A generating device and generating method for a micro reaction unit

Abstract

The present invention discloses a generating device for a micro reaction unit, comprising: a microfluidic chip, the fluid channel structure inside which includes: a control unit, at least one first fluid channel containing a first-phase fluid therein; at least one second fluid channel containing a second-phase fluid therein, the second-phase fluid and the first-phase fluid being two immiscible fluids; a plurality of reaction substance injection channels respectively communicating with the first fluid channel and used for transporting reaction substances into the first fluid channel; one or more detectors respectively electrically connected to the control unit, and one or more driving devices respectively electrically connected to the control unit. The present invention also discloses a method for generating a micro reaction unit. The present invention can selectively add different reaction substances into the micro reaction unit according to a certain rule, thereby improving the overall reaction efficiency, saving the dosage of key reaction substances, and ensuring the accuracy of the reaction result.

Description

Technical Field

[0001] The present invention relates to a droplet generation technology, and specifically to a generation device and a generation method for a micro reaction unit. Background Art

[0002] In recent years, biochemical reactions carried out within micro reaction units at the microliter or nanoliter level have become a hot topic in academic research and industrial applications. For example, in digital PCR technology, by distributing nucleic acid templates, reaction solutions, primers, and probes into tiny reaction units, higher detection sensitivity and absolute quantitative detection of the starting sample nucleic acid molecules can be obtained. In high-throughput single-cell sequencing technology, by distributing a single cell, a reaction solution, and encoded microspheres into a micro reaction unit, tens of thousands of cells can be analyzed simultaneously, revealing the expression of all genes within the entire genome at the single-cell level, which is very conducive to studying the expression heterogeneity among cells. The above technologies have developed rapidly in recent years and have made important contributions to the development of life science research and clinical diagnosis and treatment technologies.

[0003] Currently, the methods for realizing micro reaction units are mainly divided into micro cavities formed based on micro-nano processing technologies and micro droplets generated based on microfluidic technologies. Compared with micro cavities, the micro droplet method based on microfluidic technology is more widely used. However, whether it is the micro cavity or the micro droplet technology, the distribution of the reaction substances entering the micro reaction units in the current products is basically based on the Poisson distribution principle, that is, each micro reaction unit is independent of each other, and the distribution of the reaction substances follows randomness. In this case, the proportion and distribution method of different substances in the micro reaction unit cannot be accurately controlled, so it is necessary to use a certain relationship for correction during the analysis and calculation of the reaction results, which will inevitably affect the accuracy of the experimental results. On the other hand, some reaction substances do not enter the interior of the micro reaction unit, resulting in waste of reaction substances, especially for some rare and precious biochemical samples or reagents. In some cases, the generated micro reaction units include multiple types, and some or most of the micro reaction unit types are "invalid reaction units" outside the preset expectations. Since the composition and distribution of the reaction substances contained in the micro reaction unit do not meet the experimental preset expectations, it also causes waste of reaction substances, especially for some expensive reaction substances or precious biochemical samples, greatly affecting the cost and economy of the reaction.

[0004] See Figure 1 and Figure 2, in the micro - reaction unit generation structure 10 of the microfluidic chip, it includes a first fluid channel 110 and a second fluid channel 120. The first fluid channel 110 contains a first - phase fluid 111, and the second fluid channel 120 contains a second - phase fluid 121. The first fluid channel is connected to one or more reaction - substance injection channels, and fluids containing different types of reaction substances are injected into the first fluid channel through the reaction - substance injection channels. The reaction substances include but are not limited to the following types, for example: cells, bacteria, exosomes, virus particles, magnetic beads, encoded microspheres, gel microspheres, drug - loaded microspheres, artificially synthesized biological particles, reaction reagents, etc. Different types of reaction substances are injected into the first - phase fluid channel through their corresponding reaction - substance injection channels, and the process of their entering the first fluid channel follows the principle of randomness. Therefore, when the first - phase fluid 111 containing different types of reaction substances enters the second - phase fluid channel 120 to generate micro - reaction units, the composition and distribution of the reaction substances also follow the principle of randomness.

[0005] Therefore, in the micro - reaction units in the prior art, it is difficult to precisely control the proportion and distribution method of different substances inside, which affects the accuracy of experimental results, and there is also a phenomenon of waste of reaction substances. Summary of the Invention

[0006] The purpose of the present invention is to provide a device for generating micro - reaction units to solve the problems raised in the above - mentioned background technology.

[0007] To achieve the above - mentioned purpose, the present invention provides the following technical solution: A device for generating micro - reaction units, comprising:

[0008] A control unit,

[0009] At least one first fluid channel, which contains a first - phase fluid inside the first - phase fluid channel;

[0010] At least one second fluid channel, which contains a second - phase fluid inside the second fluid channel (120), and the second - phase fluid and the first - phase fluid are two immiscible fluids;

[0011] A plurality of reaction - substance injection channels, which are respectively communicated with the first fluid channel and are used for transporting reaction substances into the first fluid channel;

[0012] One or more detectors, which are respectively electrically connected to the control unit and are used for identifying the reaction substances inside the first fluid channel and / or the second fluid channel and feeding back a specified signal to the control unit;

[0013] One or more driving devices, which are respectively electrically connected to the control unit and are used for starting the driving effect after receiving the control instruction issued by the control unit, and then changing the fluid movement direction of the corresponding reaction substances.

[0014] Preferably, the second fluid channel includes a plurality of second-phase fluid injection channels communicating with the inflow direction of the first-phase fluid.

[0015] Preferably, the reactant injection channel includes a first reactant injection channel, a second reactant injection channel, and a third reactant injection channel.

[0016] The first reactant injection channel intersects with the first-phase fluid channel at a first intersection point; the second reactant injection channel intersects with the first-phase fluid channel at a second intersection point.

[0017] The third reactant injection channel intersects with the first-phase fluid channel at a third intersection point.

[0018] The first intersection point, the second intersection point, and the third intersection point are completely coincident, partially coincident, or non-coincident.

[0019] Preferably, it further includes a second reactant control channel. The second reactant control channel includes a first flow direction segment and a second flow direction segment. The second reactant injection channel is communicated with the first flow direction segment of the second reactant control channel. The second reactant enters the first flow direction segment of the second reactant control channel from the second reactant control channel entrance and flows out of the second flow direction segment of the second reactant control channel through the second reactant control channel exit.

[0020] Preferably, the detector is a first detector. The first detector is arranged outside the first reactant injection channel, and its detection port faces the inside of the first reactant injection channel, for identifying the first reactant (131) and feeding back a specified signal.

[0021] The driving device is a first driving device. The first driving device is arranged outside the first flow direction segment of the second reactant control channel. The first driving device receives the specified signal sent by the first detector and issues a driving force to deflect the second reactant and drive it to the second reactant injection channel.

[0022] Preferably, a sorting channel extends outward from the pipe of the second fluid channel. The detector further includes a second detector. The second detector is arranged outside the second fluid channel, and its detection port faces the inside of the second fluid channel. The second detector is electrically connected to the control unit, for identifying whether a specific reactant is contained in the first micro reaction unit generated and passing through in the second fluid channel and feeding back a specified signal.

[0023] Preferably, the driving device further includes a second driving device, which is arranged outside the intersection of the sorting channel and the second fluid channel. The second driving device is electrically connected to the control unit and starts and drives the first micro reaction unit into the sorting channel to flow out when receiving a control instruction issued by the control unit.

[0024] The second micro reaction unit generated and passed through in the second fluid channel flows out from the outlet of the second fluid channel.

[0025] Preferably, it further includes a first reaction substance control channel, which includes a first flow direction section and a second flow direction section. The first reaction substance injection channel is communicated with the first flow direction section of the first reaction substance control channel. The liquid containing the first reaction substance enters the first flow direction section of the first reaction substance control channel from the inlet of the first reaction substance control channel and flows out of the second flow direction section of the first reaction substance control channel through the outlet of the first reaction substance control channel.

[0026] Preferably, the first detector is alternatively set as a first reactant detector and a second reactant detector. The first reactant detector is arranged outside the third flow direction section of the first reaction substance control channel, and the second reactant detector is arranged outside the first flow direction section of the second reaction substance control channel. The first reactant detector and the second reactant detector are respectively electrically connected to the control unit.

[0027] The first driving device is alternatively set as a first reactant driving device and a second reactant driving device. The first reactant driving device is arranged outside the third flow direction section of the first reaction substance control channel, and the second reactant driving device is arranged outside the first flow direction section of the second reaction substance control channel. The first reactant driving device and the second reactant driving device are respectively electrically connected to the control unit.

[0028] Preferably, the liquid containing the first reaction substance and the liquid containing the second reaction substance are both concentrated or diluted before entering the first phase fluid channel, and the liquid is a solution, a suspension or an emulsion.

[0029] Preferably, the reaction substance is pretreated with a signal source that can be detected by the detector. The detector is an optical signal sensor, a camera, an electric inductor or a magnetic inductor, and the signal source is adapted to the detector.

[0030] Preferably, a signal emitting module is arranged on the detector, and a signal receiving module adapted to the signal emitting module is arranged on the control unit.

[0031] Preferably, the second fluid channel is alternatively provided as a second-phase fluid storage cavity, which communicates with the first fluid channel, and the second-phase fluid storage cavity contains the immobile second-phase fluid therein.

[0032] The present invention also discloses a method for generating a micro reaction unit, which uses the above-mentioned generating device and includes the following steps:

[0033] S1: Dilute or concentrate the liquid concentrations of different reaction substances according to preset test conditions;

[0034] S2: Add the liquids containing different reaction substances into the corresponding reaction substance injection channels so that only one reaction substance can pass through the detection and identification area each time;

[0035] S3: Identify one or several reaction substances entering the corresponding fluid channels through a detector, and feedback a specified signal to the control unit. After analysis, the control unit issues a control instruction to the driving device and controls the driving device to apply a driving effect to the reaction substances in one or several corresponding fluid channels, so that their flow directions are changed at the fluid channel intersection;

[0036] S4: Through the identification by the detector and the intervention of the driving device, two or more reaction substances enter the first-phase fluid channel according to a preset desired ratio and distribution method;

[0037] S5: Driven by an external pressure, the first-phase fluid (111) enters the second fluid channel (120) to form a micro reaction unit containing one or more reaction substances.

[0038] Compared with the prior art, the present invention has the following beneficial effects: The micro reaction unit generated by using the generating device of the present invention is different from the generation method of the micro reaction unit based on the Poisson distribution in the traditional technology. In the micro reaction unit generated by the present invention, different reaction substances can be selectively added into the micro reaction unit according to a certain rule, so as to improve the overall reaction efficiency, save the usage amount of key reaction substances, and ensure the accuracy of the reaction result. Description of the Drawings

[0039] Figure 1 is a schematic structural diagram of the generating device of the micro reaction unit in the prior art of the present invention;

[0040] Figure 2 is a schematic structural diagram of the generating device of the micro reaction unit in the prior art of the present invention when different reaction substances are added;

[0041] Figure 3Schematic diagram of the structure for generating a micro reaction unit in the first embodiment of the present invention;

[0042] Figure 4 Schematic diagram of the structure for generating a micro reaction unit in the first embodiment of the present invention after adding reaction substances;

[0043] Figure 5 For the present invention Figure 4 Schematic diagram of the first reaction substance and the spacing between adjacent first reaction substances in;

[0044] Figure 6 Schematic diagram of the state when the first reaction substance enters the detection position in the first embodiment of the present invention;

[0045] Figure 7 Schematic diagram of the combination of the first reaction substance and the second reaction substance in the first embodiment of the present invention;

[0046] Figure 8 Schematic diagram of the structure for generating a micro reaction unit in the second embodiment of the present invention;

[0047] Figure 9 Schematic diagram of the structure for generating a micro reaction unit in the third embodiment of the present invention;

[0048] Figure 10 Schematic diagram of the structure of the detector of the present invention;

[0049] Figure 11 Schematic diagram of the structure for generating a micro reaction unit in the fourth embodiment of the present invention;

[0050] Figure 12 Schematic diagram of the structure of the microfluidic chip of the present invention;

[0051] Figure 13 Is Figure 12 Enlarged view of the structure within the dashed box 20 of;

[0052] Figure 14 Three - dimensional schematic diagram after applying the first detector above the microfluidic chip;

[0053] Figure 15 Schematic diagram of a way for the detector to detect the first reaction substance;

[0054] Figure 16 Schematic diagram of another way for the detector to detect the first reaction substance;

[0055] Figure 17 Schematic diagram of the structure when the driving device adopts a driving method;

[0056] Figure 18Schematic structural diagram of a drive device adopting another driving method. Detailed implementation manners

[0057] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0058] Refer to Figure 3 、 Figure 11 The present invention provides a generating device for a micro reaction unit, including:

[0059] A control unit,

[0060] At least one first fluid channel 110, in which a first-phase fluid 111 is contained;

[0061] At least one second fluid channel 120, in which a second-phase fluid 121 is contained. The second-phase fluid 121 and the first-phase fluid 111 are two immiscible fluids. Thus, when the first-phase fluid 111 is squeezed into the second-phase fluid 121, the first-phase fluid will maintain an independent shape, that is, a micro unit, and will not be dispersed or incorporated into the second-phase fluid 121;

[0062] A plurality of reaction substance injection channels, which are respectively communicated with the first fluid channel 110 and are used for transporting reaction substances into the first fluid channel 110;

[0063] One or more detectors, which are respectively electrically connected to the control unit. The detectors are used to identify the reaction substances inside the first fluid channel 110 and / or the second fluid channel 120 and feedback a specified signal to the control unit;

[0064] One or more drive devices, which are respectively electrically connected to the control unit. The drive devices are used to start the driving effect after receiving the control instructions sent by the control unit, and then change the fluid movement direction of the reaction substances inside the corresponding fluid channels.

[0065] In the above technical solutions, the control unit, the first fluid channel 110, the second fluid channel 120, and the plurality of reaction substance injection channels form a fluid channel structure 20 for generating micro reaction units. The fluid channel structure 20 belongs to the structure on the microfluidic chip 30. The detectors and the drive devices may or may not be part of the microfluidic chip 30. For example, they can be set in the instrument equipment. After the microfluidic chip 30 is added to the instrument equipment, they cooperate with each other.

[0066] In the present invention, a detector is adopted to identify reaction substances inside a fluid channel, and a specified signal is fed back to a control unit according to the detected reaction substances. The control unit analyzes the specified signal to judge the state of the reaction substances, and issues a control instruction as needed according to the state of the injected reaction substances. After receiving the control instruction issued by the control unit, a driving device starts to play a driving role, thereby changing the movement direction of the reaction substances. Such a technical solution can selectively add different reaction substances into a micro reaction unit according to a certain rule, so as to improve the overall reaction efficiency, save the dosage of key reaction substances, and ensure the accuracy of the reaction result.

[0067] See Figure 3 , in one embodiment, the reaction substance injection channels include a first reaction substance injection channel 112, a second reaction substance injection channel 113, and a third reaction substance injection channel 114. 112a, 113a, and 114a are respectively the inlets of the first reaction substance injection channel, the second reaction substance injection channel, and the third reaction substance injection channel. Different types of reaction substances are respectively added into the first reaction substance injection channel 112, the second reaction substance injection channel 113, and the third reaction substance injection channel 114.

[0068] The first reaction substance injection channel 112 intersects with the first fluid channel 110 at a first intersection point 112b, the second reaction substance injection channel 113 intersects with the first fluid channel 110 at a second intersection point 113b, and the third reaction substance injection channel 114 intersects with the first fluid channel 110 at a third intersection point 114b. The first intersection point 112b, the second intersection point 113b, and the third intersection point 114b completely coincide, partially coincide, or do not coincide. That is, in some designs, different reaction substance injection channels intersect with the first fluid channel 110 at the same position. In other designs, different reaction substance injection channels intersect with the first fluid channel 110 at different positions respectively, that is, the positions of the above-mentioned intersection points 112b, 113b, and 114b in the first-phase fluid channel 110 can coincide, or several of them coincide, or do not coincide at all. The first to third reaction substance injection channels here are only for explaining the content of the present invention and its related technical information, and do not have any restrictive effect. In some designs, the number of reaction substance injection channels can be less than three or more than three.

[0069] The first fluid channel 110 is connected to one or more reaction substance injection channels. Fluids containing different types of reaction substances are injected into the first fluid channel 110 through the reaction substance injection channels and gradually move in the direction of the second fluid channel 120.

[0070] The second fluid channel 120 includes a plurality of second-phase fluid injection channels 122 that communicate with the inflow direction of the first-phase fluid 111. For example, Figure 3 one second-phase fluid injection channel 122 can be provided above and below the second fluid channel 120 respectively, which penetrate up and down. The second-phase fluid 121 can be injected into the second fluid channel 120 through the second-phase fluid injection channels 122 on both the upper and lower sides.

[0071] When a preset driving pressure and flow rate are applied to the inlets of the fluid channels of the microfluidic chip, the second-phase fluid 121 will generate a fluid shear force when passing through the intersection 120a through the injection channel 122, and then cut the first-phase fluid 111 entering the second fluid channel 120, thereby generating tiny reaction units 140 containing the first-phase fluid 111 in the second-phase fluid 121.

[0072] See Figure 12 and Figure 13 In the microfluidic chip 30 used in the present invention, the fluid channel structure 20 for generating tiny reaction units is shown within the dashed box. In the microfluidic chip 30, a first reactant addition chamber 31, a second reactant addition chamber 32, a third reactant addition chamber 33, a second-phase fluid addition chamber 34, a reaction collection chamber 35, and a second reactant recovery chamber 36 are provided. The first reactant 131, the second reactant 132, and the third reactant 133 enter the corresponding reactant injection channels (the first reactant injection channel 112, the second reactant injection channel 113, and the third reactant injection channel 114) in the microfluidic chip 30 through the first reactant addition chamber 31, the second reactant addition chamber 32, and the third reactant addition chamber 33 respectively. The second-phase fluid 121 is injected into the second fluid channel 120 through the second-phase fluid addition chamber 34. The dripping second reactant 132 is collected through the second reactant recovery chamber 36, and the generated tiny reaction objects are collected through the reaction collection chamber 35.

[0073] See Figure 3 and Figure 4 、 Figure 5 and Figure 14, the present invention further includes a second reactant control channel 152. The second reactant control channel 152 includes a first flow direction segment and a second flow direction segment. The second reactant injection channel 113 communicates with the first flow direction segment of the second reactant control channel 152 through an intersection 113a. The first reactant 131 and the third reactant 133 are injected into the first fluid channel 110 through the inlets 112a and 114a of the first reactant injection channel 112 and the third reactant injection channel 114. The second reactant 132 does not directly enter the first fluid channel 110 through the second reactant injection channel 113, but enters the first flow direction segment of the second reactant control channel 152 through the second reactant control channel inlet 152a, and flows out of the second flow direction segment of the second reactant control channel 152 through the outlet 152b of the second reactant control channel.

[0074] The detector can be optionally set as the first detector 155. The first detector 155 is used to detect the reactants inside the reactant injection channel. The first detector 155 is arranged outside the first reactant injection channel 112, and its detection port faces the inside of the first reactant injection channel 112, for identifying the first reactant 131 and feedbacking a specified signal according to the injection situation of the first reactant 131.

[0075] The driving device is the first driving device 160. The driving device is used to drive the reactants flowing through the channel and change their flow directions. The first driving device 160 is arranged outside the first flow direction segment of the second reactant control channel 152, and emits a driving force to deflect the second reactant 132 and drive it into the second reactant injection channel (113). See Figure 6 , 170 is the driving effect exerted by the first driving device 160, and its acting position in the second reactant control channel 152 is 152c.

[0076] Figure 4 For Figure 3 The schematic diagram after adding reactants in the shown embodiment. In this embodiment, the first reactant 131 is a kind of biological particle, the second reactant 132 is a kind of microsphere, and the third reactant 133 is a reaction reagent. Among them, a biological particle binds to a microsphere containing biological information, and enters a tiny reaction unit together with a certain amount of reaction reagent, so as to complete the reaction target preset by the experiment. The second reactant 132 enters the second reactant control channel 152 through the second reactant control channel inlet 152a, and flows out of the second reactant control channel 152 along the outlet 152b of the second reactant control channel.

[0077] Figure 4In it, the first detector 155 is used to detect the situation of the first reactant 131 entering the first reactant injection channel. When the first reactant 131 enters the first reactant injection channel 112 and passes through position 112c, it will be sensed by the first detector 155 and a specified signal will be fed back to the control unit. Figure 4 At the moment shown in, there is no indication that the first reactant 131 is at the detection position 112c. At this time, the first detector 155 does not feed back a specified signal to the control unit.

[0078] In order to control the composition and distribution of reactants in the micro reaction unit, in this embodiment, the liquid containing the first reactant 131 is concentrated or diluted to a limited extent. The liquid is a solution, suspension or emulsion, so that the first reactant 131 can only enter the first reactant injection channel 112 one by one through the entrance of the first reactant injection channel, and the interval distance 181 between adjacent first reactants 131 is much larger than the size of the first reactant 131 itself. The liquid containing the first reactant 131 can be diluted before the experiment and then added into the microfluidic chip, or a dilution device for the liquid of the first reactant 131 can be designed using the microfluidic chip structure, so that the first reactant 131 is at a dilution concentration that meets the experimental requirements before entering the first reactant injection channel 112.

[0079] In this embodiment, the second reactant 132 is concentrated or diluted in a certain proportion and then injected into the second reactant control channel 152, so that the second reactants 132 entering the channel are arranged more closely and only one second reactant 132 can pass through each time. The liquid containing the second reactant 132 can be concentrated or diluted before the experiment and then added into the microfluidic chip, or a concentration device for the liquid of the second reactant 132 can be designed using the microfluidic chip structure. The liquid can be a solution, suspension or emulsion. 182 is the interval distance between the second reactants in the second reactant control channel 152. In this embodiment, the interval distance 182 between the second reactants 132 is 1 to 20 times the size of the second reactant 132 itself. Preferably, the interval distance 182 should be set to 1.5 to 4 times the size of the second reactant 132 itself. In order to accurately control the combination of the first reactant 131 and the second reactant 132 in the first fluid channel 110, see Figure 4 and Figure 5 should control the interval distance 181 to be greater than the interval distance 182. Usually, the interval distance 181 is controlled to be 1.5 to 200 times the interval distance 182. To ensure a high reaction efficiency, preferably, the interval distance 181 can be set to 3 to 100 times the interval distance 182.

[0080] SeeFigure 6 , Figure 6 The figure shows the state when the first reactant 131 enters the detection position 112c. At this time, the first detector 155 detects that the first reactant 131 enters the detection position 112c in the first reactant injection channel 112, and then feeds back a specified signal to the control unit. After receiving the specified signal from the first detector, the control unit issues an instruction to activate the first driving device 160 and generate a driving effect 170, forcing a second reactant 132 at the internal intersection 113a of the second reactant control channel 152 to change its flow direction and thus enter the second reactant injection channel 113.

[0081] The positions where the first detector 155 and the first driving device 160 act in the fluid channel, as well as the fluid velocities of driving the first reactant 131 liquid and the second reactant 132 liquid, are pre-calculated and precisely designed respectively, so that when a first reactant 131 reaches the first fluid channel 110 after passing through the detection position 112c, it can just combine with a reaction reagent of a second reactant 132 and a required third reactant 133, and the relative positions among the components are smaller than the average size of a micro reaction unit, as Figure 7 shown. In this way, when the first-phase fluid 111 of the reaction reagent containing a first reactant 131, a second reactant 132 and a part of the third reactant 133 enters the second fluid channel 120, micro reaction units are generated, and the components contained inside the micro reaction units are completely in line with the experimental preset expectations in terms of reactant distribution. When the first reactant 131 is not detected, the first detector 155 will not feed back a specified signal, so that the first driving device 160 will not generate a driving effect, and no second reactant 132 will be injected into the second reactant injection channel 113.

[0082] In this embodiment, since the liquid containing the first reactant 131 is diluted or concentrated in a certain proportion, and when the first reactant 131 enters the detection position 112c, a second reactant 132 will be sent into the second reactant injection channel 113. Each first reactant 131 and a second reactant 132 enter the inside of the first fluid channel 110 in pairs. When the first detector 155 does not detect the first reactant 131, no second reactant 132 will enter the first fluid channel 110. Therefore, as long as the experimental conditions are accurately controlled, the micro reaction units collected in the second fluid channel 120 only contain two types, 141 and 145. Since each first reactant 131 can be fully utilized, effective micro reaction units are generated.

[0083] In the second reactant control channel 152, it will only be injected into the first-phase fluid channel 110 when the first detector detects the first reactant 131. Other second reactants 132 are discharged through the outlet 152b. The outlet 152b can be connected to a recovery chamber to recover the unused second reactants 132 and use them for the next test. In this way, the device and method proposed by the present invention not only greatly reduce the types of micro reaction units, making the difficulty of the next reaction and structural analysis greatly reduced, but also greatly increase the proportion of effective reaction units collected, thereby greatly improving the reaction efficiency. In addition, the device and method proposed by the present invention make full use of reactants, greatly reducing the waste of reactants and improving the economy of the entire test. This is particularly important for some reactants that are difficult to obtain or expensive.

[0084] See Figure 8 , in some other embodiments, the fluid channel structure 20 generated by the micro reaction unit can also be replaced with the structure of the fluid channel structure 21, and the generated micro reaction units can be further optimized. Specifically, a sorting channel 125 extends outward from the second fluid channel 120. The sorting channel 125 can be arranged in the middle or other positions of the second fluid channel 120. The sorting channel 125 communicates with the second-phase fluid channel 120 through the intersection 125a.

[0085] See Figure 11 , in some other embodiments, the second fluid channel 120 can be alternatively arranged as a second-phase fluid storage chamber 130. The second-phase fluid storage chamber 130 communicates with the first fluid channel 110, and the second-phase fluid storage chamber 130 contains an immobile second-phase fluid 121 inside. In this structure, when the first reactant 131 and the second reactant 132 enter the second-phase fluid storage chamber 130 through the first fluid channel 110, under the action of fluid shear force and surface tension, the first-phase fluid 111 containing the first reactant 131 and the second reactant 132 forms micro reaction units in the second-phase fluid 121. In this embodiment, there is no sorting channel.

[0086] The detector further includes a second detector 156, which is disposed outside the second fluid channel 120 and has its detection port facing the interior of the second fluid channel 120. The second detector 156 is electrically connected to the control unit. The second detector 156 is used to detect whether a specific reaction substance is contained in the micro reaction unit, specifically referring to the first reaction substance 131 and the second reaction substance 132 in this embodiment, and feeds a specified signal back to the control unit. The working principle, type, installation method, and signal generation method of the second detector 156 may be the same as or different from those of the first detector 155, as long as the type of the micro reaction unit can be identified inside the second-phase fluid channel 120 through the second detector 156.

[0087] The driving device further includes a second driving device 161, which is disposed outside the intersection of the sorting channel 125 and the second fluid channel 120. The second driving device 161 is electrically connected to the control unit. After the micro reaction unit 145 is identified by the detector 156, the control unit sends a control instruction to the second driving device 161. The second driving device 161 starts and, under the driving action 171 it issues, drives the first micro reaction unit 145 into the sorting channel 125 to flow out, so that only one type of micro reaction unit 141 is collected at the outlet 120b of the second-phase fluid channel 120. The working principle, type, installation method, and action generation method of the second driving device 161 may be the same as or different from those of the first driving device 160, as long as it can generate a driving action and separate two different types of micro reaction units in the microfluidic channel.

[0088] See Figure 9 , in another embodiment, the fluid channel structure 20 formed by the micro reaction unit can also be replaced with the structure of the fluid channel structure 22. That is, on the basis of the fluid channel structure 20, a first reaction substance control channel 151 is added. The first reaction substance control channel 151 includes a third flow direction segment and a fourth flow direction segment. The first reaction substance injection channel 112 is communicated with the third flow direction segment of the first reaction substance control channel 151. The liquid containing the first reaction substance 131 enters the third flow direction segment of the first reaction substance control channel 151 from the inlet of the first reaction substance control channel 151 and flows out of the fourth flow direction segment of the first reaction substance control channel 151 through the outlet of the first reaction substance control channel 151. Both the first reaction substance 131 and the second reaction substance 132 are transported in their corresponding first reaction substance control channel 151 and second reaction substance control channel 152 and flow towards the recovery chamber.

[0089] In Figure 8Based on the described embodiments, the first detector 155 can be alternatively provided as a first reactant detector 15501 and a second reactant detector 15502. The first reactant detector 15501 is provided outside the third flow direction section of the first reaction substance control channel 151, and the second reactant detector 15502 is provided outside the first flow direction section of the second reaction substance control channel 152. The first reactant detector 15501 and the second reactant detector 15502 are respectively used to detect the reaction substances in the first reaction substance control channel 151 and the second reaction substance control channel 152, and the first reactant detector 15501 and the second reactant detector 15502 are respectively electrically connected to the control unit. When detecting the corresponding reaction substances, they will feedback a specified signal to the control unit.

[0090] Correspondingly, the first driving device 160 can be alternatively provided as a first reactant driving device 16001 and a second reactant driving device 16002. The first reactant driving device 16001 is provided outside the third flow direction section of the first reaction substance control channel 151, and the second reactant driving device 16002 is provided outside the first flow direction section of the second reaction substance control channel 152. The first reactant driving device 16001 and the second reactant driving device 16002 are respectively electrically connected to the control unit. After the control unit receives the specified signals fed back by the first reactant detector 15501 and / or the second reactant detector 15502, it issues a control instruction to control the first reactant driving device 16001 and / or the second reactant driving device 16002 to change the flow direction of the reaction substances in the channel.

[0091] In this embodiment solution, the liquid containing the first reaction substance 131 and the liquid containing the second reaction substance 132 are both concentrated or diluted before entering the first fluid channel 110, so that the first reaction substance 131 and the second reaction substance 132 are closely arranged in the corresponding first reaction substance control channel 151 and the second reaction substance control channel 152, and sequentially pass through the detection area in order. After accurate calculation and experimental design, the first reactant driving device 16001 installed on the first reaction substance control channel 151 and the second reactant driving device 16002 installed on the second reaction substance control channel 152 are started according to a certain predetermined program after receiving the feedback signals sent by their respective detectors, so that one first reaction substance 131 and one second reaction substance 132 enter the first fluid channel 110 simultaneously.

[0092] Preferably, the reaction substances in the present invention are pretreated with a signal source that can be detected by the detector. The detector is an optical signal sensor or a camera or an electric inductor or a magnetic inductor, and the signal source is adapted to the detector, so that the reaction substances with the signal source can be quickly found by the detector.

[0093] In one embodiment, the detector is an optical signal sensor, which realizes the identification of the reaction substances entering the channel by detecting the optical signals bound to the reaction substances.

[0094] In another embodiment, the detector can be a CMOS or CCD camera. By taking pictures of the reaction substances inside the first fluid channel 110 and / or the second fluid channel 120 and using computer analysis algorithms to analyze the images formed by the reaction substances, the reaction substances at that location can be identified.

[0095] In another embodiment, the detector is an electrical or magnetic sensor, etc. The reaction substances are pre-bound to an object that can interact with the detector. For example, the reaction substances are pre-treated to have magnetism or conductivity, and when the reaction substances pass through the detection area inside the flow channel, they are sensed by the corresponding detector.

[0096] Figure 10 Shown is the detector in another embodiment. Different from the above description, the detector is directly integrated with the side wall or bottom surface of the microfluidic chip during the microfluidic chip processing, and a micro-sensor is formed thereon for identifying the reaction substances.

[0097] In order to realize the timely transmission of the signals detected by the detector to the control unit, in the present invention, it is preferably that a signal emitting module is provided on the detector, and a signal receiving module adapted to the signal emitting module is provided on the control unit. By transmitting the signals, the control unit can grasp the motion state of the reaction substances in real time.

[0098] For example, see Figure 15 , which is a method for a detector 155 to detect a first reaction substance 131. As shown in the figure, the detector 155 emits a detection action into the microfluidic channel to form a detection feedback signal. When no first reaction substance 131 enters the detection area, the detection signal remains unchanged; conversely, when the first reaction substance 131 enters the detection area, it causes a change in the detection signal, which is sensed by the detector, thereby realizing the detection action on the first reaction substance 131.

[0099] Figure 16 This is another detection method of the detector. At this time, the detector 155 is an image generation device, such as a CCD sensor, etc. By taking pictures of the first reaction substance before and after or recording a video, and analyzing the obtained images, it is detected whether the first reaction substance 131 has passed.

[0100] Similarly, in some embodiments, the driving device may be an element disposed outside the first fluid channel 110 and / or the second fluid channel 120, which acts on the reaction substances flowing through the inside of the channel by releasing a physical field, thereby changing the flow direction of the reaction substances. For example, dielectrophoresis, surface acoustic waves, and bulk acoustic waves used in airport microfluidic technology can all be used as the driving device in this case.

[0101] In some other embodiments, the driving device may also be an external mechanical element that changes the flow direction of the reaction substances inside the flow channel by extrusion or mechanical action.

[0102] For example, referring to Figure 14 , the driving device 160 is a non-contact driving method, that is, electrodes are fabricated in the microfluidic chip and an electrical signal is applied to the electrodes, so that dielectrophoresis or surface acoustic wave phenomena can occur in the microfluidic channel, etc., and then used to change the flow direction of the second reaction substance in the flow channel. This is a commonly used method in laboratories.

[0103] The driving device can also be of a contact type. For example, by applying an external force to squeeze the flow channel, the second reaction substance changes its flow direction inside the microfluidic channel, as shown in Figure 17 . When no first reaction substance passes through, the driving device 160 retracts to the initial position and the microfluidic channel resumes its original shape.

[0104] Figure 18 is another driving method of the driving device 160. By applying pressure in the channel 1601 relative to a channel 113, when the second reaction substance 132 passes through, a part of the fluid flows out of the channel 1601 and enters the channel 113, thereby changing the flow direction of the second reaction substance. In addition, there are some other implementation methods. For example, a fluid valve is installed at the intersection 113a to switch the flow direction of the second reaction substance. At this time, the driving device 160 is a valve circuit system and its corresponding control device.

[0105] The present invention also discloses a method for generating a micro reaction unit, which uses the above-mentioned generating device and includes the following steps:

[0106] S1: Dilute or concentrate the liquid concentrations of different reaction substance-containing liquids according to preset test conditions;

[0107] S2: Add different reaction substance-containing liquids into the corresponding reaction substance injection channels so that only one reaction substance can pass through the detection and identification area each time;

[0108] The channels are multiple reaction substance injection channels.

[0109] S3: Identify one or more reactants entering the corresponding fluid channels through a detector, and feedback a specified signal to the control unit. After analysis, the control unit issues a control instruction to the driving device and controls the driving device to exert a driving effect on the reactants in one or more corresponding fluid channels, causing them to change the flow direction at the fluid channel intersection;

[0110] S4: Through the identification of the detector and the intervention of the driving device, enable two or more reactants to enter the first-phase fluid channel according to a preset desired ratio and distribution method;

[0111] S5: Driven by an external pressure, the first-phase fluid (111) enters the second fluid channel (120) to form a tiny reaction unit containing one or more reactants.

[0112] The generating device and generating method of a tiny reaction unit proposed by the present invention have the following technical effects:

[0113] (1) By controlling the time sequence of the first reactant and the second reactant entering the first fluid channel, the types of reactants contained in the micro-droplets are greatly reduced, facilitating the generation of the expected reaction results;

[0114] (2) Except for specific types of tiny reaction units, the reaction collection unit does not contain other types that are inevitable in traditional methods, greatly reducing the data analysis difficulty of the reaction results;

[0115] (3) By adding a detector and a driving device, the generated micro-droplets can be further sorted, so that the collection unit only contains the tiny reaction units of the only expected type, and this result cannot be achieved by all the methods in the prior art;

[0116] (4) For some precious or rare reactants, they are fully utilized in the reaction, no invalid micro-droplets are generated, the utilization rate and cost of the reactants are improved, and high-quality reaction results are ensured;

[0117] In summary, the tiny reaction units generated by the generating device of the present invention are different from the generating method of tiny reaction units based on Poisson distribution in the traditional technology. In the tiny reaction units generated by the present invention, different reactants can be selectively added to the tiny reaction units according to a certain rule, thereby improving the overall reaction efficiency, saving the dosage of key reactants, and ensuring the accuracy of the reaction results.

[0118] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "upper", "lower", "front", "rear", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation to the present invention.

[0119] In the description of the present invention, it should be noted that unless otherwise clearly specified and defined, the terms "installed", "connected", and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood through specific circumstances.

[0120] The above detailed description is made on the preferred embodiments of this patent. However, this patent is not limited to the above embodiments. Various changes can be made without departing from the spirit of this patent within the scope of knowledge possessed by those of ordinary skill in the art.

Claims

1. A generating device for a micro reaction unit, comprising: A control unit, At least one first fluid channel (110), wherein the first fluid channel (110) contains a first-phase fluid (111); At least one second fluid channel (120), wherein the second fluid channel (120) contains a second-phase fluid (121), and the second-phase fluid (121) and the first-phase fluid (111) are two immiscible fluids; A plurality of reaction substance injection channels, respectively communicating with the first fluid channel (110) and used for transporting reaction substances into the first fluid channel (110); One or more detectors, respectively electrically connected to the control unit and used for identifying reaction substances inside the first fluid channel (110) and the second fluid channel (120) and feeding back a specified signal to the control unit; One or more driving devices, respectively electrically connected to the control unit and used for starting a driving effect after receiving a control instruction issued by the control unit, thereby changing the fluid movement direction of the corresponding reaction substances; The reaction substance injection channels include a first reaction substance injection channel (112), a second reaction substance injection channel (113) and a third reaction substance injection channel (114); the first reaction substance injection channel (112) intersects with the first fluid channel (110) at a first intersection point (112b); the second reaction substance injection channel (113) intersects with the first fluid channel (110) at a second intersection point (113b); the third reaction substance injection channel (114) intersects with the first fluid channel (110) at a third intersection point (114b); the first intersection point (112b), the second intersection point (113b) and the third intersection point (114b) are completely coincident, partially coincident or non - coincident; A second reaction substance control channel (152), the second reaction substance control channel (152) includes a first flow direction segment and a second flow direction segment, the second reaction substance injection channel (113) communicates with the first flow direction segment of the second reaction substance control channel (152), the second reaction substance (132) enters the first flow direction segment of the second reaction substance control channel (152) from the second reaction substance control channel entrance (152a) and flows out of the second flow direction segment of the second reaction substance control channel (152) through the second reaction substance control channel exit (152b); The detector is a first detector (155), the first detector (155) is arranged outside the first reaction substance injection channel (112), and its detection port faces the inside of the first reaction substance injection channel (112) for identifying the first reaction substance (131) and feeding back a specified signal, The driving device is the first driving device (160), which is arranged outside the first flow direction section of the second reactant control channel (152). The first driving device (160) receives the specified signal sent by the first detector (155), and emits a driving force to deflect the second reactant (132) and drive it to the second reactant injection channel (113).

2. The generating device of a micro reaction unit according to claim 1, characterized in that: The second fluid channel (120) includes a plurality of second-phase fluid injection channels (122) communicating with the inflow direction of the first-phase fluid (111).

3. The generating device of a micro reaction unit according to claim 1, characterized in that, A sorting channel (125) extends outward from the pipeline of the second fluid channel (120). The detector further includes a second detector (156), which is arranged outside the second fluid channel (120), and its detection port faces the inside of the second fluid channel (120). The second detector (156) is electrically connected to the control unit and is used to identify whether the first micro reaction unit (145) generated and passing through in the second fluid channel (120) contains the first reactant and the second reactant, and feedback a specified signal.

4. The generating device of a micro reaction unit according to claim 3, characterized in that, The driving device further includes a second driving device (161), which is arranged outside the intersection of the sorting channel (125) and the second fluid channel (120). The second driving device (161) is electrically connected to the control unit, and when receiving the control instruction sent by the control unit, it starts and drives the first micro reaction unit (145) to flow out into the sorting channel (125). The second micro reaction unit (141) generated and passing through in the second fluid channel (120) flows out from the outlet of the second fluid channel (120).

5. The generating device for a micro reaction unit according to claim 4, wherein It further includes a first reactant control channel (151), which includes a third flow direction section and a fourth flow direction section. The first reactant injection channel (112) communicates with the third flow direction section of the first reactant control channel (151). The liquid containing the first reactant enters the third flow direction section of the first reactant control channel (151) from the inlet of the first reactant control channel (151), and flows out of the fourth flow direction section of the first reactant control channel (151) through the outlet of the first reactant control channel (151).

6. The generating device of a micro reaction unit according to claim 5, characterized in that, The first detector (155) is set as the first reactant detector (15501) and the second reactant detector (15502). The first reactant detector (15501) is arranged outside the third flow direction section of the first reactant control channel (151), and the second reactant detector (15502) is arranged outside the first flow direction section of the second reactant control channel (152). The first reactant detector (15501) and the second reactant detector (15502) are respectively electrically connected to the control unit. The first driving device (160) is set as a first reactant driving device (16001) and a second reactant driving device (16002). The first reactant driving device (16001) is arranged outside the third flow direction section of the first reactant control channel (151), and the second reactant driving device (16002) is arranged outside the first flow direction section of the second reactant control channel (152). The first reactant driving device (16001) and the second reactant driving device (16002) are electrically connected to the control unit respectively.

7. The generating device of a micro reaction unit according to claim 1, wherein Before entering the first fluid channel (110), the liquid containing the first reactant (131) and the liquid containing the second reactant (132) are both concentrated or diluted first. The liquid is a solution, a suspension or an emulsion.

8. The generating device of a micro reaction unit according to claim 1, characterized in that The reactant is pretreated and has a signal source that can be detected by the detector. The detector is an optical signal sensor, a camera, an electrical inductor or a magnetic inductor. The signal source is adapted to the detector.

9. The generating device for a micro reaction unit according to claim 1, wherein A signal emitting module is arranged on the detector, and a signal receiving module adapted to the signal emitting module is arranged on the control unit.

10. The generating device of a micro reaction unit according to claim 1, characterized in that, The second fluid channel (120) is set as a second-phase fluid storage cavity (130). The second-phase fluid storage cavity (130) is communicated with the first fluid channel (110), and the second-phase fluid storage cavity (130) contains the non-flowing second-phase fluid (121) inside.

11. A method for generating a micro reaction unit, which uses the generating device described in any one of claims 1-10, characterized in that, It includes the following steps: S1: Dilute or concentrate the liquid concentrations of different reactant-containing liquids according to preset test conditions; S2: Add the different reactant-containing liquids into the corresponding reactant injection channels so that only one reactant can pass through the detection and identification area each time; S3: The detector identifies one or several reactants entering the corresponding fluid channel and feeds back a specified signal to the control unit. After analysis, the control unit issues a control instruction to the driving device and controls the driving device to apply a driving action to one or several reactants in the corresponding fluid channel, so that the flow direction is changed at the fluid channel intersection; S4: Through the identification of the detector and the intervention of the driving device, two or more reactants enter the first fluid channel according to the preset desired ratio and distribution method; S5: Driven by an external pressure, the first-phase fluid (111) enters the second fluid channel (120) to form a tiny reaction unit containing one or more reactants.

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