Cells in Micropatterned Hydrogels: Applications in Biosensing
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Cells in Micropatterned Hydrogels: Applications in Biosensing Won-Gun Koh and Michael Pishko Department of Chemical Engineering, The Pennsylvania University, 104 Fenske, University Park, PA 16802-4420 ABSTRACT Here we will discuss the development of arrays of mammalian cells of differing phenotype integrated with microfluidics and microsensors for applications such as drug screening and used to monitor cellular effects of multiple chemical and biological candidates. To fabricate these arrays, we immobilized either single or small groups of cells in 3-dimensional poly(ethylene glycol) hydrogel microstructures fabricated on plastic or glass surfaces. These microstructures were created using either photolithography or printed using microarray robots. The resulting hydrogel microstructures were fabricated to dimensions as small as 10 microns in diameter with aspect ratios as high as 1.4. The gels were highly swollen with water to permit mass transfer of nutrients and potential analytes to the cells, and cell adhesion molecules were immobilized in the gel to allow cell attachment and spreading. Cell viability was confirmed using fluorescent assays and ESEM used to verify complete cell encapsulation. The specific and non-specific response of these cells to target molecules was monitored using optical or electrochemical detectors and analyzed to quantify the effect of these agents on the different phenotypes present in the array. INTRODUCTION Cell-based biosensing devices for applications such as high-throughput drug screening require accurate positioning of cells into arrays that can be addressed (preferably using optical methods) and integrated with microfluidic channels for sample introduction.[1-4] Much research has been conducted in the area of cell patterning using chemical or lithographic methods for the spatial control of cell adhesion and growth. In most of these applications, anchorage dependent cells are immobilized on a twodimensional substrate. However, in a two-dimensional system, non-adherent cells are difficult to immobilize and adherent cells such as fibroblasts and hepatocytes are in an unnatural environment, i.e. in tissue they exist in a three-dimensional hydrogel matrix consisting of other cells, proteins, and polysaccharides. As the result, the response of these cells to drug candidates may be very different than that of the same cells in their native tissue. One strategy to overcome the problems associated with a two-dimensional culture system is to encapsulate cells inside a three-dimensional hydrogel matrix. Originally cell encapsulation technologies using hydrogels were developed for tissue engineering or therapeutic cell transplantation to prevent rejection of the transplanted cells by the host’s immune system.[5-7] Hydrogels have been widely used because of their high water content, softness, pliability, biocompatibility, and easily controlled mass transfer properties, essential for allowing the transport of nutrients to and waste products from the O5.5.1 Downloaded from https://www.cambridge.or
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