CN110560184A

CN110560184A - Microfluidic chip, microfluidic reaction system and driving method

Info

Publication number: CN110560184A
Application number: CN201810573810.4A
Authority: CN
Inventors: 闵小平; 葛胜祥; 张师音; 张东旭; 苏晓崧; 付达; 翁振宇; 陈文堤; 翁祖星; 宋浏伟; 张军; 夏宁邵
Original assignee: Xiamen Wantai Kairui Biological Technology Co Ltd; Xiamen University
Current assignee: Xiamen Wantai Kairui Biological Technology Co Ltd; Xiamen University
Priority date: 2018-06-06
Filing date: 2018-06-06
Publication date: 2019-12-13

Abstract

The disclosure relates to a microfluidic chip, a microfluidic reaction system and a reaction method. The microfluidic chip (100) comprises: 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 a sampling mechanism disposed on the reaction chip body (110) and communicating with the at least one flow channel, 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 chamber (131, 132, 133). The reaction chip body is provided with the sampling mechanism, and the sampling mechanism is used for extracting the reagent sample from the reagent storage structure independent of the micro-fluidic chip, so that the dependence on the reagent storage and release structure in the reaction chip body can be reduced or eliminated, the overall structure design of the micro-fluidic chip is simplified, and the storage requirement of the chip is reduced.

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

Point-Of-Care Testing (POCT) is any test performed by a hospital professional or non-professional outside the Testing center, also called bedside Testing. The integrated detector or portable instrument is used for implementing on-site convenient detection, the detection waiting time is reduced, the complex detection process is simplified, the traditional instrument equipment requiring higher maintenance cost is replaced, and the dependence of clinical application on high-end instruments and a central hospital detection center is relieved. Therefore, POCT technology is currently becoming a research and development hotspot in the field of medical diagnosis technology.

The micro-fluidic Chip technology appears in the early 90 s of the 20 th century, and is matched with a corresponding driving and detecting instrument, and the common reagent storage and release, uniform mixing, dilution, washing, reaction, result monitoring and other experimental steps in diagnosis and detection can be realized on one Chip by controlling the fluid, so that the whole detection system (the Chip and the instrument) is small and exquisite, the integration level is high, the detection flow can be simplified on the premise of not losing the detection sensitivity, the requirements on detection personnel and environmental conditions are reduced, and the field detection is realized. Therefore, the microfluidic chip highly meets the development requirements of the POCT detection technology based on the characteristics of miniaturization, integration and automation of the microfluidic chip, and has important significance for optimizing clinical detection.

In the related art, the microfluidic chip is provided with a reaction structure and a related structure for storing and releasing a reagent, so that the microfluidic chip is complex in overall structure design, difficult to industrialize and higher in requirement on chip storage. In addition, when the microfluidic chip is used, a mixing reaction of various reagents is often required, and the conventional microfluidic chip is difficult to adaptively adjust the types and volumes of the reagents after storing the reagents.

Disclosure of 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 reliable long-term storage of a reagent.

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

The reaction chip body is provided with at least one flow channel and at least one reaction cavity, and the at least one flow channel is directly communicated or valve-controlled communicated with the at least one reaction cavity respectively; and

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

In some embodiments, the sampling mechanism comprises:

A sample injection needle in selective communication with all or part of the at least one reaction chamber;

wherein the body of the injection needle has a hollow channel, and a tip portion of the body is accessible to the reagent storage structure.

in some embodiments, the sampling mechanism further comprises:

And the diameter of the open-hole needle is larger than that of the sample injection needle, and a channel for the sample injection needle to enter is formed on the reagent storage structure.

in some embodiments, the reaction chamber comprises a first port in communication with the flow channel and a second port operatively connected to a gas-driven device, the reaction chamber being configured to input or output a reagent sample via the flow channel under gas drive of the gas-driven device.

In some embodiments, the gas-driven apparatus comprises:

A peristaltic pump, vacuum pump or syringe pump having a flexible tube; and

A vacuum cup disposed at an end of the hose for selectively forming a sealed connection with the second port.

in some embodiments, a flexible sealing material is provided at the second port, the gas-driven apparatus comprising:

a syringe having a needle portion penetrable by the flexible sealing material.

In some embodiments, the reaction chip body further comprises a control valve disposed in series on a 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 connected to each reaction chamber through the flow channel, and is configured to control gating and/or opening degree control of the flow channel between the reaction chambers and/or between the sampling mechanism and each reaction chamber.

In some embodiments, the plurality of reaction chambers includes 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.

In some embodiments, the plurality of reaction chambers includes 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.

In some embodiments, a waste liquid adsorbent material is disposed within the second reaction chamber.

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

the aforementioned microfluidic chip, and

a reagent storage structure having a plurality of storage bins for storing reagent samples.

In some embodiments, the storage bin 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.

In some embodiments, the sampling mechanism comprises a sample needle that can enter the lyophilization magazine when driven and inject a dissolution solution into the lyophilization magazine and then draw the lyophilized reagent dissolved by the dissolution solution into the reaction chamber.

In some embodiments, the storage cartridge comprises a cartridge 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 further comprises:

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

In some embodiments, in the plurality of washing liquid compartments storing different washing liquids, the liquid level of the washing liquid is configured to be sequentially increased in the washing order.

In some embodiments, the reagent storage structure comprises a waste reservoir for receiving waste fluid discharged by the sampling mechanism.

in another aspect of the present disclosure, there is provided a driving method based on the foregoing microfluidic reaction system, including:

sampling working conditions are as follows: extracting at least one reagent sample from a reagent storage structure through a sampling mechanism of the microfluidic chip and providing the reagent sample to a reaction cavity of the microfluidic chip;

Reaction conditions are as follows: at least one reagent sample is received through the reaction chamber to perform a reaction process of the reagent sample.

in some embodiments, the method further comprises, under the sampling condition:

Forming a channel on the reagent storage structure through the open-hole needle of the sampling mechanism for the sample injection needle of the sampling mechanism to enter;

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

In some embodiments, further comprising:

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

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

And driving the freeze-drying reagent dissolved by the dissolving solution to be sucked into the reaction cavity through the sample injection needle by a gas driving device.

therefore, according to the embodiment of the disclosure, the sampling mechanism is arranged on the reaction chip body, and the sampling mechanism is used for extracting the reagent sample from the reagent storage structure independent of the microfluidic chip, so that the dependence on the reagent storage and release structure in the reaction chip body can be reduced or eliminated, the overall structure design of the microfluidic chip is simplified, and the storage requirement of the chip is reduced.

drawings

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

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

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

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

fig. 3 is a schematic diagram schematically illustrating the structure of a microfluidic reaction system according to still further embodiments of the present disclosure.

it should be understood that the dimensions of the various parts shown in the figures are not drawn to scale. Further, the same or similar reference numerals denote the same or similar components.

Detailed Description

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 merely illustrative and is in no way intended to limit the disclosure, its application, or uses. The present disclosure may be embodied in many different forms and is not limited to the embodiments described herein. 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: the relative arrangement of parts and steps set forth in these embodiments should be construed as exemplary only and not as limiting unless otherwise specifically noted.

the use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather are used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that the element preceding the word covers the element listed after the word, and does not exclude the possibility that other elements are also covered. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.

In the present disclosure, when a specific device is described as being located between a first device and a second device, there may or may not be intervening devices between the specific device and the first device or the second device. When a particular device is described as being coupled to other devices, that particular device may be directly coupled to the other devices without intervening devices or may be directly coupled to the other devices with intervening devices.

All terms (including technical or scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs unless specifically defined otherwise. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate.

Fig. 1 is a schematic diagram schematically illustrating 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 compartments 210 for storing reagent samples. The storage chamber 210 can be used for storing reagent samples in various forms, and can also be used for storing various auxiliary liquid media for testing, such as a dissolving solution or a 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-drying reagents. The liquid reagent is a reagent in a liquid form, and the lyophilized reagent is a reagent prepared by a vacuum freeze-sublimation drying method (also referred to as lyophilization), and is usually in a powder form, and a shaping agent may be added so that the reagent is in a dough form. In other embodiments, the storage bins 210 may further include at least one wash fluid bin for storing the same or different wash fluids. These washing solutions can be used to wash internal or external structures of the microfluidic chip 100, or to wash other devices for testing. In still other embodiments, the reagent storage structure 200 may further include a waste liquid bin for receiving waste liquid discharged from the sampling mechanism, thereby facilitating waste liquid collection during experiments performed on the microfluidic chip 100.

In the structural arrangement of the cartridge, referring to some of the embodiments illustrated in fig. 1, the cartridge 210 comprises a cartridge body. The cartridge body can be made of a biocompatible material, such as a metal or alloy material, a polymeric material, or an inorganic material, for example, so as to be non-reactive for prolonged contact with the reagents. The cartridge body has an open end and a closed end 211. The open end is sealed by a sealing film 220. The reagent may be injected into the storage space within the cartridge body through the open end. And the sealing film 220 may be sealed at the open end by heat pressing, laser welding, or gluing. The sealing film 220 may also be made of a biocompatible material, such as a plastic film or a metal foil composite film (e.g., an aluminum foil composite film, etc.). The sealing film 220 can realize high barrier properties such as good airtightness, moisture resistance, oxygen resistance and the like, so that long-term sealed storage of the reagent can be realized.

Depending on the sampling requirement, the sealing membrane 220 may be configured to locally rupture when subjected to a predetermined pressure, such that the sampling mechanism can access the sample of the reagent in the cartridge body through the ruptured portion. In other embodiments, the sealing membrane 220 may be removable from or resealable to the open end to adjust the amount or type of reagent in the chamber as desired.

referring to fig. 1, in some embodiments, closed end 211 is configured in the shape of a cone (e.g., the shape of a cone or pyramid, etc., with or without a conical tip). Thus, when the closed end 211 is at the lowest position (corresponding to the bottom of the chamber body), the sampling mechanism can enter the chamber body and reach the closed end 211, so as to suck the reagent sample in the chamber body more completely and avoid or reduce the residue of the reagent sample in the chamber body.

In fig. 1, the reagent storage structure 200 may be provided in the form of a reagent strip extending along a straight line, i.e., a plurality of storage compartments 210 are arranged in series or at intervals along a straight line. In other embodiments, the reagent storage structure 200 may be configured as a ring, a circle, a rectangle, an irregular shape, etc., and the plurality of storage bins 210 may be distributed according to the overall shape of the reagent storage structure 200, such as forming a rectangular, circular, or annular array, etc. The cartridge 210 may 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 may be adjusted by the arrangement of the cartridge 210.

In some embodiments, the reagent storage structure 200 has a simple structure, is easy to manufacture, and is easy to be industrially produced, so as to reduce the cost through mass production. In other embodiments, the reagents in the reagent storage structure 200 may be adjusted in type or amount as needed to accommodate different experimental requirements.

In addition, the reagent storage structure 200 can adopt a mature and reliable sealing mode at present, so that the long-term storage of the reagent is realized. In some embodiments, the requirement of the storage environment of the reagent storage structure 200 can be relatively reduced by storing the freeze-dried reagent, and the reagent can be stored for a long time at normal temperature, so that the reagent can be conveniently taken out of a laboratory in the reaction detection process, and field detection can be realized.

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, namely a reaction chamber 131, a reaction chamber 132 and a reaction chamber 133, are disposed in the reaction chip body 110. The reaction chamber 131, the reaction chamber 132, and the reaction chamber 133 are also communicated with a flow channel 141, a flow channel 142, and a flow channel 143, respectively. The reaction cavity and the flow channel can be directly communicated, and valve control communication can also be realized through a control valve. In other embodiments, a single reaction chamber or a single flow channel may be disposed in the reaction chip body 110.

The sampling mechanism is disposed on the reaction chip body 110 and is in communication with at least one flow channel for extracting a reagent sample from the reagent storage structure 200 independent of the microfluidic chip 100 and providing the reagent sample to the reaction chamber. The operation of mixing, reacting, washing and/or waste liquid discharging of the reagent sample can be realized through the reaction cavity, and on the basis, comparatively complicated diagnostic detection processes such as immunization, molecules and the like can be realized more easily. In some embodiments, the reagent sample may not be stored in the reaction chip body 110, and the reagent sample may be extracted from the reagent storage structure 200 only when needed by the sampling mechanism. By stripping the reagent storage and release parts of the reaction chip body 110, the structural design and preservation of the reaction chip body 110 can be simplified, so that the microfluidic chip 100 is easier to be industrially produced, and the cost is reduced by batch production. In addition, the storage of the reagent and the separation of the reaction chip of the reagent enable the experiment steps and the experiment parameters of the biochemical experiment to be adjusted adaptively according to the actual needs, thereby increasing the universality of the biochemical experiment.

in fig. 1, the sampling mechanism is in communication 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 a certain flow channel (e.g. the flow channel 141) gated by the control valve 150 is used to connect the reaction chamber (e.g. the reaction chamber 131) connected to the flow channel. Accordingly, the reagent sample, the reaction product or the waste liquid in each reaction chamber can also be discharged to the outside of other reaction chambers or chips through the flow channel. Such as reagent samples, reaction products or waste fluids, are discharged outwardly via the sampling mechanism.

Referring to fig. 1, the sampling mechanism may include a sample needle 121. The body of the needle 121 may be made of plastic or metal, and is non-reactive with the reagent and resistant to acid and alkali. The needle body of the sample injection 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 as to input the sucked reagent into a certain reaction chamber or reaction chambers, or output substances in the certain reaction chamber or reaction chambers to the outside of the chip. In addition, the needle body of the injection needle 121 may be configured to be smooth inside and outside to reduce reagent residues.

When the needle 121 is moved toward each other relative to the reagent storage structure 200, the tip portion of the needle body of the needle 121 can enter the reagent storage structure 200. In order to realize the opposite movement of the injection needle 121 with respect to the reagent storage structure 200, a driving device (e.g., a micro driving motor, an air cylinder, etc.) may be disposed on the reaction chip body 110, and the movement of the injection needle 121 may be driven. In other embodiments, a driving device may also be provided to drive the reaction chip body 110 to move so as to drive the sample injection needle 121 to move. Still alternatively, the reagent storage structure 200 is driven to move by a driving device to realize the movement of the sample injection needle 121 relative to the reagent storage structure 200.

The sample injection needle 121 may penetrate into the reagent storage structure 200 under the action of a driving means (e.g., a motor). For example, the injection needle 121 penetrates a sealing film 220 provided on the storage compartment 210, in order to access the reagent inside the storage compartment 210. For some embodiments in which closed end 211 is configured as a cone, sample needle 121 may reach closed end 211 to more completely aspirate the reagent sample within storage compartment 210, avoiding or reducing carryover of the reagent sample.

It has been mentioned previously that the cartridge 210 in some embodiments may comprise a freeze-dried cartridge. Because the freeze-drying reagent in the freeze-drying storage bin is in a powder state, the sample injection needle 121 can be driven to enter the freeze-drying storage bin, and the dissolving solution is injected into the freeze-drying storage bin, so that the freeze-drying reagent is dissolved under the soaking of the dissolving solution, and the dissolved freeze-drying reagent is formed. The lyophilized reagent dissolved by the dissolution solution can then be sucked into the corresponding reaction chamber by the injection needle 121. The solution injected by the sample injection needle 121 may come from the microfluidic chip 100 itself, or from other storage bins of the reagent storage structure 200, or from other sources.

The injection needle, the reaction chamber, the flow channel and the like may be used in multiple experiments or multiple experimental steps of a single experiment. In order to avoid sample contamination in a subsequent experiment or a subsequent experiment step caused by sample carry-over in a previous experiment or an experiment step, the sample injection needle, the reaction cavity or the flow channel can be cleaned when needed. For example, after the reaction in one reaction chamber is completed, a cleaning solution is injected into the reaction chamber to wash the reaction chamber, and the reaction chamber is allowed to perform the following experimental steps after the cleaning.

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

In the case where a plurality of times of washing are required, the liquid level of the washing liquid may be configured to be sequentially increased in the washing order in a plurality of washing liquid bins storing different washing liquids. When the washing is performed according to the washing sequence, the front washing liquid attached to the outer wall of the sampling needle 121 can be cleaned by the rear washing liquid with a higher liquid level.

Referring to fig. 1, in some embodiments, the reaction chamber includes at least two ports. For example, in fig. 1, the reaction chamber 131 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 133 b. The first ports 131a, 132a, 133a may communicate with the flow passages 141, 142, 143, respectively. These flow channels can be controlled by the control valve 150 included in the reaction chip body 110 to enable gating and/or opening control between the flow channels and other flow channels, reaction chambers or sampling mechanisms. The control valve 150 is also connected to each reaction chamber 131, 132, 133 through a flow channel, and is used for controlling the 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.

In fig. 1, the second ports 131b, 132b, 133b are operatively connected to the gas driving device 300. Accordingly, the reaction chambers 131, 132, 133 may be configured to input or output a reagent sample through the flow channels under gas driving of the gas driving device 300. That is, the input or output of the reaction chamber can be realized by controlling the gas pressure by the gas driving device. When the gas driving device injects gas into the reaction cavity, the gas pressure in the reaction cavity is increased, so that the substances in the reaction cavity are discharged to other reaction cavities, flow channels or the outside of the chip through the flow channels. When the gas driving device sucks gas from the reaction cavity, the gas pressure in the reaction cavity is reduced to form negative pressure, so that other reaction cavities, flow channels or substances outside the chip flow into the reaction cavity. Through the operation of the gas driving device, the sequential acquisition of a plurality of reagents in the reagent storage structure by matching with the sampling mechanism can realize the sequential release, mixing, multi-step transfer reaction and the like of the plurality of reagents in the reagent storage structure 200, so that the design and control of the microfluidic reaction system are simpler, and the reliability is higher.

In some embodiments, the reaction chip body 110 includes a plurality of reaction chambers to achieve biochemical reactions of the reagent samples in several steps. Included among these reaction chambers is a first reaction chamber (e.g., reaction chambers 131 and 132 in fig. 1). The first port on the first reaction cavity, which is used for being connected with the flow channel, is positioned at the bottom of the first reaction cavity. When the gas driving device 300 evacuates the first reaction chamber, the liquid reagent is sucked into the first reaction chamber, and the liquid level of the liquid reagent is higher than the first port. And continuously pumping until the liquid reagent is completely sucked into the first reaction cavity, continuously sucking air and controlling the air suction speed, so that air can form bubbles and break above the liquid level of the liquid reagent, and the liquid reagent cannot be sucked out of the first reaction cavity. Through the reaction cavity structure and the air suction mode, a plurality of different liquid reagents can be sequentially sucked into the same first reaction cavity for reaction according to experimental requirements. When the gas driving device 300 blows gas into the first reaction chamber, the liquid substance in the first reaction chamber can be discharged.

In other embodiments, the reaction chip body includes a plurality of reaction chambers to perform biochemical reactions of the reagent samples in several steps. Included among these reaction chambers is a second reaction chamber (e.g., reaction chamber 133 in fig. 1). And a first port which is arranged on the second reaction cavity and is used for being connected with the flow channel is positioned at the top of the second reaction cavity. When the gas driving device 300 evacuates the second reaction chamber, the liquid reagent is 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 second reaction chamber structure is difficult to discharge, and can be used as a waste liquid chamber for receiving waste liquid. Further, a waste liquid adsorbing material, such as filter paper or the like, may be disposed in the second reaction chamber to fix the waste liquid by adsorbing the waste liquid. Of course, the second reaction chamber may also be used for reaction of a reagent sample, and multiple reagents may be respectively sucked into the second reaction chamber for reaction through the air suction effect of the gas driving device 300 on the second reaction chamber.

the number and type of reaction chambers in the reaction chip body 110 can be designed and selected according to the experimental needs. 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 apparatus 300 includes: a peristaltic pump 310 having a hose 320 and a vacuum chuck 330. A vacuum cup 330 is disposed at an end of the hose 320 for selectively forming a sealing connection with a second port (e.g., second ports 131b, 132b, 133b in fig. 1) of a different reaction chamber. In this embodiment, the peristaltic pump 310 can pump a smaller flow of gas by alternately squeezing and releasing the pump tube to realize the pressure change in the reaction chamber, which can meet the requirement of the microfluidic chip for transporting the reagent sample. When it is desired to control the aspiration or discharge of liquid reagents from a certain reaction chamber, a vacuum chuck 330 may be connected to a second port of the reaction chamber. One peristaltic pump 310 can perform sucking or discharging operation of a plurality of reaction chambers in a time-sharing manner. The vacuum chuck 330 can be positionally adjusted by a driving mechanism (e.g., a motor, etc.) to change the connection relationship with the second port of a different reaction chamber. In another embodiment, peristaltic pump 310 may be replaced with a syringe pump, a vacuum pump, or any other pump capable of driving air in the hose.

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

In contrast to the embodiments of the present disclosure that have been described previously, gas-powered device 300' of fig. 2 may include a syringe 340 having a tip segment 341. And a flexible sealing material 350, such as rubber, silicone or other elastic polymer material, may be disposed on at least a portion of the second port of the reaction chamber. When a laboratory technician needs to operate a certain reaction chamber, the needle head 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 maintains the sealed state of the reaction chamber. The experimenter can operate the injector 340 to inject gas into the reaction chamber or suck gas from the reaction chamber, thereby changing the gas pressure in the reaction chamber, as required by the experiment. The flexible sealing material 350 can enable the injector 340 to drive the reagent in the reaction chamber and simultaneously realize good sealing of the reaction chamber, and is particularly suitable for scenes with high sealing requirements in some reaction processes.

referring to fig. 3, in some embodiments, the sampling mechanism further includes a bore needle 122. The diameter of the open-hole needle 122 is larger than that of the sample injection needle 121, so as to form a channel on the reagent storage structure 200 for the sample injection needle 121 to enter. In other words, when the injection needle 121 needs to enter a certain storage bin, a larger-sized hole can be formed on the sealing film 220 of the storage bin through the hole-forming needle 122. The needle 121 can then enter the opening in the sealing membrane 220 directly without contacting or rubbing against the sealing membrane 220. Therefore, the reagent on the outer wall of the injection needle 121 can be effectively prevented from being adhered to the sealing film 220 to cause pollution. The perforating needle can be made of metal or plastic materials, and can be hollow or solid.

In fig. 3, the open-hole needle 122 may be fixedly disposed at one side of the sample injection needle 121, and the actions of opening the open-hole needle and inserting the sample injection needle are respectively realized by the relative movement between the reagent storage structure 200 and the sampling mechanism. In other embodiments, the open pore needle 122 may also be configured to be retractable with respect to the reaction chip body, and the open pore needle 122 may be disposed adjacent to the sample injection needle 121 or surround the sample injection needle 121 through a hollow portion of the open pore needle 122. When tapping is desired, the tapping needle 122 can be extended and retracted after tapping. This may reduce relative movement between the reagent storage structure 200 and the sampling mechanism.

in the embodiments of the present disclosure described above, the microfluidic chip 100 or the reagent storage structure 200 may be designed as a disposable product as needed to avoid contamination between reagent samples. In yet other embodiments, the microfluidic chip 100 or the reagent storage structure 200 may also be designed for multiple uses. The microfluidic chip and the reagent storage structure can be manufactured by common existing materials (such as plastics, metals and the like) by common processes (such as injection molding and the like) in the medical appliance industry, so that the material and process cost is reduced.

Based on any one of the foregoing embodiments of the microfluidic reaction system, the present disclosure further provides a corresponding driving method, including steps under a sampling condition and a reaction condition, where under the sampling condition, at least one reagent sample may be extracted from the reagent storage structure 200 by a sampling mechanism of the microfluidic chip 100 and provided to a reaction chamber of the microfluidic chip 100. And under the reaction working condition, at least one reagent sample can be received through the reaction cavity so as to carry out the reaction process of the reagent sample.

In some embodiments, the sampling condition may further include: a channel is formed on the reagent storage structure 200 through the open-bore needle 122 of the sampling mechanism for entry of a sample needle 121 of the sampling mechanism. The sample injection needle 121 is then driven along the channel into the reagent storage structure 200 in order to draw a reagent sample from the reagent storage structure 200.

In addition, for the extraction of the freeze-dried reagent, the sampling condition can further include: the injection needle 121 is driven to enter a freeze-drying storage bin in the reagent storage structure 200, and a dissolving solution is injected into the freeze-drying storage bin. And 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 cavity through the sample injection needle 121.

In other embodiments, the driving method may further comprise the step of purging the operation, namely: and washing the sample injection needles 121 in at least one washing liquid bin in the reagent storage structure 200 in sequence according to a washing sequence.

In the present specification, a plurality of embodiments are described in a progressive manner, the emphasis of each embodiment is different, and the same or similar parts between the embodiments are referred to each other. For the method embodiment, since the whole and related steps have corresponding relations with the contents in the microfluidic chip and the microfluidic reaction system embodiment, the description is relatively simple, and the relevant points can be referred to the partial description of the corresponding embodiment.

thus, various embodiments of the present disclosure have been described in detail. Some details that are well known in the art have not been described in order to avoid obscuring the concepts of the present disclosure. It will be fully apparent to those skilled in the art from the foregoing description how to practice the presently disclosed embodiments.

Although some specific embodiments of the present disclosure have been described in detail by way of example, it should be understood by those skilled in the art that the foregoing examples are for purposes of illustration only and are not intended to limit the scope of the present disclosure. It will be understood by those skilled in the art that various changes may be made in the above embodiments or equivalents may be substituted for elements thereof without departing from the scope and spirit of the present disclosure. The scope of the present disclosure is defined by the appended claims.

Claims

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:

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').