title: Use of a highly parallel microfluidic flow cell array to determine therapeutic drug dose response curves.
abstract: A high-throughput, microfluidic flow cell array (MFCA) system has been modified to enable drug screening against small-volume cell-, and tissue cultures. The MFCA is composed of a 3D channel network that simultaneously flows fluids through forty-eight 830 μm by 500 μm flow cells, which physically divide and fluidically seal an existing culture into multiple compartments when docked onto the surface of a cell or tissue culture dish. The modified system provides temperature (37 °C) and CO2/pH level controls, while continuously flowing solutions (media or other liquid such as drug suspensions) over the cells/tissues. These assays were enhanced and validated using inverted microscopy and fluorescent staining techniques which also allow real time viability and toxicity assessments. This work presents the results of this new generation in vitro drug testing assay performed using this modified MFCA system. This setup allows the testing of 48 drug combinations on 48 different cell-, tissue specimen at once under flow conditions. All 48 flow cells were utilized to test 5 different concentrations of cisplatin (CDDP). CDDP solutions in various concentrations were continually flowed over cultured human ovarian cancer cells for 48 h. Viability assessments were performed using red-orange calcein and SYTOX ® Green nucleic acid stains. Cells were imaged at the beginning and end of the experiment (48 h). In order to compare and validate MFCAs suitability as drug screening assay, MTT assays were performed on cells. We found that both, MTT and MFCA assays generated dose-response curves with similar profiles. Innovative advantages of the MFCA system include the ability of handling smaller amounts of solutions compared to conventional and current state of the art drug screening and cell viability/toxicity methods. It also provides the ability to continually deliver fresh solution to the cell samples, while eliminating wastes that are produced. Based on our here reported findings MFCA may have a strong potential of providing a more physiological model than current state of the art static MTT assays.
authors.affiliation: Department of Bioengineering, University of Utah, 36 S Wasatch Drive Room 3100, Salt Lake City, 84112, UT, USA. jesusmuguruza@gmail.com.
authors.forename: Jesús A
authors.identifier: 0000-0001-9300-5983
authors.initials: JA
authors.lastname: Arellano
authors.affiliation: Department of Mechanical Engineering, University of Utah, 1495 E 100 S Room 1550 MEK, Salt Lake City, 84112, UT, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Howell
authors.affiliation: Department of Mechanical Engineering, University of Utah, 1495 E 100 S Room 1550 MEK, Salt Lake City, 84112, UT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Gammon
authors.affiliation: Obstetrics and Gynecology, University of Utah, 30 N 1900 E Room 2B200, Salt Lake City, 84132-2101, UT, USA.
authors.forename: Sungpil
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Bioengineering, University of Utah, 36 S Wasatch Drive Room 3100, Salt Lake City, 84112, UT, USA.|Obstetrics and Gynecology, University of Utah, 30 N 1900 E Room 2B200, Salt Lake City, 84132-2101, UT, USA.
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janát-Amsbury
authors.affiliation: Department of Bioengineering, University of Utah, 36 S Wasatch Drive Room 3100, Salt Lake City, 84112, UT, USA.|Department of Mechanical Engineering, University of Utah, 1495 E 100 S Room 1550 MEK, Salt Lake City, 84112, UT, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Gale
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D057166:High-Throughput Screening Assays / Q000295:instrumentation*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D056656:Lab-On-A-Chip Devices; D013696:Temperature
keywords: Microfluidics; Personalized medicine