Research Of Anti-tumor Drug Screening Cell Chip Based On3D Cell Printing Technique

Multi-disciplines integrating is a distinctive feature of the development of science andtechnology in21Century.3D cell printing is the most forward technique in Bio-manufacturingwhich merges life science, information science, material science and manufacturing science.3D cellprinting and cell chip provide a highly valuable tool for tissue engineering, drug screening and otherfields. In this study, the biomimetic multi-tissue models in vitro, which were prepared by3D cellprinting technique and cell chip, could be used for drug screening.In this study, firstly, we introduced the domestic and foreign status of3D cell printing, cellchip and drug screening，and analyzed the possibility of introducing3D cell printing and cell chipinto drug screening. Based on the mechanism of3D cell printing and cell chip, we chose IDEsbiosensor for cell impedance monitoring and studied the measuring principle, parameter, materialsand processing flow of the biosensors. Then we designed and manufactured a cell chip, whichintegrates several groups of IDEs. The electrochemical workstation was used for performancetesting of cell chip, and results showed that the chip could precisely detect the cellelectrophysiology.Secondly, we displayed the3D-Bioprinter and introduced its system composition and functions.We chose biological material for scaffolds, the material ratio and material compatibility testing ofdifferent materials were also studied. After that, we printed the materials on the chip, and studiedthe forming and curing characteristics and the effects of materials on the sensitivity.Thirdly, according to the forming principle and the structure of the cell chip, we designed thescaffold structure that would be printed on the surface of biosensor. This chapter emphaticallyanalyses the effects of the parameters, including temperature, nozzle size, slice thickness, scanningspeed, extrusion speed and others on the porosity, micropore shape and aperture size. We obtainedthe structural image of the scaffold using swept source optical coherence tomography (SSOCT)system, and the cell activity was detected by immunofluorescence.Finally, we chose suitable electrolyte and test frequency by comparing the results of DMEM,PBS solution and potassium ferrocyanide solution. Then, the HMSC-H and HO-8910cells wereassembled within the gelatin/alginate mixture on the chip using3D cell printing. Based on thiscells-loaded chip, the hepatoxicity or antitumor effect of both CTX and DDP were measuredrespectively. Our results showed that a good cell growth of HMSC-H or HO-8910cells could beobserved in the3D structure. The change of impedance caused by cell proliferation could be precisely detected by the chip at104Hz using DMEM as electrolyte solution. Using this chip-basedin vitro drug screening model, we simultaneously detect the hepatotoxicity and antitumor effect ofthe drugs. Meanwhile, the efficacy of these drugs, which require hepatic metabolism for activationsuch as CTX, could also be evaluated in the same chip. In summary, our results revealed that thebiomimetic multi-tissue models, which were prepared by3D cell printing technology on the cellchip, show great potential for the application in drug screening.