Abstract
We present a novel method to rapidly assess drug efficacy in targeted cancer therapy, where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells. We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy. Currently commercially available devices for the automated analysis of cell viability are based on staining, which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis. Our approach requires as little as 20 μL of volume and avoids staining allowing for further downstream molecular analysis. To the best of our knowledge, this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning, particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier, to assess viability of cells without staining or labelling.
Highlights
Cancer continues to be one of the leading causes of death worldwide
In this work we present a novel method to rapidly assess drug efficacy in targeted cancer therapy, where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells
In this work we built a device capable of rapidly analyzing cell viability without staining of cells, which allows for further downstream molecular analysis
Summary
Cancer continues to be one of the leading causes of death worldwide. The primary treatment options for cancer include surgery[1], chemotherapy[2], radiation therapy[3], hormonal therapy[4], targeted therapy[5], and palliative care[6]. The choice of therapy mainly depends upon the type and stage of cancer, legal issues, clinical infrastructure, past response rates, and the patient’s health conditions. Chemotherapy is non-specific and results in killing non-targeted cells, which results in many side effects including hair loss and serious gastrointestinal issues. In this work we present a novel method to rapidly assess drug efficacy in targeted cancer therapy, where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells. “Activated” matriptase, a membrane-bound protease, is overexpressed in various epithelial cancer cells, including B-cell lymphoma, multiple myeloma, and epithelial carcinomas[7,8]. Given the importance of matriptase in tumor behavior and its expression on a wide variety of tumor cell types, the targeted delivery of cancer drugs to the tumor site shows great promise for enhancing drug efficacy and minimizing toxicity toward
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