Research On Heart-on-a-chip With Integrating Mechanical Stimulation And Force-electrical Sensors

The heart-on-a-chip provides a reliable in vitro culture model for the study of heart disease and cardiovascular disease.It reproduces the physiological characteristics and basic functions of the heart and is widely used in pathological models,drug screening and mechanism research.In pathological model studies,in order to better simulate the cardiac physiological environment,mechanical stimulation is often used to optimize cardiomyocyte contractile stress or abnormalize cardiomyocytes(such as ischemia,hypoxia,myocardial hypertrophy,etc.).Fluorescence immunoassay is often used to quantify the effect of mechanical stimulation on cardiomyocyte contractile stress and degree of development.However,it is limited to semi-quantitative analysis,and fluorescence breakpoint detection causes cell death,resulting in the inability to dynamically monitor the growth status of cardiomyocytes,which limits long-term physiological monitoring in myocardial pathological models.In order to achieve longterm assessment of the growth of cardiomyocytes under different mechanical stimulation,avoiding invasive cell testing,it is important to design a multi-information fusion heart organ chip by integrating multi-sensor in dynamic monitoring.In the study of mechanical stimulation on cardiomyocyte development,contractile stress is an important mechanical indicator of cardiomyocyte growth and development,and its size can reflect the effect of mechanical stimulation on cardiomyocyte growth.In addition,troponin I as a structural protein of cardiomyocytes,it is expressed in an amount that can further reflect the magnitude of contractile stress.By integrating sensors to dynamically monitor these mechanical and biochemical indicators,it can mutually verify the effect of mechanical stimulation on cardiomyocyte development.In this study,the heart-on-a-chip is proposed to integrate mechanical stimulation,mechanical sensor,cell culture,electrochemical sensor modules.The designed and prepared heart-on-a-chip was used for the detection of cell contraction stress and c Tn I concentration under different mechanical stimulation.By the relationship between the magnitude of contractile stress and the concentration of c Tn I,the growth of cardiomyocytes under different mechanical stimulation was mutually verified.The results showed that less than 25% mechanical stimulation(5%-20%)enhanced the contractile stress of cardiomyocytes and promoted the maturation of cardiomyocytes.The concentration range of c Tn I was 0.47±0.12 pg/ml ～ 2.52±0.19 pg/ml.25% of mechanical stimulation may cause apoptosis of cardiomyocytes,and 30% of mechanical stimulation leads to the death of a large number of cardiomyocytes.The designed cardiac organ chip can be used to monitor the growth and development of cardiomyocytes under different mechanical stimulation in the long term.