The Research of Automated Multifunctional Cellular Physiological Analyzer with Integrated Chip
|Keywords||Cytosensor The cells physiological parameters analysis Integrated chip Cell multi- parameter analysis Microelectrode array (MEA) Light addressable potentiometric sensor (LAPS) The cells electrical impedance sensor (ECIS)|
The cell sensor (Cell-Based Biosensor, CBB) use of living cells as a transducer, and feel the stimulus signal will be generated a lot of different types of changes, such as cell metabolism, and action potential, and the electrical impedance changes. The two transducers connected with the cell can be detected from the cell changes, and these cells measured signal is converted to the electrical signal, thus fed to the electrical system. Different cell sensor based on the detection of physiological parameters, used two transducers microelectrode array (Microelectrodes Array MEA), light addressable potentiometric sensor (Light Addressable Potentiometric Sensor, LAPS), cell electrical impedance sensor (Electric Cell- substrate Impedance Sensor, ECIS). During cell physiological experiments, a single parameter monitoring often only reflect the physiological activity of the cells from one area, but the complexity of the test environment (noise source culture medium after long-term testing of electrode corrosion, etc.) will interfere with the test results reveal the mechanism of cellular activity you need to complete comprehensive analysis on a variety of physiological parameters. In order to achieve the concentration of extracellular ion (microenvironment detection), extracellular action potentials and electrophysiological impedance three physiological parameters simultaneously detect, using a combination of electronic technology and biomedical technology, developed a multifunctional chip Automatic cell physiological parameter analyzer. The instrument has a short analysis time, sample consumption and high efficiency. During the measurement process can automatically adjust the temperature, humidity and CO2 concentration in the measuring chamber, in order to meet the environmental requirements of the cell growth. The same time through the autosampler system can achieve a fully automated analysis capabilities. It can be widely used in the field of cell physiology, drug screening and environmental testing. In addition, the instrument can achieve the detection of the real-time quantification of the cell physiological state in the single cells, the conductivity of the cell network, and drug effects. Uses a unique the chip interface device and board-circuit design, the instrument is suitable for the detection of a variety of cells, as well as a variety of different chip demand. This thesis research and innovation: a proposed theoretical analysis model and simulation of multi-functional chip design paper presents an integrated MEA, the LAPS and ECIS as one of the the novel of cell physiology detection chip design thinking to solve the three physiological parameters of the cell extracellular action potentials, extracellular ion concentrations and cell impedance simultaneous detection of a number of key issues. First study the basic theory of multi-functional chip detector cell physiological parameters. How to feel the stimulation signal from outside through the cells as a transducer analysis expounded with cell metabolism, cell action potential, the impedance characteristics of cell membrane, and cell adhesion and migration related cell basic characteristics, and gives the cells feel two transducer coupled model different types of output signals to external stimuli, and eventually come to a theoretical model of the sensor cell. Secondly multifunction integrated chips MEA sensing unit, ECIS sensing unit, and the the LAPS sensing unit portion Electrocardiology model. Integrated chip sensing unit design parameters of the test results on simulation results, optimize the design parameters of the chip, and provides a theoretical support for multi-function chip and instrument design. Second, to achieve the design of the analyzer system design and manufacture of the multi-cell physiology integrated chip ECIS, the APS, MEA sensing unit corresponding detection circuit, the design of the environment control system of the measuring chamber temperature, humidity, and CO2 concentration strictly controlled, such that it be maintained in the cells are the most suitable for the growth environment, the design of the automatic injection system to control the injection pump and a kind of pump off and speed, thereby completing the culture fluid and drug autosampler and a waste liquid cleaning automated analysis. The entire physiological signal acquisition process is controlled by a central control circuit, the signal data and obtain preliminary analysis by the USB interface to transfer to the computer, computer design software for data collection, storage, and post-analysis and other functions. Analyzer through unique chip interface device and circuit function module motherboard design, can be adapted to different chip design. The final design of the analyzer prototype of a multifunctional cell physiology, flexible expansion and development towards industrialization, the demand for multi-parameter analysis of cell physiology. To achieve the detection and analysis of cell physiology integrated multi-function parameters first prototype of the analyzer test evaluation, including tests of LAPS, ECIS, MEA chip detection circuit indicators, as well as environmental control system and autosampler The testing of the system. The results show that the performance of the sensor chip and instrument to meet the actual requirements analysis. Secondly, based on the multi-functional chip, cell physiological parameter detection of typical experimental test of the the paper developed cell physiology analyzer biomedical applications. The the the LAPS sensor unit integrated chip renal cell acidification rate in the 5 - fluorouracil under testing. MEA integrated chip sensor unit detects neonatal rat cardiomyocytes extracellular action potential changes in the role of tetrodotoxin (TTX). Integrated chip ECIS sensing unit to detect cell migration, growth and proliferation, as well as the process of death. The experimental results show that the analyzer can be used for a comprehensive analysis of the cells in a variety of physiological parameters. Cultured myocardial cells in the drug effect experiments, indicating that the instrument can be simultaneously detected in a single experiment to impedance of the myocardial cells, extracellular action potentials and the process of changes in the concentration of extracellular Ca2 three parameters. The data analysis showed that the three physiological parameters was to the evaluation of a variety of indicators parameters of the cell in drug action, such as the evaluation of drug cardiotoxicity. Preliminary experimental results show that, the paper developed multifunctional cell physiology analyzer will have broad application prospects in the field of biomedicine.