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Microfluidic Platform with Multiplexed Electronic Detection for Spatial Tracking of Particles
Published on: March 13, 2017
Drug screening on digital microfluidics for cancer precision medicine
Jiao Zhai1,2, Yingying Liu1,3, Weiqing Ji4
1State Key Laboratory of Analog and Mixed-Signal VLSI, Institute of Microelectronics, University of Macau, Macau SAR, China.
Abstract:
Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm2 chip in a device measuring 23 × 16 × 3.5 cm3. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.
Insights
This study presents a novel digital microfluidic system for precise cancer drug screening using primary tumor cells. The system enhances drug discovery for personalized cancer medicine, improving treatment outcomes.
Area of Science:
- Oncology
- Biotechnology
- Microfluidics
Background:
- In-vitro primary tumor cell culture shows promise for personalized cancer diagnosis.
- Limited tumor cell numbers, particularly in early-stage cancer, restrict the application of current drug screening methods.
Purpose of the Study:
- To develop a digital microfluidic system for high-throughput drug screening using primary tumor cells.
- To establish a validated protocol for precision medicine in cancer treatment.
Main Methods:
- A digital microfluidic system with smart control logic was designed for parallel drug screening on a compact chip.
- The system's efficacy was validated using a breast cancer mouse model and patient-derived liver cancer specimens.
- Exome sequencing was employed to correlate gene mutations with drug response.
Main Results:
- The microfluidic system successfully screened drugs, demonstrating tumor suppression in mice and patients treated with effective drugs.
- Ineffective drugs identified by the system showed no significant therapeutic effect compared to controls.
- On-chip drug screening results consistently correlated with the absence of specific gene mutations.
Conclusions:
- The developed digital microfluidic system and protocol advance precision medicine for cancer treatment.
- This technique holds potential for personalized therapeutic strategies in oncology and other diseases.

