CN110560184A - Microfluidic chip, microfluidic reaction system and driving method - Google Patents

Abstract

The disclosure relates to a microfluidic chip, a microfluidic reaction system and a reaction method. The microfluidic chip (100) includes: a reaction chip body (110), having at least one flow channel and at least one reaction chamber (131, 132, 133), and the at least one flow channel is respectively connected to the at least one reaction chamber (131 , 132, 133) direct communication or valve-controlled communication; and a sampling mechanism, arranged on the reaction chip body (110), and communicated with the at least one flow channel, for independent from the microfluidic chip ( The reagent storage structure (200) of 100) extracts reagent samples and provides them to the reaction chambers (131, 132, 133). By setting a sampling mechanism on the reaction chip body and using the sampling mechanism to extract reagent samples from the reagent storage structure independent of the microfluidic chip, the dependence on the reagent storage and release structure in the reaction chip body can be reduced or eliminated, thereby simplifying the The overall structural design of the microfluidic chip reduces the storage requirements of the chip.

Description

Microfluidic chip, microfluidic reaction system and driving method

technical field

The disclosure relates to a microfluidic chip, a microfluidic reaction system and a driving method.

Background technique

Point-Of-Care Testing (POCT for short) refers to any test performed by hospital professionals or non-professionals outside the testing center, also known as bedside testing. With the help of integrated detectors or portable instruments, it implements on-site convenient detection, reduces the waiting time for detection, simplifies the cumbersome inspection process, and replaces traditional instruments that require high maintenance costs, relieving the clinical application of high-end instruments and central hospitals. Test center dependencies. Therefore, POCT technology is currently becoming a research and development hotspot in the field of medical diagnostic technology.

In the early 1990s, Microfluidic Chip technology appeared. With the corresponding driving and testing instruments, common reagent storage and release, mixing, Experimental steps such as dilution, washing, reaction, and result monitoring, so that the entire detection system (chip and instrument) is compact and highly integrated, and the detection process can be simplified without loss of detection sensitivity, reducing the burden on detection personnel and environmental conditions. Requirements, to achieve on-site testing. Therefore, based on its own characteristics of miniaturization, integration, and automation, microfluidic chips are highly in line with the development needs of POCT detection technology, and are of great significance for optimizing clinical detection.

In related technologies, in addition to the reaction structure, the microfluidic chip is also equipped with related structures for reagent storage and release, which makes the overall structural design of the microfluidic chip more complicated, and it is not easy to industrialize, and it is difficult for chip storage. The requirements are also relatively high. In addition, microfluidic chips often need to perform mixed reactions of various reagents during use, and it is difficult for existing microfluidic chips to make adaptive adjustments to the types and capacities of reagents after storing them.

Contents of the invention

In view of this, the embodiments of the present disclosure provide a microfluidic chip, a microfluidic reaction system and a driving method, which can facilitate long-term and reliable storage of reagents.

In one aspect of the present disclosure, a microfluidic chip is provided, comprising:

The reaction chip body has at least one flow channel and at least one reaction chamber, and the at least one flow channel is directly or valve-controlled connected to the at least one reaction chamber; and

The sampling mechanism is arranged on the reaction chip body and communicates with the at least one flow channel, and is used to extract reagent samples from a reagent storage structure independent of the microfluidic chip and provide them to the reaction chamber.

In some embodiments, the sampling mechanism includes:

a sampling needle selectively communicating with all or part of the at least one reaction chamber;

Wherein, the needle body of the sampling needle has a hollow channel, and the tip portion of the needle body can enter the reagent storage structure.

In some embodiments, the sampling mechanism also includes:

A holed needle with a diameter larger than that of the sampling needle is used to form a channel on the reagent storage structure for the sampling needle to enter.

In some embodiments, the reaction chamber includes a first port and a second port, the first port communicates with the flow channel, the second port is operatively connected to a gas drive device, and the reaction chamber is controlled by It is configured to input or output reagent samples through the flow channel under the gas drive of the gas drive device.

In some embodiments, the gas-driven device comprises:

Peristaltic, vacuum, or syringe pumps, with hoses; and

A vacuum suction cup is arranged at the end of the hose and is used to selectively form a sealed connection with the second port.

In some embodiments, a flexible sealing material is provided at the second port, and the gas-driven device comprises:

A syringe having a needle portion penetrating the flexible sealing material.

In some embodiments, the reaction chip body further includes a control valve, which is arranged in series on the flow path between the sampling mechanism and the reaction chamber.

In some embodiments, the reaction chip body includes a plurality of reaction chambers, and the control valve is respectively connected to each reaction chamber through the flow channel, and is used to control the reaction chambers and/or the sampling mechanism. Gating and/or opening control of flow passages between each of the reaction chambers.

In some embodiments, the plurality of reaction chambers includes a first reaction chamber, and the first port on the first reaction chamber for connecting with the flow channel is located at the bottom of the first reaction chamber.

In some embodiments, the plurality of reaction chambers includes a second reaction chamber on which the first port for connecting with the flow channel is located at the top of the second reaction chamber.

In some embodiments, a waste liquid adsorption material is provided in the second reaction chamber.

In one aspect of the present disclosure, a microfluidic reaction system is provided, comprising:

the aforementioned microfluidic chip, and

The reagent storage structure has multiple storage bins for storing reagent samples.

In some embodiments, the storage bin includes at least one of the following:

a liquid reservoir for storing liquid reagents; and

Freeze-drying bins for storing freeze-dried reagents.

In some embodiments, the sampling mechanism includes a sampling needle, which can enter the freeze-drying storage chamber when driven, and inject a solution into the freeze-drying storage chamber, and then the The lyophilized reagent dissolved in the lysate is pipetted into the reaction chamber.

In some embodiments, the storage bin includes a bin body having an open end sealed by a sealing membrane and a closed end configured in a cone shape.

In some embodiments, the storage bin also includes:

At least one washing liquid compartment for storing the same or different washing liquids.

In some embodiments, in the multiple washing liquid bins storing different washing liquids, the liquid level of the washing liquid is configured to increase sequentially according to the washing order.

In some embodiments, the reagent storage structure includes a waste liquid container for receiving waste liquid discharged from the sampling mechanism.

In another aspect of the present disclosure, a driving method based on the aforementioned microfluidic reaction system is provided, including:

Sampling working condition: at least one reagent sample is extracted from the reagent storage structure through the sampling mechanism of the microfluidic chip, and provided to the reaction chamber of the microfluidic chip;

Reaction working condition: receiving at least one reagent sample through the reaction chamber, so as to carry out the reaction process of the reagent sample.

In some embodiments, the sampling conditions also include:

forming a passage for the sampling needle of the sampling mechanism to enter on the reagent storage structure through the hole needle of the sampling mechanism;

Driving the needle along the channel into the reagent storage structure to draw a reagent sample from the reagent storage structure.

In some embodiments, also include:

Cleaning working condition: the sampling needle is washed sequentially in at least one washing liquid compartment in the reagent storage structure according to the washing order.

In some embodiments, the sampling conditions also include:

driving the injection needle into the freeze-drying storage compartment in the reagent storage structure, and injecting a dissolving solution into the freeze-drying storage compartment;

The freeze-dried reagent dissolved by the dissolving solution is driven by a gas driving device to be sucked into the reaction chamber through the injection needle.

Therefore, according to an embodiment of the present disclosure, by setting a sampling mechanism on the reaction chip body and using the sampling mechanism to extract reagent samples from the reagent storage structure independent of the microfluidic chip, it is possible to reduce or eliminate the need for reagent storage in the reaction chip body. And the dependence of the release structure, thereby simplifying the overall structure design of the microfluidic chip and reducing the storage requirements of the chip.

Description of drawings

The accompanying drawings, which constitute a part of this specification, illustrate the embodiments of the disclosure and together with the description serve to explain the principles of the disclosure.

The present disclosure can be more clearly understood from the following detailed description with reference to the accompanying drawings, in which:

FIG. 1 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to some embodiments of the present disclosure;

FIG. 2 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to other embodiments of the present disclosure;

Fig. 3 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to some other embodiments of the present disclosure.

It should be understood that the sizes of the various parts shown in the drawings are not drawn according to the actual scale relationship. In addition, the same or similar reference numerals denote the same or similar members.

Detailed ways

Various exemplary embodiments of the present disclosure will now be described in detail with reference to the accompanying drawings. The description of the exemplary embodiments is illustrative only, and in no way restricts the disclosure, its application or uses. The present disclosure can be implemented in many different forms and is not limited to the embodiments described here. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. It should be noted that unless specifically stated otherwise, the relative arrangement of components and steps set forth in these embodiments should be construed as illustrative only and not as limiting.

"First", "second" and similar words used in the present disclosure do not indicate any order, quantity or importance, but are only used to distinguish different parts. Words like "comprising" or "comprising" mean that the elements preceding the word cover the elements listed after the word, and do not exclude the possibility of also covering other elements. "Up", "Down", "Left", "Right" and so on are only used to indicate the relative positional relationship. When the absolute position of the described object changes, the relative positional relationship may also change accordingly.

In the present disclosure, when it is described that a specific device is located between a first device and a second device, there may or may not be an intervening device between the specific device and the first device or the second device. When it is described that a specific device is connected to other devices, the specific device may be directly connected to the other device without an intervening device, or may not be directly connected to the other device but has an intervening device.

All terms (including technical terms or scientific terms) used in the present disclosure have the same meaning as understood by one of ordinary skill in the art to which the present disclosure belongs, unless otherwise specifically defined. It should also be understood that terms defined in, for example, general-purpose dictionaries should be interpreted as having meanings consistent with their meanings in the context of the relevant technology, and should not be interpreted in idealized or extremely formalized meanings, unless explicitly stated herein Defined like this.

Techniques, methods and devices known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, such techniques, methods and devices should be considered part of the description.

Fig. 1 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to some embodiments of the present disclosure.

In FIG. 1 , the microfluidic reaction system includes a microfluidic chip 100 and a reagent storage structure 200 . The reagent storage structure 200 is independent of the microfluidic chip 100 and has a plurality of storage bins 210 for storing reagent samples. The storage compartment 210 can be used to store reagent samples in various forms, and can also be used to store various auxiliary liquid media for testing, such as dissolving solution or washing solution.

In some embodiments, the storage bin 210 may include at least one of: a liquid storage bin for storing liquid reagents and a freeze-drying storage bin for storing freeze-dried reagents. Liquid reagents refer to reagents in liquid form, while lyophilized reagents refer to reagents made by vacuum freeze-sublimation drying (also known as freeze-drying), usually in powder form, and plasticizers can also be added to make the reagents agglomerate shape. In some other embodiments, the storage bin 210 may also include at least one washing liquid bin for storing the same or different washing liquids. These cleaning solutions can be used to clean the internal or external structure of the microfluidic chip 100, or to clean other experimental devices. In some other embodiments, the reagent storage structure 200 may also include a waste liquid bin for receiving the waste liquid discharged from the sampling mechanism, so as to provide convenience for the microfluidic chip 100 to collect waste liquid during experiments.

Regarding the structural configuration of the storage bin, referring to some embodiments shown in FIG. 1 , the storage bin 210 includes a bin body. The chamber body can be made of biocompatible materials, such as metal or alloy materials, polymer materials or inorganic materials, so as not to react with reagents for a long time. The cartridge body has an open end and a closed end 211 . The open end is sealed by a sealing membrane 220 . Reagents can be injected into the storage space within the cartridge through the open end. The sealing film 220 can be sealed at the open end by heat pressing, laser welding or adhesive. The sealing film 220 can also be made of biocompatible materials, such as plastic film or metal foil composite film (such as aluminum foil composite film, etc.). The sealing film 220 can achieve high barrier properties such as good airtightness, moisture resistance, and oxygen resistance, so as to realize long-term sealed storage of reagents.

According to the requirement of sampling, the sealing film 220 can be set to be partially ruptured after being subjected to a preset pressure, so that the sampling mechanism can obtain the reagent sample in the chamber through the ruptured part. In some other embodiments, the sealing film 220 can also be set to be detachable from the open end or resealable on the open end, so as to adjust the amount or type of the reagent in the chamber as required.

Referring to FIG. 1 , in some embodiments, the closed end 211 is configured in the shape of a cone (eg, a cone or a pyramid with or without a cone tip, etc.). In this way, when the closed end 211 is at the lowest position (equivalent to the bottom of the warehouse body), the sampling mechanism can enter the warehouse body and reach the closed end 211, so as to absorb the reagent sample in the warehouse body more completely, avoiding or reducing the residue of the reagent sample in the warehouse body .

In FIG. 1 , the reagent storage structure 200 can be arranged in the form of reagent strips extending along a straight line, that is, a plurality of storage bins 210 are arranged continuously or at intervals along a straight line. In some other embodiments, the reagent storage structure 200 can also be arranged in a ring shape, a circle shape, a rectangle shape, or an irregular shape, etc., and a plurality of storage bins 210 can be distributed according to the overall shape of the reagent storage structure 200, such as forming a rectangle, a circle, etc. Shaped or circular arrays, etc. The storage compartment 210 can also be separated from the reagent storage structure 200 or added to the reagent storage structure 200 , and the overall shape of the reagent storage structure 200 can also be adjusted by the arrangement of the storage compartment 210 .

In some of the above-mentioned embodiments, the reagent storage structure 200 has a relatively simple structure, which is convenient for manufacture and industrial production, so as to reduce costs through mass production. In some other embodiments, the reagents in the reagent storage structure 200 can be adjusted in type or quantity as required, so as to meet different experimental requirements.

In addition, the reagent storage structure 200 can adopt a relatively mature and reliable sealing method at present, so as to realize long-term storage of reagents. In some embodiments, through the storage of freeze-dried reagents, the requirements for the storage environment of the reagent storage structure 200 can be relatively reduced, which is conducive to the long-term storage of reagents at room temperature, thereby facilitating the reaction detection process to go out of the laboratory and realize on-site detection .

Referring to FIG. 1 , in some embodiments, a microfluidic chip 100 includes: a reaction chip body 110 and a sampling mechanism. The reaction chip body 110 has at least one flow channel and at least one reaction chamber. In FIG. 1 , three reaction chambers are provided in the reaction chip body 110 , namely a reaction chamber 131 , a reaction chamber 132 and a reaction chamber 133 . The reaction chamber 131 , the reaction chamber 132 and the reaction chamber 133 are respectively connected with a flow channel 141 , a flow channel 142 and a flow channel 143 . The reaction chamber and the flow channel can be connected directly, or valve-controlled communication can be realized through a control valve. In some other embodiments, a single reaction chamber or a single flow channel may also be set in the reaction chip body 110 .

The sampling mechanism is arranged on the reaction chip body 110 and communicated with at least one flow channel for extracting reagent samples from the reagent storage structure 200 independent of the microfluidic chip 100 and providing them to the reaction chamber. Operations such as mixing, reacting, washing and/or draining of reagent samples can be realized through the reaction chamber, and on this basis, relatively complex diagnostic detection processes such as immunity and molecules can be more easily realized. In some embodiments, no reagent samples are stored in the reaction chip body 110 , and the reagent samples are only extracted from the reagent storage structure 200 through the sampling mechanism when needed. By peeling off the reagent storage and release parts of the reaction chip body 110, the structural design and storage of the reaction chip body 110 can be simplified, so that the industrial production of the microfluidic chip 100 is easier, so as to reduce costs through mass production. In addition, by separating the storage of reagents from the reaction chip of reagents, the experimental steps and experimental parameters of biochemical experiments can be adjusted according to actual needs, thereby increasing the versatility of biochemical experiments.

In FIG. 1 , the sampling mechanism communicates with the reaction chamber 131 , the reaction chamber 132 and the reaction chamber 133 through the control valve 150 and the flow channel, respectively. The reagent obtained by the sampling mechanism can reach the control valve 150 through the flow channel 144, and then through a certain flow channel (such as the flow channel 141) selected by the control valve 150 to connect to the reaction chamber (such as the reaction chamber 131) connected to the flow channel. ). Correspondingly, the reagent samples, reaction products or waste liquid in each reaction chamber can also be discharged to other reaction chambers or the outside of the chip through the flow channel. For example, a reagent sample, a reaction product or a waste liquid is discharged to the outside through a sampling mechanism.

Referring to FIG. 1 , the sampling mechanism may include a sampling needle 121 . The needle body of the sampling needle 121 can be made of plastic or metal, which can not react with reagents and has acid and alkali resistance. The needle body of the sampling needle 121 has a hollow channel, and is selectively communicated with all or part of at least one reaction chamber in the reaction chip body 110, so that the absorbed reagent is input into one or some reaction chambers, or Output one or some substances in the reaction chamber to the outside of the chip. In addition, the needle body of the sampling needle 121 can be configured to be smooth inside and outside, so as to reduce reagent residue.

When the sampling needle 121 moves toward the reagent storage structure 200 , the tip portion of the needle body of the sampling needle 121 can enter the reagent storage structure 200 . In order to realize the relative movement of the sampling needle 121 relative to the reagent storage structure 200 , a driving device (such as a miniature driving motor, an air cylinder, etc.) can be provided on the reaction chip body 110 to drive the movement of the sampling needle 121 . In some other embodiments, a driving device may also be set to drive the movement of the reaction chip body 110 to drive the movement of the injection needle 121 . Alternatively, the reagent storage structure 200 is driven by a driving device to move the injection needle 121 relative to the reagent storage structure 200 .

The sampling needle 121 can penetrate into the reagent storage structure 200 under the action of a driving device (such as a motor). For example, the sampling needle 121 pierces the sealing film 220 provided on the storage bin 210 to obtain the reagent inside the storage bin 210 . For some embodiments where the closed end 211 is configured in a cone shape, the sampling needle 121 can reach the closed end 211 so as to more completely absorb the reagent sample in the storage chamber 210 and avoid or reduce the residue of the reagent sample.

It has been mentioned above that the storage bin 210 in some embodiments may comprise a freeze-drying storage bin. Since the freeze-dried reagent in the freeze-dried storage bin is in a powder form, the injection needle 121 can be driven into the freeze-dried storage bin, and a dissolving solution is injected into the freeze-dried storage bin, so that the freeze-dried reagent is dissolved under the immersion of the dissolving solution, A dissolved lyophilized reagent is formed. The freeze-dried reagent dissolved by the lyophilizing solution can then be sucked into the corresponding reaction chamber by the injection needle 121 . The solution injected by the injection needle 121 may come from the microfluidic chip 100 itself, or from other storage chambers of the reagent storage structure 200, or from other sources.

Injection needles, reaction chambers, flow channels, etc. may be used in multiple experiments or multiple experimental steps in a single experiment. In order to avoid sample contamination in subsequent experiments or subsequent experimental steps caused by sample carryover in previous experiments or experimental steps, the injection needle, reaction chamber or flow channel can be cleaned when necessary. For example, after the reaction in a reaction chamber is completed, a cleaning solution is injected into the reaction chamber for washing, and the reaction chamber is allowed to perform subsequent experimental steps after being cleaned.

In order to facilitate the cleaning of the reaction chamber and flow channel, the storage bin 210 in some embodiments may further include at least one washing liquid bin for storing the same or different washing liquids. When the sampling needle 121 sucks the washing liquid from the washing liquid chamber, the hollow channel inside can achieve the effect of washing. In order to keep the outer wall of the sampling needle 121 clean, the liquid level of the washing liquid can be higher than the liquid reagent liquid level in the storage compartment for storing reagent samples. When washing, the sampling needle 121 can be used to suck up the washing liquid several times in a small amount, so as to obtain a better washing effect.

For the situation where multiple washings are required, the liquid levels of the washing liquids can be configured to increase sequentially in the order of washing in multiple washing liquid bins storing different washing liquids. In this way, when washing is performed according to the washing sequence, it is ensured that the previous washing liquid attached to the outer wall of the injection needle 121 can be washed by the later washing liquid with a higher liquid level.

Referring to FIG. 1 , in some embodiments, the reaction chamber includes at least two ports. For example, the reaction chamber 131 in FIG. 1 includes a first port 131a and a second port 131b, the reaction chamber 132 includes a first port 132a and a second port 132b, and the reaction chamber 133 includes a first port 133a and a second port 133b. The first ports 131a, 132a, 133a can communicate with the flow channels 141, 142, 143, respectively. These flow channels can realize gating and/or opening control between themselves and other flow channels, reaction chambers or sampling mechanisms through the control valve 150 included in the reaction chip body 110 . The control valve 150 is also respectively connected to each reaction chamber 131, 132, 133 through a flow channel, and is used to control the gating and opening of the flow channel between each reaction chamber 131, 132, 133 and/or between the sampling mechanism and each reaction chamber. / or opening control.

In FIG. 1 , the second ports 131b, 132b, 133b are operatively connected to the gas drive device 300 . Correspondingly, the reaction chambers 131 , 132 , 133 can be configured to input or output reagent samples through the flow channels under the gas drive of the gas drive device 300 . That is to say, the input or output of the reaction chamber can be realized through the control of the gas pressure by the gas driving device. When the gas driving device injects gas into the reaction chamber, the air pressure in the reaction chamber will increase, so that the substances in the reaction chamber will be discharged to other reaction chambers, flow channels or the outside of the chip through the flow channel. However, when the gas driving device sucks gas from the reaction chamber, the air pressure in the reaction chamber will be reduced to form a negative pressure, so that other reaction chambers, flow channels or substances outside the chip flow into the reaction chamber. Through the operation of the gas drive device, in conjunction with the sequential acquisition of various reagents in the reagent storage structure by the sampling mechanism, the sequential release, mixing, and multi-step transfer reactions of various reagents in the reagent storage structure 200 can be realized, so that the micro The design and control of the fluidic reaction system are simpler and more reliable.

In some embodiments, the reaction chip body 110 includes a plurality of reaction chambers to realize several steps of biochemical reactions of reagent samples. Among these reaction chambers are included first reaction chambers (for example, reaction chambers 131 and 132 in FIG. 1 ). The first port on the first reaction chamber for connecting with the flow channel is located at the bottom of the first reaction chamber. When the gas driving device 300 pumps air into the first reaction chamber, the liquid reagent will be sucked into the first reaction chamber, and the liquid level of the liquid reagent is higher than the first port. Continue to pump air until the liquid reagent is completely sucked into the first reaction chamber, then continue to inhale and control the suction speed, so that the air can form bubbles and burst above the liquid reagent liquid surface, and the liquid reagent will not be sucked out of the first reaction chamber . Through the structure of the reaction chamber and the suction method, various liquid reagents can be sucked into the same first reaction chamber sequentially according to the experimental requirements for reaction. And when the gas driving device 300 blows air into the first reaction chamber, the liquid substance in the first reaction chamber can be discharged.

In some other embodiments, the reaction chip body includes a plurality of reaction chambers to realize several steps of biochemical reactions of reagent samples. Included among these reaction chambers is a second reaction chamber (eg, reaction chamber 133 in FIG. 1 ). The first port on the second reaction chamber for connecting with the flow channel is located at the top of the second reaction chamber. When the gas driving device 300 pumps air into the second reaction chamber, the liquid reagent will be sucked into the second reaction chamber, and the first port is always higher than the liquid level of the liquid reagent. The liquid reagent in the structure of the second reaction chamber is difficult to be discharged, and can be used as a waste liquid chamber for receiving waste liquid. Further, a waste liquid adsorption material, such as filter paper, can also be arranged in the second reaction chamber, so as to fix the waste liquid by absorbing the waste liquid. Of course, the second reaction chamber can also be used for the reaction of reagent samples, and various reagents can be sucked into the second reaction chamber by the pumping action of the gas driving device 300 to the second reaction chamber for reaction.

The number and types of reaction chambers in the reaction chip body 110 can be designed and selected according to experimental requirements. For example, in some embodiments, only the first reaction chamber or the second reaction chamber may be included, and in other embodiments, both the first reaction chamber and the second reaction chamber may be included, and a suitable reaction chamber may be selected according to experimental needs.

Referring to FIG. 1 , in some embodiments, a gas drive device 300 includes a peristaltic pump 310 having a hose 320 and a vacuum chuck 330 . The vacuum suction cup 330 is disposed at the end of the hose 320 for selectively forming a sealed connection with the second ports of different reaction chambers (such as the second ports 131b, 132b, 133b in FIG. 1 ). In this embodiment, the peristaltic pump 310 can pump a small flow rate of gas by alternately squeezing and releasing the pump tube, so as to realize the air pressure change in the reaction chamber, which can meet the needs of the microfluidic chip for the delivery of reagent samples . When it is necessary to control a certain reaction chamber to suck or discharge liquid reagent, the vacuum chuck 330 can be connected to the second port of the reaction chamber. One peristaltic pump 310 can realize the suction or discharge operation of multiple reaction chambers in different periods. The position of the vacuum chuck 330 can be adjusted through a driving mechanism (such as a motor, etc.), so as to change the connection relationship with the second ports of different reaction chambers. In another embodiment, the peristaltic pump 310 can also be replaced by various pumps that can drive air in the hose, such as a syringe pump and a vacuum pump.

Fig. 2 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to other embodiments of the present disclosure.

Compared with the previously described embodiments of the present disclosure, the gas driving device 300' in FIG. 2 may include a syringe 340 having a needle portion 341. On the second port of at least part of the reaction chamber, a flexible sealing material 350 can be provided, such as rubber, silica gel or other elastic polymer materials. When an experimenter needs to operate a certain reaction chamber, the needle portion 341 of the syringe 340 can penetrate the flexible sealing material 350 of the second port of the reaction chamber. At this time, the flexible sealing material 350 still maintains the sealed state of the reaction chamber. According to the needs of the experiment, the experimenter can operate the syringe 340 to inject gas into the reaction chamber or suck gas from the reaction chamber, thereby changing the air pressure in the reaction chamber. The flexible sealing material 350 can enable the syringe 340 to drive the reagents in the reaction chamber while achieving good sealing of the reaction chamber, which is especially suitable for scenarios with high sealing requirements during the reaction process.

Fig. 3 is a schematic diagram schematically showing the structure of a microfluidic reaction system according to some other embodiments of the present disclosure.

Referring to FIG. 3 , in some embodiments, the sampling mechanism further includes a corona needle 122 . The diameter of the hole needle 122 is larger than that of the sampling needle 121 , and is used to form a channel on the reagent storage structure 200 for the sampling needle 121 to enter. In other words, when the sampling needle 121 needs to enter a storage bin, a hole of a larger size can be opened on the sealing film 220 of the storage bin through the opening needle 122 . Then, the injection needle 121 can directly enter the opening on the sealing film 220 without contacting or rubbing against the sealing film 220 . This can effectively prevent the reagents on the outer wall of the injection needle 121 from sticking to the sealing film 220 and causing contamination. The cotter can be made of metal or plastic material, which can be provided as hollow or solid.

In Fig. 3, the perforating needle 122 can be fixedly arranged on one side of the sampling needle 121, and the relative movement between the reagent storage structure 200 and the sampling mechanism can realize the actions of the perforating needle opening and the sampling needle entering the needle respectively . In some other embodiments, the perforated needle 122 can also be configured to be retractable relative to the reaction chip body, and the perforated needle 122 can be arranged adjacent to the sampling needle 121 or surrounded by the hollow part of the perforated needle 122. Sample pin 121. When the hole needs to be drilled, the needle 122 can be stretched out, and retracted after the hole is drilled. This reduces relative movement between the reagent storage structure 200 and the sampling mechanism.

In the above-mentioned embodiments of the present disclosure, the microfluidic chip 100 or the reagent storage structure 200 can be designed as a disposable product according to needs, so as to avoid contamination between reagent samples. In other embodiments, the microfluidic chip 100 or the reagent storage structure 200 can also be designed to be used multiple times. Both the microfluidic chip and the reagent storage structure can be manufactured using common existing materials (such as plastics, metals, etc.) and common processes in the medical device industry (such as injection molding, etc.), so as to reduce material and process costs.

Based on the embodiment of any of the foregoing microfluidic reaction systems, the present disclosure also provides a corresponding driving method, including steps under sampling conditions and reaction conditions, wherein, under sampling conditions, microfluidic The sampling mechanism of the chip 100 extracts at least one reagent sample from the reagent storage structure 200 and provides it to the reaction chamber of the microfluidic chip 100 . In the reaction working condition, at least one reagent sample can be received through the reaction chamber, so as to carry out the reaction process of the reagent sample.

In some embodiments, the sampling condition may further include: forming a passage for the sampling needle 121 of the sampling mechanism to enter on the reagent storage structure 200 through the opening needle 122 of the sampling mechanism. Then, the injection needle 121 is driven into the reagent storage structure 200 along the passage, so as to draw a reagent sample from the reagent storage structure 200 .

In addition, for the extraction of freeze-dried reagents, the sampling condition may also include: driving the injection needle 121 into the freeze-dried storage chamber in the reagent storage structure 200, and injecting the solution into the freeze-dried storage chamber. Then, the freeze-dried reagent dissolved by the dissolving solution is driven by the gas driving device 300 or 300' to be sucked into the reaction chamber through the injection needle 121.

In some other embodiments, the driving method may further include a step in a cleaning condition, that is, washing the sampling needle 121 in at least one washing liquid compartment in the reagent storage structure 200 in a washing order.

In this specification, multiple embodiments are described in a progressive manner, and the emphases of each embodiment are different, and the same or similar parts of each embodiment can be referred to each other. For the method embodiment, since there is a corresponding relationship between the whole and the involved steps and the content in the embodiment of the microfluidic chip and the microfluidic reaction system, the description is relatively simple. For relevant information, please refer to the corresponding part of the embodiment Just explain.

So far, the embodiments of the present disclosure have been described in detail. Certain details known in the art have not been described in order to avoid obscuring the concept of the present disclosure. Based on the above description, those skilled in the art can fully understand how to implement the technical solutions disclosed herein.

Although some specific embodiments of the present disclosure have been described in detail through examples, those skilled in the art should understand that the above examples are for illustration only, rather than limiting the scope of the present disclosure. Those skilled in the art should understand that the above embodiments can be modified or some technical features can be equivalently replaced without departing from the scope and spirit of the present disclosure. The scope of the present disclosure is defined by the appended claims.

Claims (22)

1. A microfluidic chip (100) comprising:

A reaction chip body (110) having at least one flow channel and at least one reaction chamber (131, 132, 133), the at least one flow channel being in direct or valve-controlled communication with the at least one reaction chamber (131, 132, 133), respectively; and

And the sampling mechanism is arranged on the reaction chip body (110) and is communicated with the at least one flow channel, and is used for extracting a reagent sample from a reagent storage structure (200) independent of the microfluidic chip (100) and providing the reagent sample to the reaction cavity (131, 132, 133).

2. The microfluidic chip (100) of claim 1, wherein the sampling mechanism comprises:

A sample injection needle (121) in selective communication with all or part of the at least one reaction chamber (131, 132, 133);

Wherein the body of the sample injection needle has a hollow channel, a tip portion of the body being accessible to the reagent storage structure (200).

3. The microfluidic chip (100) of claim 2, wherein the sampling mechanism further comprises:

An open-bore needle (122), the diameter of which is greater than the diameter of the sample injection needle (121), for forming a channel on the reagent storage structure (200) for the sample injection needle (121) to enter.

4. the microfluidic chip (100) according to claim 1, wherein the reaction chamber (131, 132, 133) comprises a first port (131a, 132a, 133a) and a second port (131b, 132b, 133b), the first port (131a, 132a, 133a) is in communication with the flow channel, the second port (131b, 132b, 133b) is operably connected with a gas driving device (300, 300 '), and the reaction chamber (131, 132, 133) is configured to input or output a reagent sample through the flow channel under gas driving of the gas driving device (300, 300').

5. The microfluidic chip (100) of claim 4, wherein the gas-driving device (300, 300') comprises:

A peristaltic pump (310), vacuum pump or syringe pump having a hose (320); and

A vacuum cup (330) disposed at an end of the hose (320) for selectively forming a sealed connection with the second port (131b, 132b, 133 b).

6. the microfluidic chip (100) according to claim 4, wherein a flexible sealing material (350) is provided at the second port (131b, 132b, 133b), and the gas driving device (300, 300') comprises:

A syringe (340) having a tip portion (341) penetrable by the flexible sealing material (350).

7. The microfluidic chip (100) of claim 1, wherein the reaction chip body (110) further comprises a control valve (150) disposed in series on a flow path between the sampling mechanism and the reaction chamber (131, 132, 133).

8. The microfluidic chip (100) according to claim 7, wherein the reaction chip body (110) comprises a plurality of reaction chambers (131, 132, 133), and the control valve (150) is connected to each reaction chamber (131, 132, 133) through the flow channel for controlling gating and/or opening degree control of the flow channel between each reaction chamber (131, 132, 133) and/or between the sampling mechanism and each reaction chamber (131, 132, 133).

9. The microfluidic chip (100) according to claim 8, wherein the plurality of reaction chambers (131, 132, 133) comprises a first reaction chamber, and a first port on the first reaction chamber for connection with the flow channel is located at a bottom of the first reaction chamber.

10. The microfluidic chip (100) of claim 8, wherein the plurality of reaction chambers (131, 132, 133) comprises a second reaction chamber, and a first port on the second reaction chamber for connection with the flow channel is located at a top of the second reaction chamber.

11. The microfluidic chip (100) according to claim 10, wherein a waste fluid adsorbing material is disposed in the second reaction chamber.

12. a microfluidic reaction system comprising:

a microfluidic chip (100) according to any of claims 1 to 11, and

a reagent storage structure (200) having a plurality of storage bins (210) for storing reagent samples.

13. A microfluidic reaction system according to claim 12, wherein the storage bin (210) comprises at least one of:

the liquid storage bin is used for storing a liquid reagent; and

And the freeze-drying storage bin is used for storing freeze-drying reagents.

14. Microfluidic reaction system according to claim 13, wherein the sampling mechanism comprises a sample needle (121), the sample needle (121) being able to enter the lyophilization magazine when driven and to inject a dissolution liquid into the lyophilization magazine and then to aspirate the lyophilized reagent dissolved by the dissolution liquid into the reaction chamber (131, 132, 133).

15. Microfluidic reaction system according to claim 12, wherein the storage cartridge (210) comprises a cartridge body having an open end and a closed end (211), the open end being sealed by a sealing membrane (220), the closed end (211) being configured in the shape of a cone.

16. A microfluidic reaction system according to claim 13, wherein the storage bin (210) further comprises:

At least one washing liquid bin for storing the same or different washing liquids.

17. the microfluidic reaction system according to claim 16, wherein in the plurality of washing liquid compartments storing different washing liquids, the liquid levels of the washing liquids are configured to be sequentially increased in a washing order.

18. the microfluidic reaction system according to claim 12, wherein the reagent storage structure (200) comprises a waste bin for receiving waste liquid discharged by the sampling mechanism.

19. a driving method based on the microfluidic reaction system of any one of claims 12 to 18, comprising:

sampling working conditions are as follows: extracting at least one reagent sample from a reagent storage structure (200) by a sampling mechanism of a microfluidic chip (100) and providing the sample to a reaction chamber (131, 132, 133) of the microfluidic chip (100);

reaction conditions are as follows: receiving at least one reagent sample through the reaction chamber (131, 132, 133) for performing a reaction process of the reagent sample.

20. The driving method according to claim 19, wherein, in the sampling condition, further comprising:

Forming a channel on the reagent storage structure (200) through an open-bore needle (122) of the sampling mechanism for entry of a sample needle (121) of the sampling mechanism;

driving the sample injection needle (121) along the channel into the reagent storage structure (200) so as to draw a reagent sample from the reagent storage structure (200).

21. the driving method according to claim 20, further comprising:

Cleaning working conditions are as follows: and washing the sample injection needles (121) in at least one washing liquid bin in the reagent storage structure (200) according to a washing sequence.

22. the driving method according to claim 20, wherein, in the sampling condition, further comprising:

driving the sample injection needle (121) to enter a freeze-drying storage bin in the reagent storage structure (200), and injecting a dissolving solution into the freeze-drying storage bin;

The freeze-drying reagent dissolved by the dissolving solution is driven to be sucked into the reaction cavity (131, 132, 133) through the sample injection needle (121) by a gas driving device (300, 300').