We propose an instrument system for automated, multiplexed cell- and tissue-basedexperiments (i.e. tissue microarrays) called the Microfluidic Flow Cell Array (MFCA). The MFCAconsists 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 highermagnification. The proposed instrument will be used to novel cell- and tissue-based assays in ahighly parallel manner that are otherwise difficult to perform. Our goal is to build a platform forproducing a tissue microarray that maintains many of the characteristics found in cells in vivoand allows for the investigation of cell-surface, cell-cell, and especially tumor-stromainteractions, cell toxicity studies, and tissue toxicity studies in a multiplexed fashion. As a PhaseI application, this proposal's focus is ovarian cancer tissue slice toxicity testing to determine theoptimal chemotherapeutic agents for a specific patient (i.e. personalized treatment based on thetissue reaction); however, multiple applications can be envisioned beyond ovarian cancerincluding: combinatorial cell stimulation, toxicity, or therapeutic assays, stem cell screening anddifferentiation control studies, multiplexed primary cell assays, biomaterials screening, shearstress and cell adhesion studies, and combinatorial immunohistochemistry. This platformapproach and simple integration with a microscope will allow for adoption and adaptability forresearchers worldwide.The following hypotheses and specific aims have been identified to prove the feasibility ofintegrating the microfluidic flow cell array technology with an inverted fluorescent microscope forcell and tissue based assays.Specific Aim 1. Translate end point assays for existing tissue culture approaches including theMTT Assay and digital pathology to the MFCA.Specific Aim 2. Engineer the MFCA printhead to minimize impact of the printhead docking ontothe tissue culture slice.Specific Aim 3. Optimize drug delivery of different therapeutic agents in the MFCA channelsusing to the mouse ovarian tissue slice and compare to existing tissue culture approaches.
Thesaurus Terms: Adoption;Affect;Animal Model;Antineoplastic Agents;Area;Base;Biocompatible Materials;Biological Assay;Cancer Diagnosis;Cell Adhesion;Cell Communication;Cell Culture Techniques;Cell Surface;Cells;Cessation Of Life;Characteristics;Chemotherapeutic Agent;Clinic;Clinical;Clinical Application;Colony-Forming Units Assay;Combinatorial;Controlled Study;Custom;Detection;Diagnosis;Digital;Disease;Disease Model;Dna;Docking;Drug Combinations;Drug Delivery Systems;Early Identification;End Point Assay;Engineering;Epithelial Ovarian Cancer;Fluorescence Microscope;Future;Goals;Head;Immunohistochemistry;Improved;In Vivo;Individual;Innovation;Instrument;Intention;Investigation;Killings;Legal Patent;Malignant Female Reproductive System Neoplasm;Malignant Neoplasm Of Ovary;Malignant Neoplasms;Medicine;Methods;Microfluidics;Microscope;Modeling;Molecular Recognition;Mortality Vital Statistics;Mus;Novel;Organ;Outcome;Ovarian Tissue;Pathology;Patients;Pharmaceutical Preparations;Phase;Play;Preclinical Drug Evaluation;Printing;Product Development;Proteins;Prototype;Public Health Relevance;Publications;Reaction;Regimen;Research;Research Personnel;Research Study;Risk;Screening;Shear Stress;Slice;Spottings;Staging;Surface;Surface Plasmon Resonance;Survival Rate;System;Technology;Testing;Therapeutic;Therapeutic Agents;Tissue Culture;Tissue Microarray;Tissues;Tool;Toxic Effect;Toxicity Tests;Translating;Treatment Protocols;Tumor;Tumor Progression;United States;Woman;
