Study on melanin enhanced third harmonic generation in a live cell model.

Melanin dominates the endogenous contrasts of in vivo third harmonic generation (THG) imaging of human skin. A recent study investigated the THG in melanin solution and a linear relationship between melanin concentration and THG intensity was reported, in contrast to the expected nonlinear relationship. Since melanin hydrocolloid solution is very different from the skin tissue, here we report our study on the origin of the melanin-enhanced THG by using a live cell model. Different from the previous conclusion, our live cell study has indicated an initial nonlinear process where the THG intensity was enhanced according to the 3.5th power of melanin mass density (MMD). When the MMD is higher than 11 mg/ml, a transition from the resonance-enhanced THG to the high-order hyper-Rayleigh scattering process occurs. This saturation phenomenon of the virtual-transition-based THG nonlinear process is attributed to the multi-melanosome-induced scattering within the sub-femtoliter focal volume.