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Optica Publishing Group
  • 2015 European Conference on Lasers and Electro-Optics - European Quantum Electronics Conference
  • (Optica Publishing Group, 2015),
  • paper JSII_1a_3

Optofluidic-Plasmonic Handheld Biosensor for High-Throughput and Label-Free Monitoring of Molecular Interactions

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Abstract

We introduce a high-throughput and field deployable handheld biosensor that can simultaneously measure multiple specific disease markers without the need for any labeling and sophisticated sample preparation protocols.[1,2] The presented biodetection platform (Figures 1a) combines microfluidics based plasmonic microarrays with lensfree dual-color on-chip imaging. This compact device comprises a plasmonic substrate, containing arrays of nanohole arrays, which is simultaneously illuminated by two different color light emitting diodes (LEDs) adjusted to the right and left sides of the plasmonic mode of the nanohole arrays. This illumination pattern, after interacting with the plasmonic interface, is detected by a Complementary Metal–Oxide–Semiconductor (CMOS) imager, creating two diffraction patterns for each plasmonic pixel at the detector array. As shown in Figure 1b, the refractive index change of the medium neighboring the plasmonic substrates causes a spectral shift in the peak wavelength of the plasmonic mode, boosting the signal in one of the diffraction patterns (mismatching between plasmonic mode and LED response decreases) while decreasing the other one (mismatching increases). We then perform quantitative analysis of refractive index change based on the ratiometric analysis of the acquired dual diffraction patterns. For the sensitivity analysis, we measure and quantify sugar solutions with various concentrations, ranging from 0.055 mol/L to 1.1 mol/L (Figure 1c). Based on the bulk solution experiments, we calculate a detection limit (minimum detectable refractive index change) of our biosensing platform, as small as 2 × 10−3 RIU, which is a highly advantageous number for ultra-sensitive biosensing applications. We also employ our optofluidic biosensor device to quantitatively analyze the interactions of protein-protein complexes. We perform time-lapse experiments within microfluidic channels to monitor the association phase of protein IgG (200 μg/mL) onto protein AG (100 μg/mL). Over 80 minutes of constant injection of IgG proteins, the binding process exhibits an exponential rise in the dual-wavelength lensfree sensor (Figure 1d). We validate the binding events using a spectrometer before and after the association phase, yielding a 6 nm shift in the peak wavelength obtained from three independent sensors (Figure 1d-inset). Based on our analytical model for the association phase, we obtain (spectrometer analysis) Δλ = 6.448×(1 − e−0.0005333t) and (lensfree analysis) IR = 0.10188×(1 e−0.0005333t) where Δλ is the peak wavelength shift from the initial peak wavelength at time t and IR is the intensity ratio change from the initial intensity ratio at time t. These two relations show that two measurements provide similar exponential constants, 0.0005333 and 0.0005685 for data from optical spectrometer and lensfree sensor, respectively. These results prove that our handheld biosensor can be reliably used for real-time analysis of biomolecular binding kinetics in a cost-effective and ultra-sensitive manner.

© 2015 IEEE

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