WO2025217812A1 - 微流控芯片、样本处理系统及其应用、以及样本处理方法 - Google Patents

微流控芯片、样本处理系统及其应用、以及样本处理方法

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Publication number
WO2025217812A1
WO2025217812A1 PCT/CN2024/088070 CN2024088070W WO2025217812A1 WO 2025217812 A1 WO2025217812 A1 WO 2025217812A1 CN 2024088070 W CN2024088070 W CN 2024088070W WO 2025217812 A1 WO2025217812 A1 WO 2025217812A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample processing
sample
chamber
storage chamber
microfluidic chip
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/088070
Other languages
English (en)
French (fr)
Inventor
陆灏
陈泽华
孙磊林
牛子华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
MGI Tech Co Ltd
Original Assignee
MGI Tech Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by MGI Tech Co Ltd filed Critical MGI Tech Co Ltd
Priority to PCT/CN2024/088070 priority Critical patent/WO2025217812A1/zh
Publication of WO2025217812A1 publication Critical patent/WO2025217812A1/zh
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers

Definitions

  • 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.
  • samples Before conducting biochemical reactions in the fields of biology, medicine, chemical engineering, etc., samples usually need to be pre-processed. For example, before gene sequencing, the original biological samples need to undergo a large number of operations or biochemical reactions, such as filtration, purification, circularization, amplification, etc., in order to obtain samples (such as sequencing libraries) that can be accepted by detection instruments such as gene sequencers.
  • biochemical reactions such as filtration, purification, circularization, amplification, etc.
  • the present application also provides a sample processing system and a sample processing method using the aforementioned microfluidic chip, as well as a biochemical reaction system and a biochemical detection system using the sample processing system.
  • an embodiment of the present application provides a microfluidic chip, wherein the microfluidic chip includes at least one sample processing area, and the sample processing area includes: a sample processing chamber and multiple storage chambers, wherein the sample processing chamber is used to provide space for sample processing; the multiple storage chambers are used to store samples, and the multiple storage chambers include a first storage chamber, a second storage chamber, and a third storage chamber, wherein the first storage chamber and the second storage chamber can both be connected to the sample processing chamber, and the first storage chamber and the second storage chamber are not connected to the sample processing chamber at the same time, and the third storage chamber is not connected to the sample processing chamber, and the third storage chamber has a first interface, and the first interface is used to interact with a pipetting device to transfer the sample located in the third storage chamber to the sample processing chamber.
  • a first on-off component is provided between the first storage chamber and the sample processing chamber, and the first on-off component is used to control the connection or disconnection between the first storage chamber and the sample processing chamber.
  • a second on-off component is provided between the second storage chamber and the sample processing chamber, and the second on-off component is used to control the connection or disconnection between the second storage chamber and the sample processing chamber. The first on-off component and the second on-off component are not opened at the same time.
  • the first on-off component includes at least one of a capillary valve, a steam trap, a siphon valve, and an active valve;
  • the second on-off component includes at least one of a capillary valve, a steam trap, a siphon valve and an active valve.
  • the active valve includes at least one of a paraffin valve and a pneumatic valve.
  • the sample processing area further includes a temporary storage chamber, which is connected to the sample processing chamber, and the temporary storage chamber has a second interface, which is used to interact with the pipetting device to transfer the sample located in the third storage chamber to the temporary storage chamber.
  • a mixing zone is provided between the first storage chamber and the sample processing chamber.
  • 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 connected to 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 connected to 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 circumference of the microfluidic chip.
  • a driving device on which the microfluidic chip is detachably mounted, is used to drive the second sample in the first storage chamber and the third sample in the second storage chamber to be transferred to the sample processing chamber respectively.
  • the driving device drives the microfluidic chip to rotate around a rotation center to generate centrifugal force, and the centrifugal force is used to drive the second sample located in the first storage chamber and the third sample located in the second storage chamber to be transferred to the sample processing chamber respectively.
  • the pipetting device is used to transfer the first sample located in the third storage chamber to the temporary storage chamber, and the driving device is also used to drive the first sample located in the temporary storage chamber to be transferred to the sample processing chamber.
  • the pipetting device can perform linear motion along a first direction and a second direction perpendicular to each other, wherein the first direction is the radial direction of rotation of the microfluidic chip, and the second direction is a direction perpendicular to the rotation plane of the microfluidic chip.
  • the pipetting device includes 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, and the end of the pipetting arm away from the fixed arm is located at the microfluidic chip away from the The pipetting arm is located on one side of the driving device, and the pipetting arm can perform linear motion along the first direction and the second direction.
  • the sample processing system further includes a temperature control device, which is used to provide the sample processing chamber with a temperature required for a biochemical reaction.
  • the temperature control device is disposed on a side of the microfluidic chip close to the driving device, and the temperature control device can move toward or away from the microfluidic chip.
  • an embodiment of the present application provides a sample processing method, including:
  • microfluidic chip is the microfluidic chip described above;
  • the first sample and the second sample undergo a first processing process in the sample processing chamber to obtain a first processing product
  • the first processed product and the third sample undergo a second processing process in the sample processing chamber to obtain a second processed product.
  • the sample processing area further includes the temporary storage chamber
  • the step of transferring the first sample in the third storage chamber to the sample processing chamber includes:
  • a driving device provides driving force for the microfluidic chip to transfer the first sample in the temporary storage chamber to the sample processing chamber.
  • the two third storage chambers are respectively a sample chamber for storing the first sample and a buffer chamber for storing the buffer, and the step of transferring the first sample in the third storage chamber to the temporary storage chamber by using the pipetting device includes:
  • a first volume of the first sample is transferred from the sample chamber to the temporary storage chamber by the pipetting device, and a second volume of the buffer is transferred from the buffer chamber to the temporary storage chamber by the pipetting device, wherein the sum of the first volume and the second volume is equal to the volume of all the first samples stored in the sample chamber.
  • the first sample and the second sample are transferred to the sample processing chamber simultaneously, including:
  • a second centrifugal force is provided to the microfluidic chip by a driving device, so that the first storage chamber is connected to the sample processing chamber, and the second storage chamber is disconnected from the sample processing chamber, and the first mixture in the first storage chamber is driven to be transferred to the sample processing chamber.
  • a mixing zone is provided between the first storage chamber and the sample processing chamber. Before the first mixture is transferred to the sample processing chamber, the method further includes:
  • the first mixture is mixed in the mixing zone.
  • the step of driving the third sample in the second storage chamber to be transferred to the sample processing chamber includes:
  • a third centrifugal force is provided to the microfluidic chip by a driving device, so that the second storage chamber is connected to the sample processing chamber, and the third sample in the second storage chamber is driven to be transferred to the sample processing chamber.
  • the method further includes:
  • the second processing product in the sample processing chamber is taken out by a pipetting device.
  • an embodiment of the present application provides a biochemical reaction system, which includes a control module and the sample processing system as described above that is communicatively connected to the control module.
  • an embodiment of the present application provides a biochemical detection system, which includes a detection module and the sample processing system as described above, wherein the sample processing system is used to process the sample to obtain a product, and the detection module is used to detect the product.
  • the samples in the first storage chamber and the second storage chamber can be transferred step by step to the same sample processing chamber, so that a multi-step sample processing process (such as a biochemical reaction process) can be carried out in the same sample processing chamber, that is, different reagent storage chambers can be used to input different reagent samples into the same sample processing chamber in sequence and carry out multi-step reactions, which reduces sample loss, makes the design of the temperature control device simpler, and reduces the cost.
  • a multi-step sample processing process such as a biochemical reaction process
  • the pipette is only used to transfer samples and output the final processed reaction products, and does not participate in the sample addition and mixing in the intermediate steps. Due to the existence of the rotational motion of the microfluidic chip, the pipette only needs to move along the radial direction of the microfluidic chip to reach every corner of the chip, which reduces the degree of freedom of movement, range of motion and system complexity of the pipette, and reduces the cost and volume of the sample processing system.
  • FIG1 is a system framework diagram of a sample processing system in one embodiment of the present application.
  • FIG2 is a schematic structural diagram of a microfluidic chip in an embodiment of the present application.
  • FIG3 is a schematic structural diagram of a sample processing area in FIG2 .
  • FIG4A is a schematic structural diagram of a siphon valve in an embodiment of the present application.
  • 4B and 4C are schematic structural diagrams of a steam trap according to an embodiment of the present application.
  • FIG4E is a schematic structural diagram of a paraffin valve in one embodiment of the present application.
  • FIG4F is a schematic structural diagram of a pneumatic valve in one embodiment of the present application.
  • FIG5 is a schematic structural diagram of a microfluidic chip in another embodiment of the present application.
  • FIG6 is a flow chart of a sample processing method in one embodiment of the present application.
  • FIG7 is a schematic structural diagram of a biochemical reaction system in one embodiment of the present application.
  • FIG8 is a schematic structural diagram of a biochemical detection system in one embodiment of the present application.
  • FIG9A is a schematic structural diagram of a specific implementation of the microfluidic chip shown in FIG2 .
  • 9B to 9K are schematic diagrams of a sample processing process using the microfluidic chip of FIG. 9A .
  • FIG9L is a schematic structural diagram of a microfluidic chip including multiple sample processing areas shown in FIG9A in one embodiment of the present application.
  • FIG10A is a schematic structural diagram of a second specific implementation of the microfluidic chip shown in FIG2 .
  • 10B to 10H are schematic diagrams of a process of performing sample processing using the microfluidic chip of FIG. 10A .
  • FIG. 11A is a schematic structural diagram of a third specific implementation of the microfluidic chip shown in FIG. 2 .
  • 11B to 11H are schematic diagrams of a sample processing process using the microfluidic chip of FIG. 11A .
  • a component when referred to as being “fixed to” or “mounted on” another component, it may be directly on the other component or there may be a central component. When a component is referred to as being “disposed on” another component, it may be directly on the other component or there may be a central component.
  • the term “and/or” includes all and any combinations of one or more of the relevant listed items.
  • Centrifugal microfluidics uses a centrifugal device to drive the microfluidic chip to rotate around a rotation center to generate centrifugal force.
  • the centrifugal force can realize the transfer, mixing, reaction and other processing processes of the samples in the microfluidic chip within the corresponding cavity.
  • centrifugal microfluidics technology relies on the rotation of the microfluidic chip itself to provide power, it does not require the introduction of an additional power source, and the instrument occupies a small space.
  • the corresponding samples can be pre-packaged in the microfluidic chip, which is conducive to dry operation. After use, the waste liquid is discarded with the chip, and the system does not need to be cleaned.
  • centrifugal microfluidic chips still have the following defects during application: First, they are not compatible with the input of trace samples of uncertain volume (for example, 3 ⁇ l is required for a sample with a concentration of a, and 5 ⁇ l is required for a sample with a concentration of b).
  • trace samples of uncertain volume for example, 3 ⁇ l is required for a sample with a concentration of a, and 5 ⁇ l is required for a sample with a concentration of b.
  • An embodiment of the present application provides a sample processing system 1000, which includes a microfluidic chip 100, a driving device 200 and a pipetting device 300.
  • the microfluidic chip 100 can be detachably mounted on the driving device 200, and the driving device 200 is used to provide a driving force, and the driving force is used to drive the sample in the microfluidic chip 100 to transfer between different cavities.
  • the pipetting device 300 can also be used to transfer samples in different cavities in the microfluidic chip 100.
  • the microfluidic chip 100 can be a centrifugal microfluidic chip
  • the driving device 200 can be a centrifugal device.
  • the driving device 200 drives the microfluidic chip 100 to rotate around a rotation center a to increase the centrifugal force for the microfluidic chip 100. Under the action of the centrifugal force, the sample can be transferred, mixed, and other processes in the microfluidic chip 100. It is understandable 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, and other driving sources, such as pressure drive, may also be used.
  • the microfluidic chip 100 includes at least one sample processing area 10, and the sample processing area 10 includes: a sample processing chamber 101 and a plurality of storage chambers 102.
  • the sample processing chamber 101 can be used to provide space for sample processing (such as mixing, reaction, etc.).
  • the plurality of storage chambers 102 are used to store samples, and the samples can be, for example, biological samples required for biochemical substance analysis (biological samples can be human blood samples, tissue samples or saliva samples, etc.), reagents used for biochemical analysis, and liquid samples such as buffers.
  • the samples can also be a mixture of biological samples, reagents and buffers.
  • the plurality of storage chambers 102 can include a first storage chamber 104, a second storage chamber 105 and a third storage chamber 106.
  • the first storage chamber 104 and the second storage chamber 105 can both be connected to the sample processing chamber 101, so that the samples in the first storage chamber 104 and the second storage chamber 105 can be transferred to the sample processing chamber 101.
  • the first storage chamber 104 and the second storage chamber 105 are not simultaneously connected to the sample processing chamber 101. That is, the samples in the first storage chamber 104 and the second storage chamber 105 can be added to the sample processing chamber 101 in steps (or sequentially), thereby achieving the purpose of performing multiple biochemical reactions in the same sample processing chamber 101.
  • the third storage chamber 106 is not connected to the sample processing chamber 101.
  • the third storage chamber 106 has a first interface 161, which is used to interact with the pipetting device 300 to transfer the sample in the third storage chamber 106 to the sample processing chamber 101, thereby achieving the transfer of samples of uncertain volumes from the third storage chamber 106 to the sample processing chamber 101. It will be understood that the number of the first storage chamber 104, the second storage chamber 105, and the third storage chamber 106 can be specifically designed based on the number of sample types required for the actual reaction.
  • the biological sample can be stored in the third storage cavity 106 of the microfluidic chip 100 provided in this 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.
  • the pipetting device 300 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 conjunction with the rotation of the microfluidic chip 100. Specifically, the pipetting device 300 can move linearly along a first direction R and a second direction Z that are perpendicular to each other.
  • the first direction R can be the radial direction of the rotation of the microfluidic chip 100
  • the second direction Z is perpendicular to the rotation plane of the microfluidic chip 100.
  • the second direction Z can be a vertical direction.
  • the degrees of freedom of movement of the pipetting device 300 can be reduced (for example, the traditional XYZ axis movement can be converted to RZ movement), the range of motion can be reduced, the complexity of operating the pipetting device 300 can be simplified, the structural complexity of the sample processing system 1000 can be reduced, and the cost and volume of the sample processing system 1000 can be reduced.
  • the first interface 161 can be an opening opened on the upper surface of the microfluidic chip 100. A certain sample can be dripped into the third storage cavity 106 manually or automatically through the first interface 161. After the liquid filling is completed, the first interface 161 is sealed by a layer of sealing film. When the sample in the third storage cavity 106 needs to be transferred, the sealing film on the first interface 161 is removed in advance.
  • a first on-off assembly 141 is provided between the first storage chamber 104 and the sample processing chamber 101.
  • the first on-off assembly 141 is used to control the connection or disconnection between the first storage chamber 104 and the sample processing chamber 101.
  • a second on-off assembly 151 is provided between the second storage chamber 105 and the sample processing chamber 101.
  • the second on-off assembly 151 is used to control the connection or disconnection between the second storage chamber 105 and the sample processing chamber 101.
  • the first on-off assembly 141 and the second on-off assembly 151 are not opened at the same time, thereby achieving the purpose of transferring samples from the first storage chamber 104 and the second storage chamber 105 to the sample processing chamber 101 respectively.
  • the first on-off component 141 can be a valve-type on-off control structure
  • the second on-off component 151 can also be a valve-type on-off control structure.
  • the first on-off component 141 and the second on-off component 151 can both include at least one of valves such as a capillary valve, a hydrophobic valve, a siphon valve, and an active valve.
  • the capillary valve as shown in FIG4A
  • the hydrophobic valve as shown in FIG4B and FIG4C both use local surface tension differences to cause liquid stagnation.
  • the siphon valve is a curved flow channel design, in which there is a local flow channel (such as point A in FIG4D), and the local flow channel A is 1.5 meters away from the core.
  • the center of rotation of the chip is closer than the upstream cavity. This local flow channel can be called a crest.
  • a gas cavity is designed to connect the liquid flow channel with a deformable film.
  • the air pressure pushes the film to deform, thereby squeezing the liquid flow channel to achieve the closure of the flow channel.
  • the above capillary valves, steam traps, siphon valves and active valves are four major categories. The specific structural form can be designed according to actual needs.
  • the sample processing area 10 further includes a temporary storage chamber 103, which is used to temporarily store samples.
  • the temporary storage chamber 103 is connected to the sample processing chamber 101.
  • the temporary storage chamber 103 and the sample processing chamber 101 can be directly connected. It is understandable that in other embodiments, the temporary storage chamber 103 and the sample processing chamber 101 can also be indirectly connected, for example, they can be connected to the sample processing chamber 101 through the first storage chamber 104 or the second storage chamber 105.
  • the number of third storage cavities 106 can be multiple, and multiple third storage cavities 106 are independently set to store different samples.
  • two third storage cavities 106 can be set, namely a sample cavity 162 for storing biological samples and a buffer cavity 163 for storing buffer.
  • Both the first storage cavity 104 and the second storage cavity 105 can be provided with a fourth interface that communicates with the outside world.
  • This fourth interface allows samples to be placed in the corresponding storage cavity in advance, and does not affect the sample's ability to flow into other pipes or cavities during rotation.
  • the fourth interface can be an opening on the top surface of the microfluidic chip 100. Through this fourth interface, a sample can be drip-fed into the first storage cavity 104 and the second storage cavity 105 manually or automatically. After liquid filling, the fourth interface is sealed with a sealing membrane.
  • the microfluidic chip 100 is further provided with at least one vent hole, through which the sample processing chamber 101 , the first storage chamber 104 and the second storage chamber 105 are all connected to the external environment.
  • first interface 161 , the second interface 131 , the third interface 111 , the fourth interface and the vent are all pre-sealed by a sealing film to ensure that the pre-stored sample in the microfluidic chip 100 does not leak.
  • the microfluidic chip 100 may include a first edge 11 and a second edge 12 that are arranged opposite to each other.
  • the third storage cavity 106 may be arranged near the first edge 11, the sample processing cavity 101 may be arranged near the second edge 12, and the first storage cavity 104 and the second storage cavity 105 may be arranged between the sample processing cavity 101 and the third storage cavity 106.
  • the first edge 11 may be arranged near the rotation center a.
  • the above-mentioned layout facilitates the first storage cavity 104 and the second storage cavity 105 to be arranged between the sample processing cavity 101 and the third storage cavity 106.
  • the samples in the chamber 104 and the second storage chamber 105 are transferred to the sample processing chamber 101 by the action of centrifugal force.
  • multiple third storage cavities 106 can be arranged along the rotation radius of the microfluidic chip 100, or can be arranged along the rotation circumference of the microfluidic chip 100. This arrangement design facilitates the pipetting device 300 to transfer samples in different third storage cavities 106, which can further simplify the transfer path.
  • the microfluidic chip 100 can be fan-shaped, circular, rectangular, or other regular or irregular shapes, and can be designed according to actual needs.
  • the microfluidic chip 100 can be fan-shaped or circular.
  • the center of the microfluidic chip 100 is the rotation center a
  • the first edge 11 is set close to the center of the microfluidic chip 100.
  • the multiple third storage cavities 106 can be arranged along the radial direction of the microfluidic chip 100. When the temporary storage cavity 103 is set close to the first edge 11, the temporary storage cavity 103 and any third storage cavity 106 can be arranged along the circumference of the microfluidic chip 100.
  • the multiple third storage cavities 106 and the temporary storage cavity 103 can be arranged along the radial direction of the microfluidic chip 100.
  • the above design of the third storage cavity 106 and the temporary storage cavity 103 can further facilitate the transfer of samples by the pipetting device 300 and further simplify the transfer path.
  • the microfluidic chip 100 can include multiple sample processing areas 10. By providing multiple sample processing areas 10, the multiple sample processing areas 10 can perform the same or different biochemical reactions, thereby improving the space utilization of the microfluidic chip 100 and increasing the efficiency and throughput of sample processing. Specifically, when the microfluidic chip 100 is a circular chip, the multiple sample processing areas 10 can be arranged along the circumference of the microfluidic chip 100.
  • the pipetting device 300 may include a fixed arm 301 and a pipetting arm 302.
  • the fixed arm 301 may be positioned at the rotation center a.
  • One end of the pipetting arm 302 is positioned on the fixed arm 301.
  • the end of the pipetting arm 302, distal to the fixed arm 301, is located on a side of the microfluidic chip 100 distal to the drive device 200.
  • the pipetting arm 302 is capable of linear motion along a first direction R and a second direction Z.
  • the end of the pipetting arm 302 can cooperate with a pipette tip to aspirate and release a sample to transfer the sample. It is understood that the pipetting device 300 may also be positioned in other locations.
  • the sample processing system 1000 may further include a temperature control device 400 .
  • the temperature control device 400 is used to adjust the temperature of the microfluidic chip 100 , at least to provide the sample processing chamber 101 with the temperature required for biochemical reactions.
  • the temperature control device 400 can be located below the microfluidic chip 100. Specifically, the temperature control device 400 is located on a side of the microfluidic chip 100 close to the driving device 200. The temperature control device 400 can be moved toward or away from the microfluidic chip 100. When the microfluidic chip 100 needs to be heated, the temperature control device 400 can be driven to move to the bottom surface of the microfluidic chip 100. When 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 will be appreciated that the microfluidic chip 100 can also be controlled to move toward or away from the temperature control device 400.
  • an embodiment of the present application provides a method for processing a sample using the aforementioned sample processing system 1000 , specifically comprising the following steps:
  • step S1 a microfluidic chip 100 is provided.
  • the specific structure of the microfluidic chip 100 can be found in the above content and will not be described in detail here.
  • Step S2 transferring the first sample in the third storage chamber 106 to the sample processing chamber 101 .
  • a second sample Prior to step S2, a second sample must be pre-sealed in the first storage chamber 104, and a third sample must be pre-sealed in the second storage chamber 105. This can be done manually by the user or by a pipetting device. The first sample is then transferred to the third storage chamber 106 via the pipetting device 300.
  • the first sample can be a biological sample
  • the second sample can be the first reagent
  • the third sample can be the second reagent.
  • Step S2 specifically includes the following steps:
  • step S21 the first sample in the third storage chamber 106 is transferred to the temporary storage chamber 103 by the pipetting device 300 .
  • the microfluidic chip 100 is mounted on the driving device 200 and the microfluidic chip 100 is kept stationary.
  • the liquid transfer device 300 is used to transfer the microfluidic chip 100 to the driving device 200.
  • the first interface 161 absorbs a certain volume of the first sample from the third storage chamber 106 and transfers the first sample to the temporary storage chamber 103.
  • the aspirated volume of the first sample is calculated based on the concentration of the first sample.
  • step S22 the driving device 200 is started to increase the driving force of the driving device 200 to drive the first sample in the temporary storage chamber 103 to be transferred into the sample processing chamber 101 .
  • the driving device 200 when the driving device 200 is a centrifugal device, the driving device 200 drives the microfluidic chip 100 to rotate around a rotation center a, thereby increasing the centrifugal force. Under the action of the centrifugal force, the sample in the temporary storage chamber 103 will be further transferred to the sample processing chamber 101.
  • the third storage chamber 106 may be two, for example, one being the sample chamber 162 and the other being the buffer chamber 163.
  • the pipetting device 300 is used to first remove x ⁇ l of sample from the sample chamber 162, then remove (20-x) ⁇ l of buffer from the buffer chamber 163, and then transfer all 20 ⁇ l of the mixed liquid to the sample processing chamber 101.
  • the sample chamber 162, the second interface 131 of the temporary storage chamber 103, the vent 108, and the third interface 111 of the sample processing chamber 101 are sealed with a pre-applied film to prevent leakage of liquid within the microfluidic chip 100.
  • a fixed volume of the first sample is then input into the sample chamber 162 using the pipetting device 300.
  • Step S3 driving the second sample in the first storage chamber 104 to be transferred into the sample processing chamber 101 .
  • the driving device 200 provides a driving force, under the action of which the second sample in the first storage chamber 104 is transferred to the sample processing chamber 101.
  • the driving force may be centrifugal force, which opens the first on-off assembly 141, allowing the second sample to enter the sample processing chamber 101 and mix 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 chamber 105 does not enter the sample processing chamber 101.
  • step S3 includes the following steps:
  • step S31 a first centrifugal force is applied to the microfluidic chip 100 .
  • the first sample in the temporary storage chamber 103 is transferred to the first storage chamber 104 and forms a first mixture with the second sample in the first storage chamber 104 .
  • step S32 a second centrifugal force is provided to the microfluidic chip 100 .
  • the first storage chamber 104 is connected to the sample processing chamber 101 , and the second storage chamber 105 is disconnected from the sample processing chamber 101 , and the first mixture is transferred to the sample processing chamber 101 .
  • a mixing zone is provided between the first storage chamber 104 and the sample processing chamber 101 .
  • the method further includes:
  • the first mixture is mixed in the mixing zone.
  • step S4 the first sample and the second sample undergo a first processing process in the sample processing chamber 101 to obtain a first processing product.
  • the first processing process can be a simple sample mixing, or a biochemical reaction between the first sample and the second sample.
  • the first processing process is a first reaction between the first sample and the second sample to obtain a first product.
  • the second sample may be a first reagent required for a biochemical reaction.
  • Step S5 driving the third sample in the second storage chamber 105 to be transferred to the sample processing chamber 101 .
  • the driving device 200 provides a driving force, under the action of which the third sample in the second storage chamber 105 is transferred into the sample processing chamber 101.
  • the driving force may be a third centrifugal force.
  • the second on-off assembly 151 opens, connecting the second storage chamber 105 with the sample processing chamber 101, thereby allowing the third sample to enter the sample processing chamber 101 and mix with the first processing product.
  • the third sample may be a second reagent required for a biochemical reaction.
  • step S6 the third sample and the first processed product undergo a second processing process in the sample processing chamber 101 to obtain a second processed product.
  • the second treatment process can be a simple sample mixing, or a biochemical reaction between the third sample and the first product.
  • the second treatment process is a second reaction between the third sample and the first product to obtain the second product.
  • Step S7 taking out the second processing product in the sample processing chamber 101 by using the pipetting device 300 .
  • the pipetting device 300 takes out the final product in the sample processing chamber 101 via the third interface 111 .
  • the number of storage chambers 102 for storing reagents can be designed according to the number of reagent types actually added to the biochemical reaction and the number of reaction steps, and the reagent transfer and biochemical reaction can be carried out according to step S3 and step S4, or step S5 and step S6.
  • a temperature control strategy is applied to the sample processing chamber 101 to achieve temperature fluctuations within the sample. 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 along the rotation axis, thereby enabling the temperature control device 400 to control the temperature of the sample processing chamber 101.
  • the sample processing system 1000 provided in the embodiment of the present application has the following beneficial effects:
  • 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 a multi-step sample processing process (such as a biochemical reaction process) can be performed in the same sample processing cavity 101, that is, different reagent storage cavities can successively input different reagent samples into the same sample processing cavity 101 and perform multi-step reactions, thereby reducing sample loss, making the design of the temperature control device 400 simpler and lowering the cost.
  • a multi-step sample processing process such as a biochemical reaction process
  • the pipetting device 300 is only used to transfer samples and output the final processed reaction products, and does not participate in the sample addition and mixing in the intermediate steps. Due to the existence of the rotational motion 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, which reduces the degree of freedom of movement, the range of movement and the system complexity of the pipetting device 300, and reduces the cost and volume of the sample processing system 1000.
  • an embodiment of the present application further provides a biochemical reaction system 2000, which may include a control module 2100 and the aforementioned sample processing system 1000 in communication with the control module 2100.
  • the biochemical reaction system 2000 may be, for example, a library construction instrument or a sequencer. That is, the aforementioned sample processing system 1000 may be integrated into the library construction instrument or sequencer for constructing a gene sequencing library.
  • an embodiment of the present application further provides a biochemical detection system 3000.
  • This biochemical detection system 3000 may include a detection module 3100 and the aforementioned sample processing system 1000.
  • the sample processing system 1000 is configured to process a sample to obtain a product, and the detection module 3100 is configured to detect the product.
  • a biochemical reaction is performed using the aforementioned sample processing system 1000 to obtain a reaction product, which can then be detected by the detection module 3100.
  • the detection module 3100 may be, for example, a fluorescence detection module.
  • microfluidic chips with different implementation forms are given below, and the aforementioned microfluidic chip is further illustrated by describing specific embodiments.
  • this embodiment provides a microfluidic chip 100 a having a structural form.
  • the microfluidic chip 100 a based on the aforementioned microfluidic chip 100 , specifically defines the structural form of the first on-off component 141 , the second on-off component 151 , and the arrangement of the temporary storage chamber 103 .
  • the first on-off component 141 may include a siphon valve 142, which has a peak a1 (i.e., the local area of the flow channel of the siphon valve 142 closest to the rotation center a).
  • a1 i.e., the local area of the flow channel of the siphon valve 142 closest to the rotation center a.
  • the first storage chamber 104 is connected to the sample processing chamber 101 through the siphon valve 142 and the first flow channel 143.
  • the siphon valve 142 can realize the connection or disconnection between the first storage chamber 104 and the sample processing chamber 101.
  • the second on-off assembly 151 may include a siphon valve 152 and a capillary valve 153, wherein the siphon valve 152 has two peaks, namely peak b1 and peak b2, and the capillary valve 153 is located between the two peaks b1 and b2.
  • the second storage chamber 105 is connected to the sample processing chamber 101 through the siphon valve 152, the capillary valve 153, and the second flow channel 154.
  • the cooperation of the siphon valve 152 and the capillary valve 153 can achieve the connection or disconnection between the second storage chamber 105 and the sample processing chamber 101.
  • the first on-off assembly 141 and the second on-off assembly 151 can be opened at different stages by controlling the magnitude of the centrifugal force, thereby achieving the purpose of not connecting the first storage chamber 104 and the second storage chamber 105 to the sample processing chamber 101 at the same time.
  • the working process and working principle of the first on-off component 141 and the second on-off component 151 will be described in detail later in the sample processing method.
  • the microfluidic chip 100a is roughly fan-shaped or circular, and the center of the microfluidic chip 100a is the rotation center a.
  • the temporary storage chamber 103 is set near the rotation center a. At this time, the temporary storage chamber 103 is directly connected to the first storage chamber 104, and is connected to the sample processing chamber 101 through the first storage chamber 104.
  • the microfluidic chip 100a there are two third storage chambers 106, namely a sample chamber 162 and a buffer chamber 163.
  • the sample chamber 162 and the buffer chamber 163 are arranged along the radial direction of the microfluidic chip 100a, and the temporary storage chamber 103 and the buffer chamber 163 are arranged along the circumferential direction of the microfluidic chip 100a.
  • a mixing zone is provided between the first storage chamber 104 and the sample processing chamber 101.
  • the mixing zone is formed by bending the first flow channel 143 connecting the first storage chamber 104 and the sample processing chamber 101.
  • the first flow channel 143 between the first on-off component 141 and the sample processing chamber 101 can be bent multiple times to form a folded structure, so that preliminary mixing can be achieved when the sample flows through this area.
  • vent 108 In the microfluidic chip 100a, only one vent 108 may be provided. Specifically, the vent 108 is connected to the first storage chamber 104, the second storage chamber 105 and the sample processing chamber 101 through a microchannel, thereby realizing the connection between the aforementioned three chambers and the atmosphere, so as to facilitate the smooth transfer of samples between different chambers during the centrifugation process.
  • the method for processing a sample using the microfluidic chip 100 a includes the following steps:
  • the first and second storage chambers 104 and 105 contain fixed volumes (e.g., 20 ⁇ l and 40 ⁇ l) of the first and second reagents, respectively.
  • the buffer chamber 163 of the third storage chamber 106 contains a fixed volume (e.g., 20 ⁇ l) of buffer.
  • the sample chamber 162, the second interface 131 of the temporary storage chamber 103, the vent 108, and the third interface 111 of the sample processing chamber 101 are sealed with a pre-applied film to prevent leakage of liquid within the microfluidic chip 100a.
  • the user tears off a portion of the film to allow the sample chamber 162, the temporary storage chamber 103, and the vent 108 to communicate with the outside world.
  • a fixed volume (e.g., 20 ⁇ l) of biological sample is then introduced into the sample chamber 162 via the pipetting device 300.
  • the microfluidic chip 100a enters the automated sample processing flow.
  • step 1 as shown in FIG. 9B and FIG. 1 , the microfluidic chip 100 a remains stationary, and the pipetting device 300 moves radially to the sample chamber 162 to absorb x ⁇ l of the biological sample, where the specific value of x is determined by measuring the concentration of the biological sample.
  • step 2 as shown in FIG. 9C and FIG. 9D , combined with FIG. 1 , the microfluidic chip 100a remains stationary, and the pipetting device 300 moves along the The microfluidic chip 100a moves radially to the buffer chamber 163 to absorb (20-x) ⁇ l of buffer. Further, the microfluidic chip 100a rotates so that the second interface 131 of the temporary storage chamber 103 reaches the bottom of the pipetting device 300. The pipetting device 300 transfers the mixture of the biological sample and buffer with a total volume of 20 ⁇ l into the temporary storage chamber 103.
  • step 3 as shown in FIG9E and in combination with FIG1 , the driving device 200 drives the microfluidic chip 100a to rotate at a relatively high speed (e.g., 1000 rpm) from rest. Centrifugal force drives the 20 ⁇ l mixture of the biological sample and the buffer solution to the first storage chamber 104. At the same time, part of the sample in the first storage chamber 104 enters the siphon valve 142, and part of the sample in the second storage chamber 105 enters the siphon valve 152, until the liquid levels in the siphon valves 142 and 152 are flush with the liquid levels of the remaining samples in the two chambers (i.e., the distance from the center of the circle is the same).
  • a relatively high speed e.g. 1000 rpm
  • step 4 the driving device 200 controls the microfluidic chip 100a to reduce the speed from the higher speed to a lower speed (e.g., 600 rpm).
  • a lower speed e.g. 600 rpm.
  • the liquid level in the siphon valve 142 will pass over the peak a1 under the action of capillary force, and achieve preliminary mixing in the curved mixing zone formed by the downstream first flow channel 143, and finally enter the sample processing chamber 101.
  • the siphon valve 152 has two peaks b1 and b2 and a capillary valve 153.
  • the capillary valve 153 can be set to be unable to open at a lower speed.
  • step 5 as shown in FIG. 9G and in conjunction with FIG. 1 , after the liquid sample (a mixture of the first reagent, the biological sample, and the buffer) in the first storage chamber 104 completely reaches the sample processing chamber 101, the microfluidic chip 100a is controlled to stop rotating and interact with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve temperature control operations on the sample processing chamber 101 and perform the first reaction.
  • the microfluidic chip 100a is controlled to stop rotating and interact with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve temperature control operations on the sample processing chamber 101 and perform the first reaction.
  • step 6 as shown in FIG. 9H and FIG. 9I , and in conjunction with FIG. 1 , after the first reaction is completed, the lower surface 110 of the sample processing chamber 101 is separated from the temperature control device 400 , and the microfluidic chip 100a is controlled to rotate again at a higher speed (e.g., 1000 rpm). At this time, the centrifugal force is sufficient to open the capillary valve 153 . The microfluidic chip 100a is then decelerated to a lower speed (e.g., 600 rpm), and the second reagent further passes over the second wave peak b2 of the siphon valve 152 and finally reaches the sample processing chamber 101 through the second flow channel 154.
  • a higher speed e.g. 1000 rpm
  • step 7 as shown in FIG9J and in conjunction with FIG1 , after the second reagent in the second storage chamber 105 has completely reached the sample processing chamber 101, the microfluidic chip 100a is controlled to rotate alternately in the forward and reverse directions at a certain acceleration to achieve uniform mixing of the sample in the sample processing chamber 101.
  • the microfluidic chip 100a can also be controlled to accelerate or decelerate in one direction to achieve the mixing effect.
  • the microfluidic chip 100a stops rotating and interacts with the temperature control device 400 through the surface 110 below the sample processing chamber 101 to achieve a temperature increase or decrease in the sample processing chamber 101 and perform the second reaction.
  • step 8 as shown in FIG9K and in conjunction with FIG1 , after the second reaction is complete, the combined radial motion of the pipetting device 300 and the circumferential rotation of the microfluidic chip 100a causes the pipetting device 300 to reach above the third interface 111 and interact with the third interface 111, thereby removing the reactants from the sample processing chamber 101. This concludes the sample processing process.
  • FIG9L shows a microfluidic chip 100 a including multiple sample processing areas 10 , which includes four independent modules as shown in FIG9A , and can realize simultaneous processing of four different samples.
  • this embodiment provides a microfluidic chip 100 b having a second structural form.
  • the microfluidic chip 100 b specifically defines the structural forms of the first on-off component 141 and the second on-off component 151, as well as the arrangement of the temporary storage chamber 103, based on the aforementioned microfluidic chip 100.
  • the temporary storage chamber 103 is connected to the first storage chamber 104, and the first storage chamber 104 is connected to the second storage chamber 104.
  • the chamber 105 is connected via a third on-off assembly 107, which can connect or disconnect the first storage chamber 104 and the second storage chamber 105.
  • the third on-off assembly 107 can also include at least one of a capillary valve, a steam trap, a siphon valve, and an active valve.
  • the first on-off component 141 may include a siphon valve 144 having a peak a2.
  • the first storage chamber 104 is connected to the sample processing chamber 101 via the siphon valve 144, and the connection or disconnection between the first storage chamber 104 and the sample processing chamber 101 can be achieved through the siphon valve 144.
  • the second on-off component 151 may include a siphon valve 155 having a peak b3.
  • the second storage chamber 105 is connected to the sample processing chamber 101 via the siphon valve 155 and the second flow channel 154, and the connection or disconnection between the second storage chamber 105 and the sample processing chamber 101 can be achieved through the siphon valve 155.
  • the third on-off component 107 may include a siphon valve. By setting the siphon valve, the connection or disconnection between the first storage chamber 104 and the second storage chamber 105 can be achieved.
  • the centrifugal force can be controlled to open the first on-off assembly 141, the second on-off assembly 151, and the third on-off assembly 107 at different stages, thereby preventing simultaneous communication between the first storage chamber 104 and the second storage chamber 105 and the sample processing chamber 101.
  • the on-off principle of the siphon valve is the same as that in the first embodiment. The process and principle of achieving communication will be described in detail in the subsequent sample processing method.
  • the microfluidic chip 100 b is roughly fan-shaped or circular, the center of the microfluidic chip 100 b is the rotation center a, and the temporary storage chamber 103 is disposed near the rotation center a.
  • the microfluidic chip 100b there are two third storage chambers 106, namely a sample chamber 162 and a buffer chamber 163.
  • the sample chamber 162 and the buffer chamber 163 are arranged along the radial direction of the microfluidic chip 100b, and the temporary storage chamber 103 and the buffer chamber 163 are arranged along the circumferential direction of the microfluidic chip 100b.
  • a mixing zone is provided between the first storage chamber 104 and the sample processing chamber 101.
  • the mixing zone is formed by bending the first flow channel 143 connecting the first storage chamber 104 and the sample processing chamber 101.
  • the first flow channel 143 between the first on-off component 141 and the sample processing chamber 101 can be bent multiple times to form a folded structure, so that preliminary mixing can be achieved when the sample flows through this area.
  • vents 108 In the microfluidic chip 100b, only two vents 108 may be provided.
  • One vent 108 is connected to the first storage chamber 104, thereby simultaneously connecting the first storage chamber 104 and the second storage chamber 105 to the atmosphere.
  • the other vent 108 is connected to the sample processing chamber 101, thereby further connecting the sample processing chamber 101 to the atmosphere.
  • the method for processing a sample using a microfluidic chip 100 b includes the following steps:
  • the initial state of the microfluidic chip 100 b is substantially the same as that of Example 1. Please refer to the aforementioned Example 1 and no further details will be given here.
  • the microfluidic chip 100b enters the automated sample processing process, which specifically includes the following steps:
  • step 1 and step 2 the processing methods of the sample and the buffer solution are basically the same as those in Example 1. Please refer to step 1 and step 2 of the aforementioned Example 1, and no further details will be given here.
  • step 3 as shown in FIG10B and in combination with FIG1 , the driving device 200 drives the microfluidic chip 100 b to rotate at a relatively high speed (e.g., 1000 rpm) from rest. Centrifugal force drives the 20 ⁇ l mixture of sample and buffer to the first storage chamber 104. At the same time, part of the sample in the first storage chamber 104 enters the siphon valve 144, and part of the sample in the second storage chamber 105 enters the siphon valve 155, until the liquid levels in the siphon valves 144 and 155 are flush with the liquid levels of the remaining samples in the two chambers.
  • a relatively high speed e.g. 1000 rpm
  • step 4 the driving device 200 controls the microfluidic chip 100b to reduce the higher speed to a lower speed (e.g., 600 rpm).
  • a lower speed e.g. 600 rpm.
  • the liquid level in the siphon valve 144 will be lowered by the capillary force.
  • the second storage chamber 105 is not connected to the atmosphere, the second reagent therein cannot pass through the siphon valve 155 .
  • step 5 as shown in FIG10D and in combination with FIG1 , when the liquid sample (a mixture of the first reagent, the biological sample, and the buffer) in the first storage chamber 104 passes through the curved first flow channel 143 to achieve preliminary mixing and finally reaches the sample processing chamber 101 completely, the microfluidic chip 100b is controlled to stop rotating and interacts with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve temperature increase and decrease operations on the sample processing chamber 101 and perform the first reaction.
  • the microfluidic chip 100b is controlled to stop rotating and interacts with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve temperature increase and decrease operations on the sample processing chamber 101 and perform the first reaction.
  • step 6 as shown in Figures 10E and 10F, combined with Figure 1, after the first reaction is completed, the lower surface 110 of the sample processing chamber 101 is separated 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) again, and then slows down to a lower speed (e.g., 600 rpm).
  • a higher speed e.g. 1000 rpm
  • a lower speed e.g. 600 rpm
  • the second storage chamber 105 can actually be connected to the atmosphere through the third on-off component 107 (e.g., a siphon valve), so that the second reagent in the second storage chamber 105 can pass over the peak b3 of the siphon valve 155 and finally reach the sample processing chamber 101.
  • the third on-off component 107 e.g., a siphon valve
  • step 7 as shown in FIG10G and in conjunction with FIG1 , after the second reagent in the second storage chamber 105 has completely reached the sample processing chamber 101, the microfluidic chip 100b is controlled to rotate alternately in the forward and reverse directions at a certain acceleration to achieve uniform mixing of the liquid in the sample processing chamber 101.
  • the microfluidic chip 100b can also be controlled to accelerate or decelerate in one direction to achieve the mixing effect.
  • the microfluidic chip 100b stops rotating and interacts with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve a temperature increase or decrease in the sample processing chamber 101 and perform the second reaction.
  • step 8 as shown in FIG10H and in conjunction with FIG1 , after the second reaction is completed, the radial motion of the pipetting device 300 and the circumferential rotation of the microfluidic chip 100b are combined to allow the pipetting device 300 to reach the top of the third interface 111 and interact with the third interface 111, thereby removing the reactants from the sample processing chamber 101. This concludes the sample processing process.
  • This embodiment provides a microfluidic chip 100c with a structural form. Based on the aforementioned microfluidic chip 100, the microfluidic chip 100c specifically defines the structural form of the first on-off component 141, the second on-off component 151, and the setting method of the temporary storage cavity 103.
  • the temporary storage chamber 103 is directly connected to the sample processing chamber 101.
  • the first on-off component 141 and the second on-off component 151 can both be active valves, specifically paraffin valves.
  • the temperature control device 400 can also provide temperature for the first on-off component 141 and the second on-off component 151 to open the active valves.
  • the temperature control device 400 can heat the first on-off component 141 and the second on-off component 151 at different stages, thereby opening them at different stages, so as to achieve non-simultaneous communication between the first storage chamber 104 and the second storage chamber 105 and the sample processing chamber 101.
  • the microfluidic chip 100 c is roughly fan-shaped or circular, the center of the microfluidic chip 100 c is the rotation center a, and the temporary storage chamber 103 is disposed near the rotation center a.
  • the microfluidic chip 100c there are two third storage chambers 106, namely a sample chamber 162 and a buffer chamber 163.
  • the temporary storage chamber 103, the sample chamber 162 and the buffer chamber 163 are arranged along the radial direction of the microfluidic chip 100c.
  • vent 108 In the microfluidic chip 100b, only one vent 108 may be provided. Specifically, the vent 108 is connected to the first storage chamber 104, the second storage chamber 105 and the sample processing chamber 101 through a microchannel, thereby realizing the connection between the aforementioned three chambers and the atmosphere, so as to facilitate the smooth transfer of samples between different chambers during the centrifugation process.
  • the method for processing a sample using a microfluidic chip 100 c includes the following steps:
  • the initial state of the microfluidic chip 100 c is substantially the same as that of Example 1. Please refer to the aforementioned Example 1 and no further details will be given here.
  • the microfluidic chip 100c enters the automated sample processing process, which specifically includes the following steps:
  • step 1 and step 2 as shown in FIG11B , the processing method of the sample and the buffer solution is basically the same as that in Example 1. Please refer to step 1 and step 2 of the aforementioned Example 1, and no further details will be given here.
  • step 3 as shown in FIG11C and in conjunction with FIG1 , the driving device 200 drives the microfluidic chip 100 c to rotate at a relatively high speed (e.g., 1000 rpm) from rest. Centrifugal force drives the 20 ⁇ l mixture of sample and buffer solution directly from the temporary storage chamber 103 into the sample processing chamber 101.
  • a relatively high speed e.g. 1000 rpm
  • step 4 as shown in FIG11D and in combination with FIG1 , the microfluidic chip 100 c is controlled to stop rotating by the driving device 200 , and the paraffin valve 145 is heated by interacting with the temperature control device 400 through the lower surface 112 of the paraffin valve 145 to melt the solid paraffin into liquid.
  • the microfluidic chip 100 c is then controlled to rotate to transfer the first reagent from the first storage chamber 104 to the sample processing chamber 101.
  • step 5 as shown in FIG11E and in conjunction with FIG1 , after the first reagent in the first storage chamber 104 has completely reached the sample processing chamber 101, the microfluidic chip 100c is controlled to rotate alternately in the forward and reverse directions at a certain acceleration to achieve uniform mixing of the liquid in the sample processing chamber 101.
  • the microfluidic chip 100c can also be controlled to accelerate or decelerate in one direction to achieve the mixing effect.
  • the microfluidic chip 100c is controlled to stop rotating and interact with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve the temperature increase and decrease operation of the sample processing chamber 101 to perform the first reaction.
  • step 6 as shown in FIG11F and in combination with FIG1 , after the first reaction is completed, the lower surface 110 of the sample processing chamber 101 is separated from the temperature control device 400, and the lower surface 113 of the paraffin valve 156 interacts with the temperature control device 400 to heat the paraffin valve 156, melting the solid paraffin into liquid.
  • the microfluidic chip 100 c is then controlled to rotate to transfer the second reagent from the second storage chamber 105 to the sample processing chamber 101.
  • step 7 as shown in FIG11G and in conjunction with FIG1 , after the second reagent in the second storage chamber 105 has completely reached the sample processing chamber 101, the microfluidic chip 100c is controlled to rotate alternately in the forward and reverse directions at a certain acceleration to achieve uniform mixing of the liquid in the sample processing chamber 101.
  • the microfluidic chip 100c can also be controlled to rotate in one direction at an acceleration or deceleration rate to achieve the mixing effect.
  • the microfluidic chip 100c stops rotating and interacts with the temperature control device 400 through the lower surface 110 of the sample processing chamber 101 to achieve a temperature increase or decrease in the sample processing chamber 101 and perform the second reaction.
  • step 8 as shown in FIG11H and in conjunction with FIG1 , after the second reaction is complete, the combined radial motion of the pipetting device 300 and the circumferential rotation of the microfluidic chip 100c causes the pipetting device 300 to reach above the third interface 111 and interact with the third interface 111, thereby removing the reactants from the sample processing chamber 101. This concludes the sample processing process.

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Abstract

一种微流控芯片、样本处理系统及其应用、以及样本处理方法，该微流控芯片包括样本处理腔体和多个存储腔体，样本处理腔体用于为样本处理提供空间；多个存储腔体用于存储样本，多个存储腔体包括第一存储腔体、第二存储腔体和第三存储腔体，第一存储腔体和第二存储腔体均可与样本处理腔体连通，且第一存储腔体和第二存储腔体与样本处理腔体不同时连通，第三存储腔体与样本处理腔体不连通，第三存储腔体具有与移液装置交互的第一接口。本申请通过微流控芯片的结构设计，可以实现不同腔体向同一样本处理腔体内先后输入不同样本并进行多步反应，降低了样本损耗，温控装置的设计更简单，成本更低。

Description

微流控芯片、样本处理系统及其应用、以及样本处理方法 技术领域
本申请涉及生物或化学样本处理技术领域，尤其涉及一种微流控芯片、样本处理系统及其应用、以及样本处理方法。
背景技术
在生物、医疗、化工等领域进行生化反应之前，通常需要对样本进行前处理，例如，在基因测序之前，需要对原始生物样本进行大量的操作或生化反应，如过滤、提纯、环化、扩增等，从而获得可被基因测序仪等检测仪器所接受的样本(例如测序文库)。
目前，虽然部分操作已经在移液工作站上实现了自动化，但由于样本的多样性和不同样本类型下处理策略的复杂性，大量繁琐的操作仍然高度依赖人工，耗时长，效率低，同时需要消耗大量一次性吸头，耗材成本高，对环境危害大；且需要匹配多种仪器设备，例如聚合酶链反应(Polymerase Chain Reaction，PCR)仪，提高了设备成本和体积。
发明内容
鉴于此，为了解决以上技术问题中的至少之一，有必要提出一种微流控芯片。
另外，本申请还提供了应用前述微流控芯片的样本处理系统、样本处理方法、以及应用该样本处理系统的生化反应系统和生化检测系统。
第一方面，本申请实施例提供一种微流控芯片，所述微流控芯片包括至少一个样本处理区域，所述样本处理区域包括：样本处理腔体和多个存储腔体，所述样本处理腔体用于为样本处理提供空间；所述多个存储腔体用于存储样本，所述多个存储腔体包括第一存储腔体、第二存储腔体和第三存储腔体，所述第一存储腔体和所述第二存储腔体均可与所述样本处理腔体连通，且所述第一存储腔体和所述第二存储腔体与所述样本处理腔体不同时连通，所述第三存储腔体与所述样本处理腔体不连通，所述第三存储腔体具有第一接口，所述第一接口用于与移液装置交互，以将位于所述第三存储腔体内的样本转移至所述样本处理腔体。
在一些可能的实施例中，所述第一存储腔体与所述样本处理腔体之间设有第一通断组件，所述第一通断组件用于控制所述第一存储腔体与所述样本处理腔体之间的连通或断开，所述第二存储腔体与所述样本处理腔体之间设有第二通断组件，所述第二通断组件用于控制所述第二存储腔体与所述样本处理腔体之间的连通或断开，所述第一通断组件和所述第二通断组件不同时打开。
在一些可能的实施例中，所述第一通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种；
所述第二通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种。
在一些可能的实施例中，所述主动阀包括石蜡阀和气动阀中的至少一种。
在一些可能的实施例中，所述样本处理区域还包括暂存腔体，所述暂存腔体与所述样本处理腔体连通，所述暂存腔体具有第二接口，所述第二接口用于与所述移液装置交互，以将位于所述第三存储腔体内的样本转移至所述暂存腔体。
在一些可能的实施例中，所述暂存腔体与所述样本处理腔体直接连通；或所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通。
在一些可能的实施例中，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通，所述第一存储腔体与所述样本处理腔体之间设有混合区。
在一些可能的实施例中，所述混合区通过连通所述第一存储腔体与所述样本处理腔体的第一流道弯曲形成。
在一些可能的实施例中，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通，所述第一存储腔体还可与所述第二存储腔体连通，所述第一存储腔体与所述第二存储腔体之间设有第三通断组件，所述第三通断组件用于控制所述第一存储腔体和所述第二存储腔体之间的连通和断开。
在一些可能的实施例中，所述第三通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种。
在一些可能的实施例中，所述微流控芯片包括相对设置的第一边缘和第二边缘，所述第三存储腔体靠近所述第一边缘，所述样本处理腔体靠近所述第二边缘，所述第一存储腔体和所述第二存储腔体位于所述样本处理腔体与所述第三存储腔体之间。
在一些可能的实施例中，所述微流控芯片为扇形或圆形，所述第一边缘靠近所述微流控芯片的圆心，当所述暂存腔体与所述样本处理腔体直接连通时，所述暂存腔体靠近所述第二边缘，所述第三存储腔体与所述暂存腔体沿所述微流控芯片的径向排列；当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通时，所述暂存腔体靠近所述第一边缘，所述第三存储腔体与所述暂存腔体沿所述微流控芯片的周向排布。
在一些可能的实施例中，所述微流控芯片包括多个所述样本处理区域，多个所述样本处理区域沿所述微流控芯片的周向排布。
在一些可能的实施例中，所述样本处理腔体具有第三接口，所述第三接口用于供所述移液装置将位于所述样本处理腔体内的样本取出；
所述微流控芯片上还设有至少一个通气孔，所述样本处理腔体、所述第一存储腔体和所述第二存储腔体通过所述通气孔与外界环境连通。
第二方面，本申请实施例提供了一种样本处理系统，包括：
微流控芯片，所述微流控芯片为如上所述微流控芯片；
移液装置，所述移液装置用于与所述第三存储腔体的第一接口交互，以将位于所述第三存储腔体的第一样本转移至所述样本处理腔体；以及
驱动装置，所述微流控芯片可拆卸设于所述驱动装置上，所述驱动装置用于驱动位于所述第一存储腔体内的第二样本和位于所述第二存储腔体内的第三样本分别转移至所述样本处理腔体。
在一些可能的实施例中，所述驱动装置驱动所述微流控芯片绕一旋转中心旋转以产生离心力，所述离心力用于驱动位于所述第一存储腔体内的第二样本和位于所述第二存储腔体内的第三样本分别转移至所述样本处理腔体。
在一些可能的实施例中，当所述样本处理区域还包括所述暂存腔体时，所述移液装置用于将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体，所述驱动装置还用于驱动位于所述暂存腔体内的所述第一样本转移至所述样本处理腔体。
在一些可能的实施例中，所述移液装置可沿相互垂直的第一方向和第二方向做直线运动，所述第一方向为所述微流控芯片的旋转径向，所述第二方向为垂直所述微流控芯片的旋转平面的方向。
在一些可能的实施例中，所述移液装置包括固定臂和移液臂，所述固定臂设于所述旋转中心，所述移液臂的一端设于所述固定臂上，所述移液臂远离所述固定臂的一端位于所述微流控芯片远离所述 驱动装置的一侧，且所述移液臂可沿所述第一方向和所述第二方向做直线运动。
在一些可能的实施例中，所述样本处理系统还包括温控装置，所述温控装置用于为所述样本处理腔体提供生化反应所需的温度。
在一些可能的实施例中，当所述第一通断组件或所述第二通断组件为石蜡阀时，所述温控装置还用于加热所述第一通断组件或所述第二通断组件。
在一些可能的实施例中，所述温控装置设于所述微流控芯片靠近所述驱动装置的一侧，所述温控装置可朝向或远离所述微流控芯片移动。
第三方面，本申请实施例提供了一种样本处理方法，包括：
提供微流控芯片，所述微流控为如上所述的微流控芯片；
将所述第三存储腔体内的第一样本转移至所述样本处理腔体；
驱动所述第一存储腔体内的第二样本转移至所述样本处理腔体；
所述第一样本和所述第二样本在所述样本处理腔体进行第一处理过程，以得到第一处理产物；
驱动所述第二存储腔体内的第三样本转移至所述样本处理腔体；以及
所述第一处理产物和所述第三样本在所述样本处理腔体进行第二处理过程，以得到第二处理产物。
在一些可能的实施例中，当所述样本处理区域还包括所述暂存腔体时，
所述将所述第三存储腔体中的第一样本转移至所述样本处理腔体中的步骤包括：
通过移液装置将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体；以及
通过驱动装置为所述微流控芯片提供驱动力，以将位于所述暂存腔体中的所述第一样本转移至所述样本处理腔体。
在一些可能的实施例中，当所述第三存储腔体的数量为两个时，两个所述第三存储腔体分别为用于存储第一样本的样本腔体和用于存储缓冲液的缓冲液腔体，所述通过移液装置将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体的步骤包括：
通过所述移液装置将第一体积的所述第一样本由所述样本腔体转移至所述暂存腔体，并通过所述移液装置将第二体积的所述缓冲液由所述缓冲液腔体转移至所述暂存腔体，其中，所述第一体积和所述第二体积之和等于所述样本腔体内存储的所有所述第一样本的体积。
在一些可能的实施例中，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通时，所述第一样本和所述第二样本转移至所述样本处理腔体同步进行，包括：
通过驱动装置为所述微流控芯片提供第一离心力，以驱动位于所述暂存腔体内的所述第一样本转移至所述第一存储腔体并与所述第二样本形成第一混合物；以及
通过驱动装置为所述微流控芯片提供第二离心力，以使所述第一存储腔体与所述样本处理腔体连通，且所述第二存储腔体与所述样本处理腔体断开，并驱动位于所述第一存储腔体内的所述第一混合物转移至所述样本处理腔体。
在一些可能的实施例中，所述第一存储腔体与所述样本处理腔体之间设有混合区，在所述第一混合物转移至所述样本处理腔体之前，所述方法还包括：
在所述第二离心力的作用下，所述第一混合物在所述混合区进行混合。
在一些可能的实施例中，所述驱动所述第二存储腔体内的第三样本转移至所述样本处理腔体中的步骤包括：
通过驱动装置为所述微流控芯片提供第三离心力，以使所述第二存储腔体与所述样本处理腔体连通，并驱动位于所述第二存储腔体内的所述第三样本转移至所述样本处理腔体中。
在一些可能的实施例中，在得到所述第二处理产物之后，所述方法还包括：
通过移液装置将所述样本处理腔体内的所述第二处理产物取出。
第四方面，本申请实施例提供一种生化反应系统，所述生化反应系统包括控制模块和与所述控制模块通信连接的如上所述的样本处理系统。
第五方面，本申请实施例提供一种生化检测系统，所述生化检测系统包括检测模块和如上所述的样本处理系统，所述样本处理系统用于处理样本以得到产物，所述检测模块用于检测所述产物。
本申请实施例提供的样本处理系统具有如下有益效果：
(1)通过微流控芯片的结构设计，可以实现第一存储腔体和第二存储腔体内的样本分步转移至同一个样本处理腔体内，以实现同一样本处理腔体内可以进行多步样本处理过程(如生化反应过程)，即实现不同试剂存储腔体向同一样本处理腔体内先后输入不同的试剂样本并进行多步反应，降低了样本损耗，温控装置的设计更简单，成本更低。
(2)通过微流控芯片配合移液装置，可以实现不确定体积样本的转移，克服了现有微流控方案难以转移腔体内部分液体的缺点。
(3)移液装置只用于转移样本和最后处理完的反应产物的输出，不参与中间步骤的样本添加和混匀，由于微流控芯片旋转运动的存在，移液装置只需要沿着微流控芯片的径向移动就可以到达芯片的每一个角落，减少了移液装置的运动自由度、运动行程范围和系统复杂度，降低了样本处理系统的成本和体积。
(3)由于移液装置不参与中间步骤的样本添加和混匀，大幅减少了一次性耗材(如吸头)的使用，甚至可以完全不使用一次性吸头，而采用可重复使用的试剂针，并在微流控芯片执行中间步骤时并行进行试剂针的清洗，从而缩短系统运行时间。
附图说明
为了更清楚地说明本申请实施例的技术方案，下面将对本申请实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本申请一实施例中样本处理系统的系统框架图。
图2是本申请一实施例中微流控芯片的结构示意图。
图3为图2中一个样本处理区域的结构示意图。
图4A是本申请一实施例中虹吸阀的结构示意图。
图4B与图4C是本申请一实施例中疏水阀的结构示意图。
图4D是本申请一实施例中毛细阀的结构示意图。
图4E是本申请一实施例中石蜡阀的结构示意图。
图4F是本申请一实施例中气动阀的结构示意图。
图5是本申请另一实施例中微流控芯片的结构示意图。
图6是本申请一实施例中样本处理方法的流程图。
图7是本申请一实施例中生化反应系统的结构示意图。
图8是本申请一实施例中生化检测系统的结构示意图。
图9A是图2所示微流控芯片的一种具体实现方式的结构示意图。
图9B至图9K是采用图9A的微流控芯片进行样本处理的过程示意图。
图9L是本申请一实施例中包含多个图9A中的样本处理区域的微流控芯片的结构示意图。
图10A是图2所示微流控芯片的第二种具体实现方式中的结构示意图。
图10B至图10H是采用图10A的微流控芯片进行样本处理的过程示意图。
图11A是图2所示微流控芯片的第三种具体实现方式的结构示意图。
图11B至图11H是采用图11A的微流控芯片进行样本处理的过程示意图。
如下具体实施方式将结合上述附图进一步说明本申请。
具体实施方式
以下将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
需要说明的是，当组件被称为“固定于”、“安装于”另一个组件，它可以直接在另一个组件上或者也可以存在居中的组件。当一个组件被认为是“设置于”另一个组件，它可以是直接设置在另一个组件上或者可能同时存在居中组件。本文所使用的术语“及/或”包括一个或多个相关的所列项目的所有的和任意的组合。
目前生化反应过程中对样本的处理可以采用离心微流控技术实现，离心微流控技术是通过离心装置驱动微流控芯片绕一旋转中心转动，以产生离心力，离心力可以实现微流控芯片中的样本在相应腔体内的转移、混匀、反应等处理过程。离心微流控技术由于依靠微流控芯片自身旋转来提供动力，不需要引入额外的动力源，仪器所占空间体积小。其次，微流控芯片内可以提前封装相应的样本，有利于实现干式运行，使用后废液随芯片废弃，系统无需清洗。
然而，本申请发明人在研究中发现，现有的离心微流控芯片在应用过程中还存在以下缺陷：第一，无法兼容不确定体积的微量样本的输入(比如对于浓度为a的样本需要输入3μl，而对于浓度为b的样本需要输入5μl)，以基因测序文库的构建为例，由于在流程的开始需要根据单链DNA的浓度来计算实际的生物样本的投入体积，我们需要将实际计算得到的特定体积的生物样本在微流控芯片中进行转移，然而在通常的离心微流控技术中，液体都是整体从一个腔体移动到另一个腔体的，很难精确控制某个腔室中一部分体积的液体的移动。第二，难以实现不同腔体向同一个腔体先后输送不同试剂并进行多步反应(例如腔体A先向腔体C输送试剂1进行反应1，然后腔体B再向腔体C输送试剂2进行反应2)，还是以基因测序文库的构建为例，在第一次PCR反应后还需要加入新的试剂，然后再进行第二次的PCR反应，这在现有的离心微流控芯片中两次反应需要分别在两个腔体中进行，导致需加热的区域面积增大，成本更高，温控策略也变得更复杂。
为了解决以上缺陷中的至少之一，请参阅图1，本申请实施例提供了一种样本处理系统1000，该样本处理系统1000包括微流控芯片100、驱动装置200以及移液装置300。其中，微流控芯片100可拆卸设于所述驱动装置200上，驱动装置200用于提供驱动力，所述驱动力用于驱动微流控芯片100内样本在不同腔体内转移。移液装置300也可以用于微流控芯片100内不同腔体内样本的转移。具体地，微流控芯片100可以是离心微流控芯片，驱动装置200可以是离心装置，通过驱动装置200驱动微流控芯片100绕一旋转中心a旋转，以为微流控芯片100提高离心力，在离心力的作用下可以实现样本在微流控芯片100内的转移、混合等过程。可以理解的，该微流控芯片100不限于离心微流控芯片，驱动装置200也不限于离心装置，还可以采用其他驱动源，例如压力驱动。
请一并结合参阅图2与图3所示，为本申请实施例提供的微流控芯片100的结构示意图，该微流控芯片100包括至少一个样本处理区域10，所述样本处理区域10包括：样本处理腔体101和多个存储腔体102。其中，样本处理腔体101可以用于为样本处理(例如混合、反应等)提供空间。所述多个存储腔体102用于存储样本，所述样本例如可以是生化物质分析所需的生物样本(生物样本可以是人体血液样本、组织样本或唾液样本等)、生化分析用到的试剂以及缓冲液等液体样本，所述样本也可以是生物样本、试剂以及缓冲液等的混合物。所述多个存储腔体102可以包括第一存储腔体104、第二存储腔体105和第三存储腔体106。第一存储腔体104和第二存储腔体105均可以与样本处理腔体101连通，从而可以使第一存储腔体104和第二存储腔体105内的样本转移至样本处理腔体101内。且第一存储腔体104和第二存储腔体105与样本处理腔体101不同时连通，即，第一存储腔体104和第二存储腔体105内的样本可以实现分步(或者具有先后顺序)加入样本处理腔体101内，以实现同一样本处理腔体101内进行多步生化反应的目的。第三存储腔体106与样本处理腔体101不连通，第三存储腔体106具有第一接口161，第一接口161用于与移液装置300交互，以将位于第三存储腔体106内的样本转移至样本处理腔体101中，从而可以实现由第三存储腔体106至样本处理腔体101的不确定体积样本的转移。可以理解的，第一存储腔体104、第二存储腔体105和第三存储腔体106的数量可以根据实际的反应所需的样本种类的多少具体设计。以基因测序文库的构建为例，可以在本实施例提供的微流控芯片100中的第三存储腔体106内存储生物样本，第一存储腔体104内存储第一种试剂，第二存储腔体105内存储第二种试剂。
当微流控芯片100为离心微流控芯片时，配合微流控芯片100的旋转，移液装置300只需要沿着微流控芯片100的旋转径向移动就可以到达微流控芯片100的每一个角落，具体地，移液装置300可沿相互垂直的第一方向R和第二方向Z做直线运动，第一方向R可以为微流控芯片100的旋转径向，第二方向Z垂直微流控芯片100的旋转平面，第二方向Z可以是竖直方向。因此，通过微流控芯片100的旋转搭配移液装置300，可以减少移液装置300的运动自由度(例如，可以从传统的XYZ轴运动变成RZ运动)，减少了运动行程范围，简化了操作移液装置300的复杂度，降低了样本处理系统1000的结构复杂度，同时还降低了样本处理系统1000的成本和体积。
在一些实施例中，第一接口161可以为开设在微流控芯片100上表面的开孔，通过第一接口161可使用手动或自动方式将某种样本滴灌至第三存储腔体106内，完成液体灌装后，第一接口161通过一层密封的膜完成封闭，在需要进行第三存储腔体106内样本转移时，提前将第一接口161上密封的膜去除。
在一些实施例中，第一存储腔体104与样本处理腔体101之间设有第一通断组件141，第一通断组件141用于控制第一存储腔体104与样本处理腔体101之间的连通或断开。第二存储腔体105与样本处理腔体101之间设有第二通断组件151，第二通断组件151用于控制第二存储腔体105与样本处理腔体101之间的连通或断开，且第一通断组件141和第二通断组件151不同时打开，从而实现第一存储腔体104和第二存储腔体105能分别向样本处理腔体101内转移样本的目的。
在一些实施例中，第一通断组件141可以是阀类通断控制结构，第二通断组件151也可以是阀类通断控制结构。当微流控芯片100为离心微流控芯片时，第一通断组件141和第二通断组件151均可以包括毛细阀、疏水阀、虹吸阀以及主动阀等阀中的至少一种。其中，毛细阀(如图4A所示)和疏水阀(如图4B与图4C所示)都是利用局部的表面张力差异造成液体停滞，在微流控芯片转速大于某个阈值后，这种表面张力差异不再足以抵抗离心力从而阀被冲开失效，以实现不同腔体的连通。如图4D所示，虹吸阀是一种弯曲流道设计，其中存在一局部流道(如图4D中A点)，该局部流道A距离芯 片的旋转中心要比上游腔体更近，可以称该局部流道为波峰，当芯片转速维持在高位时，离心力把液位维持在无法到达所述局部流道A(波峰)的状态；当芯片转速降低时，液位在毛细力帮助下越过所述局部流道A(波峰)，从而液体整体经由局部流道A转移到下游腔体，因此，虹吸阀在使用时需要对转速有一个先加速再减速的控制过程。主动阀是需要外源输入来启动的阀，即需要通过外部提供助力才能实现阀的开启，如石蜡阀(如图4E所示)，需对石蜡阀进行加热使其融化后才可打开，又如气动阀(如图4F所示)，设计一个气体腔体与液体流道通过可形变的薄膜连接，当气体腔体充气时，气压推动薄膜变形从而挤压液体流道，来实现流道的封闭。以上毛细阀、疏水阀、虹吸阀以及主动阀为四大类，具体结构形式可以根据实际需要设计。
请参阅图5所示，样本处理区域10还包括暂存腔体103，暂存腔体103用于暂存样本，暂存腔体103与样本处理腔体101连通，这里，暂存腔体103与样本处理腔体101可以直接连通。可以理解的，在其他实施例中，暂存腔体103与样本处理腔体101也可以间接连通，例如可以通过第一存储腔体104或第二存储腔体105与样本处理腔体101连通。暂存腔体103具有第二接口131，所述第二接口131用于供移液装置与暂存腔体103进行交互，例如向暂存腔体103转移样本，即暂存腔体103可以为敞口设置，可以便于向暂存腔体103内转移样本。利用移液装置可以将位于第三存储腔体106内的样本转移至暂存腔体103内，进一步使暂存腔体103内的样本转移至样本处理腔体101内。具体地，当微流控芯片100为离心微流控芯片时，可以在离心力的作用下进一步使暂存腔体103内的样本转移至样本处理腔体101内。
在一些实施例中，第三存储腔体106的数量可以为多个，多个第三存储腔体106独立设置以存储不同的样本，例如，本实施例中，第三存储腔体106可以设置两个，分别为用于存储生物样本的样本腔体162和用于存储缓冲液的缓冲液腔体163。
请再次参阅图1与图2所示，样本处理腔体101具有第三接口111，所述第三接口111用于与移液装置300交互，供移液装置300将位于样本处理腔体101内的样本取出。并且第三接口111的设置不影响样本处理腔体101内的样本在旋转作用下流动。在一些实施例中，第三接口111为开设在微流控芯片100的上表面的开孔，并通过一层密封的膜使第三接口111处于初始封闭状态，当需要将样本处理腔体101内的样本取出时，通过人工或自动方式穿刺所述膜，使吸管或试剂针与样本接触，从而实现样本的抽取，这里的样本可以是反应产物，也可以是单纯混匀后的混合物等。
第一存储腔体104和第二存储腔体105上均可以设置与外界连通的第四接口，通过第四接口可将样本提前放置到相应的存储腔体中，并且第四接口不影响样本在旋转作用下流动至其它管路或腔体中。在一些实施例中，第四接口可以为开设在微流控芯片100上表面的开孔，通过第四接口可使用手动或自动方式将某种样本滴灌至第一存储腔体104和第二存储腔体105内，完成液体灌装后，第四接口通过一层密封的膜完成封闭。
微流控芯片100上还设有至少一个通气孔，样本处理腔体101、第一存储腔体104和第二存储腔体105均通过所述通气孔与外界环境连通。
可以理解的，第一接口161、第二接口131、第三接口111、第四接口和通气孔均通过密封的膜预先密封，保证微流控芯片100内的预存的样本不会泄露。
请再次参阅图2与图3所示，微流控芯片100可以包括相对设置的第一边缘11和第二边缘12，第三存储腔体106可以靠近第一边缘11设置，样本处理腔体101可以靠近第二边缘12设置，第一存储腔体104和第二存储腔体105可以设置在样本处理腔体101与第三存储腔体106之间。当微流控芯片100安装在驱动装置200上后，第一边缘11可以靠近旋转中心a设置，前述布局方式方便将第一存储 腔体104和第二存储腔体105内的样本通过离心力的作用转移至样本处理腔体101内。
在一些实施例中，多个第三存储腔体106可以沿微流控芯片100的旋转半径方向排布，或者也可以沿微流控芯片100的旋转周向排布，此种排布设计，便于移液装置300对不同第三存储腔体106内的样本进行转移，能进一步简化转移路径。
微流控芯片100可以为扇形、圆形、矩形、或其他规则或不规则的形状，可以根据实际需求进行设计。在一些实施例中，微流控芯片100可以为扇形或圆形，此时，微流控芯片100的圆心即旋转中心a，第一边缘11靠近微流控芯片100的圆心设置，多个第三存储腔体106可以沿微流控芯片100的径向排布，当暂存腔体103靠近第一边缘11设置时，暂存腔体103与任一第三存储腔体106可以沿微流控芯片100的周向排布。若暂存腔体103靠近样本处理腔体101设置，此时，多个第三存储腔体106与暂存腔体103可以沿微流控芯片100的径向排布。同理，以上第三存储腔体106与暂存腔体103的设计，能进一步方便移液装置300对样本的转移，进一步简化转移路径。
请参阅图2与图3所示，微流控芯片100可以包括多个样本处理区域10，通过设置多个样本处理区域10，此时，多个样本处理区域10可以进行相同的生化反应，也可以进行不同的生化反应，可以提高微流控芯片100的空间利用率，提高样本处理的效率和通量。具体地，当微流控芯片100为圆形芯片，多个所述样本处理区域10可以沿微流控芯片100的周向排布。
请再次参阅图1与图2所示，移液装置300可以包括固定臂301和移液臂302，固定臂301可以设于所述旋转中心a，移液臂302的一端设于固定臂301上，移液臂302远离固定臂301的一端位于微流控芯片100远离驱动装置200的一侧，且移液臂302可沿第一方向R和第二方向Z做直线运动。移液臂302的端部可以配合吸头对样本进行吸取和释放，以转移样本。可以理解的，移液装置300也可以设置在其他位置。
请再次参阅图1所示，样本处理系统1000还可以包括温控装置400，温控装置400用于为微流控芯片100进行温度调节，至少为样本处理腔体101提供生化反应所需的温度。
在一些实施例中，温控装置400可以位于微流控芯片100的下方，具体地，温控装置400设于微流控芯片100靠近驱动装置200的一侧，温控装置400可朝向或远离微流控芯片100移动。当需要对微流控芯片100进行加热时，可以驱动温控装置400移动至微流控芯片100的下表面，当停止加热，并需要旋转微流控芯片100时，可以驱动温控装置400移动离开微流控芯片100。可以理解的，还可以控制微流控芯片100朝向或远离温控装置400移动。
请参阅图6所示，一并结合参阅图1与图2，本申请实施例提供了采用前述样本处理系统1000进行样本处理的方法，具体包括以下步骤：
步骤S1，提供微流控芯片100，该微流控芯片100的具体结构请参见前述内容，此处不做过多赘述。
步骤S2，将第三存储腔体106中的第一样本转移至样本处理腔体101。
在步骤S2之前，需要在第一存储腔体104内预先封存第二样本，在第二存储腔体105内预先封存第三样本，具体可以由用户手动输入或由移液装置输入。并将第一样本通过移液装置300转移到第三存储腔体106内。以基因测序文库的构建为例，第一样本可以是生物样本，第二样本可以是第一试剂，第三样本可以是第二试剂。
步骤S2具体包括以下步骤：
步骤S21，通过移液装置300将位于第三存储腔体106内的第一样本转移至暂存腔体103中。
将微流控芯片100安装在驱动装置200上，并保持微流控芯片100静止，使用移液装置300经由 第一接口161在第三存储腔体106吸取一定体积的第一样本，并将第一样本转移至暂存腔体103内。其中，第一样本的吸取体积根据第一样本的浓度计算得出。
步骤S22，启动驱动装置200，通过驱动装置200提高驱动力，以驱动暂存腔体103内的第一样本转移至样本处理腔体101内。
具体地，当驱动装置200为离心装置时，通过驱动装置200带动微流控芯片100绕一旋转中心a旋转，进而提高离心力，在离心力的作用下，位于暂存腔体103内的样本会进一步转移至样本处理腔体101内。
在一些实施例中，第三存储腔体106可以是两个，例如，一个为样本腔体162，一个是缓冲液腔体163，上述步骤S2中变为，使用移液装置300先从样本腔体162中取出xμl样本，再从缓冲液腔体163中取出(20–x)μl缓冲液，再将20μl的混合液体全部转移到样本处理腔体101中。具体地，微流控芯片100使用前，样本腔体162、暂存腔体103的第二接口131、通气孔108、样本处理腔体101的第三接口111由一层预先贴好的膜密封，保证微流控芯片100内液体不会泄漏，使用时由用户撕开部分的膜，使得样本腔体162、暂存腔体103和通气孔108与外界连通，随后通过移液装置300输入固定体积的第一样本到样本腔体162内。
步骤S3，驱动第一存储腔体104内的第二样本转移至样本处理腔体101内。
具体地，通过驱动装置200提供驱动力，在所述驱动力的作用下，将位于第一存储腔体104内的第二样本转移至样本处理腔体101内。该驱动力可以是离心力，在离心力的作用下，第一通断组件141开启，从而使第二样本进入样本处理腔体101内与第一样本混合，注意此时第二通断组件151并未开启，第二存储腔体105中的第三样本不会进入样本处理腔体101。
在其他实施例中，当暂存腔体103通过第一存储腔体104与样本处理腔体101连通时，第一样本与第二样本同时转移到样本处理腔体101内，所述步骤S3包括以下步骤：
步骤S31，为微流控芯片100提供第一离心力，在所述第一离心力的作用下，位于暂存腔体103内的第一样本转移至第一存储腔体104并与第一存储腔体104内的第二样本形成第一混合物。
步骤S32，为微流控芯片100提供第二离心力，在第二离心力的作用下，第一存储腔体104与样本处理腔体101连通，且第二存储腔体105与样本处理腔体101断开，所述第一混合物转移至样本处理腔体101。
在一些实施例中，第一存储腔体104与样本处理腔体101之间设有混合区，在所述第一混合物转移至样本处理腔体101之前，所述方法还包括：
在所述第二离心力的作用下，所述第一混合物在所述混合区进行混合。
步骤S4，第一样本与第二样本在样本处理腔体101内进行第一处理过程，得到第一处理产物。
可以理解的，第一处理过程可以是简单的样本混合，也可以是第一样本与第二样本进行生化反应。具体地，该第一处理过程为第一样本与第二样本发生第一反应，得到第一产物。
在一些实施例中，第二样本可以为生化反应所需的第一试剂。
步骤S5，驱动第二存储腔体105内的第三样本被转移至样本处理腔体101。
具体地，通过驱动装置200提供驱动力，在所述驱动力的作用下，位于第二存储腔体105内的第三样本被转移至样本处理腔体101内。该驱动力可以是第三离心力，在第三离心力的作用下，第二通断组件151开启，第二存储腔体105与样本处理腔体101连通，从而使第三样本进入样本处理腔体101内与第一处理产物混合。
在一些实施例中，第三样本可以为生化反应所需的第二试剂。
步骤S6，第三样本与第一处理产物在样本处理腔体101内发生第二处理过程，以得到第二处理产物。
可以理解的，第二处理过程可以是简单的样本混合，也可以是第三样本与第一产物进行生化反应。具体地，该第二处理过程为第三样本与第一产物发生第二反应，得到第二产物。
步骤S7，通过移液装置300将样本处理腔体101内的第二处理产物取出。
具体地，移液装置300经由第三接口111将样本处理腔体101内的最终产物取出。
可以理解的，可以根据实际添加生化反应所需的试剂类型的多少和反应步骤的数量设计用于存储试剂的存储腔体102的数量，并根据步骤S3与步骤S4，或步骤S5与步骤S6进行试剂的转移和生化反应。
在一些实施例中，步骤S4和S5当发生生化反应时，需对样本处理腔体101施加某种温度控制策略，使其内样本实现升降温。具体地，在步骤S4和S6过程中，微流控芯片100停止旋转，通过控制温控装置400与微流控芯片100在旋转轴方向发生相对移动，从而使得温控装置400可对样本处理腔体101的区域进行变温控制。
本申请实施例提供的样本处理系统1000具有如下有益效果：
(1)通过微流控芯片100的结构设计，可以实现第一存储腔体104和第二存储腔体105内的样本分步转移至同一个样本处理腔体101内，以实现同一样本处理腔体101内可以进行多步样本处理过程(如生化反应过程)，即实现不同试剂存储腔体向同一样本处理腔体101内先后输入不同的试剂样本并进行多步反应，降低了样本损耗，温控装置400的设计更简单，成本更低。
(2)通过微流控芯片100配合移液装置300，可以实现不确定体积样本的转移，克服了现有微流控方案难以转移腔体内部分液体的缺点。
(3)移液装置300只用于转移样本和最后处理完的反应产物的输出，不参与中间步骤的样本添加和混匀，由于微流控芯片100旋转运动的存在，移液装置300只需要沿着微流控芯片100的径向移动就可以到达芯片的每一个角落，减少了移液装置300的运动自由度、运动行程范围和系统复杂度，降低了样本处理系统1000的成本和体积。
(3)由于移液装置300不参与中间步骤的样本添加和混匀，大幅减少了一次性耗材(如吸头)的使用，甚至可以完全不使用一次性吸头，而采用可重复使用的试剂针，并在微流控芯片100执行中间步骤时并行进行试剂针的清洗，从而缩短系统运行时间。
请参阅图7所示，本申请实施例还提供了一种生化反应系统2000，该生化反应系统2000可以包括控制模块2100和与控制模块2100通信连接的前述样本处理系统1000。在基因测序领域，该生化反应系统2000例如可以是建库仪或测序仪，即可以将前述样本处理系统1000集成在建库仪或测序仪中，用于进行基因测序文库的构建。
请参阅图8所示，本申请实施例还提供了一种生化检测系统3000，该生化检测系统3000可以包括检测模块3100和前述样本处理系统1000，所述样本处理系统1000用于处理样本以得到产物，所述检测模块3100用于检测所述产物。采用前述样本处理系统1000进行生化反应得到反应产物，之后可以通过检测模块3100对反应产物进行检测，该检测模块3100例如可以是荧光检测模块。
以下给出了三种具有不同实现形式的微流控芯片，通过对具体实施例的描述，以对前述微流控芯片做进一步说明。
实施例1
请参阅图9A所示，一并结合参阅图1，本实施例提供了一种结构形式的微流控芯片100a，该微流控芯片100a在前述微流控芯片100的基础上具体限定了第一通断组件141、第二通断组件151的结构形式，以及暂存腔体103的设置方式。
在微流控芯片100a中，第一通断组件141可以包括一个虹吸阀142，虹吸阀142具有一个波峰a1(即虹吸阀142的流道距离旋转中心a最近的局部区域)，具体地，第一存储腔体104通过虹吸阀142和第一流道143实现与样本处理腔体101的连通，通过虹吸阀142可以实现第一存储腔体104与样本处理腔体101之间的连通或断开。在一些实施例中，第二通断组件151可以包括一个虹吸阀152和一个毛细阀153，其中，虹吸阀152具有两个波峰，分别为波峰b1和波峰b2，毛细阀153位于两个波峰b1和b2之间，具体地，第二存储腔体105通过虹吸阀152、毛细阀153和第二流道154实现与样本处理腔体101的连通，通过虹吸阀152和毛细阀153的配合可以实现第二存储腔体105与样本处理腔体101之间的连通或断开。通过第一通断组件141与第二通断组件151的设计，可以通过控制离心力的大小来实现第一通断组件141与第二通断组件151在不同的阶段打开的目的，进而可以实现第一存储腔体104和第二存储腔体105与样本处理腔体101之间不同时连通。第一通断组件141与第二通断组件151的作用过程及作用原理后续在样本处理方法中进行详细描述。
微流控芯片100a大致为扇形或圆形，微流控芯片100a的圆心即为旋转中心a，暂存腔体103设置在靠近旋转中心a设置，此时，暂存腔体103直接与第一存储腔体104连通，并通过第一存储腔体104与样本处理腔体101连通。
在微流控芯片100a中，第三存储腔体106的数量为两个，分别为样本腔体162和缓冲液腔体163，样本腔体162和缓冲液腔体163沿微流控芯片100a的径向排布，暂存腔体103与缓冲液腔体163沿微流控芯片100a的周向排布。
在微流控芯片100a中，第一存储腔体104与样本处理腔体101之间设有混合区，混合区通过连通第一存储腔体104与样本处理腔体101的第一流道143弯曲形成，可以通过将第一通断组件141与样本处理腔体101之间的第一流道143进行多次弯折形成折叠结构，当样本流经此处时可以实现初步混合。
在微流控芯片100a中，可以只设置一个通气孔108，具体通气孔108通过微流道与第一存储腔体104、第二存储腔体105和样本处理腔体101连通，进而实现前述三个腔体与大气连通，以便于离心过程中样本在不同腔体之间的顺利转移。
请参阅图9A至图9K所示，一并结合参阅图1，使用微流控芯片100a进行样本处理的方法包括以下步骤：
初始状态下，如图9A所示，一并结合图1所示，第一存储腔体104和第二存储腔体105内已分别封装有固定体积(例如20μl、40μl)的第一试剂和第二试剂，第三存储腔体106的缓冲液腔体163内已封装有固定体积(例如20μl)的缓冲液，样本腔体162、暂存腔体103的第二接口131、通气孔108、样本处理腔体101的第三接口111由一层预先贴好的膜密封，保证微流控芯片100a内液体不会泄漏。微流控芯片100a使用前，由用户撕开部分的膜，使得样本腔体162、暂存腔体103和通气孔108与外界连通，随后通过移液装置300输入固定体积(如20μl)的生物样本到样本腔体162内。
上述初始状态准备结束后，微流控芯片100a进入自动化样本处理流程。
第1步，如图9B所示，一并结合图1所示，微流控芯片100a保持静止，移液装置300沿径向移动到样本腔体162吸取生物样本xμl，x的具体取值通过测定生物样本的浓度决定。
第2步，如图9C与图9D所示，一并结合图1所示，微流控芯片100a保持静止，移液装置300沿 径向移动到缓冲液腔体163吸取缓冲液(20-x)μl，进一步地，微流控芯片100a旋转使暂存腔体103的第二接口131到达移液装置300的下方，移液装置300将总体积为20μl的生物样本和缓冲液的混合液转移到暂存腔体103内。
第3步，如图9E所示，一并结合图1所示，驱动装置200驱动微流控芯片100a从静止开始以较高的转速(如1000rpm)开始旋转，离心力驱动20μl的生物样本和缓冲液的混合物到达第一存储腔体104，与此同时，第一存储腔体104的部分样本进入虹吸阀142内，第二存储腔体105的部分样本进入虹吸阀152内，直至虹吸阀142和152内的液面与两个腔体内剩余样本的液面齐平(即与圆心的距离相同)。
第4步，如图9F所示，一并结合图1所示，通过驱动装置200控制微流控芯片100a在上述较高的转速降低到较低的转速(例如600rpm)，此时由于离心力变小，虹吸阀142内的液面将在毛细力的作用下越过波峰a1，并在下游的第一流道143形成的弯曲的混合区中实现初步混匀，最终进入样本处理腔体101内；而此时，虹吸阀152存在两个波峰b1和b2和一个毛细阀153，毛细阀153可以被设置为在较低的转速时无法开启，当虹吸阀152内的液面在毛细力的作用下越过第一个波峰b1后，由于毛细阀153的存在，样本会停留在毛细阀153处，并不会进一步越过第二个波峰b2进入样本处理腔体101内。
第5步，如图9G所示，一并结合图1所示，当第一存储腔体104中的液体样本(第一试剂、生物样本和缓冲液的混合液)完全到达样本处理腔体101后，控制微流控芯片100a停止旋转，并通过样本处理腔体101的下表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第一反应。
第6步，如图9H与图9I所示，一并结合图1所示，第一反应结束后，样本处理腔体101的下表面110与温控装置400脱离，并控制微流控芯片100a重新以较高的转速(如1000rpm)旋转，此时离心力足以打开毛细阀153；随后微流控芯片100a降速至较低的转速(如600rpm)，第二试剂进一步越过虹吸阀152的第二个波峰b2，并最终经第二流道154到达样本处理腔体101内。
第7步，如图9J所示，一并结合图1所示，当第二存储腔体105中的第二试剂完全到达样本处理腔体101后，控制微流控芯片100a以某个加速度正向和反向交替旋转，实现样本处理腔体101内的样本混匀。在另一种实施方式中，也可以控制微流控芯片100a往一个方向加减速旋转来实现混匀的效果。混匀完成后，微流控芯片100a停止旋转，并通过样本处理腔体101下方的表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第二反应。
第8步，如图9K所示，一并结合图1所示，当第二反应结束后，通过移液装置300的径向运动和微流控芯片100a的周向旋转运动的组合，使得移液装置300到达第三接口111上方，并与第三接口111交互，从而将样本处理腔体101内的反应物取出。至此，样本处理流程结束。
如图9L所示展示了包含有多个样本处理区域10的微流控芯片100a，其包含了4个如图9A所示的独立模块，可以实现4种不同样本的同步处理。
实施例2
请参阅图10A所示，一并结合参阅图1，本实施例提供了第二种结构形式的微流控芯片100b，该微流控芯片100b在前述微流控芯片100的基础上具体限定了第一通断组件141、第二通断组件151的结构形式，以及暂存腔体103的设置方式。
在微流控芯片100b中，暂存腔体103与第一存储腔体104连通，且第一存储腔体104与第二存储 腔体105通过第三通断组件107连通，第三通断组件107可以实现第一存在腔体104与第二存储腔体105的连通或断开。其中，第三通断组件107也可以包括毛细阀、疏水阀、虹吸阀以及主动阀等阀中的至少一种。
具体地，在微流控芯片100b中，第一通断组件141可以包括一个虹吸阀144，虹吸阀144具有一个波峰a2，具体地，第一存储腔体104通过虹吸阀144实现与样本处理腔体101的连通，通过虹吸阀144可以实现第一存储腔体104与样本处理腔体101之间的连通或断开。第二通断组件151可以包括一个虹吸阀155，其中，虹吸阀155具有一个波峰b3，具体地，第二存储腔体105通过虹吸阀155和第二流道154实现与样本处理腔体101的连通，通过虹吸阀155可以实现第二存储腔体105与样本处理腔体101之间的连通或断开。第三通断组件107可以包括一个虹吸阀，通过设置虹吸阀可以实现第一存储腔体104与第二存储腔体105之间的连通或断开。
通过第一通断组件141、第二通断组件151与第三通断组件107的设计，可以通过控制离心力的大小来实现第一通断组件141、第二通断组件151与第三通断组件107在不同的阶段打开，进而可以实现第一存储腔体104和第二存储腔体105与样本处理腔体101之间不同时连通。其中虹吸阀的通断原理与前述实施例1中相同，具体在后续样本处理方法中详细描述实现连通的过程及原理。
微流控芯片100b大致为扇形或圆形，微流控芯片100b的圆心即为旋转中心a，暂存腔体103设置在靠近旋转中心a设置。
在微流控芯片100b中，第三存储腔体106的数量为两个，分别为样本腔体162和缓冲液腔体163，样本腔体162和缓冲液腔体163沿微流控芯片100b的径向排布，暂存腔体103与缓冲液腔体163沿微流控芯片100b的周向排布。
在微流控芯片100b中，第一存储腔体104与样本处理腔体101之间设有混合区，混合区通过连通第一存储腔体104与样本处理腔体101的第一流道143弯曲形成，可以通过将第一通断组件141与样本处理腔体101之间的第一流道143进行多次弯折形成折叠结构，当样本流经此处时可以实现初步混合。
在微流控芯片100b中，可以只设置两个通气孔108，一个通气孔108与第一存储腔体104连通，可以同时实现第一存储腔体104和第二存储腔体105与大气连通。另一个通气孔108与样本处理腔体101连通，进而实现样本处理腔体101与大气连通。
请参阅图10A至图10H所示，一并结合参阅图1，使用微流控芯片100b进行样本处理的方法包括以下步骤：
如图10A所示，微流控芯片100b的初始状态与实施例1基本一致，请参见前述实施例1，这里不做过多赘述。
初始状态准备结束后，微流控芯片100b进入自动化样本处理流程，具体包括以下步骤：
第1步和第2步，样本和缓冲液的处理方式与实施例1基本一致请参见前述实施例1的第1步和第2步，这里不做过多赘述。
第3步，如图10B所示，一并结合图1所示，驱动装置200驱动微流控芯片100b从静止开始以某个较高的转速(如1000rpm)开始旋转，离心力驱动20μl的样本和缓冲液的混合液到达第一存储腔体104，与此同时，第一存储腔体104的部分样本进入虹吸阀144内，第二存储腔体105的部分样本进入虹吸阀155内，直至虹吸阀144和155内的液面与两个腔体内剩余样本的液面齐平。
第4步，如图10C所示，一并结合图1所示，通过驱动装置200控制微流控芯片100b在上述较高的转速降低到较低的转速(例如600rpm)，此时由于离心力变小，虹吸阀144内的液面将在毛细力作 用下越过波峰a2。此时，由于第二存储腔体105未与大气连通，其内的第二试剂将无法越过虹吸阀155。
第5步，如图10D所示，一并结合图1所示，当第一存储腔体104中的液体样本(第一试剂、生物样本和缓冲液的混合液)经过弯曲的第一流道143实现初步混匀，并最终完全到达样本处理腔体101，控制微流控芯片100b停止旋转，并通过样本处理腔体101下表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第一反应。
第6步，如图10E与图10F所示，一并结合图1所示，第一反应结束后，样本处理腔体101下表面110与温控装置400脱离，驱动装置200控制微流控芯片100b重新以较高的转速(如1000rpm)旋转，并随后降速至较低的转速(如600rpm)，此时由于第一存储腔体104内的液体已经完全排走，第二存储腔体105实际上通过第三通断组件107(例如虹吸阀)可以与大气连通，从而第二存储腔体105内的第二试剂可以越过虹吸阀155的波峰b3，并最终到达样本处理腔体101内。
第7步，如图10G所示，一并结合图1所示，当第二存储腔体105中的第二试剂完全到达样本处理腔体101后，控制微流控芯片100b以某个加速度正向和反向交替旋转，实现样本处理腔体101内的液体混匀。在另一种实施方式中，也可以控制微流控芯片100b往一个方向加减速旋转来实现混匀的效果。混匀完成后，微流控芯片100b停止旋转，并通过样本处理腔体101下表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第二反应。
第8步，如图10H所示，一并结合图1所示，第二反应结束后，当第二反应结束后，通过移液装置300的径向运动和微流控芯片100b的周向旋转运动的组合，使得移液装置300到达第三接口111上方，并与第三接口111交互，从而将样本处理腔体101内的反应物取出。至此，样本处理流程结束。
实施例3
请参阅图11A，一并结合参阅图1，本实施例提供了一种结构形式的微流控芯片100c，该微流控芯片100c在前述微流控芯片100的基础上具体限定了第一通断组件141、第二通断组件151的结构形式，以及暂存腔体103的设置方式。
在微流控芯片100c中，暂存腔体103与样本处理腔体101直接连通。第一通断组件141和第二通断组件151均可以是主动阀，具体可以为石蜡阀。此时温控装置400还可以为第一通断组件141和第二通断组件151提供温度，以实现主动阀的开启，可以通过温控装置400对第一通断组件141和第二通断组件151在不同阶段进行加热，从而实现二者在不同阶段的开启，以实现第一存储腔体104和第二存储腔体105与样本处理腔体101之间不同时连通。
微流控芯片100c大致为扇形或圆形，微流控芯片100c的圆心即为旋转中心a，暂存腔体103设置在靠近旋转中心a设置。
在微流控芯片100c中，第三存储腔体106的数量为两个，分别为样本腔体162和缓冲液腔体163，暂存腔体103、样本腔体162和缓冲液腔体163沿微流控芯片100c的径向排布。
在微流控芯片100b中，可以只设置一个通气孔108，具体通气孔108通过微流道与第一存储腔体104、第二存储腔体105和样本处理腔体101连通，进而实现前述三个腔体与大气连通，以便于离心过程中样本在不同腔体之间的顺利转移。
请参阅图11A至图11H所示，一并结合参阅图1，使用微流控芯片100c进行样本处理的方法包括以下步骤：
如图11A所示，微流控芯片100c的初始状态与实施例1基本一致，请参见前述实施例1，这里不做过多赘述。
初始状态准备结束后，微流控芯片100c进入自动化样本处理流程，具体包括以下步骤：
第1步和第2步，如图11B所示，样本和缓冲液的处理方式与实施例1基本一致请参见前述实施例1的第1步和第2步，这里不做过多赘述。
第3步，如图11C所示，一并结合图1所示，驱动装置200驱动微流控芯片100c从静止开始以某个较高的转速(如1000rpm)开始旋转，离心力驱动20μl的样本和缓冲液的混合液直接从暂存腔103进入样本处理腔体101内。
第4步，如图11D所示，一并结合图1所示，通过驱动装置200控制微流控芯片100c停止旋转，并通过石蜡阀145下表面112与温控装置400交互，实现对石蜡阀145的加热，使固态的石蜡融化成液态，再控制微流控芯片100c旋转，实现第一试剂从第一存储腔体104到样本处理腔体101的转移。
第5步，如图11E所示，一并结合图1所示，当第一存储腔体104中的第一试剂完全到达样本处理腔体101后，控制微流控芯片100c以某个加速度正向和反向交替旋转，实现样本处理腔体101内的液体混匀。在另一种实施方式中，也可以控制微流控芯片100c往一个方向加减速旋转来实现混匀的效果。混匀完成后，控制微流控芯片100c停止旋转，并通过样本处理腔体101下表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第一反应。
第6步，如图11F所示，一并结合图1所示，第一反应结束后，样本处理腔体101下表面110与温控装置400脱离，通过石蜡阀156下表面113与温控装置400交互，实现对石蜡阀156的加热，使固态的石蜡融化成液态，再控制微流控芯片100c旋转，实现第二试剂从第二存储腔体105到样本处理腔体101的转移。
第7步，如图11G所示，一并结合图1所示，当第二存储腔体105中的第二试剂完全到达样本处理腔体101后，控制微流控芯片100c以某个加速度正向和反向交替旋转，实现样本处理腔体101内的液体混匀。在另一种实施方式中，也可以控制微流控芯片100c往一个方向加减速旋转来实现混匀的效果。混匀完成后，微流控芯片100c停止旋转，并通过样本处理腔体101下表面110与温控装置400交互，实现对样本处理腔体101的升降温操作，进行第二反应。
第8步，如图11H所示，一并结合图1所示，当第二反应结束后，通过移液装置300的径向运动和微流控芯片100c的周向旋转运动的组合，使得移液装置300到达第三接口111上方，并与第三接口111交互，从而将样本处理腔体101内的反应物取出。至此，样本处理流程结束。
最后应说明的是，以上实施例仅用以说明本申请的技术方案而非限制，尽管参照较佳实施例对本申请进行了详细说明，本领域的普通技术人员应当理解，可以对本申请的技术方案进行修改或等同替换，而不脱离本申请技术方案的精神和范围。

Claims (31)

  1. 一种微流控芯片，其特征在于，包括至少一个样本处理区域，所述样本处理区域包括：
    样本处理腔体，所述样本处理腔体用于为样本处理提供空间；以及
    多个存储腔体，所述多个存储腔体用于存储样本，所述多个存储腔体包括第一存储腔体、第二存储腔体和第三存储腔体，所述第一存储腔体和所述第二存储腔体均可与所述样本处理腔体连通，且所述第一存储腔体和所述第二存储腔体与所述样本处理腔体不同时连通，所述第三存储腔体与所述样本处理腔体不连通，所述第三存储腔体具有第一接口，所述第一接口用于与移液装置交互，以将位于所述第三存储腔体内的样本转移至所述样本处理腔体。
  2. 如权利要求1所述的微流控芯片，其特征在于，所述第一存储腔体与所述样本处理腔体之间设有第一通断组件，所述第一通断组件用于控制所述第一存储腔体与所述样本处理腔体之间的连通或断开，所述第二存储腔体与所述样本处理腔体之间设有第二通断组件，所述第二通断组件用于控制所述第二存储腔体与所述样本处理腔体之间的连通或断开，所述第一通断组件和所述第二通断组件不同时打开。
  3. 如权利要求2所述的微流控芯片，其特征在于，所述第一通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种；
    所述第二通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种。
  4. 如权利要求3所述的微流控芯片，其特征在于，所述主动阀包括石蜡阀和气动阀中的至少一种。
  5. 如权利要求1所述的微流控芯片，其特征在于，所述样本处理区域还包括暂存腔体，所述暂存腔体与所述样本处理腔体连通，所述暂存腔体具有第二接口，所述第二接口用于与所述移液装置交互，以将位于所述第三存储腔体内的样本转移至所述暂存腔体。
  6. 如权利要求5所述的微流控芯片，其特征在于，所述暂存腔体与所述样本处理腔体直接连通；或所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通。
  7. 如权利要求6所述的微流控芯片，其特征在于，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通，所述第一存储腔体与所述样本处理腔体之间设有混合区。
  8. 如权利要求7所述的微流控芯片，其特征在于，所述混合区通过连通所述第一存储腔体与所述样本处理腔体的第一流道弯曲形成。
  9. 如权利要求6所述的微流控芯片，其特征在于，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通，所述第一存储腔体还可与所述第二存储腔体连通，所述第一存储腔体与所述第二存储腔体之间设有第三通断组件，所述第三通断组件用于控制所述第一存储腔体和所述第二存储腔体之间的连通和断开。
  10. 如权利要求9所述的微流控芯片，其特征在于，所述第三通断组件包括毛细阀、疏水阀、虹吸阀以及主动阀中的至少一种。
  11. 如权利要求6所述的微流控芯片，其特征在于，所述微流控芯片包括相对设置的第一边缘和第二边缘，所述第三存储腔体靠近所述第一边缘，所述样本处理腔体靠近所述第二边缘，所述第一存储腔体和所述第二存储腔体位于所述样本处理腔体与所述第三存储腔体之间。
  12. 如权利要求11所述的微流控芯片，其特征在于，所述微流控芯片为扇形或圆形，所述第一边缘靠近所述微流控芯片的圆心，当所述暂存腔体与所述样本处理腔体直接连通时，所述暂存腔体靠近所述第二边缘，所述第三存储腔体与所述暂存腔体沿所述微流控芯片的径向排列；当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通时，所述暂存腔体靠近所述第一边缘，所述第三存储腔体与所述暂存腔体沿所述微流控芯片的周向排布。
  13. 如权利要求12所述的微流控芯片，其特征在于，所述微流控芯片包括多个所述样本处理区域，多个所述样本处理区域沿所述微流控芯片的周向排布。
  14. 如权利要求1所述的微流控芯片，其特征在于，所述样本处理腔体具有第三接口，所述第三接口用于供所述移液装置将位于所述样本处理腔体内的样本取出；
    所述微流控芯片上还设有至少一个通气孔，所述样本处理腔体、所述第一存储腔体和所述第二存储腔体通过所述通气孔与外界环境连通。
  15. 一种样本处理系统，其特征在于，包括：
    微流控芯片，所述微流控芯片为如权利要求1至14中任意一项所述微流控芯片；
    移液装置，所述移液装置用于与所述第三存储腔体的第一接口交互，以将位于所述第三存储腔体的第一样本转移至所述样本处理腔体；以及
    驱动装置，所述微流控芯片可拆卸设于所述驱动装置上，所述驱动装置用于驱动位于所述第一存储腔体内的第二样本和位于所述第二存储腔体内的第三样本分别转移至所述样本处理腔体。
  16. 如权利要求15所述的样本处理系统，其特征在于，所述驱动装置驱动所述微流控芯片绕一旋转中心旋转以产生离心力，所述离心力用于驱动位于所述第一存储腔体内的第二样本和位于所述第二存储腔体内的第三样本分别转移至所述样本处理腔体。
  17. 如权利要求15所述的样本处理系统，其特征在于，当所述样本处理区域还包括所述暂存腔体时，所述移液装置用于将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体，所述驱动装置还用于驱动位于所述暂存腔体内的所述第一样本转移至所述样本处理腔体。
  18. 如权利要求16所述的样本处理系统，其特征在于，所述移液装置可沿相互垂直的第一方向和第二方向做直线运动，所述第一方向为所述微流控芯片的旋转径向，所述第二方向为垂直所述微流控芯片的旋转平面的方向。
  19. 如权利要求18所述的样本处理系统，其特征在于，所述移液装置包括固定臂和移液臂，所述固定臂设于所述旋转中心，所述移液臂的一端设于所述固定臂上，所述移液臂远离所述固定臂的一端位于所述微流控芯片远离所述驱动装置的一侧，且所述移液臂可沿所述第一方向和所述第二方向做直线运动。
  20. 如权利要求15所述的样本处理系统，其特征在于，还包括温控装置，所述温控装置用于为所述样本处理腔体提供生化反应所需的温度。
  21. 如权利要求20所述的样本处理系统，其特征在于，当所述第一通断组件或所述第二通断组件为石蜡阀时，所述温控装置还用于加热所述第一通断组件或所述第二通断组件。
  22. 如权利要求20所述的样本处理系统，其特征在于，所述温控装置设于所述微流控芯片靠近所述驱动装置的一侧，所述温控装置可朝向或远离所述微流控芯片移动。
  23. 一种样本处理方法，其特征在于，包括：
    提供微流控芯片，所述微流控为如权利要求1至14中任意一项所述的微流控芯片；
    将所述第三存储腔体内的第一样本转移至所述样本处理腔体；
    驱动所述第一存储腔体内的第二样本转移至所述样本处理腔体；
    所述第一样本和所述第二样本在所述样本处理腔体进行第一处理过程，以得到第一处理产物；
    驱动所述第二存储腔体内的第三样本转移至所述样本处理腔体；以及
    所述第一处理产物和所述第三样本在所述样本处理腔体进行第二处理过程，以得到第二处理产物。
  24. 如权利要求23所述的样本处理方法，其特征在于，当所述样本处理区域还包括所述暂存腔体 时，
    所述将所述第三存储腔体中的第一样本转移至所述样本处理腔体中的步骤包括：
    通过移液装置将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体；以及
    通过驱动装置为所述微流控芯片提供驱动力，以将位于所述暂存腔体中的所述第一样本转移至所述样本处理腔体。
  25. 如权利要求23所述的样本处理方法，其特征在于，当所述第三存储腔体的数量为两个时，两个所述第三存储腔体分别为用于存储第一样本的样本腔体和用于存储缓冲液的缓冲液腔体，所述通过移液装置将位于所述第三存储腔体内的所述第一样本转移至所述暂存腔体的步骤包括：
    通过所述移液装置将第一体积的所述第一样本由所述样本腔体转移至所述暂存腔体，并通过所述移液装置将第二体积的所述缓冲液由所述缓冲液腔体转移至所述暂存腔体，其中，所述第一体积和所述第二体积之和等于所述样本腔体内存储的所有所述第一样本的体积。
  26. 如权利要求24所述的样本处理方法，其特征在于，当所述暂存腔体通过所述第一存储腔体与所述样本处理腔体连通时，所述第一样本和所述第二样本转移至所述样本处理腔体同步进行，包括：
    通过驱动装置为所述微流控芯片提供第一离心力，以驱动位于所述暂存腔体内的所述第一样本转移至所述第一存储腔体并与所述第二样本形成第一混合物；以及
    通过驱动装置为所述微流控芯片提供第二离心力，以使所述第一存储腔体与所述样本处理腔体连通，且所述第二存储腔体与所述样本处理腔体断开，并驱动位于所述第一存储腔体内的所述第一混合物转移至所述样本处理腔体。
  27. 如权利要求26所述的样本处理方法，其特征在于，所述第一存储腔体与所述样本处理腔体之间设有混合区，在所述第一混合物转移至所述样本处理腔体之前，所述方法还包括：
    在所述第二离心力的作用下，所述第一混合物在所述混合区进行混合。
  28. 如权利要求26所述的样本处理方法，其特征在于，所述驱动所述第二存储腔体内的第三样本转移至所述样本处理腔体中的步骤包括：
    通过驱动装置为所述微流控芯片提供第三离心力，以使所述第二存储腔体与所述样本处理腔体连通，并驱动位于所述第二存储腔体内的所述第三样本转移至所述样本处理腔体中。
  29. 如权利要求23所述的样本处理方法，其特征在于，在得到所述第二处理产物之后，所述方法还包括：
    通过移液装置将所述样本处理腔体内的所述第二处理产物取出。
  30. 一种生化反应系统，其特征在于，包括控制模块和与所述控制模块通信连接的样本处理系统，所述样本处理系统为如权利要求15至21中任意一项所述的样本处理系统。
  31. 一种生化检测系统，其特征在于，包括检测模块和如权利要求15至21中任意一项所述的样本处理系统，所述样本处理系统用于处理样本以得到产物，所述检测模块用于检测所述产物。
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