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Updated: Jun 4, 2025

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A High-Throughput and Logarithm-Serial-Dilution Microfluidic Chip for Combinational Drug Screening on Tumor

Xingyang Yan1, Deng Tan1,2, Lei Yu3

  • 1Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 999077, Hong Kong, China.

ACS Pharmacology & Translational Science
|December 19, 2024
PubMed
Summary

This study introduces a novel microfluidic chip for advanced tumor organoid drug screening. The device enables precise, high-throughput testing of multiple drug concentrations, advancing precision medicine applications.

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Area of Science:

  • Biotechnology
  • Microfluidics
  • Cancer Research

Background:

  • Tumor organoids are key models for precision medicine.
  • Microfluidics enhances high-throughput drug screening of tumor organoids.
  • Traditional microfluidic gradient generators have limited drug concentration ranges.

Purpose of the Study:

  • To develop a microfluidic chip with continuous dilution capabilities for generating logarithmic drug concentration gradients.
  • To create a "mathematical-circuit-chip" model for designing advanced microfluidic drug screening devices.
  • To enable high-throughput drug screening using patient-derived tumor organoids for precision medicine.

Main Methods:

  • Designed and fabricated a microfluidic chip with two orthogonally arranged layers.
  • Each layer features a dilution network for 5-fold gradients and a tumor organoid culture module.
  • Utilized a "mathematical-circuit-chip" model for chip design.
  • Employed syringe pumps for drug and medium delivery to an open culture chamber array.

Main Results:

  • Developed a microfluidic chip capable of generating logarithmic stepwise drug concentration gradients.
  • The chip provides 36 distinct drug concentration conditions for two drug types.
  • Successfully conducted drug screening experiments on patient-derived tumor organoids.

Conclusions:

  • The novel microfluidic chip significantly enhances high-throughput drug screening for patient-derived organoids.
  • This technology represents a substantial advancement towards the goals of precision medicine.
  • The developed chip overcomes limitations of traditional microfluidic gradient generators.