Application of organoids-on-a-chip based on microfluidic technology in precision medicine of lung cancer

Lung cancer is the most common malignant tumor in the world in terms of morbidity and mortality. There is a pressing need to improve the overall survival rate through personalized treatment. Specifically, customized drug screening and the research and development of a new drug are crucial. With the development of in vitro three-dimensional culture technology, patients-derived organoids (PDOs) can preserve the true genetic heterogeneity of original tumors, which has been investigated in many fields, such as disease modeling and drug discovery. However, limitations are hindering further clinical translation and application. Therefore, an active effort has been made to optimize organoid culture technology to enhance its usability. Organoids-on-a-chip is an extension of organoids in biotechnology, which can effectively compensate for the shortcomings of traditional organoid culture technology. Taking microfluidic chip technology as the core, the organoids-on-a-chip can automatically and accurately mimic the micro-environment that organoid culture needs, such as biochemical factors, oxygen and shear force through microchannel processing or manipulating small fluid at the microenvironment level. Furthermore, it simulates the cell-cell and cell-extracellular matrix interactions and reshapes the biochemical and biomechanical characteristics of the tumor microenvironment, which is expected to better translate the results from basic cancer research to precision medicine. In this review, we first summarize the advantages of organoids-on-a-chip based on microfluidics as a personalized drug screening model, including precise control of the physical and chemical environmental factors, simulating the tumor microenvironment and significantly improving throughput and dynamic and continuous monitoring of organoids. Then, the latest progress of organoids-on-a-chip based on microfluidic technology in lung cancer research is summarized. These devices help researchers explore the complex tumor-stromal cell interactions of angiogenesis and tumor metastasis in TME of lung cancer, which can accelerate the research of related molecular mechanisms and drug analysis. This can also significantly reduce the quantity requirement of PDOs culture. PDOs can react quickly in a microfluidic chip, with less reagent consumption and simple manual operation, which significantly simplifies the complicated drug screening process at an early stage. Additionally, we discuss the application prospects and development directions of organoids-on-a-chip for lung cancer; it is proposed that the integrated platform based on microfluidics and sensors can explore the tumorigenesis of lung cancer and discover potential biomarkers, which will create new opportunities for personalized diagnosis and treatment. Finally, we study the drug screening process of PDOs, aiming to promote precision medicine by optimizing and improving the drug screening process. In conclusion, organoids-on-a-chip have the advantage of being controllable, high-throughput and dynamic and can be continuously monitored, which provides the possibilities of large-scale and automatic standardization of PDOs culture. It is of great significance to improve the success rate of organoid model construction and the accuracy of drug screening and expand the application scope of organoids. Although still in the development stage, and there are many challenges to be overcome, we believe that soon, organoids-on-a-chip will lay the foundation for the widespread application of lung cancer organoids in the new era of personalized and precision medicine.