Hierarchically structured materials, inspired by sophisticated structures found in nature, are finding increasing applications in a variety of fields. Here, we describe the fabrication of wrinkled gold nanoparticle films, which leverage the structural tunability of gold nanoparticles to program the wavelength and amplitude of gold wrinkles. We have carefully examined the structural evolution and tuning of these wrinkled surfaces through varying nanoparticle parameters (diameter, number of layers, density) and substrate parameters (number of axes constrained during wrinkling) through scanning electron microscopy and cross-sectional transmission electron microscopy. It is found that nanoparticle layers of sufficient density are required to obtain periodical wrinkled structures. It was also found that tuning the nanoparticle diameter and number of layers can be used to program the wrinkle wavelength and amplitude by changing the film thickness and mechanical properties. This dual degree of tunability, not previously seen with continuous films, allows us to develop one of the smallest wrinkles developed to date with tunability in the sub-100 nm regime. The effect of the induced structural tunability on the enhancement of the intensity of the 4-mercaptopyridine Raman spectra is also studied through the application of these devices as substrates for surface-enhanced Raman spectroscopy (SERS), where wrinkling proves to be an effective method for enhancing the SERS signal in cases where there is an inherently low density of gold nanoparticles.

Physical characterization of an ultrasound contrast agent (UCA) aids in its safe and effective use in diagnostic and therapeutic applications. The goal of this study was to investigate the impact of temperature on the size distribution, shell properties, and stability of Definity, a U.S. Food and Drug Administration-approved UCA used for left ventricular opacification. A Coulter counter was modified to enable particle size measurements at physiologic temperatures. The broadband acoustic attenuation spectrum and size distribution of Definity were measured at room temperature (25 °C) and physiologic temperature (37 °C) and were used to estimate the viscoelastic shell properties of the agent at both temperatures. Attenuation and size distribution was measured over time to assess the effect of temperature on the temporal stability of Definity. The attenuation coefficient of Definity at 37 °C was as much as 5 dB higher than the attenuation coefficient measured at 25 °C. However, the size distributions of Definity at 25 °C and 37 °C were similar. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10 ± 0.07 × 10 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10 ± 0.04 × 10 kg/s at 37 °C, respectively. Size-dependent differences in dissolution rates were observed within the UCA population at both 25 °C and 37 °C. Additionally, cooling the diluted UCA suspension from 37 °C to 25 °C accelerated the dissolution rate. These results indicate that although temperature affects the shell properties of Definity and can influence the stability of Definity, the size distribution of this agent is not affected by a temperature increase from 25 °C to 37 °C.

Physical characterization of ultrasound contrast agents (UCAs) is important for their efficacious use in theragnostic applications. The goal of this study was to elucidate the impact of temperature on the size distribution and shell properties of Definity®, an FDA-approved clinical UCA. A Coulter counter (Multisizer IV) was modified to enable size measurements of UCAs at elevated temperatures. The size distribution and attenuation spectrum of Definity® was measured at room temperature (25 °C) and physiological temperature (37 °C), and used to estimate the shell stiffness and viscosity of the agent at both temperatures. The attenuation coefficient of Definity® increased by as much as 5 dB at 37 °C relative to 25 °C. The highest increase in attenuation was observed at 10 MHz, the resonance frequency of Definity®. However, no significant difference was observed in the size distribution of Definity® at 25 °C and 37 °C. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10-6 ± 0.07 × 10-6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10-6 ± 0.04 × 10-6 kg/s at 37 °C. These results indicate that the change in shell properties mediates the change in acoustic behavior of Definity® at physiological temperature.

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