Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Cancers
Ekaterina I Galanzha, Vladimir P Zharov

Abstract

Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1-10 CTC/mL) due to the small volume of blood samples (5-10 mL). Consequently, they can miss up to 103-104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102-103 times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC's capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5-4 h dependi...Continue Reading

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Methods Mentioned

BETA
biopsy
flow cytometry
Fluorescence
fluorescence imaging
light scattering
flow
transmission
transfection
xenografts
xenograft

Software Mentioned

Cell Search

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