Single cell detection using multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence microscopy (Conference Presentation)

Abstract

Successful development of a multimodal imaging system for the detection of live single cells is critical for enhancing diagnosis and treatment of diseases at an early stage. Recently, photoacoustic microscopy (PAM) and optical coherence tomography (OCT) have been investigated as high resolution, non-invasive imaging techniques for the detection of single cells. However, most cancerous cells lack sufficient endogenous contrast. The aim of the current study is to develop a multimodal imaging system that combines PAM, OCT, and fluorescence microscopy (FM) for the detection of single cells with the assistance of gold nanoparticles as contrast agents. Three different type of ultra-pure colloidal cluster gold nanoparticles (GNPs) were fabricated and functionalized with ligands. The synthesized GNPs, average particle size of 10, 20 nm, and 60 nm (cluster GNPs), were evaluated. Cluster nanoparticles were achieved by combining an average of 3 to4 colloidal GNPs. The peak absorption of GNPs is 532 nm (bare) and 650 nm (cluster). The functionalized GNPs were delivered into different cells (HeLa, OZ3, bovine retinal endothelial, and bovine brain endothelial cells) at various concentrations (0, 12.5, 25 and 50 µg/mL). The treated cells with GNPs were imaged using the custom-built multimodal PAM, OCT, and FM system. The PAM contrast was enhanced linearly with the increasing in GNP concentration. The OCT contrast was also increased up to 2 fold in comparison with control. FM results showed the position of accumulated GNPs co-registered with the dark field images. The proposed multimodal imaging system may provide a potential tool for the detection and imaging of live single cells.