Microfluidic chip, sample treatment system and use thereof, and sample treatment method

Abstract

A microfluidic chip, a sample treatment system and a use thereof, and a sample treatment method. The microfluidic chip comprises a sample treatment cavity and a plurality of storage cavities; the sample treatment cavity is used for providing space for sample treatment; the plurality of storage cavities are used for storing samples; the plurality of storage cavities include a first storage cavity, a second storage cavity and a third storage cavity; both the first storage cavity and the second storage cavity can be communicated with the sample treatment cavity, but the first storage cavity and the second storage cavity are not communicated with the sample treatment cavity at the same time, and the third storage cavity is not communicated with the sample treatment cavity; and the third storage cavity is provided with a first interface interacting with a pipetting device. In the present application, by means of the structural design of the microfluidic chip, different samples can be sequentially input into a same sample treatment cavity from different cavities, and multi-step reaction is carried out, reducing sample loss; and a temperature control device involves simpler design and lower cost.

Description

Microfluidic chip, sample processing system and its application, and sample processing method TECHNICAL FIELD

[0001] The present application relates to the technical field of biological or chemical sample processing, and in particular to a microfluidic chip, a sample processing system and its application, and a sample processing method. BACKGROUND

[0002] Before biochemical reactions are carried out in the fields of biology, medicine, and chemical industry, the samples usually need to be pretreated. For example, before gene sequencing, a large number of operations or biochemical reactions such as filtering, purification, cyclization, and amplification need to be performed on the original biological samples, so as to obtain samples (for example, sequencing libraries) that can be accepted by detection instruments such as gene sequencers.

[0003] At present, although some operations have been automated on a pipetting workstation, due to the diversity of samples and the complexity of processing strategies under different sample types, a large number of tedious operations still highly depend on manual work, which is time-consuming, low in efficiency, consumes a large number of disposable tips, is high in consumable cost, is harmful to the environment, and needs to match a plurality of instruments and equipment such as a polymerase chain reaction (PCR) instrument, thereby increasing the equipment cost and volume.

[0004] SUMMARY

[0005] In view of this, in order to solve at least one of the above technical problems, it is necessary to provide a microfluidic chip.

[0006] In addition, the present application also provides a sample processing system, a sample processing method, and a biochemical reaction system and a biochemical detection system using the sample processing system.

[0007] In a first aspect, the present application provides a microfluidic chip, which comprises at least one sample processing region, and the sample processing region comprises a sample processing cavity and a plurality of storage cavities. The sample processing cavity is used to provide space for sample processing. The plurality of storage cavities are used to store samples, and the plurality of storage cavities comprise a first storage cavity, a second storage cavity, and a third storage cavity. The first storage cavity and the second storage cavity are both in communication with the sample processing cavity, and the first storage cavity and the second storage cavity are not simultaneously in communication with the sample processing cavity. The third storage cavity is not in communication with the sample processing cavity, and the third storage cavity has a first interface. The first interface is used to interact with a pipetting device to transfer the sample in the third storage cavity to the sample processing cavity.

[0008] In some possible embodiments, a first on-off assembly is provided between the first storage cavity and the sample processing cavity, the first on-off assembly being configured to control the communication or disconnection between the first storage cavity and the sample processing cavity, a second on-off assembly is provided between the second storage cavity and the sample processing cavity, the second on-off assembly being configured to control the communication or disconnection between the second storage cavity and the sample processing cavity, and the first on-off assembly and the second on-off assembly are not opened at the same time.

[0009] In some possible embodiments, the first on-off assembly comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve, and an active valve.

[0010] The second on-off assembly comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve, and an active valve.

[0011] In some possible embodiments, the active valve comprises at least one of a paraffin valve and a pneumatic valve.

[0012] In some possible embodiments, the sample processing region further comprises a temporary storage cavity, the temporary storage cavity being in communication with the sample processing cavity, and the temporary storage cavity having a second interface configured to interact with the pipetting device to transfer the sample in the third storage cavity to the temporary storage cavity.

[0013] In some possible embodiments, the temporary storage cavity is in direct communication with the sample processing cavity, or the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity.

[0014] In some possible embodiments, when the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, a mixing zone is provided between the first storage cavity and the sample processing cavity.

[0015] In some possible embodiments, the mixing zone is formed by bending a first flow channel that communicates the first storage cavity and the sample processing cavity.

[0016] In some possible embodiments, when the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, the first storage cavity is further in communication with the second storage cavity, and a third on-off assembly is provided between the first storage cavity and the second storage cavity, the third on-off assembly being configured to control the communication or disconnection between the first storage cavity and the second storage cavity.

[0017] In some possible embodiments, the third on-off assembly comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve, and an active valve.

[0018] In some possible embodiments, the microfluidic chip comprises a first edge and a second edge arranged oppositely, the third storage cavity is close to the first edge, the sample processing cavity is close to the second edge, and the first storage cavity and the second storage cavity are located between the sample processing cavity and the third storage cavity.

[0019] In some possible embodiments, the microfluidic chip is fan-shaped or circular, the first edge is close to the center of the microfluidic chip, when the temporary storage cavity is directly communicated with the sample processing cavity, the temporary storage cavity is close to the second edge, and the third storage cavity and the temporary storage cavity are arranged along the radial direction of the microfluidic chip; when the temporary storage cavity is communicated with the sample processing cavity through the first storage cavity, the temporary storage cavity is close to the first edge, and the third storage cavity and the temporary storage cavity are arranged along the circumferential direction of the microfluidic chip.

[0020] In some possible embodiments, the microfluidic chip comprises a plurality of sample processing regions, and the plurality of sample processing regions are arranged along the circumferential direction of the microfluidic chip.

[0021] In some possible embodiments, the sample processing cavity has a third interface for the pipetting device to take out the sample in the sample processing cavity.

[0022] The microfluidic chip further comprises at least one vent hole, and the sample processing cavity, the first storage cavity and the second storage cavity are communicated with the external environment through the vent hole.

[0023] In a second aspect, the embodiments of the present application provide a sample processing system, comprising:

[0024] a microfluidic chip, which is the microfluidic chip as described above;

[0025] a pipetting device, which is used to interact with the first interface of the third storage cavity to transfer the first sample in the third storage cavity to the sample processing cavity; and

[0026] a driving device, and the microfluidic chip is detachably arranged on the driving device, and the driving device is used to drive the second sample in the first storage cavity and the third sample in the second storage cavity to be transferred to the sample processing cavity, respectively.

[0027] In some possible embodiments, the driving device drives the microfluidic chip to rotate around a rotation center to generate a centrifugal force, and the centrifugal force is used to drive the second sample in the first storage cavity and the third sample in the second storage cavity to be transferred to the sample processing cavity, respectively.

[0028] In some possible embodiments, when the sample processing region further comprises the temporary storage cavity, the pipetting device is configured to transfer the first sample in the third storage cavity to the temporary storage cavity, and the driving device is further configured to drive the first sample in the temporary storage cavity to the sample processing cavity.

[0029] In some possible embodiments, the pipetting device can move linearly along a first direction and a second direction, the first direction being a rotating radial direction of the microfluidic chip, and the second direction being a direction perpendicular to a rotating plane of the microfluidic chip.

[0030] In some possible embodiments, the pipetting device comprises a fixed arm and a pipetting arm, the fixed arm is arranged at the rotating center, one end of the pipetting arm is arranged on the fixed arm, and the other end of the pipetting arm away from the fixed arm is located at a side of the microfluidic chip away from the driving device, and the pipetting arm can move linearly along the first direction and the second direction.

[0031] In some possible embodiments, the sample processing system further comprises a temperature control device configured to provide a biochemical reaction required temperature for the sample processing cavity.

[0032] In some possible embodiments, when the first on-off component or the second on-off component is a paraffin valve, the temperature control device is further configured to heat the first on-off component or the second on-off component.

[0033] In some possible embodiments, the temperature control device is arranged at a side of the microfluidic chip close to the driving device, and the temperature control device can move towards or away from the microfluidic chip.

[0034] In a third aspect, an embodiment of the present application provides a sample processing method, comprising:

[0035] providing a microfluidic chip, the microfluidic chip being as described above;

[0036] transferring a first sample in the third storage cavity to the sample processing cavity;

[0037] driving a second sample in the first storage cavity to the sample processing cavity;

[0038] performing a first processing process on the first sample and the second sample in the sample processing cavity to obtain a first processing product;

[0039] driving a third sample in the second storage cavity to the sample processing cavity; and

[0040] The first processing product and the third sample are subjected to a second processing procedure in the sample processing cavity to obtain a second processing product.

[0041] In some possible embodiments, when the sample processing region further comprises the temporary storage cavity,

[0042] The step of transferring the first sample in the third storage cavity to the sample processing cavity comprises:

[0043] transferring the first sample in the third storage cavity to the temporary storage cavity by a pipetting device; and

[0044] providing a driving force for the microfluidic chip by a driving device to transfer the first sample in the temporary storage cavity to the sample processing cavity.

[0045] In some possible embodiments, when the number of the third storage cavities is two, the two third storage cavities are respectively a sample cavity for storing a first sample and a buffer cavity for storing a buffer, and the step of transferring the first sample in the third storage cavity to the temporary storage cavity by the pipetting device comprises:

[0046] transferring a first volume of the first sample from the sample cavity to the temporary storage cavity by the pipetting device, and transferring a second volume of the buffer from the buffer cavity to the temporary storage cavity by the pipetting device, wherein the sum of the first volume and the second volume is equal to the volume of all the first sample stored in the sample cavity.

[0047] In some possible embodiments, when the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, the transferring of the first sample and the second sample to the sample processing cavity is performed synchronously, comprising:

[0048] providing a first centrifugal force for the microfluidic chip by a driving device to drive the first sample in the temporary storage cavity to be transferred to the first storage cavity and form a first mixture with the second sample; and

[0049] providing a second centrifugal force for the microfluidic chip by a driving device to make the first storage cavity in communication with the sample processing cavity and the second storage cavity disconnected from the sample processing cavity, and drive the first mixture in the first storage cavity to be transferred to the sample processing cavity.

[0050] In some possible embodiments, a mixing region is arranged between the first storage cavity and the sample processing cavity, and before the first mixture is transferred to the sample processing cavity, the method further comprises:

[0051] Under the action of the second centrifugal force, the first mixture is mixed in the mixing area.

[0052] In some possible embodiments, the step of driving the third sample in the second storage cavity to the sample processing cavity comprises:

[0053] The microfluidic chip is provided with a third centrifugal force by the driving device, so that the second storage cavity is in communication with the sample processing cavity, and the third sample in the second storage cavity is driven to the sample processing cavity.

[0054] In some possible embodiments, after obtaining the second processing product, the method further comprises:

[0055] The second processing product in the sample processing cavity is taken out by the pipetting device.

[0056] In a fourth aspect, the embodiments of the present application provide a biochemical reaction system, which comprises a control module and a sample processing system as described above connected in communication with the control module.

[0057] In a fifth aspect, the embodiments of the present application provide a biochemical detection system, which comprises a detection module and a sample processing system as described above, the sample processing system being used for processing a sample to obtain a product, and the detection module being used for detecting the product.

[0058] The sample processing system provided by the embodiments of the present application has the following beneficial effects:

[0059] (1) Through the structural design of the microfluidic chip, the samples in the first storage cavity and the second storage cavity can be transferred step by step to the same sample processing cavity, so that the same sample processing cavity can perform a multi-step sample processing process (such as a biochemical reaction process), that is, different reagent samples can be inputted into the same sample processing cavity in sequence and multi-step reactions can be performed, thereby reducing sample loss, and the design of the temperature control device is simpler and the cost is lower.

[0060] (2) Through the microfluidic chip cooperating with the pipetting device, the transfer of samples with uncertain volumes can be realized, and the shortcoming that part of the liquid in the cavity is difficult to transfer in the existing microfluidic scheme is overcome.

[0061] (3) The pipetting device is only used for transferring samples and the output of the final processed reaction products, and does not participate in the sample addition and mixing of the intermediate steps. Due to the rotational movement of the microfluidic chip, the pipetting device only needs to move along the radial direction of the microfluidic chip to reach every corner of the chip, reducing the movement freedom, movement stroke range and system complexity of the pipetting device, and reducing the cost and volume of the sample processing system.

[0062] (3) Since the pipetting device does not participate in the sample addition and mixing of the intermediate steps, the use of disposable consumables (such as pipette tips) is greatly reduced, and even no disposable pipette tips can be used, and reusable reagent needles can be used, and the reagent needles can be cleaned in parallel when the microfluidic chip performs the intermediate steps, thereby shortening the system running time. BRIEF DESCRIPTION OF DRAWINGS

[0063] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments of the present application will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0064] FIG. 1 is a system framework diagram of a sample processing system in an embodiment of the present application.

[0065] FIG. 2 is a structural schematic diagram of a microfluidic chip in an embodiment of the present application.

[0066] FIG. 3 is a structural schematic diagram of a sample processing region in FIG. 2.

[0067] FIG. 4A is a structural schematic diagram of a siphon valve in an embodiment of the present application.

[0068] FIGS. 4B and 4C are structural schematic diagrams of a hydrophobic valve in an embodiment of the present application.

[0069] FIG. 4D is a structural schematic diagram of a capillary valve in an embodiment of the present application.

[0070] FIG. 4E is a structural schematic diagram of a paraffin valve in an embodiment of the present application.

[0071] FIG. 4F is a structural schematic diagram of a pneumatic valve in an embodiment of the present application.

[0072] FIG. 5 is a structural schematic diagram of a microfluidic chip in another embodiment of the present application.

[0073] FIG. 6 is a flowchart of a sample processing method in an embodiment of the present application.

[0074] FIG. 7 is a structural schematic diagram of a biochemical reaction system in an embodiment of the present application.

[0075] Figure 8 is a schematic diagram of a biochemical detection system according to an embodiment of the present application.

[0076] Figure 9A is a schematic diagram of a specific implementation of the microfluidic chip shown in Figure 2.

[0077] Figures 9B to 9K are schematic diagrams of the process of sample processing using the microfluidic chip shown in Figure 9A.

[0078] Figure 9L is a schematic diagram of a microfluidic chip including multiple sample processing regions shown in Figure 9A according to an embodiment of the present application.

[0079] Figure 10A is a schematic diagram of a second specific implementation of the microfluidic chip shown in Figure 2.

[0080] Figures 10B to 10H are schematic diagrams of the process of sample processing using the microfluidic chip shown in Figure 10A.

[0081] Figure 11A is a schematic diagram of a third specific implementation of the microfluidic chip shown in Figure 2.

[0082] Figures 11B to 11H are schematic diagrams of the process of sample processing using the microfluidic chip shown in Figure 11A.

[0083] The following detailed description will further describe the present application with reference to the above mentioned figures. DETAILED DESCRIPTION

[0084] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the figures in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application.

[0085] It should be noted that when a component is referred to as being "fixed" or "mounted" to another component, it can be directly on the other component or there can be an intermediate component between them. When a component is referred to as being "disposed" on another component, it can be directly disposed on the other component or there can be an intermediate component between them. The term "and / or" as used herein includes all possible combinations of one or more of the associated listed items.

[0086] Currently, the sample processing in biochemical reaction process can be achieved by using centrifugal microfluidic technology. The centrifugal microfluidic technology is to drive the microfluidic chip to rotate around a rotation center by a centrifugal device to generate centrifugal force. The centrifugal force can realize the transfer, mixing, reaction and other processing processes of the sample in the microfluidic chip. The centrifugal microfluidic technology does not need to introduce an additional power source because it relies on the rotation of the microfluidic chip itself to provide power, and the space volume occupied by the instrument is small. Secondly, the corresponding sample can be packaged in the microfluidic chip in advance, which is conducive to realizing dry operation, and the waste liquid is discarded with the chip after use, and the system does not need to be cleaned.

[0087] However, the present inventors found in research that the existing centrifugal microfluidic chip has the following defects in the application process: first, it cannot be compatible with the input of micro-sample with uncertain volume (for example, 3 μl for a sample with concentration a, and 5 μl for a sample with concentration b). Taking the construction of a gene sequencing library as an example, since the actual input volume of the biological sample needs to be calculated according to the concentration of single-stranded DNA at the beginning of the process, we need to transfer the specific volume of biological sample calculated to the microfluidic chip. However, in the usual centrifugal microfluidic technology, the liquid is moved as a whole from one cavity to another, and it is difficult to accurately control the movement of a part of the volume of liquid in a certain chamber. Second, it is difficult to realize the successive delivery of different reagents from different cavities to the same cavity and the multi-step reaction (for example, cavity A first delivers reagent 1 to cavity C for reaction 1, and then cavity B delivers reagent 2 to cavity C for reaction 2). Taking the construction of a gene sequencing library as an example, after the first PCR reaction, new reagents need to be added, and then the second PCR reaction is carried out. In the existing centrifugal microfluidic chip, the two reactions need to be carried out in two cavities respectively, which leads to an increase in the area of the heating region, higher cost, and more complex temperature control strategy.

[0088] To solve at least one of the above defects, please refer to FIG. 1, an embodiment of the present application provides a sample processing system 1000, which comprises a microfluidic chip 100, a driving device 200 and a pipetting device 300. The microfluidic chip 100 is detachably arranged on the driving device 200, and the driving device 200 is configured to provide a driving force for driving the sample in the microfluidic chip 100 to transfer in different cavities. The pipetting device 300 can also be used to transfer the sample in different cavities in the microfluidic chip 100. Specifically, the microfluidic chip 100 can be a centrifugal microfluidic chip, and the driving device 200 can be a centrifugal device. The microfluidic chip 100 is driven to rotate around a rotation center a by the driving device 200, so as to improve the centrifugal force of the microfluidic chip 100. Under the action of the centrifugal force, the sample in the microfluidic chip 100 can be transferred, mixed and the like. It can be understood that the microfluidic chip 100 is not limited to a centrifugal microfluidic chip, and the driving device 200 is not limited to a centrifugal device. Other driving sources can also be used, such as pressure driving.

[0089] Please refer to the structure schematic diagram of the microfluidic chip 100 provided by the embodiment of the present application shown in FIG. 2 and FIG. 3. The microfluidic chip 100 includes at least one sample processing region 10, which includes a sample processing cavity 101 and a plurality of storage cavities 102. The sample processing cavity 101 can be used to provide space for sample processing (such as mixing, reaction, etc.). The plurality of storage cavities 102 are used to store samples, which can be biological samples (such as human blood samples, tissue samples, or saliva samples, etc.) required for biochemical substance analysis, reagents and buffer liquid samples used for biochemical analysis, or mixtures of biological samples, reagents and buffer liquid samples. The plurality of storage cavities 102 can include a first storage cavity 104, a second storage cavity 105, and a third storage cavity 106. The first storage cavity 104 and the second storage cavity 105 can both communicate with the sample processing cavity 101, so that the samples in the first storage cavity 104 and the second storage cavity 105 can be transferred to the sample processing cavity 101. The first storage cavity 104 and the second storage cavity 105 do not communicate with the sample processing cavity 101 at the same time, that is, the samples in the first storage cavity 104 and the second storage cavity 105 can be added to the sample processing cavity 101 step by step (or in a certain order) to achieve the purpose of multi-step biochemical reaction in the same sample processing cavity 101. The third storage cavity 106 does not communicate with the sample processing cavity 101, and the third storage cavity 106 has a first interface 161 for interacting with a pipetting device 300 to transfer the sample in the third storage cavity 106 to the sample processing cavity 101, thereby achieving the transfer of an uncertain volume of sample from the third storage cavity 106 to the sample processing cavity 101. It can be understood that the number of the first storage cavity 104, the second storage cavity 105, and the third storage cavity 106 can be designed according to the actual number of sample types required for the reaction. For example, in the construction of a gene sequencing library, the biological sample can be stored in the third storage cavity 106 of the microfluidic chip 100 provided by the embodiment, the first reagent can be stored in the first storage cavity 104, and the second reagent can be stored in the second storage cavity 105.

[0090] When the microfluidic chip 100 is a centrifugal microfluidic chip, the pipetting device 300 only needs to move along the radial direction of the rotation of the microfluidic chip 100 to reach every corner of the microfluidic chip 100 in cooperation with the rotation of the microfluidic chip 100. Specifically, the pipetting device 300 can move linearly along the first direction R and the second direction Z perpendicular to each other, the first direction R can be the radial direction of the rotation of the microfluidic chip 100, and the second direction Z is perpendicular to the rotation plane of the microfluidic chip 100, and the second direction Z can be the vertical direction. Therefore, by cooperating the rotation of the microfluidic chip 100 with the pipetting device 300, the freedom degree of motion of the pipetting device 300 can be reduced (for example, it can be changed from the traditional XYZ axis motion to RZ motion), the motion stroke range is reduced, the complexity of operating the pipetting device 300 is simplified, the structural complexity of the sample processing system 1000 is reduced, and the cost and volume of the sample processing system 1000 are also reduced.

[0091] In some embodiments, the first interface 161 can be an opening on the upper surface of the microfluidic chip 100. Through the first interface 161, a certain sample can be drip irrigated into the third storage cavity 106 by manual or automatic method. After completing the liquid filling, the first interface 161 is closed by a sealed film. When sample transfer in the third storage cavity 106 is needed, the sealed film on the first interface 161 is removed in advance.

[0092] In some embodiments, a first on-off component 141 is arranged between the first storage cavity 104 and the sample processing cavity 101, and the first on-off component 141 is used to control the communication or disconnection between the first storage cavity 104 and the sample processing cavity 101. A second on-off component 151 is arranged between the second storage cavity 105 and the sample processing cavity 101, and the second on-off component 151 is used to control the communication or disconnection between the second storage cavity 105 and the sample processing cavity 101, and the first on-off component 141 and the second on-off component 151 are not opened at the same time, so as to realize the purpose that the first storage cavity 104 and the second storage cavity 105 can respectively transfer samples into the sample processing cavity 101.

[0093] In some embodiments, the first on-off component 141 can be a valve type on-off control structure, and the second on-off component 151 can also be a valve type on-off control structure. When the microfluidic chip 100 is a centrifugal microfluidic chip, the first on-off component 141 and the second on-off component 151 can each include at least one of a capillary valve, a hydrophobic valve, a siphon valve, and an active valve. Among them, the capillary valve (as shown in FIG. 4A) and the hydrophobic valve (as shown in FIGS. 4B and 4C) are both caused by local surface tension difference to cause liquid stagnation. When the rotation speed of the microfluidic chip is greater than a certain threshold, the surface tension difference is no longer sufficient to resist the centrifugal force, and the valve is opened and fails to realize the communication of different cavities. As shown in FIG. 4D, the siphon valve is a curved flow channel design, in which there is a local flow channel (such as point A in FIG. 4D), which is closer to the rotation center of the chip than the upstream cavity. The local flow channel A can be referred to as a wave crest. When the rotation speed of the chip is maintained at a high level, the centrifugal force maintains the liquid level in a state that cannot reach the local flow channel A (wave crest). When the rotation speed of the chip is reduced, the liquid level passes the local flow channel A (wave crest) with the help of capillary force, so that the liquid as a whole is transferred to the downstream cavity through the local flow channel A. Therefore, the siphon valve needs to have a control process of accelerating first and then decelerating in use. The active valve is a valve that needs to be activated by an external source, that is, the opening of the valve needs to be achieved by providing external assistance. For example, a paraffin valve (as shown in FIG. 4E) needs to be heated to melt before it can be opened. For example, a pneumatic valve (as shown in FIG. 4F) designs a gas cavity connected with a liquid flow channel through a deformable membrane. When the gas cavity is inflated, the air pressure pushes the membrane to deform and thus squeezes the liquid flow channel to realize the closure of the flow channel. The above capillary valve, hydrophobic valve, siphon valve, and active valve are four categories, and the specific structural form can be designed according to actual needs.

[0094] Referring to FIG. 5, the sample processing region 10 further comprises a temporary storage cavity 103 for temporarily storing the sample, and the temporary storage cavity 103 is in communication with the sample processing cavity 101. In this embodiment, the temporary storage cavity 103 is directly in communication with the sample processing cavity 101. It can be understood that in other embodiments, the temporary storage cavity 103 can also be indirectly in communication with the sample processing cavity 101, for example, the temporary storage cavity 103 can be in communication with the sample processing cavity 101 through the first storage cavity 104 or the second storage cavity 105. The temporary storage cavity 103 has a second interface 131 for the pipette to interact with the temporary storage cavity 103, for example, to transfer the sample to the temporary storage cavity 103. The temporary storage cavity 103 can be open to facilitate the transfer of the sample into the temporary storage cavity 103. The sample in the third storage cavity 106 can be transferred into the temporary storage cavity 103 by the pipette, and the sample in the temporary storage cavity 103 can be further transferred into the sample processing cavity 101. Specifically, when the microfluidic chip 100 is a centrifugal microfluidic chip, the sample in the temporary storage cavity 103 can be further transferred into the sample processing cavity 101 under the action of centrifugal force.

[0095] In some embodiments, the number of the third storage cavities 106 can be multiple, and multiple third storage cavities 106 are independently provided to store different samples. For example, in this embodiment, two third storage cavities 106 are provided, which are a sample cavity 162 for storing a biological sample and a buffer cavity 163 for storing a buffer.

[0096] Referring to FIGS. 1 and 2 again, the sample processing cavity 101 has a third interface 111 for interacting with the pipette 300, so that the pipette 300 can take out the sample in the sample processing cavity 101. The third interface 111 does not affect the flow of the sample in the sample processing cavity 101 under the action of rotation. In some embodiments, the third interface 111 is an opening on the upper surface of the microfluidic chip 100, and a sealed membrane is provided to keep the third interface 111 in an initial closed state. When it is necessary to take out the sample in the sample processing cavity 101, the membrane is pierced by manual or automatic means, so that the pipette or reagent needle contacts the sample, thereby achieving the extraction of the sample. Here, the sample can be a reaction product, or a simple mixture after mixing, etc.

[0097] The fourth interface can be arranged on the first storage cavity 104 and the second storage cavity 105, and the fourth interface can be used to place the sample in the corresponding storage cavity in advance. The fourth interface does not affect the sample flowing to other pipelines or cavities under the action of rotation. In some embodiments, the fourth interface can be an opening arranged on the upper surface of the microfluidic chip 100. The fourth interface can be used to drip some samples into the first storage cavity 104 and the second storage cavity 105 by manual or automatic methods. After the liquid filling is completed, the fourth interface is closed by a sealed film.

[0098] The microfluidic chip 100 further comprises at least one vent hole. The sample processing cavity 101, the first storage cavity 104 and the second storage cavity 105 are all connected with the outside environment through the vent hole.

[0099] It can be understood that the first interface 161, the second interface 131, the third interface 111, the fourth interface and the vent hole are all pre-sealed by a sealed film, so as to prevent the pre-stored sample in the microfluidic chip 100 from leaking.

[0100] Referring to FIGS. 2 and 3 again, the microfluidic chip 100 can comprise a first edge 11 and a second edge 12 arranged oppositely. The third storage cavity 106 can be arranged close to the first edge 11. The sample processing cavity 101 can be arranged close to the second edge 12. The first storage cavity 104 and the second storage cavity 105 can be arranged between the sample processing cavity 101 and the third storage cavity 106. When the microfluidic chip 100 is installed on the driving device 200, the first edge 11 can be arranged close to the rotation center a. The above layout mode facilitates the sample in the first storage cavity 104 and the second storage cavity 105 to be transferred to the sample processing cavity 101 by the action of centrifugal force.

[0101] In some embodiments, a plurality of third storage cavities 106 can be arranged along the radial direction of the rotation radius of the microfluidic chip 100, or can be arranged along the circumferential direction of the rotation of the microfluidic chip 100. Such arrangement design facilitates the pipetting device 300 to transfer the sample in different third storage cavities 106, and can further simplify the transfer path.

[0102] The microfluidic chip 100 can be a fan shape, a circle shape, a rectangle shape, or other regular or irregular shapes, and can be designed according to actual needs. In some embodiments, the microfluidic chip 100 can be a fan shape or a circle shape, in which case the center of the microfluidic chip 100, i.e., the rotation center a, and the first edge 11 are arranged close to the center of the microfluidic chip 100, and the plurality of third storage cavities 106 can be arranged along the radial direction of the microfluidic chip 100. When the temporary storage cavity 103 is arranged close to the first edge 11, the temporary storage cavity 103 and any third storage cavity 106 can be arranged along the circumferential direction of the microfluidic chip 100. If the temporary storage cavity 103 is arranged close to the sample processing cavity 101, the plurality of third storage cavities 106 and the temporary storage cavity 103 can be arranged along the radial direction of the microfluidic chip 100. Similarly, the above design of the third storage cavities 106 and the temporary storage cavity 103 can further facilitate the transfer of the sample by the pipetting device 300, and further simplify the transfer path.

[0103] Referring to FIGS. 2 and 3, the microfluidic chip 100 can include a plurality of sample processing regions 10. By arranging a plurality of sample processing regions 10, the plurality of sample processing regions 10 can perform the same biochemical reaction or different biochemical reactions, which can improve the space utilization of the microfluidic chip 100 and improve the efficiency and throughput of sample processing. Specifically, when the microfluidic chip 100 is a circular chip, the plurality of sample processing regions 10 can be arranged along the circumferential direction of the microfluidic chip 100.

[0104] Referring to FIGS. 1 and 2, the pipetting device 300 can include a fixed arm 301 and a pipetting arm 302. The fixed arm 301 can be arranged at the rotation center a, one end of the pipetting arm 302 is arranged on the fixed arm 301, and the other end of the pipetting arm 302 away from the fixed arm 301 is located on the side of the microfluidic chip 100 away from the driving device 200, and the pipetting arm 302 can move linearly along the first direction R and the second direction Z. The end of the pipetting arm 302 can cooperate with the pipette tip to suck and release the sample to transfer the sample. It can be understood that the pipetting device 300 can also be arranged at other positions.

[0105] Referring again to FIG. 1, the sample processing system 1000 can further include a temperature control device 400 for temperature adjustment of the microfluidic chip 100, and at least providing a temperature required for biochemical reaction for the sample processing cavity 101.

[0106] In some embodiments, the temperature control device 400 can be located below the microfluidic chip 100, specifically, the temperature control device 400 is arranged on the side of the microfluidic chip 100 close to the driving device 200, and the temperature control device 400 can move towards or away from the microfluidic chip 100. When heating of the microfluidic chip 100 is needed, the temperature control device 400 can be driven to move to the lower surface of the microfluidic chip 100, and when the heating is stopped and the microfluidic chip 100 needs to be rotated, the temperature control device 400 can be driven to move away from the microfluidic chip 100. It can be understood that the microfluidic chip 100 can also be controlled to move towards or away from the temperature control device 400.

[0107] Referring to FIG. 6, in combination with FIGS. 1 and 2, the method for sample processing provided by the embodiments of the present application using the aforementioned sample processing system 1000 is specifically provided, and includes the following steps:

[0108] In step S1, a microfluidic chip 100 is provided, and the specific structure of the microfluidic chip 100 is described above and will not be repeated here.

[0109] In step S2, the first sample in the third storage cavity 106 is transferred to the sample processing cavity 101.

[0110] Before step S2, the second sample needs to be pre-sealed in the first storage cavity 104, and the third sample needs to be pre-sealed in the second storage cavity 105, which can be manually input by the user or input by the pipetting device. The first sample is transferred to the third storage cavity 106 by the pipetting device 300. Taking the construction of a gene sequencing library as an example, the first sample can be a biological sample, the second sample can be a first reagent, and the third sample can be a second reagent.

[0111] Step S2 specifically includes the following steps:

[0112] In step S21, the first sample in the third storage cavity 106 is transferred to the temporary storage cavity 103 by the pipetting device 300.

[0113] The microfluidic chip 100 is installed on the driving device 200, and the microfluidic chip 100 is kept stationary. A certain volume of the first sample is sucked in the third storage cavity 106 by the pipetting device 300 through the first interface 161, and the first sample is transferred to the temporary storage cavity 103. The volume of the first sample is calculated according to the concentration of the first sample.

[0114] In step S22, the driving device 200 is started, and the driving force of the driving device 200 is increased to drive the first sample in the temporary storage cavity 103 to be transferred to the sample processing cavity 101.

[0115] Specifically, when the driving device 200 is a centrifugal device, the microfluidic chip 100 is driven to rotate around a rotation center a by the driving device 200, thereby increasing the centrifugal force. Under the action of the centrifugal force, the sample in the temporary storage cavity 103 is further transferred into the sample processing cavity 101.

[0116] In some embodiments, the third storage cavity 106 can be two, for example, one is a sample cavity 162 and the other is a buffer cavity 163. In the above step S2, the pipetting device 300 is used to first take x μl of sample from the sample cavity 162, then take (20-x) μl of buffer from the buffer cavity 163, and then transfer 20 μl of the mixed liquid into the sample processing cavity 101. Specifically, before use, the sample cavity 162, the second interface 131 of the temporary storage cavity 103, the vent hole 108, and the third interface 111 of the sample processing cavity 101 are sealed by a layer of pre-stuck film to ensure that the liquid in the microfluidic chip 100 does not leak. When in use, the user tears off part of the film to make the sample cavity 162, the temporary storage cavity 103, and the vent hole 108 communicate with the outside world, and then a fixed volume of the first sample is input into the sample cavity 162 through the pipetting device 300.

[0117] Step S3, driving the second sample in the first storage cavity 104 to be transferred into the sample processing cavity 101.

[0118] Specifically, the driving device 200 provides a driving force, and under the action of the driving force, the second sample in the first storage cavity 104 is transferred into the sample processing cavity 101. The driving force can be a centrifugal force. Under the action of the centrifugal force, the first on-off assembly 141 is opened, so that the second sample enters the sample processing cavity 101 and mixes with the first sample. Note that the second on-off assembly 151 is not opened at this time, and the third sample in the second storage cavity 105 will not enter the sample processing cavity 101.

[0119] In other embodiments, when the temporary storage cavity 103 communicates with the sample processing cavity 101 through the first storage cavity 104, the first sample and the second sample are simultaneously transferred into the sample processing cavity 101, and the step S3 includes the following steps:

[0120] Step S31, providing a first centrifugal force for the microfluidic chip 100, and under the action of the first centrifugal force, the first sample in the temporary storage cavity 103 is transferred into the first storage cavity 104 and forms a first mixture with the second sample in the first storage cavity 104.

[0121] Step S32, a second centrifugal force is provided for the microfluidic chip 100, under the action of the second centrifugal force, the first storage cavity 104 is in communication with the sample processing cavity 101, and the second storage cavity 105 is disconnected with the sample processing cavity 101, and the first mixture is transferred to the sample processing cavity 101.

[0122] In some embodiments, a mixing area is arranged between the first storage cavity 104 and the sample processing cavity 101, and before the first mixture is transferred to the sample processing cavity 101, the method further comprises:

[0123] Under the action of the second centrifugal force, the first mixture is mixed in the mixing area.

[0124] Step S4, the first sample and the second sample are subjected to a first processing process in the sample processing cavity 101 to obtain a first processing product.

[0125] It can be understood that the first processing process can be simple sample mixing, or biochemical reaction of the first sample and the second sample. Specifically, the first processing process is a first reaction of the first sample and the second sample to obtain a first product.

[0126] In some embodiments, the second sample can be a first reagent required for biochemical reaction.

[0127] Step S5, a third sample in the second storage cavity 105 is driven to be transferred to the sample processing cavity 101.

[0128] Specifically, a driving force is provided by the driving device 200, under the action of the driving force, the third sample in the second storage cavity 105 is transferred to the sample processing cavity 101. The driving force can be a third centrifugal force, under the action of the third centrifugal force, the second on-off assembly 151 is opened, the second storage cavity 105 is in communication with the sample processing cavity 101, so that the third sample enters the sample processing cavity 101 and mixes with the first processing product.

[0129] In some embodiments, the third sample can be a second reagent required for biochemical reaction.

[0130] Step S6, a second processing process of the third sample and the first processing product occurs in the sample processing cavity 101 to obtain a second processing product.

[0131] It can be understood that the second processing process can be simple sample mixing, or biochemical reaction of the third sample and the first product. Specifically, the second processing process is a second reaction of the third sample and the first product to obtain a second product.

[0132] Step S7, the second processing product in the sample processing cavity 101 is taken out by the pipetting device 300.

[0133] Specifically, the pipetting device 300 takes out the final product in the sample processing cavity 101 via the third interface 111.

[0134] It can be understood that the number of storage cavities 102 for storing reagents can be designed according to the number of reagent types actually added and the number of reaction steps, and the transfer of reagents and biochemical reactions are performed according to steps S3 and S4, or steps S5 and S6.

[0135] In some embodiments, steps S4 and S5 need to apply a certain temperature control strategy to the sample processing cavity 101 when the biochemical reaction occurs, so that the sample in it can realize temperature rise and fall. Specifically, during steps S4 and S6, the microfluidic chip 100 stops rotating, and the temperature control device 400 is controlled to move relative to the microfluidic chip 100 in the direction of the rotation axis, so that the temperature control device 400 can control the temperature of the region of the sample processing cavity 101.

[0136] The sample processing system 1000 provided by the embodiments has the following beneficial effects:

[0137] (1) Through the structural design of the microfluidic chip 100, the samples in the first storage cavity 104 and the second storage cavity 105 can be transferred step by step to the same sample processing cavity 101, so that the same sample processing cavity 101 can realize a multi-step sample processing process (such as a biochemical reaction process), that is, different reagent storage cavities can input different reagent samples into the same sample processing cavity 101 and perform multi-step reactions, thereby reducing sample loss, and the design of the temperature control device 400 is simpler and the cost is lower.

[0138] (2) Through the cooperation of the microfluidic chip 100 and the pipetting device 300, the transfer of samples with uncertain volumes can be realized, overcoming the shortcomings of the existing microfluidic scheme that it is difficult to transfer part of the liquid in the cavity.

[0139] (3) The pipetting device 300 is only used for transferring samples and outputting the final processed reaction product, and does not participate in the addition and mixing of samples in the intermediate steps. Due to the rotational movement of the microfluidic chip 100, the pipetting device 300 only needs to move along the radial direction of the microfluidic chip 100 to reach every corner of the chip, reducing the movement freedom, movement stroke range and system complexity of the pipetting device 300, and reducing the cost and volume of the sample processing system 1000.

[0140] (3) Since the pipetting device 300 does not participate in the intermediate steps of sample addition and mixing, the use of disposable consumables (such as pipette tips) is greatly reduced, and even no disposable pipette tips can be used, and reusable reagent needles can be used, and the reagent needles can be cleaned in parallel when the microfluidic chip 100 performs the intermediate steps, thereby shortening the system running time.

[0141] Referring to FIG. 7, the biochemical reaction system 2000 can include a control module 2100 and the aforementioned sample processing system 1000 connected in communication with the control module 2100. In the field of gene sequencing, the biochemical reaction system 2000 can be, for example, a library construction instrument or a sequencer, i.e., the aforementioned sample processing system 1000 can be integrated in the library construction instrument or the sequencer for performing construction of a gene sequencing library.

[0142] Referring to FIG. 8, the biochemical detection system 3000 can include a detection module 3100 and the aforementioned sample processing system 1000, wherein the sample processing system 1000 is used to process a sample to obtain a product, and the detection module 3100 is used to detect the product. The aforementioned sample processing system 1000 is used to perform biochemical reactions to obtain reaction products, and then the detection module 3100 can be used to detect the reaction products, which can be, for example, a fluorescence detection module.

[0143] Three microfluidic chips with different implementation forms are given below, and the aforementioned microfluidic chip is further described through the description of specific embodiments.

[0144] Embodiment 1

[0145] Referring to FIG. 9A, and also referring to FIG. 1, the microfluidic chip 100a in this embodiment provides a structural form, which specifically defines the structural form of the first on-off assembly 141 and the second on-off assembly 151, and the arrangement of the temporary storage cavity 103 based on the aforementioned microfluidic chip 100.

[0146] In the microfluidic chip 100a, the first on-off assembly 141 can include a siphon valve 142, the siphon valve 142 has a wave crest a1 (i.e. the local area closest to the rotation center a of the flow channel of the siphon valve 142), specifically, the first storage cavity 104 is communicated with the sample processing cavity 101 through the siphon valve 142 and the first flow channel 143, and the communication or disconnection between the first storage cavity 104 and the sample processing cavity 101 can be realized through the siphon valve 142. In some embodiments, the second on-off assembly 151 can include a siphon valve 152 and a capillary valve 153, wherein the siphon valve 152 has two wave crests, namely wave crest b1 and wave crest b2, and the capillary valve 153 is located between the two wave crests b1 and b2, specifically, the second storage cavity 105 is communicated with the sample processing cavity 101 through the siphon valve 152, the capillary valve 153 and the second flow channel 154, and the communication or disconnection between the second storage cavity 105 and the sample processing cavity 101 can be realized through the cooperation of the siphon valve 152 and the capillary valve 153. Through the design of the first on-off assembly 141 and the second on-off assembly 151, the purpose of opening the first on-off assembly 141 and the second on-off assembly 151 at different stages can be realized by controlling the size of the centrifugal force, and then the communication between the first storage cavity 104 and the second storage cavity 105 and the sample processing cavity 101 at different times can be realized. The action process and principle of the first on-off assembly 141 and the second on-off assembly 151 are described in detail in the sample processing method.

[0147] The microfluidic chip 100a is roughly fan-shaped or circular, and the center of the microfluidic chip 100a is the rotation center a, and the temporary storage cavity 103 is arranged close to the rotation center a, at this time, the temporary storage cavity 103 is directly communicated with the first storage cavity 104, and communicated with the sample processing cavity 101 through the first storage cavity 104.

[0148] In the microfluidic chip 100a, the number of the third storage cavities 106 is two, which are the sample cavity 162 and the buffer cavity 163, and the sample cavity 162 and the buffer cavity 163 are arranged along the radial direction of the microfluidic chip 100a, and the temporary storage cavity 103 and the buffer cavity 163 are arranged along the circumferential direction of the microfluidic chip 100a.

[0149] In the microfluidic chip 100a, a mixing zone is arranged between the first storage cavity 104 and the sample processing cavity 101, and the mixing zone is formed by bending the first flow channel 143 which communicates the first storage cavity 104 and the sample processing cavity 101, and the first flow channel 143 between the first on-off assembly 141 and the sample processing cavity 101 can be formed into a folding structure by multiple bending, which can realize preliminary mixing when the sample flows through this place.

[0150] In the microfluidic chip 100a, only one vent hole 108 can be provided, which is in communication with the first storage cavity 104, the second storage cavity 105 and the sample processing cavity 101 through microfluidic channels, so as to realize the communication of the three cavities with the atmosphere, thereby facilitating the smooth transfer of the sample between different cavities during centrifugation.

[0151] Referring to FIGS. 9A to 9K, and in combination with FIG. 1, the method for processing a sample using the microfluidic chip 100a includes the following steps:

[0152] In the initial state, as shown in FIG. 9A, and in combination with FIG. 1, a fixed volume (for example, 20 μl, 40 μl) of the first reagent and the second reagent has been respectively packaged in the first storage cavity 104 and the second storage cavity 105, a fixed volume (for example, 20 μl) of the buffer has been packaged in the buffer cavity 163 of the third storage cavity 106, and the sample cavity 162, the second interface 131 of the temporary storage cavity 103, the vent hole 108 and the third interface 111 of the sample processing cavity 101 are sealed by a layer of pre-stuck film, so as to ensure that the liquid in the microfluidic chip 100a will not leak. Before use, the user tears part of the film to make the sample cavity 162, the temporary storage cavity 103 and the vent hole 108 communicate with the outside, and then inputs a fixed volume (for example, 20 μl) of the biological sample into the sample cavity 162 through the pipetting device 300.

[0153] After the above initial state preparation is completed, the microfluidic chip 100a enters the automatic sample processing process.

[0154] In the first step, as shown in FIG. 9B, and in combination with FIG. 1, the microfluidic chip 100a remains stationary, and the pipetting device 300 moves radially to the sample cavity 162 to suck the biological sample x μl, and the specific value of x is determined by measuring the concentration of the biological sample.

[0155] In the second step, as shown in FIGS. 9C and 9D, and in combination with FIG. 1, the microfluidic chip 100a remains stationary, and the pipetting device 300 moves radially to the buffer cavity 163 to suck the buffer (20-x) μl. Further, the microfluidic chip 100a is rotated to make the second interface 131 of the temporary storage cavity 103 reach below the pipetting device 300, and the pipetting device 300 transfers the mixture of the biological sample and the buffer with a total volume of 20 μl into the temporary storage cavity 103.

[0156] Step 3, as shown in FIG. 9E, in combination with FIG. 1, the driving device 200 drives the microfluidic chip 100a to rotate from static state at a high speed (e.g. 1000 rpm), the centrifugal force drives the mixture of 20 μl of biological sample and buffer to reach the first storage cavity 104, at the same time, part of the sample in the first storage cavity 104 enters the siphon valve 142, part of the sample in the second storage cavity 105 enters the siphon valve 152, until the liquid level in the siphon valves 142 and 152 is flush with the liquid level of the remaining sample in the two cavities (i.e. the same distance from the center).

[0157] Step 4, as shown in FIG. 9F, in combination with FIG. 1, the microfluidic chip 100a is controlled by the driving device 200 to reduce from the above-mentioned high speed to a low speed (e.g. 600 rpm), at this time, due to the smaller centrifugal force, the liquid level in the siphon valve 142 will overcome the wave crest a1 under the action of capillary force, and realize preliminary mixing in the curved mixing area formed by the downstream first flow channel 143, and finally enter the sample processing cavity 101; at this time, the siphon valve 152 has two wave crests b1 and b2 and a capillary valve 153, the capillary valve 153 can be set to be unable to open at a low speed, when the liquid level in the siphon valve 152 overcomes the first wave crest b1 under the action of capillary force, due to the existence of the capillary valve 153, the sample will stop at the capillary valve 153, and will not further overcome the second wave crest b2 to enter the sample processing cavity 101.

[0158] Step 5, as shown in FIG. 9G, in combination with FIG. 1, when the liquid sample (the mixture of the first reagent, the biological sample and the buffer) in the first storage cavity 104 completely reaches the sample processing cavity 101, the microfluidic chip 100a is controlled to stop rotating, and the lower surface 110 of the sample processing cavity 101 interacts with the temperature control device 400 to realize the temperature rising and falling operation of the sample processing cavity 101, and the first reaction is carried out.

[0159] Step 6, as shown in FIG. 9H and FIG. 91, in combination with FIG. 1, after the first reaction is completed, the lower surface 110 of the sample processing cavity 101 is separated from the temperature control device 400, and the microfluidic chip 100a is controlled to rotate at a high speed (e.g. 1000 rpm) again, at this time the centrifugal force is sufficient to open the capillary valve 153; then the microfluidic chip 100a is reduced to a low speed (e.g. 600 rpm), the second reagent further overcomes the second wave crest b2 of the siphon valve 152, and finally reaches the sample processing cavity 101 through the second flow channel 154.

[0160] Step 7, as shown in FIG. 9J, in combination with FIG. 1, when the second reagent in the second storage cavity 105 reaches the sample processing cavity 101 completely, the microfluidic chip 100a is controlled to rotate forward and reverse alternately at a certain acceleration to realize the mixing of the sample in the sample processing cavity 101. In another embodiment, the microfluidic chip 100a can also be controlled to rotate in one direction with acceleration and deceleration to realize the mixing effect. After the mixing is completed, the microfluidic chip 100a stops rotating, and interacts with the temperature control device 400 through the surface 110 below the sample processing cavity 101 to realize the temperature rising and falling operation of the sample processing cavity 101, and performs the second reaction.

[0161] Step 8, as shown in FIG. 9K, in combination with FIG. 1, when the second reaction is completed, the radial movement of the pipetting device 300 and the circumferential rotation movement of the microfluidic chip 100a are combined to make the pipetting device 300 reach above the third interface 111 and interact with the third interface 111, so as to take out the reactants in the sample processing cavity 101. Thus, the sample processing process is completed.

[0162] As shown in FIG. 9L, the microfluidic chip 100a containing a plurality of sample processing regions 10 is shown, which contains four independent modules as shown in FIG. 9A, and can realize the synchronous processing of four different samples.

[0163] Embodiment 2

[0164] Referring to FIG. 10A, in combination with FIG. 1, the present embodiment provides a second structural form of the microfluidic chip 100b, which specifically defines the structural form of the first on-off assembly 141 and the second on-off assembly 151, and the setting mode of the temporary storage cavity 103 on the basis of the aforementioned microfluidic chip 100.

[0165] In the microfluidic chip 100b, the temporary storage cavity 103 is in communication with the first storage cavity 104, and the first storage cavity 104 and the second storage cavity 105 are in communication through the third on-off assembly 107, which can realize the communication or disconnection of the first storage cavity 104 and the second storage cavity 105. Among them, the third on-off assembly 107 can also include at least one of the valves such as capillary valve, hydrophobic valve, siphon valve and active valve.

[0166] Specifically, in the microfluidic chip 100b, the first on-off component 141 can include a siphon valve 144, the siphon valve 144 has a wave crest a2, specifically, the first storage cavity 104 is communicated with the sample processing cavity 101 through the siphon valve 144, and the communication or disconnection between the first storage cavity 104 and the sample processing cavity 101 can be realized through the siphon valve 144. The second on-off component 151 can include a siphon valve 155, wherein the siphon valve 155 has a wave crest b3, specifically, the second storage cavity 105 is communicated with the sample processing cavity 101 through the siphon valve 155 and the second flow channel 154, and the communication or disconnection between the second storage cavity 105 and the sample processing cavity 101 can be realized through the siphon valve 155. The third on-off component 107 can include a siphon valve, and the communication or disconnection between the first storage cavity 104 and the second storage cavity 105 can be realized by setting the siphon valve.

[0167] Through the design of the first on-off component 141, the second on-off component 151 and the third on-off component 107, the first on-off component 141, the second on-off component 151 and the third on-off component 107 can be opened at different stages by controlling the size of the centrifugal force, thereby realizing the communication between the first storage cavity 104 and the second storage cavity 105 and the sample processing cavity 101 at different times. The on-off principle of the siphon valve is the same as that in the foregoing embodiment 1, and the process and principle of realizing the communication are described in detail in the subsequent sample processing method.

[0168] The microfluidic chip 100b is roughly fan-shaped or circular, and the center of the microfluidic chip 100b is the rotation center a, and the temporary storage cavity 103 is arranged close to the rotation center a.

[0169] In the microfluidic chip 100b, the number of the third storage cavities 106 is two, which are a sample cavity 162 and a buffer cavity 163, and the sample cavity 162 and the buffer cavity 163 are arranged along the radial direction of the microfluidic chip 100b, and the temporary storage cavity 103 and the buffer cavity 163 are arranged along the circumferential direction of the microfluidic chip 100b.

[0170] In the microfluidic chip 100b, a mixing area is arranged between the first storage cavity 104 and the sample processing cavity 101, the mixing area is curved by the first flow channel 143 which communicates the first storage cavity 104 and the sample processing cavity 101, and the first flow channel 143 between the first on-off component 141 and the sample processing cavity 101 can be folded to form a folding structure, so that the sample can be mixed when flowing through the folding structure.

[0171] In the microfluidic chip 100b, only two air holes 108 can be provided, one air hole 108 is in communication with the first storage cavity 104, which can simultaneously realize the communication of the first storage cavity 104 and the second storage cavity 105 with the atmosphere. The other air hole 108 is in communication with the sample processing cavity 101, thereby realizing the communication of the sample processing cavity 101 with the atmosphere.

[0172] Referring to FIGS. 10A to 10H, and in combination with FIG. 1, the method for sample processing using the microfluidic chip 100b includes the following steps:

[0173] As shown in FIG. 10A, the initial state of the microfluidic chip 100b is basically the same as that of Embodiment 1. Please refer to the aforementioned Embodiment 1, which will not be described in detail here.

[0174] After the initial state is prepared, the microfluidic chip 100b enters the automatic sample processing process, which includes the following steps:

[0175] The first step and the second step, the processing method of the sample and the buffer is basically the same as that of Embodiment 1. Please refer to the first step and the second step of the aforementioned Embodiment 1, which will not be described in detail here.

[0176] The third step, as shown in FIG. 10B, and in combination with FIG. 1, the driving device 200 drives the microfluidic chip 100b to rotate at a certain high speed (such as 1000 rpm) from static state, the centrifugal force drives 20 μl of the mixture of the sample and the buffer to reach the first storage cavity 104, at the same time, part of the sample in the first storage cavity 104 enters the siphon valve 144, and part of the sample in the second storage cavity 105 enters the siphon valve 155, until the liquid level in the siphon valves 144 and 155 is flush with the liquid level of the remaining sample in the two cavities.

[0177] The fourth step, as shown in FIG. 10C, and in combination with FIG. 1, the microfluidic chip 100b is controlled by the driving device 200 to reduce from the above-mentioned high speed to a lower speed (for example, 600 rpm), at this time, due to the smaller centrifugal force, the liquid level in the siphon valve 144 will overcome the wave crest a2 under the action of capillary force. At this time, since the second storage cavity 105 is not in communication with the atmosphere, the second reagent in it cannot overcome the siphon valve 155.

[0178] The fifth step, as shown in FIG. 10D, and in combination with FIG. 1, when the liquid sample (the mixture of the first reagent, the biological sample and the buffer) in the first storage cavity 104 is preliminarily mixed through the curved first flow channel 143 and finally completely reaches the sample processing cavity 101, the microfluidic chip 100b is controlled to stop rotating, and the temperature control device 400 is interacted through the lower surface 110 of the sample processing cavity 101 to realize the temperature rising and falling operation of the sample processing cavity 101, and the first reaction is carried out.

[0179] Step 6, as shown in FIG. 10E and FIG. 10F, and in combination with FIG. 1, after the first reaction, the lower surface 110 of the sample processing cavity 101 is detached from the temperature control device 400, and the driving device 200 controls the microfluidic chip 100b to rotate at a higher speed (e.g., 1000 rpm) and then to rotate at a lower speed (e.g., 600 rpm). At this time, since the liquid in the first storage cavity 104 has been completely drained, the second storage cavity 105 can actually communicate with the atmosphere through the third on-off assembly 107 (e.g., a siphon valve), so that the second reagent in the second storage cavity 105 can pass over the wave crest b3 of the siphon valve 155 and finally reach the sample processing cavity 101.

[0180] Step 7, as shown in FIG. 10G, and in combination with FIG. 1, when the second reagent in the second storage cavity 105 completely reaches the sample processing cavity 101, the microfluidic chip 100b is controlled to rotate in a certain acceleration in the forward direction and in the reverse direction alternately to realize the mixing of the liquid in the sample processing cavity 101. In another embodiment, the microfluidic chip 100b can also be controlled to rotate in one direction with acceleration and deceleration to achieve the mixing effect. After the mixing is completed, the microfluidic chip 100b stops rotating, and the lower surface 110 of the sample processing cavity 101 interacts with the temperature control device 400 to realize the temperature rising and falling operation of the sample processing cavity 101, and the second reaction is performed.

[0181] Step 8, as shown in FIG. 10H, and in combination with FIG. 1, after the second reaction, the radial movement of the pipetting device 300 and the circumferential rotation movement of the microfluidic chip 100b are combined to make the pipetting device 300 reach above the third interface 111 and interact with the third interface 111, so as to take out the reaction substance in the sample processing cavity 101. Thus, the sample processing process is completed.

[0182] Example 3

[0183] Referring to FIG. 11A, and in combination with FIG. 1, the present embodiment provides a microfluidic chip 100c in a structural form, which specifically defines the structural form of the first on-off assembly 141 and the second on-off assembly 151, and the setting manner of the temporary storage cavity 103 on the basis of the aforementioned microfluidic chip 100.

[0184] In the microfluidic chip 100c, the temporary storage cavity 103 is directly communicated with the sample processing cavity 101. The first on-off component 141 and the second on-off component 151 can be active valves, specifically paraffin valves. At this time, the temperature control device 400 can also provide temperature for the first on-off component 141 and the second on-off component 151 to realize the opening of the active valves. The first on-off component 141 and the second on-off component 151 can be heated at different stages by the temperature control device 400, so as to realize the opening of the two at different stages, so as to realize the non-simultaneous communication between the first storage cavity 104 and the second storage cavity 105 and the sample processing cavity 101.

[0185] The microfluidic chip 100c is roughly fan-shaped or circular, and the center of the microfluidic chip 100c is the rotation center a, and the temporary storage cavity 103 is arranged close to the rotation center a.

[0186] In the microfluidic chip 100c, the number of the third storage cavities 106 is two, which are the sample cavity 162 and the buffer cavity 163, and the temporary storage cavity 103, the sample cavity 162 and the buffer cavity 163 are arranged along the radial direction of the microfluidic chip 100c.

[0187] In the microfluidic chip 100b, only one air hole 108 can be arranged, and specifically the air hole 108 is communicated with the first storage cavity 104, the second storage cavity 105 and the sample processing cavity 101 through the microfluidic channel, so as to realize the communication between the above three cavities and the atmosphere, so as to facilitate the smooth transfer of the sample between different cavities during the centrifugation process.

[0188] Please refer to FIGS. 11A to 11H, and refer to FIG. 1, the method for processing the sample using the microfluidic chip 100c includes the following steps:

[0189] As shown in FIG. 11A, the initial state of the microfluidic chip 100c is basically the same as that of the embodiment 1, please refer to the aforementioned embodiment 1, which will not be repeated here.

[0190] After the initial state is prepared, the microfluidic chip 100c enters the automatic sample processing process, which specifically includes the following steps:

[0191] The first step and the second step, as shown in FIG. 11B, the processing mode of the sample and the buffer is basically the same as that of the embodiment 1, please refer to the first step and the second step of the aforementioned embodiment 1, which will not be repeated here.

[0192] The third step, as shown in FIG. 11C, and refer to FIG. 1, the driving device 200 drives the microfluidic chip 100c to start rotating at a certain high speed (such as 1000 rpm) from static state, and the centrifugal force drives the mixture of 20 μl of sample and buffer to directly enter the sample processing cavity 101 from the temporary storage cavity 103.

[0193] Step 4, as shown in FIG. 11D, in combination with FIG. 1, the microfluidic chip 100c is controlled to stop rotating by the driving device 200, and the lower surface 112 of the paraffin valve 145 interacts with the temperature control device 400 to heat the paraffin valve 145, so that the solid paraffin melts into liquid, and then the microfluidic chip 100c is controlled to rotate to transfer the first reagent from the first storage cavity 104 to the sample processing cavity 101.

[0194] Step 5, as shown in FIG. 11E, in combination with FIG. 1, when the first reagent in the first storage cavity 104 completely reaches the sample processing cavity 101, the microfluidic chip 100c is controlled to rotate forward and reverse alternately at a certain acceleration to mix the liquid in the sample processing cavity 101. In another embodiment, the microfluidic chip 100c can also be controlled to rotate at a certain acceleration in one direction to achieve the mixing effect. After mixing, the microfluidic chip 100c is controlled to stop rotating, and the lower surface 110 of the sample processing cavity 101 interacts with the temperature control device 400 to heat the sample processing cavity 101, and the first reaction is carried out.

[0195] Step 6, as shown in FIG. 11F, in combination with FIG. 1, after the first reaction is completed, the lower surface 110 of the sample processing cavity 101 is separated from the temperature control device 400, the lower surface 113 of the paraffin valve 156 interacts with the temperature control device 400 to heat the paraffin valve 156, so that the solid paraffin melts into liquid, and then the microfluidic chip 100c is controlled to rotate to transfer the second reagent from the second storage cavity 105 to the sample processing cavity 101.

[0196] Step 7, as shown in FIG. 11G, in combination with FIG. 1, when the second reagent in the second storage cavity 105 completely reaches the sample processing cavity 101, the microfluidic chip 100c is controlled to rotate forward and reverse alternately at a certain acceleration to mix the liquid in the sample processing cavity 101. In another embodiment, the microfluidic chip 100c can also be controlled to rotate at a certain acceleration in one direction to achieve the mixing effect. After mixing, the microfluidic chip 100c is controlled to stop rotating, and the lower surface 110 of the sample processing cavity 101 interacts with the temperature control device 400 to heat the sample processing cavity 101, and the second reaction is carried out.

[0197] Step 8, as shown in FIG. 11H, in combination with FIG. 1, when the second reaction is completed, the radial movement of the pipetting device 300 and the circumferential rotation movement of the microfluidic chip 100c are combined to make the pipetting device 300 reach above the third interface 111 and interact with the third interface 111, so as to take out the reactants in the sample processing cavity 101. Thus, the sample processing process is completed.

[0198] It should be noted that the above-mentioned embodiments are only used to illustrate the technical solutions of the present application but not to limit the present application. Although the present application is described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalent replaced without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A microfluidic chip, characterized by, The sample processing region comprises at least one sample processing area, the sample processing area comprises: a sample processing cavity for providing space for sample processing; and a plurality of storage cavities for storing samples, the plurality of storage cavities comprising a first storage cavity, a second storage cavity and a third storage cavity, the first storage cavity and the second storage cavity are both in communication with the sample processing cavity, and the first storage cavity and the second storage cavity are not simultaneously in communication with the sample processing cavity, the third storage cavity is not in communication with the sample processing cavity, and the third storage cavity has a first interface for interacting with a pipetting device to transfer a sample in the third storage cavity to the sample processing cavity.

2. The microfluidic chip of claim 1, wherein, A first on-off component is provided between the first storage cavity and the sample processing cavity, the first on-off component is used to control the communication or disconnection between the first storage cavity and the sample processing cavity, a second on-off component is provided between the second storage cavity and the sample processing cavity, the second on-off component is used to control the communication or disconnection between the second storage cavity and the sample processing cavity, and the first on-off component and the second on-off component are not opened at the same time.

3. The microfluidic chip of claim 2, wherein, The first on-off component comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve and an active valve. The second on-off component comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve and an active valve.

4. The microfluidic chip of claim 3, wherein, The active valve comprises at least one of a paraffin valve and a pneumatic valve.

5. The microfluidic chip of claim 1, wherein, The sample processing region further comprises a temporary storage cavity in communication with the sample processing cavity, the temporary storage cavity has a second interface for interacting with the pipetting device to transfer the sample in the third storage cavity to the temporary storage cavity.

6. The microfluidic chip of claim 5, wherein, The temporary storage cavity is directly in communication with the sample processing cavity; or the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity.

7. The microfluidic chip of claim 6, wherein, When the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, a mixing zone is provided between the first storage cavity and the sample processing cavity.

8. The microfluidic chip of claim 7, wherein, The mixing zone is formed by bending a first flow channel that communicates the first storage cavity and the sample processing cavity.

9. The microfluidic chip of claim 6, wherein, When the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, the first storage cavity can also be in communication with the second storage cavity, a third on-off component is provided between the first storage cavity and the second storage cavity, the third on-off component is used to control the communication and disconnection between the first storage cavity and the second storage cavity.

10. The microfluidic chip of claim 9, wherein, The third on-off component comprises at least one of a capillary valve, a hydrophobic valve, a siphon valve and an active valve.

11. The microfluidic chip of claim 6, wherein, The microfluidic chip comprises oppositely arranged first and second edges, the third storage cavity is close to the first edge, the sample processing cavity is close to the second edge, and the first and second storage cavities are located between the sample processing cavity and the third storage cavity.

12. The microfluidic chip of claim 11, wherein, The microfluidic chip is fan-shaped or circular, the first edge is close to the center of the microfluidic chip, when the temporary storage cavity is directly communicated with the sample processing cavity, the temporary storage cavity is close to the second edge, and the third storage cavity is arranged along the radial direction of the microfluidic chip.

13. The microfluidic chip of claim 12, wherein, The microfluidic chip comprises a plurality of sample processing regions, and the plurality of sample processing regions are arranged along the circumferential direction of the microfluidic chip.

14. The microfluidic chip of claim 1, wherein, The sample processing cavity is provided with a third interface, and the third interface is used for the pipetting device to take out the sample in the sample processing cavity. The microfluidic chip is further provided with at least one vent hole, and the sample processing cavity, the first storage cavity and the second storage cavity are communicated with the external environment through the vent hole.

15. A sample processing system, comprising: Comprise: The microfluidic chip is as claimed in any one of claims 1 to 14; The pipetting device is used for interacting with the first interface of the third storage cavity to transfer the first sample in the third storage cavity to the sample processing cavity; And The driving device is used for driving the second sample in the first storage cavity and the third sample in the second storage cavity to be transferred to the sample processing cavity, respectively.

16. The sample processing system of claim 15, wherein, The driving device drives the microfluidic chip to rotate around a rotation center to generate a centrifugal force, and the centrifugal force is used for driving the second sample in the first storage cavity and the third sample in the second storage cavity to be transferred to the sample processing cavity, respectively.

17. The sample processing system of claim 15, wherein, When the sample processing region further comprises the temporary storage cavity, the pipetting device is used for transferring the first sample in the third storage cavity to the temporary storage cavity, and the driving device is further used for driving the first sample in the temporary storage cavity to be transferred to the sample processing cavity.

18. The sample processing system of claim 16, wherein, The pipetting device can move linearly along a first direction and a second direction perpendicular to each other, the first direction is the radial direction of the rotation of the microfluidic chip, and the second direction is perpendicular to the rotation plane of the microfluidic chip.

19. The sample processing system of claim 18, wherein, The pipetting device comprises a fixed arm and a pipetting arm, the fixed arm is arranged at the rotation center, one end of the pipetting arm is arranged on the fixed arm, the end of the pipetting arm away from the fixed arm is located on the side of the microfluidic chip away from the driving device, and the pipetting arm can move linearly along the first direction and the second direction.

20. The sample processing system of claim 15, wherein, Further comprising a temperature control device, the temperature control device is used for providing a temperature required for biochemical reaction for the sample processing cavity.

21. The sample processing system of claim 20, wherein, When the first on-off component or the second on-off component is a paraffin valve, the temperature control device is further used for heating the first on-off component or the second on-off component.

22. The sample processing system of claim 20, wherein, The temperature control device is arranged on the side of the microfluidic chip close to the driving device, and the temperature control device can move towards or away from the microfluidic chip.

23. A method of sample processing, comprising: Comprise: Providing a microfluidic chip, the microfluidic chip is as claimed in any one of claims 1 to 14; Transferring the first sample in the third storage cavity to the sample processing cavity; Driving the second sample in the first storage cavity to transfer to the sample processing cavity; The first sample and the second sample in the sample processing cavity are subjected to a first processing process to obtain a first processing product; Driving the third sample in the second storage cavity to transfer to the sample processing cavity; And The first processing product and the third sample in the sample processing cavity are subjected to a second processing process to obtain a second processing product.

24. The sample processing method of claim 23, wherein, When the sample processing region further comprises the temporary storage cavity, The step of transferring the first sample in the third storage cavity to the sample processing cavity comprises: Transferring the first sample in the third storage cavity to the temporary storage cavity by a pipetting device; and Providing driving force for the microfluidic chip by a driving device to transfer the first sample in the temporary storage cavity to the sample processing cavity.

25. The sample processing method of claim 23, wherein, When the number of the third storage cavities is two, the two third storage cavities are respectively a sample cavity for storing a first sample and a buffer cavity for storing a buffer, and the step of transferring the first sample in the third storage cavity to the temporary storage cavity by a pipetting device comprises: Transferring a first volume of the first sample from the sample cavity to the temporary storage cavity by the pipetting device, and transferring a second volume of the buffer from the buffer cavity to the temporary storage cavity by the pipetting device, wherein the sum of the first volume and the second volume is equal to the volume of all the first sample stored in the sample cavity.

26. The sample processing method of claim 24, wherein, When the temporary storage cavity is in communication with the sample processing cavity through the first storage cavity, the transfer of the first sample and the second sample to the sample processing cavity is performed synchronously, comprising: Providing a first centrifugal force for the microfluidic chip by a driving device to drive the first sample in the temporary storage cavity to transfer to the first storage cavity and form a first mixture with the second sample; and Providing a second centrifugal force for the microfluidic chip by a driving device to make the first storage cavity in communication with the sample processing cavity, and the second storage cavity is disconnected from the sample processing cavity, and drive the first mixture in the first storage cavity to transfer to the sample processing cavity.

27. The sample processing method of claim 26, wherein, A mixing zone is provided between the first storage cavity and the sample processing cavity, and before the first mixture is transferred to the sample processing cavity, the method further comprises: The first mixture is mixed in the mixing zone under the action of the second centrifugal force.

28. The sample processing method of claim 26, wherein, The step of driving the third sample in the second storage cavity to transfer to the sample processing cavity comprises: The driving device provides a third centrifugal force for the microfluidic chip, so that the second storage cavity is communicated with the sample processing cavity, and the third sample in the second storage cavity is driven to move into the sample processing cavity.

29. The sample processing method of claim 23, wherein, After obtaining the second processing product, the method further comprises: The second processing product in the sample processing cavity is taken out by a pipetting device.

30. A biochemical reaction system, characterized in that: A sample processing system as claimed in any one of claims 15 to 21.

31. A biochemical detection system, characterized by, A detection module and a sample processing system as claimed in any one of claims 15 to 21, wherein the sample processing system is used to process a sample to obtain a product, and the detection module is used to detect the product.

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