WGM Sensors for future diagnostics: small molecules to whole organisms

In a world facing constant challenges from diseases and pathogens, rapid diagnosis is crucial. Whispering gallery mode (WGM) resonators present an advanced sensor technology suitable for the detection of various analytes. Like surface plasmon resonance (SPR), they offer highly sensitive and selective measurements, ideal for medical diagnostics. Traditional WGM resonators, however, are immobilized on surfaces near optical couplers, making their production complex and costly. Nevertheless, a more recent approach employs polystyrene microspheres localized to cavities in fluidic chips as resonators, simplifying preparation and functionalization and displaying enhanced performance. Here, we assess the applicability of those sensors to different analyte sizes, ranging from small molecules (<1000 Da) to whole organisms. By employing different detection strategies, we confirm the applicability of the WGM sensors for detecting a wide range of targets.

The study focuses on L. pneumophila, TEM-1 beta-lactamase, aztreonam, and meropenem as representatives of these three major groups. We show that the detection was successful for all chosen analytes, while small molecules required additional signal amplification through a sandwich approach. Results of the analysis of the protein measurements showed an LOD of 0.09 μM and an LOQ of 0.28 μM with a R² greater than 0.99. Additionally, a comparative measurement demonstrates that the WGM is more sensitive than the widely used gold standard SPR (LOD 0.34 μM; LOQ 1.12 μM). Taken together, our work demonstrates the applicability of the WGM sensors to pathogen detection, protein quantification or small molecule analysis with an improved sensitivity compared to current gold standard methods.