Development of micropatterned cell-sensing surfaces

Abstract

Microfabricated surfaces have been widely utilized for defining adhesion of single cells or groups of cells of various kinds. Beyond simple control of cell attachment, it is often important to monitor the molecules released by cells. Co-immobilizing miniature sensors alongside cells enables more sensitive detection of secreted factors and may allow for such detection to happen within the context of local microenvironment. Methods for interfacing cells and sensors are central to the notion of local in situ detection of cell function. This chapter describes the use of hydrogel photolithography for integrating cells and sensing elements on culture surfaces. Two types of micropatterned sensing surfaces are described: (1) arrays of microwells for single cell capture that contain antibodies against secreted proteins and (2) entrapment of enzymes inside hydrogel microstructures for local detection of cell metabolism. In both cases, poly(ethylene glycol) hydrogel lithography was employed to control cell attachment, in the second approach hydrogel structures also carried enzymes and functioned as sensors. The development of robust cell/sensor interfaces has implications for diagnostics, tissue engineering, and drug screening.

Keywords: Biosensors; Biosensors for cell analysis; Cell micropatterning; Cellular micropatterning; Heterotypic cellular interactions; Hydrogel photolithography; Microfabrication; Paracrine signaling.