An internal circulation microfluidic chip and in vitro detection device

Abstract

The present invention discloses an internal circulation microfluidic chip and an in vitro detection device, which relate to the field of experimental containers or vessels, wherein the exhaust hole of the reaction unit is connected to the sample loading chamber, forming an internal air circulation on the microfluidic chip, which has the advantages of few components, simple assembly, low cost, etc., and the entire reaction and detection process after the sample loading can be completely sealed, free from external contamination, and improve the credibility of the test results. In addition, the upper end of the exhaust flow channel is provided with a second groove and a third groove connected in sequence to form a stop valve to ensure that the liquid sample in the reaction chamber can be cut off within a specific required height range under the capillary force and gravity pressure difference to avoid the occurrence of mixed liquid. The liquid inlet flow channel extends vertically along the tangent of the reaction chamber and is arranged on the side wall of the reaction chamber, and the lower end of the exhaust flow channel is provided with a second groove at the top of the side wall of the reaction chamber, which acts as a capillary valve. The second groove acts as a capillary valve to inhibit the liquid sample from entering the exhaust flow channel and allow the gas in the reaction chamber to be discharged in time.

Description

Technical Field

[0001] The present invention relates to the field of experimental containers or vessels, in particular to an internal circulation microfluidic chip and an in vitro detection device. Background Art

[0002] Microfluidic chip technology, known as a laboratory on a chip, integrates all aspects of an experiment on a single chip. Microfluidic chips offer advantages such as high integration, compact size, minimal reagent usage, low cost, and ease of operation.

[0003] The existing microfluidic chips have the following problems: (1) Existing microfluidic chips all adopt a gas exhaust design, that is, the exhaust hole of the reaction unit leads to the outside of the chip body. In order to isolate external pollution and prevent the liquid sample from being discharged through the exhaust hole, the surface of the chip body needs to be sealed with a hydrophobic breathable membrane, as well as accessories such as a cover plate to protect the hydrophobic breathable membrane. There are many parts, and each part needs to be processed and assembled, which requires many steps and high production costs. (2) In the reaction unit, the liquid inlet flow channel and the exhaust flow channel of the reaction chamber are arranged opposite to each other. After the liquid sample enters the reaction chamber from the liquid inlet flow channel, it is easy to block the exhaust flow channel, resulting in some gas in the reaction chamber being unable to be discharged, forming bubbles; as the freeze-dried balls in the reaction chamber contact and dissolve with the liquid sample, a hollow space is formed in the reaction chamber, forming large bubbles, which affect the detection results. During this period, small bubbles formed by adding samples or dissolving freeze-dried balls in the liquid sample will also converge towards the large bubbles, further affecting the detection results. Summary of the Invention

[0004] The purpose of the present invention is to provide an internal circulation microfluidic chip and an in vitro detection device, which is mainly intended to overcome the problems in the prior art of adopting a gas exhaust design, which is easily susceptible to external contamination, has many parts, many processes, and high production costs.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] An internal circulation microfluidic chip includes a chip body provided with at least one reaction unit, the reaction unit including a liquid inlet channel, a reaction chamber and an exhaust channel connected in sequence along the liquid flow direction, a sample loading chamber is vertically provided at the upper end of the chip body; a liquid outlet is provided at the bottom of the sample loading chamber, and the liquid outlet is connected to the liquid inlet channel, and at least one exhaust hole is horizontally extended on the side wall of the sample loading chamber, the exhaust hole is conical, and the narrow end of the cone is located on the inner side wall of the sample loading chamber, and the wide end of the cone is connected to the exhaust channel.

[0007] Furthermore, the front end face and / or rear end face of the above-mentioned chip body are provided with several of the above-mentioned reaction units; in the above-mentioned reaction units, the exhaust flow channel is vertically extended, and the lower end of the exhaust flow channel is connected to the top of the side wall of the above-mentioned reaction chamber, and the upper end of the exhaust flow channel is provided with a second groove and a third groove connected in sequence; the width of the above-mentioned second groove gradually increases from bottom to top, the width of the above-mentioned third groove is equal to or greater than the width of the second groove, and the depth of the third groove is greater than the depth of the second groove; the front end face and / or rear end face of the above-mentioned chip body are also provided with an air collection groove, which is connected to several of the above-mentioned third grooves, and the tapered wide end of the above-mentioned exhaust hole is connected to the above-mentioned air collection groove.

[0008] Furthermore, the depth ratio of the second groove to the third groove is 1:2 to 1:3.

[0009] Furthermore, the upper half of the third groove is opened inside the air collecting groove.

[0010] Furthermore, the third groove is extended horizontally, and the plurality of reaction units are arranged horizontally and spaced apart on the front end surface and / or the rear end surface of the chip body.

[0011] Furthermore, the front end face and the rear end face of the chip body are both provided with a plurality of reaction units, forming two front and rear reaction unit groups; the chip body is provided with a mounting portion for assembling a heating element between the two reaction unit groups.

[0012] Furthermore, the lower end surface of the chip body is provided with a strip-shaped groove serving as the mounting portion.

[0013] Furthermore, the upper end of the sample adding cavity protrudes from the chip body.

[0014] Furthermore, the chip body is provided with the liquid outlet holes, the flow diversion holes and the liquid diversion flow channel which are sequentially connected along the liquid flow direction, and the liquid diversion flow channel is connected to the liquid inlet flow channels of the plurality of reaction units.

[0015] Furthermore, a first groove is provided at one end of the exhaust channel connected to the reaction chamber, and the depth of the first groove is greater than the depth of the exhaust channel and less than the depth of the reaction chamber.

[0016] Furthermore, the width and length of the first groove are both equal to or less than 1 mm, and the depth ratio of the first groove to the reaction chamber is 1:2 to 2:3.

[0017] Furthermore, the liquid inlet channel is extended along a tangent line of the reaction chamber and is arranged on a side wall of the reaction chamber.

[0018] Furthermore, the liquid inlet channel includes a first side wall and a second side wall, the first side wall coincides with the tangent line, the second side wall and the reaction chamber are on the same side of the tangent line, and the second side wall is smoothly connected to the side wall of the reaction chamber through a round chamfer.

[0019] An in vitro detection device comprises a detector and an internal circulation microfluidic chip having a structure as described above, wherein the detector is used to detect a liquid sample in a reaction chamber.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] First, in the present invention, the exhaust holes of the reaction units are connected to the sample loading chamber, forming an internal air circulation on the microfluidic chip. The solution in the sample loading chamber can be filled with each reaction unit by cooperating with the effect of gravity. Compared with the external air circulation method of the existing microfluidic chip, the hydrophobic breathable membrane set at the exhaust hole and the cover plate to prevent the hydrophobic breathable membrane from being contaminated by the outside world are saved. It has the advantages of fewer components, simple assembly, and low cost. In addition, the entire reaction and detection process after the sample loading can be completely sealed to avoid external contamination, thereby improving the credibility of the detection results. The conical exhaust hole can prevent the liquid sample in the confluence tank from flowing back into the sample loading chamber, and can also ensure that the liquid sample will not overflow from the exhaust hole and block the exhaust flow channel during the sample loading process.

[0022] Secondly, in the present invention, the exhaust channel is vertically arranged, and a second groove and a third groove are sequentially connected at the upper end of the exhaust channel. The second and third grooves form a shutoff valve at the upper end of the exhaust channel, ensuring that the liquid sample in the reaction chamber is shut off within a specified height range under capillary force and gravitational pressure differential, preventing the liquid sample from overflowing upward and avoiding mixing caused by the overflowed liquid sample flowing into another reaction unit or back into the sample chamber.

[0023] Third, in the present invention, a second groove is provided at the lower end of the exhaust channel. This groove acts as a capillary valve, preventing the liquid sample from entering the exhaust channel. Once the liquid sample on the bottom of the reaction chamber wraps around it, the gas above the liquid sample is first squeezed into the exhaust channel before the liquid sample enters the second groove, effectively preventing the formation of large bubbles inside the reaction chamber.

[0024] Fourthly, in the present invention, the liquid inlet channel extends vertically along the tangent line of the reaction chamber and is disposed in the sidewall of the reaction chamber. This creates a widening asymmetric notch in the sidewall, which helps to disrupt the interfacial energy at the front end of the liquid flow. Furthermore, gravity allows the liquid flow to initially fill the bottom of the sidewall of the reaction chamber, spreading upward from the bottom. This helps to discharge gases from the reaction chamber toward the exhaust channel and prevents the formation of large bubbles within the reaction chamber. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is an exploded view of the internal circulation microfluidic chip in the present invention.

[0026] Figure 2 This is the main view of the chip body in the present invention.

[0027] Figure 3 In the present invention, the chip body is along Figure 2 Cross-sectional view in the AA direction.

[0028] Figure 4 for Figure 1 , a partial enlarged view of part B.

[0029] Figure 5 for Figure 1 , a partial enlarged view of part C. DETAILED DESCRIPTION

[0030] The specific embodiments of the present invention are described below with reference to the accompanying drawings. In order to fully understand the present invention, many details are described below, but for those skilled in the art, the present invention can be implemented without these details.

[0031] like Figures 1 to 3 As shown, an internal circulation microfluidic chip includes a reaction unit 13, a sealing cover 2 and a pressure-sensitive membrane 3. A sample loading chamber 10 is vertically provided at the upper end of the reaction unit 13, and eight reaction units 13 are provided on the front end face and the rear end face of the reaction unit 13. Two pressure-sensitive membranes 3 are sealed and attached to the front end face and the rear end face of the reaction unit 13, respectively. The sealing cover 2 can be detachably arranged at the opening of the sample loading chamber 10. Of course, the reaction unit 13 and the pressure-sensitive membrane 3 can also be arranged only on the front end face of the reaction unit 13, or only on the rear end face of the reaction unit 13, and the number of reaction units 13 can be increased or decreased as needed, and is not limited to eight.

[0032] like Figures 1 to 3 As shown, preferably, the upper end of the sample loading cavity 10 protrudes from the chip body 1 , and the sealing cover 2 is fastened to the opening of the sample loading cavity 10 by interference fit.

[0033] like Figures 1 to 3 As shown, a plurality of reaction units 13 are horizontally spaced and arranged on the front surface and / or the rear surface of the chip body 1 .

[0034] like Figures 1 to 3 As shown, the front end face and the rear end face of the reaction unit 13 are each provided with eight reaction units 13, forming two reaction unit groups. The chip body 1 is provided with a mounting portion 16 for assembling a heating element (not shown in the figure) between the two above-mentioned reaction unit groups. When the detection item requires heating, the heating element is placed on the mounting portion 16 to heat the two above-mentioned reaction unit groups simultaneously. The heating element can be an existing electric hot plate. Preferably, the lower end face of the chip body 1 is provided with a strip groove serving as the mounting portion 16.

[0035] like Figures 1 to 3 As shown, Figures 1 to 3As shown, the reaction unit 13 includes a liquid inlet channel 131, a reaction chamber 132, and an exhaust channel 133, which are sequentially connected along the liquid flow direction. A cold dry ball (not shown) is placed inside the reaction chamber 132. The bottom of the sample loading chamber 10 is provided with a liquid outlet 101. The liquid outlet 101 is connected to the liquid inlet channel 131 of each reaction unit 13 through the diversion hole 121 and the liquid diversion channel 122, thereby allowing the liquid sample in the sample loading chamber 10 to flow into each reaction unit 13.

[0036] like Figures 1 to 4 As shown, the liquid inlet channel 131 extends along a tangent line e of the reaction chamber 132 and is disposed on the sidewall of the reaction chamber 132. This arrangement not only prevents the liquid sample from entering the reaction chamber 132 and directly rushing into the exhaust channel 122, thereby hindering gas discharge, but also forms a notch in the sidewall of the reaction chamber 132. The notch is asymmetrical, which helps to reduce the interfacial energy at the front end of the liquid flow, making it easier for the liquid sample to enter the reaction chamber 132.

[0037] like Figures 1 to 4 As shown, specifically, the liquid inlet channel 131 includes a first sidewall 131-1 and a second sidewall 131-2. The first sidewall 131-1 coincides with the tangent line e, while the second sidewall 131-2 and the reaction chamber 132 are on the same side of the tangent line e. The second sidewall 131-2 smoothly connects to the sidewall of the reaction chamber 132 via a rounded chamfer 131-21. The rounded chamfer 131-21 can widen the gap and exacerbate the asymmetry. In conjunction with gravity, it can better allow the liquid sample to fill toward the bottom of the reaction chamber 132 and contact the cold dry ball (not shown in the figure), thereby facilitating the discharge of gas from the reaction chamber 132 and preventing the formation of large bubbles in the reaction chamber 132 along with the solution in the cold dry ball.

[0038] like Figures 1 to 4 As shown, the exhaust channel 133 extends vertically, and a first groove 1331 is provided at the lower end of the exhaust channel 133, which is connected to the top of the side wall of the reaction chamber 132. The depth of the first groove 1331 is greater than the depth of the exhaust channel 133 and less than the depth of the reaction chamber 132. The first groove 1331 acts as a capillary valve, preventing the liquid sample in the reaction chamber 132 from entering before the gas and blocking the exhaust channel 131. When the reaction chamber 132 is gradually filled with the liquid sample, the gas is first squeezed into the exhaust channel 131. As the liquid sample spreads toward the first groove 1331, the liquid sample will converge into the first groove 1331, thereby preventing the gas in the reaction chamber 132 from being unable to be discharged.

[0039] like Figures 1 to 4 As shown, the width and length of the first groove 1331 are both equal to or less than 1 mm, and the depth ratio of the first groove 1331 to the reaction chamber 132 is 1:2 to 2:3.

[0040] like Figures 1 to 4As shown, preferably, the cross-sectional profile of the first groove 1331 is in an inverted U shape.

[0041] like Figures 1 to 5 As shown, the upper end of the exhaust channel 133 is provided with a second groove 1332 and a third groove 1333 that are connected in sequence. The second groove 1332 and the third groove 1333 form a stop valve to ensure that the liquid sample entering the exhaust channel 133 is intercepted at the position of the second groove 1332 under the capillary force and the gravitational pressure difference and cannot continue to overflow upward. The liquid sample is confined inside the reaction chamber 132 and the exhaust channel 133, which can effectively ensure the ratio of cold dry bulbs to liquid sample in the reaction chamber 132.

[0042] Specifically, when the liquid sample in the exhaust channel 133 rises to the valve mouth position (i.e., the junction of the second groove 1332 and the third groove 1333) due to capillary action, the characteristics of the annular groove cause the cross-section of the liquid sample to undergo a sudden change in both depth and width, thereby forming a certain capillary valve resistance, which inhibits the liquid sample from continuing to rise.

[0043] like Figures 1 to 5 As shown, preferably, the depth ratio of the second groove 1332 to the third groove 1333 is 1:2 to 1:3. The depth of the third groove 1333 is preferably 0.6 mm to 1.2 mm.

[0044] like Figures 1 to 3 As shown, two exhaust holes 15 are horizontally extended from the sidewall of the sample loading chamber 10. The two exhaust holes 15 are respectively connected to the two reaction unit groups. Of course, the number of exhaust holes 15 is not limited to two. The purpose is to connect the exhaust flow channels 133 of all reaction units 13 to the sample loading chamber 10, forming an internal circulation air channel between the sample loading chamber 10 and the reaction units 13.

[0045] like Figures 1 to 5 As shown, the exhaust hole 15 is conical, and the narrow end of the cone is located on the inner wall of the sample loading chamber 10, and the wide end of the cone is connected to the exhaust channel 133. In order to enable one exhaust hole 15 to connect to the eight reaction units 13 of the same reaction unit group, the front end face and the rear end face of the chip body 1 are both provided with a gas collection groove 14, and the wide end of the cone-shaped exhaust hole 15 is opened in the gas collection groove 14, and the eight exhaust channels 133 of the same reaction unit group are connected to the gas collection groove 14. Preferably, the diameter of the narrow end of the cone-shaped exhaust hole 15 is less than or equal to 2 mm. The conical exhaust hole can prevent the liquid sample in the collection groove from flowing back into the sample loading chamber, and can also ensure that the liquid sample will not overflow from the exhaust hole and block the exhaust channel during the loading process.

[0046] like Figures 1 to 5 As shown, specifically, the gas collection groove 14 is extended horizontally, and the eight third grooves 1333 of the same reaction unit group are arranged horizontally and spaced apart and connected to the gas collection groove 14 .

[0047] like Figures 1 to 5 As shown, preferably, the upper half of the third groove 1333 is disposed within the gas conduit 14. The lower half of the third groove 1333 protrudes downward from the gas conduit 14. If a liquid sample enters the third groove 1333, the lower half of the third groove 1333 can be used to contain the liquid sample, preventing the liquid sample from entering the gas conduit 14 and forming cross-flow.

[0048] like Figures 1 to 5 As shown, an in vitro detection device includes a detector and an internal circulation microfluidic chip having the structure described above. The detector has a detection station for placing the microfluidic chip, which is used to detect liquid samples in each reaction chamber 132. The specific structure and detection principle of the detector are related to the prior art and will not be described in detail here.

[0049] The above is only a specific implementation of the present invention, but the design concept of the present invention is not limited to this. Any non-substantial changes to the present invention using this concept shall be deemed as an infringement of the protection scope of the present invention.

Claims

1. An internal circulation microfluidic chip, comprising a chip body (1) provided with at least one reaction unit (13), wherein the reaction unit (13) comprises a liquid inlet channel (131), a reaction chamber (132), and an exhaust channel (133) sequentially connected along a liquid flow direction, a sample loading chamber (10) being vertically provided at the upper end of the chip body (1); a liquid outlet (101) being provided at the bottom of the sample loading chamber (10), and the liquid outlet (101) being connected to the liquid inlet channel (131), characterized in that: The side wall of the sample adding chamber (10) is horizontally extended to be provided with at least one exhaust hole (15), the exhaust hole (15) is tapered, and the narrow end of the tapered hole is located on the inner side wall of the sample adding chamber (10), and the wide end of the tapered hole is connected to the exhaust flow channel (133), the exhaust flow channel (133) is vertically extended, and the lower end of the exhaust flow channel (133) is connected to the top of the side wall of the reaction chamber (132); the liquid inlet flow channel (131) is extended along the tangent line (e) of the reaction chamber (132) and is provided on the side wall of the reaction chamber (132).

2. The internal circulation microfluidic chip according to claim 1, characterized in that: The front end face and / or the rear end face of the chip body (1) are provided with a plurality of the reaction units (13); the upper end of the exhaust flow channel (133) is provided with a second groove (1332) and a third groove (1333) which are connected in sequence; the width of the second groove (1332) gradually increases from bottom to top, the width of the third groove (1333) is equal to or greater than the width of the second groove (1332), and the depth of the third groove (1333) is greater than the depth of the second groove (1332); The front end face and / or the rear end face of the chip body (1) are further provided with an air collection groove (14), the air collection groove (14) being connected to the plurality of third grooves (1333), and the tapered wide end of the exhaust hole (15) being connected to the air collection groove (14).

3. The internal circulation microfluidic chip according to claim 2, characterized in that: The depth ratio of the second groove (1332) to the third groove (1333) is 1:2 to 1:

3.

4. An internal circulation microfluidic chip according to claim 2 or 3, characterized in that: The upper half of the third groove (1333) is opened inside the air collecting groove (14).

5. The internal circulation microfluidic chip according to claim 2, characterized in that: The third groove (1333) is extended horizontally, and a plurality of the reaction units (13) are arranged horizontally and spaced apart on the front end surface and / or the rear end surface of the chip body (1).

6. An internal circulation microfluidic chip according to claim 1, 2, 3 or 5, characterized in that: The front end face and the rear end face of the chip body (1) are both provided with a plurality of reaction units (13), forming two front and rear reaction unit groups; the chip body (1) is provided with a mounting portion (16) for assembling a heating element between the two reaction unit groups.

7. An internal circulation microfluidic chip according to claim 1, 2, 3 or 5, characterized in that: A first groove (1331) is provided at one end of the exhaust channel (133) communicating with the reaction chamber (132); the depth of the first groove (1331) is greater than the depth of the exhaust channel (133) and less than the depth of the reaction chamber (132).

8. The internal circulation microfluidic chip according to claim 7, characterized in that: The width and length of the first groove (1331) are both equal to or less than 1 mm, and the depth ratio of the first groove (1331) to the reaction chamber (132) is 1:2 to 2:

3.

9. The internal circulation microfluidic chip according to claim 1, characterized in that: The liquid inlet channel (131) comprises a first side wall (131-1) and a second side wall (131-2), the first side wall (131-1) and the tangent line (e) coincide with each other, the second side wall (131-2) and the reaction chamber (132) are on the same side of the tangent line (e), and the second side wall (131-2) is smoothly connected to the side wall of the reaction chamber (132) via a rounded chamfer (131-21).

10. An in vitro detection device, characterized in that: The invention comprises a detector and an internal circulation microfluidic chip as described in any one of claims 1 to 9, wherein the detector is used to detect a liquid sample in a reaction chamber.

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