Research On Wireless Real-time Multichannel On-chip Temperature Measurement System And Multicellular Temperature Measurement

Temperature is the key parameter of life,and cells are the basic unit of life.The measurement of cellular temperature not only can provide an understanding for various cell events,but also grasp the pathological state of cells and allow the development of diagnostic and therapeutic techniques for some diseases.However,inappropriate means of detection may significantly affect the cell status,and then affect the measurement of cell temperature.As the normal growing conditions of cells are 37?,5%CO2,as well as saturated humidity,and the cells form a complex cellular society,it is important to measure the cellular temperature in their normal growth without damaging themselves and destroying their population behavior.In this paper,a wireless real-time multi-channel on-chip temperature measurement system based on thin film platinum resistors is designed to realize cellular temperature measurement.The system has been applied to measure the temperature changes of various drugs on cells.Combining with other biological methods,the correlation between temperature changes and other cellular behaviors has been evaluated.The mechanism of temperature changes was also explored.The main work includes the following aspects:1.A wireless real-time in-situ temperature measurement system for in-situ real-time cellular measurement was designed.Intermittent measurement(the ratio of measurement time to dormancy time is 1:1)and a smaller excitation current(less than 0.14 mA)were used to reduce the self-heating of thermal resistors.Two reverse excitation currents were used for two adjacent measurements and their average value was obtained to reduce the influence of ambient noise on measurement.A high resistance accuracy was obtained by using a high precision reference resistor(10 kQ,0.005%,0.1 ppm)and four-wire measurement mode.The voltage ratio of the reference resistance and the sensor was obtained to ensure the precise measurement under a low current.Each channel was tested by a high precision reference resistor(1 kQ,0.01%,5 ppm)and compensated through the software correction.Using wireless technology and battery power supply,the data obtained in the incubator were transmitted to the PC outside by wireless receiving system.The circuit resistance resolution was 20 mQ,which corresponds to a temperature resolution of less than 0.01?.2.Preliminary cellular temperature measurement was carried out with the designed system.Combined with cell activity and morphological changes of cells under the action of drugs,it was found that with the increase of norepinephrine concentration,the cell temperature of HMEC-1 cell group also elevated gradually.The volume of HMEC-1 cells decreased gradually under the action of norepinephrine.Different drug concentrations had little effect on cell viability.3.Temperature changes of HMEC-1 cells induced by LPS at different concentrations were measured.The optimal concentration of LPS was determined according to the level of inflammatory factors,cell activity and ATP level.It was found that when LPS of different concentration acted on HMEC-1 cells,the cellular temperature change caused by an intermediate concentration of LPS was the biggest,while the inflammatory factors level was the highest,and the activity of cells was the lowest.In the course of inflammation,there is an approximate linear relationship between temperature and ATP content in the cell temperature change range of 0-0.45?.4.Inflammatory cells induced by LPS were repaired with different concentrations of norepinephrine.It was found that the intermediate concentration of norepinephrine showed a good repair effect to inflammatory HMEC-1 cells on that the temperature change of cell population was the most obvious,cell viability increased,and the level of inflammatory factors decreased.In the process of inflammation repair,there is an approximate asymptotic relationship between cell temperature and ATP content in the cell temperature change range of O?-0.45?.5.The temperature changes of melanoma cell A375 treated with different cold and hot drugs were measured and the mechanism was preliminarily explored.It was found that hypaaconitine has a similar effect on melanoma cells as GSK,while baicalin has a similar effect as HC.Combined with the change of intracellular Ca2+ concentration,it is speculated that the thermosensitive drug hypaconitine may cause the cell temperature to rise by acting on the thermosensitive receptor TRPV4 on A375 cell,while the cold drug baicalin may cause the cell temperature to decrease by acting on the thermosensitive receptor TRPV4 on A375 cell.