Label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters by linear-array-based photoacoustic tomography

Abstract

Circulating tumor cell (CTC) clusters, arising from multicellular groupings in a primary tumor, greatly elevate the metastatic potential of cancer compared with single CTCs. High-throughput detection and quantification of CTC clusters are important for understanding the tumor metastatic process and improving cancer therapy. Here, we applied a linear-array-based photoacoustic tomography (LA-PAT) system and improved the image reconstruction for label-free high-throughput CTC cluster detection and quantification <italic<in vivo</italic<. The feasibility was first demonstrated by imaging CTC cluster <italic<ex vivo</italic<. The relationship between the contrast-to-noise ratios (CNRs) and the number of cells in melanoma tumor cell clusters was investigated and verified. Melanoma CTC clusters with a minimum of four cells could be detected, and the number of cells could be computed from the CNR. Finally, we demonstrated imaging of injected melanoma CTC clusters in rats <italic<in vivo</italic<. Similarly, the number of cells in the melanoma CTC clusters could be quantified. The data showed that larger CTC clusters had faster clearance rates in the bloodstream, which agreed with the literature. The results demonstrated the capability of LA-PAT to detect and quantify melanoma CTC clusters <italic<in vivo</italic< and showed its potential for tumor metastasis study and cancer therapy.

Quantitative photoacoustic elastography of Young’s modulus in humans

“…The spatial resolutions of QPAE are 86 μm in the axial direction, 119 μm in the lateral direction, and 1237 μm in the elevational direction, determined by the linear-array-based photoacoustic imaging probe 26 . The minimum detectable displacement is 18.3 μm, which is determined by the data acquisition sampling rate of 84 MHz and the average speed of sound in biological tissue of 1540 m/s.…”

New advances in microfluidic flow cytometry

“…PAFC utilizes the photoacoustic (PA) effect that is based on nonradiative conversion of absorbed laser energy into heat accompanied by acoustic waves . This noninvasive detection technique has been successfully used to differentiate the circulating tumor cells (CTCs) in the blood vessels . The frequencies used in the traditional photoacoustic systems are less than 100 MHz, which cannot detect the spectral features related to the size and sound speed of cell that occur within the 100–500 MHz frequency range .…”

Linear-array-based photoacoustic tomography for label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters

“…To image melanoma CTC clusters, we applied an LA-PAT system based on a handheld probe and improved the image reconstruction 22,23 . A tunable optical parametric oscillator laser (680 to 970 nm, 20-Hz pulse repetition rate) was used for illumination.…”