25 Apr Microfluidic Device Offers New Way to Screen Cancer Drugs at Single-Cell Level
In the field of cancer research, the ability to study the response of individual cells to different drugs is critical. Traditional methods of drug screening often involve large populations of cells, making it difficult to understand the variability of cellular responses. However, recent advances in microfluidic technology have made it possible to screen drugs at the single-cell level, providing valuable insights into drug efficacy and cellular heterogeneity. A recent paper published in Microsystems and Nanoengineering describes a microfluidic device designed for high-throughput single-cell drug screening. The device consists of two main components: a concentration-gradient drug generator and a single-cell capture array. The drug generator is capable of producing three different drug concentration gradients, which are then delivered to the single-cell capture array. The capture array consists of 24 individual chambers, each containing 180-205 capture units for single-cell capture.
” We propose that this system provides a flexible and controllable platform for the study of pharmacological functions and other fields involving concentration gradients and single-cell analytical operations. “, the authors explained.
“a Schematic diagram of the integrated microfluidic device. b The detailed design of a single-cell capture device. The various channels are shown with different colors to visualize the microfluidic device’s different components. Red and green indicate the fluidic channels of cells and reagents, respectively, and blue shows the control channels and valves. c Schematic of manipulation of single-cell capture according to cell size and deformability. The procedure consists of three steps: cell infusion, single-cell capture, and reagent infusion” Reproduced from Shen, S., Zhang, F., Zhang, Y. et al. Construction of multiple concentration gradients for single-cell level drug screening. Microsyst Nanoeng 9, 46 (2023) under Creative Commons Attribution 4.0 International License.
The authors of the study used the microfluidic chip to study the interaction of two common anti-cancer drugs, 5-fluorouracil (5-FU) and cisplatin (DDP), on two different cancer cell lines, HepG2 and MCF-7. The device was able to produce a range of drug concentrations in each chamber, allowing the researchers to study the effect of different drug concentrations on individual cells. The results showed that the response of cells to the drugs was highly variable, with some cells exhibiting resistance to even the highest drug concentrations.
In addition to studying the efficacy of drugs on individual cells, the device was also used to study the effect of cellular heterogeneity on drug resistance. The authors found that cells with smaller size and higher deformability were more resistant to the drugs than larger, less deformable cells.
Overall, this study demonstrates the potential of microfluidic devices for high-throughput single-cell drug screening. By allowing researchers to study the response of individual cells to different drugs, these devices could lead to the development of more effective cancer treatments tailored to the needs of individual patients.
“By using multiple-concentration gradient generators to form different concentration series, the system can be combined with a single-cell capture device to achieve 5-FU and DDP with different doses on HepG2 and MCF-7 cell lines at the level of single-cell biology applicability. Moreover, multifunctional studies of multiconcentration drug-induced tumor responses could be conducted simultaneously in a precisely controlled device. We anticipate that our work can provide a starting point for studying the sensitivity of multiple antineoplastic agents in single cells and for effectively screening monotherapy and combination therapy. “, the authors concluded.
Figures are reproduced from Shen, S., Zhang, F., Zhang, Y. et al. Construction of multiple concentration gradients for single-cell level drug screening. Microsyst Nanoeng 9, 46 (2023). https://doi.org/10.1038/s41378-023-00516-0 under Creative Commons Attribution 4.0 International License.
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