Detection chip and detection device

Abstract

The utility model discloses a detection chip and a detection device. The detection chip comprises a sample adding groove, a separation unit, a flow dividing unit, at least one injection groove, at least one detection groove and at least one waste liquid unit. By using the detection chip disclosed by the utility model, the functions of separating, reacting and cleaning a sample to be detected on a single chip can be realized only by adjusting the rotation direction and the acceleration during centrifugation, and the detection of the sample can be conveniently and quickly completed. In addition, a stepped groove in the waste liquid unit can further avoid the problem of backflow of waste liquid.

Description

TECHNICAL FIELD

[0001] The utility model relates to a kind of detection chip, detection device and detection method applied to biological detection technical field, the detection chip can be realized in single chip to the function of separating, reaction and washing of sample to be measured, and the step groove contained in waste liquid unit can further avoid the problem of waste liquid backflow. BACKGROUND

[0002] There are many physiological or clinical information detection substances in body fluid samples such as plasma, urine and saliva, so that medical personnel or testing units can quickly understand the physical condition of individuals.

[0003] The sensitivity of detection methods is increasing, the application range of biological detection is rapidly expanding, the operation threshold is gradually reduced, and the commercial value is becoming increasingly important. Among them, enzyme-linked immunosorbent assay (ELISA) is also a commonly used biological detection technology.

[0004] However, in order to ensure the accuracy of the test results, the sample needs to go through a series of operations such as centrifugation, reaction, washing, etc. in the detection process. In the prior art, the method of detecting substances in the sample generally first centrifuges with a large centrifuge, and then transfers to a special detection instrument for reaction, washing and detection.

[0005] Such segmented operation not only increases the risk of sample contamination, but also requires operators to have high professional knowledge. Further, with the development of microfluidic control technology, although the existing detection chip can realize sample separation, an integrated technology that completes all detection processes on the same detection chip has not yet been invented. SUMMARY

[0006] To solve the problems mentioned in the prior art, the utility model provides a detection chip and a detection device. The detection chip includes a sample addition groove, a separation unit, a flow splitting unit, at least one detection groove, at least one injection groove, and at least one waste liquid unit.

[0007] The separation unit is connected to the sample addition groove, and the flow splitting unit is connected to the separation unit. The at least one detection groove is connected to the flow splitting unit, and the at least one injection groove is connected to a flow channel that communicates with the flow splitting unit and each of the at least one detection groove. Finally, the at least one waste liquid unit is connected to the at least one detection groove. Each of the at least one waste liquid unit includes a step groove.

[0008] Based on the foregoing detection chip, the detection device of the utility model includes a driving mechanism. Specifically, the detection chip is detachably connected to the driving mechanism.

[0009] The above brief description of the present application is intended to provide a basic understanding of the several aspects and technical features of the present application. The brief description of the present application is not a detailed description of the present application, and therefore its purpose is not to particularly list the key or important elements of the present application, nor to define the scope of the present application, but only to present several concepts of the present application in a simple manner. BRIEF DESCRIPTION OF DRAWINGS

[0010] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the drawings required to be used in the embodiment or prior art description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and those skilled in the art can obtain other drawings according to the structure of these drawings without labor.

[0011] Figure 1 is a structural schematic diagram of a detection chip in most embodiments of the present application.

[0012] Figure 2 is a structural schematic diagram of a separation unit of a detection chip in most embodiments of the present application.

[0013] Figure 3 is a structural schematic diagram of a shunt unit of a detection chip in most embodiments of the present application.

[0014] Figure 4 is a structural schematic diagram of a shunt unit in a specific embodiment.

[0015] Figure 5 is a structural schematic diagram of an injection groove in a specific embodiment.

[0016] Figure 6 is a structural schematic diagram of a detection groove in a specific embodiment.

[0017] Figure 7 is a structural schematic diagram of a detection chip waste liquid unit in a specific embodiment.

[0018] Figure 8 is a structural schematic diagram of a waste liquid unit in a specific embodiment.

[0019] Figures 9 to 11 is a structural schematic diagram of a detection chip in different embodiments.

[0020] Figure 12 is a structural schematic diagram of a detection device in most embodiments of the present application.

[0021] Figure 13 is a structural schematic diagram of a detection device in a specific embodiment.

[0022] Figure 14 is a flow chart of the detection method in a preferred embodiment of the utility model.

[0023] Figure 15 is a schematic diagram of the chip operation method in a preferred embodiment of the utility model.

[0024] In the drawings, 1-detection chip, 10-rotation center, 21-sample adding groove, 211-sample adding hole, 22-separation unit, 221-first flow channel, 222-separation groove, 223-first micro flow channel, A1-first connection end, A2-second connection end, A3-first turning end, 23-flow separation unit, 231-flow separation channel, 232-quantitative groove, 233-second micro flow channel, 234-liquid storage groove, 2341-first liquid storage cavity, 2342-second liquid storage cavity, 235-first micro flow valve, 24-injection groove, 240-accommodation space, 241-limiting sill, 25-detection groove, 251-first detection cavity, 252-second detection cavity, 26-waste liquid unit, 261-third micro flow channel, 262-waste liquid groove, 263-second micro flow valve, 264-exhaust hole, 265-step groove, B1-third connection end, B2-second turning end, B3-fourth connection end, 3-driving mechanism, 4-magnetic mechanism, 41-magnetic block, D-detection device, (A)-(F)-steps, a-g-states. DETAILED DESCRIPTION

[0025] The technology in the embodiments of the utility model will be described clearly and completely below with reference to the drawings in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, rather than all the embodiments. Based on the embodiments in the utility model, all the other embodiments obtained by those skilled in the art without labor belong to the scope of protection of the utility model.

[0026] Please refer to Figure 1 , Figure 1 is a structural schematic diagram of the detection chip in most embodiments of the utility model. As shown in Figure 1 , Figure 1 The detection chip 1 in the embodiments comprises a sample adding groove 21, a separation unit 22, a flow separation unit 23, at least one injection groove 24, at least one detection groove 25 and at least one waste liquid unit 26 arranged outwardly from the rotation center 10.

[0027] Among them, Figure 1 The separation unit 22 in the embodiments is connected with the sample adding groove 21. The separation unit 22 is used for separating the to-be-detected sample into groups that can be detected subsequently, i.e. detection samples, according to the density gradient. As for the rest of the samples, because the density of the rest of the samples is different from that of the detection samples, the samples with other densities are retained in the separation unit 22 as a group.

[0028] Next, the shunt unit 23 of the present embodiment is connected with the separation unit 22. The shunt unit 23 is used to shunt the detection sample after density gradient separation into at least one detection slot 25. The at least one injection slot 24 is connected with the detection slot 25, and the injection slot 24 is used to inject reaction solution, cleaning solution or substrate into the detection slot 25.

[0029] Further, the at least one detection slot 25 of the present embodiment is connected with the shunt unit 23. The detection slot 25 is used to receive the shunted detection sample. In the present embodiment, the following processes are mainly carried out in the detection slot 25.

[0030] First, the detection sample reacts with the reaction solution injected through the injection slot 24, and the intermediate and impurities are obtained by centrifugation. Next, the intermediate is cleaned by the cleaning solution injected through the injection slot 24 to remove the impurities. Finally, the intermediate reacts with the substrate injected through the injection slot 24 and completes the detection.

[0031] After the detection is completed, the at least one waste liquid unit 26 of the present embodiment is connected with the detection slot 25, and the waste liquid unit 26 is mainly used to collect the waste liquid output from the detection slot 25 in the above processes.

[0032] Next, please refer to Figure 2 , Figure 2 is a structural schematic diagram of the separation unit of the detection chip in most embodiments of the present application. As shown in Figure 2 , the separation unit 22 in the present embodiment includes a first flow channel 221, a separation slot 222 and a first micro flow channel 223. Figure 2 Among them, the first flow channel 221 is used to control the movement of the detection sample from the sample adding slot 21 to the separation slot 222, and the separation slot 222 is used to separate the sample to be detected into the detection sample and other density samples according to the density gradient. Next, the first micro flow channel 223 is used to control the movement of the detection sample from the separation slot 222 to the shunt unit 23.

[0033] Specifically, the first flow channel 221 of the present embodiment is connected with the sample adding slot 21 and the separation slot 222 respectively. In the present embodiment, the first micro flow channel 223 includes a first connection end A1, a second connection end A2 and a first turning end A3.

[0034] Among them, the first connection end A1 is connected with the separation slot 22, and the first connection end A1 is located at the first radius. The second connection end A2 is connected with the shunt unit 23, and the second connection end A2 is located at the second radius. The first turning end A3 is located between the first connection end A1 and the second connection end A2, and the first turning end A3 is located at the third radius.

[0035]

[0036] ​Wherein, the third radius is smaller than the first radius, and the first radius is smaller than the second radius. And the first radius, the second radius and the third radius respectively refer to the distance between the first connecting end A1, the second connecting end A2 and the first turning end A3 and the center of the whole detection chip 1 (or the mass center point).

[0037] Please further refer to Figure 3 , Figure 3 is the structural schematic diagram of the detection chip shunting unit in most embodiments of the utility model. As shown in Figure 3 , the shunting unit 23 of this embodiment comprises a shunting flow channel 231, at least one dosing groove 232, at least one second micro-flow channel 233 and a liquid storage groove 234.

[0038] Wherein, the shunting flow channel 231 is used for receiving the detection sample delivered by the first micro-flow channel 223. In the shunting flow channel 231, the detection sample is first distributed to the dosing groove 232, and the excess detection sample is distributed to the liquid storage groove 234.

[0039] The dosing groove 232 of this embodiment is used for the quantitative pre-distribution of the detection sample, and the second micro-flow channel 233 is used for controlling the movement of the detection sample from the dosing groove 232 to the detection groove 25. Specifically, one end of the shunting flow channel 231 of this embodiment is connected with the second connecting end A2 of the first micro-flow channel 223, and the other end is connected with the liquid storage groove 234. At least one dosing groove 232 is connected on the shunting flow channel 231 between the second connecting end A2 and the liquid storage groove 234, and at least one second micro-flow channel 233 is connected on the dosing groove 232.

[0040] Further, refer to Figure 4 , Figure 4 is the structural schematic diagram of the shunting unit in a specific embodiment. Based on Figure 4 , in a specific embodiment, the first micro-flow valve 235 is arranged on the second micro-flow channel 233. The first micro-flow valve 235 can improve the control force of the second micro-flow channel 233 on the movement of the detection sample from the dosing groove 232 to the detection groove 25.

[0041] Further, based on another specific embodiment of Figure 4 , the shunting flow channel 231 is in the shape of a spiral, and the included angle between the liquid storage groove 234 at the end of the shunting flow channel 231 and the circumferential line presented by the shunting flow channel 231 is not less than 20°. The shunting flow channel 231 designed in this way is more helpful for collecting the residual detection sample in the shunting flow channel 231 to the liquid storage groove 234 after shunting.

[0042] Please refer to Figure 4 , in Figure 4In another embodiment, the liquid storage tank 234 is provided with a first liquid storage cavity 2341 and a second liquid storage cavity 2342. The depth difference between the first liquid storage cavity 2341 and the second liquid storage cavity 2342 is not less than 2mm. The depth difference helps maintain the liquid-gas interface line and prevents the liquid in the liquid storage tank 234 from flowing back.

[0043] Referring to Fig. 4, a structure diagram of the injection tank 24 in an embodiment is shown. Based on the embodiment, Figure 5 Figure 5 Referring to Fig. 5, a structure diagram of the injection tank 24 in an embodiment is shown. Based on the embodiment, Figure 5 In the embodiment, the injection tank 24 is provided with a limiting sill 241, thereby forming a containing space 240. In the containing space 240, dry reagents or freeze-dried reagents can be pre-embedded to reduce the risk of contamination that is usually caused by using liquid reagents. When the dry reagents or freeze-dried reagents need to be used, the pre-embedded dry reagents or freeze-dried reagents can be activated by injecting activators into the injection tank 24.

[0044] Referring to Fig. 6, a structure diagram of the detection tank 25 in an embodiment is shown. Based on the embodiment, Figure 6 Figure 6 Referring to Fig. 7, a structure diagram of the detection tank 25 in an embodiment is shown. Based on the embodiment, Figure 6 In the embodiment, the detection tank 25 is provided with a first detection cavity 251 and a second detection cavity 252, and the height difference between the first detection cavity 251 and the second detection cavity 252 is not less than 2mm. The depth difference helps maintain the liquid-gas interface line and keeps the liquid surface consistent during detection, thereby improving the detection accuracy.

[0045] Referring to Fig. 8, a structure diagram of the detection chip waste liquid unit in an embodiment is shown. Based on the embodiment, Figure 7 Figure 7 Referring to Fig. 9, a structure diagram of the detection chip waste liquid unit in an embodiment is shown. Based on the embodiment, Figure 7 In the embodiment, the waste liquid unit 26 includes a third microfluidic channel 261 and a waste liquid tank 262. One end of the third microfluidic channel 261 is connected to the detection tank 25, and the other end is connected to the waste liquid tank 262. In this embodiment, the third microfluidic channel 261 is used to control the movement of the waste liquid from the detection tank 25 to the waste liquid tank 262.

[0046] The third microfluidic channel 261 in the embodiment includes a third connection end B1, a second turning end B2, and a fourth connection end B3. The third connection end B1 is connected to the detection tank 25, and the third connection end B1 is located at the fourth radius. The fourth connection end B3 is connected to the waste liquid tank 262, and the fourth connection end B3 is located at the fifth radius.

[0047] ​​​As for the second turning end B2, it is located between the third connecting end A1 and the fourth connecting end A2, and the second turning end B2 is located at the sixth radius. The sixth radius is smaller than the fourth radius, and the fourth radius is smaller than the fifth radius. The fourth radius, the fifth radius and the sixth radius respectively represent the distance between the third connecting end B1, the fourth connecting end B3 and the second turning end B2 and the center of the detection chip 1 (or the mass center point).

[0048] Further, please refer to Figure 8 , Figure 8 is a structural schematic diagram of the waste liquid unit in an embodiment. Based on Figure 8 , at least one second microfluidic valve 263 is arranged on the third microfluidic channel 261 in the embodiment, which can improve the control of the third microfluidic channel 261 on the movement of the waste liquid from the detection groove 25 to the waste liquid groove 262.

[0049] Further, please refer to Figure 8 , in another embodiment based on Figure 8 , the waste liquid groove 262 is provided with an exhaust hole 264, so that the exhaust of the gas in the waste liquid groove 262 helps to collect the waste liquid.

[0050] Please refer to Figure 8 , in another embodiment based on Figure 8 , a stepped groove 265 can be arranged in the waste liquid groove 262. The depth difference of the stepped groove 265 can help to maintain the liquid-gas interface line and prevent the waste liquid in the waste liquid groove 262 from flowing back.

[0051] Please refer to Figures 9 to 11 , Figures 9 to 11 is a structural schematic diagram of the detection chip in different embodiments.

[0052] As shown in Figure 9 , Figure 9 , the circular detection chip 1 in the embodiment is composed of a sample adding groove 21, a separation unit 22, a flow splitting unit 23, two injection grooves 24, one detection groove 25 and one waste liquid unit 26.

[0053] However Figure 10 , the detection chip 1 shown in the embodiment is different from Figure 9 . The sample adding groove 21 corresponds to four detection grooves 25 at the same time. That is Figure 10 , the embodiment only needs to add sample once, so as to realize the simultaneous detection of four different requirements. Of course, according to different detection requirements and quantities, the sample adding groove 21 can be designed to correspond to multiple detection grooves 25, and the utility model is not limited. In Figure 11 , the embodiment of the detection chip 1 shown in the embodiment is different from Figure 10The difference between the embodiments is that the detection chip 1 is divided into a fan-shaped disc, and a single detection chip 1 can correspond to a single detection object, thereby reducing the waste of the detection chip 1.

[0054] Referring to Figure 12 , Figure 12 is a structural schematic diagram of a detection device in most embodiments of the utility model. The detection device D in the embodiment comprises a driving mechanism 3 and the detection chip 1 mentioned in any one of the foregoing embodiments. Moreover, the detection chip 1 is detachably arranged on the driving mechanism 3. The driving mechanism 3 provides rotating power to drive the detection chip 1 to rotate, so as to realize detection of a sample to be detected in the detection chip 1.

[0055] Further, referring to Figure 13 , Figure 13 is a structural schematic diagram of a detection device in a specific embodiment. Figure 13 The detection device D in the embodiment further comprises a magnetic force mechanism 4 for applying a magnetic field force to the detection groove 25 in the detection chip 1.

[0056] With the magnetic field force of the magnetic force mechanism 4, the intermediate body and the second reactant can be intercepted in the detection groove, so as to avoid being thrown out of the detection groove 25 during centrifugation. Specifically, a plurality of magnetic blocks 41 are arranged on the magnetic force mechanism 4 along the circumferential direction of the detection chip 1. The magnetic blocks 41 can be away from or close to the detection groove 25, so as to control the position of the intermediate body and the second reactant in the detection groove 25. Of course, by controlling the position of the magnetic blocks 41, the mixing or cleaning process during the reaction in the detection groove 25 can also be assisted.

[0057] Referring to Figure 9 , Figure 14 and 15 , Figure 14 is a flow chart of a detection method in a preferred embodiment of the utility model; Figure 15 is a schematic diagram of a detection chip operation method in a preferred embodiment of the utility model.

[0058] The embodiment will further elaborate the detailed implementation of the detection method embodiment based on the structure of the detection chip 1 shown in the Figure 9 embodiment.

[0059] Firstly, step (A) is to add a sample to be detected into a sample adding groove. Specifically, step (A) is to add the sample to be detected into the sample adding groove 21 of the detection chip 1. Then, step (B) is to further drive the detection chip to rotate, and separate the sample to be detected from the sample adding groove into a detection sample (such as Figure 15 state a).

[0060] In step (B), the present embodiment centrifugates at a first rotation speed, so that the sample to be tested enters the separation groove 222 through the first flow channel 211, and separates the sample to be tested into a detection sample and other samples of different densities (e.g. Figure 15 State b). Step (C) is then performed, in which the detection sample is transported to the corresponding at least one detection groove through the flow splitting unit.

[0061] In step (C), the rotation direction is changed, and the detection sample is centrifugated at a second rotation speed so that the liquid level of the detection sample in the first micro flow channel 223 breaks through the first turning end A3 and enters the flow splitting channel 231. Under the action of the centrifugal force, the detection sample in the flow splitting channel 231 is first distributed to the quantification groove 232, and the excess detection sample is all collected to the liquid storage groove 234 (e.g. Figure 15 State c).

[0062] Step (D) is then performed, in which at least one reaction liquid is added to the at least one detection groove through the at least one injection groove, so that the detection sample and the at least one reaction liquid are mixed and cultured to obtain a mixed liquid containing at least one intermediate, and then centrifugation is performed to remove a waste liquid in the mixed liquid.

[0063] In step (D), the detection sample in the quantification groove 232 is centrifugated at a third rotation speed to break through the first micro flow valve 235 and enter the detection groove 25 (e.g. Figure 15 State d). Step (E) is then performed, in which a cleaning liquid is added to the at least one detection groove through the at least one injection groove, so that the cleaning liquid cleans the at least one intermediate.

[0064] In step (E), the reaction liquid is added to the injection groove 24, and centrifugated at a fourth rotation speed, so that the reaction liquid enters the detection groove 25. Then, while the rotation direction is alternately changed, the detection groove 25 is heated and treated, so that the detection sample and the reaction liquid are mixed and cultured to obtain a mixed liquid containing the intermediate (e.g. Figure 15 State e).

[0065] Finally, step (F) is performed, in which at least one substrate is added to the at least one detection groove through the at least one injection groove to react, and the reaction result presented in the at least one detection groove is detected. In this step, the present embodiment first centrifugates the detection groove 25 at a fifth rotation speed so that the waste liquid in the detection groove 25 breaks through the second micro flow valve 263 and enters the waste liquid groove 262, and obtains the intermediate containing impurities in the detection groove 25. At the same time, the cleaning liquid is added to the injection groove 24, and then centrifugated at the fourth rotation speed so that the cleaning liquid enters the detection groove 25.

[0066] Based on the above process, then through the forward and reverse rotation, the cleaning fluid to the intermediate thorough cleaning, and then the fifth speed centrifugation, containing impurities of the cleaning fluid break second micro flow valve 263 into the waste tank 262, and in the detection tank 25 get high purity intermediate (such as Figure 15 State f). Then add the substrate into the injection tank 24, while the fourth speed centrifugation, so that the substrate into the detection tank 25, and then through the forward and reverse rotation and at the same time on the detection tank 25 heating treatment, realize the uniform mixing and reaction of the intermediate and substrate (such as Figure 15 State g). After the reaction is finished, it can be detected by the detection device D for analysis.

[0067] In the above detection method for the selection of the sample, especially the immune detection is most suitable, especially the detection of antigen in blood. In the above embodiment, the detection sample is preferably blood plasma, and the reaction solution preferably contains a capture carrier with antibody on the surface and an enzyme-labeled antibody. The capture carrier is preferably magnetic beads, and the enzyme used in the enzyme-labeled antibody is preferably alkaline phosphatase (ALP). The substrate is preferably any one of AMPPD, CDP-Star or APS-5.

[0068] When magnetic beads are used as capture carriers for detecting antigens in blood, the external magnetic field can be used to realize intermediate screening and intermediate interception in the detection tank 25, and by adjusting the distribution position of the magnetic field, the intermediate can be washed to different degrees.

[0069] In another embodiment, when the embodiment shown in Figure 10 or 11 is selected, that is, a single sample injection tank 21 corresponds to multiple detection tanks 25, and the pre-set granular reagent in the injection tank 21, the difference from the above detection process is that the reaction solution in the above detection process is replaced by an activation solution to dissolve and activate the granular reagent in the injection tank 21, and then the dissolved granular reagent is transported to the detection tank 25 by centrifugation.

[0070] Since the reaction solution is a liquid, the shelf life after opening is short and the possibility of contamination is large, so the pre-set granular reagent can reduce the waste of the reaction solution and greatly reduce the probability of contamination, ensuring the accuracy of the detection.

[0071] Of course, the above-mentioned detection chip, detection device and detection method can also be used for full automatic detection of various indicators in human or animal urine, saliva, semen, spinal cord or amniotic fluid and other body fluids; in addition, the utility model can also be used in the field of food safety to detect toxic and harmful substances, bacteria or viruses in food; similarly, the utility model can be used in the field of pharmaceuticals and chemical industry to detect various pharmaceutical ingredients and chemical products.

[0072] The above detailed description is only a preferred embodiment of the present application, and cannot limit the scope of the present application. The simple equivalent changes and modifications made according to the scope and content of the present application are still within the scope of the present application. The above is only a preferred embodiment of the present application, and does not limit the patent scope of the present application. Any equivalent structure transformation or direct / indirect application in other related technical fields under the utility model concept of the present application is included in the patent protection scope of the present application.

Claims

1. A detection chip, characterized by, The chip comprises: a loading slot; a separation unit connected to the loading slot; a splitting unit connected to the separation unit; at least one detection slot connected to the splitting unit; at least one injection slot connected to a flow channel of the splitting unit and each of the at least one detection slot; and at least one waste unit connected to the at least one detection slot; wherein each of the at least one waste unit comprises a step slot.

2. The detection chip of claim 1, wherein, Each of the at least one waste unit comprises: a third microfluidic channel connected to each of the detection slot; and a waste slot connected to the third microfluidic channel.

3. The detection chip of claim 2, wherein, Each of the at least one waste unit further comprises a second microfluidic valve disposed on the third microfluidic channel.

4. A detection device, characterized in that The detection device comprises: a driving mechanism; and the detection chip of any one of claims 1-3, which is detachably connected to the driving mechanism.

5. The detection device of claim 4, wherein, The detection device further comprises a magnetic force mechanism, which applies a magnetic field to at least a portion of the at least one detection slot in the detection chip.

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