Microfluidic systems show great promise for single-cell analysis; however, as these technologies mature, their utility must be validated by studies of biologically relevant processes. An important biomedical application of these systems is characterization of
tumor cell heterogeneity. In this work, we used a robust microfluidic platform to explore the heterogeneity of
enzyme activity in single cells treated with a chemotherapeutic
drug. Using chemical cytometry, we measured
peptide degradation in the U937
acute myeloid leukemia (AML) cell line in the presence and absence of the
aminopeptidase inhibitor
Tosedostat (CHR-2797). The analysis of 99 untreated cells revealed rapid and consistent degradation of the
peptide reporter within 20 min of loading. Results from
drug-treated cells showed inhibited, but ongoing degradation of the reporter. Because the device operates at an average sustained throughput of 37 ± 7 cells/h, we were able to sample cells over the course of this time-dependent degradation. In data from 498 individual
drug-treated cells, we found a linear dependence of degradation rate on amount of substrate loaded superimposed upon substantial heterogeneity in
peptide processing in response to inhibitor treatment. Importantly, these data demonstrated the potential of microfluidic systems to sample biologically relevant analytes and time-dependent processes in large numbers of single cells.