3). https://doi.org/10.1093/braincomms/fcae151.
- Huber, H., et al. (2024). Biomarkers of Alzheimer’s disease and neurodegeneration in dried blood spots—A new collection method for remote settings. Alzheimer s & Dementia, 20(4), pp.2340–2352. https://doi.org/10.1002/alz.13697.
About Wesley Straub
Wesley Straub obtained his B.S. in Chemistry magna cum laude from Boston University and a Ph.D. from the University of California San Francisco. After working on producing, purifying, and characterizing several biosimilars, recombinant
blood factors, and novel biotherapeutics, he entered the life science technology field with Forte Bio. He has contributed to the development and launch of over 25 hardware, software, and reagent products across BLI, capillary sequencing, qPCR, and Simoa technologies.
About Quanterix
From discovery to diagnostics, Quanterix’s ultrasensitive biomarker detection is fueling breakthroughs only made possible through its unparalleled sensitivity and flexibility. The Company’s Simoa® technology has delivered the gold standard for earlier biomarker detection in blood, serum or plasma, with the ability to quantify proteins that are far lower than the Limit of Quantification (LoQ) of conventional analog methods.
Its industry-leading precision instruments, digital immunoassay technology and CLIA-certified Accelerator laboratory have supported research that advances disease understanding and management in neurology, oncology, immunology, cardiology and infectious disease. Quanterix has been a trusted partner of the scientific community for nearly two decades, powering research published in more than 2,500 peer-reviewed journals.
Find additional information about the Billerica, Massachusetts-based company at https://www.quanterix.com or follow us on Twitter and LinkedIn.
Quanterix’s Simoa® technology drives advances in Alzheimer’s disease research presented at 2022 Clinical Trials On Alzheimer’s Disease (CTAD) conference