Real-time photoacoustic flow cytography and photothermolysis of single circulating melanoma cells in vivo

Abstract

Metastasis is responsible for as many as 90% of cancer-related deaths, and the deadliest skin cancer, melanoma, has a high propensity for metastasis. Since hematogenous spread of circulating tumor cells (CTCs) is cancer's main route of metastasis, detecting and destroying CTCs can impede metastasis and improve patients' prognoses. Extensive studies employing exogenous agents to detect tumor-specific biomarkers and guide therapeutics to CTCs have achieved promising results, but biosafety remains a critical concern. Taking another approach, physical detection and destruction of CTCs is a safer way to evaluate and reduce metastasis risks. Melanoma cells strongly express melanosomes, providing a striking absorption contrast with the blood background in the red to near-infrared spectrum. Exploiting this intrinsic optical absorption contrast of circulating melanoma cells, we coupled dual-wavelength photoacoustic flow cytography with a nanosecondpulsed laser killing mechanism that specifically targets melanoma CTCs. We have successfully achieved in vivo label-free imaging of rare single CTCs and CTC clusters in mice. Further, the photoacoustic signal from a CTC immediately hardware-triggers a lethal pinpoint laser irradiation that lyses it on the spot in a thermally confined manner. Our technology can facilitate early inhibition of metastasis by clearing circulating tumor cells from vasculature.

Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue

“…Several groups have detected melanoma CTCs using photoacoustic measurements 26 – 29 and high-speed OR-PAM 30 – 32 Because melanoma cells produce melanin with a broad absorption spectrum, OR-PAM at the fundamental wavelength of NIR lasers, such as 1064 nm, can detect melanoma cells with high sensitivity. Their results suggested an advantage of OR-PAM over existing CTC assays that use blood samples to avoid sampling errors.…”