Online calibration method for microwell plate incubator

Abstract

The invention provides an online calibration method for a microplate incubator, and relates to the field of online calibration of incubators. The online calibration method for the microplate incubator comprises a measurement module, a modular design and a development principle; according to the online calibration method for the microplate incubator, metering technical specifications are compiled for various types of microplate incubators which are massively used at present, calibration items and calibration methods of the microplate incubators are standardized, and quantity value traceability work of key technical parameters of the microplate incubators is carried out; and important technical guarantee is provided for accurate and reliable quantity value of the microplate incubator and safe and effective use of the microplate incubator. The specification content comprises that specific provisions are made on the application range, terms, measurement units, measurement performance requirements, calibration conditions, measurement instruments and equipment, calibration items, calibration methods, uncertainty evaluation of measurement results and the like of laws and regulations. The performance parameter test specification comprises main calibration items.

Description

Technical Field

[0001] The invention relates to the technical field of incubator online calibration, and in particular to an online calibration method for a microplate incubator. Background Art

[0002] As my country's bioanalysis technology is developing towards high throughput, high sensitivity and multifunctionality, the microplate incubator with vibration function, as the basic instrument for high throughput analysis, needs to meet the requirements of micro-quantification, automation and integration. At present, the technology of microplate detection instruments with temperature control and vibration functions in China is mature, and the accuracy has reached the foreign level, but there is a lack of calibration devices and calibration methods for multifunctional microplate incubators in China. In order to ensure and improve the accuracy of microplate incubators, adapt to the rapid development of the medical and bioanalysis industries, and meet the needs of domestic and foreign markets, the project developed an online calibration device for microplate incubators and studied calibration methods. It will be used to calibrate the metrological performance of microplate incubators, including indicators such as the temperature indication error range, temperature uniformity, and speed indication error range of the microplate incubator. This will solve the problem that microplate incubators cannot be effectively traced, provide accurate traceability of measurement values ​​for the production and use process supervision of microplate incubators, improve the reliability and effectiveness of microplate incubator registration inspections, production quality inspections, and test results, promote the standardization of microplate incubator products and the upgrading of quality inspection technologies, and lead and drive the high-quality development and progress of medical and bioanalysis related industries. Summary of the invention

[0003] The purpose of the present invention is to provide an online calibration method for a microplate incubator, which solves the problems raised in the above-mentioned background technology.

[0004] Technical Solution

[0005] To achieve the above objectives, the present invention is implemented through the following technical solutions: A method for online calibration of a microplate incubator, comprising a measurement module, a modular design and development principle

[0006] The measurement module includes a temperature measurement module and a speed measurement module. These two modules are used to measure the temperature accuracy, distribution uniformity, temperature fluctuation and speed accuracy of the microplate incubator. The two measurement modules send the collected data to the computer host computer through wireless transmission (such as Bluetooth, WiFi, GPRS / 4G), and the host computer records and processes the data.

[0007] 2. Data communication and host computer software development

[0008] Since the microplate incubator has many calibration parameters and two measuring sensor modules, the amount of data collected is very large. Manual recording and calculation is not only labor-intensive but also error-prone. Therefore, it is necessary to develop appropriate host computer software to automatically collect, record and process a large amount of experimental data. This not only greatly improves the detection efficiency, but also improves the accuracy of the calculation.

[0009] The difficulty lies in the fact that the data transmission speed and data integrity of the two measurement modules must be guaranteed. Secondly, the host computer must be able to identify the two modules. Once the data has a problem, it can be accurately located to find the problem of the microplate incubator. To address the problem, the WiFi module is used for data communication and a unique address is assigned to each module to solve the related problem.

[0010] 3. Calibration Method Study

[0011] Metrology technical specifications are compiled for various types of microplate incubators that are currently in widespread use to standardize the calibration items and methods of microplate incubators, and to carry out traceability work on the measurement values ​​of key technical parameters of microplate incubators, providing important technical guarantees for the accurate and reliable measurement values ​​of microplate incubators and their safe and effective use.

[0012] The contents of the specification include: specific provisions on the scope of application of the regulations, terminology and measurement units, metrological performance requirements, calibration conditions and measuring instruments and equipment, calibration items, calibration methods and uncertainty assessment of measurement results. The main calibration items included in the performance parameter test specification are: temperature indication error, temperature uniformity, temperature fluctuation, speed indication error and other parameters.

[0013] Furthermore, as described Figure 1 As shown in the figure, the temperature measurement unit has the same appearance as the microplate and can be placed directly on the microplate incubator. Figure 2 As shown in Figure 1, there are 5 temperature measurement points distributed in the temperature measurement unit. Figure 3 As shown, the temperature detection unit consists of 1. copper cap; 2. temperature sensor; 3. base; 4. circuit board; 5. protection board. The temperature probe is placed between the copper cap and the base to form a temperature probe. The entire probe is directly fixed on the PCB board, and then a protection board is added to protect the circuit. The copper cap is made of brass material with good thermal conductivity and fast temperature response. The overall structure uses PCB as the base, wireless transmission mode, and the structure is light and simple without multiple parts.

[0014] Furthermore, as described Figure 4 As shown in the figure, the rotation speed is detected by laser. The laser sensor is placed on a tripod and the laser probe is aimed at the device to be tested. The measurement can be carried out easily and conveniently. Figure 5As shown, 1 is the laser transmitting and receiving window, 2 is the tripod mounting hole, and 3 is the charging port; the laser probe is compact in size, easy to install, and rechargeable, and does not require an external power supply.

[0015] Furthermore, the laser vibrometer developed using the Doppler effect vibrometer method generally includes two parts: an optical interference system and a signal acquisition and processing system. The working principle of the optical interference system and its internal optical path are as follows: Figure 6 As shown. The laser emits a laser beam with a frequency of f0, which is divided into two beams by a spectroscope. One beam is used as a reference light, and a laser beam with a frequency of f0+fm is obtained by modulating the laser beam with an acousto-optic modulator; the other beam is used as a measurement light and is projected onto the surface of the vibrating object. According to the Doppler effect, the measurement light reflected from the surface of the vibrating object will produce a Doppler frequency shift f△, so the frequency of the measurement light is f0±f△. The reflected measurement light interferes with the reference light that has undergone frequency deviation. For a HeNe laser with a wavelength λ of 632.8nm, a maximum frequency deviation of 64MHz will be generated when the maximum speed of the object is 20m / s. However, the Doppler frequency shift is much smaller than that of a laser with a frequency of 4.74×1014Hz, and it is not easy to detect. Therefore, the laser external modulation technology is used, and the acousto-optic modulator is used to make the reference light produce a fixed frequency deviation, and then the reference light and the measurement light interfere with each other, and the optical signal is converted into an electrical signal through a photodetector. The photodetector consists of a photodiode and a low noise amplifier (LNA), and its basic function is to convert the optical signal into an electrical signal. The electrical signal output from the photodetector can be expressed as (assuming that the maximum amplitude of the output signal is constant and normalized to 1, and the DC component and noise are removed):

[0016] u(t)=sin(2Πf m t+m f ×sin(2Πf s t))

[0017] Where fs is the vibration frequency of the object surface, fm is the reference light modulation frequency, and mf is the frequency modulation index. The frequency modulation index is the ratio of the Doppler frequency shift to the vibration frequency, that is,

[0018]

[0019] The optical interference measurement signal carries information such as the speed, displacement, acceleration, and vibration frequency of the object's vibration. The vibration information can only be obtained through signal demodulation, filtering, and amplification by the signal acquisition and processing system. The signal acquisition and processing system is equipped with demodulation cards with different functions, and the microcontroller can select the range and filtering method to be tested according to the needs.

[0020] Furthermore, the signal acquisition and processing system is generally designed based on the principle of modularization. The basis of modularization is to strictly distinguish between the optical and electronic processing parts. The design of the controller can configure different modules to correspond to different signal requirements. Figure 7 shown.

[0021] Furthermore, the high-frequency signal with the information of the measured object transmitted from the optical interference system is demodulated from the velocity or displacement signal by a signal acquisition and processing system equipped with a corresponding demodulation card, and the signal enters the low-frequency stage through filtering. After being processed by an analog filtering module, an analog-to-digital conversion module and a digital filtering module, the vibration information of the measured object can be obtained.

[0022] The present invention provides an online calibration method for a microplate incubator, which has the following beneficial effects:

[0023] This online calibration method for microplate incubators is aimed at compiling metrological technical specifications for various types of microplate incubators currently in large quantities, in order to standardize the calibration items and calibration methods of microplate incubators, and to carry out the traceability of the key technical parameters of microplate incubators, so as to provide important technical guarantees for the accurate and reliable measurement of microplate incubators and their safe and effective use. The contents of the specifications include: specific provisions on the scope of application of the regulations, terminology and measurement units, metrological performance requirements, calibration conditions and measuring instruments and equipment, calibration items, calibration methods and uncertainty assessment of measurement results. The main calibration items included in the performance parameter test specifications are: temperature indication error, temperature uniformity, temperature fluctuation, speed indication error and other parameters. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a detection schematic diagram of the present invention;

[0025] Figure 2 This is the detection point distribution diagram of the present invention;

[0026] Figure 3 It is a schematic diagram of the structure of the present invention;

[0027] Figure 4 It is a detection schematic diagram of the present invention;

[0028] Figure 5 It is a schematic diagram of the laser probe of the present invention;

[0029] Figure 6 This is a schematic diagram of the working principle of the optical interference system of the laser vibrometer of the present invention;

[0030] Figure 7 This is a schematic diagram of the laser vibrometer signal acquisition and processing system module of the present invention. DETAILED DESCRIPTION

[0031] like Figure 1-7 As shown, the embodiment of the present invention provides an online calibration method for a microplate incubator, including a measurement module, a modular design and development principle

[0032] The measurement module includes a temperature measurement module and a speed measurement module. These two modules are used to measure the temperature accuracy, distribution uniformity, temperature fluctuation and speed accuracy of the microplate incubator. The two measurement modules send the collected data to the computer host computer through wireless transmission (such as Bluetooth, WiFi, GPRS / 4G), and the host computer records and processes the data.

[0033] 2. Data communication and host computer software development

[0034] Since the microplate incubator has many calibration parameters and two measuring sensor modules, the amount of data collected is very large. Manual recording and calculation is not only labor-intensive but also error-prone. Therefore, it is necessary to develop appropriate host computer software to automatically collect, record and process a large amount of experimental data. This not only greatly improves the detection efficiency, but also improves the accuracy of the calculation.

[0035] The difficulty lies in the fact that the data transmission speed and data integrity of the two measurement modules must be guaranteed. Secondly, the host computer must be able to identify the two modules. Once the data has a problem, it can be accurately located to find the problem of the microplate incubator. To address the problem, the WiFi module is used for data communication and a unique address is assigned to each module to solve the related problem.

[0036] 3. Calibration Method Study

[0037] Metrology technical specifications are compiled for various types of microplate incubators that are currently in widespread use to standardize the calibration items and methods of microplate incubators, and to carry out traceability work on the measurement values ​​of key technical parameters of microplate incubators, providing important technical guarantees for the accurate and reliable measurement values ​​of microplate incubators and their safe and effective use.

[0038] The contents of the specification include: specific provisions on the scope of application of the regulations, terminology and measurement units, metrological performance requirements, calibration conditions and measuring instruments and equipment, calibration items, calibration methods and uncertainty assessment of measurement results. The main calibration items included in the performance parameter test specification are: temperature indication error, temperature uniformity, temperature fluctuation, speed indication error and other parameters.

[0039] like Figure 1 As shown in the figure, the temperature measurement unit has the same appearance as the microplate and can be placed directly on the microplate incubator. Figure 2 As shown in Figure 1, there are 5 temperature measurement points distributed in the temperature measurement unit. Figure 3 As shown, the temperature detection unit consists of 1. copper cap; 2. temperature sensor; 3. base; 4. circuit board; 5. protection board. The temperature probe is placed between the copper cap and the base to form a temperature probe. The entire probe is directly fixed on the PCB board, and then a protection board is added to protect the circuit. The copper cap is made of brass material with good thermal conductivity and fast temperature response. The overall structure uses PCB as the base, wireless transmission mode, and the structure is light and simple without multiple parts.

[0040] like Figure 4 As shown in the figure, the rotation speed is detected by laser. The laser sensor is placed on a tripod and the laser probe is aimed at the device to be tested. The measurement can be carried out easily and conveniently. Figure 5 As shown, 1 is the laser transmitting and receiving window, 2 is the tripod mounting hole, and 3 is the charging port; the laser probe is compact in size, easy to install, and rechargeable, and does not require an external power supply.

[0041] Laser vibrometers developed using the Doppler effect vibrometer method generally include two parts: an optical interference system and a signal acquisition and processing system. The working principle of the optical interference system and its internal optical path are as follows: Figure 6 As shown. The laser emits a laser beam with a frequency of f0, which is divided into two beams by a spectroscope. One beam is used as a reference light, and a laser beam with a frequency of f0+fm is obtained by modulating the laser beam with an acousto-optic modulator; the other beam is used as a measurement light and is projected onto the surface of the vibrating object. According to the Doppler effect, the measurement light reflected from the surface of the vibrating object will produce a Doppler frequency shift f△, so the frequency of the measurement light is f0±f△. The reflected measurement light interferes with the reference light that has undergone frequency deviation. For a HeNe laser with a wavelength λ of 632.8nm, a maximum frequency deviation of 64MHz will be generated when the maximum speed of the object is 20m / s. However, the Doppler frequency shift is much smaller than that of a laser with a frequency of 4.74×1014Hz, and it is not easy to detect. Therefore, the laser external modulation technology is used, and the acousto-optic modulator is used to make the reference light produce a fixed frequency deviation, and then the reference light and the measurement light interfere with each other, and the optical signal is converted into an electrical signal through a photodetector. The photodetector consists of a photodiode and a low noise amplifier (LNA), and its basic function is to convert the optical signal into an electrical signal. The electrical signal output from the photodetector can be expressed as (assuming that the maximum amplitude of the output signal is constant and normalized to 1, and the DC component and noise are removed):

[0042] u(t)=sin(2Πf m t+m f ×sin(2Πf s t))

[0043] Where fs is the vibration frequency of the object surface, fm is the reference light modulation frequency, and mf is the frequency modulation index. The frequency modulation index is the ratio of the Doppler frequency shift to the vibration frequency, that is,

[0044]

[0045] The optical interference measurement signal carries information such as the speed, displacement, acceleration, and vibration frequency of the object's vibration. The vibration information can only be obtained through signal demodulation, filtering, and amplification by the signal acquisition and processing system. The signal acquisition and processing system is equipped with demodulation cards with different functions, and the microcontroller can select the range and filtering method to be tested according to the needs.

[0046] Signal acquisition and processing systems are generally designed based on the principle of modularization. The basis of modularization is to strictly distinguish between optical and electronic processing parts. The design of the controller can configure different modules to correspond to different signal requirements. Figure 7 shown.

[0047] The high-frequency signal with the information of the object under test transmitted from the optical interference system is demodulated into its velocity or displacement signal by a signal acquisition and processing system equipped with a corresponding demodulation card, and then enters the low-frequency stage through filtering signal. After being processed by analog filtering module, analog-to-digital conversion module and digital filtering module, the vibration information of the object under test can be obtained.

Claims

1. A method for online calibration of a microplate incubator, comprising a measuring module, characterized in that: Said 1. Modular design and development principles The measurement module includes a temperature measurement module and a speed measurement module. These two modules are used to measure the temperature accuracy, distribution uniformity, temperature fluctuation and speed accuracy of the microplate incubator. The two measurement modules send the collected data to the computer host computer through wireless transmission (such as Bluetooth, WiFi, GPRS / 4G), and the host computer records and processes the data.

2. Data communication and host computer software development Since the microplate incubator has many calibration parameters and two measuring sensor modules, the amount of data collected is very large. Manual recording and calculation is not only labor-intensive but also error-prone. Therefore, it is necessary to develop appropriate host computer software to automatically collect, record and process a large amount of experimental data. This not only greatly improves the detection efficiency, but also improves the accuracy of the calculation. The difficulty lies in the fact that the data transmission speed and data integrity of the two measurement modules must be guaranteed. Secondly, the host computer must be able to identify the two modules. Once the data has a problem, it can be accurately located to find the problem of the microplate incubator. To address the problem, the WiFi module is used for data communication and a unique address is assigned to each module to solve the related problem.

3. Calibration Method Study Metrology technical specifications are compiled for various types of microplate incubators that are currently in widespread use to standardize the calibration items and methods of microplate incubators, and to carry out traceability work on the measurement values ​​of key technical parameters of microplate incubators, providing important technical guarantees for the accurate and reliable measurement values ​​of microplate incubators and their safe and effective use. The contents of the specification include: specific provisions on the scope of application of the regulations, terminology and measurement units, metrological performance requirements, calibration conditions and measuring instruments and equipment, calibration items, calibration methods and uncertainty assessment of measurement results. The main calibration items included in the performance parameter test specification are: temperature indication error, temperature uniformity, temperature fluctuation, speed indication error and other parameters.

2. The method for online calibration of a microplate incubator according to claim 1, characterized in that: As shown in Figure 1, the appearance of the temperature measurement unit is consistent with the microplate, and can be directly placed on the microplate incubator. As shown in Figure 2, 5 temperature measurement points are distributed in the temperature measurement unit. As shown in Figure 3, the temperature detection unit consists of 1. copper cap; 2. temperature sensor; 3. base; 4. circuit board; 5. protection board. The temperature probe is placed between the copper cap and the base to form a temperature probe. The entire probe is directly fixed on the PCB board, and then a protection board is added to protect the circuit. The copper cap is made of brass material with good thermal conductivity and fast temperature response. The overall structure uses PCB as the base, wireless transmission mode, and the structure is light and simple without multiple parts.

3. The method for online calibration of a microplate incubator according to claim 1, characterized in that: As shown in FIG. 4 , the rotation speed is detected by laser. The laser sensor is placed on a tripod and the laser probe is aimed at the device to be tested for measurement. The measurement is simple and convenient. As shown in Figure 5, 1 is the laser transmitting and receiving window, 2 is the tripod mounting hole, and 3 is the charging port; the laser probe is compact in size, easy to install, and rechargeable, and does not require an external power supply.

4. The method for online calibration of a microplate incubator according to claim 1, characterized in that: The laser vibrometer developed using the Doppler effect vibrometer method generally includes two parts: an optical interference system and a signal acquisition and processing system. The working principle of the optical interference system and its internal optical path are shown in Figure 6. The laser emits a laser beam with a frequency of f0, which is divided into two beams by a spectroscope. One beam is used as a reference light, and is modulated by an acousto-optic modulator to obtain a laser beam with a frequency of f0+fm; the other beam is used as a measurement light and is projected onto the surface of the vibrating object. According to the Doppler effect, the measurement light reflected from the surface of a vibrating object will produce a Doppler frequency shift f△, so the frequency of the measurement light is f0±f△. The reflected measurement light interferes with the frequency-shifted reference light. For a HeNe laser with a wavelength λ of 632.8nm, a maximum frequency deviation of 64MHz will be generated when the maximum speed of the object is 20m / s. However, the Doppler frequency shift is much smaller than the laser with a frequency of 4.74×1014Hz and is not easy to detect. Therefore, laser external modulation technology is used, and an acousto-optic modulator is used to make the reference light produce a fixed frequency deviation, and then the reference light and the measurement light interfere with each other, and the optical signal is converted into an electrical signal through a photodetector. The photodetector consists of a photodiode and a low-noise amplifier (LNA), and its basic function is to convert the optical signal into an electrical signal. The electrical signal output from the photodetector can be expressed as (assuming that the maximum amplitude of the output signal is constant and normalized to 1, and the DC component and noise are removed): u(t)=sin(2Πf m t+m f ×sin(2Πf s t)) Where fs is the vibration frequency of the object surface, fm is the reference light modulation frequency, and mf is the frequency modulation index. The frequency modulation index is the ratio of the Doppler frequency shift to the vibration frequency, that is, The optical interference measurement signal carries information such as the speed, displacement, acceleration, and vibration frequency of the object's vibration. The vibration information can only be obtained through signal demodulation, filtering, and amplification by the signal acquisition and processing system. The signal acquisition and processing system is equipped with demodulation cards with different functions, and the microcontroller can select the range and filtering method to be tested according to the needs.

5. The method for online calibration of a microplate incubator according to claim 1, characterized in that: The signal acquisition and processing system is generally designed based on the principle of modularization. The basis of modularization is to strictly distinguish between optical and electronic processing parts. The design of the controller can configure different modules to correspond to different signal requirements. The signal flow of the signal acquisition and processing system is shown in Figure 7.

6. The method for online calibration of a microplate incubator according to claim 1, characterized in that: The high-frequency signal with the information of the measured object transmitted from the optical interference system is demodulated to obtain the velocity or displacement signal through a signal acquisition and processing system equipped with a corresponding demodulation card, and the signal enters the low-frequency stage through filtering. After being processed by an analog filtering module, an analog-to-digital conversion module and a digital filtering module, the vibration information of the measured object can be obtained.

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