Fueling Diagnostic Innovation with Non-Invasive Biomarker Detection Technologies

Non-invasive fluid biomarkers are at the forefront of diagnostic innovation, offering clinicians and patients a clearer view into health and disease without the need for invasive procedures. From the detection of cell-free DNA (cfDNA) in circulation to multiplex detection of disease-related proteins in blood and cerebrospinal fluid (CSF), these advances are driving earlier, more precise disease detection and monitoring. Improvements in non-invasive biomarker detection technologies are accelerating an industry-wide shift to personalized care, enabling real-time insights into disease risk and progression, therapeutic response, and overall health.

The Evolving Landscape of Non-Invasive Biomarker Detection

Interest in biomarkers has increased exponentially over the last several decades, transforming the depth and breadth of data informing drug development, clinical care, and more. In more recent years, we’ve witnessed FDA approvals of a growing number of biomarker tests for various cancers, Alzheimer’s disease, and other conditions, as well as the rising commercial presence of wellness-focused biomarker panel tests.

While cfDNA and liquid biopsy techniques have garnered considerable attention, a parallel and equally powerful trend is unfolding in protein-based biomarker discovery. Protein signatures capture functional changes in real time, reflecting not only the presence of disease but also its impact, progression, and response to therapy. In oncology, panels measuring multiple proteins are beginning to improve specificity and sensitivity over single-marker tests. Protein biomarkers are also enabling earlier detection of neurological conditions such as Alzheimer’s disease, Parkinson’s disease, and ALS, often before clinical symptoms are present. [1]

Biomarker discovery and development require researchers to consider the relevance of a given biomarker in the context of a specific sample type, as well as the scalability and clinical viability of a diagnostic tool. For example, CSF measurement presents unique advantages for diagnosing and monitoring neurological disorders, providing direct insights into central nervous system-derived protein signatures. Many disease-relevant biomarkers are present at much higher concentrations in CSF than in blood or other biological fluids, enabling detection at lower thresholds and greater diagnostic confidence. [2] Conversely, blood-based biomarker tests are less invasive, requiring a simple blood draw rather than a lumbar puncture. This ease of sampling translates to greater scalability and accessibility of blood-based diagnostic tools. However, because blood-based biomarkers are typically less abundant, more sensitive assays and detection platforms are necessary for accurate quantification and detection.  

Broadening Diagnostic Insights with Multiplex Panels

Assessing multiple biomarkers in parallel offers distinct advantages over single-marker approaches, particularly in overcoming the inherent variability in levels of individual proteins. Multiplexing enables more comprehensive disease profiling, capturing the interplay of biological pathways involved in tumor proliferation, neurodegeneration, or immune response. This breadth supports differential diagnosis, where overlapping clinical symptoms may mask underlying causes, and it is often difficult to obtain a high-confidence diagnosis with a single protein biomarker. Additionally, multiplex assessment can help clarify “signal vs. noise” in diagnosis. In instances where elevation of a single protein could be indicative of numerous conditions or even a benign state, capturing a parallel shift of several relevant biomarkers can reduce the risk of false positives or negatives.

Biomarker panels are also converging with the rise of broader omics strategies, integrating proteomics, genomics, and metabolomics to characterize disease signatures across multiple dimensions. For example, CancerSEEK is a blood-based test currently under development that measures a panel of eight protein biomarkers alongside cfDNA mutations associated with eight common cancer types. Because many genetic markers are associated with multiple cancers, incorporating protein biomarkers with genomic analysis supports early and localized cancer detection. [3]

More recently, Alzheimer’s disease panels measuring amyloid-beta, tau, and neurofilament light chain in CSF and blood have entered the clinic. The relative levels of these proteins can provide evidence of Alzheimer’s pathology, helping inform diagnostic decisions and stage disease progression. [4] Together, these approaches are shaping a future in dynamic networks of biomarkers can help us identify and characterize disease states not adequately captured through single-marker tests.

The Role of High-Affinity Antibodies and Ultrasensitive Platforms in Further Innovation

High-affinity, rigorously validated antibodies are the cornerstone of reliable protein biomarker detection, ensuring consistent performance across assays and populations. Their specificity is especially critical when measuring low-abundance proteins, where background noise or cross-reactivity with other biomolecules present in a sample can easily obscure meaningful signals.

Validated, well-characterized antibodies with consistent performance have also been instrumental in driving advances in ultrasensitive detection platforms. For example, digital ELISA, which uses antibody-coated, fluorescently labeled beads to detect proteins at a single-molecule level, enables researchers to measure many biomarkers below the limit of detection of traditional methods. [5] This, in turn, introduces new possibilities for non-invasive measurement of low-abundance biomarkers.

To accelerate advances in biomarker discovery and testing, Aviva has developed a recombinant antibody platform to deliver high-affinity antibodies and validated antibody pairs to increase the sensitivity of protein biomarker detection with a wide range of detection methods. This platform streamlines high-throughput antibody discovery, affinity assessment, and functional testing, paving the way for innovative immunoassay development across targets and modalities. [6]

Leveraging strong technical expertise and proven workflows, Aviva supplies partners with highly specific and consistent antibody tools that help scientists move from target identification to assay validation, serving as a trusted partner from basic research through diagnostic development.

References

[1] DeMarshall C, Viviano J, Sahin M, Nagele R; the Parkinson’s Study Group (PSG), and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Presymptomatic Detection and Monitoring of Alzheimer’s Disease Using a Multi‐Disease Diagnostic Platform Employing Autoantibodies as Blood‐based Biomarkers. Alzheimers Dement. 2025 Jan 9;20(Suppl 2):e087141. doi: 10.1002/alz.087141.
[2] Barro C, Zetterberg H. The blood biomarkers puzzle - A review of protein biomarkers in neurodegenerative diseases. J Neurosci Methods 361: 109281 (2021).
[3] Bravo-Merodio L, Williams JA, Gkoutos GV. et al. -Omics biomarker identification pipeline for translational medicine. J Transl Med 17, 155 (2019). https://doi.org/10.1186/s12967-019-1912-5
[4] U.S. Food and Drug Administration. FDA Clears First Blood Test Used in Diagnosing Alzheimer’s Disease. May 16, 2025. https://www.fda.gov/news-events/press-announcements/fda-clears-first-blood-test-used-diagnosing-alzheimers-disease
[5] Falzone YM, Domi T, Mandelli A, et al. Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis. Eur J Neurol. 2022;29(7):1930-1939. doi:10.1111/ene.15321
[6] Wallace RL, Bibikov S, Ganz T et al. A recombinant antibody platform for discovery and development of high affinity antibody pairs for diagnostic applications. Poster presented at Alzheimer’s Association International Conference 2025.