Tissue microenvironment and cellular imaging

Small tissue constructs comprising several cell types within a three-dimensional environment can better mimic tissue, and may provide a better system to screen and validate drugs than current two-dimensional monolayer cultures. We developed a microfluidic flow-focusing method to rapidly and reproducibly create multicellular, 3-D spheroids that can better model several aspects of the tumour in vivo, including diffusion gradients of O2 and drugs. When evaluating effects of drugs on arrays of micro-tissues in high content screening, we will need to image deep within the tissues to assess parameters such as cell viability at the tissue cores or drug penetration into the tissue as a function of time. We have developed an on-chip method to rapidly clear arrays of 3-D cell cultures and micro-tissues, compatible with two-photon microscopy to track drug and nanomedicine penetration into the tissues.