Abstract

The rapid qualitative assessment of surface markers on cancer cells can allow for point-of-care prediction of patient response to various cancer drugs. Preclinical studies targeting cells with an antibody to “activated” matriptase conjugated to a potent toxin show promise as a selective treatment for a variety of solid tumors. In this paper, we implemented a novel technique for electrical detection of proteins on surfaces of cancer cells using multi-frequency microfluidic impedance cytometry. The biosensor, consists of two gold microelectrodes on a glass substrate embedded in a PDMS microfluidic channel, is used in conjugation with immuno-magnetic separation of cancer cells, and is capable of differentiating between bare magnetic beads, cancer cells and bead-cell aggregates based on their various impedance and frequency responses. We demonstrated proof-of-concept based on detection of “activated” matriptase proteins on the surface of cultured Mantle cells.

Highlights

  • IntroductionOne of the key processes playing a role in modulation of the tumor environment is (membrane-anchored) proteolysis[3]

  • One of the key processes playing a role in modulation of the tumor environment is proteolysis[3]

  • There is great interest in developing technologies that can be used for analysing circulating tumor cells, the ability to analyse dissociated cancer cells obtained from a tissue biopsy is of great importance in predicting patient response to targeted therapies

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Summary

Introduction

One of the key processes playing a role in modulation of the tumor environment is (membrane-anchored) proteolysis[3]. The gold standard technology for cancer cell isolation and marker assessment is the CellSearch CTC (Circulating Tumor Cells) Test, which uses magnetic bead based pre-concentration and fluorescent tagging of the cells and fluorescently analyzing the cell surfaces[10]. There is great interest in developing technologies that can be used for analysing circulating tumor cells, the ability to analyse dissociated cancer cells obtained from a tissue biopsy is of great importance in predicting patient response to targeted therapies. We envision using this technique to isolate tumor cells from complex samples (like dissociated cells obtained from a tissue biopsy) to predict cancer patient response to novel targeted therapeutics using anti-neoplastic agents conjugated with anti-matriptase antibody. We emphasize that our proposed technique can be used in conjunction with the above mentioned immuno-magnetic based cancer cell separation techniques to either characterize matriptase levels on tumor cells obtained from a biopsy and dissociated into cell suspension or circulating tumor cells directly from blood

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