Development of a cardiac-drug screening system based on the Cardiac-and-Piezoelectric Hybrid Platform
| Autor: | Chiou-Fong Yang, 楊秋鳳 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 The first step of drug development is drug screening. It is a very time consuming and is a very expensive process. In the development of cardiac drug, the concentration and frequency of cardiac tissue are important indicators to determine whether the compound is effective. To quantify concentration curve and frequency of cardiac tissue, most of monitor systems are base on optical system to monitor the deformation of substrate, including high-resolution cameras and laser displacement meter.Image analysis software are used to estimate the strain and stress of cardiac tissue. However, using image analyzing processhas some limitations: First, the analysis is based on substrate deformation, its force porfile is an indirect estimation. Second, the optical system need to be processed by experienced specialists, and it is hard to become an automatic process. Finally, it cannot perform laege number of detection at the same time. To achieve an automatic, real-time and direct measurement of cardiac force profile, we developed a cardiac–drug screening system. The system is based on Cardiac-and-piezoelectric hybrid platform based on a polyvinylidene fluoride (PVDF) flexible film as a substrate to monitor the concentraction of cardiomyocytes. The cardiac-drug screening system shields the environmental noise from the environment, microgrooves and extracellular matrix are used to promote the growth of cardiomyocytes, and cardiac contracting behaviors are measured through the electrical signals generated by the deformation induced by cardiomyocytes. Finally, the cardiac-drug screen system was tested with two commercial drugs, isoproterenol and Metoprolol. The results of the drug test using isoproterenol resulted in a significant increase in cardiomyocyte frequency and amplitude, and the EC50 calculated using commercial software was 200 nM, which was within the numerical error range mentioned in the reference. Metoprolol was also used. It was found that the frequency and amplitude of cardiomyocytes were decreasing, and the IC50 of 368 μM was within the numerical error range mentioned in the refernce. On the other hand, isoproterenol was found to exceed the EC50 concentration of 62 nM in the study. Cardiomyocytes increased the exertion intensity by 45%, which proved that isoproterenol also has the function of regulating the contracting strength. It is verified that the piezoelectric membrane can be used as a sensor to simultaneously measure the beating frequency and the amplitude. This verifies the feasibility of the automatic and direct detection of cardiomyocyte contracting signals in this system, and we successfully achieve the goal of performing a large number of preliminary drug screening tests. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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