Related Experiment Video
Updated: Nov 2, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation
Haimeng Pei1, Mei Yu1, Defang Dong1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China tangb@sdnu.edu.cn lilu5252@163.com.
Abstract:
Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy. Although considerable efforts have been directed at drug screening in living cells, performing repeated drug sensitivity analysis using patient-derived primary tumor cells at the single-cell level remains challenging. Here, we present an efficient approach to assess phenotype-related drug sensitivity at the single-cell level using patient-derived circulating tumor cells (CTCs) based on a drug sensitivity microfluidic chip (DS-Chip). The DS-Chip consists of a drug gradient generator and parallel cell traps, achieving continuous single CTC capture, drug gradient distributions, drug stimulation, fluorescent probe labeling and three-color fluorescence imaging. Based on the established DS-Chip, we investigated the drug sensitivity of single cells by simultaneously monitoring epithelial-mesenchymal transition (EMT) biomarkers and apoptosis in living cells, and verified the correlation between EMT gradients and drug sensitivity. Using the new approach, we further tested the optimal drug response dose in individual CTCs isolated from 5 cancer patients through fluorescence analysis of EMT and apoptosis. The DS-Chip allows noninvasive and real-time measurements of the drug sensitivity of a patient's tumor cells during therapy. This developed approach has practical significance and can effectively guide drug selection and therapeutic evaluation for personalized medicine.
Insights
This study introduces a microfluidic chip for real-time, single-cell drug sensitivity analysis in circulating tumor cells (CTCs). This technology enables personalized cancer therapy by guiding drug selection and evaluating treatment effectiveness noninvasively.
Area of Science:
- Biomedical Engineering
- Oncology
- Microfluidics
Background:
- Tumor cell drug sensitivity is heterogeneous, necessitating real-time monitoring for personalized therapy.
- Current methods for single-cell drug sensitivity analysis using patient-derived cells are challenging.
- Circulating tumor cells (CTCs) offer a minimally invasive source for monitoring tumor response.
Purpose of the Study:
- To develop an efficient microfluidic approach for assessing phenotype-related drug sensitivity at the single-cell level.
- To enable real-time, noninvasive monitoring of patient tumor cell drug responses.
- To guide personalized medicine by optimizing drug selection and therapeutic evaluation.
Main Methods:
- Development of a drug sensitivity microfluidic chip (DS-Chip) with drug gradient generation and cell trapping.
- Simultaneous monitoring of epithelial-mesenchymal transition (EMT) biomarkers and apoptosis in single CTCs.
- Fluorescence imaging and analysis of drug-induced changes in EMT and apoptosis in patient-derived CTCs.
Main Results:
- The DS-Chip successfully captured single CTCs and applied drug gradients for sensitivity assessment.
- A correlation between EMT gradients and drug sensitivity was established.
- Optimal drug response doses were determined for individual CTCs from five cancer patients.
Conclusions:
- The developed DS-Chip provides a novel method for noninvasive, real-time drug sensitivity measurements in patient tumor cells.
- This approach has significant potential to guide drug selection and therapeutic evaluation in personalized cancer medicine.
- The technology facilitates dynamic monitoring of patient drug responses during therapy.
