UC Merced

Lab-on-a-chip (LOC) technologies have revolutionized the fields of quantitative biology, tissue engineering, diagnostics, etc. However, the LOC implementations in the studies of small model organisms remain relatively low and are constrained in a small research community due to the complexity and high cost in the device development. For zebrafish research in particular, similar zebrafish-on-a-chip (ZOC) designs have been repeatedly used and some of the needs in zebrafish studies are far from fulfilled. The goal for this dissertation is to develop novel ZOCs and an overall zebrafish testing system to assist and accelerate zebrafish studies.In this dissertation, I reported the development of novel ZOC systems for automated zebrafish embryo positioning and flowthrough assays. The ZOCs are fabricated by a rapid and inexpensive 3D LCD stereolithography assisted prototyping method which is suitable for the labs with limited budgets. A simple computational fluid dynamic based analytical model was developed and validated to estimate ZOC’s embryo trapping potential as well as to guide future ZOC designs. Moreover, the operational conditions in the ZOC were evaluated and optimized via both simulations and experiments. To examine the ZOC’s feasibility in zebrafish studies, I showed the zebrafish embryo can be cultured in ZOC’s flowthrough environment and the embryonic development as well as embryo behavior can be affected by alternating the fluidic conditions. To fill the gap for the ZOC-based whole mount zebrafish immunohistochemistry, the whole mount zebrafish Caspase-3 antibody staining procedure was streamlined and accelerated using the ZOC. At last, the versatile ZOC design can be easily modified into a concentration gradient generator and was used for high resolution embryo caffeine dose-response screening. I foresee the developments, and applications of ZOCs will be accelerated in zebrafish research due to the growing needs for the laboratory automation as well as the increasing accessibility of LOC and 3D printing technologies. In addition, the continued input efforts from both academia and industry will facilitate the emergence of highly integrated zebrafish testing systems for fully automated zebrafish procedures.