Imaging of drugs in cells: an on-chip system for development and testing of new therapies

A model cell culture tool designed to represent the in vivo environment will be developed to enable the examination of toxicological affects in vitro, changes to cells when in a perturbed state and quantitative analysis of endogenous and exogenous chemical species inside cells. This will allow us to develop methods to test drug efficacy in cell culture to produce greater mechanistic information and reduce animal use in the search for new medicines to treat patients with, for example, respiratory, inflammatory and cardiovascular diseases.

We have recently demonstrated the 3 dimensional cellular distributions of small molecules in a variety of cells using Time of Flight Secondary Ion Mass Spectrometry (ToF SIMS). Current sample preparation involves freezing and dehydrating adherent cells but the system does not yet have sufficient spatial resolution to determine the distribution of the dosed molecule at the organelle level. This work is being performed in collaboration between GSK, the University of Nottingham and the National Physical Laboratory. We propose to combine this study with the 3D printing and cell manipulation expertise at the University to enable the imaging of small molecules within cells grown in a more relevant 3 dimensional culture tool. The goal of this project is to use 3D printing to generate a hydrogel chip containing cells spatially arrayed within a printed structure supplied with micro fluidic channels to dose individual cells. Compounds will be passed along the channels and allowed to incubate with cells within the matrix to enable real time observation using microscopy.