A lab-on-a-chip

Abstract

The on-chip lab disclosed in the present invention includes a sample inlet, a reaction zone, and a waste liquid pool, wherein the inlet of the reaction zone is connected to the sample inlet through a flow channel, and the outlet of the reaction zone is connected to the waste liquid pool through a flow channel; the reaction zone includes at least two reactors connected in sequence, wherein the inlet and outlet of the reaction zone are respectively connected to a first pump body through a flow channel, and the first pump body drives the liquid in the flow channel to circulate in the at least two reactors under the drive of the pump head, wherein different reactants are attached to the inner surfaces of different reactors. In this way, the first pump body can drive the liquid in the flow channel to circulate in the at least two reactors in the reaction zone under the drive of the pump head, and the sample contacts each reactor multiple times in the reaction zone, and each reactor can fully contact the sample in the flow channel, thereby reducing the sample amount during multiple tests of the on-chip lab.

Description

Technical Field

[0001] The present invention relates to the field of testing technology, and in particular to a laboratory on a chip. Background Art

[0002] Lab-on-a-chip technology integrates the basic operating units of sample preparation, reaction, separation, and detection in the biological, chemical, and medical analysis process onto a micron-scale chip to automatically complete the entire analysis process. Due to its huge potential in the fields of biology, chemistry, and medicine, it has developed into a new research field that intersects biology, chemistry, medicine, fluids, electronics, materials, and mechanics.

[0003] Currently, a sample can usually only be used for one test. When multiple tests are required, multiple samples need to be obtained for separate tests. However, large-scale sampling may affect the target, and in some cases it is even impossible to obtain a large number of samples.

[0004] It can be seen that in the existing technology, how to reduce the sample size during multiple tests in the on-chip laboratory has become a technical problem that needs to be solved urgently. Summary of the invention

[0005] In view of this, the present invention proposes a lab-on-a-chip to solve the above technical problems.

[0006] First, to achieve the above-mentioned purpose, the present invention proposes a lab-on-chip, which includes:

[0007] A sample inlet, a reaction zone and a waste liquid pool, wherein the inlet of the reaction zone is connected to the sample inlet through a flow channel, and the outlet of the reaction zone is connected to the waste liquid pool through a flow channel;

[0008] The reaction zone includes at least two reactors connected in sequence, and the inlet and outlet of the reaction zone are respectively connected to the first pump body through flow channels. The first pump body drives the liquid in the flow channel to circulate in the at least two reactors under the drive of the pump head, wherein different reactants are attached to the inner surfaces of different reactors.

[0009] Optionally, the lab-on-a-chip further comprises a reagent area, and the reagent area is connected to the inlet of the reaction area through a flow channel;

[0010] The reagent area includes at least three reagent packs, and a valve is provided between each reagent pack and the entrance of the reaction area. When one of the valves is opened, the liquid in the reagent pack corresponding to the valve flows into the entrance of the reaction area under the pressure of external force.

[0011] Optionally, a pre-treatment zone is provided between the sample inlet and the inlet of the reaction zone, and the pre-treatment zone is used to pre-treat the sample;

[0012] The pre-treatment area includes a filter disposed between the sample inlet and the inlet of the reaction area.

[0013] Optionally, the pre-treatment zone further comprises a first separator disposed between the filter and the inlet of the reaction zone, and the first separator is used to remove bubbles doped in the sample.

[0014] Optionally, the pretreatment area also includes a second pump body arranged between the sample inlet and the filter, and the second pump body supplies air to the flow channel between the sample inlet and the filter under the drive of the pump head to squeeze the sample in the flow channel to flow toward the filter.

[0015] Optionally, the pre-treatment area further includes a capillary blood collection tube of preset capacity, and the sample inlet is a blood collection port of the capillary blood collection tube.

[0016] Optionally, the on-chip lab further comprises a cover body, and the cover body is used to close the sample inlet after the sample is injected into the sample inlet.

[0017] Optionally, a second separator is provided at the outlet of the waste liquid pool, and the second separator is used to discharge bubbles from the waste liquid pool.

[0018] Optionally, the on-chip lab further comprises a traction clamp, and the traction clamp is used to achieve a clamp connection between the on-chip lab and a detection device.

[0019] Optionally, a first check valve is provided between two adjacent reagent packages, a second check valve is provided between the inlet of the pretreatment zone and the reaction zone, and a third check valve is provided between the first pump body and the inlet of the reaction zone.

[0020] Optionally, the inner wall of the flow channel is subjected to surface hydrophilic treatment.

[0021] Compared with the prior art, the on-chip lab proposed in the present invention includes a sample inlet, a reaction zone and a waste liquid pool, wherein the inlet of the reaction zone is connected to the sample inlet through a flow channel, and the outlet of the reaction zone is connected to the waste liquid pool through a flow channel; the reaction zone includes at least two reactors connected in sequence, wherein the inlet and outlet of the reaction zone are respectively connected to a first pump body through a flow channel, and the first pump body drives the liquid in the flow channel to circulate in the at least two reactors under the drive of the pump head, wherein different reactants are attached to the inner surfaces of different reactors. In this way, the on-chip lab provided by the present invention is provided with a first pump body connected to the inlet and outlet of the reaction zone, and can drive the liquid in the flow channel to circulate in the at least two reactors in the reaction zone under the drive of the pump head, and each reactor can fully contact with the sample in the flow channel, thereby reducing the sample amount during multiple tests of the on-chip lab. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a connection diagram of a lab-on-a-chip provided by an embodiment of the present invention.

[0023] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0024] It should be understood that the specific embodiments described herein are only used to explain the present invention, and are not used to limit the present invention.

[0025] See also Figure 1 , Figure 1 FIG. 1 is a schematic diagram of a connection of a lab-on-a-chip provided by an embodiment of the present invention. Figure 1 As shown, the on-chip lab 100 includes a sample inlet 10 , a reaction zone 30 , and a waste liquid pool 40 . The inlet of the reaction zone 30 is connected to the sample inlet 10 through a flow channel 50 , and the outlet of the reaction zone 30 is connected to the waste liquid pool 40 through a flow channel 50 .

[0026] The reaction zone 30 includes at least two reactors 31 connected in sequence, that is, the at least two reactors 31 are connected in series, and the inlet and outlet of the reaction zone 30 are respectively connected to the first pump body 32 through the flow channel 50. The first pump body 32 drives the liquid in the flow channel 50 to circulate in the at least two reactors 31 under the drive of the pump head. Different reactants are attached to the inner surfaces of different reactors 31 for testing different items. The number of the at least two reactors 31 can be set according to the detection needs. In this embodiment, the number of the at least two reactors 31 can be set to 6, for example Figure 1 31A, 31B, 31C, 31D, 31E, 31F in the reactor 31. The inner channel of the reactor 31 may be in an "S" shape. In the embodiment of the present invention, the reactor 31 may be manufactured by a hot pressing film laminating process.

[0027] The waste liquid pool 40 is used to collect waste liquid. For example, after the liquid reacts in the reaction zone 30, it will flow into the waste liquid pool 40. In this embodiment, the channel in the waste liquid pool 40 is a serpentine structure with a diameter of no more than 3 mm.

[0028] In some embodiments of the present invention, other equipment may be used to pre-treat the sample, and then the pre-treated sample may be directly injected into the sample inlet 10. In other embodiments of the present invention, the on-chip laboratory 100 may also include a pre-treatment area 60, and the pre-treatment area 60 performs pre-treatment on the sample. For example, when the sample is whole blood and the required test sample is plasma, if the on-chip laboratory 100 does not include the pre-treatment area 60, the collected whole blood may be separated in the laboratory, and then the separated plasma may be injected into the sample inlet 10. If the on-chip laboratory 100 includes the pre-treatment area 60, the collected whole blood may be directly injected into the sample inlet 10, and the pre-treatment area 60 performs pre-treatment on the collected whole blood.

[0029] In some embodiments of the present invention, the on-chip lab 100 may further include a reagent inlet, which is connected to the inlet of the reaction zone 30 through a flow channel, and the tester may inject the reagent required for the reaction into the reaction zone 30 through the reagent inlet. The on-chip lab 100 may also include a reagent zone, in which the reagent required for the reaction is pre-injected.

[0030] In an embodiment of the present invention, the on-chip lab includes a sample inlet, a reaction zone, and a waste liquid pool, the inlet of the reaction zone is connected to the sample inlet through a flow channel, and the outlet of the reaction zone is connected to the waste liquid pool through a flow channel; the reaction zone includes at least two reactors connected in sequence, the inlet and outlet of the reaction zone are respectively connected to a first pump body through a flow channel, and the first pump body drives the liquid in the flow channel to circulate in the at least two reactors under the drive of the pump head, wherein different reactants are attached to the inner surfaces of different reactors. In this way, the on-chip lab provided by the present invention is provided with a first pump body connected to the inlet and outlet of the reaction zone, and can drive the liquid in the flow channel to circulate in the at least two reactors in the reaction zone under the drive of the pump head, and each reactor can fully contact with the sample in the flow channel, thereby reducing the sample amount during multiple tests of the on-chip lab.

[0031] Optionally, the lab-on-a-chip further comprises a reagent area, and the reagent area is connected to the inlet of the reaction area through a flow channel;

[0032] The reagent area includes at least three reagent packs, and a valve is provided between each reagent pack and the entrance of the reaction area. When one of the valves is opened, the liquid in the reagent pack corresponding to the valve flows into the entrance of the reaction area under the pressure of external force.

[0033] In this embodiment, the on-chip lab 100 further includes a reagent area 20, which is connected to the inlet of the reaction area 30 through a flow channel. The reagent area 20 includes at least three reagent packs 21, and a valve 22 is provided between each reagent pack 21 and the inlet of the reaction area 30. When one of the valves 22 is opened, the liquid in the reagent pack 21 corresponding to the valve 22 flows into the inlet of the reaction area 30 under the pressure of an external force.

[0034] When the valve 22 is in the open state, the reagent pack 21 can squeeze the liquid in the reagent pack 21 into the flow channel 20 under the pressure of external force, and flow into the entrance of the reaction zone 30 through the flow channel 50. The number of the reagent packs 21 is not less than four, and the specific number can be set according to the detection needs. The volumes of the reagent packs 21 can be the same or different. In this embodiment, the number of the reagent packs 21 can be 6, for example Figure 1 As shown in 21A, 21B, 21C, 21D, 21E, 21F, the volume of each reagent pack 21 is 100uL. Each reagent pack corresponds to a valve, for example Figure 1 22A, 22B, 22C, 22D, 22E, 22F shown.

[0035] It is understood that in order to prevent the reagent pack 21 from flowing into the adjacent empty pack under external force, a check valve is provided between adjacent reagent packs 21, and the reagent packs 21 are squeezed one by one from right to left during squeezing. For example, when the number of the reagent packs 21 is four, that is, including Figure 1 When the reagent packs 21A, 21B, 21C, and 21D are shown in the figure, if the on-chip lab 100 is used for antigen detection, the liquid in the reagent pack 21A is a cleaning liquid, the liquid in the reagent pack 21B is an enzyme-labeled antibody, the liquid in the reagent pack 21C is a cleaning liquid, and the liquid in the reagent pack 21D is a substrate. It can be understood that when multiple tests are performed, the liquid included in the reagent pack 21B is a mixed enzyme, and the mixed enzyme includes all enzymes used to implement the multiple tests.

[0036] During the test, after the sample is injected into the reaction area 30, the first pump body 32 circulates between the at least two reactors 31 under the action of the pump head, so that the sample is fully in contact with the reactant attached to the inner surface of each reactor 31, and the analyte in the sample reacts with the reactant corresponding to the analyte in the reactor 31, thereby adhering to the surface of the reactor 31. The analyte can be an antigen or an antibody, and correspondingly, the reactant can be an antibody or an antigen. It can be understood that when the analyte is an antigen, its corresponding reactant is an antibody that can bind to the antigen; when the analyte is an antibody, its corresponding reactant is an antigen that can bind to the antibody. The valve 22A corresponding to the reagent pack 21A is opened, and the reagent pack 21A is squeezed so that the cleaning solution in the reagent pack 21A flows into the reaction area 30, which is used to clean the unbound sample in the reaction area 30 (for example, cleaning the unbound antigen or antibody in the reaction area 30). Further, the valve 22B corresponding to the reagent pack 21B is opened, and the reagent pack 21B is squeezed, so that the enzyme-labeled antibody in the reagent pack 21B flows into the reaction area 30 for reaction. Specifically, the enzyme-labeled antibody reacts with the analyte (i.e., the antigen or antibody in the sample) attached to the surface of the reactor 31, and finally adheres to the surface of the reactor 31. The valve 22C corresponding to the reagent pack 21C is opened, and the reagent pack 21C is squeezed, so that the cleaning liquid in the reagent pack 21C flows into the reaction area 30, which is used to clean the enzyme-labeled antibody remaining in the reaction area 30. Finally, the valve 22D corresponding to the reagent pack 21D is opened, and the reagent pack 21D is squeezed, so that the substrate in the reagent pack 21D flows into the reaction area 30 to react with the enzyme-labeled antibody attached to the surface of each reactor 31, and the content of the analyte is detected by detecting the light intensity data in each reactor 31.

[0037] It should be noted that if there are a lot of enzyme-labeled antibodies remaining in the reaction area 30, it is easy to have a greater impact on the test results. Therefore, the capacity of the reagent pack 21C can be set larger than that of other reagent packs, and more cleaning liquid can be used to clean the reaction area 30. In some embodiments, considering that the external extrusion device can only extrude reagent packs of the same specification, the cleaning agent can be poured into a plurality of consecutive reagent packs 21.

[0038] Optionally, a pre-treatment zone is provided between the sample inlet and the inlet of the reaction zone, and the pre-treatment zone is used to pre-treat the sample;

[0039] The pre-treatment area includes a filter disposed between the sample inlet and the inlet of the reaction area.

[0040] In this embodiment, a pre-processing area 60 is provided between the sample inlet 10 and the entrance of the reaction area 30, and the pre-processing area 60 is used to pre-process the sample. Specifically, the pre-processor 60 includes a filter 61, which is provided between the sample inlet 10 and the entrance of the reaction area 30 and is used to filter the sample.

[0041] In the case of using a centrifuge to separate samples, in order to avoid wasting testing resources, it is usually necessary to wait until a certain batch of samples is accumulated before starting the centrifuge for separation, and then further testing is performed. In this embodiment, the pre-treatment area 60 can also filter the samples, and there is no need for prior centrifugation operations. Testing can be performed at any time to achieve rapid testing.

[0042] In addition, for example, it usually takes at least 10 minutes to separate the sample using a centrifuge, while it only takes 2 minutes to filter the sample through the pre-treatment zone 60. It can be seen that compared with the centrifugal operation, the pre-treatment zone 60 in this embodiment can effectively reduce the time for filtering the sample, thereby speeding up the detection speed.

[0043] Optionally, the filter is arranged at a position close to the inlet of the reaction zone.

[0044] In this embodiment, the filter 61 is disposed near the entrance of the reaction zone 30, so that the distance that the filtered sample (eg, plasma) flows into the entrance of the reaction zone 30 can be shortened, thereby reducing the waste of the filtered sample.

[0045] Optionally, the pre-treatment zone further comprises a first separator disposed between the filter and the inlet of the reaction zone, and the first separator is used to remove bubbles doped in the sample.

[0046] In this embodiment, the pre-treatment area 60 further includes a first separator 62 . The first separator 62 is disposed between the filter 61 and the inlet of the reaction area 30 , and is used to remove bubbles mixed in the sample.

[0047] It is understandable that bubbles are inevitably introduced during the sample injection process. In this embodiment, a first separator 62 is provided between the filter 61 and the entrance of the reaction zone 30. The first separator 62 is used to remove bubbles mixed in the sample, thereby effectively preventing the reaction volume from being occupied by bubbles and improving the detection accuracy.

[0048] Optionally, the pretreatment area also includes a second pump body arranged between the sample inlet and the filter, and the second pump body supplies air to the flow channel between the sample inlet and the filter under the drive of the pump head to squeeze the sample in the flow channel to flow toward the filter.

[0049] In this embodiment, the pre-treatment area 60 further includes a second pump body 63 disposed between the sample inlet 10 and the filter 61. The second pump body 63 supplies air to the flow channel 50 between the sample inlet 10 and the filter 61 under the drive of the pump head, so as to squeeze the sample in the flow channel 50 to flow toward the filter 61. In this way, the sample filtration can be effectively accelerated, thereby reducing the filtration time and speeding up the detection speed.

[0050] In some embodiments of the present invention, a third pump body (not shown) may be further provided between the filter 61 and the reaction zone 30. Driven by the pump head, the third pump body may push the plasma remaining in the flow channel 50 to flow into the reaction zone 30, thereby effectively improving the utilization rate of the plasma.

[0051] Optionally, the pre-treatment area further includes a capillary blood collection tube of preset capacity, and the sample inlet is a blood collection port of the capillary blood collection tube.

[0052] It is understandable that during the sampling process, the user may not be clear about the specific sampling volume. Too little sample will affect the test results or even lead to failure to detect, and too much sample will cause unnecessary waste. In this embodiment, a capillary blood sampling tube 64 of preset capacity is set in the pre-treatment area 60, and the sample inlet 10 is the blood sampling port of the capillary blood sampling tube 64. The sample flows in through the capillary blood sampling tube 64. When the channel of the capillary blood sampling tube 64 of preset capacity is filled, the detection can be started. The preset capacity can be set according to the required sample volume, and the preset capacity is not less than the sample volume. For example, when the sample volume is 100uL, the preset capacity can be set to 200uL.

[0053] Optionally, the on-chip lab further comprises a cover body, and the cover body is used to close the sample inlet after the sample is injected into the sample inlet.

[0054] When a second pump body 63 is provided between the sample inlet 10 and the filter 61 , the sample inlet 10 needs to be sealed after the sample is injected into the sample inlet 10 , so as to prevent the second pump body 63 from pumping the sample out of the sample inlet 10 when working.

[0055] In this embodiment, the on-chip lab 100 further includes a cover 11 , and the cover 11 is used to close the sample inlet 11 after the sample is injected into the sample inlet 11 , thereby preventing the second pump 20 from pumping the sample out from the sample inlet 10 when working.

[0056] Optionally, a second separator is provided at the outlet of the waste liquid pool, and the second separator is used to discharge bubbles from the waste liquid pool.

[0057] In this embodiment, a second separator 70 is disposed at the outlet of the waste liquid pool 40 , and the second separator 70 is used to discharge bubbles from the waste liquid pool 40 .

[0058] In some embodiments of the present invention, when the pre-treatment area 60 is provided with the second pump body 63, the second pump body 63 can be directly connected to the second separator 70, so that the second pump body 63 can inhale air from the waste liquid pool 40 when working. After the air in the waste liquid pool 40 passes through the second separator 70, the impurities have been filtered out by the second separator 70, thereby effectively ensuring that the second pump body 63 inhales clean air.

[0059] Optionally, the on-chip lab further comprises a traction clamp, and the traction clamp is used to achieve a clamp connection between the on-chip lab and a detection device.

[0060] In this embodiment, the on-chip lab 100 further includes a traction clamp (not shown), which is used to achieve a clamping connection between the on-chip lab 100 and a detection device.

[0061] Optionally, a first check valve is provided between two adjacent reagent packages, a second check valve is provided between the inlet of the pretreatment zone and the reaction zone, and a third check valve is provided between the first pump body and the inlet of the reaction zone.

[0062] In this embodiment, a first check valve 23 is provided between two adjacent reagent packs 21. The first check valve 23 can prevent the liquid in the reagent pack from flowing into the adjacent empty pack when one of the reagent packs is squeezed, thereby effectively reducing the waste of liquid.

[0063] A second check valve 80 is provided between the pre-treatment zone 60 and the entrance of the reaction zone 30 , and the second check valve 80 prevents the liquid from bypassing the second pump body 63 when the pre-treatment zone 60 is working and / or the liquid in the reagent pack 21 is poured into the reaction zone 30 .

[0064] A third check valve 90 is disposed between the first pump body 32 and the inlet of the reaction zone 30 , and the third check valve 90 is used to prevent liquid from flowing back to the first pump body 32 when the first pump body 32 is working.

[0065] Optionally, the inner wall of the flow channel is subjected to surface hydrophilic treatment.

[0066] In this embodiment, the inner wall of the flow channel 50 is treated with hydrophilic surface, which can reduce the adhesion of the sample in the flow channel 15, improve the utilization rate of the sample, and effectively reduce the generation of bubbles. Preferably, the size of the flow channel 15 is not less than 3 mm.

[0067] It is understandable that the inner wall of the flow channel 50 can be directly made of hydrophilic material, or made of hydrophobic material and then subjected to hydrophilic treatment. For example, it can be made of plastics such as polypropylene, polyethylene, polymethyl methacrylate, etc., and then subjected to hydrophilic treatment to make its surface hydrophilic.

[0068] Optionally, a first grating hole 24 is provided at a position corresponding to each reagent pack 21, and a second grating hole 33 is provided at a position corresponding to each reactor 31. The first grating hole 24 and the second grating hole 33 are used to realize accurate positioning of the reagent pack 21 and the reactor 31 when the on-chip lab 100 is connected to a detection device, so that the detection device can know the specific position of each reagent pack 12 and each reactor 31, thereby successfully completing the detection process.

[0069] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A lab-on-a-chip, characterized in that: The on-chip lab comprises a sample inlet, a reaction zone and a waste liquid pool, wherein the inlet of the reaction zone is connected to the sample inlet through a flow channel, and the outlet of the reaction zone is connected to the waste liquid pool through a flow channel; The reaction zone includes at least two reactors connected in sequence, the inlet and outlet of the reaction zone are respectively connected to the first pump body through a flow channel, and the first pump body drives the liquid in the flow channel to circulate in the at least two reactors under the drive of the pump head, wherein different reactants are attached to the inner surfaces of different reactors; Wherein, the on-chip laboratory further comprises a reagent area, and the reagent area is connected to the inlet of the reaction area through a flow channel; The reagent area includes at least three reagent packs, each of which is provided with a valve between the reagent pack and the entrance of the reaction area, and when one of the valves is opened, the liquid in the reagent pack corresponding to the valve flows into the entrance of the reaction area under the pressure of external force; Among them, a first check valve is arranged between two adjacent reagent packages, a second check valve is arranged between the pre-treatment zone and the inlet of the reaction zone, and a third check valve is arranged between the first pump body and the inlet of the reaction zone.

2. The lab-on-a-chip according to claim 1, wherein: A pre-treatment area is provided between the sample inlet and the inlet of the reaction area, and the pre-treatment area is used to pre-treat the sample; The pre-treatment area includes a filter disposed between the sample inlet and the inlet of the reaction area.

3. The lab-on-a-chip according to claim 2, wherein: The pre-treatment zone further includes a first separator disposed between the filter and the inlet of the reaction zone, and the first separator is used to remove bubbles doped in the sample.

4. The lab-on-a-chip according to claim 2, wherein: The pre-treatment area also includes a second pump body arranged between the sample inlet and the filter. The second pump body supplies air to the flow channel between the sample inlet and the filter under the drive of the pump head to squeeze the sample in the flow channel to flow toward the filter.

5. The lab-on-a-chip according to claim 2, wherein: The pre-treatment area also includes a capillary blood collection tube with a preset capacity, and the sample inlet is a blood collection port of the capillary blood collection tube.

6. The lab-on-a-chip according to claim 1, wherein: The on-chip lab further includes a cover body, which is used to close the sample inlet after the sample is injected into the sample inlet.

7. The lab-on-a-chip according to claim 1, wherein: The outlet of the waste liquid pool is provided with a second separator, and the second separator is used to discharge the bubbles in the waste liquid pool.

8. The lab-on-a-chip according to claim 1, wherein: The on-chip lab also includes a traction clamping position, and the traction clamping position is used to realize a clamping connection between the on-chip lab and a detection device.

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