Introduction: Drug Screening
Most of the efforts in personalized medicine have focused on the selection of treatment for a particular patient based on genomic data, which are becoming more accessible due to the progress in sequencing technologies. Although there have been some impressively successful cases, the genomics of cancer are usually very complex, and despite the growing knowledge about the mutations that arise, there is still a limited understanding of how they affect the drug response [1]. Therefore, to increase patient survival, new approaches are urgently needed to develop effective treatment methods, such as tools for assessing the response of a drug to tumor cells before drug treatment [2].
Methods: Three-dimensional (3D) Cell Culture
Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are convenient and straightforward but are unable to capture the complexity of biological processes. Animal models are costly, time-consuming, and often fail to replicate human activity. In vitro three-dimensional (3D) models, such as spheroids, have characteristics such as close cell-cell interactions, lactic acidosis, and hypoxia, which can better mimic in vivo conditions and increase screening accuracy for new antitumor strategies. Spheroids are self-aggregation of cells without matrix or physical support [4]. However, due to the lack of control over the size of the spheroid, the response to anticancer drugs varies with conventional spheroid culture methods [3]. The uniformity of spheroids is also critical to get precise drug responses. When the size of the spheroids is not uniform, the permeability of nutrients, gas, and drug is different in each spheroid and elicits diverse drug responses [5]. For drug screening, planar cultured cell models are usually used to test drug efficacy and toxicity. However, planar cultured cells differ from human three-dimensional organs or tissues in vivo. For stimulating the human 3D organs or tissues, 3D spheroids are developed by culturing a small aggregate of cells that reside around the extracellular matrix and interact with other cells in liquid media [6]. The effectiveness of 3D cell culture techniques has been tested and verified extensively in recent years and is considered a viable alternative to traditional cell culture methods. The 3D culture techniques have also recently been combined with high-throughput methods for drug screening and assessment [1].
Results: Conventional techniqes for 3D Cell Culture for Drug Screening
3D cell arrays are widely used today for drug screening applications. Of these, scaffold-free 3D cell arrays such as low adhesion plates, micro pattern plates, and hanging drop microplates are currently most commonly used. Self-aggregation of cells is an essential point of this method. Besides, these 3D cell arrays will include scaffolds such as hydrogels and meshes to mimic cell-to-extracellular matrix interactions and tissue-specific properties. These microplate-based 3D cell arrays require sophisticated equipment such as robotic arms, detectors, and software for handling solution and data processing. Also, they are associated with several advantages, such as their reproducibility, simplicity of use for handling cultures, and the ability to treat and analyze multicellular spheroids. However, this robotic equipment still suffers from several technical problems such as high cost, poor handling of small amounts of liquid, and contamination of cell culture [5].
Conclusion: 3D Cell Culture in Microfluidics for Drug Screening
Microfluidic technology allows the user to perform cellbased assays in tiny volumes, thus opening up a screen of minimal material, such as a primary cell or patient biopsy. Accordingly, microfluidics has recently been successfully applied to the testing of several individual drugs against cancer cells [1]. Compared to single-drug therapies, drug combinations have emerged as therapeutics for many diseases, particularly cancers, due to the difficulties of treatment and cellular heterogeneity [9]. Wan et al. Described the use of microfluidic devices to generate hundreds of spheroids of various types of cancer cells, including patient-derived cancer cells [3]. In another study, Theresa Mulholland et al. present a microfluidic platform that allows drug screening of cancer cell-rich multicellular spheroids derived from tumor biopsies, enabling extensive anti-cancer compound screening before treatment [8]. Finally, microfluidics is emerging as a promising technology for both clinical precision medicine and industrial-scale drug discovery [9].
Keywords: microfluidics, drug screening, 3D cell culture, cancer, drug combination