EAGER: Feasibility of approaches for cell-based sensing on chip

点击翻译按钮获取中文摘要

Chemical detection using biological cells that live on the surface of an integrated circuit chip is a promising approach to identifying odors, disease, and pathogens. For example, the principal investigators have previously demonstrated that a chip can be used to detect electrical signals generated by odor-sensing cells taken from the nose when those cells are exposed to particular odors. Despite decades of research into olfactory sensors, we are still using animals, primarily dogs for odor detection; a cell-phone like device for odor detection would have widespread applications throughout society. This project aims to develop technology that overcomes the main practical challenge for devices based on cell-based sensing: the need to supply cells to these devices. Storage or supply of cells prior to device use has been challenging: shipping cells to the device location so that they can be loaded into it just prior to use is infeasible in many scenarios, as is keeping the cells alive for long periods of time during which power may be unavailable and environmental temperatures are varying. A dryable animal cell line that can be cultured in the lab and methods for genetically engineering these cells has recently been developed by others. The proposed research will lay the necessary groundwork for using such cells on chip for cell-based sensing, so that the cells can be stored in stasis on chip and later re-animated by the addition of water. The long term goal of the research is to develop a bionose-on-a-chip that can be used in a hand-held device for odor identification, replacing dogs in applications such as security, explosives detection, and search and rescue, and opening new possibilities for monitoring food safety and origin, controlling industrial processes, and even diagnosing disease. The proposed work comprises three efforts to demonstrate the feasibility of using dryable cell lines on chip. First, a gel system will be established that is compatible with cell patterning and subsequent dessication. In the bionose application, cells expressing distinct olfactory receptors will be patterned onto particular sensing electrodes within a hydrogel host matrix, then dried in situ. The host hydrogel should be compatible with culture of cells, maintain mechanical integrity during and after drying, and support rapid exchange of ions and small molecules. A range of gel systems that can be patterned using a bioplotter will be studied. Second, the integrated circuit sensing chip will be packaged and integrated with microfluidics. This will facilitate the dehydration-rehydration process and promote testing of the system with odorants. Both conventional micro-molding and 3-dimensional printing will be evaluated. Third, the design of the on-chip micro-electrodes that monitor the electrical activity of the odorant cells will be optimized through modeling and simulation to maximize detection of the signals and to minimize anticipated crosstalk between different cell populations on the same chip. These developments will lay the groundwork not only for the bionose-on-a-chip application, but also other cell-based bioelectronic sensing devices. The proposed work is challenging because microfluidics and other organ on a chip approaches must be coupled with state of the art circuit technologies and cutting edge biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.