Abstract

We present a microfluidic surface-enhanced Raman scattering (SERS) sensor for rapid and label-free biomolecular detection. Our sensor design mitigates a common limiting factor in microfluidic SERS sensors that utilize integrated nanostructures: low-efficiency transport of biomolecules to nanostructured surface which adversely impacts sensitivity. Our strategy is to increase the total usable nanostructured surface area, which provides more adsorption sites for biomolecules. Specifically, a nanoporous gold disk (NPGD) array, a highly effective SERS substrate, has been monolithically integrated inside a microfluidic chip. Individual NPGD is known to feature an order of magnitude larger surface area than its projected disk area. The increased surface area arises from nanoscale pores and ligaments three-dimensionally distributed in the NPGD, which manifest themselves as high-density SERS hot-spots. High-density NPGD arrays further guarantee large coverage of these hot-spots on the microchannel floor. The sensor performance has been demonstrated using Rhodamine 6G to quantify spatial uniformity and determine the shortest detection time. Next, the sensor is applied to detect two biomolecules, dopamine and urea, with unprecedented detection limit and speed compared to other existing microfluidic SERS sensors. The sensor holds great promise in point-of-care applications for various biomolecular detections.

Highlights

  • Detection and identification of molecules in a rapid, sensitive, and cost-effective manner play an essential role in the point-ofcare applications

  • Using urea detection as an example, the only quantitative result we have identified on microfluidic surface-enhanced Raman scattering (SERS) using Au-coated nanodome arrays was previously mentioned.[36]

  • After the microchannel was filled with the solution for 10 min, SERS spectra were acquired from different locations with 10 s acquisition time each

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Summary

Introduction

Detection and identification of molecules in a rapid, sensitive, and cost-effective manner play an essential role in the point-ofcare applications. Microfluidic platforms hold great promise in achieving this purpose due to their distinct advantages such as small sample and reagent consumption, fast reaction and analysis times, environmental and user friendliness, and low cost.[1,2] To date, a variety of methods have been developed and applied within microfluidic systems for molecular sensing, including electrochemical,[3,4,5] mechanical,[6,7] mass spectrometric,[8,9] and optical (i.e., fluorescence,[10] absorbance,[11] Raman spectroscopy,[12] surface plasmon resonance,[13] and chemiluminescence14) detection techniques Among these available methodologies, surface-enhanced Raman scattering (SERS)-based detection techniques have attracted much attention because of their “fingerprinting” capability for label-free and multiplexed sensing. In order to improve SERS signals, colloid nanoparticles were effectively concentrated by geometrical barriers.[32,33] Adenine molecules lower than 10 pM were detected,[32] but this can be a relatively time-consuming process, because the sample was prepared by an activation agent (i.e., sodium chloride) to increase

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