Towards Biochemical Sensing With Gold Nanoparticles Through Suppression Of Nonlinear Photoacoustic Signal Generation

We propose a new method for biochemical sensing using photoacoustic (PA) excitation of gold nanoparticles (GNPs) to achieve real-time detection of transient biomarkers. Our approach is based on the effect of a particle coating on nonlinear PA signal generation combined with our recently-developed serial PA tomographic imaging method. We have shown the ability to image the three-dimensional spatial distribution of GNPs that produce nonlinear PA signal with respect to fluence. If the occurrence of this nonlinearity is made dependent on the presence of transient biochemical markers, for example through the degradation of a nonlinearity-quenching particle coating, our serial PA tomographic imaging method can be extended for real-time three-dimensional in situ imaging of these biomarkers. Our early-stage proof-of-concept experimental results presented here show that coating GNPs that exhibit nonlinear PA signal generation behavior is an effective method to remove the nonlinear effect. The coefficient of determination (R-2) of a linear fit to the PA signal as a function of fluence can be effectively used to differentiate the coated GNPs and the GNPs without coating. This differentiation can also be achieved using the second order coefficient to a quadratic fit to the PA signal vs. fluence data.