A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs

Hattersley, Samantha M.; Sylvester, Deborah C.; Dyer, Charlotte E.; Stafford, Nicholas D.; Haswell, Stephen J.; Greenman, John

Abstract

Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and ‘‘interrogation’’ of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release ‘off-chip’ over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.

Citation

Hattersley, S. M., Sylvester, D. C., Dyer, C. E., Stafford, N. D., Haswell, S. J., & Greenman, J. (2012). A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs. Annals of biomedical engineering, 40(6), 1277-1288. https://doi.org/10.1007/s10439-011-0428-9

• Journal Article Type: Article
• Acceptance Date: Oct 1, 2011
• Online Publication Date: Oct 15, 2011
• Publication Date: 2012-06
• Journal: ANNALS OF BIOMEDICAL ENGINEERING
• Print ISSN: 0090-6964
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 40
• Issue: 6
• Pages: 1277-1288
• DOI: https://doi.org/10.1007/s10439-011-0428-9
• Keywords: Head and neck squamous cell carcinoma; 5-fluorouracil; Cisplatin; Lactate dehydrogenase; Cytochrome c
• Public URL: https://hull-repository.worktribe.com/output/424105
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10439-011-0428-9