KR101944352B1 - Experimental apparatus for the cellular metabolism measurement and a method measuring cellular metabolism using the same. - Google Patents

Abstract

The present invention relates to an apparatus for measuring cell metabolism and a method for measuring cell metabolism. The present invention achieves the uniformity of the well-specific measurement and automates the calibration process of the experimental equipment, thereby increasing the accuracy of the cell metabolism measurement, minimizing the time required for calibration and improving the ease of use.

Description

TECHNICAL FIELD The present invention relates to a cell metabolism measuring apparatus and a cell metabolism measuring method.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automated laboratory apparatus, and more particularly to a cell metabolism measurement laboratory apparatus.

Cellular metabolism measurement is to measure hydrogen ion concentration, oxygen concentration, carbon dioxide concentration and so on. Hydrogen ion concentration, oxygen concentration, and carbon dioxide concentration represent the degree of cellular metabolism and are widely used as an indicator of cell activity. Therefore, the cell metabolism measurement experiment can be usefully used in the biopharmaceutical industry such as new drug discovery and development, pharmacokinetic test, empirical analysis, and the food industry.

 Conventional cell metabolism measurement devices use optical detection methods. Optical detection technology is simpler in configuration than conventional electrochemical methods and does not cause electromagnetic noise, and is widely used because of its small size and easy fabrication. However, since it is inevitable to use a plurality of micro-test tubes for experiments and various experiments in the experimental group and the control group, it is necessary to use the micro- There is a problem that it is difficult to obtain accurate experimental results. In addition, since it is required to perform various experiments in one study and each experiment requires a considerable amount of time, it is very important to utilize the cell metabolism measurement device efficiently in order to obtain the results in a short time. to be.

Korean Patent Registration No. 10-1155136

SUMMARY OF THE INVENTION Accordingly, the present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to achieve uniformity of measurement by wells.

Also, it is possible to automate calibration process of experimental equipments, thereby minimizing the time required for calibration and improving convenience of use.

In order to accomplish the above object, the apparatus for measuring cell metabolism, which is operated to perform the cell metabolism measurement test method according to the present invention, may include an XY drive stage table, a microplate, a sensor board, a cartridge, a drug injector, . The microplate includes a plurality of wells having a sensor membrane on its bottom surface. The sensor board may be arranged such that a measurement sensor including a light emitting element and a light receiving element mounted on the X-Y drive stage table is perpendicular to the sensor film. The cartridge may contain a plurality of medicaments. And the drug injector may be configured to inject the drug of the cartridge into the well and may be plural. The control unit may drive the X-Y driving stage table to control the apparatus to move the microplate relative to the measurement position where the optical measurement is performed or the drug injector, thereby performing the cell metabolism measurement. The cell metabolism measurement test method performed by the cell metabolism measurement apparatus may include an initialization step and a measurement value determination step. The initialization step may set the drive parameters of the respective elements of the sensor board by sensor correction data for each element of the sensor board and drive the respective sensor elements by the drive parameters of the respective elements of the sensor board. In the measurement value determination step, the measurement value can be determined by converting the measured physical quantity into the cell metabolism quantity according to the measurement characteristic data set for each well.

 Also, the physical quantity measured in the cell metabolism measurement method of the cell metabolism measurement apparatus may be a physical quantity related to the time taken for the light-receiving element sensing current of the sensor board to reach the trigger level after the light-emitting element of the sensor board is driven by the square wave.

In addition, the initialization step may include a sensor correction step and a measurement characteristic determination step. The sensor calibration step can determine and set the sensor calibration data that corrects circuit deviation and mechanical deviation of each element of the sensor board through standard solution injection and measurement. In the measurement characteristic determination step, the measurement characteristic data can be set by determining measurement characteristics for each well through injection and measurement of a plurality of standard solutions.

On the other hand, the sensor correction data may be a trigger level for determining the light emitting element drive parameter and whether or not the light receiving element is to receive light.

Further, the driving parameter of the light emitting device may be an amplification factor of the voltage control amplifier.

Further, the trigger level of the light receiving element can be set by software in the control section. In addition, the measurement characteristic data determined through the measurement characteristic determination step can be stored as a lookup table to be referred to in a cell metabolism measurement.

On the other hand, the cell metabolism measurement apparatus may include an X-Y driving stage table, a microplate, a sensor board, a cartridge, a drug injector, and a control unit. The microplate includes a plurality of wells having a sensor film on its underside and can be mounted on the X-Y drive stage table. The sensor board may be arranged so that the measurement sensor including the light emitting element and the light receiving element corresponds to the sensor film perpendicularly. The cartridge may be a plurality of receptacles containing the medicament. And the drug injector may be a plurality of configured to inject the drug of the cartridge into the well. The control unit drives the XY driving stage table to control the apparatus to move the microplate relative to the measuring position where the optical measurement is performed or the drug injector, thereby controlling the progress of the cell metabolism measurement. Decision instructions. The initialization commands can set the drive parameters of the respective elements of the sensor board with the sensor correction data set for each element of the sensor board, and drive the sensor elements with drive parameters of the respective elements. The measurement value determination commands access the recording medium storing the program including the measurement value determination commands for converting the measured physical quantity into the cell metabolism amount according to the measurement characteristic data set for each well to determine the measurement value, .

The measurement value determination commands may include a physical quantity measurement command to measure a physical quantity related to a time required for the light-receiving element sensing current to reach the trigger level after driving the light-emitting element with a square wave.

The initialization commands may also include sensor calibration commands and measurement characteristic determination commands. The sensor calibration commands can be set and determined by sensor calibration data that corrects circuit deviations and mechanical deviations of each element of the sensor board through standard solution injection and measurement. The measurement characteristic determination commands can set the measurement characteristic data by determining measurement characteristics for each well through injection and measurement of a plurality of standard solutions.

On the other hand, the sensor correction commands may include adjustment commands for driving parameter of the sensor board element. The adjustment commands of the driving parameter of the sensor board element adjust the trigger level for determining whether each light emitting element drive parameter or each light receiving element receives light so that the difference between the correction reference value and the measured physical quantity falls within a predetermined reference value tolerance range And can be set.

In addition, the adjustment commands of the driving parameters of the sensor board element may include a gain adjustment command. The amplification factor adjustment command can adjust and set the driving signal of the light emitting element by setting the driving parameter for each light emitting element as the amplification factor of the voltage control amplifier.

In addition, the adjustment commands of the driving parameter of the sensor board element may include a trigger level adjustment command. The trigger level adjustment command can adjust and set the trigger level for each light receiving element by software.

In addition, the measurement characteristic determination commands may include a measurement characteristic data storage command. The measurement characteristic data storing instruction may store the measurement characteristic data of the respective elements of the determined sensor board as a lookup table to be referred to in the cell metabolism measurement.

On the other hand, the cell metabolism measurement apparatus may further include optical components. The optical component is positioned on each of the light emitting elements, and the deviation of the incident angle due to the mounting deviation of the light emitting element can be compensated.

In addition, the apparatus for measuring cell metabolism may further include a sealing lid capable of moving vertically up and down and moving downward to seal at least one of the wells of the microplate.

According to the present invention, the accuracy of cell metabolism measurement can be increased by performing correction for compensating for optical detection deviations for each well.

By implementing the cell metabolism measurement device to operate automatically, the time required to perform various experiments is minimized.

1 is a perspective view of an apparatus for measuring cell metabolism according to an embodiment.
FIG. 2 is a perspective view of the inside of the housing of the cell metabolism measurement apparatus shown in FIG. 1. FIG.
3 is a partially exploded perspective view of the inside of the housing shown in Fig.
FIG. 4 is a block diagram showing a microplate and a sensor board of an apparatus for measuring cell metabolism according to an embodiment.
FIG. 5A shows a physical quantity measurement period according to an aspect of a cell metabolism measurement method of the cell metabolism measurement apparatus according to one embodiment. FIG.
FIG. 5B shows a physical quantity measurement period according to another aspect of the cell metabolism measurement method of the cell metabolism measurement apparatus according to the embodiment of the present invention.
6 is a flowchart illustrating a method of calibrating a sensor of a cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 7 is a flowchart illustrating a method of determining measurement characteristics of a cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 8 illustrates sensor board elements and a control unit of a cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 9 is a block diagram of a program of a cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 10 is a block diagram of measurement value determination commands of the cell metabolism measurement apparatus according to an embodiment of the present invention.
11 is a block diagram of initialization commands of the cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 12 is a block diagram of sensor calibration commands of the cell metabolism measurement apparatus according to an embodiment of the present invention.
FIG. 13 is a block diagram of commands for adjusting driving parameters of a sensor board device according to an embodiment of the cell metabolism measurement apparatus according to an embodiment.
FIG. 14 is a block diagram of commands for adjusting driving parameters of a sensor board device according to another embodiment of the cell metabolism measurement apparatus according to an embodiment.
FIG. 15 is a block diagram illustrating measurement characteristics determination commands of the cell metabolism measurement apparatus according to an embodiment of the present invention.
16 is a block diagram showing a microplate, a sensor board, and a lens of an apparatus for measuring cell metabolism according to an embodiment.

Hereinafter, a method and an apparatus for measuring cell metabolism according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings. Here, the same reference numerals are used for the same components, and repeated descriptions and known functions and configurations that may obscure the gist of the present invention will not be described in detail. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art. Accordingly, the shapes and sizes of the elements in the drawings and the like can be exaggerated for clarity.

FIG. 1 is a perspective view of an apparatus for measuring cell metabolism according to an embodiment of the present invention, FIG. 2 is a perspective view of the interior of the housing of the apparatus for measuring cell metabolism shown in FIG. 1, FIG. 4 is a block diagram showing a microplate 300 and a sensor board 500 of a cell metabolism measurement apparatus according to an embodiment of the present invention.

1 and 2, the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment includes an XY drive stage table 400, a microplate 300, a sensor board 500, a cartridge 100 ), A drug injector (200), and a control unit (700).

The cell metabolism measurement apparatus includes a housing 10 surrounding a device and an electronic component. The housing 10 includes mechanisms and electronic components such as a cartridge 100, a drug injector 200, a microplate 300, an XY driving stage table 400, and a sensor board 500. As shown in FIG. 1, the housing 10 may include a front cover 11 that opens and closes the front surface. The number of the cartridges 100 may be plural. Or one, and can be physically partitioned to have a plurality of accommodation spaces. In one embodiment, at least one mounting hole 12 for mounting the cartridge 100 is formed on the housing 10, and the cartridge 100 in which the medicine is accommodated is mounted in the mounting hole 12. As shown in FIG. 1, the mounting holes 12 may be four, and the cartridges 100 may be mounted in the respective mounting holes 12. The housing 10 may include a hole cover 13 for covering the mounting hole 12.

Each of the cartridges 100 may contain a plurality of medicines. The cartridge 100 can also accommodate different medications. The user can select drugs for the experiment by using the cartridges 100. Drugs include Oligomycin, 2, 4-Dintrophenol (2,4-DNP) or Carbonylcyanide-p-trifluourmethoxyphenylhydrazone (FCCP) , And Antimycin A, and the like. The cartridges 100 are connected to the drug injectors 200 by piping, and supply the medicines to the positionally fixed drug injector 200 through the piping.

The injector 200 is configured to inject the drug of the cartridge 100 into the well and may be a plurality of injectors. That is, the drug injector 200 is a structure for injecting the drug into the well of the microplate 300. In one embodiment, drug injector 200 is a syringe pump with a three-way valve. The number of the drug injectors 200 is plural, which is equal to the number of the cartridges 100 or the number of physically partitioned accommodation spaces. The drug injectors 200 are connected to the cartridges 100 in a one-to-one correspondence with the piping. In one embodiment, drug injector 200 is a syringe pump with a three-way valve. The drug injector 200 receives and holds the drug from the cartridge 100 through the piping, and discharges the held drug.

The X-Y driving stage table 400 is a table movable together with the X-axis and Y-axis, that is, the horizontal up-down and left-right direction in accordance with the driving of the X-Y driving stage in unison with the X-Y driving stage. Therefore, the microplate 300 can move along the X and Y axes. By moving and controlling the XY driving stage table 400, the specific well 310 of the microplate 300 can be moved to any one of the drug injectors 200 It can be placed in one subordinate. This means that the desired drug can be injected automatically per well 310. In addition, stirring can be naturally performed in the well 310 according to the movement of the X-Y driving stage table 400. Therefore, the control unit 700 may control the XY driving stage table 400 for the purpose of stirring. [0154] Also, after the cell metabolism measurement apparatus is injected with the prescribed drug for each well, The control unit 700 may control the XY driving stage table 400 in advance to measure the XY driving stage table 400 so that the XY driving stage table 400 is positioned at the measuring position The control unit 700 may move the XY driving stage table 400 to the measurement position in advance in order to determine the sensor correction or measurement characteristic as in the initialization step described later. May move and control the XY drive stage table 400 to the reference position or may remain as the measurement position. The well-defined user-defined protocol is used to automatically perform the measurement process on a well-by-well basis. The well-defined user- In accordance with an aspect, the cell metabolism assay device may further include a graphical user interface that supports well-defined user-specific protocol input. The user can set the user-defined protocol for each well via the graphical user interface. [0040] On the other hand, before performing the control according to the user-defined protocol, the controller 700 controls the position of the XY driving stage table 400 For example, the control unit 700 may control the driving of the XY driving stage And a reference position is recognized by using a limit switch. Since such a position recognition technique is widely known, a detailed description is omitted.

The microplate 300 includes a plurality of wells having sensor films, and is mounted on the XY driving stage table. The microplate 300 may have a sensor membrane on its bottom surface according to one aspect. The microplate 300 includes a plurality of wells 310, wherein the number of wells may be 6, 12, 24, 48, 96, and so on. Each well 310 accommodates cells and may include both a sensor membrane 311 for detecting dissolved oxygen (DO) and a sensor membrane 312 for detecting pH. The sensor film for DO detection and the sensor film for pH detection may be a fluorescent sensor film coated with a fluorescent dye. The ruthenium complex (tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II), Ru (dpp) ₃ ²⁺ ) can be used as the fluorescent dye of the sensor film for DO detection. As fluorescent dyes, hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) can be used. The ruthenium complex (Rudpp) generates strong fluorescence in the fluorescent dye for oxygen detection and has a long quantum yield and long fluorescence lifetime. Detection of dissolved oxygen using a ruthenium complex uses the principle of fluorescence attenuation by molecular oxygen, which consumes the energy released by the oxygen molecule as a result of the emission of fluorescent dye falling to the ground state as a result of excitation. The fluorescence intensity is decreased. Decreasing fluorescence intensity is inversely proportional to the concentration of oxygen molecules. In other words, the ruthenium complex is excited by light at 480 nm and is converted to a ground state, emitting 510 nm fluorescence. And the HPTS used for pH detection can generate strong fluorescence and is not toxic. Fluorescent pH detection utilizes the principle that fluorescence occurs when a fluorescent dye is quantized or unquantized by acid or alkali. When irradiated with light of 405 nm, HPTS absorbs electrons, excites them, and converts them to a ground state, emitting 510 nm fluorescence.

The sensor board 500 is arranged so that the measurement sensor including the light emitting element and the light receiving element corresponds to the sensor film. The sensor board 500 may be mounted on the sensor housing 20 and integrally provided on the X-Y driving stage table 400. The microplate 300 is positioned on the sensor board 500. 4, the sensor board 500 includes a pair of DO detection light emitting devices 522 vertically corresponding to the sensor film for DO detection provided for each well 310 of the microplate 300 And a light receiving element 511 that includes a pair of pH detecting light emitting elements 521 vertically corresponding to the sensor film for pH detection provided for each well 310 have. A light emitting diode (LED) may be used as the light emitting element, and a photodiode or a phototransistor may be used as the light receiving element. When the DO detection light emitting element 522 irradiates light, the DO detection fluorescence sensor film emits fluorescence, so that the DO detection light receiving element 512 receives the emitted fluorescence. When the pH detecting light emitting device 521 is irradiated with light, the pH detecting fluorescent sensor film emits fluorescence, so that the pH detecting light receiving device 511 receives the emitted fluorescence.

The control unit 700 drives the XY driving stage table 400 to control the apparatus to move the microplate 300 relative to the measuring position where the optical measurement is performed or the drug injector 200 to perform the cell metabolism measurement do. The control unit 700 may include at least a part of at least one processor, a field-programmable gate array (FPGA), a micro control unit (MCU), or the like. The controller 700 may be composed of a single controller or a plurality of controllers. In the latter case, the control unit 700 may include a main control unit 700 and an auxiliary control unit 700 which is separated from the main control unit 700 and can transmit / receive data. The control unit 700 can control the movement of the X-Y driving stage table 400, drive-control the drug injector 200, and control the optical measurement. Also, the DO concentration and the pH can be measured by analyzing the electrically received signal received through the light receiving element of the sensor board 500 with respect to at least one well 310 of the microplate 300. In addition, other control functions for device operation can be performed.

 The cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment may include an initialization step and a measurement value determination step.

The initialization step of the cell metabolism measurement method of the cell metabolism measurement apparatus is performed by setting the drive parameters of the respective elements of the sensor board 500 with the sensor correction data of each element of the sensor board 500 and setting the drive parameters To drive the respective sensor elements. The initialization means to reset the driving characteristics of the sensor board 500. The optical characteristics of the respective elements of the sensor board 500 are susceptible to change by movement of the microplate 300 or over time. Therefore, the cell metabolism measurement apparatus needs to recalibrate the optical characteristic deviations of the respective elements of the sensor board 500 according to predetermined conditions before actual measurement of the wells of the microplate 300 is performed. In the cell metabolism measurement apparatus according to one aspect, the user can input a condition for performing the initialization step through the touch screen module or other input device, and set the control condition in the control unit 700. For example, the initialization step progress condition may be set so that the initialization step is performed before execution of each cell metabolism measurement experiment. As another example, the user may set an initialization step progress condition in the controller 700 to proceed to the initialization step when the cell metabolism measurement experiment apparatus reaches the preset number of experiments. On the other hand, the initialization step may proceed for all the wells of the microplate 300. Alternatively, the initialization step may be performed only for specific wells. For example, the degree of change in sensor characteristics of each sensor of the sensor board 500 is monitored based on sensor correction data generated every time the cell metabolism measurement apparatus performs sensor correction, The initialization step can be performed only for the wells that deviate from the initialization step.

On the other hand, the sensor correction data is data generated by the control unit 700 or the user in a predetermined process for each element constituting the sensor board 500 in the initialization step. The apparatus for measuring cell metabolism according to one embodiment can monitor physical quantities measured by wells through an output device. Further, when the sensor correction step is in progress in the initialization step, the controller 700 may cause the output device to output an indication that correction is necessary for the well where the measured physical quantity deviates from the correction allowable reference deviation. In this case, the user may monitor the indication of the need to calibrate the output device, e.g., the physical quantity value that deviates from the calibration tolerance deviation, and manually set the value of the sensor calibration data through the input device. Also, the user can refer to a predetermined guideline when setting the sensor correction data. The predetermined guideline may be a guideline for generating sensor calibration data that is completed through a preliminary experiment. The user manually inputs sensor correction data through an input device of the cell metabolism measurement apparatus, for example, a touch screen or a keyboard, referring to a predetermined guide line, and controls the sensor board 500 The sensor calibration data can be generated by adjusting the driving parameters of each element of the sensor calibration data.

The control unit 700 of the cell metabolism measurement apparatus according to an embodiment can perform a predetermined process of generating sensor correction data according to an aspect by executing a predetermined program. The predetermined program according to one aspect can be programmed to adjust the drive parameters of the respective elements of the sensor board 500 until the deviation between the predetermined reference value and the physical quantity measured for each well falls within the range of the predetermined reference value tolerance . In addition, the predetermined program is such that the drive parameter of each of the elements of the sensor board 500, which causes the deviation between the correction physical quantity reference value and the physical quantity measured for each well to fall within the range of the predetermined correction physical quantity reference value allowable deviation, Lt; RTI ID = 0.0 > of sensor calibration data. ≪ / RTI > The predetermined program may then be programmed to store the generated sensor correction data in the correction memory 911 and set the stored correction memory 911 to the drive parameters of the respective elements of the sensor board 500. [ Next, the predetermined program may be programmed so that the elements of each of the sensor boards 500 are driven by the drive parameters of the elements of each of the sensor boards 500 set. On the other hand, the driving parameters of the respective elements of the sensor board 500 may be parameters related to the optical characteristics of the light emitting element or the electrical characteristics generated by the light amount sensed by the light receiving element. On the other hand, when the control unit 700 generates the sensor correction data and sets the drive parameters of the respective elements of the sensor board 500 with the generated sensor correction data, the drive parameters of the set elements are subjected to the next initialization step A predetermined program can be programmed to keep each value of the sensor board 500 as a default value until then, and to drive each element of the sensor board 500 as a default value thereafter. This initialization step can compensate for the optical detection deviations of the wells through sensor correction of the respective elements of the sensor board 500, thereby increasing the accuracy of the measurement.

Meanwhile, the step of determining the measurement value of the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment is a step of determining the measurement value by converting the measured physical quantity into the cell metabolism amount according to the measurement characteristic data set for each well . The physical quantities measured by the cell metabolism measurement apparatus are those which can be measured experimentally as a physical quantity reflecting the cellular metabolism, which is an index of the degree of cellular activity that the cell metabolizes.

 The control unit 700 can convert the physical quantity measured with reference to the measurement characteristic data by executing a predetermined program into the cell metabolism quantity and determine the converted cell metabolism quantity as the measurement value. The predetermined program may be programmed to set the measurement characteristic data for each well in the initialization step. More specifically, the predetermined program may be programmed to instruct the control unit 700 to inject the well-specific standard solution for a specific substance such as dissolved oxygen or hydrogen ions for each concentration in the initialization step and to measure each of the physical quantities accordingly. have. In addition, the predetermined program may be programmed to analyze the measured physical quantity by well concentration per well concentration per well and to set the measured characteristic data on the basis of the analysis result. The predetermined program may be further programmed to store the set measurement characteristic data in the correction memory 911. [

Accordingly, in the cell metabolism measurement according to the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment, the control unit 700 refers to the measurement characteristic data stored in the correction memory 911, The measured value can be determined.

On the other hand, the predetermined program according to one aspect of the measurement value determination step may be a program for analyzing trends of the physical quantities corresponding to the concentrations of the standard solution of a specific substance and programming the resultant value as a linear or curved function, . Or a predetermined program according to another aspect of the measurement determination step may be programmed to store measurement characteristic data in the form of a look-up table.

On the other hand, the measurement characteristic data may be a data set of the dissolved oxygen concentration and the corresponding physical quantity or a set of data of the pH and the physical quantity for the data set.

FIG. 5A is a diagram illustrating a physical quantity measurement interval according to an aspect of a cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment, and FIG. 5B is a graph illustrating a measurement method of a cell metabolism measurement apparatus And a physical quantity measurement section for each well according to another aspect.

5A and 5B, the physical quantities measured according to the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment are obtained by driving the light emitting elements of the sensor board 500, Is a physical quantity related to the time required for the light receiving element sensing signal to reach the trigger level. The cell metabolism measurement method of the cell metabolism measurement apparatus according to the present invention is based on the fact that since it is difficult to accurately measure the light amount in using the optical detection technique, A method of measuring a physical quantity is used.

The physical quantity related to the time based on a certain criterion can be set according to various aspects. Among these, two aspects shown in Figs. 5A and 5B will be described as follows. Each of the y-axes of the graph shown above the graphs shown in Figs. 5A and 5B is a graph showing the waveform of the driving current signal 901, which is a kind of signal for driving the light emitting element, Each of the y-axes of the graph shown in the lower part represents the sensing signal of the light-receiving element generated by the light emitted from the light-emitting element when another light generated by the reaction of the sensor film of the micro- The waveform of the sensing current signal 902, which is a kind of the sensing current signal 902, is shown. The x-axis of each graph shown in Figs. 5A and 5B is the time domain.

First, the physical quantity related to the time based on the specific criterion shown in FIG. 5A has a starting point of a rectangular wave for driving the light emitting element as a starting point, and a trigger for determining whether or not the light receiving element sensing current is received by the light receiving element (954), the measurement delay value, which is the period from the end point of the first arrival at the level. The control unit 700 counts the physical quantity related to the time according to one aspect. The controller 700 according to an aspect may count a physical quantity related to time using a microprocessor. For example, the control unit 700 may start counting at a start point, stop counting when the end point is reached, and measure a physical quantity related to time. For example, if you measure with a counter that counts 10,000 times per second, if you count 10 times from the start point to the end point, the time related physical quantity can be 0.001 seconds or 10 times.

Next, the physical quantity related to the time based on the specific criterion shown in FIG. 5B has a falling edge of a rectangular wave for driving the light emitting element as a starting point, and determines whether or not the light receiving element sensing current is received by the light receiving element Means a measurement delay value 2 (955), which is a period that reaches the trigger level for the second time, that is, a period in which the waveform of the sensing current of the light receiving element falls in a period in which the trigger level is reached. The control unit 700 counts the physical quantity related to the time according to one aspect. The controller 700 according to an aspect may count a physical quantity related to time using a microprocessor. For example, the control unit 700 may start counting at a start point, stop counting when the end point is reached, and measure a physical quantity related to time. For example, if you measure with a counter that counts 10,000 times per second, if you count 10 times from the start point to the end point, the time related physical quantity can be 0.001 seconds or 10 times.

The physical quantities associated with a time based on a particular criterion can include two aspects, measured delay value 1 (954) or measured delay value 2 (955), shown in Figures 5A and 5B. It may also include two aspects that differ from the starting point 1 950 or the starting point 2 951 shown in FIGS. 5A and 5B and the combination of the starting point and the ending point at the end point 1 952 or the end point 2 953. However, the measurement target can be set by defining the measurement reference so that the end point does not precede the starting point.

FIG. 6 is a flowchart illustrating a method of calibrating a sensor of a cell metabolism measurement apparatus according to an embodiment of the present invention, and FIG. 7 is a flowchart illustrating a method of determining measurement characteristics of a cell metabolism measurement apparatus according to an embodiment of the present invention.

As shown in FIGS. 6 and 7, the initialization step includes a sensor correction step and a measurement characteristic determination step. The sensor correction step is a step of determining and setting sensor correction data for correcting circuit deviation and mechanical deviation of each element of the sensor board 500 through standard solution injection and measurement. The measurement characteristic determination step is a step of determining the measurement characteristics for each well through the injection and measurement of a plurality of standard solutions and setting measurement characteristic data.

 The sensor calibration step of the cell metabolism measurement method of the cell metabolism measurement device according to one embodiment may be a step progressing in the order of the flowchart of the sensor calibration method shown in FIG. The method for determining the measurement characteristics of the cell metabolism measurement apparatus of the present invention using the optical detection technique can use the dissolved oxygen concentration or the hydrogen ion concentration as an index indicating the degree of cell metabolism. In addition, a pair of light-emitting elements and a light-receiving element for wells for measurement of each indicator are separately provided in the well. Accordingly, in the sensor calibration step, the sensor calibration steps for the sensor can be performed according to the type of the indicator indicating the degree of cell metabolism. On the other hand, when the sensor correction step is divided according to the type of indicator indicating the degree of cell metabolism, the order of the progression is independent of the function of correction, and therefore, Each sensor calibration step can proceed in sequence. That is, when the cell calibration step for the standard solution of dissolved oxygen and the cell calibration step for the standard solution of the hydrogen ion concentration are carried out, the sensor calibration for the two types of cell metabolism indicators does not proceed simultaneously, Cell calibration can be performed on the standard solution followed by cell calibration for the standard solution of hydrogen ion concentration. Each calibration may be progressed from standard solution injection 913 to calibration 921 according to the sequential flow of the sensor calibration method flow chart shown in FIG.

 For example, after performing the sensor calibration step in the case where the dissolved oxygen concentration is used as an index indicating the degree of cellular metabolism, the sensor calibration step may be performed in the case of using the hydrogen ion concentration as an index indicating the degree of cellular metabolism. First, when the dissolved oxygen concentration is used as an index indicating the degree of cellular metabolism, the case of performing the sensor calibration step will be described as follows. According to the sequential flow of the sensor calibration method flow chart shown in FIG. 6, a standard solution of the dissolved oxygen concentration can be first injected into the plurality of wells of the microplate 300 (913). A standard solution of dissolved oxygen concentration can be tap water having a dissolved oxygen concentration of 17.2%. Next, the physical quantity is measured for each well after the standard solution is injected (914). Next, the correction physical quantity reference value may be calculated by calculating the well-measured physical quantities measured at the sensor-corrected physical quantity measurement 914 in accordance with a predetermined reference (913). The correction physical quantity reference value refers to a value used as a reference for correcting each of the elements of the sensor board 500 in the sensor correction step. The correction physical reference value according to one aspect may be an average of the physical quantities according to the well measured by the physical quantity measurement 914 by the control unit 700. The average of the physical quantities per well measured by the physical quantity measurement 914 by the control unit 700 may be an arithmetic average, an absolute average, or a median value. Next, whether the difference between the measured physical quantity and the calculated correction physical quantity reference value is within a predetermined correction physical quantity reference value allowable deviation range can be confirmed (916). The correction physical quantity reference value allowable deviation can be set according to various aspects. For example, the physical quantity reference value allowable deviation may be preset to x% of the corrected physical quantity reference value. In this case, whether or not the difference between the measured physical quantity and the calculated corrected physical quantity reference value is within x% of the corrected physical quantity reference value is checked in the confirmation step 916 of whether or not it is within the correction physical quantity reference value allowable deviation range. The remaining steps of the sensor correction step may be divided into the case where the difference between the next measured physical quantity and the calculated correction physical quantity reference value is within the allowable deviation range of the predetermined correction physical quantity reference value,

 First, when the difference between the measured physical quantity and the calculated correction physical quantity reference value is within a predetermined correction physical quantity reference value allowable deviation range, sensor calibration data of the well is detected by the drive parameter of each device of the sensor board 500 (918). Next, drive parameters of the respective elements of the sensor board 500 may be set with the sensor correction data generated for each element of each sensor board 500, and set to a default value until the next initialization step is performed (919 ). Next, each of the sensor elements of the sensor board 500 is driven (920) with drive parameters of the respective elements of the set sensor board 500. When the step 920 is completed, it can be regarded that the calibration is completed (921).

 If the difference between the measured physical quantity and the calculated correction physical quantity reference value does not fall within the predetermined correction physical quantity reference value allowable deviation range, it is possible to measure the physical quantity after appropriately adjusting the driving parameter for each device of the sensor board 500 917). Then, the flow returns to step 916 to check whether the measured physical quantity is within the allowable deviation of the correction physical quantity reference value (916). The next can proceed in accordance with the flow chart as shown in Fig.

 Meanwhile, a method of adjusting driving parameters for each device of the sensor board 500 such that the difference between the measured physical quantity and the calculated correction physical quantity reference value is within the predetermined correction physical quantity reference value allowable deviation range, The user inputs driving parameters of the respective elements of the sensor board 500 to the input device until the measured physical quantity is within the allowable deviation of the correction physical quantity reference while monitoring the output device.

 The method of adjusting the driving parameter for each element of the sensor board 500 such that the difference between the measured physical quantity and the calculated correction physical quantity reference value is within the allowable deviation range of the predetermined correction physical quantity reference value may be a physical quantity to be measured according to another aspect, 500) It is possible to execute a program that is otherwise programmed depending on which device-specific drive parameter is set. For example, a physical quantity to be measured is set to the physical quantity of the rising edge method shown in FIG. 5 to adjust driving parameters for each device of the sensor board 500. As a more specific example, the correction physical quantity reference value is 0.005 seconds, the physical quantity measured in the third well is 0.006 seconds, and the correction physical quantity reference value allowable deviation is 10% of the correction physical quantity. In this case, since the difference between the measured physical quantity and the correction physical quantity reference value deviates from the correction physical quantity reference value allowable deviation range, the adjustment step shown in FIG. 6 is performed. Since the measured physical quantity is larger than the corrected physical quantity reference value, the adjustment step according to one aspect is performed by appropriately adjusting such as lowering the trigger level of the light receiving element sensing current or raising the drive current value of the light emitting element, The program programmed in the recording medium 48 can be executed so that the difference is within the allowable deviation range of the correction physical quantity reference value.

Next, the sensor calibration step may be carried out when the hydrogen ion concentration is used as an index indicating the degree of cell metabolism. As shown in FIG. 6, when the hydrogen ion concentration is used as an index indicating the degree of cell metabolism, in the case where the dissolved oxygen concentration is used as an index indicating the degree of cellular metabolism, the sensor calibration step is performed in the same manner as the sensor calibration step do. However, the standard solution of the hydrogen ion concentration and the standard of the dissolved oxygen concentration may be different in the step 1 of the sensor calibration step. The apparatus for measuring cell metabolism according to the present invention is characterized in that a pair of the light emitting element and the light receiving element for measuring the dissolved oxygen concentration of the sensor board 500 vertically corresponding to each well of the microplate 300 is a light emitting element And may be different from the pair of light receiving elements. Accordingly, when the sensor calibration method of the cell metabolism measurement method of the cell metabolism measurement apparatus according to the present invention is performed, the sensor calibration process for the standard solutions of different kinds of materials to be measured is performed, It has the feature that the sensor can be calibrated by using the elements.

The measurement characteristic determination step of the cell metabolism measurement method of the cell metabolism measurement apparatus according to one embodiment may be a step proceeding according to the order of the flowchart of the measurement characteristic determination method shown in FIG. And the measurement characteristic data is set for each well in the measurement characteristic determination step. In addition, the measurement characteristic determination step may be a step subsequent to the cell correction step in the initialization step. As in the case of the sensor correction step of the controller 700, the progress of the determination of the measurement characteristic of the controller 700 may be performed by the sensor board 500 of the well, which is a device configuration for measuring and adjusting according to the index substance indicating the degree of cell metabolism Since the light emitting element and the light receiving element pair may be different, the progress of the series of measurement characteristic determination steps proceeds according to the indicator substance indicating the degree of cellular metabolism. The control unit 700 proceeds to a measurement characteristic determination step of the indicator material indicating the degree of cell metabolism according to an aspect of the present invention. The order of the indicator material indicating the degree of cell metabolism is determined in advance in the order set in the control unit 700 . ≪ / RTI >

As described above, the measurement characteristic determination step is performed after the sensor correction step is performed during the initialization step. The control unit 700 may proceed according to the flowchart shown in FIG. 7 in the course of the measurement characteristic determination step. The 'N' value shown in FIG. 7 is a value preset in the controller 700, which means 'N' of the N standard solutions having different concentrations from the standard solution performed in the sensor correction step. The 'n' value may be set to '0' in the controller 700 before the first step of the measurement characteristic determination step proceeds. 'N' may refer to the cumulative number of different concentrations of standard solution injected for determination of the measurement characteristics for a particular indicator substance representing cell metabolism. The first step of the measurement characteristic determination step may be a step 923 of injecting a standard solution of the n-th specific substance for determination of measurement characteristics into the well of the microplate 300. Further, the value of 'n' may be incremented by 1 each time the step 923 is performed. Next, measurement of the physical quantity per well may be performed after the standard solution of the n-th specific substance is injected (924). When measuring the physical quantity for each well 924, the controller 700 calculates sensor calibration data, which is the default value of the drive parameters of the respective elements of the sensor board 500 stored in the memory 910 by the respective elements of the sensor board 500, And the physical quantity at this time can be measured. Next, the physical quantity value for each well measured at 924 in the measurement of the physical quantity for each well may be stored in the correction memory 911 (925). Next, it is checked whether the 'n' value of the standard solution of the n-th specific substance for measurement property determination reaches the 'N' value. At this time, if 'n' has reached 'N', the process proceeds to the next step. If not, the process returns to the first step 923 of the measurement characteristic determination step to determine (923), (924), The process of step 926 may be performed again. When 'n' has reached 'N', the next step is to measure the physical quantity per well of the N-th specific substance standard solution from the first specific substance standard solution for determination of measurement characteristics stored in the correction memory 911, The process of setting the measurement characteristic data for each well on the basis of the physical quantity 929 may be performed (927). The physical quantity 929 measured by the well after the sensor calibration may mean the physical quantity 917 measured by the well when the cell metabolism correction step shown in FIG. 6 is completed up to step 921. Next, the process of storing the measurement characteristic data for each well, which is set in the setting 927, may be stored in the correction memory 911 (928).

The sensor correction data of the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment may be a trigger level for determining the light emitting element driving parameter and whether or not the light receiving element receives light according to an aspect. The light emitting element driving parameter may be a light emitting element driving current parameter for driving the light emitting element according to an aspect, and may be, for example, a pulse width of a current. According to another aspect, the light emitting element driving parameter may be the gain of the voltage control amplifier adjusting the current driving the light emitting element. The trigger level for determining whether light is received by the light receiving element can be determined from the sensor film in the waveform of the current generated by the reaction of the light receiving element of the sensor board 500 corresponding to the sensor film It is an indicator used as a scale.

Therefore, the sensor correction data according to an aspect of the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment is adjusted by appropriately adjusting the trigger level for determining whether the light-emitting element drive current parameter or the light- By adjusting the physical quantity until it comes within a predetermined allowable deviation so as to be close to the correction physical quantity reference value to be corrected.

FIG. 8 shows elements of a sensor board 500 and a controller 700 of a cell metabolism measurement apparatus according to an embodiment of the present invention.

As shown in FIG. 8, the cell metabolism measurement method of the cell metabolism measurement apparatus uses the amplification factor of the voltage control amplifier 905 as a driving parameter of the light emitting device 906. Since the voltage control amplifier 905 is a well-known technique, a detailed description thereof will be omitted because it may obscure the gist of the present invention. The driving parameter of the light emitting element 906 may be a driving current parameter of the light emitting element 906 according to an aspect. The light emitting device 906 may be positioned on the sensor board vertically corresponding to each well according to a specific substance to be measured in the sensor film of each well. Specific substances to be measured include, for example, dissolved oxygen or hydrogen ions. The light emitting device 906 may be a light emitting diode (LED). Power supply for driving the light emitting element 906 is required for the light emitting element 906 to emit light as shown in FIG. The driving power for the light emitting element 906 may be supplied to the light emitting element 906 through the voltage control amplifier 905. [ The control unit 700 can be manually adjusted by setting the amplification factor of the voltage control amplifier 905 to the control unit 700 through the input of the user according to an aspect of the amplification factor of the voltage control amplifier 905. [ The control unit 700 can adjust the amplification factor of the voltage control amplifier 905 by executing a program having the amplification factor of the voltage control amplifier 905 as a variable according to another aspect.

When the user directly inputs the amplification factor of the voltage control amplifier 905 to the input device to adjust the driving current parameter of the light emitting device 906, The value may vary depending on the physical quantity to be measured and the allowable deviation of the correction physical quantity reference value. For example, after the light emitting element 906 of the sensor board 500 shown in FIG. 5 is driven by a square wave, a physical quantity related to the time required for the sensing current of the light receiving element 907 of the sensor board 500 to reach the trigger level And the like. In this case, if the difference between the measured physical quantity and the correction physical quantity reference value deviates from the correction physical quantity reference value allowable deviation and the measured physical quantity is larger than the correction physical quantity reference value, the user sets the amplification rate of the voltage control amplifier 905 The sensor correction data can be generated and set so as to adjust the physical quantity downward. Of course, it is also possible to generate and set the sensor correction data by adjusting the amplification factor of the voltage control amplifier 905 as well as other parameters for driving the elements of the sensor board 500 to be described later.

 The controller 700 may include a microprocessor to adjust the gain of the voltage control amplifier 905 through a predetermined digital signal processing. For example, the digital signal processing may include a step in which the controller 700 transmits the driving current of the light emitting element 906 and the measured physical quantity to the input signal of the microprocessor. The digital signal processing includes a process of determining whether the amplification rate or the trigger level of the voltage control amplifier 905 is raised or lowered according to a preset reference based on an input signal, and setting a value of each parameter can do. In the cell metabolism measurement experiment apparatus, the control unit 700 transmits the digital signal processing signal processed by the microprocessor to the input signal of the voltage control amplifier 905 via the digital analog inverter 908, so that the gain of the voltage control amplifier 905 It is possible to include a configuration of a predetermined circuit so as to be able to adjust the voltage.

As shown in Fig. 8, the trigger level of the light receiving element 907 can be set by software in the control section 700. [ The light receiving element 907 may be positioned on the sensor board vertically corresponding to each well according to a specific substance to be measured in the sensor film 960 of each well. Specific substances to be measured include, for example, dissolved oxygen or hydrogen ions. The light receiving element 907 may be a photodiode or a phototransistor. The light receiving element 907 generates current by sensing the light emission of the sensor film 960 that emits in response to the light emission of the light emitting element 906 and driving the light receiving element 907. The apparatus for measuring cell metabolism according to one embodiment can adjust the trigger level of the light receiving element 907 by setting the trigger level of the light receiving element 907 in the controller 700 through a user's input according to one aspect. The control unit 700 of the cell metabolism measurement apparatus according to an exemplary embodiment may execute a predetermined program using a microprocessor to adjust and set a trigger level that is a measure for sensing the current generated by the light receiving element 907 . The controller 700 may further include an amplifier for amplifying a current generated by the light receiving element 907, and a waveform shaping unit for shaping the current waveform amplified through the amplifier. The waveform shaping part may be a Schmitt trigger. As is well known, the Schmitt trigger shapes the voltage of the signal to 1 and 0 by comparing it to the trigger level. In addition, the apparatus for measuring cell metabolism according to an embodiment of the present invention may be configured such that the driving current of the light receiving element 907 is converted into a digital signal by a controller (not shown) so that the controller 700 performs digital signal processing, 700 to be transmitted to the analog-to-digital converter (909). Accordingly, the control unit 700 can set the trigger level of the light receiving element 907 by transmitting the transmitted digital signal to the microprocessor and processing the digital signal according to a predetermined logic. More specifically, the control unit 700 transmits the current passed through the light receiving sensor to the microprocessor and the measured physical quantity to the input signal of the microprocessor, and outputs the trigger level of the light receiving element 907 according to a predetermined reference Can be adjusted.

The measurement characteristic data determined through the measurement characteristic determination step of the cell metabolism measurement method of the cell metabolism measurement apparatus according to one embodiment is stored as a lookup table to be referred to in the cell metabolism measurement according to one aspect.

The lookup table may be generated by modifying the measurement characteristic data generated as a result of performing step 6 of FIG. 7 by the controller 700 in the form of an unprocessed array according to an aspect. The control unit 700 of the cell metabolism measurement apparatus may compare measured physical quantities with a look-up table to determine a measured value at a concentration of a specific substance corresponding to a physical quantity having the same value. If the physical quantity equal to the measured physical quantity does not exist in the lookup table, the controller 700 can calculate the concentration of the specific substance represented by the measured physical quantity through the correction after the predetermined calculation. For example, if the measured physical quantity is x2 and x2 is the closest value to x2 and is between x1 and x3 where data is present on the look-up table, then by taking the median value, the value of (x1 + x3) / 2 By taking the corresponding y value, a measurement that is a concentration of a specific substance can be calculated and determined.

The look-up table may be obtained by processing the measurement characteristic data according to another aspect and transforming the resultant data into an array form. That is, the controller 700 analyzes the concentration of the specific substance and the trend of the corresponding physical quantity from the measurement characteristic data of each well stored in the correction memory 911 as a result of the cell metabolism measurement experiment apparatus proceeding to the measurement characteristic determination step of FIG. An array of lookup tables can be created as a result.

FIG. 1 is a perspective view of an apparatus for measuring cell metabolism according to an embodiment of the present invention, FIG. 2 is a perspective view of the interior of the housing of the apparatus for measuring cell metabolism shown in FIG. 1, FIG. 4 is a block diagram showing a microplate 300 and a sensor board 500 of a cell metabolism measurement apparatus according to an embodiment of the present invention. And FIG. 9 is a block diagram of a program of an apparatus for measuring cell metabolism according to an embodiment.

1 and 2, the apparatus for measuring cell metabolism according to an embodiment includes an XY driving stage table 400, a microplate 300, a sensor board 500, a cartridge 100, a drug injector 200, and a control unit 700.

The number of the cartridges 100 may be plural. Or one, and can be physically partitioned to have a plurality of accommodation spaces. In one embodiment, at least one mounting hole 12 for mounting the cartridge 100 is formed on the housing 10, and the cartridge 100 in which the medicine is accommodated is mounted in the mounting hole 12. As shown in FIG. 1, the mounting holes 12 may be four, and the cartridges 100 may be mounted in the respective mounting holes 12. The housing 10 may include a hole cover 13 for covering the mounting hole 12.

Each of the cartridges 100 may contain a plurality of medicines. The cartridge 100 can also accommodate different medications. The user can select drugs to be used in the experiment for each cartridge 100. Drugs include Oligomycin, 2,4-Diprophenol (2,4-DNP) or Carbonylcyanide-p-trifluourmethoxyphenylhydrazone (FCCP) , And Antimycin A, and the like. The cartridges 100 are connected to the drug injectors 200 by piping, and supply the medicines to the positionally fixed drug injector 200 through the piping.

The injector 200 is configured to inject the drug of the cartridge 100 into the well and may be a plurality of injectors. That is, the drug injector 200 is a structure for injecting the drug into the well of the microplate 300. In one embodiment, drug injector 200 is a syringe pump with a three-way valve. The number of the drug injectors 200 is plural, which is equal to the number of the cartridges 100 or the number of physically partitioned accommodation spaces. The drug injectors 200 are connected to the cartridges 100 in a one-to-one correspondence with the piping. In one embodiment, drug injector 200 is a syringe pump with a three-way valve. The drug injector 200 receives and holds the drug from the cartridge 100 through the piping, and discharges the held drug.

The X-Y driving stage table 400 is a table movable together with the X-axis and Y-axis, that is, the horizontal up-down and left-right direction in accordance with the driving of the X-Y driving stage in unison with the X-Y driving stage. Therefore, the microplate 300 can move along the X and Y axes. By moving and controlling the XY driving stage table 400, the specific well 310 of the microplate 300 can be moved to any one of the drug injectors 200 It can be placed in one subordinate. This means that the desired drug can be injected automatically per well 310. In addition, stirring can be naturally performed in the well 310 according to the movement of the X-Y driving stage table 400. Therefore, the control unit 700 may control the movement of the X-Y driving stage table 400 for the purpose of stirring. In addition, after the cell metabolism measurement apparatus tests the XY driving stage table 400 so as to perform the bio-chemical reaction in the well for a predetermined time after injecting the predetermined drug for each well, the XY driving stage table 400 measures It is possible to control the movement to be located at the position. Alternatively, the control unit 700 may move the X-Y driving stage table 400 to the measurement position in advance. For example, in order to determine a sensor calibration or measurement characteristic, such as an initialization step, the controller 700 may move the X-Y drive stage table 400 to a measurement position in advance. Then, the controller 700 may control the movement of the X-Y driving stage table 400 to the reference position or may leave the measuring position as it is. Then, the operation can be continued until all the measurements are completed according to the well-customized protocol. The well-defined custom protocol is information for automatically performing the measurement process for each well. The well-customization protocol may include user-defined drug doses, drug types, and post-drug latency information predefined by the user. According to one aspect, the cell culture experimental apparatus may further include a graphical user interface that supports well-defined user-specific protocol inputs. The user can set the well-defined user-defined protocol through the graphical user interface. Meanwhile, the controller 700 may perform position control for recognizing a reference position of the X-Y driving stage table 400 before performing control according to a user-defined protocol. For example, the control unit 700 recognizes the reference position using a limit switch of the X-Y driving stage. Since such a position recognition technique is widely known, a detailed description thereof will be omitted.

The microplate 300 includes a plurality of wells having sensor films, and is mounted on the XY driving stage table. The microplate 300 may have a sensor film on its bottom surface according to one aspect. The microplate 300 includes a plurality of wells 310, wherein the number of wells may be 6, 12, 24, 48, 96, and so on. Each well 310 accommodates cells and includes both a sensor membrane 311 for detecting dissolved oxygen (DO) and a sensor membrane 312 for detecting pH. The sensor film for DO detection and the sensor film for pH detection may be a fluorescent sensor film coated with a fluorescent dye. The ruthenium complex (tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II), Ru (dpp) ₃ ²⁺ ) can be used as the fluorescent dye of the sensor film for DO detection. As fluorescent dyes, hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) can be used.

The ruthenium complex (Rudpp) generates strong fluorescence in the fluorescent dye for oxygen detection and has a long quantum yield and long fluorescence lifetime. Detection of dissolved oxygen using a ruthenium complex uses the principle of fluorescence attenuation by molecular oxygen, which consumes the energy released by the oxygen molecule as a result of the emission of fluorescent dye falling to the ground state as a result of excitation. The fluorescence intensity is decreased. Decreasing fluorescence intensity is inversely proportional to the concentration of oxygen molecules. In other words, the ruthenium complex is excited by light at 480 nm and is converted to a ground state, emitting 510 nm fluorescence. And the HPTS used for pH detection can generate strong fluorescence and is not toxic. Fluorescent pH detection utilizes the principle that fluorescence occurs when a fluorescent dye is quantized or unquantized by acid or alkali. When irradiated with light of 405 nm, HPTS absorbs electrons, excites them, and converts them to a ground state, emitting 510 nm fluorescence.

The sensor board 500 is arranged so that the measurement sensor including the light emitting element 906 and the light receiving element corresponds to the sensor film. The sensor board 500 may be mounted on the sensor housing 20 and integrally provided on the X-Y driving stage table 400. The microplate 300 is positioned on the sensor board 500. 4, the sensor board 500 includes a pair of DO detection light emitting devices 522 vertically corresponding to the sensor film for DO detection provided for each well 310 of the microplate 300 And a light receiving element 511 that includes a pair of pH detecting light emitting elements 521 vertically corresponding to the sensor film for pH detection provided for each well 310 have. A light emitting diode (LED) may be used as the light emitting element, and a photodiode or a phototransistor may be used as the light receiving element. When the DO detection light emitting element 522 irradiates light, the DO detection fluorescence sensor film emits fluorescence, so that the DO detection light receiving element 512 receives the emitted fluorescence. When the pH detecting light emitting device 521 is irradiated with light, the pH detecting fluorescent sensor film emits fluorescence, so that the pH detecting light receiving device 511 receives the emitted fluorescence.

1 and 2, the control unit 700 drives the X XY driving stage table 400 to move the microplate 300 relative to the measurement position at which the optical measurement is performed or to the measurement position where the optical measurement is performed, The driving parameter of each element of the sensor board 500 is set by the sensor correction data set for each element of the sensor board 500 and the driving parameter of each element And a program 49 including measurement value determination commands 51 for determining a measurement value by converting the measured physical quantity into a cell metabolism quantity in accordance with measurement characteristic data set for each well ) To access the recording medium 48 and controls the apparatus by executing the program 49. [

 As shown in FIG. 9, the apparatus for measuring cell metabolism according to an embodiment can set a predetermined command to the controller 700 through a user input / output unit according to an aspect.

That is, the control unit 700 accesses and fetches and executes the predetermined programs 49 constituted by the initialization commands 50 or the measurement value determination commands 51 stored in the recording medium according to the user's input, The initialization step or the measurement value determination step according to the cell metabolism measurement method of the cell metabolism measurement apparatus can be performed. In addition, according to another aspect of the present invention, the cell metabolism measurement apparatus can automatically cause the controller 700 to perform the initialization step or the measurement value determination step according to predetermined conditions in the controller 700 without inputting the user. The predetermined condition in the control unit 700 may be a default value of the drive parameter of each element of the sensor board 500 stored in the correction memory 911 or a user defined protocol stored in the user defined protocol memory 912 have. The control unit 700 connects to the predetermined programs 49 constituted by the initialization commands 50 or the measurement value determination commands 51 stored in the recording medium according to predetermined conditions and outputs the initialization commands 50 or The measurement value determination commands 51 may be fetched and executed to advance the initialization step or the measurement value determination step.

Meanwhile, the initialization command of the cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment sets drive parameters of the respective elements of the sensor board 500 as sensor correction data for each device of the sensor board 500 And may be a command for driving each of the sensor elements as a driving parameter of each of the set elements. The control unit 700 accesses the initialization commands 50 connected in accordance with the logical flow stored in the program 49 of the recording medium 48 and fetches the initialization commands 50 So that the initialization steps can be performed by executing the initialization instructions 50. [ The initialization means to reset the driving characteristics of the sensor board 500. The optical characteristics of the respective elements of the sensor board 500 are susceptible to change by movement of the microplate 300 or over time. Therefore, the cell metabolism measurement apparatus needs to recalibrate the optical characteristic deviations of the respective elements of the sensor board 500 according to predetermined conditions before actual measurement of the wells of the microplate 300 is performed.

In the cell metabolism measurement experiment apparatus according to one aspect, the user can input the condition for executing the initialization command through the touch screen module or the input device, and the controller 700 can set the command execution condition in the controller 700. For example, the initialization command execution condition can be set in the control unit 700 so that the initialization command is executed before execution of each cell metabolism measurement experiment. As another example, when the cell metabolism measurement apparatus has calibrated the individual elements of the sensor board 500, when the predetermined number of experiments corresponding to the number of times that the optical characteristic deviation becomes more than the reference value again, To the control unit 700 so as to execute the program.

On the other hand, the initialization command can be executed for all the wells of the microplate 300. Or the degree of change in sensor characteristics of each device of the sensor board 500 is monitored based on the sensor correction data generated every time the cell metabolism measurement apparatus performs sensor correction, Only the wells may cause the control unit 700 to execute the initialization command.

 On the other hand, the sensor correction data is data generated by the control unit 700 or the user in a predetermined process for each element constituting the sensor board 500 in the initialization step. The apparatus for measuring cell metabolism according to an embodiment may include a predetermined input device and an output device according to an aspect. The user can monitor the physical quantity measured by the well through the output device. Also, the user manually inputs the sensor calibration data through an input device of the cell metabolism measurement test apparatus, for example, a touch screen or a keyboard, referring to the sensor calibration data generation guide data generated through the experiments performed in advance, To adjust the driving parameters of each element of the sensor board 500 to generate sensor correction data.

The control unit 700 of the cell metabolism measurement apparatus according to an exemplary embodiment of the present invention may perform the process of generating sensor correction data according to an aspect by connecting the predetermined program 49 of the recording medium 48 and executing one or more commands . For example, in a predetermined program 49 of the recording medium 48, until the deviation between the calculated correction physical quantity reference value and the physical quantity measured for each well falls within the range of the predetermined correction physical quantity reference value allowable deviation, May be pre-programmed to adjust the drive parameters of the devices. The driving parameter of each of the elements of the sensor board 500 may be a parameter related to the optical characteristic of the light emitting element or the electrical characteristic generated by the light amount sensed by the light receiving element.

On the other hand, the control unit 700 can execute the predetermined program 49 of the recording medium 48 to generate the sensor correction data, and then store the sensor correction data in the correction memory 911. [ Further, the controller 700 may set the sensor correction data stored in the correction memory 911 as the drive parameters of the elements of the sensor board 500. The control unit 700 can drive the elements of the sensor board 500 according to driving parameters of the elements of the sensor board 500.

On the other hand, the predetermined program 49 of the recording medium 48 executed by the control unit 700 stores the stored sensor correction memory 911 in the memory of the respective elements of the sensor board 500 until the next initialization step It can be pre-programmed to keep its value as the default of the drive parameters and drive each element of the sensor board 500 in the physical quantity measurement to the value stored in the sensor correction memory 911 which is the default value. The execution of such an initialization command can compensate the optical detection deviations of each well of the sensor board 500 through calibration, thereby increasing the accuracy of measurement.

Meanwhile, the measurement value determination command of the cell metabolism measurement apparatus according to an embodiment is a command to determine a measurement value by converting the measured physical quantity into a cell metabolism amount referring to measurement characteristic data set for each well. The physical quantities measured by the cell metabolism measurement apparatus are those which can be measured experimentally as a physical quantity reflecting the cellular metabolism, which is an index of the degree of cellular activity that the cell metabolizes.

On the other hand, the measurement value determination commands 51 may include a series of measurement-related commands related to the cell metabolism measurement. The measurement value determination commands 51 may include a drug injector movement command, a measurement position movement command, a sensor correction data application command, a physical quantity measurement related command, a cell metabolism measurement value calculation command, and the like. The drug injector movement command may be an instruction related to moving the X-Y driving stage table 400 to the drug injector. Also, the measurement position movement command may be an instruction related to moving the X-Y driving stage table 400 to the measurement position. The sensor calibration data apply command may be an instruction that the controller 700 accesses the memory 910 and applies the sensor calibration data to a predetermined variable of the program 49 of the recording medium 48. [ The physical quantity measurement related command may be a command related to measuring physical quantity. Also, the command to calculate the cell metabolism measurement value may be an instruction related to determining the measured value by converting the measured physical quantity into the cell metabolism quantity according to the set measurement data. According to an aspect, the controller 700 may perform a cell metabolism measurement by executing a program 49 configured to sequentially execute the instructions in accordance with a user defined protocol. For example, when the control unit 700 executes the cell metabolism measurement command, it executes a drug injector movement command to place a specific well of the microplate 300 at a specific drug injector 200 position according to a user-defined protocol, Can be injected into the well. Next, the control unit 700 executes a measurement position movement command to move the XY driving stage table to the microplate 300 injected with the drug at the measurement position after the measurement wait time has elapsed, and then perform the cell metabolism measurement for the specific well Can be performed. Next, the controller 700 executes the initialization command by executing the sensor correction data application command, and executes the initialization command by executing the sensor calibration data applying command to the sensor board 500 in accordance with the drive parameter of each element of the sensor board 500 stored in the correction memory 911 To drive the devices. Then, the control unit 700 can execute the physical quantity measurement related command and measure the physical quantity of the corresponding well. Finally, the control unit 700 can calculate the metabolism amount of cells by referring to the measurement characteristic data stored in the correction memory 911 by measuring the physical quantity of the corresponding well measured by executing the cell metabolism measurement value calculation command.

On the other hand, the control unit 700 can execute the predetermined program 49 of the recording medium 48 constituted by the initialization commands 50 to set the measurement characteristic data for each well. More specifically, the predetermined program 49 of the recording medium 48 executes the initialization commands 50 to measure the physical quantity according to the standard solution concentration of the specific substance for each well, Lt; / RTI > Certain materials may be dissolved oxygen or hydrogen ions. More specifically, the predetermined program 49 of the recording medium 48 is an initialization unit for analyzing the trends of the data of the concentrations of the standard solution of the specific substance and the corresponding physical quantities for each well and setting the analysis result as measurement characteristic data May be programmed to consist of instructions (50). The control unit 700 can also store the measurement characteristic data set by executing the initialization instructions 50 of the predetermined program 49 of the recording medium 48 in the correction memory 911. [ The cell metabolism measurement apparatus according to an embodiment can determine the measured value by converting the measured physical quantity into the cell metabolism amount by referring to the measurement characteristic data stored in the correction memory 911 during the cell metabolism measurement.

Meanwhile, the measurement value determination commands 51 may be programmed to store measured characteristic data in the form of a linear or curved function as a result of analyzing trends of physical quantities corresponding to concentrations of a standard solution of a specific substance according to an aspect. . Or measurement determination commands 51 may be programmed to store measurement characteristic data in the form of a look-up table according to another aspect. On the other hand, the measurement characteristic data may be a data set of the dissolved oxygen concentration and the corresponding physical quantity or a set of data of the pH and the physical quantity for the data set.

FIG. 5A is a diagram illustrating a physical quantity measurement interval according to an aspect of a cell metabolism measurement method of the cell metabolism measurement apparatus according to an embodiment, and FIG. 5B is a graph illustrating a measurement method of a cell metabolism measurement apparatus And a physical quantity measurement section for each well according to another aspect.

FIG. 10 is a block diagram of the measurement value determination commands 51 of the cell metabolism measurement apparatus according to an embodiment.

The measurement value determination commands 51 of the cell metabolism measurement apparatus according to one embodiment are related to the time required for the light receiving element sensing signal to reach the trigger level after driving the light emitting element as shown in Figs. 5A and 5B And a physical quantity measurement command (52) for measuring a physical quantity. The signal for driving the light emitting element can be a spherical file according to an aspect. Further, the sensing signal of the light receiving element may be a sensing current according to an aspect. As shown in FIG. 10, the apparatus for measuring cell metabolism according to an embodiment may allow the controller 700 to execute a predetermined command through a user input / output unit according to an aspect. That is, the control unit 700 connects to predetermined programs 49 constituted by the physical quantity measurement command word 52 stored in the recording medium according to the user's input, fetches and executes the physical quantity measurement command 52, You can proceed. In addition, according to another aspect of the present invention, the cell metabolism measurement apparatus can automatically cause the controller 700 to perform the physical quantity measurement according to predetermined conditions in the controller 700 without inputting the user. The predetermined condition in the control unit 700 may be a user-specified protocol stored in the memory 910. [ The control unit 700 can connect to the predetermined programs 49 constituted by the physical quantity measurement command word 52 stored in the recording medium according to predetermined conditions, fetch and execute the program, and proceed with physical quantity measurement.

The physical quantities associated with a time based on a particular criterion can include two aspects, measured delay value 1 (954) or measured delay value 2 (955), shown in Figures 5A and 5B. It may also include two aspects that differ from the starting point 1 950 or the starting point 2 951 shown in FIGS. 5A and 5B and the combination of the starting point and the ending point at the end point 1 952 or the end point 2 953. However, the measurement target can be set by defining the measurement reference so that the end point does not precede the starting point.

FIG. 11 shows a block diagram of the initialization commands 50 of the cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 11, the initialization commands 50 of the cell metabolism measurement apparatus according to an embodiment include sensor correction commands 60 and measurement characteristic determination commands 90. The sensor calibration instructions 60 are instructions for determining and setting sensor calibration data to correct for circuit deviations and mechanical deviations of the respective elements of the sensor board 500 through standard solution injection and measurement. The measurement characteristic determination commands 90 are commands for setting measurement characteristic data by determining measurement characteristics for each well through injection and measurement of a plurality of standard solutions.

As shown in FIG. 11, the apparatus for measuring cell metabolism according to an exemplary embodiment may control the controller 700 so that the controller 700 executes predetermined commands through a user input / output unit according to an aspect. That is, the control unit 700 connects to predetermined programs 49, which are composed of sensor correction commands 60 or measurement characteristic determination commands 90 stored in the storage medium according to the input of the user, The sensor calibration step or the measurement characteristic determination step of the cell metabolism measurement method of the cell metabolism measurement apparatus according to one embodiment can be manually performed by fetching and executing the measurement characteristic determination command 90 or the measurement characteristic determination command 90. [ In addition, according to another aspect of the present invention, the control unit 700 may automatically set the control unit 700 in accordance with a predetermined condition in the control unit 700, The correction step or the measurement characteristic determination step may be performed. The predetermined condition in the control unit 700 may be a user-specified protocol stored in the user-defined protocol memory 912 according to an aspect. The control unit 700 may perform a cell metabolism measurement experiment according to a predetermined condition, for example, and may automatically perform an initialization step before the experiment of the microplate 300 according to a predetermined setting of the controller 700. [ The control unit 700 is connected to predetermined programs 49 constituted by the sensor correction commands 60 or the measurement characteristic determination commands 90 stored in the recording medium when the controller 700 proceeds to the initialization step, (60) or the measurement characteristic determination commands (90) to execute the sensor correction step or the measurement characteristic determination step.

The sensor calibration instructions 60 of the cell metabolism measurement device according to one embodiment may be the instructions which are progressed in the order of the flowchart of the sensor calibration method shown in FIG. On the other hand, the method for determining the measurement characteristics of the cell metabolism measurement apparatus of the present invention using the optical detection technique uses dissolved oxygen concentration or hydrogen ion concentration as an index indicating the degree of cell metabolism. In addition, a pair of light-emitting elements and a light-receiving element for wells for measurement of each indicator are separately provided in the well. Therefore, when the sensor correction command is executed, it can be classified according to the kind of indicator indicating the degree of cell metabolism. Since the order of forward and backward processes is independent of the function of correction in dividing the sensor correction command in accordance with the type of index indicating the degree of cell metabolism, Each sensor calibration step can proceed. In other words, if a cell correcting command is performed on an indicator indicating the degree of two types of cell metabolism, the sensor calibration for two types of cell metabolism indicators is not performed simultaneously. For example, Proceed with the cell calibration for a standard solution of hydrogen ion concentration. Each calibration may be progressed from standard solution injection 913 to calibration 921 according to the sequential flow of the sensor calibration method flow chart shown in FIG. The execution of the sensor correction command according to another aspect may be performed by selecting between dissolved oxygen concentration and hydrogen ion concentration as an index indicating the degree of cellular metabolism according to user specification.

As an example of the execution of the sensor correction command, a sensor correction command when the hydrogen ion concentration is used as an index indicating the degree of cell metabolism after executing the sensor correction command in the case of using the dissolved oxygen concentration as an index indicating the degree of cell metabolism . First, a description will be made of a case where the sensor correction command is executed when the dissolved oxygen concentration is used as an index indicating the degree of cell metabolism. The sensor calibration commands 60 include standard solution injection command 930, well physical quantity measurement command 931, correction physical quantity reference value calculation command, sensor calibration necessity confirmation command 933, adjustment of the driving parameter of the sensor board element, Measurement command 934, sensor calibration data generation and storage and drive command 935, and the like. These can be explained in correspondence with the respective steps of the sensor correction method shown in Fig. That is, the standard solution injection command 930 is sent to the standard solution injection step 913 of the sensor correction step, the well physical quantity measurement command 931 to step 914, and the correction physical quantity reference value calculation command 932 to step 915 , The sensor calibration necessity confirmation command 933 is sent to step 916 and the adjustment of the driving parameter of the sensor board element and the physical quantity measurement command 934 are executed in step 917. In step 917, 935) may correspond to steps {918, (919), and (920)}. When the control unit 700 executes the program 49 including the sensor correction commands 60, the order of execution of the respective commands may be the same as that of the sensor correction method of FIG. 6 corresponding thereto. That is, when the program 49 including the sensor correction instructions 60 is executed, the first instruction to be executed is the standard solution injection instruction 930. A standard solution of dissolved oxygen concentration can be tap water having a dissolved oxygen concentration of 17.2%. The next instruction to be executed is the well-specific physical quantity measurement command 931. That is, by executing the physical quantity measurement instruction 931 for each well, a physical quantity representing the dissolved oxygen concentration is measured for each well. The next instruction to be executed is a correction physical quantity reference value calculating instruction. The corrected physical quantity reference value can be calculated through calculation according to a predetermined criterion of the physical quantities of the wells measured as a result of execution of the physical quantity measurement instruction word 931 in the sensor correction step by executing the correction physical quantity reference value calculation instruction. The correction physical quantity reference value refers to adjusting each of the elements of the sensor board 500 when adjusting a driving parameter of a sensor board element to be described later and executing a physical quantity measurement command 934, . The correction physical reference value according to one aspect may be an average of physical quantities per well measured by the control unit 700 executing the physical quantity measurement instruction 931 for each well. The average used may be an arithmetic average, an absolute average, or a median. Next, the execution of the sensor correction necessity confirmation command 933 can perform an operation of checking whether the difference between the measured physical quantity and the calculated correction physical quantity reference value is within the predetermined correction physical quantity reference value allowable deviation range. The correction physical quantity reference value allowable deviation can be set according to various aspects. For example, the physical quantity reference value allowable deviation may be preset to x% of the corrected physical quantity reference value. In this case, the execution of the sensor correction necessity confirmation command 933 can check whether or not the difference between the measured physical quantity and the calculated correction physical quantity reference value is within x% of the correction physical quantity reference value. The remaining commands of the sensor correction commands 60 can be executed by dividing the difference between the next measured physical quantity and the calculated corrected physical quantity reference value into a predetermined correction physical quantity reference value allowable deviation range or not.

 First, in the case of a well in which the difference between the measured physical quantity and the calculated correction physical quantity reference value is within the predetermined correction physical quantity reference value allowable deviation range, the sensor correction data generation and storage and drive instruction 935 is executed. That is, by executing the physical quantity measurement command 931 for each well, the drive parameters for each element of the sensor board 500 at the time of measuring the physical quantity can be generated as the sensor correction data of the well. The execution of the sensor correction data generation and storage and drive command 935 is followed by sensor correction data generation and storage and drive command 935 and sensor correction data generated by the sensor board 500 The driving parameter of each element of the sensor board 500 may be set to a default value until the initialization step is advanced. Further, the execution of the sensor correction data generation and storage and drive command 935 can drive the respective sensor elements of the sensor board 500 as drive parameters of the respective elements of the sensor board 500 set.

 When the difference between the measured physical quantity and the calculated reference value of the correction physical quantity does not fall within the allowable deviation range of the predetermined correction physical quantity reference value, the drive parameter of the sensor board 500 is appropriately adjusted, The adjustment of the drive parameters and the physical quantity measurement command 934 can be executed. Then, the sensor calibration necessity confirmation command 933 for confirming whether the measured physical quantity is within the allowable deviation of the correction physical quantity reference value is executed again. 6, when the measured physical quantity is out of the allowable deviation of the correction physical quantity reference value, the sensor correction necessity confirmation command 933 is issued again, To execute the instructions corresponding to each of the sensor correction steps described above in accordance with the flowchart shown in Fig.

 On the other hand, according to an aspect of the present invention, a method of adjusting drive parameters for each device of the sensor board 500 such that the difference between the measured physical quantity and the calculated correction physical quantity reference value falls within a predetermined correction physical quantity reference value tolerance range. The output device of the cell metabolism measurement apparatus according to the cell metabolism measurement apparatus according to an embodiment of the present invention is monitored and repeated until the measured physical quantity is within the allowable deviation of the reference value of the corrected physical quantity, 500 are repeatedly set and adjusted.

The method of adjusting the driving parameter for each element of the sensor board 500 such that the difference between the measured physical quantity and the calculated correction physical quantity reference value is within the allowable deviation range of the predetermined correction physical quantity reference value may be a physical quantity to be measured according to another aspect, 500 may be programmed into the program 49 of the recording medium 48 depending on which device-specific drive parameter is set. For example, the physical quantity to be measured is set to the physical quantity of the rising edge method shown in FIG. 5, and the driving parameter for each device of the sensor board 500 is adjusted. As a more specific example, the correction physical quantity reference value is 0.005 seconds, the physical quantity measured in the third well is 0.006 seconds, and the correction physical quantity reference value allowable deviation is 10% of the correction physical quantity. In this case, since the difference between the measured physical quantity and the corrected physical quantity reference value deviates from the corrected physical quantity reference value allowable deviation range, it is possible to execute the adjustment of the drive parameter and the physical quantity measurement command 934 shown in Fig. Adjustment of the driving parameter of the sensor board element according to one aspect and execution of the physical quantity measurement command 934 are performed by lowering the trigger level of the light-receiving element sensing current or decreasing the driving current value of the light-emitting element because the measured physical quantity is larger than the correction physical quantity reference value The difference between the measured physical quantity and the correction physical quantity reference value can be made to fall within the correction physical quantity reference value allowable deviation range.

Next, the sensor correction commands 60 may be performed when the hydrogen ion concentration is used as an index indicating the degree of cell metabolism. As shown in FIG. 6, when the hydrogen ion concentration is used as an index indicating the degree of cell metabolism, the sensor calibration step is performed in the same manner as the sensor calibration step when the dissolved oxygen concentration is used as an index indicating the degree of cellular metabolism . In other words, in the cell metabolism measurement experiment apparatus according to the present invention, the pair of the light emitting element and the light receiving element for measuring the dissolved oxygen concentration of the sensor board 500 vertically corresponding to each well of the microplate 300 measures the hydrogen ion concentration The light emitting element and the light receiving element may be different from each other. When the pair of the light emitting element and the light receiving element adjusted and driven by the execution of the sensor correction command in the case of using the hydrogen ion concentration as an index indicating the degree of cellular metabolism is used as an index indicating the degree of cellular metabolism The pair of the light emitting element and the light receiving element adjusted and driven by the execution of the sensor correction command may be different. Further, the standard solution of the hydrogen ion concentration and the dissolved oxygen concentration to be injected into the well may be different when the control unit 700 executes the standard solution injection command. Accordingly, when the sensor calibration method of the cell metabolism measurement method of the cell metabolism measurement apparatus according to the present invention is performed, the sensor calibration process for the standard solutions of different kinds of materials to be measured is performed, It has the feature that the sensor can be calibrated by using the elements.

The measurement characteristic determination commands 90 of the cell metabolism measurement apparatus according to an exemplary embodiment may be the commands that the controller 700 executes in accordance with the flowchart of the measurement characteristic determination method shown in FIG. The execution of the measurement characteristic determination commands 90 is characterized in that the measurement characteristic data is executed for each well. The measurement characteristic determination commands 90 are commands for executing the cell correction commands of the initialization commands 50 and then executing them. The execution of the measurement characteristic determination commands 90 of the control unit 700 is performed in the same manner as the execution of the sensor correction commands 60 of the control unit 700, Since the light emitting element and the light receiving element pair of the well-specific sensor board 500 may be different, the execution of the series of measurement characteristic determination commands 90 is divided according to the indicator substance indicating the degree of cellular metabolism. In order to implement the measurement characteristic determination commands 90 for the indicator substance indicating the degree of cell metabolism, the control unit 700 determines the order according to the indicator substance indicating the degree of cell metabolism in accordance with the built-in program 49 It can proceed in order.

Execution of the measurement characteristic determination commands 90 as described above is executed after executing the sensor correction commands 60 of the initialization commands 50. [ The 'N' value shown in FIG. 7 may be 'N' of the N standard solutions having different concentrations from the standard solution when the sensor correction command is executed with the preset value to the controller 700. The 'n' value may be set to '0' in the controller 700 before the first step of the measurement characteristic determination step proceeds. 'N' may refer to the cumulative number of different concentrations of standard solution injected for determination of the measurement characteristics for a particular indicator substance representing cell metabolism. The measurement characteristic determination commands 90 may include instructions corresponding to the respective steps of the flowchart shown in FIG. The measurement characteristic determination commands 90 include an nth standard solution injection command 940 for determination of measurement characteristics, a physical quantity measurement command for each well, a physical quantity storage command 942 for each well, an additional standard solution injection and measurement confirmation command 943, Characteristic data setting command 944, measurement characteristic data storing command 945 for each well, and the like. The n-th standard solution injection command 940 for determining the measurement characteristic includes the step 923 of the measurement characteristic determination method, the measurement command for the well for the measurement of the property 924 of the measurement characteristic determination method, The method step 925 and the additional standard solution injection and measurement confirmation command 943 are executed in the step 926 of the measurement characteristic determination method and the measurement characteristic data setting command 944 in the well are determined in the step 927 of the measurement characteristic determination method, The well-specific measurement characteristic data storage command 945 may correspond to the measurement characteristic determination method step 928. [ When the control unit 700 executes the program including the measurement characteristic determination commands 90, the execution order of each of the instructions may be the same as that of the measurement characteristic determination method of FIG. 7 corresponding thereto. That is, when the program 49 including the measurement characteristic determination commands 90 is executed, the first instruction executed may be the nth standard solution injection command 940 for determining the measurement characteristics. The control unit 700 is configured to execute the n-th standard solution injection command 940 for determination of the measurement characteristics so as to execute the injection of the standard solution of the n-th specific substance for measurement characteristic determination into the well of the microplate 300 It is a standard solution injection instruction of the n-th specific substance. Further, the value of 'n' may be incremented by 1 each time the step 923 is performed. The next instruction to be executed may be the well-to-well physical quantity measurement command 1 (941). The control unit 700 determines whether or not each element of the sensor board 500 is a sensor correction value that is a default value of a drive parameter of each element of the sensor board 500 stored in the correction memory 911, It can be driven according to the data. The next instruction to be executed may be a command for storing the physical quantity per well measured by the well physical quantity measurement instruction 1 (941) in the correction memory 911 by the well physical quantity storage instruction 942. [ The next instruction to be executed may be an instruction to confirm whether the 'n' has reached the 'N' value with the additional standard solution injection and measurement confirmation command 943. If the control unit 700 determines that 'n' reaches 'N' when executing the additional standard solution injection and measurement confirmation command 943, it executes the fifth instruction of the measurement characteristic determination commands 90, It is possible to return to the first command of the measurement characteristic determination commands 90. [ Therefore, in this case, it is possible to execute the above-described instructions corresponding to the steps of (923), (924), (925), and (926) according to the flowchart shown in the flowchart of the measurement characteristic determination method of FIG. If the control unit 700 determines that 'n' has reached 'N' as a result of executing the additional standard solution injection and measurement confirmation command 943, the instruction to be executed is the well-specific measurement characteristic data setting command 944. The control unit 700 executes the measurement characteristic data setting command 944 for each well to calculate the well specific physical quantity of the N-th specific substance standard solution from the first specific substance standard solution for measurement characteristic determination, which is stored in the correction memory 911, The measurement characteristic data for each well can be set based on the physical quantity measured by the well obtained by executing the measurement data 60 for the well. The next instruction to be executed is the measurement characteristic data storing instruction 945 for each well. The control unit 700 can store the well-specific measurement characteristic data set in the well-specific measurement characteristic data setting command 944 in the correction memory 911 by executing the well-specific measurement characteristic data storing command word 945. [

On the other hand, when the sensor correction commands 60 are executed, the operation of the apparatus can be described. First, the apparatus for measuring cell metabolism according to an embodiment of the present invention may be configured such that when a user inputs or when a predetermined initialization step execution step is started in the control unit 700, (49) and fetch and execute a series of initialization commands (50). First, the control unit 700 can execute the standard solution injection command. At this time, the control unit 700 of the cell metabolism measurement apparatus may execute a drug injector movement command to move the X-Y driving stage table 400, on which the microplate 300 is mounted, to the drug injector. It is also possible to inject the standard solution into the predetermined well by executing other operation related commands of the program 49 including the drug injector movement command. At this time, the controller 700 controls the drug injector 200 so that the drug injector corresponding to the cartridge 100 accommodating the standard solution for performing the sensor correction step in one-to-one correspondence injects the drug into the target well . Then, the control unit 700 may move the X-Y driving stage table 400 to the measurement position by executing a measurement position movement command after a pre-measurement waiting time after the predetermined drug injection. Next, the control unit 700 can execute the physical quantity measurement command 1 (941) for each well to advance the physical quantity measurement to the predetermined well, for example, the user specified well. If the control unit 700 executes the physical quantity measurement command 1 (941) according to one aspect, it can execute the sensor calibration data application command that may be logically connected to the physical quantity measurement command 1 (941) per well. The controller 700 executes the sensor calibration data application command so that the controller 700 accesses the memory 910 and applies the sensor calibration data to the sensor board of the program 49 of the recording medium 48 . Accordingly, the control unit 700 may proceed to drive the sensor board 500 before measuring a physical quantity, which will be described later, or to prepare a value for setting a value for measuring a physical quantity. The control unit 700 may proceed to the remaining step of executing the well-to-well physical quantity measurement command 1 (941) of the control unit 700 after completing the preparation step of the physical quantity measurement. That is, the cell metabolism measurement experiment apparatus can perform the physical quantity measurement on the well to be measured by applying the sensor correction data. Next, the control unit 700 executes a correction physical quantity reference value calculation instruction to calculate a corrected physical quantity reference value based on the measured physical quantities as a result of execution of the physical quantity measurement instruction word by the well, The correction physical quantity reference value can be calculated using the apparatus. Next, the control unit 700 may execute the sensor correction necessity confirmation command 933 to check whether the measured physical quantity is within the correction physical quantity reference value allowable deviation. If the measured physical quantity as a result of executing the sensor calibration necessity confirmation command (933) is within the allowable deviation of the correction physical quantity reference value, the sensor correction data generation and storage and drive command (935) Command 934 can be executed. The control unit 700 adjusts the driving parameter of the sensor board 500 according to a preset reference when adjusting the driving parameter of the sensor board device and the physical quantity measurement command 934, It is possible to execute the necessity confirmation command (933) to determine whether to add the sensor correction. If the physical quantity measured as a result of the execution of the sensor calibration necessity confirmation command 933 is within the allowable deviation of the correction physical quantity reference value, the sensor correction data generation and storage and drive command 935 are executed, The correction data may be generated and stored in the correction memory 911 and set to drive the elements of each of the sensor boards 500 with the stored sensor correction data to complete the sensor correction step.

FIG. 12 is a block diagram of the sensor calibration commands 60 of the cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 12, the sensor correction commands 60 of the cell metabolism measurement apparatus according to an embodiment are set such that the difference between the correction reference value and the measured physical quantity falls within a predetermined reference value tolerance range, Adjustment commands 70 of the driving parameter of the sensor board element for adjusting and setting the parameter or the trigger level for determining whether or not each light receiving element receives light. The light emitting element driving parameter may be a light emitting element driving current parameter according to an aspect.

As shown in FIG. 12, in an apparatus for measuring cell metabolism according to an embodiment, a control unit 700 controls the controller 700 to execute driving parameter adjustment commands 70 through a user input / Can be controlled. That is, the control unit 700 is connected to predetermined programs 49 composed of adjustment commands 70 of driving parameter of the sensor board element stored in the recording medium according to the input of the user, The adjustment commands 70 of the sensor board element of the adjustment step of the sensor correction step of the cell metabolism measurement experiment apparatus according to the embodiment shown in FIG. 6 are executed by fetching and executing the adjustment instructions of the adjustment instructions 70, So that the generation of the sensor correction data can be manually proceeded in step 5. In addition, according to another aspect of the present invention, the apparatus for measuring cell metabolism measurement may automatically determine whether the controller 700 senses a sensor of a cell metabolism measurement apparatus according to an embodiment shown in FIG. 6, Adjustment of the drive parameter for each element of the sensor board 500 in the adjustment step of the correction step and generation of the sensor correction data in step 5 may be performed. The predetermined condition in the control unit 700 may be a user-specified protocol stored in the user-defined protocol memory 912 according to an aspect. The control unit 700 may perform a cell metabolism measurement experiment according to a predetermined condition, for example, and may automatically perform an initialization step before the experiment of the microplate 300 according to a predetermined setting of the controller 700. [ Accordingly, when the controller 700 proceeds to the initialization step, it connects to the predetermined programs 49 constituted by the adjustment commands 70 of the drive parameter of the sensor board element stored in the recording medium, Adjustment of the driving parameters of the sensor board 500 in the adjustment step of the sensor calibration step of the cell metabolism measurement apparatus according to the embodiment shown in FIG. 6, The generation of the correction data can be proceeded.

On the other hand, the light emitting element driving current parameter may be a pulse width of a current driving the light emitting element according to an aspect. According to another aspect, the light emitting element driving current parameter may be the gain of the voltage control amplifier adjusting the current driving the light emitting element. The trigger level for determining whether light is received by the light receiving element can be determined from the sensor film in the waveform of the current generated by the reaction of the light receiving element of the sensor board 500 corresponding to the sensor film It is an indicator used as a scale.

Accordingly, the controller 700 of the cell metabolism measurement apparatus according to an embodiment accesses the adjustment commands 70 of the driving parameter of the sensor board element, fetches and adjusts the driving parameter adjustment commands 70 of the sensor board element, The trigger level for determining whether the light emitting element driving current parameter or the light receiving element is received can be appropriately adjusted so that the measured physical quantity can be adjusted until it comes within a predetermined allowable deviation to be close to the correction physical quantity reference value to be corrected. As a result, the controller 700 sets the trigger level for determining whether each light-emitting element drive current parameter or the light-receiving element is received or not, when the difference between the correction reference value and the measured physical quantity is equal to a preset reference value tilt deviation, Data can be generated.

FIG. 13 is a block diagram showing a configuration of commands for adjusting driving parameters of a sensor board device according to an embodiment of the cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 13, the driving parameter adjustment commands 70 of the sensor board element of the cell metabolism measurement experiment apparatus according to an embodiment use the driving parameter for each light emitting element as the amplification rate of the voltage control amplifier 905, And an amplification factor adjustment command 80 for adjusting and setting the driving current of the amplifier. The driving parameter for each light emitting device may be a driving current parameter for each light emitting device according to an aspect.

As shown in FIG. 13, the apparatus for measuring cell metabolism according to an embodiment may control the controller 700 so that the controller 700 executes the gain adjustment command 80 through the user input / output unit according to an aspect. That is, the control unit 700 accesses the predetermined programs 49 constituted by the amplification rate adjustment command 80 stored in the recording medium according to the input of the user, fetches the amplification rate adjustment command 80 The amplification factor of the light emitting element can be set according to a predetermined reference. The predetermined criterion may be an amplification factor adjustment guideline of the predetermined light emitting device according to an aspect, or may be a know-how of a skilled cell metabolism measurement experiment researcher according to another aspect. One of the input devices may include a touch screen in accordance with aspects of the cell metabolism measurement device. For example, the user may touch a well to be corrected in a plurality of wells of the microplate 300 arranged on the touch screen. Then, a calibration tab is selected in the property window of the corresponding well, and the amplification factor of the voltage control amplifier 905 of the light emitting element is selected as a tap among a plurality of adjustment parameters, and the amplification factor value can be directly input or a target value can be selected from the list have.

Meanwhile, when the user's amplification rate control command 80 is used through the input unit of the cell metabolism measurement apparatus, the cell metabolism measurement apparatus may be in a stopped state and not performing the operation related to the cell metabolism measurement . In addition, even when performing an operation related to the cell metabolism measurement according to another aspect, it is also possible to execute the amplification rate adjustment command 80 after executing the pause operation of the apparatus through the input device of the cell metabolism measurement experiment apparatus. According to another aspect of the present invention, the control unit 700 may automatically adjust the amplification factor of the voltage control amplifier 905 of the light emitting device according to predetermined conditions in the control unit 700 without the user's input. The predetermined condition may be a user defined protocol stored in the user defined protocol memory 912 according to an aspect. The control unit 700 may perform a cell metabolism measurement experiment according to a predetermined condition, for example, and may automatically perform an initialization step before the experiment of the microplate 300 according to a predetermined setting of the controller 700. [ Accordingly, when the controller 700 proceeds to the initialization step, it connects to the predetermined programs 49 configured to include the amplification rate adjustment command 80 stored in the recording medium, fetches and executes the amplification rate adjustment command 80, The sensor correction data can be generated by adjusting the amplification factor of the control amplifier 905. [ Certain programs 49 configured to include the amplification factor adjustment command 80 according to one aspect may be configured such that the control unit 700 controls the driving parameter adjustment commands 70 of the sensor board element in executing the amplification factor adjustment command 80, And then execute the amplification adjustment command 80 after executing the amplification adjustment command 80. [ The predetermined programs 49 configured to include the amplification rate adjustment command 80 according to another aspect may be configured such that the controller 700 does not execute the adjustment commands 70 of the driving parameter of the sensor board element and only the amplification rate adjustment command 80 , And so on.

Since the voltage control amplifier 905 is a well-known technique, a detailed description thereof will be omitted because it may obscure the gist of the present invention. The light emitting device may be located on the sensor board vertically corresponding to two or more wells depending on the well and depending on the specific material to be measured, for example dissolved oxygen or hydrogen ions. The light emitting device may be a light emitting diode (LED). Power supply for driving the light emitting element 906 is required for the light emitting element 906 to emit light as shown in FIG. Therefore, the device for measuring cell metabolism according to one aspect may include a circuit configuration in which driving power for the light emitting element 906 is supplied to the light emitting element 906 through the voltage control amplifier 905.

According to an embodiment of the cell metabolism measurement apparatus according to an embodiment, the user directly inputs the amplification factor and the control unit 700 controls the voltage control amplifier 905 of the light emitting element 906 to execute the amplification adjustment command 80. [ Can be adjusted manually. The apparatus for measuring cell metabolism according to an embodiment may further include a program 49 that includes a gain adjustment command 80 that automatically sets the amplification factor of the voltage control amplifier 905 as the control unit 700 according to another aspect The amplification factor of the voltage control amplifier 905 can be adjusted.

Meanwhile, when the cell metabolism measurement experiment apparatus according to an embodiment adjusts the amplification rate of the voltage control amplifier 905 by executing the amplification rate adjustment command 80 through the input of the amplification value of the user, The gain control value of the amplifier 905 may vary depending on the measured physical quantity and the allowable deviation of the correction physical quantity reference value. For example, after the light emitting element 906 of the sensor board 500 shown in FIG. 5 is driven by a square wave, a physical quantity related to a time required for the light receiving element sensing current of the sensor board 500 to reach the trigger level is measured . In this case, if the difference between the measured physical quantity and the correction physical quantity reference value deviates from the correction physical quantity reference value allowable deviation and the measured physical quantity is larger than the correction physical quantity reference value, the user sets the amplification rate of the voltage control amplifier 905 The sensor correction data can be generated and set so as to adjust the physical quantity downward. Of course, in addition to the gain adjustment command 80 for adjusting the amplification factor of the voltage control amplifier 905, other commands for adjusting other parameters for driving the elements of the sensor board 500, described below, It can also be set.

 Meanwhile, the control unit 700 can adjust the amplification factor of the voltage control amplifier 905 by executing a gain adjustment command 80 through a predetermined digital signal processing including or using a microprocessor. For example, when the control unit 700 executes the gain adjustment command 80, the digital signal processing is performed such that the microprocessor controls the predetermined controller 700 to control the driving current of the light emitting element 906 and the measured physical quantity Signal, and determining whether to increase or decrease the amplification rate according to a predetermined reference based on the input signal. In the cell metabolism measurement experiment apparatus, the control unit 700 transmits the digital signal processing signal processed by the microprocessor to the input signal of the voltage control amplifier 905 via the digital analog inverter 908, so that the gain of the voltage control amplifier 905 It is possible to include a configuration of a predetermined circuit so as to be able to adjust the voltage.

FIG. 14 shows a block diagram of the calibration command 70 for adjusting the driving parameters of the sensor board device according to another embodiment of the cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 14, the adjustment commands 70 for adjusting the driving parameters of the sensor board element of the cell metabolism measurement apparatus according to an embodiment include a trigger level adjusting command (see FIG. 14) for adjusting and setting a trigger level for each light receiving element by software 81).

As shown in FIG. 14, in an apparatus for measuring cell metabolism according to an embodiment, the controller 700 can control the controller 700 to execute the trigger level adjusting command 81 through the user input / output unit . That is, the control unit 700 accesses the predetermined programs 49 constituted by the trigger level adjustment instruction word 81 stored in the storage medium according to the input of the user, and outputs the trigger level adjustment instruction word 81 The trigger level of the light receiving element can be set in accordance with a predetermined criterion. The predetermined criterion may be a trigger level adjustment guideline of a light receiving element predetermined according to an aspect, or may be a know-how of a skilled cell metabolism measurement experiment researcher according to another aspect. One of the input devices may include a touch screen in accordance with aspects of the cell metabolism measurement device. For example, the user may touch a well to be corrected in a plurality of wells of the microplate 300 arranged on the touch screen. Then, a calibration tab is selected in the property window of the corresponding well, and a trigger level adjustment instruction (81) tab of the light receiving element is selected among a plurality of adjustment parameters, so that the trigger level can be directly input or the target value can be selected from the list.

Meanwhile, when the user's trigger level adjustment command 81 is used through the input unit of the cell metabolism measurement apparatus, the cell metabolism measurement apparatus may be stopped in a state where the apparatus is not related to the cell metabolism measurement have. In addition, even when performing an operation related to the cell metabolism measurement according to another aspect, it is also possible to execute the amplification rate adjustment command 80 after executing the pause operation of the apparatus through the input device of the cell metabolism measurement experiment apparatus. According to another aspect of the present invention, the control unit 700 may automatically adjust the trigger level of the light receiving element according to predetermined conditions in the control unit 700 without the user's input. The predetermined condition may be a user defined protocol stored in the user defined protocol memory 912 according to an aspect. The control unit 700 may perform a cell metabolism measurement experiment according to a predetermined condition, for example, and may automatically perform an initialization step before the experiment of the microplate 300 according to a predetermined setting of the controller 700. [ Accordingly, when the control unit 700 proceeds to the initialization step, it connects to the predetermined programs 49 configured to include the trigger level adjusting instruction 81 stored in the recording medium, and fetches and executes the trigger level adjusting instruction 81 The sensor correction data can be generated by adjusting the trigger level which is a measure for detecting the light reception state of the light receiving element. Certain programs 49 configured to include a trigger level adjustment instruction 81 according to an aspect of the present invention may be configured such that the control unit 700 controls the adjustment of the driving parameter of the sensor board 500 element To execute the trigger level adjustment command 81 after executing the command. The predetermined programs 49 configured to include the trigger level adjustment instruction 81 according to another aspect may be configured such that the control unit 700 does not execute the adjustment instruction of the driving parameter of the sensor board 500, Or the like.

8, the trigger level of the light receiving element 907 can be set in software by the controller 700 executing the trigger level adjusting command 81. [ The light receiving element 907 may be located on the sensor board vertically corresponding to two or more wells depending on the well and depending on the specific material to be measured, for example dissolved oxygen or hydrogen ions. The light receiving element 907 may be a photodiode or a phototransistor. The light receiving element 907 generates a current by sensing the light emission of the sensor film that emits in response to the light emission of the light emitting element 906 and driving the light receiving element 907. The apparatus for measuring cell metabolism according to one embodiment can adjust the trigger level of the light receiving element 907 by setting the trigger level of the light receiving element 907 in the controller 700 through a user's input according to one aspect. The apparatus for measuring cell metabolism according to an embodiment may include a microprocessor in which a predetermined program 49 is embedded according to an aspect. Accordingly, the controller 700 can adjust or set the trigger level, which is a scale for sensing the current generated by the light receiving element 907, as a software through the microprocessor. In order to process the trigger level in a software manner through a microprocessor, the cell metabolism measurement apparatus according to one embodiment is configured to generate a digital signal by passing the driving current of the light receiving element 907 through the analog digital converter 909, 700). ≪ / RTI > Accordingly, the control unit 700 can set the trigger level of the light receiving element 907 to the digital signal transmitted according to the predetermined program 49 of the microprocessor. That is, the controller 700 transmits the current passing through the light receiving sensor to the microprocessor and the measured physical quantity to the input signal of the microprocessor, and adjusts the trigger level of the light receiving element 907 according to a predetermined reference, Can be set.

FIG. 15 is a block diagram of measurement characteristic determination commands 90 of the cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 15, the measurement characteristic determination commands 90 of the device for measuring cell metabolism according to an embodiment may include measurement characteristic data of the respective elements of the determined sensor board 500 as a lookup table And a measurement characteristic data storing instruction 92 for storing measurement characteristic data.

As shown in FIG. 15, in an apparatus for measuring cell metabolism according to an embodiment, the controller 700 may control the controller 700 to execute the measurement characteristic data storing command 92 through the user input / output unit have. That is, the control unit 700 connects to the predetermined programs 49 constituted by the measurement characteristic data storing command 92 stored in the recording medium according to the input of the user and outputs the measurement characteristic data storing command 92 The measurement characteristic data of each element of the sensor board 500 can be stored as a lookup table to be referred to in the cell metabolism measurement. The look-up table may be one that has been transformed into an unprocessed arrangement of measurement characteristic data according to one aspect. The control unit 700 of the cell metabolism measurement apparatus may compare measured physical quantities with a look-up table to determine a measured value at a concentration of a specific substance corresponding to a physical quantity having the same value. If the physical quantity equal to the measured physical quantity does not exist in the lookup table, the controller 700 can calculate the concentration of the specific substance represented by the measured physical quantity through the correction after the predetermined calculation. For example, if the measured physical quantity is x2 and x2 is the closest value to x2 and is between x1 and x3 where data is present on the look-up table, then by taking the median value, the value of (x1 + x3) / 2 By taking the corresponding y value, a measurement that is a concentration of a specific substance can be calculated and determined.

The look-up table may be modified in the form of an array of data resulting from processing and processing the measurement characteristic data according to another aspect. That is, the controller 700 analyzes the concentration of the specific substance and the trend of the corresponding physical quantity from the measurement characteristic data of each well stored in the correction memory 911 as a result of the cell metabolism measurement experiment apparatus proceeding to the measurement characteristic determination step of FIG. An array of lookup tables can be created as a result.

16 is a block diagram showing a microplate 300, a sensor board 500, and a lens of a cell metabolism measurement apparatus according to an embodiment.

As shown in FIG. 16, the apparatus for measuring cell metabolism according to an embodiment may further include optical components positioned above each of the light emitting devices to compensate for a deviation in the incident angle due to mounting errors of the light emitting devices.

The optical components may be, for example, optical lenses. The optical lens has a single lens or a lens assembly in which several lenses are combined. The lens of the apparatus for measuring cell metabolism according to the present invention may use a single lens or a lens assembly. The lens according to one aspect may use a plano-convex lens 900 that is ideal for collimation and focusing applications using monochromatic illumination. The convex surface of the lens is directed to the light source of the light emitting device so that the light source of the light emitting device is collimated and focused to be incident on the sensor film so that the deviation of the incident angle of each light emitting device can be reduced. In addition to the plano-convex lens 900, the lens may further include a plano-concave lens for expanding the optical focal length. However, it is possible to mount a predetermined combination of lenses, which can minimize the deviation of the angle of incidence of the light source of the light emitting device into the sensor film of the microplate 300, at a predetermined position above the light emitting device. The lens may be installed by inserting between the sensor board 500 and the microplate 300 while being mounted on a mounting member such as a plate according to an aspect. The plate has a lens mounting structure corresponding to an upper portion of each of the light emitting elements and capable of mounting respective lenses corresponding to the respective wells of the microplate 300 corresponding to each of the light emitting elements, Lt; / RTI > The lens may be installed on each of the light emitting elements using a predetermined lens mounting member on the sensor board 500 according to another aspect.

As shown in FIGS. 1, 2 and 3, the apparatus for measuring cell metabolism according to an embodiment of the present invention includes a microplate 300, which is vertically movable in a vertical direction and moves downward to seal at least one well of the microplate 300 And may further include a cover 600. The sealing lid 600 is a cover for sealing all the wells 310 of the microplate 300. The sealing lid 600 may seal all of the wells of the microplate 300 according to an aspect or may seal part of the microplate 300 according to another aspect. 3, the lower portion of the sealing lid 600 is convex in shape to completely seal the wells 310 corresponding to the wells 310 of the microplate 300, The convex portion may be made of a rubber material. As shown in FIG. 2, the sealing lid 600 may be located at one side of the inside of the housing 10, and the position is referred to as a measurement position for measuring DO concentration and pH. According to an aspect, the sealing lid 600 is movable along the Z-axis, that is, the vertical direction. To this end, it is a matter of course that a Z-axis drive motor is provided. The control unit 700 drives and controls the Z-axis driving motor to move the sealing lid 600 up and down. The control unit 700 moves the XY driving stage table 400 to the measurement position and moves the sealing lid 600 downward in order to perform optical measurement on at least one well 310 of the microplate 300 To close the microplate 300, and then perform optical measurement. When the measurement is completed, the sealing lid 600 is moved upward and separated from the microplate 300. The reason why the microplate 300 is sealed in this manner is to block the supply of oxygen to the well during the optical measurement to ensure accurate measurement.

While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, It is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and similarities. Accordingly, the scope of the present invention should be construed as being limited to the embodiments described, and it is intended that the scope of the present invention encompasses not only the following claims, but also equivalents thereto.

The present invention is industrially applicable in the field of cell metabolism measurement technology.

10: Housing
11: Front cover
12: Mounting hole
13: Hall cover
20: Sensor housing
30: Display module
100: Cartridge
200: drug injector
300: Microplate
310: Well
311: Sensor film for DO detection
312: Sensor membrane for pH detection
320: light shield plate
321: Filter Home
330: Permeate filter
400: XY driving stage table
500: Sensor board
48: Recording medium
49: Program
50: Initialization instructions
51: Measurement value determination commands
52: Physical quantity measurement command
60: Sensor calibration commands
70: Adjustment commands of driving parameter of sensor board element
80: Gain adjustment command
81: Trigger level adjustment command
91: Physical quantity measurement command
90: Measurement characteristic decision command
92: Measurement characteristic data save command
510:
520:
511: Receiving element for pH detection
512: Light receiving element for DO detection
521: Light emitting element for pH detection
522 Light emitting device for DO detection
600: Sealing lid
700:
900: plane-convex lens
901: drive current signal
902: sensing current signal
905: Voltage Controlled Amplifier (VCA)
906: Light emitting element
907: Light receiving element
908: Digital Analog Inverter
909: Analog to Digital Converters
910: Memory
911: Calibration memory
912: User-defined protocol memory
930: Standard injection instruction
931: Instruction to measure physical quantity by well
932: correction physical quantity reference value calculating instruction
933: Sensor calibration necessity confirmation command
934: Adjustment of drive parameter of sensor board element and measurement command of physical quantity
935: Sensor calibration data creation, storage and drive command
940: nth standard solution injection command for determination of measurement characteristics,
941: Measurement command for physical quantity per well,
942: instruction to store physical quantity per well,
943: Additional standard solution injection and measurement confirmation command
944: Measurement property data setting command for each well,
945: Measurement property data storing instruction for each well
950: starting point 1
951: Starting point 2
952: Endpoint 1
953: Endpoint 2
954: Measurement delay value 1
955: Measurement delay value 2
960: Sensor membrane

Claims (16)

XY driving stage table;
A microplate including a plurality of wells having a sensor film and mounted on the XY driving stage table;
A sensor board arranged so that a measurement sensor including a light emitting element and a light receiving element corresponds to the sensor film;
A plurality of cartridges containing drugs;
A plurality of drug injectors configured to inject a drug in the cartridge into the well; And
A controller for driving the XY driving stage table to control the apparatus to move the microplate relative to the measurement position where the optical measurement is performed or the drug injector;
1. A method for cell metabolism measurement experimentation carried out by an apparatus for measuring cell metabolism comprising:
An initialization step of setting drive parameters of respective elements of the sensor board with sensor correction data for each element of the sensor board and driving each of the sensor elements with drive parameters of the respective elements of the sensor board;
Determining a measurement value by converting the measured physical quantity into a cell metabolism quantity according to measurement characteristic data set for each well;
, ≪ / RTI &
Wherein the initializing step includes a sensor calibration step of determining and setting sensor calibration data for correcting a circuit deviation and a mechanical deviation of each element of the sensor board through standard solution injection and measurement, And determining a measurement characteristic for each well through the injection and measurement of a plurality of standard solutions at a predetermined concentration, and setting the measurement characteristic data for each well.
The method of claim 1, wherein the measured physical quantity is
Wherein the sensor is a physical quantity related to a time required for the light receiving element sensing signal of the sensor board to reach the trigger level after driving the light emitting element of the sensor board.
delete 2. The method according to claim 1,
A method for measuring cell metabolism in a cell metabolism measurement apparatus, which is a trigger level for determining light emitting element drive parameters and whether light is received or not.
5. The method according to claim 4, wherein the driving parameter of the light emitting device is an amplification factor of the voltage control amplifier.
5. The method of claim 4, wherein the trigger level of the light receiving element is set by software in a control unit.
The method according to claim 1,
Wherein the determined measurement characteristic data is stored as a look-up table to be referred to in the measurement of cell metabolism.
XY driving stage table;
A microplate including a plurality of wells having a sensor film and mounted on the XY driving stage table;
A sensor board arranged so that a measurement sensor including a light emitting element and a light receiving element corresponds to the sensor film;
A plurality of cartridges containing drugs;
A plurality of drug injectors configured to inject a drug in the cartridge into the well; And
And driving the XY driving stage table to control the progress of the cell metabolism measurement by controlling the apparatus so that the microplate moves relative to the measurement position where the optical measurement is performed or the drug injector,
An initialization instruction for setting driving parameters of respective elements of the sensor board by sensor correction data set for each element of the sensor board and driving the sensor elements by driving parameters of the respective elements, A control unit for controlling the apparatus by accessing a recording medium storing a program including measurement value determination commands for determining a measurement value in terms of a cell metabolism amount according to data and executing the program;
, ≪ / RTI &
The initialization commands include sensor calibration commands to determine and set sensor calibration data to correct circuit deviations and mechanical deviations of each element of the sensor board through standard solution injection and measurement, And determining measurement characteristics for each well through a plurality of standard solution injections and measurements of concentration, and setting measurement characteristic data for each well.
9. The method of claim 8, wherein the measurement value determination instructions are:
And a physical quantity measurement command for measuring a physical quantity related to a time required for the light receiving element sensing signal to reach the trigger level after driving the light emitting element.
delete 9. The apparatus of claim 8, wherein the sensor calibration instructions:
The driving parameter of the sensor board element for adjusting and setting the trigger level for determining whether each light emitting element drive parameter or each light receiving element receives light is determined so that the difference between the correction reference value and the measured physical quantity falls within the predetermined reference value tolerance range An apparatus for measuring cell metabolism, comprising calibration instructions.
12. The method of claim 11, wherein the instructions for adjusting the drive parameters of the sensor board element comprise:
And an amplification factor adjustment command for adjusting and setting the driving signal of the light emitting element by setting the driving parameter for each light emitting element as the amplification factor of the voltage control amplifier.
12. The apparatus of claim 11, wherein the drive parameter adjustment commands of the sensor board element are:
And a trigger level adjustment command for adjusting and setting a trigger level for each light receiving element by software.
9. The apparatus of claim 8, wherein the measurement characteristic determination instructions are:
And a measurement characteristic data storing instruction for storing the measurement characteristic data of each of the elements of the determined sensor board as a lookup table to be referred to in a cell metabolism measurement.
9. The method of claim 8,
And an optical component positioned above each of the light emitting elements to compensate for the deviation of the incident angle due to the mounting deviation of the light emitting element.
9. The method of claim 8,
A sealing lid capable of moving vertically up and down and moving downward to seal at least one of the wells of the microplate;
Wherein the cell metabolism measurement apparatus further comprises:

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