Non-Destructively Quantifying the Whole-Course Growth and Drug-Response of PDOs by an Automatic Microfluidic System Utilizing Chemiluminescence Detection.

Abstract

Patient-derived organoids (PDOs) have become promising tools in precision medicine research. While conventional imaging techniques provide morphological assessment, they fail to reveal crucial molecular-level changes. Monitoring secreted biomarkers presents an alternative approach that can deliver real-time physiological data throughout the growth and drug response process. In this study, the non-destructive quantification for the whole-course growth and drug-response of PDOs is first realized using a multifunctional microfluidic chip-based system that integrates culturing, drug incubation, and biomarker detection. To validate the feasibility of this method, Carcinoembryonic Antigen (CEA), a broad biomarker, is selected to investigate its correlation with both organoid growth (over 6 days) and drug response (over 72 h).  The stable culture of organoids within the device is enabled by the integrated system, with net CEA accumulation being continuously monitored to assess growth rate. Additionally, finer-resolution drug response monitoring is achieved by measuring the same organoids at multiple intervals. The drug testing results demonstrated concordance with clinical outcomes in patients. Such continuous monitoring of biomarkers has the potential to effectively respond to the growth and drug-response of the PDOs, with a fine-grained interpretation of organoids being provided as a patient prognostic evaluation.