Microfluidic chip

Abstract

The present invention discloses a microfluidic chip, which has the advantages that through holes are opened at the intersections of the microchannels on the substrate, and communication joints for connecting outlet capillary tubes, inlet capillary tubes or capillary gel electrodes are bonded above the through holes; when the outlets of the Y-shaped microchannels are blocked, negative and positive electroosmotic monolithic column preparation liquids can be added from the first and second interfaces, and the negative and positive electroosmotic monolithic columns are polymerized in the microchannels of the pump area under ultraviolet light irradiation during dynamic flow, so that the present microfluidic chip can be used as an electroosmotic pump; when the first and second interfaces are blocked, chromatographic separation monolithic column preparation liquid is added from the communication joint, and the chromatographic separation monolithic column is polymerized in the exposed separation area microchannels under ultraviolet light irradiation, so that the present microfluidic chip can be used as a chromatographic separation chip; or a combination of the two enables the present microfluidic chip to be used as a monolithic column electroosmotic pump-chromatographic separation combined chip; thereby enabling the present microfluidic chip to have multiple functions and be capable of large-scale commercial applications.

Description

Technical Field

[0001] The present invention belongs to the technical field of micro total analysis systems, and in particular relates to a microfluidic chip. Background Art

[0002] Microfluidic chips are a hot area in the development of current micro total analysis systems. Microfluidic chip analysis uses the chip as an operation platform, is based on analytical chemistry, relies on microelectromechanical processing technology, has a microchannel network as its structural feature, and has life science as its current main application object. It is the focus of the development in the field of current micro total analysis systems. The goal is to integrate the functions of an entire laboratory, including sampling, dilution, reagent addition, reaction, separation, detection, etc. on the microfluidic chip, and it can be used multiple times. Due to different application functions, the styles of microfluidic chips will change.

[0003] Among them, the electroosmotic pump drives the fluid movement according to the principle of electroosmotic drive. It has the characteristics of continuous infusion, no pulsation, no movable parts, no mechanical wear and material fatigue, and avoids micro-leakage of check valves and dynamic seals. It is a relatively successful microfluidic driving and control technology at present and has a wide application prospect on microfluidic chips. The chromatographic separation monolithic column is used to separate the passing test samples so that the chromatograph can analyze and obtain the chromatogram of the test samples, and it has a good market prospect in the detection field.

[0004] However, no microfluidic chip that can integrate a monolithic column electroosmotic pump and / or a chromatographic separation monolithic column has been found on the market, and there is an urgent need for development. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a microfluidic chip that can integrate a monolithic column electroosmotic pump and / or a chromatographic separation monolithic column on its microchannels.

[0006] The technical solution adopted by the present invention to solve the above technical problem is: a microfluidic chip, including a permanently bonded substrate and cover plate, and a Y-shaped microchannel between the substrate and the cover plate. The first interface and the second interface are opened on the substrate. The micro-pipes in the pump area are between the first interface and the intersection of the microchannel, and between the second interface and the intersection of the microchannel. The micro-pipes in the separation area are between the intersection of the microchannel and the outlet of the separation micro-pipe. The substrate is provided with a through hole extending along the thickness direction of the substrate at the intersection of the microchannels, and a communication joint for connecting a feed capillary, a discharge capillary or a capillary gel electrode is bonded on the through hole.

[0007] Compared with the prior art, the advantages of the present invention are as follows: a through-hole perpendicular to the microchannels is provided at the intersection of the microchannels on the substrate, and a communication joint is bonded on the through-hole. The communication joint can be used to connect a feed capillary as a feed port, connect a discharge capillary as a discharge port, or connect a capillary gel electrode as an electric field decoupler; when the outlet of the separation microchannel is blocked, negative and positive electroosmotic monolithic column preparation liquids can be added from the first interface and the second interface. Under ultraviolet light irradiation during dynamic flow, a negative and positive electroosmotic monolithic column is polymerized in the microchannels in the pump area, enabling the present microfluidic chip to be used as an electroosmotic pump chip; when the first and second interfaces are blocked, a chromatographic separation monolithic column preparation liquid is added from the communication joint to the microchannels in the separation area, and a chromatographic separation monolithic column is polymerized in the exposed microchannel section in the separation area under ultraviolet light irradiation, enabling the present microfluidic chip to be used as a chromatographic separation chip; or after a negative and positive electroosmotic monolithic column is polymerized in the microchannels in the pump area, a chromatographic separation monolithic column is polymerized in the microchannels in the separation area, and the communication joint is connected to a capillary gel electrode as an electric field decoupler, enabling the present microfluidic chip to be used as a combined chip of monolithic column electroosmotic pump-chromatographic separation; thus, the present microfluidic chip has multiple functions and can be commercially applied on a large scale.

[0008] Preferably, a light-shielding paper covering the separation area microchannels and the intersection of the microchannels is adhered to the top surface of the substrate. It is used to cover the separation area microchannels and the intersection of the microchannels to prevent the negative and positive electroosmotic monolithic column preparation liquids from polymerizing at the intersection of the microchannels and causing blockage of the through-hole.

[0009] As an improvement, an exposure area exposing a section of the separation area microchannel is provided on the light-shielding paper. During the process of adding the chromatographic separation monolithic column preparation liquid, when the section of the separation area microchannel in the exposure area is filled, the outlet of the separation microchannel is blocked, and a chromatographic separation monolithic column is polymerized on this section of the separation area microchannel under ultraviolet light irradiation.

[0010] Preferably, pressure-resistant metal sheets are bonded to the bottom surface of the cover plate and are respectively located below the first interface and the second interface. It is used to enhance the pressure resistance of the first interface and the second interface with the lowest mechanical pressure resistance on the cover plate, reinforce the pressure-resistant weak points of the present microfluidic chip, and can increase the maximum pressure resistance of the present microfluidic chip to 10 MPa, enabling the flushing pressure of the negative and positive electroosmotic monolithic column and the chromatographic separation monolithic column to be increased, improving the working performance of the negative and positive electroosmotic monolithic column and the chromatographic separation monolithic column, that is, increasing the electroosmotic back pressure of the negative and positive electroosmotic monolithic column and accelerating the chromatographic separation speed of the detected sample.

[0011] Preferably, a pressure-resistant metal sheet is also bonded to the bottom surface of the cover plate below the intersection of the microchannels. To improve the pressure resistance performance of the present microfluidic chip.

[0012] Preferably, the outlets of the microchannels are provided on the side walls of the substrate and the cover plate. To improve the pressure resistance performance of the present microfluidic chip. Brief Description of the Drawings

[0013] Figure 1 This is a top perspective view of the present invention (the Y-shaped microchannel is not shown, and the capillary, two-way joint and plug are connected at the outlet).

[0014] Figure 2 This is a top perspective view of the present invention (the Y-shaped microchannel is shown, and the first interface and the second interface are connected to the sampling tubes of the negative and positive electroosmotic monolithic column preparation solutions).

[0015] Figure 3 is Figure 2 an enlarged view of area A of

[0016] Figure 4 This is a bottom perspective view of the present invention (the Y-shaped microchannel is not shown, the capillary, two-way joint and plug are connected at the outlet, and the first interface and the second interface are connected to the sampling tubes of the negative and positive electroosmotic monolithic column preparation solutions).

[0017] Figure 5 This is a bottom perspective view of the present invention (the Y-shaped microchannel is shown, the connecting joint is omitted, the capillary, two-way joint and plug are connected at the outlet, and the first interface and the second interface are connected to the sampling tubes of the negative and positive electroosmotic monolithic column preparation solutions).

[0018] As shown in the figure: 1. Substrate, 1-1. First interface, 1-2. Second interface, 1-3. Microchannel in the pump area, 1-4. Microchannel in the separation area, 1-5. Outlet of the separation microchannel, 1-6. Through hole, 2. Cover plate, 3. Connecting joint, 4. Capillary, 5. Two-way joint, 6. Plug, 7. Light-shielding paper, 7-1. Exposure area, 8. Compressive metal sheet, 9. Sampling tube. Detailed Description of the Invention

[0019] The present invention will be further described in detail below with reference to the embodiments in the drawings.

[0020] This embodiment is Figures 1 to 5 shown as a microfluidic chip, including a substrate 1 and a cover plate 2 bonded permanently. There is a Y-shaped microchannel with an elliptical cross-section between the substrate 1 and the cover plate 2. The first interface 1-1 and the second interface 1-2 are opened on the substrate 1. Between the first interface 1-1 and the second interface 1-2 and the intersection of the microchannel is the microchannel in the pump area 1-3. The two microchannels in the pump area 1-3 are symmetrically arranged or have the same total volume; between the intersection of the microchannel and the outlet 1-5 of the separation microchannel is the microchannel in the separation area 1-4; the substrate 1 is provided with a through hole 1-6 (also called a vertical hole, perpendicular to the Y-shaped microchannel) extending along the thickness direction of the substrate 1 at the intersection of the microchannel. A connecting joint 3 for connecting the feed capillary as the feed port, connecting the discharge capillary as the discharge port or connecting the capillary gel electrode as the electric field decoupler is bonded above the through hole 1-6.

[0021] Preferably, a light-shielding paper 7 covering the microchannels in the separation zone 1-4 and the microchannel intersections is pasted on the top surface of the substrate 1. Most preferably, an exposure area 7-1 (i.e., an area without the light-shielding paper 7 or permeable to ultraviolet light) exposing a section of the microchannels in the separation zone 1-4 is provided on the light-shielding paper 7. The light-shielding paper 7 can be directly a black light-shielding tape, which can prevent ultraviolet light from passing through.

[0022] Preferably, pressure-resistant metal sheets 8 are adhesively bonded to the bottom surface of the cover plate 2 and are respectively disposed below the first interface 1-1, the second interface 1-2 and the microchannel intersections, and the maximum pressure resistance of the present microfluidic chip can be increased to 10 MPa. Since the apertures of the first interface 1-1 and the second interface 1-2 are 1.6 mm, the cover plate 2 bears pressure alone at this position during flushing, and the pressure-bearing area is the largest and it is most likely to be broken. When the pressure-resistant metal sheets 8 are not adhesively bonded, the maximum pressure borne by the cover plate 2 below the first interface 1-1 and the second interface 1-2 is about 6 MPa; followed by the position below the microchannel intersections, that is, below the through hole 1-6. The cover plate 2 also bears pressure alone at this position during flushing, but the area of the through hole 1-6 is smaller than that of the first interface 1-1 and the second interface 1-2, and the maximum pressure is slightly higher, about 8 MPa.

[0023] Preferably, the separation microchannel outlet 1-5 is provided at the bonding position of the side walls of the substrate 1 and the cover plate 2. The aperture of the separation microchannel outlet 1-5 is 0.37 mm, and the separation microchannel outlet 1-5 is a transverse hole, which has limited influence on the pressure resistance of the present microfluidic chip with an overall thickness of 3.4 mm to 3.8 mm.

[0024] In this microfluidic chip, the substrate 1 and the cover plate 2 are made of optical glass with a thickness of 1.7 mm to 1.9 mm. During the manufacturing process of this microfluidic chip, conventional photolithography and etching are first performed on the chromium-coated glass substrates of the substrate 1 and the cover plate 2, so that an elliptical cross-section Y-shaped microchannel can be formed after the permanent bonding of the substrate 1 and the cover plate 2. The depth of the Y-shaped microchannel is 50 µm, that is, the depth of the Y-shaped microchannel in the upper half of the substrate 1 and the cover plate 2 is 25 µm each; the microchannels 1-3 in the pump area are arranged in a meandering shape, with a single length of about 12 cm, the width of the microchannels 1-3 in the pump area is 120-130 µm, and the microchannels 1-4 in the separation area are also arranged in a meandering shape, with a length of about 12 cm, and the width of the microchannels 1-4 in the separation area is 200-210 µm. Then, the punching operations of the first interface 1-1, the second interface 1-2, and the through hole 1-6 on the substrate 1 are carried out: after the substrate 1 is bonded to the glass gasket, the first interface 1-1 and the second interface 1-2 are first polished. The apertures of the first interface 1-1 and the second interface 1-2 after polishing are 1.6 mm. After replacing the drill bit, the through hole 1-6 first drills the outer hole from the top surface of the substrate 1, and the drilling depth of the outer hole is about 1 mm. The aperture of the outer hole after polishing is 0.37 mm. After the substrate 1 and the glass gasket are separated by water bath, the substrate 1 is turned over and bonded to the glass gasket again, and the inner hole of the through hole 1-6 is drilled from the microchannel intersection of the substrate 1 until the outer hole is penetrated. The drilling depth of the inner hole is less than 1 mm, and the aperture of the inner hole of the through hole 1-6 is 0.12 mm to 0.15 mm. After the substrate 1 and the cover plate 2 are bonded with 502 glue (with the side with the microchannel facing each other), the lateral punching operation of the separation microchannel outlet 1-5 is carried out. The aperture of the separation microchannel outlet 1-5 is 0.35 mm. The substrate 1 and the cover plate 2 are separated by water bath, and the substrate 1 and the cover plate 2 are cleaned and surface-treated in concentrated sulfuric acid and then sealed. Sealing (also called permanent bonding) is carried out in a high-temperature furnace at 400-600 °C. After permanent bonding, the separation microchannel outlet 1-5 is polished, and the aperture after polishing is 0.37 mm to obtain the chip body. When bonding the connection joint 3 (using the Upchurch Scientific joint of IDEX Health & Science LLC) to the chip body, a capillary is inserted into the outer hole of the through hole 1-6 for positioning, and it can prevent the inner hole of the through hole 1-6 from being blocked after the bonding material of the Upchurch Scientific joint melts.

[0025] Then, connect a capillary 4 (apply a small amount of epoxy glue on the outside of the capillary) to the outlet 1-5 of the separation microchannel on the chip body. Then, connect a two-way joint 5 and a plug 6 to the free end of the capillary 4. Paste a light-shielding paper 7 on the top surface of the substrate 1 of the chip body, adhesively connect a compressive metal sheet 8 (using epoxy glue or ultraviolet curable glue) to the bottom surface of the cover plate 2 of the chip body, and connect a sampling tube 9 (apply epoxy glue on the outside of the PFA Teflon tube) to the first interface 1-1 and the second interface 1-2 of the substrate 1 of the chip body. Among them, the light-shielding paper 7 and the compressive metal sheet 8 can be used as additional accessories and operated during later use. The size of the compressive metal sheet 8 can be adjusted according to the compressive requirements.

[0026] It should be noted that during the polymerization process of the negative and positive electroosmotic monolithic columns on this microfluidic chip, the first interface 1-1 serves as the feed port for the preparation solution of the negative electroosmotic monolithic column, and the second interface 1-2 serves as the feed port for the preparation solution of the positive electroosmotic monolithic column. When the outlet 1-5 of the separation microchannel is blocked, a discharge capillary is installed in the connection joint 3 for use as the outlet; when introducing the preparation solution of the chromatographic separation monolithic column, a feed capillary is installed in the connection joint 3 for use as the feed port for the preparation solution of the chromatographic separation monolithic column; when flushing the chromatographic separation monolithic column, a feed capillary is installed in the connection joint 3 to connect the liquid phase pump loaded with the flushing solution and the shunt capillary, and the residual preparation solution of the chromatographic separation monolithic column is discharged from the outlet 1-5 of the separation microchannel; when flushing the negative and positive electroosmotic monolithic columns, the first interface 1-1 and the second interface 1-2 are connected and then connected to the liquid phase pump loaded with the flushing solution, and shunt capillaries are connected to both shunt branches. When the outlet 1-5 of the separation microchannel is blocked, a discharge capillary is installed in the connection joint 3. Under the shunt pressure relief of the shunt capillary, the liquid phase pump pushes the flushing solution to discharge the residual preparation solution of the negative and positive electroosmotic monolithic columns from the connection joint 3; when adding the detection sample, a feed capillary is installed in the connection joint 3 and connected to the syringe pump for use as the feed port for the detection sample and the mobile phase; during chromatographic separation detection, a capillary gel electrode is installed in the connection joint 3, a positive high-voltage power supply is connected between the first interface 1-1 and the capillary gel electrode, and a negative high-voltage power supply is connected between the second interface 1-2 and the capillary gel electrode. The connection joint 3 and the capillary gel electrode form an electric field decoupler to eliminate part of the internal consumption of the electroosmotic flow when the electroosmotic flows converge, thereby increasing the driving force for the detection sample and the mobile phase and improving the separation speed of the detection sample; after the detection is completed, the outlet 1-5 of the separation microchannel is opened, and the connection joint 3 is connected to the liquid phase pump loaded with the mobile phase and the shunt capillary to flush the working fluid for electroosmosis and the mobile phase out of the outlet 1-5 of the separation microchannel. That is to say, this microfluidic chip can integrate the negative and positive electroosmotic monolithic columns with the chromatographic separation monolithic column and can be used for repeated electroosmotic pump-driven chromatographic separation detection. Of course, this microfluidic chip can also be used only as an electroosmotic pump chip (only for the polymerization and flushing of the negative and positive electroosmotic monolithic columns) or a chromatographic separation chip (only for the polymerization and flushing of the chromatographic separation monolithic column). Here, it should be noted that the electric field decoupler is a device that can allow charges to pass through but isolate other fluids from passing through. That is, after the connection joint 3 is connected to the capillary gel electrode, it can respectively conduct the electric field circuits of the negative and positive electroosmotic monolithic columns, and the working fluid can only flow in the Y-shaped microchannel and flow to the separation microchannel 1-4 and will not flow out from the connection joint 3.

[0027] In this embodiment, the substrate 1 is above the cover plate 2. Contrary to the usual technical name, this is mainly because the substrate 1 is the core component of this microfluidic chip and plays more roles, while the cover plate 2 only serves to seal. Based on the design concept of this microfluidic chip, swapping the names of the substrate and the cover plate, or replacing them with other similar names, shall be regarded as within the protection scope of the present invention.

Claims

1. A microfluidic chip, comprising a substrate (1) and a cover plate (2) bonded permanently, and a Y-shaped microchannel between the substrate (1) and the cover plate (2). A first interface (1-1) and a second interface (1-2) are opened on the substrate (1), and micro-pipes of a pump area (1-3) are arranged between the first interface (1-1) and the intersection of the microchannel and between the second interface (1-2) and the intersection of the microchannel; characterized in that, Between the microchannel intersection and the outlet (1-5) of the separation microchannel is the separation zone microchannel (1-4); a through hole (1-6) extending in the thickness direction of the substrate (1) is provided at the microchannel intersection of the substrate (1), and a communication joint (3) for connecting a feed capillary, a discharge capillary or a capillary gel electrode is bonded on the through hole (1-6); a light-shielding paper (7) covering the separation zone microchannel (1-4) and the microchannel intersection is pasted on the top surface of the substrate (1); the outlet (1-5) of the separation microchannel is arranged at the bonding position of the side walls of the substrate (1) and the cover plate (2).

2. The microfluidic chip according to claim 1, wherein: An exposure area (7-1) exposing a section of the separation zone microchannel (1-4) is provided on the light-shielding paper (7).

3. The microfluidic chip according to claim 1, characterized in that: Compressive metal sheets (8) respectively arranged below the first interface (1-1) and the second interface (1-2) are bonded to the bottom surface of the cover plate (2).

4. The microfluidic chip according to claim 1, characterized in that: A compressive metal sheet (8) is also bonded below the microchannel intersection on the bottom surface of the cover plate (2).

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