Simple, Large-Scale Fabrication of Uniform Raman-Enhancing Substrate with Enhancement Saturation

Abstract

It is well-known that gold nanoparticle (AuNP) clusters generate strong surface-enhanced Raman scattering (SERS). In order to produce spatially uniform Raman-enhancing substrates at a large scale, we synthesized vertically perforated three-dimensional (3D) AuNP stacks. The 3D stacks were fabricated by first hydrothermally synthesizing ZnO nanowires perpendicular to silicon wafers followed by repetitively performing liquid-phase deposition of AuNPs on the tops and side surfaces of the nanowires. During the deposition process, the nanowires were shown to gradually dissolve away, leaving hollow vestiges or perforations surrounded by stacks of AuNPs. Simulation studies and experimental measurements reveal these nanoscale perforations serve as light paths that allow the excitation light to excite deeper regions of the 3D stacks for stronger overall Raman emission. Combined with properly sized nanoparticles, this feature maximizes and saturates the Raman enhancement at 1-pM sensitivity across the entire wafer-scale substrate, and the saturation improves the wafer-scale uniformity by a factor of 6 when compared to nanoparticle layers deposited directly on a silicon wafer substrate. Using the 3D-stacked substrates, quantitative sensing of adenine molecules yielded concentrations measurements within 10% of the known value. Understanding the enhancing mechanisms and engineering the 3D stacks have opened a new method of harnessing the intense SERS observed in nanoparticle clusters and realize practical SERS substrates with significantly improved uniformity suitable for quantitative chemical sensing.

Surface-Enhanced Raman Spectroscopy-Based Label-Free Insulin Detection at Physiological Concentrations for Analysis of Islet Performance

“…Using our method, we characterized the insulin concentrations in pancreatic islet secretions that were collected under low and high glucose conditions. The measurements obtained using our approach showed excellent consistency and paralleled the concentrations obtained using an enzyme-linked immunosorbent assay (ELISA).The fabrication of the SERS substrate was described in detail by Yang et al 33 A summary of the fabrication has been provided in the Supporting Information ( Figure S1). The cross-sectional view of the 3D Au-NP SERS substrate acquired using scanning electron microscopy (SEM) is shown in Figure 1a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 6 insulin concentration.…”

“…[31][32][33][34] The sensors were batch-fabricated using a simple two-step process that produced 3 dimensional (3D) gold-nanoparticle (Au-NP) clusters packed densely in a vertical, pillar-like arrangement. 33 The 3D pillar-like geometry of the clusters adsorb and excite insulin molecules with vertically packed plasmonic hotspots uniformly over a large surface area for enhanced Raman emissions. This geometry provides significantly stronger and more spatially uniform enhancement than previously used substrates and greatly improved the detection limit.…”

“…The fabrication of the SERS substrate was described in detail by Yang et al 33 A summary of the fabrication has been provided in the Supporting Information ( Figure S1). The cross-sectional view of the 3D Au-NP SERS substrate acquired using scanning electron microscopy (SEM) is shown in Figure 1a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 6 insulin concentration.…”

“…[27][28][29][30] In this study, we report highly sensitive SERS-based insulin sensing at clinically relevant concentrations using a non-resonant SERS substrate with strong signal enhancement and wafer- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 5 scale uniformity. [31][32][33][34] The sensors were batch-fabricated using a simple two-step process that produced 3 dimensional (3D) gold-nanoparticle (Au-NP) clusters packed densely in a vertical, pillar-like arrangement. 33 The 3D pillar-like geometry of the clusters adsorb and excite insulin molecules with vertically packed plasmonic hotspots uniformly over a large surface area for enhanced Raman emissions.…”

“…Given the size of insulin molecules, even if there were a second layer sitting on top of the first layer, the second layer would be too far away from the surface to significantly benefit from the near-field enhancement on the surface, and the Raman-emission contribution by the second and/or third layers would be minimal. 39 The signal-to-noise ratio (SNR) at 100 pM was calculated to be approximately 8.5, and the theoretical detection limit was calculated to be 35 pM for a minimum acceptable SNR of 3.For typical SERS substrates, even a small displacement of the incident laser could often lead to a huge change in Raman signal intensity due to non-uniformly distributed SERS hotspots.In order to improve the consistency of SERS measurements, recent focus has been placed on improving the chip-scale measurement uniformity either by implementing better substrates, [31][32][33][34] or employing better measurement strategies such as areal averaging, 35-36 which involves scanning a larger area on the substrate to collect and average more Raman-signal data points as opposed to 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 making a single point measurement. Two-dimensional (2D) mapping of Raman spectra was performed over a 1×1 mm 2 area with a step size of 20 µm on a chip coated with a 10-nM insulin solution (Figure 2c).…”