Multi-module emulsion microdroplet generation control device
阅读说明：本技术 一种多模块的乳液微滴生成控制装置 (Multi-module emulsion microdroplet generation control device ) 是由 司远 徐仕强 吕洋 褚春旭 于 2019-10-22 设计创作，主要内容包括：本发明涉及一种多模块的乳液微滴生成控制装置,包括：可更换式压力产生模块,其包括彼此独立设置的正压产生模块、负压产生模块和正负混合压产生模块；比例阀,与可更换式压力产生模块可拆卸地连接；固定板,固定有多个气体通道,各个所述通道的一端与比例阀连通,另一端具有电磁阀,所有电磁阀一起组成电磁阀阵列。本装置特点是多模块、多通道或单通道独立生成,在不污染压缩泵或真空泵的情况下实现乳液微滴的生成,微滴大小均匀可控,生成速率稳定；本装置可实现生成单个通道微滴、也可实现连续生成多个通道微滴,方便灵活,尺寸可控。(The invention relates to a multi-module emulsion microdroplet generation control device, which comprises: the replaceable pressure generating module comprises a positive pressure generating module, a negative pressure generating module and a positive and negative mixed pressure generating module which are arranged independently; a proportional valve removably connected to the replaceable pressure generating module; and the fixed plate is fixedly provided with a plurality of gas channels, one end of each channel is communicated with the proportional valve, the other end of each channel is provided with an electromagnetic valve, and all the electromagnetic valves form an electromagnetic valve array together. The device is characterized in that the device can independently generate a plurality of modules, a plurality of channels or a single channel, the generation of emulsion microdroplets can be realized under the condition of not polluting a compression pump or a vacuum pump, the size of the microdroplets is uniform and controllable, and the generation rate is stable; the device can generate single channel droplets and can also generate a plurality of channel droplets continuously, and is convenient, flexible and controllable in size.)
1. A multi-module emulsion droplet generation control device, comprising:
the replaceable pressure generating module comprises a positive pressure generating module, a negative pressure generating module and a positive and negative mixed pressure generating module which are arranged independently;
a proportional valve removably connected with the replaceable pressure generating module;
the gas mixing device comprises a fixing plate, wherein a plurality of gas channels which are independent from each other are fixed on the fixing plate, one end of each channel is communicated with a proportional valve, the other end of each channel is provided with an electromagnetic valve, and all the electromagnetic valves form an electromagnetic valve array together.
2. Emulsion droplet generation control device according to claim 1, wherein the number of channels is 1 to 7, preferably 2 to 7.
3. The emulsion droplet generation control device of claim 1, further comprising a channel selection unit that divides each channel into a proportional valve connection portion and a solenoid-containing portion that are not in communication with each other across the plurality of gas channels, the channel selection unit having a through hole sized to match each channel such that the channel is in communication when the proportional valve connection portion, the through hole, and the solenoid-containing portion of the channel are aligned.
4. An emulsion droplet generation control device according to claim 3, wherein the number of channels is 2 to 12, preferably 4 to 8.
5. The emulsion droplet generation control device of claim 1,
the positive pressure generating module comprises a compression pump, an air bottle, a pressure sensor and a drying cylinder;
the negative pressure generating module comprises a vacuum pump, an air bottle, a pressure sensor and a drying cylinder;
the positive and negative mixed pressure generating module comprises a vacuum pump, a compression pump, a gas cylinder, a pressure sensor and a drying cylinder;
wherein one end of each vacuum pump and/or compression pump is connected with the corresponding gas cylinder, and the other end of each vacuum pump and/or compression pump is connected with the corresponding drying cylinder, and the drying cylinders contain drying agents to ensure that pipelines near the gas cylinders are dry;
each pressure sensor is connected with each gas cylinder and used for detecting and feeding back pressure change in the gas cylinders;
each gas cylinder can be detachably connected with one end of the proportional valve.
6. The emulsion droplet generation control device of claim 1, wherein in operation, the solenoid valve of the emulsion droplet generation control device is connected to a microfluidic chip,
when the positive pressure generation module is selected to be connected with the proportional valve, the preparation of emulsion microdroplets is completed through positive pressure;
when the negative pressure generating module is selected to be connected with the proportional valve, the preparation of emulsion microdroplets is completed by positive pressure;
when the positive and negative mixed pressure generation module is selected to be connected with the proportional valve, the preparation of the emulsion microdroplets is completed by positive pressure and negative pressure.
7. An emulsion droplet generation control device according to claim 1, wherein the channel selection unit comprises a channel selection chamber and a linear motor controlling the channel selection chamber to move in a direction of the channel selection unit across the plurality of gas channels,
the through hole is positioned in the channel selection cavity, when the linear motor controls the channel selection cavity to move so that the proportional valve connecting part, the through hole and the electromagnetic valve containing part of a certain channel are aligned, the channel is conducted, and the air tightness is ensured.
8. The channel selection unit of claim 7, wherein the channel selection unit can be placed in a plurality of different positions by the linear motor to communicate with all the channels, and only the same channel is allowed to be communicated each time while the other channels are closed due to being blocked.
9. An emulsion droplet generation control device according to claim 3 or 7, wherein the through hole is cylindrical.
10. The apparatus according to claim 1, wherein the array of solenoid valves is connectable to a microfluidic chip, and the apparatus prepares the emulsion droplets by controlling on/off of each solenoid valve to open/close a corresponding channel interface.
Technical Field
The application relates to a multi-module emulsion microdroplet generation control device, which is used for controlling the generation of emulsion microdroplets of a microfluidic chip and belongs to the technical field of biological detection.
Background
The emulsion microdroplet technology is a micro-nano technology for dividing continuous fluid into emulsion microdroplets with discrete nano-scale volumes and the volumes below the discrete nano-scale volumes in a micro-scale channel by utilizing the interaction between flow shearing force and surface tension. It is a new technology for manipulating the volume of emulsion droplets that has been developed in recent years.
The basic process of emulsion droplet formation is: two mutually insoluble liquids are used, one of which is used as a continuous phase and the other is used as a dispersed phase, and the dispersed phase is in a micro volume (10)-15-10-9L) units form a dispersed and continuous phase, and droplets are formed to move in the channel.
Most of the existing emulsion microdroplet generating devices control a multi-channel emulsion microdroplet generating pool by using single positive pressure or negative pressure under the action of a pressure pump to push a continuous phase and a disperse phase to move so as to form emulsion microdroplets at intersections. The method for controlling multi-channel liquid to simultaneously generate emulsion droplets by using the injection pump (positive pressure or negative pressure action of the pressure pump) may cause differences in the uniformity and consistency of the size of the emulsion droplets due to the simultaneous control of multiple channels to simultaneously generate emulsion droplets; and only emulsion microdroplets with a single size can be generated, and a plurality of different kinds of emulsion microdroplets cannot be generated; and the phenomenon of inflexible multichannel exists, the method is only suitable for the condition of a large number of samples, and a small number of samples are generated at the same time, so that waste is easily caused.
The existing digital PCR device of International brand Bio-Rad is to generate 8-channel emulsion droplets simultaneously, is not flexible, and generates only one size of emulsion droplets.
The present inventors have made extensive studies on biochips for many years and actively developed novel biochips which can be autonomously controlled, and the present invention is one of the achievements. It not only can replace the related international products, but also can realize better effect.
Disclosure of Invention
As can be seen from the above, most of the existing emulsion droplet generating devices are capable of generating emulsion droplets of different sizes by using a single positive pressure or negative pressure under the action of a pressure pump; and because of the simultaneous generation of emulsion droplets in multiple channels, the gas may form turbulence, cyclone and/or vortex in the multiple channels, resulting in non-uniform pressure between the channels, and the emulsion droplets generated in this way have uniform and consistent size differences, and the generation rate is also unstable, thereby increasing systematic errors in analysis using multiple microfluidic chips. In addition, the method is suitable for the condition of large sample size, and the waste phenomenon exists under the condition of small sample size, so that the method is not flexible enough.
In view of the above problems, in order to overcome the deficiencies in the prior art, the present invention provides a multi-module and multi-channel generation control device, which can selectively generate emulsion droplets without polluting a compression pump (vacuum pump), can simultaneously control the formation of emulsion droplets of 1 to 7 channels, and can form emulsion droplets of different sizes.
In addition, the invention can control a single channel to independently generate emulsion microdroplets or sequentially and continuously generate a plurality of channel emulsion microdroplets in a multi-channel emulsion microdroplet generating device through a specific channel selection unit, and even under the condition that the emulsion microdroplets are continuously generated by multiple channels, the formed emulsion microdroplets have uniform and controllable size and stable generation rate, and can be matched with a plurality of biochips to prepare the emulsion microdroplets; convenient and flexible, and controllable size. Moreover, since the number of channels to be used can be freely selected without using all the channels to generate emulsion droplets, the method is suitable for conditions with a large amount of sample and also for conditions with a small amount of sample.
The object of the present invention is achieved by a multi-module emulsion droplet generation control device described below.
In particular, the present invention provides a multi-module emulsion droplet generation control device comprising:
the replaceable pressure generating module comprises a positive pressure generating module, a negative pressure generating module and a positive and negative mixed pressure generating module which are arranged independently;
a proportional valve removably connected with the replaceable pressure generating module;
the gas mixing device comprises a fixing plate, wherein a plurality of gas channels which are independent from each other are fixed on the fixing plate, one end of each channel is communicated with a proportional valve, the other end of each channel is provided with an electromagnetic valve, and all the electromagnetic valves form an electromagnetic valve array together.
In one embodiment, the number of channels is 1 to 7, preferably 2 to 7.
It should be noted that the positive pressure generating module, the negative pressure generating module and the positive-negative mixed pressure generating module in the pressure generating module are separately provided, and they may be individually operated and provided to be replaceable. In practical cases, the pressure generating module can be detached and placed separately. When the pressure generating module is used, a user can select the pressure generating module with the corresponding function according to actual preparation requirements, and the pressure generating module is replaced and installed on the proportional valve, so that emulsion microdroplets can be generated through positive pressure, emulsion microdroplets can be generated through negative pressure or emulsion microdroplets can be generated through positive and negative pressure mixing.
The proportional valve can accurately control the output pressure, and further control the size of the generated emulsion droplets.
And the solenoid valves forming the solenoid valve array are used for adjusting the on-off of each passage.
By the above embodiments, the present invention enables the generation of a plurality of emulsion droplets of different sizes by the replacement of the pressure generating module, and in particular enables the generation of emulsion droplets in a corresponding number of microfluidic chips simultaneously under the control of 1 to 7 channels, preferably 2 to 7 channels.
In a preferred embodiment, the emulsion droplet generation control device of the present invention further comprises a channel selection unit that divides each of the plurality of gas channels into a proportional valve connection portion and a solenoid-containing portion that are not connected, across the plurality of gas channels, the channel selection unit having a through hole (one through hole) sized to match each of the channels such that the channel is connected when the proportional valve connection portion, the through hole, and the solenoid-containing portion of the channel are aligned.
In embodiments comprising a channel selection unit, the number of channels is 2 to 12, preferably 4 to 8.
In one embodiment, the positive pressure generating module comprises a compression pump, a gas cylinder, a pressure sensor, and a drying cylinder;
the negative pressure generating module comprises a vacuum pump, an air bottle, a pressure sensor and a drying cylinder;
the positive and negative mixed pressure generating module comprises a vacuum pump, a compression pump, a gas cylinder, a pressure sensor and a drying cylinder;
wherein one end of each vacuum pump and/or compression pump is connected with the corresponding gas cylinder, and the other end of each vacuum pump and/or compression pump is connected with the corresponding drying cylinder, and the drying cylinders contain drying agents to ensure that pipelines near the gas cylinders are dry;
each pressure sensor is connected with each gas cylinder and used for detecting and feeding back pressure change in the gas cylinders;
each gas cylinder can be detachably connected with one end of the proportional valve.
Wherein, the vacuum pump is used for providing negative pressure, and the compression pump is used for providing positive pressure.
In one embodiment, in operation, the solenoid valve of the emulsion droplet generation control device is connected to a microfluidic chip,
when the positive pressure generation module is selected to be connected with the proportional valve, the preparation of emulsion microdroplets is completed through positive pressure;
when the negative pressure generating module is selected to be connected with the proportional valve, the preparation of emulsion microdroplets is completed by positive pressure;
when the positive and negative mixed pressure generation module is selected to be connected with the proportional valve, the preparation of the emulsion microdroplets is completed by positive pressure and negative pressure.
In one embodiment, the channel selection unit comprises a channel selection chamber and a linear motor controlling the movement of the channel selection chamber in a direction of the channel selection unit across the plurality of gas channels,
the through hole is positioned in the channel selection cavity, when the linear motor controls the channel selection cavity to move so that the proportional valve connecting part, the through hole and the electromagnetic valve containing part of a certain channel are aligned, the channel is conducted, and the air tightness is ensured.
Specifically, only when the motor drives the channel selection unit to move the through hole to the interrupted (notched) portion of a certain channel, the two separated portions (the proportional valve connection portion, the portion containing the solenoid valve) of the channel and the through hole are aligned in position to integrally form a complete gas channel, and the channel can be conducted at this time, so that the preparation of the emulsion droplets is performed. The through holes need to be closely fitted to the respective channels to ensure airtightness when aligned.
In one embodiment, the channel selection unit can be located at a plurality of different positions through the linear motor to communicate with all the channels, and when the channels are communicated, only the same channel is allowed to be communicated each time, and the rest channels are closed due to being shielded.
In this embodiment, after the generation of the emulsion droplet controlled by one channel is finished, the linear motor may drive the channel selection unit so that the through hole is aligned with two separate portions (a proportional valve connection portion, a solenoid-containing valve portion) of the other channel, and the generation of the emulsion droplet controlled by the channel is performed. Controlling the plurality of channels sequentially in this manner generates emulsion droplets in sequence.
In this case, compared with the prior art apparatus represented by the Bio-Rad digital PCR apparatus which simultaneously produces 8-channel emulsion droplets, since only one channel is communicated at a time, the prior art apparatus eliminates the phenomenon that the size of the emulsion droplets is uniform and the production rate is stable because the pressure between the channels is not uniform and the emulsion droplets are not uniform and uniform in size.
In one embodiment, the electromagnetic valve array can be connected to a microfluidic chip, and the emulsion microdroplets are prepared by controlling the on/off of each electromagnetic valve and opening/closing the corresponding channel interface.
Compared with the prior art, the invention has the advantages that:
the emulsion microdroplet generation control device capable of independently generating multiple modules, multiple channels or single channel provided by the invention selects the corresponding modules to install according to the requirement of emulsion microdroplet preparation, and is flexible, simple and convenient; under the condition of ensuring that a compression pump (a vacuum pump) is not polluted, the generation of emulsion microdroplets is realized, the size of the formed emulsion microdroplets is uniform and controllable, the generation rate is stable, and the preparation of the emulsion microdroplets can be matched with various biochips; the device can generate single-channel emulsion microdroplets and also can continuously generate a plurality of channel emulsion microdroplets, and the size is controllable. No waste and material saving.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be 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 some embodiments described in the present application, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 shows a schematic diagram of an emulsion droplet generation control device (negative pressure) according to an embodiment of the present invention;
FIG. 2 shows a schematic diagram of the emulsion droplet generation control device (positive pressure) in one embodiment of the present invention;
FIG. 3 shows a schematic diagram of the emulsion droplet generation control device (mixing pressure) in one embodiment of the present invention;
fig. 4 is a diagram showing a model of a channel selection unit according to an embodiment of the present invention.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. 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.
In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular 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 otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
The present invention provides a multi-module emulsion droplet generation control device, as shown in fig. 1-3, comprising: the positive pressure/negative pressure/positive and negative mixed pressure generation modules are independently arranged, and can independently work to control the generation of emulsion microdroplets. Each individual module of the positive pressure/negative pressure/positive and negative mixed pressure generating module comprises a compression pump (for providing positive pressure) and/or a vacuum pump (for providing negative pressure), a gas cylinder, a pressure sensor, a drying cylinder.
Specifically, the device comprises a positive pressure generating module, a negative pressure generating module and a positive and negative mixed pressure generating module; the pressure sensor is connected with the gas cylinder, one end of the compression pump (vacuum pump) is connected with the gas cylinder, and the other end of the compression pump (vacuum pump) is connected with the drying cylinder. The gas cylinder is connected with one end of a proportional valve, and eight gas pipe channels are led out from the proportional valve and connected with a channel selection unit. The electromagnetic valve array comprises eight electromagnetic valves for adjusting the on-off of the passage; a channel selection unit: the channel selection unit comprises a channel selection cavity and a linear motor, a cylindrical through hole which is tightly matched with the guide pipe is formed in the channel selection cavity, the air tightness is good when the two holes are completely butted, and eight pipelines on the left side and the right side of the cavity are fixed on a fixing plate.
The operation of the emulsion droplet formation control apparatus of the present invention will be described in detail below.
FIG. 1 shows a schematic diagram of the emulsion droplet generation control device (negative pressure) in one embodiment of the present invention. When it is intended to generate emulsion droplets by negative pressure, a negative pressure generating module is selectively installed in the apparatus. At this time, as shown in fig. 1, the emulsion droplet generation control means (negative pressure) includes a negative pressure generation module; a
FIG. 2 shows a schematic diagram of the emulsion droplet generation control device (positive pressure) in one embodiment of the present invention. When it is intended to generate emulsion droplets by positive pressure, a positive pressure generating module is selectively installed in the apparatus. At this time, as shown in fig. 2, the emulsion droplet generation control means (positive pressure) includes a positive pressure generation module; a
FIG. 3 shows a schematic diagram of the emulsion droplet generation control device (mixing pressure) in one embodiment of the present invention. When the generation of the emulsion droplets is intended to be controlled by both positive and negative pressure, a positive and negative pressure generating module is optionally installed in the apparatus. At this time, as shown in fig. 3, the emulsion droplet generation control means (mixing pressure) includes a positive and negative mixing pressure generation module; a
In order to more clearly describe the structure of the channel selection unit of the present invention, one embodiment thereof is given below. As shown in fig. 4, the
In operation, the plurality of channels in the emulsion droplet generation control device are connected one to a plurality of microfluidic chips at the ports of the solenoid valves. Optionally, a pressure generating module (e.g., a positive pressure generating module) is installed to interface the through-hole with the left and right corresponding conduits of a channel that is in fluid communication. The power supply of the pressure generating module, for example, the positive pressure generating module, is turned on, and the solenoid valve of the turned-on channel is turned on, at which time the compressed air drives the gas through the channel into the microfluidic chip connected to the channel, thereby generating emulsion droplets in the microfluidic chip.
When the generation of the emulsion microdroplets in the microfluidic chip controlled by the channel is finished, the electromagnetic valve of the channel is closed, and the power supply of the pressure generation module is closed. The channel selection unit is then moved so that the through-holes are aligned with the left and right ducts of the other channel. The above operation is repeated to generate emulsion droplets in the microfluidic chip under control of another channel.
In this way, the device can realize the control of the generation of the emulsion droplets through a single channel, and also can realize the continuous control of a plurality of channels to generate the emulsion droplets in turn. For example, the emulsion droplets may be generated sequentially in 2 to 12, preferably 4 to 8 channels.
In the case of continuously controlling a plurality of channels to generate emulsion droplets, compared with the prior art device represented by a Bio-Rad digital PCR device which simultaneously generates 8-channel emulsion droplets, since only one channel is communicated at a time, the phenomenon that the sizes of the emulsion droplets are not uniform and inconsistent because the pressure between the channels is not uniform in the prior art device is eliminated, and the formed emulsion droplets are uniform in size and stable in generation rate. Moreover, the number of channels to be used can be freely selected, so that the method is suitable for the condition of a large number of samples and also suitable for the condition of a small number of samples.
As an alternative embodiment, the emulsion droplet generation control device of the present invention may not include the
In operation, a plurality of channels in the emulsion droplet generation control device are connected to a corresponding plurality of microfluidic chips at the ports of the solenoid valves. A pressure generating module (e.g., a positive pressure generating module) is optionally installed. And opening a power supply of a pressure generation module, such as a positive pressure generation module, and opening the electromagnetic valve of the conducted channel, wherein the compressed air drives the gas to pass through all the channels and enter the microfluidic chips connected with the channels, so that emulsion droplets are generated in the microfluidic chips. In this embodiment, the present invention enables the generation of a plurality of different sizes of emulsion droplets by the replacement of the pressure generating module, in particular the generation of emulsion droplets in a corresponding number of microfluidic chips simultaneously under the control of 1 to 7 channels, preferably 2 to 7 channels. Compared with the prior art, the device is more convenient and flexible.
There are, of course, many other specific embodiments of the invention and these are not to be considered as limiting. All technical solutions formed by using equivalent substitutions or equivalent transformations fall within the scope of the claimed invention.
- 上一篇：一种医用注射器针头装配设备
- 下一篇：一种化学实验用多功能移液设备