CN116286320A - PCR thermal cycle device and control method - Google Patents
PCR thermal cycle device and control method Download PDFInfo
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- CN116286320A CN116286320A CN202211261886.6A CN202211261886A CN116286320A CN 116286320 A CN116286320 A CN 116286320A CN 202211261886 A CN202211261886 A CN 202211261886A CN 116286320 A CN116286320 A CN 116286320A
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- 238000000034 method Methods 0.000 title claims abstract description 36
- 230000007246 mechanism Effects 0.000 claims abstract description 86
- 238000005382 thermal cycling Methods 0.000 claims abstract description 18
- 238000004925 denaturation Methods 0.000 claims description 22
- 230000036425 denaturation Effects 0.000 claims description 22
- 238000012546 transfer Methods 0.000 claims description 17
- 238000000605 extraction Methods 0.000 claims description 10
- 238000004861 thermometry Methods 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims 1
- 238000009529 body temperature measurement Methods 0.000 abstract description 8
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 239000000523 sample Substances 0.000 description 107
- 230000008569 process Effects 0.000 description 13
- 238000010839 reverse transcription Methods 0.000 description 12
- 230000003321 amplification Effects 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 238000003199 nucleic acid amplification method Methods 0.000 description 9
- 238000000137 annealing Methods 0.000 description 7
- 238000001514 detection method Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000006872 improvement Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
- B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
- B01L7/5255—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones by moving sample containers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The application relates to the technical field of rapid molecular diagnosis, in particular to a PCR thermal cycling device and a control method. The PCR thermal cycling device comprises a first constant temperature tank, a moving mechanism and a control module, wherein the moving mechanism is used for synchronously moving the capillary tube and the temperature measuring module into the first constant temperature tank or taking out the capillary tube and the temperature measuring module from the first constant temperature tank so as to control the temperature of a sample contained in the capillary tube through the first constant temperature tank; the temperature measurement is used for detecting temperature, and the control module is configured to: the control module is provided with a first set temperature, when the temperature measured by the temperature measuring module in the first constant temperature tank reaches the first set temperature, the control module immediately controls the moving mechanism to take out the capillary tube from the first heat tank, so that the temperature of the sample in the capillary tube can be indirectly monitored through the temperature measuring module, and the sample in the capillary tube can be timely taken out from the first constant temperature tank when the temperature of the sample in the capillary tube reaches a first temperature threshold value.
Description
The present application is a divisional application of patent application with the application number 2021114807285, and the name of "PCR thermal cycle device and control method".
Technical Field
The application relates to the technical field of rapid molecular diagnosis, in particular to a PCR thermal cycling device and a control method.
Background
In molecular diagnosis, the amplification process of a sample is generally performed in a PCR thermal cycler, which is currently provided with a plurality of thermostats such as a high temperature cell, a low temperature cell, and an optical cell, and a capillary tube is circulated in the plurality of thermostats a plurality of times in a predetermined cycle to perform the amplification process.
In the process of high-speed transfer of the capillary, the temperature of the sample needs to be monitored, and the time when the sample is taken out of the constant temperature tank is determined, so that the thermal cycle of denaturation, annealing and extension is completed. However, since the capillary volume is very small, the temperature rise and fall rate of the sample in the high temperature tank and the low temperature tank is very fast, and the real-time temperature of the sample cannot be accurately monitored, so that the timing of the capillary tube to be taken out of the constant temperature tank is difficult to determine. In the related art, a fixed time is adopted to control capillary transfer or a rapid response temperature detection device is correspondingly arranged so that the sample of the capillary meets the temperature requirements of each cycle process, but the temperature rising and falling speed of the sample in a constant temperature tank is very high, so that the requirements on the reaction sensitivity and the material quality of a rapid response temperature sensor and a control device are very high, and the method solves the problem of sample temperature control to a certain extent, but still can bring the problems of low reliability and high cost of PCR thermal cycle.
Disclosure of Invention
The invention aims to provide a PCR thermal cycle device and a control method, which can improve the detection efficiency and reliability of PCR thermal cycle.
The invention provides a PCR thermal cycling device, which comprises a moving mechanism, a first constant temperature tank and a control module, wherein the first constant temperature tank is arranged on the moving mechanism; the first thermostat can be configured to have a first control temperature; the moving mechanism is provided with a capillary tube filled with a sample and a temperature measuring module, and can drive the capillary tube and the temperature measuring module to synchronously move; the control module is configured to:
controlling the moving mechanism to transfer the capillary tube and the temperature measuring module into the first constant temperature tank; when the temperature measured by the temperature measuring module reaches a first set temperature, controlling the moving mechanism to move the capillary tube out of the first constant temperature tank so that the temperature of the sample is within a first temperature threshold range after the capillary tube is moved out of the first constant temperature tank; the first control temperature is greater than the first set temperature.
Further, the first set temperature is greater than the first temperature threshold.
Further, the first temperature threshold is (94±2) °c;
The value range of the first set temperature is 90-105 ℃.
Further, the PCR thermal cycling apparatus further comprises a second thermostatic bath configurable to have a second control temperature;
the control module is further configured to:
controlling the moving mechanism to transfer the capillary tube from the first constant temperature tank into the second constant temperature tank;
when the temperature measured by the temperature measuring module reaches a second set temperature, controlling the moving mechanism to move the capillary tube out of the second constant temperature tank so that the temperature of the sample is within a second temperature threshold range after the capillary tube is moved out of the second constant temperature tank;
the second control temperature is less than the second set temperature.
Further, the second set temperature is greater than the second temperature threshold.
Further, the second temperature threshold is (57.5±2) °c;
the value range of the second set temperature is 50-70 ℃.
Further, the PCR thermal cycling apparatus further comprises a third thermostatic bath, the third thermostatic bath being configurable to have a third control temperature;
the control module is further configured to:
controlling the moving mechanism to transfer the capillary from the second thermostatic bath to the third thermostatic bath;
And after the sample in the capillary tube completes fluorescent signal acquisition in the third constant temperature tank, controlling the moving mechanism to take out the capillary tube from the third constant temperature tank.
Further, the PCR thermal cycling apparatus further comprises a fourth constant temperature tank configurable to have a fourth control temperature;
the control module is further configured to:
and controlling the moving mechanism to sequentially transfer the capillary tube to the first constant temperature tank, the fourth constant temperature tank, the second constant temperature tank and the third constant temperature tank, and enabling the capillary tube to stay in the fourth constant temperature tank with the fourth control temperature for a first preset time.
Further, the fourth control temperature is a sample denaturation target temperature.
Further, the fourth thermostatic bath can also be configured to a fifth control temperature;
the control module can be further configured to:
and controlling the moving mechanism to sequentially transfer the capillary tube to a fourth constant temperature tank with a fifth control temperature, the first constant temperature tank, the fourth constant temperature tank with the fourth control temperature, the second constant temperature tank and the third constant temperature tank, and enabling the capillary tube to stay in the fourth constant temperature tank with the fifth control temperature for a second preset time so as to complete reverse transcription of the sample.
Further, the fifth control temperature is a sample reverse transcription target temperature.
Further, the first constant temperature tank, the fourth constant temperature tank, the second constant temperature tank and the third constant temperature tank are arranged at intervals side by side in sequence.
Further, the control module is further configured to:
and when the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature, controlling the moving mechanism to take out the capillary tube from the first constant temperature tank.
Further, the control module is further configured to:
and when the capillary tube stays in the second constant temperature tank for a second set time and the temperature measured by the temperature measuring module does not reach the second set temperature, controlling the moving mechanism to take out the capillary tube from the second constant temperature tank.
Further, the temperature measuring module is a temperature sensor with a metal shell or a ceramic shell.
Further, the control module is further configured to: in the first cycle, when the temperature measured by the temperature measuring module in the first constant temperature tank reaches a third set temperature, controlling a moving mechanism to take out a capillary tube from the first constant temperature tank; the third set temperature is higher than the first set temperature.
The application also provides a control method of the PCR thermal cycling device, which comprises the following steps:
Further, in step 100:
in the first cycle, when the temperature measured by the temperature measuring module in the first constant temperature tank reaches a third set temperature, the capillary tube is taken out of the first constant temperature tank, and the third set temperature is larger than the first set temperature.
Further, step 101 is further included between the step 100 and the step 200:
the capillary tube is transferred to a fourth constant temperature tank with a fourth controlled temperature, left for a first predetermined time and taken out.
Further, the fourth constant temperature tank of the PCR thermal cycling apparatus can be configured to a sixth control temperature;
before step 100, further comprising step 100c: placing the capillary tube in a fourth constant temperature tank with sixth control temperature for a third preset time and then taking out;
preferably, the sixth control temperature is a cycle start target temperature.
Further, step 101 is further included between the step 100 and the step 200:
the capillary tube is transferred to a fourth constant temperature tank with a fourth controlled temperature, left for a first predetermined time and taken out.
Further, before the step 100, the method further includes a step 100a:
the capillary tube is placed in a fourth thermostatic bath having a fifth controlled temperature, left for a second predetermined time and transferred to the first thermostatic bath.
Further, the step 100 further includes a step 100b:
when the temperature measured by the temperature measuring module in the first constant temperature tank in the first set time does not reach the first set temperature, the control module controls the moving mechanism to take out the capillary tube from the first constant temperature tank;
and/or the number of the groups of groups,
step 200a is also included in step 200:
when the temperature measured by the temperature measuring module in the second constant temperature tank in the second set time does not reach the second set temperature, the control module controls the moving mechanism to take out the capillary tube from the second constant temperature tank.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a PCR thermal circulation device, which comprises a first constant temperature tank, a fourth constant temperature tank, a moving mechanism and a control module, wherein the fourth constant temperature tank can be configured to have a sixth control temperature, the first constant temperature tank has a constant first control temperature, a capillary tube filled with a sample and an independent temperature measuring module are arranged at the moving end of the moving mechanism at intervals, the moving mechanism can drive the capillary tube and the temperature measuring module to synchronously move, the moving mechanism can drive the capillary tube and the temperature measuring module to enter the fourth constant temperature tank first, the initial temperature is prevented from being too low due to the influence of the ambient temperature, the requirement of a first temperature threshold cannot be met rapidly in the circulation process, and the detection efficiency and the reliability of the PCR thermal circulation are improved. The moving mechanism then puts the capillary tube and the temperature measuring module together into the first constant temperature tank or takes the capillary tube and the temperature measuring module out of the first constant temperature tank together. The first constant temperature tank can control the temperature of the sample placed in the first constant temperature tank and filled in the capillary tube, such as heating or cooling; the control module is configured to: the control module is provided with a first set temperature, when the temperature measured by the temperature measuring module in the first constant temperature tank reaches the first set temperature, the control module immediately controls the moving mechanism to take out the capillary tube from the first heat tank, so that the temperature of the sample in the capillary tube is indirectly monitored through the temperature measuring module, and the temperature of the sample in the capillary tube can be always in a first temperature threshold after being taken out from the first constant temperature tank.
The invention also provides a control method of the PCR thermal cycling device, which comprises the following steps: firstly, placing a capillary tube into a fourth constant temperature tank, and taking out the capillary tube after a sample or a temperature measurement module in the capillary tube reaches a circulation initial target temperature; next, placing the capillary tube into a first constant temperature tank, and taking out when the temperature measured by the temperature measuring module reaches a first set temperature; transferring the capillary tube to a second constant temperature tank, and taking out when the temperature measured by the temperature measuring module reaches a second set temperature; transferring the capillary tube to a third constant temperature tank, and taking out after the fluorescent signal acquisition of the sample is completed; next, repeating steps 100 to 300 a predetermined number of times; thus completing the amplification process of the sample.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a PCR thermal cycling apparatus according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a capillary tube and a temperature measuring module of a PCR thermal cycle device according to an embodiment of the present invention;
FIG. 3 is a graph of the temperature of a sample in a capillary according to an embodiment of the present invention;
FIG. 4 is a graph of a temperature measurement module according to an embodiment of the present invention.
Reference numerals:
1-a first constant temperature tank, 2-a second constant temperature tank, 3-a third constant temperature tank, 4-a fourth constant temperature tank, 5-a moving mechanism, 6-a capillary tube, 7-a temperature measuring module and 8-a bracket.
Detailed Description
The following description of the embodiments of the present invention will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the invention are shown.
The components of the embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations. Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.
All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In the description of the present invention, it should be noted that the directions or positional relationships indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, are merely for convenience of describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be either fixedly connected, detachably connected, or integrally connected, for example; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
A PCR thermal cycling apparatus and a control method according to some embodiments of the present application are described below with reference to fig. 1 to 4.
Example 1
The first embodiment provides a PCR thermal cycle device, as shown in fig. 1 and 2, including a first constant temperature tank 1 and a moving mechanism 5, where the first constant temperature tank 1 has a constant first control temperature, a support 8 is provided at a moving end of the moving mechanism 5, a capillary tube 6 containing a sample and a temperature measuring module 7 are installed on the support 8 at intervals, and the moving mechanism 5 can drive the capillary tube 6 and the temperature measuring module 7 to move synchronously, so that the capillary tube 6 and the temperature measuring module 7 can be put into the first constant temperature tank 1 together or taken out of the first constant temperature tank 1 together.
The first thermostatic bath 1 is capable of controlling the temperature of a sample contained in the capillary tube 6 placed inside thereof, such as heating or cooling; in this embodiment, the first thermostatic bath 1 serves as a high temperature bath of a PCR thermal cycle device to heat a sample so that the temperature of the sample is heated to within a first temperature threshold range to complete a DNA denaturation reaction.
The temperature measurement module 7 is able to monitor the temperature of the sample as it is heated by the first thermostat 1 to ensure that the temperature of the sample within the capillary tube 6 is within a first temperature threshold after the capillary tube 6 has been moved out of the first thermostat 1. Because the capillary tube 6 is very small, the temperature measuring module 7 can not be placed in the capillary tube 6 to directly monitor the temperature of the sample, so that the temperature measured by the temperature measuring module 7 and the temperature of the sample in the capillary tube 6 have a temperature difference, in order to accurately judge the time when the capillary tube 6 moves out of the first constant temperature tank 1 according to the temperature measured by the temperature measuring module 7, the PCR thermal cycle device is further provided with a control module, and the control module is configured to: the control module is provided with a first set temperature, when the temperature measured by the temperature measuring module 7 in the first constant temperature tank 1 reaches the first set temperature, the control module immediately controls the moving mechanism 5 to take the capillary tube 6 out of the first constant temperature tank 1, so that the temperature of a sample in the capillary tube 6 is indirectly monitored through the temperature measuring module 7, the temperature of the sample in the capillary tube 6 can be ensured to be at a first temperature threshold value after being taken out of the first constant temperature tank 1, and the rapid and smooth DNA denaturation of the sample is ensured.
In this embodiment, preferably, two temperature measuring modules 7 are arranged side by side on two sides of the capillary tube, and when the temperature of any one temperature measuring module 7 reaches the first set temperature, the control module immediately controls the moving mechanism 5 to take out the capillary tube 6 from the first constant temperature tank 1, so that the risk brought by temperature uniformity is further reduced.
In this embodiment, the thermometry module 7 may be of tubular construction, inserting the temperature sensor into the water or oil inside the tube and sealing it. Preferably, the temperature measuring module 7 is a temperature sensor with a metal shell or a ceramic shell, so that the temperature measuring module 7 is not easy to crack and damage in the process of moving along with the capillary tube 6, thereby ensuring that the whole detection process is successfully completed.
However, since the material of the temperature measuring module 7 is different from that of the capillary tube 6, the transient thermal response characteristics of the two in the constant temperature tank are different, and the temperature measured by the temperature measuring module 7 and the temperature of the sample in the capillary tube 6 at the same environmental temperature are different, a stable temperature corresponding relationship needs to be established between the two. In this embodiment, the first temperature threshold is a target temperature at which the sample completes DNA denaturation, such as 95 ℃, preferably the first control temperature of the first incubator 1 ranges from 100 ℃ to 130 ℃, by setting the first control temperature well above the target temperature at which the sample completes DNA denaturation, the sample can be rapidly heated to a desired temperature and DAN denaturation completed within the first incubator 1. Preferably, the first control temperature is 120 ℃.
In this embodiment, because there are individual differences between the temperature measurement modules 7 of different materials or structures, and different transient thermal response deviations exist between the temperature measurement modules and the capillary tube 6, the value range of the first set temperature of the temperature measurement module 7 is 90-105 ℃ so as to meet the DNA denaturation temperature requirement of the sample 95 ℃; meanwhile, in order to improve the reliability of system control and reduce the control difficulty, the first temperature threshold is further set to be (94+/-2) DEG C, so that the temperature measuring modules 7 with different materials or structures can establish stable temperature corresponding relations with the capillary tube 6. Preferably, when the temperature measuring module 7 is an NTC steel tube, the first set temperature is 102 ℃; namely, when the temperature measured by the NTC steel tube reaches 102 ℃, the control module immediately controls the moving mechanism 5 to move the capillary tube 6 out of the first constant temperature tank 1, and at the moment, the temperature of the sample can be ensured to be always at (94+/-2) DEG C, so that the temperature requirement of finishing DAN denaturation in a plurality of high-speed cycles is met.
In this embodiment, preferably, the PCR thermal cycling device further includes a second thermostatic bath 2 serving as a low-temperature bath and a third thermostatic bath 3 serving as an optical bath, and the second thermostatic bath 2 is set to have a constant second control temperature, and the third thermostatic bath 3 is set to have a constant third control temperature; the control module can control the moving mechanism 5 to sequentially transfer the capillary tube 6 taken out from the first constant temperature tank 1 to the second constant temperature tank 2 and the third constant temperature tank 3, so that the sample completes cooling annealing in the second constant temperature tank 2, and completes fluorescent signal acquisition in the third constant temperature tank 3 (completed by external fluorescent signal acquisition equipment).
Preferably, the sample in the capillary 6 needs to be cooled in the second thermostatic bath 2 so that the temperature of the capillary 6 is within a second temperature threshold before reaching the third thermostatic bath 3, to meet the temperature requirement for completing DAN renaturation in a plurality of high speed cycles, preferably the second temperature threshold is (57.5±2) °c.
Since the temperature of the sample in the capillary tube 6 is still continuously reduced during the process of taking the capillary tube 6 out of the second thermostatic bath 2 and transferring it to the third thermostatic bath 3, in order to ensure that the temperature of the sample can be quickly reduced to within the second temperature threshold range before the capillary tube 6 enters the third thermostatic bath 3, the temperature of the second thermostatic bath 2, namely the second control temperature, is far lower than the second temperature threshold; preferably, the second control temperature range of the second thermostatic bath 2 is 10-25 ℃; further, the second control temperature was 15 ℃.
Meanwhile, in the process of cooling the capillary tube 6 in the second constant temperature tank 2, the temperature of the sample in the capillary tube 6 is indirectly monitored through the temperature measuring module 7, so that the time for the capillary tube 6 to move out of the second constant temperature tank 2 is determined according to the temperature measured by the temperature measuring module 7; preferably, the control module is configured to: the control module is provided with a second set temperature, and the value range of the second set temperature is preferably 50-70 ℃; when the temperature measured by the temperature measuring module 7 in the second constant temperature tank 2 reaches the second set temperature, the control module immediately controls the moving mechanism 5 to take the capillary tube 6 out of the second constant temperature tank 2, so that the temperature of the internal sample is ensured to be within the second temperature threshold range before the capillary tube 6 is transferred into the third constant temperature tank 3. Preferably, the second set temperature is 65 ℃.
It should be noted that, the specific values of the first set temperature and the second set temperature may be set according to the actual situation, for example, when the temperatures of the first thermostat 1 and the second thermostat 2 are changed, or the materials and the structures of the temperature measuring module are changed, or the first temperature threshold and the second temperature threshold to be reached by the sample are changed, the values of the first set temperature and the second set temperature may be adjusted accordingly.
Specifically, specific values of the first set temperature and the second set temperature are obtained by performing calibration compensation and temperature profile calibration on the temperature of the thermostat. For example, a temperature measuring module and a capillary tube filled with a predetermined amount of water are placed at the moving end of the moving mechanism to simulate the state of the sample filled in the capillary tube by the water, and a thermocouple is inserted in the capillary tube to collect the temperature of the sample in the capillary tube, and a thermocouple probe is connected to a temperature collector; the capillary tube and the temperature measuring module are driven to circularly move between the first constant temperature tank and the second constant temperature tank through the moving mechanism, the first extraction temperature and the second extraction temperature are set, namely, the capillary tube is moved out of the high temperature tank when the temperature of the temperature measuring module reaches the first extraction temperature, the capillary tube is moved out of the low temperature tank when the temperature of the temperature measuring module reaches the second extraction temperature, a temperature curve of a sample in the capillary tube measured by a thermocouple shown in fig. 3 is given by the temperature collector, meanwhile, a temperature curve shown in fig. 4 can be obtained according to the temperature measured by the temperature measuring module, and the two curves are regular curves with peaks and troughs; when the first extraction temperature is 102 ℃ of the first set temperature, and the second extraction temperature is 65 ℃ of the second set temperature, the peak of the temperature curve of the sample in the capillary tube can be stabilized at (94+/-2) DEG C, namely a first temperature threshold value, and the trough can be stabilized at (57.5+/-2) DEG C, namely a second temperature threshold value, so that the first set temperature and the second set temperature are determined.
In this embodiment, preferably, since the temperature measuring module 7 is inserted into the height Wen Caoshi for the first time at the beginning of a cycle, and no stable correspondence is established with the sample tube, the temperature measuring module has a different first extraction temperature setting during a plurality of cycles, the first extraction temperature of the temperature measuring module 7 being higher during the first cycle than during the subsequent cycle. For example, in 40 cycles, the temperature of the 1 st cycle process temperature measurement module is 1-4 ℃ higher than the temperature of the next 39 cycles, preferably 2 ℃, as shown in fig. 4, the first temperature of the first cycle is 104 ℃, and the first temperature of the 2 st to 39 th cycles is 102 ℃, so as to meet the first temperature threshold requirement.
In this embodiment, it is preferable that the third control temperature of the third thermostatic bath 3 is 75 deg.c to perform the medium-temperature extension of the sample placed in the capillary tube 6 inside thereof through the third thermostatic bath 3, ensuring that the sample successfully completes the fluorescent signal collection. Preferably, the control module is communicatively connected to the device for fluorescence signal acquisition, and the control module is further configured to: after the fluorescent signal collection device completes the fluorescent signal collection of the sample, the control module controls the moving mechanism 5 to move the capillary 6 out of the third constant temperature groove 3.
Preferably, the control module is further configured to: the moving mechanism 5 is controlled to drive the capillary 6 to circularly move between the first constant temperature groove 1, the second constant temperature groove 2 and the third constant temperature groove 3 for a plurality of times, so that the sample completes the amplification flow in the PCR thermal circulation device.
Example two
The second embodiment is an improvement on the basis of the above embodiment, and the technical content disclosed in the above embodiment is not repeated, and the content disclosed in the above embodiment also belongs to the content disclosed in the embodiment.
In the second embodiment, it is preferable that the PCR thermal cycle apparatus further be provided with a fourth constant temperature bath 4, the fourth constant temperature bath 4 being usable as a reverse transcription bath, and when the fourth constant temperature bath 4 is used as a reverse transcription bath, the fourth constant temperature bath 4 is set to a constant fifth control temperature, which is a sample reverse transcription target temperature; preferably, the fifth control temperature is 55 ℃; when the fourth thermostatic bath 4 is used as a reverse transcription bath, the four thermostatic baths are arranged side by side in the order of the fourth thermostatic bath 4, the first thermostatic bath 1, the second thermostatic bath 2, and the third thermostatic bath 3.
The control module is configured to: the moving mechanism 5 is controlled to sequentially transfer the capillary 6 to the fourth constant temperature tank 4, the first constant temperature tank 1, the second constant temperature tank 2 and the third constant temperature tank 3 and circulate for a plurality of times; and the sample is left in the fourth thermostatic bath 4 for a second predetermined time to complete reverse transcription, and the capillary 6 is taken out from the first thermostatic bath 1, the second thermostatic bath 2 and the third thermostatic bath 3 at the timing according to the first embodiment, so that the sample completes DNA denaturation in the first thermostatic bath 1, cooling annealing in the second thermostatic bath 2 and fluorescence signal collection in the third thermostatic bath 3.
Example III
The third embodiment is an improvement on the above embodiment, and the technical content disclosed in the above embodiment is not repeated, and the content disclosed in the above embodiment also belongs to the content disclosed in the embodiment.
In the third embodiment, preferably, the fourth thermostatic bath 4 may be used as an auxiliary denaturation bath, and when the fourth thermostatic bath 4 is used as an auxiliary denaturation bath, the fourth thermostatic bath 4 is set to a constant fourth control temperature, which is a sample denaturation target temperature; preferably, the fourth control temperature is 95 ℃; the four thermostats are arranged side by side in the order of the first thermostat 1, the fourth thermostat 4, the second thermostat 2 and the third thermostat 3.
The control module is configured to: the movement mechanism 5 is controlled to sequentially transfer the capillary 6 to the first thermostatic bath 1, the fourth thermostatic bath 4, the second thermostatic bath 2 and the third thermostatic bath 3 and circulate a plurality of times, and the sample is allowed to stay in the fourth thermostatic bath 4 for a first predetermined time so that the sample is continuously denatured in the fourth thermostatic bath 4 for a period of time, and the timing of taking out the capillary 6 from the first thermostatic bath 1, the second thermostatic bath 2 and the third thermostatic bath 3 is referred to as the first embodiment described above.
In the third embodiment, preferably, when the fourth thermostatic bath 4 is used as the auxiliary denaturation bath, the fourth thermostatic bath 4 can also be set to a constant sixth control temperature, which is a cycle start target temperature; before the first cycle starts, the moving mechanism 5 inserts the capillary tube 6 and the temperature measuring module 7 into the fourth constant temperature tank 4 with the sixth control temperature, so that the sample of the capillary tube 6 or the temperature measuring module 7 reaches the cycle starting target temperature, and the situation that the starting temperature is too low due to the influence of the ambient temperature is avoided, and the requirement of the first temperature threshold cannot be met rapidly in the cycle process. The sixth control temperature is in the range of 50-57 ℃, preferably 55 ℃. Further, the moving mechanism 5 inserts the capillary tube 6 and the temperature measuring module 7 into the fourth constant temperature tank 4 with the sixth control temperature for a predetermined time, preferably 1 minute, so as to ensure that the sample of the capillary tube 6 can reach the cycle starting target temperature, and improve the detection efficiency and reliability of the PCR thermal cycle.
Example IV
The fourth embodiment is an improvement on the above embodiment, and the technical content disclosed in the above embodiment is not repeated, and the content disclosed in the above embodiment also belongs to the content disclosed in the embodiment.
In the fourth embodiment, it is preferable that the fourth thermostatic bath 4 functions as both a reverse transcription bath and an auxiliary denaturation bath, in which case the four thermostatic baths are arranged side by side in the order of the first thermostatic bath 1, the fourth thermostatic bath 4, the second thermostatic bath 2, and the third thermostatic bath 3.
The control module is configured to: the control capillary 6 is transferred and circulated a plurality of times in the order of the fourth thermostatic bath 4, the first thermostatic bath 1, the fourth thermostatic bath 4, the second thermostatic bath 2, and the third thermostatic bath 3.
During each cycle, the temperature of the fourth thermostatic bath 4 is first set to the fifth control temperature, and the capillary tube 6 is first put into the fourth thermostatic bath 4 with the fifth control temperature for reverse transcription; after the capillary 6 is taken out of the fourth thermostatic bath 4 to be transferred into the first thermostatic bath 1, the temperature of the fourth thermostatic bath 4 is adjusted to be higher to a fourth control temperature, so that the sample can be transferred into the fourth thermostatic bath 4 with the fourth control temperature for a period of time after finishing DNA denaturation in the first thermostatic bath 1, and then the transfer to the subsequent thermostatic bath is continued.
For the timing of taking out the capillary 6 from the fourth thermostatic bath 4 for reverse transcription tank, the first thermostatic bath 1, the fourth thermostatic bath 4 serving as an auxiliary denaturation tank, the second thermostatic bath 2 and the third thermostatic bath 3, reference can be made to the above-described embodiments one to three.
Example five
The fifth embodiment is an improvement on the above embodiment, and the technical content disclosed in the above embodiment is not repeated, and the content disclosed in the above embodiment also belongs to the content disclosed in the embodiment.
In a fifth embodiment, the control module is further configured with an early warning function, preferably the control module is further configured to: the control module is provided with a first set time and a second set time, when the capillary tube 6 stays in the first constant temperature tank 1 for the first set time and the temperature measured by the temperature measuring module 7 still does not reach the first set temperature, the control module judges that the first constant temperature tank 1 or the temperature measuring module 7 is in fault and gives out fault early warning, and meanwhile, the moving mechanism 5 is controlled to take out the capillary tube 6 from the first constant temperature tank 1; or when the capillary tube 6 stays in the second constant temperature tank 2 for a second set time and the temperature measured by the temperature measuring module 7 does not reach the second set temperature yet, the control module judges that the second constant temperature tank 2 or the temperature measuring module 7 is in fault and gives out fault early warning, and meanwhile controls the moving mechanism 5 to take out the capillary tube 6 from the second constant temperature tank 2.
Examples six to nine
The control method for the PCR thermal cycler in the above embodiments is provided in one of the sixth to ninth embodiments, so that the sample completes the amplification process in the PCR thermal cycler.
Example six
In the sixth embodiment, preferably, the control method of the PCR thermal cycler includes the steps of:
when the temperature measured by the temperature measuring module reaches the first set temperature within the first set time, the capillary tube is removed from the first constant temperature tank, so that the temperature of the sample reaches the first temperature threshold range, DNA denaturation is completed, and the step 200 is continuously executed.
When the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature yet, the control module judges that the first constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the first constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
when the temperature measured by the temperature measuring module reaches the second set temperature within the second set time, the capillary tube is moved out of the second constant temperature tank, so that the temperature of the sample can reach the second temperature threshold range when the sample enters the third constant temperature tank, cooling and annealing are completed, and the step 300 is continuously executed.
When the capillary tube stays in the second constant temperature tank for a second set time and the temperature measured by the temperature measuring module does not reach the second set temperature yet, the control module judges that the second constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the second constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
And 300, setting the temperature of the third constant temperature tank to be a third control temperature, transferring the capillary tube into the third constant temperature tank by the moving mechanism so that the sample completes fluorescent signal acquisition in the third constant temperature tank, and removing the capillary tube from the third constant temperature tank after completing fluorescent signal acquisition of the sample.
Example seven
In the seventh embodiment, preferably, the control method of the PCR thermal cycling apparatus includes the steps of:
and 100c, placing the capillary tube in a fourth constant temperature tank with a sixth control temperature for a third preset time, and taking out the capillary tube to enable the sample in the capillary tube to reach the circulation starting target temperature.
when the temperature measured by the temperature measuring module reaches the first set temperature within the first set time, the capillary tube is removed from the first constant temperature tank, so that the temperature of the sample reaches the first temperature threshold range, DNA denaturation is completed, and the step 200 is continuously executed.
When the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature yet, the control module judges that the first constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the first constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
Step 101, setting the temperature of the fourth constant temperature tank to be a fourth control temperature, transferring the capillary tube removed from the first constant temperature tank into the fourth constant temperature tank with the fourth control temperature by the moving mechanism, and enabling the capillary tube to stay in the fourth constant temperature tank for a first preset time so as to enable the sample to be continuously denatured in the fourth constant temperature tank for a period of time.
when the temperature measured by the temperature measuring module reaches the second set temperature within the second set time, the capillary tube is moved out of the second constant temperature tank, so that the temperature of the sample can reach the second temperature threshold range when the sample enters the third constant temperature tank, cooling and annealing are completed, and the step 300 is continuously executed.
When the capillary tube stays in the second constant temperature tank for a second set time and the temperature measured by the temperature measuring module does not reach the second set temperature yet, the control module judges that the second constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the second constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
And 300, setting the temperature of the third constant temperature tank to be a third control temperature, transferring the capillary tube into the third constant temperature tank by the moving mechanism so that the sample completes fluorescent signal acquisition in the third constant temperature tank, and removing the capillary tube from the third constant temperature tank after completing fluorescent signal acquisition of the sample.
Example eight
In embodiment eight, preferably, the control method of the PCR thermal cycling apparatus includes the steps of:
and 100a, setting the temperature of the fourth constant temperature tank to be a fifth control temperature, and moving the capillary tube and the temperature measuring module out of the capillary tube after the capillary tube and the temperature measuring module are placed in the fourth constant temperature tank for a second preset time by the moving mechanism so as to enable the sample to finish reverse transcription in the fourth constant temperature tank with the fifth control temperature.
when the temperature measured by the temperature measuring module reaches the first set temperature within the first set time, the capillary tube is removed from the first constant temperature tank, so that the temperature of the sample reaches the first temperature threshold range, DNA denaturation is completed, and the step 200 is continuously executed.
When the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature yet, the control module judges that the first constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the first constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
when the temperature measured by the temperature measuring module reaches the second set temperature within the second set time, the capillary tube is moved out of the second constant temperature tank, so that the temperature of the sample can reach the second temperature threshold range when the sample enters the third constant temperature tank, cooling and annealing are completed, and the step 300 is continuously executed.
When the capillary tube stays in the second constant temperature tank for a second set time and the temperature measured by the temperature measuring module does not reach the second set temperature yet, the control module judges that the second constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the second constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
And 300, setting the temperature of the third constant temperature tank to be a third control temperature, transferring the capillary tube into the third constant temperature tank by the moving mechanism so that the sample completes fluorescent signal acquisition in the third constant temperature tank, and removing the capillary tube from the third constant temperature tank after completing fluorescent signal acquisition of the sample.
Example nine
In the ninth embodiment, preferably, the control method of the PCR thermal cycling apparatus includes the steps of:
and 100a, setting the temperature of the fourth constant temperature tank to be a fifth control temperature, and moving the capillary tube and the temperature measuring module out of the capillary tube after the capillary tube and the temperature measuring module are placed in the fourth constant temperature tank for a second preset time by the moving mechanism so as to enable the sample to finish reverse transcription in the fourth constant temperature tank with the fifth control temperature.
when the temperature measured by the temperature measuring module reaches the first set temperature within the first set time, the capillary tube is removed from the first constant temperature tank, so that the temperature of the sample reaches the first temperature threshold range, DNA denaturation is completed, and the step 200 is continuously executed.
When the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature yet, the control module judges that the first constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the first constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
Step 101, setting the temperature of the fourth constant temperature tank to be a fourth control temperature, transferring the capillary tube removed from the first constant temperature tank into the fourth constant temperature tank with the fourth control temperature by the moving mechanism, and enabling the capillary tube to stay in the fourth constant temperature tank for a first preset time so as to enable the sample to be continuously denatured in the fourth constant temperature tank for a period of time.
when the temperature measured by the temperature measuring module reaches the second set temperature within the second set time, the capillary tube is moved out of the second constant temperature tank, so that the temperature of the sample can reach the second temperature threshold range when the sample enters the third constant temperature tank, cooling and annealing are completed, and the step 300 is continuously executed.
When the capillary tube stays in the second constant temperature tank for a second set time and the temperature measured by the temperature measuring module does not reach the second set temperature yet, the control module judges that the second constant temperature tank or the temperature measuring module fails and gives out fault early warning, meanwhile, the moving mechanism is controlled to stop running after the capillary tube is taken out of the second constant temperature tank, the following steps are not executed, and the device is restarted after the fault is removed.
And 300, setting the temperature of the third constant temperature tank to be a third control temperature, transferring the capillary tube into the third constant temperature tank by the moving mechanism so that the sample completes fluorescent signal acquisition in the third constant temperature tank, and removing the capillary tube from the third constant temperature tank after completing fluorescent signal acquisition of the sample.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (15)
1. The PCR thermal cycle device is characterized by comprising a moving mechanism, a first constant temperature tank, a fourth constant temperature tank and a control module;
the first thermostat can be configured to have a first control temperature;
the moving mechanism is provided with a capillary tube filled with a sample and a temperature measuring module, and can drive the capillary tube and the temperature measuring module to synchronously move;
the fourth thermostat can be configured to have a sixth control temperature;
the control module is configured to:
controlling the moving mechanism to transfer the capillary tube and the temperature measuring module into the fourth constant temperature tank with the sixth control temperature, and controlling the moving mechanism to move the capillary tube out of the fourth constant temperature tank so that the sample or the temperature measuring module reaches a circulation starting target temperature after the capillary tube is moved out of the fourth constant temperature tank;
controlling the moving mechanism to transfer the capillary tube and the temperature measuring module from the fourth constant temperature tank into the first constant temperature tank;
when the temperature measured by the temperature measuring module reaches a first set temperature, controlling the moving mechanism to move the capillary tube out of the first constant temperature tank so that the temperature of the sample is within a first temperature threshold range after the capillary tube is moved out of the first constant temperature tank; the first control temperature is greater than the first set temperature.
2. The PCR thermal cycler of claim 1, wherein the movement mechanism is controlled to transfer the capillary tube and the thermometry module into the fourth constant temperature cell having the sixth controlled temperature for a third predetermined time before removal to bring the sample or the thermometry module to a cycle initiation target temperature.
3. The PCR thermal cycler of claim 1, wherein the sixth control temperature is a cycle start target temperature, the sixth control temperature being less than the first set temperature.
4. The PCR thermal cycler of claim 1, wherein the first set temperature is greater than the first temperature threshold.
5. The PCR thermal cycler of claim 1 further comprising a second thermostat configured to have a second control temperature;
the control module is further configured to:
controlling the moving mechanism to transfer the capillary tube from the first constant temperature tank into the second constant temperature tank;
when the temperature measured by the temperature measuring module reaches a second set temperature, controlling the moving mechanism to move the capillary tube out of the second constant temperature tank so that the temperature of the sample is within a second temperature threshold range after the capillary tube is moved out of the second constant temperature tank;
The second control temperature is less than the second set temperature.
6. The PCR thermal cycler of claim 5 further comprising a third thermostat configured to have a third control temperature;
the control module is further configured to:
controlling the moving mechanism to transfer the capillary from the second thermostatic bath to the third thermostatic bath;
and after the sample in the capillary tube completes fluorescent signal acquisition in the third constant temperature tank, controlling the moving mechanism to take out the capillary tube from the third constant temperature tank.
7. The PCR thermal cycler of claim 6, wherein the fourth thermostat is further configurable to have a fourth control temperature;
the control module is further configured to:
controlling the moving mechanism to sequentially transfer the capillary tube to the fourth constant temperature bath having the sixth control temperature, the first constant temperature bath, the fourth constant temperature bath having the fourth control temperature, the second constant temperature bath, and the third constant temperature bath, and allowing the capillary tube to stay in the fourth constant temperature bath having the fourth control temperature for a first predetermined time;
Wherein the fourth control temperature is a sample denaturation target temperature.
8. The PCR thermal cycler of claim 7, wherein the first, fourth, second, and third thermostats are sequentially disposed side-by-side in a spaced relationship.
9. The PCR thermal cycler of claim 1, wherein the control module is further configured to:
and when the capillary tube stays in the first constant temperature tank for a first set time and the temperature measured by the temperature measuring module does not reach the first set temperature, controlling the moving mechanism to take out the capillary tube from the first constant temperature tank.
10. A control method of a PCR thermal cycle device for a PCR thermal cycle device according to any one of claims 6 to 9; the method is characterized by comprising the following steps of:
step 100c: placing the capillary tube into a fourth constant temperature tank with sixth control temperature, and taking out the sample or the temperature measuring module in the capillary tube after reaching the circulation starting target temperature;
step 100, placing a capillary tube in a first constant temperature tank, and taking out the capillary tube when the temperature measured by a temperature measuring module reaches a first set temperature so that the temperature of a sample in the capillary tube is within a first temperature threshold range;
Step 200, transferring the capillary tube to a second constant temperature tank, and taking out the capillary tube when the temperature measured by the temperature measuring module reaches a second set temperature so that the temperature of a sample in the capillary tube is within a second temperature threshold range;
step 300, transferring the capillary tube to a third constant temperature tank, and taking out after the fluorescent signal acquisition of the sample is completed;
step 400, repeat steps 100 to 300 a predetermined number of times to complete a plurality of cycles.
11. The method according to claim 10, wherein in step 100c, the capillary is placed in a fourth constant temperature bath having a sixth control temperature for a third predetermined time, and then the sample in the capillary is taken out to reach a cycle start target temperature.
12. The method of controlling a PCR thermal cycling apparatus according to claim 10, further comprising step 101 between the step 100 and the step 200:
the capillary tube is transferred to a fourth constant temperature tank with a fourth controlled temperature, left for a first predetermined time and taken out.
13. The method of controlling a PCR thermal cycler as recited in claim 10, wherein the sixth control temperature is a cycle start target temperature.
14. The method of controlling a PCR thermal cycling apparatus according to claim 10, wherein the step 100 further comprises a step 100b of:
When the temperature measured by the temperature measuring module in the first constant temperature tank in the first set time does not reach the first set temperature, the control module controls the moving mechanism to take out the capillary tube from the first constant temperature tank.
15. The method according to claim 10, wherein in the step 400, the first extraction temperature of the temperature measuring module is higher than the first extraction temperature in the subsequent cycle.
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| CN202211261886.6A CN116286320A (en) | 2021-12-06 | 2021-12-06 | PCR thermal cycle device and control method |
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| US6787338B2 (en) * | 1990-06-04 | 2004-09-07 | The University Of Utah | Method for rapid thermal cycling of biological samples |
| CN104263634B (en) * | 2014-09-24 | 2016-08-17 | 中国科学技术大学 | A kind of streaming aggregate polymerase chain reaction circulating-heating instrument based on capillary tube and heating means |
| CN106978328A (en) * | 2016-01-15 | 2017-07-25 | 北京酷搏科技有限公司 | Thermal cycle reaction component and the real-time detection apparatus with it |
| SG10201700260XA (en) * | 2016-06-10 | 2018-01-30 | Star Array Pte Ltd | Rapid thermal cycling for sample analyses and processing |
| CN106222068A (en) * | 2016-08-22 | 2016-12-14 | 上海交通大学 | Miniature PCR system of capillary glass tube and preparation method thereof |
| CN106442454A (en) * | 2016-11-17 | 2017-02-22 | 中国科学院上海光学精密机械研究所 | Quick gene amplification detection device and quick gene amplification detection method based on fluorescent quantitation |
| CN206385166U (en) * | 2017-01-19 | 2017-08-08 | 北京凡知医学科技有限公司 | A kind of DNA cloning device |
| CN109797091B (en) * | 2019-01-17 | 2021-02-26 | 浙江大学 | Rotary type rapid double-temperature PCR amplification automatic control device and control method |
| CN110387325A (en) * | 2019-08-13 | 2019-10-29 | 广州市华南医学研究中心 | A kind of very fast PCR reaction checking device and detection method |
| CN111023613A (en) * | 2019-11-27 | 2020-04-17 | 合肥通用制冷设备有限公司 | Accurate temperature control refrigerating system |
| CN114134033B (en) * | 2021-12-06 | 2022-11-04 | 广东润鹏生物技术有限公司 | PCR thermal cycling device and control method |
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