Detection of pH-Induced Aggregation of “Smart” Gold Nanoparticles with Photothermal Optical Coherence Tomography

Abstract

Optical coherence tomography (OCT) has been widely used in biomedical imaging ever since its introduction. Photothermal optical coherence tomography (PT-OCT) is an extended OCT having molecular contrast based on intrinsic selective absorption or by using extrinsic contrast agents. This thesis demonstrates the feasibility of a novel contrast agent, namely “smart” gold nanoparticles (AuNPs), in the detection of cancer cells with PT-OCT. “Smart” AuNPs form aggregation in low pH condition, which is typical for cancer cells, and this aggregation results in shift of their absorption spectrum. A PT-OCT system was developed to detect this pH-induced aggregation by combining an OCT light source and a laser with 660 nm in wavelength for photothermal excitation. Optical detection of pH-induced aggregation was tested with solution samples at two different pH conditions. An increase in optical path length (OPL) variation was measured at mild acidic condition compared with the one at neutral condition. Detection of cancer cells was tested with cultured cell samples. Hela and fibroblast cells, as cancer and normal cells respectively, were incubated with “smart” gold nanoparticles and measured with PT-OCT. Elevated OPL variation signal was detected with the Hela cells while not much signal with the fibroblast cells. Further experiments were conducted with tumor samples ex vivo. Aggregation of “smart” AuNPs was detected with increased OPL variation compared with control AuNPs. With the novel optical property of “smart” AuNPs and high sensitivity of PT-OCT, this technique is promising for cancer targeting and detection.