Abstract
Large-scale population screening for early and accurate detection of disease is a key objective for future diagnostics. Ideally, diagnostic tests that achieve this goal are also cost-effective, fast and easily adaptable to new diseases with the potential of multiplexing. Mass spectrometry (MS), particularly MALDI MS profiling, has been explored for many years in disease diagnostics, most successfully in clinical microbiology but less in early detection of diseases. Here, we present liquid atmospheric pressure (LAP)-MALDI MS profiling as a rapid, large-scale and cost-effective platform for disease analysis. Using this new platform, two different types of tests exemplify its potential in early disease diagnosis and response to therapy. First, it is shown that LAP-MALDI MS profiling detects bovine mastitis two days before its clinical manifestation with a sensitivity of up to 70% and a specificity of up to 100%. This highly accurate, pre-symptomatic detection is demonstrated by using a large set of milk samples collected weekly over six months from approximately 500 dairy cows. Second, the potential of LAP-MALDI MS in antimicrobial resistance (AMR) detection is shown by employing the same mass spectrometric setup and similarly simple sample preparation as for the early detection of mastitis.
Highlights
Infectious diseases can have devastating effects on entire populations as recently experienced with COVID-19 and predicted for future pandemics,[1] including any compounding impact by the increasing growth of antimicrobial resistance (AMR).[2]
The speed and simplicity of MALDI is combined with the advantages of Electronic supplementary information (ESI), enabling the use of high-performing Mass spectrometry (MS) instrumentation. With this ideal in mind we developed a mass spectrometric platform that is based on the exploitation of liquid atmospheric pressure (AP) (LAP)-MALDI, which facilitates the generation of multiply charged ions and the effective use of MALDI for MS(/MS) analysis on these types of instruments.[15]
The liquid atmospheric pressure (LAP)-MALDI source is designed for use with highperforming mass spectrometers enabling the detection of heterogeneous analyte ions over a wide mass range, i.e. metabolites and other small molecules, lipids and peptides/ proteins
Summary
Infectious diseases can have devastating effects on entire populations as recently experienced with COVID-19 and predicted for future pandemics,[1] including any compounding impact by the increasing growth of antimicrobial resistance (AMR).[2]. One measure that has been frequently discussed is the use of adequate diagnostics and mass testing.[3,5] Such discussions are typically centred around test accuracy (sensitivity and speci city), speed and capacity at low cost per sample with an adaptability of the testing platform to new diseases that will allow for rapid deployment without an overreliance on the production and sourcing of disease-speci c test reagents, which could lead to supply chain issues.[6]. Such testing platform will be capable of multiplexing, i.e. detecting a range of diseases, their prognosis and/or their response to therapy in one single test, and be operational within a few days, even for newly discovered diseases, using the same instrumentation as for previous disease testing. Mass spectrometry (MS) has repeatedly been championed as a diagnostic method for highly speci c and sensitive measurement of disease-speci c biomarkers.[7,8] Its exquisite mass measurement accuracy and resolution can provide the biomarker speci city and detection space for (multiplexed) disease detection at a level conventional antigen tests cannot compete.[9–11] in combination with additional analysis modes such as MS/MS or the use of ion mobility, MS approaches can be extremely powerful with respect to detecting speci c disease biomarkers unambiguously (e.g. see Singh et al.[12])
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