US HUPO 2024: ARGO™ HT System: An Automated, Ultra-Sensitive and High-Throughput Proteomics Platform for the Blood Proteome

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Abstract

Purpose: Existing proteomic platforms often make tradeoffs between sensitivity and multiplexing capabilities and rely on labor-intensive processes. Here we introduce ARGO HT, an automated high-throughput proteomics platform specifically designed for the NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) technology, a novel immunoassay with attomolar sensitivity and high multiplexing capability. We developed a 250-plex inflammation panel and a 120-plex central nervous system (CNS) disease panel and evaluated their performance on the ARGO HT system.

Methods: The 250-plex inflammation panel contained a wide range of cytokines, chemokines, and other immune-related proteins. It was used to profile the blood of patients with autoimmune diseases (n=21) and COVID-19 at multiple time points (n=46). The 120-plex CNS panel included well-established biomarkers like neurofilament light (NfL) and phosphorylated Tau (p-Tau181, p-Tau217 and p-Tau231) as well as other targets of high relevance to neurodegenerative diseases (NDDs). It was used to analyze plasma (n=38) and cerebrospinal fluid (CSF) (n=29) samples from NDD patients and age-matched controls. Linear model analysis was performed to identify differentially abundant targets between disease and control groups. Coefficient of variation (CV) was calculated for the sample control, and target detectability above the limit of detection (LOD) was calculated for each sample set.

Results: Using 10uL samples, the inflammation and CNS disease panels demonstrated a median CV <10%. Both panels detected over 95% of the targets in plasma, and the CNS panel showed an ~80% target detectability in CSF. Linear regression analysis revealed significant differences in the abundance of both known and novel proteins between disease and control groups.

Conclusion: The benchtop ARGO system fully automates the NULISA technology and demonstrates ultrahigh sensitivity and precision. With the integration of reagents, instrumentation and software ARGO HT democratizes high-throughput proteomic analysis, opening the door to the low-abundance proteome for the discovery of novel biomarkers for early disease detection and therapeutic targets.

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.