A Cost-Effective High-Speed Clinical Diagnostics Instrument for Large Population Screening Based on Novel Liquid AP-MALDI MS Technology

Lead Research Organisation: University of Reading
Department Name: Chemistry


Based on previously funded EPSRC research (EP/L006227/1) for the 'Development of a novel MALDI mass spectrometer and technology for the generation of multiply charged ions at high sensitivity' and subsequent initial exploitation of this new technology, the proposed project will develop a new instrument that specifically fulfils key requirements in clinical diagnostics as demanded by modern medicine, in particular in the age of new pandemics such as COVID-19.

Accurate and fast characterisation of microorganisms in clinical samples are crucial for initiating optimal treatment and limiting the outbreaks of pandemics. Both accuracy and time are key to the best treatment outcome for the patient, minimising the time to recovery and more importantly minimising morbidity and mortality. In particular, the correct and rapid identification of newly discovered microbial pathogens or antimicrobial-resistant strains is important for the patient's recovery. Combined with the capability of large-scale testing, it will also allow for a better global response to (microbial) infectious diseases.

Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry (MS) profiling of organisms (biotyping) has recently been established as a superior method to classical clinical microbiology assays for the identification of clinically relevant microbes with substantially increased classification accuracy and speed of analysis. This has already led to two FDA approved systems for microbial detection and identification by MALDI MS biotyping. In the proposed project, this methodology will be substantially advanced by exploiting multiply charged ions and their co-analysis with lipids and other biomolecules on a bench-top MS/MS instrument specifically optimised for large-scale, inexpensive clinical analyses, thus leading to the next generation of superior MALDI MS biotyping for clinical use and mass testing.

The unique features of this new instrument and the associated technology will be high speed, cost-effectiveness, and high specificity by MS/MS sequencing. Combined with the unrivalled resolution of mass spectrometry this new technology will be a step-change in diagnostic testing by allowing the testing of multiple diseases within the same test run as well as being highly adaptable to new diseases without the need to develop test reagents that are disease/microbe-specific, difficult to source and therefore expensive, in particular for newly discovered diseases (cf. COVID 19). The aim is to reach a throughput level of 100,000 samples per day at high detection accuracy and low cost per sample.

From collaborating with the biopharmaceutical industry and analytical instrument manufacturers, and from research of a BBSRC-funded grant, we found that our novel AP-MALDI MS ion source provides a sensitive platform for rapid assay analysis with the potential for use in the early detection of microbial diseases. The proposed project will build on this preliminary data, develop a new tailor-made instrument for future clinical use and explore the advantages (compared to current MALDI MS biotypers) in (a) speed, (b) the elimination of biological matrix background, (c) superior MS/MS analysis, (d) greater ion signal stability, (e) multiplexing capability and (f) the simpler (and cost-effective) but more flexible sample preparation that this new technology can offer.


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Description HIP - IMPROV
Amount £8,000 (GBP)
Funding ID IMPROV 
Organisation University of Reading 
Sector Academic/University
Country United Kingdom
Start 08/2022 
Description PhD strategic studentship: Novel applications of liquid AP-MALDI MS
Amount £80,000 (GBP)
Funding ID GS23-015 
Organisation University of Reading 
Sector Academic/University
Country United Kingdom
Start 09/2023 
End 09/2026
Title A new benchtop Q-TOF mass spectrometer with LAP-MALDI ion source 
Description This new benchtop Q-TOF mass spectrometer is equipped with a LAP-MALDI ion source which allows mass spectrometry measurements using the liquid atmospheric pressure MALDI MS technique. This setup is comparable to the design of a previously developed ion source (see research grant EP/L006227/1) with slight geometric modifications to have a more compact design for benchtop mass spectrometers and is the first benchtop mass spectrometer with a LAP-MALDI ion source. 
Type Of Material Improvements to research infrastructure 
Year Produced 2022 
Provided To Others? Yes  
Impact This setup allows mass spectrometry measurements of various types of sample in a high-throughput manner, reaching subsecond cycle times per sample with all of the advantages of LAP-MALDI MS such as the generation of multiply charged ions, contactless sampling, highly stable energy deposition and great sample homogeneity (and therefore highly stable ion yields). This LAP-MALDI mass spectrometer setup, which is much more compact in its design than previous setups, might serve as a blueprint for future developments of this technology towards commercialised versions applying this technology. 
Description Website related to EPSRC award EP/V047485/1 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A word-press based website supported by the University of Reading and titled with "Fast speed diagnostics" was created describing the above EPSRC project and its project outcomes in order to inform on the research topic.
Website link: https://research.reading.ac.uk/highspeeddiagnostics
Participants providing samples for this project are referred to this website for obtaining further information.
Year(s) Of Engagement Activity 2022
URL https://research.reading.ac.uk/highspeeddiagnostics