Capture-free deactivation of CTCs in the bloodstream; a metastasis suppression method by electrostatic stimulation of the peripheral blood.

While limited investigations have been reported on CTC elimination and its profits, recently, some new works were reported on detection followed by the destruction of CTCs. Limitations and complications of CTC capturing procedures have highly reduced the chance of selective destruction of CTCs in the bloodstream in the therapeutic guidelines of the patients. Here, we selectively deactivated the invasive function of CTCs during their circulation in the bloodstream by exposing the whole blood to pure positive electrostatic charge stimulation (PPECS). Our treatment suppressed pulmonary metastasis and extended the survival of the mice had been intravenously injected by electrostatically deactivated 4T1 breast cancer CTCs. Moreover, the number of cancerous lung nodules was drastically reduced in the mice injected by treated CTCs in comparison with the non-treated cohort. Evaluating the side effect of the PPECS on the blood components revealed no major effect on the functional properties of the white blood cells, and just a negligible fraction (∼10%) was damaged during this process. This approach does not need any capturing or targeting of CTCs from the blood as it is focused on perturbing the electrical function of negatively-charged tumor cells after being exposed to positive electrostatic charges. Taken together, continuous in-vivo deactivation of CTCs by PPECS with no requirement to complicated capturing protocols may improve the survival of cancer patients.

Low frequency stimulation induces polarization-based capturing of normal, cancerous and white blood cells: a new separation method for circulating tumor cell enrichment or phenotypic cell sorting.

Separation of cancerous from normal cells is of broad importance in a large number of cancer diagnosis and treatment methods. One of the most important factors to designate and specify different cells is to study their dielectric and electric cell membrane characteristics. In this research, a label-free cytological slide chip (CSC) is designed and fabricated based on AC electric field stimulation of breast cell lines and blood cells at low frequencies (1 kHz-200 kHz). The AC-CSC traps cells based on their dielectric polarization functions which is distinct between different phenotypes of breast cells and blood cells. We learned that by using AC electric fields, each breast cell line shows a capturing response to a specific range of frequencies. The progression in cancer phenotypes decreases the cell's polarizability. Hence, characteristic frequency responses were achieved for these cells. In this study, thermal potential and electrolysis which were the main bottle neck problems in DC applied fields were completely solved. The AC-CSC could be used in CTC separation from leukocytes, a test performed based on a compound with 1% cancer cells in white blood cells (1% MDA-MB-231 : 99% WBC) which results in 90% capturing efficiency of cancer cells. Frequency dependent capturing brings so much hope that smart slides will be useful at the clinical stage in the near future.

Distinguishment of populated metastatic cancer cells from primary ones based on their invasion to endothelial barrier by biosensor arrays fabricated on nanoroughened poly(methyl methacrylate).

Determining the migratory and invasive capacity of cancer cells as well as clarifying the underlying mechanisms are most relevant for developing biosensors in cancer diagnosis, prognosis, drug development and treatment. Intravasation of metastatic cells into blood stream initiated by their invasion to vascular layer would be a significant characteristic of metastasis. Many types of biochemical and bioelectrical sensors were developed for early detection of metastasis. The simplicity of the setup, the ease of the readout, detection of the trace of rare metastatic cells and the feasibility to perform the assay with standard laboratory equipment are some of the challenges limiting the usability of the sensors in tracing the metastasis. Here we describe a biosensor based on recently reported metastatic diagnosis assay; Metas-Chip, with the assistance of nanoroughened Poly-methyl methacrylate (PMMA) layer to diagnose populated metastatic breast cells from primary cancerous ones. Retraction and detachment of Human Umbilical Vein Endothelial Cells (HUVECs) invaded by metastatic cells as a recently found phenomena is the mechanism of the action. A population of HUVECs would be detached from the gold microelectrodes, patterned on nanoroughened surface, which would lead to large changes in impedance. Here, applying biocompatible and patternable nanoroughened surface instead of using adhesive layers which might produce electrical noises resulted in great sensitivity and detectivity of the sensor. Apart from the tight interaction between endothelial cells and nanocontacts of the electrodes, using low concentration (10%) of tumor cells in this invasion assay, might enhance its application in clinical trials.