Biosensor design based on Marangoni flow in an evaporating drop

Abstract

Effective point-of-care diagnostics require a biomarker detection strategy that is low-cost and simple-to-use while achieving a clinically relevant limit of detection. Here we report a biosensor that uses secondary flows arising from surface Marangoni stresses in an evaporating drop to concentrate target-mediated particle aggregates in a visually detectable spot. The spot size increases with increasing target concentration within the dynamic range of the assay. The particle deposition patterns are visually detectable and easily measured with simple optical techniques. We use optical coherence tomography to characterize the effect of cross-sectional flow fields on the motion of particles in the presence and absence of target (aggregated and non-aggregated particles, respectively). We show that choice of substrate material and the presence of salts and glycerol in solution promote the Marangoni-induced flows that are necessary to produce signal in the proposed design. These evaporation-driven flows generate signal in the assay on a PDMS substrate but not substrates with greater thermal conductivity like indium tin oxide-coated glass. In this proof-of-concept design we use the M13K07 bacteriophage as a model target and 1 μm-diameter particles surface functionalized with anti-M13 monoclonal antibodies. Using standard microscopy-based techniques to measure the final spot size, the assay has a calculated limit-of-detection of approximately 100 fM. Approximately 80% of the maximum signal is generated within 10 minutes of depositing a 1 μL drop of reacted sample on PDMS enabling a relatively quick time-to-result.

Active accumulation of very diluted biomolecules by nano-dispensing for easy detection below the femtomolar range

“…and comparable to a very sensitive (0.006 p.p.m.) approach to gliadin determination recently described in literature 30 , thus opening the way to highsensitive detection.…”

“…Last, but not least, is the time scale of the analysis that, when operating at low concentrations, is mainly around half an hour or more 6,11 . Very recently, alternative techniques have been proposed for concentrating analytes, but still using the passive effects of the evaporation behaviour of sessile droplets [30][31][32] .…”

Nanoscale virus biosensors: state of the art

“…176,177 The OCT has helped to usher in a new era of in vivo diagnostic imaging. 178 Trantum et al 179 reported a biosensor that used secondary flows arising from surface Marangoni stresses that are necessary to produce signal in the proposed design. These evaporation-driven flows generate signal in the assay based on a polydimethylsiloxane substrate but not substrates with greater thermal conductivity like indium tin oxidecoated glass.…”

“…In this proof-of-concept design, the M13K07 bacteriophage was used as a model target. 179 Lee et al 180 described a unique system integrating several optoelectronic-based biological diagnostic tools such as an ellipsometer, a laser Doppler vibrometer/interferometer, SPR analyzer, an interference microscope, a photon tunneling microscope, an optical coherence tomography unit, and a confocal scanning microscope. This OBMorph system, useful as a powerful optical metrology diagnostic tool, can be used at the beginning of sensor chip fabrication, during the signal detection/monitoring, and in the final biological analysis.…”

Micro- and nanofluidic systems in devices for biological, medical and environmental research

“…A number of new portable microfluidic devices were reported [9] with many built-in functions for creating simpler ones [10], faster and cheaper devices [11] with better detection limits. Microfluidic device consisting of 500 channels is intended for the rapid analysis (within 20 minutes) of the integrity of the sperm DNA using fluorescent imaging [11].…”