Quantum dots for positional registration in live cell-based arrays

For a better understanding of complex biological processes, it is desirable to simultaneously follow the dynamics of multiple components in living cells or organisms in real time. An encoding scheme was developed that enables the observation of multiple cell populations with single-cell resolution. Specifically, different yeast cell types were labeled with quantum dots and added to an array of microwells, where they randomly self-assemble into the complementary-sized cavities. Quantum dots conjugated to cells externally, internally, or in combination generated unique optical patterns to differentiate various cell types in the array. For the model system described herein, cells were monitored for their lacZ expression levels through the processing of a fluorescent precursor by ß-galactosidase. The encoding schemes employed were independent of the reporter emission and had no affect on the cellular activity. The live cell array platform allowed analysis of hundreds of individual cells simultaneously and continuously in real time. By coupling this platform with quantum dot cell labeling, the utility of this array format is extended to mixed cellular populations.