Conjugating immunoassays to mass spectrometry: Solutions to contemporary challenges in clinical diagnostics

Abstract

Developments in immunoassays and mass spectrometry have independently influenced diagnostic technology. However, both techniques possess unique strengths and limitations, which define their ability to meet evolving requirements for faster, more affordable and more accurate clinical tests. In response, hybrid techniques, which combine the accessibility and ease-of-use of immunoassays with the sensitivity, high throughput and multiplexing capabilities of mass spectrometry are continually being explored. Developments in antibody conjugation methodology have expanded the role of these biomolecules to applications outside of conventional colorimetric assays and histology. Furthermore, the range of different mass spectrometry ionisation and analysis technologies has enabled its successful adaptation as a detection method for numerous clinically relevant immunological assays. Several recent examples of combined mass spectrometry-immunoassay techniques demonstrate the potential of these methods as improved diagnostic tests for several important human diseases. The present challenges are to continue technological advancements in mass spectrometry instrumentation and develop improved bioconjugation methods, which can overcome their existing limitations and demonstrate the clinical significance of these hybrid approaches.

A conformational variant of p53 (U-p53AZ) as blood-based biomarker for the prediction of the onset of symptomatic Alzheimer’s disease

“…To further improve its analytical performance, U-p53 AZ was quantified by the AlzoSure ® Predict method, a LC-ESI/MS/MS sequential technique using plasma samples from individuals at different stages of the AD continuum, available through the longitudinal AIBL cohort. Due to its high specificity in comparison with conventional techniques and its increasing accessibility at lower costs, MS has been widely used in several blood-based biomarker studies (Jannetto and Fitzgerald, 2016;Oeckl and Otto, 2019;Stevens and Pukala, 2020). By using this technique, the present study aimed to assess whether quantification of U-p53 AZ was able to assign individuals to the correct diagnostic group and determine its performance for predicting the onset of AD at the preclinical and prodromal stages.…”

“…Assessment of U-p53 has now been improved by the development of a novel antibody (Jannetto and Fitzgerald, 2016;Oeckl and Otto, 2019;Stevens and Pukala, 2020). By using this technique, the present study aimed to assess whether quantification of U-p53 AZ was able to assign individuals to the correct diagnostic group and determine its performance for predicting the onset of AD at the preclinical and prodromal stages.…”

Novel approaches for rapid detection of COVID-19 during the pandemic: A review

“…However, the high molecular weight and substantial heterogeneity create some additional challenges for the MS analysis of biological molecules. Therefore, some conjugation reagents were designed to improve the ionization and detection of biological molecules [ 68 ]. It seems MS method is a suitable alternative for PCR detection method during the pandemic.…”

Molecular markers for cervical cancer screening

“…Unfortunately, the wide dynamic concentration range of proteins in biological samples and notably in body fluids does not always allow to use targeted LC-MS without extensive sample preparation. Recent work on affinity enrichment coupled to mass spectrometry and more generic sample preparation strategies for biomarker analysis in routine clinical chemistry laboratories opens the way toward a more widespread use of LC-MS in these areas [81][82][83][84].…”