Evaluation of 120 Neurodegenerative and inflammatory Proteins in Dried Blood Spots and Plasma Spots for Population-wide biomarker Screening with NULISAseq

Topic/Product:
DBS, Neurology
Disease Area:
Sample Type:

Abstract

Objectives: Blood-based biomarker profiling holds great promise for the early detection of neurodegenerative diseases. However, standard-ization of sample collection and storage conditions is critical for reliable and accurate testing. Dried blood spots (DBS) and dried plasma spots (DPS) provide alternative collection methods for longitudinal, population-wide studies especially in remote areas with a lack of infrastructure and warrant further evaluation for compatibility with highly multiplexed proteomic platforms for profiling key markers of disease pathogenesis including pTaus, amyloid betas, and inflammatory cytokines.

Methods: Multiple commercially available dried blood spots and dried plasma spots collection devices were evaluated in comparison with matched whole blood and plasma from healthy and diseased subjects with the NULISAseq 120-plex CNS Disease Panel on the ARGO™ HT platform. Different extraction conditions and sample input volumes were tested to determine optimal conditions for detection of key neurodegenerative and inflammatory targets at high sensitivity. Pearson correlation analysis was performed to determine the concordance between matched whole blood and DBS as well as plasma and DPS.

Results: Our preliminary results show high detectability in DBS (>90%) and DPS (>85%), comparable to overall detectability in paired whole blood and plasma samples. Additionally, key CNS targets such as NFL, GFAP, pTaus (pTau-181, pTau-217 and pTau-231) showed close to 100% detectability. Overall, relative protein quantification in DBS and DPS demonstrate high correlations with matched blood and plasma respectively (r>0.75). We have developed an optimized protocol for extraction of proteins from DBS and DPS followed by evaluation with the NULISAseq technology. Our data suggests that most targets of interest are compatible with this type of collection method and DBS/DPS can be a promising substitute for blood-based profiling with added benefits of ease of collection, storage, transportation and analysis.

Authors & Affiliations

Xiao-Jun Ma1, Karl Garcia1, Tsz Tam1, Li Wang1, Sean Kim1, Niyati Jhaveri1, Xiaolei Qiu1, Bingqing Zhang1, Yuling Luo1,

1Alamar Biosciences Inc., Fremont, California, USA

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.