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The photoacoustic signal generated from specific gold nanoparticles increases nonlinearly with respect to fluence. We demonstrate experimentally that this nonlinear behavior can be quenched with a particle coating, and present a theoretical analysis to explain this behavior. This effect has the potential to be developed into a photoacoustic-based biochemical sensor.

Photoacoustic (PA) imaging is an emerging biomedical imaging modality that combines the spectroscopic-based contrast of optical imaging with the deep penetration depth capability of ultrasonic imaging.^1,2 A PA pressure pulse is generated when intensity-modulated light is absorbed by the biological target, inducing minor temperature fluctuations that create acoustic waves. For contrast enhancement in PA imaging, materials with high absorption coefficients such as nanoparticles can be employed.^3,4 Gold nanoparticles (GNPs), for example, exhibit a high surface-plasmon-resonance-based absorption cross section, and provide strong PA contrast. GNPs also enable targeted specificity because they distribute themselves at certain cell sites,³ and can be functionalized to target key molecular sites of interest.⁴ When a PA signal is generated from light absorption by a GNP, the absorbed energy rapidly diffuses to the surrounding biological fluid, where the majority of the PA signal generation occurs.^5–7 Certain GNP colloids, such as nanospheres of 100 nm in diameter and larger in water, exhibit a nonlinear PA signal strength with respect to excitation fluence, which is attributed to extreme heating of nano-scale fluid volumes surrounding the GNPs, leading to variations in the thermal expansion coefficient of the surroundings.^7,8 This causes the nonlinear PA signal generation phenomenon, because the PA signal is proportional to the thermal expansion coefficient.¹

Common coatings for nanoparticle-based PA contrast agents include polyethylene glycol and silica.⁴ Coating of GNPs has certain advantages, including increasing colloidal and thermal stability, and adding functionalization.^9,10 A nanoparticle coating can affect the PA signal because the heat transfer between the particle and the surrounding medium is influenced.¹¹ Recent reports indicate that a coating with finite heat conductance and capacity may broaden the PA pulse and deteriorate the PA signal amplitude if interfacial thermal resistance is negligible.¹² We have recently shown that this is the case with silica coating of small-diameter GNPs, whose PA signal strength is linear with respect to fluence.¹³ Other theoretical models confirm that for the nanosecond pulses employed in PA imaging, interfacial thermal resistance has no significant effect on the heat transfer process between the GNP and fluid.¹⁴ While experimental studies have previously investigated the effect of silica coating on the PA signal from GNPs, all studies in the literature have focused on small diameter GNPs that exhibit a linear PA signal with respect to fluence.^5,13

The present study investigates the effect of a particle coating on the linearity of the PA signal strength with respect to fluence. The theoretical PA-induced temperature field around a single silica-coated GNP is analyzed. We then examine experimentally measured PA signals as a function of fluence for GNPs exhibiting nonlinear signal generation, and investigate the effect of a particle coating on this nonlinearity. To close, we discuss how these results may be of importance for developing new PA-based biochemical sensors if certain conditions are met for the particle and coating properties.