QCM biosensors are widely used for the detection of a variety of pathogenic microorganisms, and there remains a need for further increases in sensitivity. The majority of QCM biosensors are operated under diffusion-limited conditions that, when used with a standard flow cell, lead to the majority of analyte being captured onto regions of the crystal surface that have limited to no mass sensitivity. Here we show that simple changes to a flow cell architecture (reduction of flow cell height) can provide increases in sensing signal. Furthermore, we show that the use of radial flow will lead to analyte capture directly in the sensitive region of a crystal, thus providing dramatic increases in the biosensor’s sensitivity. We examine this problem from both a theoretical and numerical perspective and present a new method by which to consider how changes to a sensing assay will affect sensor sensitivity. We demonstrate this experimentally through the detection of E. coli using one commercial and two custom-built flow cells having large differences in height, one of which has radial flow. We show that simple reduction in flow cell height using a standard flow cell leads to a 2.4 × in sensitivity, where the further inclusion of radial flow leads to a 5.1 × increase. We further show that these performance increases are only slightly offset by changes in the sensing noise, which were seen to vary slightly when using different flow cells. These results are directly applicable to nearly every QCM biosensor operated using affinity-based detection.
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