An Integrated Microfluidics Approach for Personalized Cancer Drug Sensitivity and Resistance Assay

Inna Desyatnik, Matan Krasner, Ludmila Frolov, Maria Ronen, Ortal Guy, Danit Wasserman, Amit Tzur, Dorit Avrahami, Efrat Barbiro-Michaely, Doron Gerber

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell-based testing. Herein, presented is a microfluidic device that combines a drug microarray with cell microscopy. The device can perform 512 experiments to test chemosensitivity and resistance to a drug array. MCF7 and 293T cells are cultured inside the device and their chemosensitivity and resistance to docetaxel, applied at various concentrations, are determined. Cell mortality is determined as a function of drug concentration and exposure time. It is found that both cell types form cluster morphology within the device, not evident in conventional tissue culture under similar conditions. Cells inside the clusters are less sensitive to drugs than dispersed cells. These findings support a heterogenous response of cancer cells to drugs. Then demonstrated is the principle of drug microarrays by testing cell response to four different drugs at four different concentrations. This approach may enable the personalization of treatment to the particular tumor and patient and may eventually improve final patient outcome.

Original languageEnglish
Article number1900001
JournalAdvanced Biosystems
Volume3
Issue number11
Early online date20 May 2019
DOIs
StatePublished - 1 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funding

I.D. and M.K. contributed equally to this work. The authors gratefully acknowledge funding by the KAMIN program from the Ministry of Industry, Trade and Labor. The authors thank Dr. Keren Levanon (The Institute of Oncology, Chaim Sheba Medical Center, Israel) for providing some of the drugs. The authors thank Tehilla Helfenbaum for her help with cell counting. The authors thank Shimon Schidorsky for his help with the optical setup.

FundersFunder number
Ministry of Industry, Trade and Labor

    Keywords

    • MCF7 cells
    • chemosensitivity and resistance assay
    • integrated microfluidics
    • personalized medicine

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