Multi-index detection chip

By quantitatively distinguishing the diluent into buffer sub-region, quantum sub-region and waste liquid sub-region on a multi-index detection chip, the precise quantification of the diluent is solved, and the existing biological detection system is low efficiency and low accuracy when detecting small samples, and efficient and accurate on-site detection is achieved.

CN108490199BActive Publication Date: 2025-03-11TSINGHUA UNIVERSITY
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Patent Information

Application Number
CN201810469916.X
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2018-05-16
Publication Date
2025-03-11
Estimated Expiration
2038-05-16

AI Technical Summary

Technical Problem

The existing biological detection systems are inefficient and have low accuracy when testing small samples, and the equipment is large, expensive and complex, making it difficult to meet the needs of fast and accurate on-site inspection.

Method used

A multi-index detection chip was designed to achieve accurate quantification of diluents by quantitatively distinguishing diluents into interconnected buffer sub-regions, quantum sub-regions and waste liquid sub-regions, integrating sample processing, buffer quantitative dilution and sample reaction, simplifying the operation process.

Benefits of technology

It significantly improves detection efficiency and detection accuracy, reduces dependence on professionals, reduces labor costs, and is suitable for rapid detection of small amounts of samples on site.

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Abstract

The present invention discloses a multi-index detection chip, which includes: a sample processing unit; a liquid storage unit, the liquid storage unit includes a connected diluent storage area and a diluent quantitative area, wherein the diluent quantitative area includes a buffer sub-area, a quantitative sub-area and a waste liquid sub-area that are interconnected, and a buffer enters the quantitative sub-area from the diluent storage area through the buffer sub-area for quantitative measurement, and the excess buffer enters the waste liquid sub-area; and a reaction unit, the reaction unit is connected to the sample processing unit and the quantitative sub-area, wherein the sample processing unit, the liquid storage unit and the reaction unit are connected to the atmosphere. By integrating sample processing, quantitative dilution of buffer and reaction of diluted samples, the operation process is simplified, and the diluent quantitative area is divided into a buffer sub-area, a quantitative sub-area and a waste liquid sub-area that are interconnected, so as to achieve accurate quantitative measurement of the diluent, and the detection efficiency and accuracy are high.
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Description

Technical Field

[0001] The present invention relates to the field of analysis and detection, and in particular to a multi-index detection chip. Background Art

[0002] Biological testing is the premise of medical diagnosis and the basic means of various related fields such as biosafety. Automated and rapid testing technology is an important development direction and has become a hot spot in rapid disease diagnosis, health monitoring, environmental and food safety testing. At present, the automated analysis and testing devices used by hospitals and testing institutions, such as fully automatic biochemical analyzers and immunoassay analyzers, use manipulators to complete various pipetting operations. They have many operating steps and use independent and diverse consumables. In addition, the system is relatively large, expensive, and has high requirements for users. It is suitable for centralized batch testing and does not meet the needs of rapid and accurate testing on site. With the development of society and the innovation and progress of the medical system, family doctors and community clinics will play an increasingly important role in disease diagnosis and medical care. The requirements for the detection technology used in these application scenarios are very different from those of large hospitals and testing institutions. The demand for batch testing of samples has dropped significantly, while the requirements for timeliness, accuracy and portability are strong. Therefore, large-scale biological detection systems based on manipulators are no longer suitable, and there is a strong demand for high-accuracy automated testing of "sample in-result out" for a small number of samples. Therefore, it is urgent to develop portable, automated, and integrated testing equipment suitable for rapid on-site testing.

[0003] Therefore, highly accurate automated multi-index detection chips need to be studied. Summary of the invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, one purpose of the present invention is to provide a multi-index detection chip, which can achieve accurate quantification of the diluent by dividing the diluent quantitative area into three interconnected sub-areas: a buffer sub-area, a quantitative sub-area, and a waste liquid sub-area, so as to significantly improve the detection efficiency and detection accuracy of the multi-index detection chip.

[0005] Therefore, according to one aspect of the present invention, the present invention provides a multi-indicator detection chip, characterized in that it includes: a sample processing unit; a liquid storage unit, the liquid storage unit includes a connected diluent storage area and a diluent quantification area, wherein the diluent quantification area includes a buffer sub-area, a quantification sub-area and a waste liquid sub-area that are interconnected, and the buffer solution enters the quantification sub-area from the diluent storage area through the buffer sub-area for quantification, and the excess buffer solution enters the waste liquid sub-area; and a reaction unit, the reaction unit is connected to the sample processing unit and the quantification sub-area, wherein the sample processing unit, the liquid storage unit and the reaction unit are connected to the atmosphere.

[0006] The multi-index detection chip according to the embodiment of the present invention integrates sample processing, quantitative dilution of buffer and reaction of diluted samples, simplifies the operation process, does not require professional operation, and saves manpower. In addition, by dividing the quantitative area of ​​the diluent into three interconnected sub-areas, namely, the buffer sub-area, the quantitative sub-area and the waste liquid sub-area, accurate quantification of the diluent is achieved, and the detection efficiency and detection accuracy of the multi-index detection chip are significantly improved.

[0007] In addition, the multi-index detection chip according to the above embodiment of the present invention may also have the following additional technical features:

[0008] According to an embodiment of the present invention, the buffer sub-area is connected to the quantitative sub-area through a first contraction channel; the quantitative sub-area is connected to the waste liquid sub-area through a second contraction channel, and the first contraction channel and the second contraction channel are located between the quantitative sub-area and the centrifugal center of the multi-index detection chip.

[0009] According to an embodiment of the present invention, the volume of the quantification sub-region is 20 μL-5 ml, and the volume of the buffer sub-region is not less than half of the volume of the quantification sub-region.

[0010] According to an embodiment of the present invention, the longitudinal sections of the buffer sub-region and the quantitative sub-region are trapezoidal.

[0011] According to an embodiment of the present invention, the ratio of the cross-sectional area at the connection between the first contraction channel and the buffer sub-area to the average radial cross-sectional area of ​​the buffer sub-area is 0.001-0.5, and the ratio of the cross-sectional area at the connection between the first contraction channel and the quantitative sub-area to the average radial cross-sectional area of ​​the quantitative sub-area is 0.001-0.5.

[0012] According to an embodiment of the present invention, the ratio of the cross-sectional area at the connection between the second contraction channel and the quantitative sub-area and the average radial cross-sectional area of ​​the quantitative sub-area is 0.001-0.5, and the ratio of the cross-sectional area at the connection between the second contraction channel and the waste liquid sub-area and the average radial cross-sectional area of ​​the waste liquid sub-area is 0.001-0.5.

[0013] According to an embodiment of the present invention, the sample processing unit includes: an injection tube; an injection blocking pit, the injection blocking pit is connected to the injection tube through a first capillary line, and the diameter of the injection blocking pit is larger than the diameter of the first capillary line; and a sample quantitative separation pool, the sample quantitative separation pool is connected to the injection blocking pit.

[0014] According to an embodiment of the present invention, the reaction unit includes: a mixing tank; a distribution pipe, the distribution pipe including: a siphon prevention pit, the siphon prevention pit is connected to the mixing tank through a second capillary tube, and the diameter of the siphon prevention pit is larger than the diameter of the second capillary tube; a liquid distribution pipe, the liquid distribution pipe is connected to the siphon prevention pit; and a plurality of reaction tanks, the plurality of reaction tanks are connected to the liquid distribution pipe.

[0015] According to an embodiment of the present invention, the mixing pool includes: a buffer zone connected to the sample processing unit via a third capillary; and a mixing zone connected to a free end of the buffer zone.

[0016] According to an embodiment of the present invention, the chip further comprises: a plurality of grooves, the plurality of grooves correspond one-to-one to the plurality of reaction pools in the thickness direction and are arranged on the back side of the reaction pools.

[0017] According to an embodiment of the present invention, the edge of the chip along the circumferential direction is sawtooth-shaped, and the reaction pools are arranged in a one-to-one correspondence with the recessed portions of the sawtooth along the radial direction.

[0018] According to an embodiment of the present invention, the reaction unit further comprises: a reaction liquid waste pool, which is connected to the distribution pipe and is located at the end of the distribution pipe away from the siphon prevention pit.

[0019] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0021] Figure 1 A schematic diagram of the structure of a multi-index detection chip according to an embodiment of the present invention is shown;

[0022] Figure 2 A schematic diagram of the structure of a multi-index detection chip according to an embodiment of the present invention is shown;

[0023] Figure 3 A partial structural schematic diagram of a multi-index detection chip according to an embodiment of the present invention is shown;

[0024] Figure 4 A schematic diagram of the structure of a multi-index detection chip according to an embodiment of the present invention is shown;

[0025] Figure 5 A schematic diagram of the structure of a multi-index detection chip according to an embodiment of the present invention is shown;

[0026] Figure 6A-6D A schematic diagram of the structure of a multi-index detection chip according to an embodiment of the present invention is shown. DETAILED DESCRIPTION

[0027] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0028] In the description of the present invention, the terms "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and do not require that the present invention must be constructed and operated in a specific orientation. Therefore, they should not be understood as limitations on the present invention.

[0029] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. Further, in the description of the present invention, unless otherwise specified, the meaning of "plurality" is two or more.

[0030] Refer to the following Figure 1-5 A multi-index detection chip 100 according to an embodiment of the present invention is described.

[0031] like Figure 1 As shown, the multi-index detection chip 100 of the embodiment of the present invention includes a sample processing unit 110, a liquid storage unit 120 and a reaction unit 130, so that the chip integrates sample processing, quantitative dilution of buffer solution and reaction of diluted samples, simplifies the operation process, does not require professional operation, and saves manpower. Figure 2 As shown, according to an embodiment of the present invention, the liquid storage unit 120 includes a connected diluent storage area 121 and a diluent quantification area 122, wherein the diluent quantification area 122 includes a buffer sub-area 123, a quantification sub-area 124 and a waste liquid sub-area 125 that are interconnected, and the buffer solution enters the quantification sub-area 124 from the diluent storage area 121 through the buffer sub-area 123 for quantification, and the accurately quantified buffer solution in the quantification sub-area 124 enters the reaction unit 130 to mix with the processed sample, while the excess buffer solution enters the waste liquid sub-area 125 and is stored in the waste liquid sub-area 125.

[0032] It should be noted that the sample processing unit 110, the liquid storage unit 120 and the reaction unit 130 are connected to the atmosphere to ensure the normal flow of the liquid in the chip. For example, the communication with the atmosphere can be achieved by using a ventilation channel. Specifically, the mixing pool 131, the sample quantitative separation pool 113 and the distribution pipe 132 are connected to the outside atmosphere through multiple ventilation channels or are connected to other structures of the chip 100 through multiple ventilation channels to achieve self-ventilation.

[0033] refer to Figure 2 According to an embodiment of the present invention, the sample processing unit 110 includes: a sample injection tube 111, a sample injection prevention pit 112 and a sample quantitative separation pool 113, wherein the sample injection prevention pit 112 is connected to the sample injection tube 111 through a first capillary line 114, and the diameter of the sample injection prevention pit 112 is larger than the diameter of the first capillary line 114; the sample quantitative separation pool 113 is connected to the sample injection prevention pit 112. Therefore, the diameter of the sample injection prevention pit 112 is significantly larger than the diameter of the first capillary line 114, thereby forming an interface valve, which can prevent excessive sample injection from entering the sample quantitative separation pool 113 in advance, so that the quantification of the sample is more accurate.

[0034] refer to Figure 3 According to an embodiment of the present invention, the buffer sub-area 123 is connected to the quantitative sub-area 124 through the first contraction channel 126, the quantitative sub-area 124 is connected to the waste liquid sub-area 125 through the second contraction channel 127, and the first contraction channel 126 and the second contraction channel 127 are located between the centrifugal center of the multi-index detection chip of the quantitative sub-area 124. Wherein, the "centrifugal center" refers to the center around which the centrifugal movement revolves when the chip is centrifuged. During centrifugation, the buffer of the buffer sub-area 123 passes through the quantitative sub-area 124 through the first contraction channel 126. When the buffer fills the quantitative sub-area 124, the excess buffer enters the waste liquid sub-area 125 through the second contraction channel 127 driven by centrifugal force. Since the error formed by the chip during centrifugal quantification is mainly reflected in the height of the liquid level, the position of the first contraction channel 126 and the second contraction channel 127 relative to the quantitative sub-area 124 is equivalent to the entrance at the top thereof. The smaller the entrance at the top, the smaller the volume change caused by the liquid level. Therefore, the smaller cross-sections of the first contraction channel 126 and the second contraction channel 127 are beneficial to reducing the volume error caused by the error in the liquid level height, thereby further improving the quantitative accuracy of the chip buffer, thereby further improving the detection accuracy of the chip.

[0035] According to an embodiment of the present invention, the ratio of the cross-sectional area at the connection between the first contraction channel 126 and the buffer sub-region 123 to the average radial cross-sectional area of ​​the buffer sub-region 123 is 0.001-0.5, wherein the radial cross-sectional area of ​​the buffer sub-region 123 refers to the cross-sectional area perpendicular to the chip 100 and from the buffer sub-region to the quantitative sub-region, and the ratio of the cross-sectional area at the connection between the first contraction channel 126 and the quantitative sub-region 124 to the average radial cross-sectional area of ​​the quantitative sub-region 124 is 0.001-0.5, wherein the radial cross-sectional area of ​​the quantitative sub-region 124 refers to the cross-sectional area perpendicular to the chip 100 and from the quantitative sub-region 124 to the buffer sub-region 123. Thus, the area ratio of the radial cross-sectional area of ​​the first contraction channel to the buffer sub-region and the quantitative sub-region is appropriate, which not only ensures the smooth flow of the buffer, but also makes the volume change caused by the change in the liquid height at the upper end of the quantitative sub-region (close to the centrifugal center) smaller, so that the quantitative determination of the quantitative sub-region is more accurate.

[0036] According to an embodiment of the present invention, the ratio of the cross-sectional area at the connection between the second contraction channel 127 and the quantitative sub-region 124 to the average radial cross-sectional area of ​​the quantitative sub-region 124 is 0.001-0.5, wherein the radial cross-sectional area of ​​the quantitative sub-region 124 refers to the cross-sectional area perpendicular to the chip 100 and from the quantitative sub-region 124 toward the buffer sub-region 123, and the ratio of the cross-sectional area at the connection between the second contraction channel 127 and the waste liquid sub-region 125 to the average radial cross-sectional area of ​​the waste liquid sub-region 125 is 0.001-0.5, wherein the radial cross-sectional area of ​​the waste liquid sub-region 125 refers to the cross-sectional area perpendicular to the chip 100 and from the waste liquid sub-region 125 toward the quantitative sub-region 124. Thus, the area ratio of the radial cross-sectional area of ​​the second contraction channel to the quantitative sub-region and the waste liquid sub-region is appropriate, which not only ensures the smooth discharge of the buffer solution to the waste liquid sub-region, but also makes the volume change caused by the change in the liquid height at the upper end of the quantitative sub-region (close to the centrifugal center) smaller, so that the quantitative determination of the quantitative sub-region is more accurate.

[0037] It should be noted that the “average radial cross-sectional area” is the average of the areas of the radial cross-sections constituting the sub-area.

[0038] Furthermore, according to some embodiments of the present invention, a diluent may be pre-packaged in the buffer sub-area 123, or a diluent injection hole may be left in the buffer sub-area 123, and the diluent is added through the injection hole when the chip is used.

[0039] According to a specific embodiment of the present invention, the volume of the quantitative sub-region 124 is 20 μL-5 ml, and the volume of the buffer sub-region 125 is not less than half of the volume of the quantitative sub-region 124. The purpose of the larger volume of the buffer sub-region 125 is to temporarily accommodate the diluent that will enter the quantitative sub-region 124. Because the cross-section of the first contraction channel 126 is small, when the diluent flows out of the diluent storage area 121 quickly under the drive of centrifugal force, the first contraction channel 126 with a smaller cross-section may not allow the diluent flowing out to completely enter the quantitative sub-region 124, so the diluent that cannot quickly enter the quantitative sub-region 124 will be temporarily stored in the buffer sub-region 125 to avoid flowing to other areas of the chip or outside the chip, affecting the chip function. Therefore, the volume of the quantitative sub-region 124 and the buffer sub-region 125 meets the needs of conventional clinical and experimental trace sample detection, and ensures the accuracy of sample detection. Further, according to an embodiment of the present invention, the radial diameter of the first contraction channel 126 and the second contraction channel 127 is 0.1-2 mm, and the length is 0.1-2 mm. Therefore, the diameters of the first contraction channel and the second contraction channel are relatively small, so that the volume of liquid therein is small, which is conducive to accurate quantification of the volume of the buffer solution.

[0040] Furthermore, if Figure 3 As shown, according to an embodiment of the present invention, the longitudinal section of the buffer sub-area 123 and the quantitative sub-area 124 is inverted trapezoidal, wherein the longitudinal section refers to the section from the center of the chip to the circumferential direction, that is, the bottom size of the buffer sub-area 123 and the quantitative sub-area 124 is small and the top size is large, which is beneficial to the demoulding of the chip during injection molding on the one hand, and is beneficial to reduce the residual liquid when the chip is centrifuged to discharge the buffer. Because under the drive of centrifugal force, the liquid will move in the direction away from the centrifugal center, so that the last small amount of liquid will converge to the upper edge close to the surface of the chip, and the capillary 142 connected to the reaction unit 130 for discharging the liquid is in this position, so it is beneficial to discharge all the liquids in the quantitative sub-area 124 and avoid liquid residue. In addition, the inverted trapezoidal structure can also avoid the diluent from trapping gas when entering the buffer sub-area 123 and the quantitative sub-area 124, thereby affecting the quantification. In summary, the above structure can improve the accuracy of buffer quantitative analysis and make the chip more accurate in analyzing the sample.

[0041] refer to Figure 4According to an embodiment of the present invention, the reaction unit 130 includes: a mixing pool 131, a distribution pipe 132 and a plurality of reaction pools 133, wherein the distribution pipe 132 includes: a siphon prevention pit 134 and a liquid distribution pipe 135, the siphon prevention pit 134 is connected to the mixing pool 131 through a second capillary line 136, and the diameter of the siphon prevention pit 134 is larger than the diameter of the second capillary line 136, the liquid distribution pipe 135 is connected to the siphon prevention pit 134, and the plurality of reaction pools 133 are connected to the liquid distribution pipe 135. The quantitative sample processed in the mixing pool is mixed with the quantitative buffer to obtain a mixed solution, and the mixed solution first passes through the siphon prevention pit 134 when it flows into the liquid distribution pipe 135 through the second capillary line 136. Since the diameter of the siphon prevention pit 134 is larger than the diameter of the second capillary line 136, it is prevented that the mixed solution in the second capillary line 136 enters the liquid distribution pipe 135 in advance, resulting in that part of the reaction pool 133 is not filled.

[0042] refer to Figure 4 According to an embodiment of the present invention, the mixing pool 131 includes: a buffer zone 138 and a mixing zone 139, wherein the buffer zone 138 is connected to the sample processing unit 110; the mixing zone 139 is connected to the free end of the buffer zone 138. The quantified sample enters the third capillary channel 141 under the action of the hydrophilic capillary force. Due to the existence of the buffer zone 138, its deeper and wider structure can act as an interface valve compared to the third capillary channel 141, so that when the chip is stationary or rotating at a low speed, the sample is blocked in the third capillary channel 141 and does not enter the mixing pool 131 in advance. Only when the chip is centrifuged at a faster speed, the quantified sample will pass through the third capillary channel and enter the mixing zone 139 via the buffer zone 138. In addition, the existence of the buffer zone 138 can reduce the length of the third capillary channel 141, thereby reducing the possible contamination residue of the hydrophilic third capillary channel 141 on the sample. In addition, the buffer zone 138 can prevent the third capillary 141 from directly contacting the sample and diluent in the mixing zone 139 during the mixing process, and prevent the sample diluted by the diluent from entering the third capillary 141, thereby contacting the remaining quantitative sample and affecting the quantification and causing contamination.

[0043] Furthermore, according to an embodiment of the present invention, the mixing zone 139 can be connected to the ventilation pipe, so as to maintain an appropriate pressure in the mixing zone 139 and facilitate the entry of liquid. Furthermore, the radial dimension of the connection between the mixing zone 139 and the ventilation pipe changes with the change of radial height, so as to avoid the liquid entering the ventilation pipe and blocking the ventilation during mixing.

[0044] Specifically, according to some embodiments of the present invention, each reaction pool 133 is fixed with dry biological indicator detection reagents, including alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, alkaline phosphatase, cholinesterase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, total protein, albumin, glycosylated albumin, total bilirubin, direct bilirubin, ammonia, urea, creatinine, uric acid, glucose, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, apolipoprotein A1, apolipoprotein B, calcium, chlorine, iron, phosphorus, sodium, potassium, and carbon dioxide.

[0045] like Figure 4 As shown, according to an embodiment of the present invention, the reaction unit 130 further includes: a reaction liquid waste liquid pool 137, which is connected to the distribution pipe 132 and is located at the end of the distribution pipe 132 away from the siphon prevention pit 134. The mixed liquid mixed in the mixing pool enters the distribution pipe 132 through the siphon prevention pit 134 under the action of centrifugal force, and enters each reaction pool 133 from the distribution pipe 132, and the excess mixed liquid enters the reaction liquid waste liquid pool 137. When there is waste liquid in the reaction liquid waste liquid pool 137, it means that the mixed liquid in each reaction pool 133 is completely filled, and when there is no waste liquid in the reaction liquid waste liquid pool 137, the mixed liquid in each reaction pool 133 may not be completely filled, that is, the amount of the mixed liquid may be insufficient. Therefore, whether the reaction pool is fully filled can be judged according to whether there is solution entering the reaction liquid waste liquid pool 137. In addition, after the mixed liquid enters the reaction tank 133, the residual liquid in the distribution pipe 132 also enters the reaction liquid waste tank 137. There is no residual liquid in the distribution pipe 132, which avoids the contact of solutions between different reaction tanks 07 and eliminates the possibility of cross contamination.

[0046] Further, according to an embodiment of the present invention, the chip 100 may be in a circular or fan-shaped structure, and the centrifugal force is generated by rotating the core 100 to drive the fluid flow in the chip 100. The positional relationship of the above structures relative to the centrifugal center of the chip is as follows: the injection tube 111 and the buffer sub-area 123 are closest to the centrifugal center, the sample quantitative separation pool 113 is located on the side of the injection tube 111 away from the centrifugal center, the quantitative sub-area 124 is located on the side of the buffer sub-area 123 away from the centrifugal center, the mixing pool 131 is located on the side of the sample quantitative separation pool 113 and the quantitative sub-area 124 away from the centrifugal center, each reaction pool 133 is located at the edge of the chip 100 farthest from the centrifugal center and is evenly distributed in the circumferential direction relative to the centrifugal center, and the distribution tube 132 is located between the reaction pool 133 and the mixing pool 131. For the quantitative sub-area 124, the buffer sub-area 123 is closer to the centrifugal center than the quantitative sub-area 124 and the waste liquid sub-area 125.

[0047] Further, according to some embodiments of the present invention, the appearance structure of the chip 100 can be fan-shaped, diamond-shaped, rectangular, triangular, elliptical or circular, etc. In other embodiments, the material of the chip 100 can be a polymer material such as polymethyl methacrylate, polycarbonate, polypropylene and other polymers, or it can be glass, metal material, or any combination of the foregoing materials. Among them, it should be noted that the reaction pool 133 needs to be formed of a transparent material. In addition, the chip 100 can be prepared by sealing and fixing by machining, injection molding, 3D printing and other methods and hot pressing sealing, laser welding, ultrasonic welding, bonding and other methods.

[0048] like Figure 5 As shown, according to an embodiment of the present invention, the chip further includes: a plurality of grooves 170, which correspond to the plurality of reaction pools 133 in the thickness direction and are arranged on the back side of the reaction pools 133. That is, a groove 140 is arranged corresponding to the back of each reaction pool 133, and the grooves 140 and the reaction pools 133 are arranged opposite to each other, so as to prevent the chip 100 from being contaminated or damaged due to contact or friction in the processing or use of the optical properties of the area where the reaction pools 133 are located.

[0049] According to an embodiment of the present invention, the circumferential edge of the chip 100 is serrated, and the reaction pool 133 is arranged in a one-to-one correspondence with the recessed portion of the sawtooth 138 along the radial direction. When the chip 100 is placed on a matching centrifugal detection device, the sawtooth structure 138 will pass through an optical detection device such as an optical switch of the matching device, thereby triggering a signal to detect the reaction pool 133 corresponding to the sawtooth structure 138.

[0050] According to some embodiments of the present invention, the chip 100 further has a positioning hole 140. Specifically, the positioning hole 140 can be a through hole, and the analysis device has a corresponding positioning protrusion or positioning column. When the positioning protrusion or positioning column extends into the positioning hole 140, the chip 100 is set at a predetermined position of the analysis device. Therefore, the positioning hole 140 is used to place the chip 100 in a fixed position of the analysis device, so as to facilitate subsequent processing.

[0051] refer to Figure 3 According to some embodiments of the present invention, the chip 100 further has a plunger valve 150, which may be a through-hole structure. The plunger valve 150 is disposed between the buffer sub-area 123 and the quantitative sub-area 124. The plunger valve 140 is opened by a special mechanical structure on the supporting centrifugal device, thereby realizing the communication between the flow paths of the diluent storage area 121 and the diluent quantitative area 122.

[0052] Further, if Figure 5As shown, there is also a contact recess 160 on the back of the chip, and the contact recess 180 is convenient for the finger to contact when the chip is taken to and placed on the instrument.

[0053] In order to facilitate the understanding of the multi-index detection chip, a method for detecting using the multi-index detection chip is provided here, which is as follows:

[0054] (1) Fig. 6A , the sample inlet of the chip sample tube 111 is brought into contact with the sample for a few seconds to absorb the sample into the sample tube 111 through hydrophilic capillary action, or the sample is directly added to the chip sample tube 111 through the sample inlet by a pipette. The liquid required for the reaction, such as a diluent, is pre-filled in the liquid storage unit 120, or is added to the liquid storage unit 120 before use. The chip after the sample injection is placed on the matching centrifugal device, and the plunger valve 150 will be pushed open by the special mechanical structure on the matching centrifugal device to achieve flow path communication between the buffer sub-area 123 and the quantitative sub-area 124.

[0055] (2) Figure 6B The chip is rotated at a high speed, such as 1000-6000rpm, by using a centrifugal device. The sample in the chip injection tube 111 is driven by centrifugal force to pass through the injection prevention pit 112 and enter the sample quantitative separation pool 113 to complete the volume quantification of the sample and the separation of particle precipitation. The liquid in the diluent storage area 121 is driven by centrifugal force to enter the diluent quantitative area 122 to complete the diluent volume quantification.

[0056] (3) The rotation speed of the chip is reduced, such as 0-600 rpm. The sample in the sample quantitative separation pool 113 fills the capillary 141 under the action of capillary force, and the liquid in the diluent quantitative zone 122 fills the capillary 142 connected to the mixing pool 131 under the action of capillary force.

[0057] (4) Figure 6C , the chip is rotated at high speed again, and the quantitative sample enters the mixing pool 131 through the capillary, and the diluent enters the mixing pool 131 from the diluent quantitative area 122, and then the volume quantitative mixing of the sample and the diluent is achieved by quickly switching the centrifugal direction or changing the centrifugal speed.

[0058] (5) The rotation speed of the chip 100 is reduced, and the liquid in the mixing pool 131 is filled with the second capillary 136 under the action of capillary force.

[0059] (6) Fig.6D, the chip is rotated at high speed again, and the liquid in the mixing pool 131 is injected into each reaction pool 133 through the second capillary 136 and the distribution tube 132, filling them one by one, and the excess sample enters the reaction liquid waste pool 137, completing the sample distribution. No liquid remains in the distribution tube 132, avoiding the contact of solutions between different reaction pools 133 and eliminating the possibility of cross contamination.

[0060] (7) The distributed sample will dissolve the reaction reagent pre-installed in the reaction pool 133, undergo biochemical reaction under incubation at a certain temperature and complete the detection.

[0061] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0062] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A multi-index detection chip, characterized in that: include: Sample processing unit; A liquid storage unit, the liquid storage unit comprising a diluent storage area and a diluent quantitative area connected to each other, wherein the diluent quantitative area comprises a buffer sub-area, a quantitative sub-area and a waste liquid sub-area connected to each other, a buffer solution enters the quantitative sub-area from the diluent storage area through the buffer sub-area for quantitative determination, and excess buffer solution enters the waste liquid sub-area; and a reaction unit, wherein the reaction unit is connected to the sample processing unit and the quantitative sub-area, Wherein, the sample processing unit, the liquid storage unit and the reaction unit are connected to the atmosphere; The buffer sub-area is connected to the quantitative sub-area via a first contraction channel; The quantitative sub-area is connected to the waste liquid sub-area via a second contraction channel. The first contraction channel and the second contraction channel are located between the quantitative sub-area and the centrifugal center of the multi-index detection chip; The ratio of the cross-sectional area at the connection between the first contraction channel and the buffer sub-region to the average radial cross-sectional area of ​​the buffer sub-region is 0.001-0.5, and the ratio of the cross-sectional area at the connection between the first contraction channel and the quantitative sub-region to the average radial cross-sectional area of ​​the quantitative sub-region is 0.001-0.

5. The ratio of the cross-sectional area at the connection between the second contraction channel and the quantitative sub-region to the average radial cross-sectional area of ​​the quantitative sub-region is 0.001-0.5, and the ratio of the cross-sectional area at the connection between the second contraction channel and the waste liquid sub-region to the average radial cross-sectional area of ​​the waste liquid sub-region is 0.001-0.5; The longitudinal sections of the buffer sub-region and the quantitative sub-region are in the shape of an inverted trapezoid; Among them, the radial cross-sectional area of ​​the buffer sub-area refers to the cross-section perpendicular to the multi-indicator detection chip and extending from the buffer sub-area toward the quantitative sub-area, and the radial cross-sectional area of ​​the quantitative sub-area refers to the cross-section perpendicular to the multi-indicator detection chip and extending from the quantitative sub-area toward the buffer sub-area; the radial cross-sectional area of ​​the waste liquid sub-area refers to the cross-sectional area perpendicular to the multi-indicator detection chip and extending from the waste liquid sub-area toward the quantitative sub-area; the longitudinal cross-sectional area refers to the cross-sectional area from the center of the multi-indicator detection chip to the circumferential direction.

2. The multi-index detection chip according to claim 1, characterized in that: The volume of the quantitative sub-region is 20 μL-5 ml, and the volume of the buffer sub-region is not less than half of the volume of the quantitative sub-region.

3. The multi-index detection chip according to claim 1, characterized in that: The sample processing unit comprises: Injection tube; an injection preventing pit, wherein the injection preventing pit is connected to the injection tube via a first capillary line, and a diameter of the injection preventing pit is larger than a diameter of the first capillary line; and A sample quantitative separation pool is connected to the sample injection prevention pit.

4. The multi-index detection chip according to claim 1, characterized in that: The reaction unit comprises: Mixing pool; A distribution pipe, comprising: A siphon prevention pit, wherein the siphon prevention pit is connected to the mixing tank via a second capillary tube, and a diameter of the siphon prevention pit is greater than a diameter of the second capillary tube; a liquid distribution pipe connected to the siphon prevention pit; A plurality of reaction tanks, wherein the plurality of reaction tanks are connected to the liquid distribution pipe, The mixing tank comprises: a buffer zone, wherein the buffer zone is connected to the sample processing unit via a third capillary line; and A mixing zone is communicated with the free end of the buffer zone.

5. The multi-index detection chip according to claim 4, characterized in that: Further including: A plurality of grooves, the plurality of grooves correspond to the plurality of reaction pools in a thickness direction and are arranged on the back side of the reaction pools.

6. The multi-index detection chip according to claim 4, characterized in that: The chip has a recessed portion at its circumferential edge, and the reaction pools are arranged in a one-to-one correspondence with the recessed portions along the radial direction.

7. The multi-index detection chip according to claim 4, characterized in that: The reaction unit further comprises: A reaction liquid waste pool is communicated with the distribution pipe and is located at the end of the distribution pipe away from the siphon prevention pit.

Citation Information

Patent Citations

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