Detection of melanoma cells in vitro using an optical detector of photoacoustic waves

Circulating tumor cells have been shown to correlate positively with metastatic disease state in patients with advanced cancer. We have demonstrated the ability to detect melanoma cells in a flow system by generating and detecting photoacoustic waves in melanoma cells. This method is similar to flow cytometry, although using photoacoustics rather than fluorescence. Previously, we used piezoelectric films as our acoustic sensors. However, such films have indicated false-positive signals due to unwanted direct interactions between photons from the high laser fluence in the flow system and the film itself. We have adapted an optical detection scheme that obviates the need for piezoelectric films.

Our photoacoustic system comprised a tunable laser system with an output of 410-710 nm with a pulse duration of 5 nanoseconds. The light was delivered by optical fiber to a glass microcuvette that contained saline buffer suspensions of melanoma and white blood cells. We used a continuous HeNe laser to provide a probe beam that reflected off of a glass and water interface in close proximity to the microcuvette. The beam was detected by a high-speed photodiode. When a photoacoustic wave was generated in the microcuvette, the wave propagated and changed the reflectance of the beam due to index of refraction change in the water. This perturbation was used to detect the presence of melanoma cells.

We determined a detection threshold of about one individual melanoma cell with no pyroelectric noise indicated in the signals.

The optical reflectance method provides sensitivity to detect small numbers of melanoma cells without created false-positive signals from pyroelectric interference, showing promise as a means to perform tests for circulating melanoma cells in blood samples.