We propose an instrument system for automated, multiplexed cell- and tissue-based experiments (i.e. tissue microarrays) called the Microfluidic Flow Cell Array (MFCA). The MFCA consists of a microfluidic flow cell array integrated with an inverted fluorescent microscope, allowing the observation of 48 flow chambers simultaneously or an individual chamber at higher magnification. The proposed instrument will be used to novel cell- and tissue-based assays in a highly parallel manner that are otherwise difficult to perform. Our goal is to build a platform for producing a tissue microarray that maintains many of the characteristics found in cells in vivo and allows for the investigation of cell-surface, cell-cell, and especially tumor-stroma interactions, cell toxicity studies, and tissue toxicity studies in a multiplexed fashion. As a Phase I application, this proposal's focus is ovarian cancer tissue slice toxicity testing to determine the optimal chemotherapeutic agents for a specific patient (i.e. personalized treatment based on the tissue reaction);however, multiple applications can be envisioned beyond ovarian cancer including: combinatorial cell stimulation, toxicity, or therapeutic assays, stem cell screening and differentiation control studies, multiplexed primary cell assays, biomaterials screening, shear stress and cell adhesion studies, and combinatorial immunohistochemistry. This platform approach and simple integration with a microscope will allow for adoption and adaptability for researchers worldwide. The following hypotheses and specific aims have been identified to prove the feasibility of integrating the microfluidic flow cell array technology with an inverted fluorescent microscope for cell and tissue based assays.
Specific Aim 1. Translate end point assays for existing tissue culture approaches including the MTT Assay and digital pathology to the MFCA.
Specific Aim 2. Engineer the MFCA printhead to minimize impact of the printhead docking onto the tissue culture slice.
Specific Aim 3. Optimize drug delivery of different therapeutic agents in the MFCA channels using to the mouse ovarian tissue slice and compare to existing tissue culture approaches.
Wasatch will engineer a Microfluidic Flow Cell Array (MFCA) which integrates a fluorescent microscope with our patented 48 channel, 3D microfluidic printing technology. The initial application for the MFCA will be ovarian cancer which kills tens of thousands of women in the United States each year. This proposal will help develop technologies and methods that could be used to determine the preferred personalized drug combination for treating a tumor. These innovations could be extended in future projects to other cancers and drug screening applications as well.
|Arellano, Jesús A; Howell, Taylor A; Gammon, James et al. (2017) Use of a highly parallel microfluidic flow cell array to determine therapeutic drug dose response curves. Biomed Microdevices 19:25|
|Davidoff, S N; Au, D; Gale, B K et al. (2015) Maximizing Fibroblast Adhesion on Protein-Coated Surfaces Using Microfluidic Cell Printing. RSC Adv 5:104101-104109|