ZnO Nanocages Decorated with Au@AgAu Yolk–Shell Nanomaterials for SERS-Based Detection of Hyperuricemia

Surface-enhanced Raman scattering (SERS) is widely recognized as a highly sensitive technology for chemical detection and biological sensing. In SERS-based biomedical applications, developing highly efficient sensing platforms based on SERS plays a pivotal role in monitoring disease biomarker levels and facilitating the early detection of cancer biomarkers. Hyperuricemia, characterized by abnormally high concentrations of uric acid (UA) in the blood, was associated with a range of diseases, such as gouty arthritis, heart disease, and acute kidney injury. Recent reports have demonstrated the correlation between UA concentrations in blood and tears. In this work, we report the fabrication of SERS substrates utilizing ZnO nanocages and yolk–shell-structured plasmonic nanomaterials for the noninvasive detection of UA in tears. This innovative SERS substrate enables noninvasive and sensitive detection of UA to prevent hyperuricemia-related diseases.


Synthesis of Au Nanorods
Au nanorods were synthesized by using a seed-mediated method. 1,2 eed solution was synthesized by adding 0.6 ml of an ice-cold NaBH 4 (10 mM) solution into the solution containing 0.25 ml of HAuCl 4 (10 mM) and 9.75 ml of CTAB (0.1 M) under vigorous stirring at room temperature.The color of the seed solution changed from yellow to brown.The growth solution was prepared by mixing 5 ml of HAuCl 4 (10 mM), 95 ml of CTAB (0.1 M), 1 ml of AgNO 3 (10 mM), and 0.55 ml of ascorbic acid (0.1 M), consecutively.The solution was homogenized by gentle shaking.To the colorless solution, 0.12 ml of freshly prepared seed solution was added and kept undisturbed in the dark for 14 h.Before use, the AuNR solution was centrifuged twice at 8000 rpm for 10 min to remove excess CTAB and re-dispersed in nanopure water.

Synthesis of Au@Ag NRs
4 ml of twice-centrifuged AuNR and 8 ml of CTAC (20 mM) were mixed at 60 °C under stirring for 20 min.1.6 ml of AgNO 3 (2 mM), 2 ml of CTAC (20 mM), and 0.8 ml of ascorbic acid (0.1M) were added under stirring at 60 °C for 4 h.The Au@Ag NRs solution was centrifuged at 8,000 rpm for 10 min and re-dispersed in 50 mM CTAC solution.

Synthesis of Yolk-shell Nanomaterials
Yolk-shell nanomaterials were synthesized by transforming the Ag shell of Au@Ag NRs into the porous shell of Au/Ag via a galvanic replacement reaction.The as-synthesized Au@Ag NRs were centrifuged and re-dispersed in CTAC solution (20 mM).HAuCl 4 aqueous solution (0.5 mM) was injected into the Au@Ag NRs solution at a rate of 0.5 ml/min under magnetic stirring until the desired LSPR wavelength was achieved.Enhancement factor (EF): The enhancement factor (EF) of yolk-shell nanomaterials-decorated ZnO nanocages was calculated by using the following equation For yolk-shell nanomaterials with size of 59.9 nm in length and 30.2 in width, the volume of yolkshell nanomaterial with AuNR core (53.5 nm in length and 14.5 nm in diameter) is estimated to be around .45800  3 =~11500 counts and =~350 counts     Raman spectrum of 2-NT in bulk was collected using 50x microscopy objective (with a numerical aperture (NA) =0.45).The approximate laser spot size of 50X objective can be obtained using the following expression: Where is the minimum waist diameter for a laser beam of a wavelength focused by an  0  objective with a numerical aperture NA.

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Figure S1.(a) SEM image of Cu 2 O nanocubes.(b) Histogram of the edge length of Cu 2 O nanocubes.

Figure S5 .Figure S6 .Figure
Figure S5.SEM images of (a) AuNRs, (b) Au@Ag NRs, and (c) yolk-shell nanomaterials.(d) Representative UV-Vis spectra of Au@Ag NRs upon addition of different volume of aqueous of HAuCl 4 solution during the galvanic replacement reaction to form the yolkshell nanomaterials.

FigureFigure S13 .Figure S14 .
Figure S12.(a) Raman spectra obtained from the yolk-shell nanomaterials-decorated ZnO nanocages with uric acid exposure at various time points.(b) The histogram of the Raman intensity at the 1127 cm -1 Raman band in (a).n=3.
Figure S3.SEM image of Zn(OH) 2 nanospheres with relatively (a) low and (b) high magnifications.