CN110116028B - Microfluidic experimental device and method - Google Patents
Microfluidic experimental device and method Download PDFInfo
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- CN110116028B CN110116028B CN201910449523.7A CN201910449523A CN110116028B CN 110116028 B CN110116028 B CN 110116028B CN 201910449523 A CN201910449523 A CN 201910449523A CN 110116028 B CN110116028 B CN 110116028B
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- 239000000243 solution Substances 0.000 claims abstract description 118
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- 239000007788 liquid Substances 0.000 claims abstract description 65
- 239000011550 stock solution Substances 0.000 claims abstract description 54
- 238000002474 experimental method Methods 0.000 claims abstract description 47
- 238000009826 distribution Methods 0.000 claims abstract description 12
- 239000012530 fluid Substances 0.000 claims description 20
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- 239000012086 standard solution Substances 0.000 claims description 12
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- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 238000012360 testing method Methods 0.000 claims description 5
- 230000007774 longterm Effects 0.000 abstract description 6
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004377 microelectronic Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
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- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
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- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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Abstract
The invention provides a microfluidic experimental device and a method, wherein the device comprises a microfluidic laboratory, and further comprises a stock solution pushing device, a liquid distribution bottle, a first microfluidic pushing device and a multi-channel switching valve which are sequentially connected through a microfluidic pipeline; the liquid outlet of multichannel diverter valve links to each other with one-level buffer bottle and second grade buffer bottle respectively, one-level buffer bottle and second grade buffer bottle respectively through second microfluid propelling movement equipment with the microfluidic laboratory links to each other. The invention can meet the requirements of multi-channel contrast experiments, shortens the time required by a plurality of groups of experiments, can realize long-term real-time regulation and control of various microenvironment parameters, simultaneously reduces manual operation, and improves the control precision of solution preparation and the stability of the experiments.
Description
Technical Field
The invention relates to the emerging cross-technology fields of fluid physics, biology, chemistry, microelectronics, biomedical engineering and the like, in particular to a microfluidic experimental device and a microfluidic experimental method.
Background
Microfluidics refers to the science and technology involved in systems using microchannels (tens to hundreds of microns in size) to process or manipulate tiny fluids, an emerging interdiscipline of chemistry, fluid physics, microelectronics, new materials, biology and biomedical engineering. Chinese patent publication No. CN108626102A discloses a microfluidic device, which includes a displacement actuator and a microfluidic chip, wherein the displacement actuator and the microfluidic chip are independent from each other; the micro-fluidic chip is provided with a micro-pipeline, the micro-pipeline is provided with an input end and an output end, and an extrusion part is arranged between the input end and the output end of the micro-pipeline; the displacement actuator has a stopper member that presses the pressing portion micro-tube. The prior biological culture experiment based on the microfluidic chip represented by the microfluidic device has the following problems: (1) the requirements of multi-chip or multi-chip multi-chamber comparison experiments, especially simultaneous comparison, cannot be met, and the time required for carrying out multiple groups of experiments is long; (2) the long-term dynamic accurate control on experimental micro-chemical (nutrient salt, pH value and the like) and physical (temperature and salinity) environments cannot be realized; (3) the traditional microfluidic control experiment or cell culture experiment is manually operated to complete liquid preparation and pushing of single prepared liquid, automation is not realized, artificial interference factors such as poor control precision of manual operation and the like exist, and stability is poor.
Disclosure of Invention
One of the purposes of the invention is to solve the problem that the prior art can not carry out comparison experiments, especially the problem that the time required for carrying out comparison and multiple groups of experiments simultaneously is long.
The invention also aims to realize long-term real-time regulation and control of various microenvironment parameters, reduce manual operation and improve the control precision and stability of the control system.
In order to achieve the above object, the present invention firstly provides a microfluidic experimental apparatus, comprising a microfluidic laboratory, and further comprising a stock solution pushing device, a liquid dispensing bottle, a first microfluidic pushing device, and a multi-channel switching valve, which are sequentially connected through a microfluidic pipeline; the liquid outlet of multichannel diverter valve links to each other with one-level buffer bottle and second grade buffer bottle respectively, one-level buffer bottle and second grade buffer bottle respectively through second microfluid propelling movement equipment with the microfluidic laboratory links to each other.
Preferably, the device further comprises a controller, and the stock solution pushing device, the first microfluid pushing device, the second microfluid pushing device and the multi-channel switching valve are respectively connected with the controller.
Preferably, a sensor is arranged in the liquid dispensing bottle and connected with the controller.
Preferably, the number of the stock solution pushing devices is N, the stock solution pushing devices are arranged in parallel, N is larger than or equal to 1, and each stock solution pushing device is respectively connected with the liquid distribution bottle.
Preferably, the number of the microfluidic laboratories is M, the microfluidic laboratories are arranged in parallel, and M is more than or equal to 1; the number of the primary buffer bottles is M, and the liquid outlet of each primary buffer bottle is connected with the corresponding microfluidic laboratory through an M-channel fluid conveying device; the number of the secondary buffer bottles is M, and the liquid outlet of each secondary buffer bottle is connected with the corresponding microfluidic laboratory through another M-channel fluid conveying device.
Preferably, the microfluidic laboratory is a microfluidic chip or a biological culture dish or a biological test box.
Preferably, the stock solution pushing device comprises a stock solution bottle and a third pushing device connected with the stock solution bottle.
Preferably, the sensor is one or more of a pH sensor, a salinity sensor, a dissolved oxygen sensor.
Preferably, the microfluidic pushing device is one of a pneumatic pump and a peristaltic pump.
The invention also provides a microfluidic experimental method based on the experimental device, which comprises the following steps:
the method comprises the following steps: respectively filling corresponding standard liquids required by experiments into the N stock solution pushing devices;
step two: the controller controls the stock solution pushing equipment to push the corresponding standard solution into the solution preparation bottle, and meanwhile, a sensor in the solution preparation bottle monitors a corresponding concentration signal of the solution in the solution preparation bottle in real time and transmits the concentration signal to the controller;
step three: the controller judges whether the received concentration signal is consistent with the actually required concentration signal, and if so, the stock solution pushing equipment is stopped to convey the standard solution to the solution preparation bottle, so that the first solution preparation is completed; if not, continuously conveying the corresponding standard liquid to the liquid preparation bottle through the stock solution pushing equipment until all concentration signals are consistent with actually required concentration signals, and finishing the first solution preparation;
step four: after the first solution preparation is finished, pushing the solution in the solution preparation bottle to a first primary buffer bottle through a first microfluid conveying device through a multi-channel switching valve;
step five: repeating the second step and the third step, sequentially completing the second solution preparation and the third solution preparation … … Mth solution preparation, and correspondingly pushing the corresponding solutions to a second primary buffer bottle and a third primary buffer bottle … … Mth primary buffer bottle;
step six: after the M primary buffer bottles finish pushing the corresponding solutions, simultaneously pushing the solutions in the M primary buffer bottles to corresponding microfluidic laboratories to perform a first group of experiments;
step seven: when the sixth step is carried out, the second step and the third step are repeated, … … th-time solution preparation of first solution preparation, second solution preparation and third solution preparation required by the next group of experiments is respectively completed, corresponding solutions are correspondingly pushed to a first secondary buffer bottle, a second secondary buffer bottle and a third … … Mth secondary buffer bottle, and the next step of operation is waited after the M secondary buffer bottles complete the pushing of the corresponding solutions;
step eight: after the first group of experiments are completed, the solutions in the M secondary buffer bottles are simultaneously pushed to corresponding microfluidic laboratories to carry out a second group of experiments.
The invention has the following positive effects:
1. in order to ensure the consistency of time, the primary buffer bottles with the same quantity as the labs (or the chambers of the same lab) are added between the liquid preparation bottles and the microfluidic lab, and all the solutions are pushed into the microfluidic lab after being prepared.
2. In order to save the time cost of liquid preparation, when the solution in the primary buffer bottle is pushed into the chip, the solution can be continuously prepared and stored in the secondary buffer bottle, time sharing multiplexing is realized, and the working efficiency is improved.
3. The pushing device for pushing the solution in the solution preparation bottle to the first-stage buffer bottle and the second-stage buffer bottle only needs one channel, and a multi-channel automatic switching valve is added behind the pushing device to complete the solution preparation of the plurality of buffer bottles.
4. The mixing liquid preparation device can meet the mixing liquid preparation of various standard liquids and control a plurality of microenvironment parameters in real time.
5. In the process of long-time observation or culture experiment, the liquid is prepared by using the corresponding microfluid pushing equipment, so that the process of manually preparing the liquid can be omitted, and the control precision cannot be influenced by the specification problem of the injector.
6. Through setting up the liquid distribution bottle, solved when doing the contrast experiment because solution is at the little difference in ratio and prepare complicated problem, can utilize the accurate and simple mixed preparation of accomplishing different solutions of same equipment.
7. The related microfluid pushing equipment has wide selectivity, and can adopt, but is not limited to peristaltic pumps, pneumatic pumps and other equipment.
8. The closed-loop regulation and control of solution preparation is formed by the feedback of a controller and a sensor, so that the real-time control of the solution preparation is realized, and the precision of the solution preparation is effectively ensured, namely the traditional control of the regulation and control of the biological culture environment based on a culture dish or a test box mainly comprises human eye observation, manual regulation and the like, and the required microfluid volume in a microfluidic laboratory is small, so that the requirement on the concentration of liquid is higher, and the real-time high-precision closed-loop regulation and control can be realized by using the high-precision sensor provided by the invention, such as pH: plus or minus 0.01; salinity: 0.1 ppt; dissolved oxygen: 0.1 mg/L.
9. The buffer bottle and the liquid distribution bottle can keep good sealing performance so as to reduce the solubility change caused by the evaporation of the solution, and can meet the air pressure requirement when an air pressure pump and the like are used as pushing equipment.
In a word, the invention can realize long-term real-time regulation and control of various microenvironment parameters, can meet the requirements of multi-channel comparison experiments, particularly simultaneous comparison, simultaneously reduces manual operation, and improves the control precision of solution preparation and the stability of the experiments.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 is a schematic view of the connection structure of the controller and various components of the present invention;
FIG. 2 is a schematic structural diagram of the microfluidic experimental device according to the present invention;
FIG. 3 is a schematic diagram of the structure of the microfluidic experimental device described in example 1.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Furthermore, it should be noted that in the description of the present invention, the terms "left", "right", "upper", "lower", "front" and "back" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for convenience of describing the product and simplifying the description, and the above-mentioned words have no special meaning, and do not indicate or imply that the device or element to be referred must have a specific orientation, be constructed in a specific orientation and operation, and thus, should not be construed as limiting the patent.
According to an aspect of the present invention, referring to fig. 1 to 2, the present invention provides a microfluidic experimental apparatus, including a microfluidic laboratory 12, further including a stock solution pushing device, a solution dispensing bottle 9, a first microfluidic pushing device 4, a multi-channel switching valve 7, which are sequentially connected through a microfluidic pipeline; the liquid outlet of the multi-channel switching valve 7 is respectively connected with a first-stage buffer bottle 10 and a second-stage buffer bottle 11, and the first-stage buffer bottle 10 and the second-stage buffer bottle 11 are respectively connected with the microfluidic laboratory 12 through a second microfluidic pushing device 5. Through set up the one-level buffer bottle with the same quantity of micro-fluidic laboratory quantity (or the cavity quantity in same laboratory) between liquid distribution bottle 9 and micro-fluidic laboratory 12, can wait that whole solutions dispose the back simultaneously to the propelling movement in the micro-fluidic laboratory, thereby realize the contrast experiment and be the contrast simultaneously, and when solution pushed in the one-level buffer bottle to the chip in, can continue to dispose solution and deposit the second grade buffer bottle, time sharing is multiplexing, the time of joining in marriage liquid has been saved, and the work efficiency is improved.
Further, in order to reduce manual operation and improve the control precision of solution preparation and the stability of an experiment, the microfluidic experimental device further comprises a controller 2, and the stock solution pushing device, the first microfluidic pushing device 4, the second microfluidic pushing device 5 and the multi-channel switching valve 7 are respectively connected with the controller 2. Preferably, the controller 2 is further connected to an upper computer 1 for controlling the operation.
Preferably, in order to realize long-term real-time regulation and control of various microenvironment parameters, a sensor 6 is further arranged in the liquid preparation bottle 9, and the sensor 6 is connected with the controller 2. The configuration of the high-precision sensor can realize real-time high-precision closed-loop regulation and control of microenvironment, such as pH: plus or minus 0.01; salinity: 0.1 ppt; dissolved oxygen: 0.1 mg/L.
Preferably, the microfluidic laboratory 12 may be a test site such as a microfluidic chip or a biological culture dish or a biological test box according to actual needs.
Preferably, the stock solution pushing device comprises a stock solution bottle 8 and a third pushing device 3 connected with the stock solution bottle, and the third pushing device 3 is connected with the controller 2. Of course, the stock solution pushing device may also be a syringe pump or a plunger pump, etc. that integrates the functions of the stock solution bottle and the third pushing device.
Preferably, the sensor 6 comprises one or more of a pH sensor, a salinity sensor and a dissolved oxygen sensor, and a measuring probe of the sensor is arranged in the dispensing bottle, so that the measurement of the microenvironment parameters (pH, salinity and the like) can be realized.
Preferably, the microfluidic pushing device (the first microfluidic pushing device, the second microfluidic pushing device, the third microfluidic pushing device) is one or more of a pneumatic pump, a peristaltic pump, a plunger pump, and a syringe pump.
Specifically, the stock solution pushing device is used for holding different standard solutions, that is, original standard solutions required by experiments and required to be prepared according to different proportions, such as a PH standard solution, a salinity standard solution, and the like. The number of the stock solution pushing devices is N, the stock solution pushing devices are arranged in parallel, N is larger than or equal to 1, and each stock solution pushing device is respectively connected with the liquid distribution bottle 9.
The liquid preparation bottle 9 is a place where the standard liquids are mixed according to different proportions.
Further, the microfluidic laboratory 12 is a laboratory, and if a contrast experiment is to be completed, a plurality of chambers may be designed in a single microfluidic laboratory, or the contrast experiment may be completed using a plurality of microfluidic laboratories, where no requirements are made on the type or material of the microfluidic laboratory. Specifically, for comparison experiments, the number of the microfluidic laboratories 12 can be M (or the number of chambers of a single microfluidic laboratory is M) and the microfluidic laboratories are arranged in parallel, wherein M is greater than or equal to 1; the number of the primary buffer bottles 10 is also M, and a liquid outlet of each primary buffer bottle 10 is connected with a corresponding microfluidic laboratory 12 through an M-channel fluid conveying device (a third microfluidic push device 5); the number of the secondary buffer bottles 11 is also M, and the liquid outlet of each secondary buffer bottle 11 is connected with the corresponding microfluidic laboratory 12 through another M-channel fluid conveying device (another third microfluidic push device 5).
The buffer bottles (the first-stage buffer bottle 10 and the second-stage buffer bottle 11) are places where the prepared solutions wait to be conveyed, and are convenient for pushing all the solutions into the corresponding microfluidic laboratories 12 after the preparation is completed.
The microfluidic pipeline is used for connecting component members (a raw material bottle, a liquid distribution bottle, a buffer bottle, a microfluidic laboratory and the like), and the material of the microfluidic pipeline is not limited and can be a silicone tube and the like.
In particular, the stock solution pushing device is used for pushing standard solution to the solution preparation bottle; the first microfluid pushing equipment is used for pushing the liquid between the liquid preparation bottle and the buffer bottle; and the second micro-fluid pushing equipment is used for pushing the buffer bottle to the liquid in the corresponding micro-fluid laboratory. Each microfluidic transfer device may be one of a plunger pump, a pneumatic pump, a peristaltic pump, a syringe pump.
The multi-channel switching valve is arranged between the liquid distribution bottle and the buffer bottle and behind the first microfluid pushing device, and is used for switching the solution delivered by the first microfluid delivery device to different pipelines through the switching valve, and only one valve pipeline is conducted at the same time.
According to another aspect of the present invention, the present invention also provides a microfluidic experimental method based on the above device, comprising the following steps:
the method comprises the following steps: respectively filling corresponding standard liquids (such as PH standard liquids, salinity standard liquids, basic liquids and the like) required by experiments into the N stock solution pushing devices;
step two: the controller controls the stock solution pushing equipment to push the corresponding standard solution into the solution preparation bottle (controlling the running time and the running speed of the equipment), and meanwhile, a sensor in the solution preparation bottle monitors the corresponding concentration signal of the solution in the solution preparation bottle in real time and transmits the concentration signal to the controller;
step three: the controller judges whether the received concentration signal is consistent with the actually required concentration signal, and if so, the stock solution pushing equipment is stopped to convey the standard solution to the solution preparation bottle, so that the first solution preparation is completed; if not, continuously conveying the corresponding standard liquid to the liquid preparation bottle through the stock solution pushing equipment until all concentration signals are consistent with actually required concentration signals, and finishing the first solution preparation;
step four: after the first solution preparation is finished, pushing the solution in the solution preparation bottle to a first primary buffer bottle through a first microfluid conveying device through a multi-channel switching valve;
step five: repeating the second step and the third step, sequentially completing the second solution preparation and the third solution preparation … … Mth solution preparation, and correspondingly pushing the corresponding solutions to a second primary buffer bottle and a third primary buffer bottle … … Mth primary buffer bottle;
step six: after the M primary buffer bottles finish pushing the corresponding solutions, simultaneously pushing the solutions in the M primary buffer bottles to corresponding microfluidic laboratories for a first group of experiments through a second pushing device with an M channel;
step seven: when the sixth step is carried out, the second step and the third step are repeated, … … th-time solution preparation of first solution preparation, second solution preparation and third solution preparation required by the next group of experiments is respectively completed, corresponding solutions are correspondingly pushed to a first secondary buffer bottle, a second secondary buffer bottle and a third … … Mth secondary buffer bottle, and the next step of operation is waited after the M secondary buffer bottles complete the pushing of the corresponding solutions;
step eight: after the first group of experiments are completed, the solutions in the M secondary buffer bottles are simultaneously pushed to corresponding microfluidic laboratories to carry out a second group of experiments through second pushing equipment of another M channel.
The experimental set-up will be illustrated in detail below by way of specific example 1 and with reference to figure 3.
Example 1
Referring to fig. 3, this embodiment 1 provides a microfluidic experimental apparatus, including a microfluidic laboratory 12, and further including a stock solution pushing device, a solution dispensing bottle 9, a first microfluidic pushing device 4, and a multi-channel switching valve 7, which are sequentially connected through a microfluidic pipeline; the liquid outlet of the multi-channel switching valve 7 is respectively connected with a first-stage buffer bottle 10 and a second-stage buffer bottle 11, and the first-stage buffer bottle 10 and the second-stage buffer bottle 11 are respectively connected with the microfluidic laboratory 12 through a second microfluidic pushing device 5.
Further, the microfluidic experimental device further comprises a controller 2, the stock solution pushing device, the first microfluidic pushing device 4, the second microfluidic pushing device 5 and the multi-channel switching valve 7 are respectively connected with the controller 2, and the controller 2 is further connected with an upper computer 1.
Further, a sensor 6 is also arranged in the liquid dispensing bottle 9, and the sensor 6 is connected with the controller 2.
Further, the microfluidic laboratory 12 is a microfluidic chip.
Further, the stock solution pushing device comprises a stock solution bottle 8 and a third pushing device 3 connected with the stock solution bottle, and the third pushing device 3 is connected with the controller 2.
Further, the sensor 6 is all of a pH sensor, a salinity sensor, and a dissolved oxygen sensor.
Further, the microfluidic push device is a peristaltic pump.
Specifically, the number of the stock solution bottles is four (stock solution bottle a, stock solution bottle B, stock solution bottle C, stock solution bottle D respectively) and the stock solution bottles are arranged in parallel, and each stock solution bottle is connected with the liquid preparation bottle through a single-channel peristaltic pump (the first microfluid conveying device).
For comparison experiments, the number of the microfluidic chips is four (namely a microfluidic chip A, a microfluidic chip B, a microfluidic chip C and a microfluidic chip D respectively) and the microfluidic chips are arranged in parallel; the number of the primary buffer bottles is four (respectively a primary buffer bottle A, a primary buffer bottle B, a primary buffer bottle C and a primary buffer bottle D), and a liquid outlet of each primary buffer bottle is connected with a corresponding microfluidic chip through a four-channel peristaltic pump (second microfluidic pushing equipment); the number of the second-stage buffer bottles is four (respectively, the second-stage buffer bottle A, the second-stage buffer bottle B, the second-stage buffer bottle C and the second-stage buffer bottle D), and the liquid outlet of each second-stage buffer bottle is connected with the corresponding microfluidic chip through another four-channel fluid conveying device (another second microfluidic pushing device).
Correspondingly, the first microfluidic delivery device is a single-channel peristaltic pump, and the multi-channel switching valve is an eight-channel switching valve (the number of channels of the switching valve is twice the number of microfluidic chips).
This embodiment 1 further provides a microfluidic experimental method based on the above experimental apparatus, including the following steps:
the method comprises the following steps: respectively filling corresponding standard liquids (such as PH standard liquid, salinity standard liquid, basic liquid and the like) required by the experiment into the four stock solution bottles;
step two: the controller controls the third fluid delivery device (corresponding single-channel peristaltic pump) to push the standard solution in the corresponding raw solution bottle into the solution distribution bottle, and meanwhile, the sensor in the solution distribution bottle monitors the corresponding concentration signal of the solution in the solution distribution bottle in real time and transmits the concentration signal to the controller;
step three: the controller judges whether the received concentration signal is consistent with the actually required concentration signal or not, and if so, the third fluid conveying equipment is stopped to convey the standard liquid to the liquid preparation bottle, so that the first solution preparation is completed; if not, continuously conveying the corresponding standard liquid to the liquid preparation bottle through the third fluid conveying equipment until all concentration signals are consistent with actually required concentration signals, and finishing the first solution preparation;
step four: after the first solution preparation is finished, pushing the solution in the solution preparation bottle into a first-stage buffer bottle A through an eight-channel switching valve by first micro-fluid conveying equipment (a single-channel peristaltic pump);
step five: repeating the second step and the third step, finishing the second solution preparation, the third solution preparation and the fourth solution preparation in sequence, and correspondingly pushing the corresponding solutions to a first-stage buffer bottle B, a first-stage buffer bottle C and a first-stage buffer bottle D;
step six: after the four primary buffer bottles finish pushing the corresponding solutions, simultaneously pushing the solutions in the four primary buffer bottles into the corresponding microfluidic chips through the four-channel peristaltic pumps to perform a first group of experiments;
step seven: when the sixth step is carried out, the second step and the third step are repeated, the first solution preparation, the second solution preparation, the third solution preparation and the fourth solution preparation required by the next group of experiments are respectively completed, corresponding solutions are pushed to a secondary buffer bottle A, a secondary buffer bottle B, a secondary buffer bottle C and a secondary buffer bottle D, and the next step of operation is waited after the pushing of the corresponding solutions in the four secondary buffer bottles is completed;
step eight: after the first group of experiments are finished, the solutions in the four secondary buffer bottles are simultaneously pushed into the corresponding microfluidic chips through another four-channel peristaltic pump to carry out a second group of experiments.
The embodiment can realize long-term real-time regulation and control of various microenvironment parameters (the real-time regulation and control of the microenvironment refers to real-time regulation and control of internal parameters such as salinity, dissolved oxygen, PH and the like in the microenvironment in the microfluidic chip, and the accurate microenvironment suitable for biological growth or experiment needs is created.
The above embodiments are only preferred embodiments of the present invention, and it should be understood that the above embodiments are only for assisting understanding of the method and the core idea of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalents and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (8)
1. A microfluidic experimental device comprises a microfluidic laboratory, and is characterized in that: the device also comprises a stock solution pushing device, a liquid preparation bottle, a first microfluid pushing device and a multi-channel switching valve which are sequentially connected through a microfluid pipeline; the liquid outlet of the multi-channel switching valve is respectively connected with a primary buffer bottle and a secondary buffer bottle, and the primary buffer bottle and the secondary buffer bottle are respectively connected with the microfluidic laboratory through second microfluidic pushing equipment;
the stock solution pushing equipment is N and arranged in parallel, and N is
1, each stock solution pushing device is respectively connected with the liquid distribution bottle;
the number of the micro-fluidic laboratories is M, the micro-fluidic laboratories are arranged in parallel, M is
1; the number of the primary buffer bottles is M, and the liquid outlet of each primary buffer bottle is connected with the corresponding microfluidic laboratory through an M-channel fluid conveying device; the number of the secondary buffer bottles is M, and the liquid outlet of each secondary buffer bottle is connected with the corresponding microfluidic laboratory through another M-channel fluid conveying device.
2. A microfluidic experimental device according to claim 1, characterized in that: the device comprises a stock solution pushing device, a first micro-fluid pushing device, a second micro-fluid pushing device and a multi-channel switching valve, and is characterized by further comprising a controller, wherein the stock solution pushing device, the first micro-fluid pushing device, the second micro-fluid pushing device and the multi-channel switching valve are respectively connected with the controller.
3. A microfluidic experimental device according to claim 2, characterized in that: a sensor is arranged in the liquid dispensing bottle and connected with the controller.
4. A microfluidic experimental device according to claim 1, 2 or 3, characterized in that: the microfluidic laboratory is a microfluidic chip or a biological culture dish or a biological test box.
5. A microfluidic experimental device according to claim 1, 2 or 3, characterized in that: the stock solution pushing equipment comprises a stock solution bottle and third pushing equipment connected with the stock solution bottle.
6. A microfluidic experimental device according to claim 3, characterized in that: the sensor is one or more of a pH sensor, a salinity sensor and a dissolved oxygen sensor.
7. A microfluidic experimental device according to claim 1, 2 or 3, characterized in that: the microfluid propelling movement equipment is one of pneumatic pump, peristaltic pump.
8. A microfluidic experimental method based on the microfluidic experimental device of any one of claims 1 to 7, comprising the steps of:
the method comprises the following steps: respectively filling corresponding standard liquids required by experiments into the N stock solution pushing devices;
step two: the controller controls the stock solution pushing equipment to push the corresponding standard solution into the solution preparation bottle, and meanwhile, a sensor in the solution preparation bottle monitors a corresponding concentration signal of the solution in the solution preparation bottle in real time and transmits the concentration signal to the controller;
step three: the controller judges whether the received concentration signal is consistent with the actually required concentration signal, and if so, the stock solution pushing equipment is stopped to convey the standard solution to the solution preparation bottle, so that the first solution preparation is completed; if not, continuously conveying the corresponding standard liquid to the liquid preparation bottle through the stock solution pushing equipment until all concentration signals are consistent with actually required concentration signals, and finishing the first solution preparation;
step four: after the first solution preparation is finished, pushing the solution in the solution preparation bottle to a first primary buffer bottle through a first microfluid conveying device through a multi-channel switching valve;
step five: repeating the second step and the third step, sequentially completing the second solution preparation and the third solution preparation … … Mth solution preparation, and correspondingly pushing the corresponding solutions to a second primary buffer bottle and a third primary buffer bottle … … Mth primary buffer bottle;
step six: after the M primary buffer bottles finish pushing the corresponding solutions, simultaneously pushing the solutions in the M primary buffer bottles to corresponding microfluidic laboratories to perform a first group of experiments;
step seven: when the sixth step is carried out, the second step and the third step are repeated, … … th-time solution preparation of first solution preparation, second solution preparation and third solution preparation required by the next group of experiments is respectively completed, corresponding solutions are correspondingly pushed to a first secondary buffer bottle, a second secondary buffer bottle and a third … … Mth secondary buffer bottle, and the next step of operation is waited after the M secondary buffer bottles complete the pushing of the corresponding solutions;
step eight: after the first group of experiments are completed, the solutions in the M secondary buffer bottles are simultaneously pushed to corresponding microfluidic laboratories to carry out a second group of experiments.
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