title: A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics.
abstract: The heterogeneity of cellular microenvironments in tumors severely limits the efficacy of most cancer therapies. We have designed a microfluidic device that mimics the microenvironment gradients present in tumors that will enable the development of more effective cancer therapies. Tumor cell masses were formed within micron-scale chambers exposed to medium perfusion on one side to create linear nutrient gradients. The optical accessibility of the PDMS and glass device enables quantitative transmitted and fluorescence microscopy of all regions of the cell masses. Time-lapse microscopy was used to measure the growth rate and show that the device can be used for long-term efficacy studies. Fluorescence microscopy was used to demonstrate that the cell mass contained viable, apoptotic, and acidic regions similar to in vivo tumors. The diffusion coefficient of doxorubicin was accurately measured, and the accumulation of therapeutic bacteria was quantified. The device is simple to construct, and it can easily be reproduced to create an array of in vitro tumors. Because microenvironment gradients and penetration play critical roles controlling drug efficacy, we believe that this microfluidic device will be vital for understanding the behavior of common cancer drugs in solid tumors and designing novel intratumorally targeted therapeutics.
authors.affiliation: Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant Street. Amherst, MA 01003-9303, USA.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Walsh
authors.forename: Brett M
authors.initials: BM
authors.lastname: Babin
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Kasinskas
authors.forename: Jean A
authors.initials: JA
authors.lastname: Foster
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: McGarry
authors.forename: Neil S
authors.initials: NS
authors.lastname: Forbes
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001419:Bacteria / Q000166:cytology; D018929:Cell Culture Techniques; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D004058:Diffusion; D004317:Doxorubicin / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin