Abstract
Rapid biosensing requires fast mass transport of the analyte to the surface of the sensing element. To optimize analysis times, both mass transport in solution and the geometry and size of the sensing element need to be considered. Small dielectric spheres, tens of microns in diameter, can act as label-free biosensors using whispering gallery mode (WGM) resonances. WGM resonances are sensitive to the effective refractive index, which changes upon analyte binding to recognition sites on functionalized resonators. The spherical geometry and tens of microns diameter of these resonators provides an efficient target for sensing while their compact size enables detection in limited volumes. Here, we explore conditions leading to rapid analyte detection using WGM resonators as label-free sensors in 10 μL sample droplets. Droplet evaporation leads to potentially useful convective mixing, but also limits the time over which analysis can be completed. We show that active droplet mixing combined with initial binding rate measurements is required for accurate nanomolar protein quantification within the first minute following injection.
Highlights
The specific detection of biological markers in complex matrices is important in early disease detection, evaluating response to treatment, and monitoring disease reoccurrence
Because of their compact size, microsphere whispering gallery mode (WGM) resonators are well suited for small volume analysis
Small volume droplet assays utilizing WGM resonators are demonstrated as a promising label-free sensing platform
Summary
The specific detection of biological markers in complex matrices is important in early disease detection, evaluating response to treatment, and monitoring disease reoccurrence. One biosensing approach capable of multiplexed, label-free detection uses light trapped in small resonators to sense analyte binding at the sensor surface [5,6,7]. Their spherical geometry and tens of microns diameters lend themselves to optimized mass transfer for rapid analysis [24,25,26] Their compact size enables accurate analysis in small volumes, enabling multiplexed sensing in sample-limited applications. Droplets on a surface undergo complex evaporation processes leading to temperature gradients which produce a natural mixing effect within the liquid [30,31,32,33,34] This can potentially increase sensor response time through improved mass transport. Initial binding rate studies in actively stirred droplets show that nanomolar protein concentrations can be quantified within minutes using the small volume assay
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