Fig. 4. Sequential and temporal drug treatment on the microfluidic platform reveals the efficacy of dynamic temporal drug treatment for personalized therapy.

a Schematic of sequential drug delivery schedules of single drugs delivered temporally in pulses to recapitulate dynamic combination chemotherapy with the platform. Colors in each row represent a different drug formulation, which can be changed on-demand. b–h Comparison of the temporal delivery for five combination chemotherapies using average caspase 3/7 signal to detect apoptosis for patient 1. All data presented as mean values ± SEM, n = 3, and normalized to positive control. c–g Comparison of temporal delivery for each of the five combination chemotherapies to their 72-h and 4-h constant delivery counterparts (i.e., all drugs in the sequence at once). Details of the drugs used in each therapy regimen are shown below the graph and described in more detail in Table 1. Time course of each drug on the x-axis is to scale. h Comparison of all investigated therapies at the end of the 72-h drug treatment period (asterisk denotes significant differences from temporal treatment, two-way ANOVA, p values from left to right; FOLFIRINOX: 8.3E-07, 7E-07; FOLFIRI: 1.7E-06, 7E-07; FOLFOX: 0.03, 0.01; Gem+5-FU: 3.9E-05, 8.3E-05; Gem+Pac: 9.6E-10, 6.16E-06). Sequentially-administered combination therapy is more efficient in inducing tumor cell death. Source data for panels c–g are available.