CN109030369B

CN109030369B - Multichannel micro-fluidic chip combined with cuvette

Info

Publication number: CN109030369B
Application number: CN201811047102.3A
Authority: CN
Inventors: 徐文峰; 廖晓玲; 徐紫宸; 杨书豪
Original assignee: Chongqing University of Science and Technology
Current assignee: Chongqing University of Science and Technology
Priority date: 2018-09-08
Filing date: 2018-09-08
Publication date: 2023-07-14
Anticipated expiration: 2038-09-08
Also published as: CN109030369A

Abstract

The invention provides a method for using a microfluidic chip combined with a cuvette, which consists of a diversion area, a mixing area and a liquid outlet area. The method is characterized in that: the whole chip is in a cuboid thick sheet shape. According to the long side of cuboid vertical arrangement, processing has each functional unit in reposition of redundant personnel district, mixed district, the play liquid district in proper order from the top. The invention solves the functional integration of heavy metal sample pretreatment in sample introduction, flow division, reagent addition and mixing, and provides a multichannel microfluidic chip for heavy metal ion detection. The beneficial effects of the invention are as follows: the diversion is uniform, the solution mixing is rapid, and the liquid outlet interface is unique and durable; can directly be connected with the cuvettes of different models, finally, the cuvettes are taken down and put into a spectrophotometer for detection, and then the parameter data can be read.

Description

Multichannel micro-fluidic chip combined with cuvette

Technical Field

The invention relates to a multichannel microfluidic chip, in particular to a multichannel microfluidic chip which is used for heavy metal ion detection and can be directly combined with cuvettes with various specifications.

Technical Field

At present, with the rapid development of various industries and manufacturing industries, the wide use of pesticides and fertilizers, the heavy metal pollution in farmlands and rivers is increasingly serious, and the heavy metal pollution is seriously threatened to the ecological environment and the human health because the heavy metal pollution has toxicity and is easy to accumulate in plants, animals and human bodies through food chains. Therefore, in order to make the detection of heavy metals simple and inexpensive, a simple, practical and low-reagent-consumption test device is an urgent need.

The micro-fluidic chip is also called a chip laboratory or a micro-total analysis system, and basic operation units of sample pretreatment, reaction, separation, detection, cell culture, separation, cracking and the like related in life science are integrated on a chip with the size of a few square centimeters by a micro-processing technology, and the whole experimental system is flexibly controlled by utilizing a micro-channel network, so that various functions of the traditional chemical or biological laboratory are realized. Since the beginning of the 90 s of the 20 th century, microfluidic chips have been widely used in analytical chemistry, synthetic chemistry, drug screening, clinical diagnostics, biotechnology, environmental testing, and the like, due to their advantages of rapid analysis, low reagent consumption, miniaturization, integration, and automation.

At present, the heavy metal ion detection apparatus generally takes a large device as a main part, and has a plurality of limitations, if a small device is available, the detection of heavy metal ions can be realized, and the detection tool with low cost can fill the gap.

Disclosure of Invention

The invention provides a multichannel micro-fluidic chip for heavy metal ion detection, which aims to solve the problems of difficult sample injection, flow division, reagent addition, mixing and collection operation of heavy metal sample pretreatment, quantitative analysis and the like, and realizes a function integrated device.

The technical scheme of the invention is that the multichannel microfluidic chip combined with the cuvette consists of a diversion area, a mixing area and a liquid outlet area. The method is characterized in that: the whole chip is in a cuboid thick sheet shape. According to the longest side of cuboid vertical arrangement, processing has each functional unit in reposition of redundant personnel district, mixed district, the play liquid district in proper order from the top.

The diversion area comprises a sample inlet at the top end, a cylindrical sample storage pool below the sample inlet, a main channel communicated below the sample storage pool, a liquid separation port and a sample separation channel. The main channel is connected with 3 sample separating channels through the liquid separating port, and the 3 sample separating channels are arranged in parallel, vertically and equidistantly after liquid separation of the liquid separating port. The width dimension of the liquid separation port is consistent with the width of the main channel, and the depth dimension of the liquid separation port is smaller than that of the main channel. The channel of the liquid dividing opening is provided with 1 dividing column and 2 small dividing columns or 1 dividing island for dividing. Two triangular liquid separation sharp angles are processed between 3 sample separation channel openings of the liquid separation opening, namely, between 2 sample separation channel openings on two sides and 1 sample separation channel opening in the middle.

The mixing area comprises a cylindrical valve cavity, a liquid collecting port and a liquid homogenizing chamber, wherein each sample separating channel is horizontally processed on the same horizontal plane, the liquid collecting port is arranged at the bottom outlet of the valve cavity, and the liquid homogenizing chamber is arranged below the liquid collecting port. The valve cavity is matched with the valve body. The valve body is a cylinder and can rotate in the valve cavity in a sealing way. The inside of the valve body is of a hollow bottle-shaped structure, the top sealing cover is processed into a fixed knob, and a reagent opening and closing opening is processed at the circle center of the knob. A through square hole is machined in the side wall of the middle of the valve body, the size of the square hole is consistent with the size of an interface of the sample separation channel and the valve cavity, and the square hole is consistent with the size of the valve cavity and the size of the liquid collecting opening. The liquid collecting port is a round table-shaped through channel with a large upper part and a small lower part, and the lower part is communicated with the liquid homogenizing chamber. The liquid homogenizing chamber consists of a cavity and a hemispherical body, and the hemispherical body is overhead at the lower part of the liquid homogenizing chamber by a supporting frame. The processing position of the liquid collecting port is arranged right above the liquid homogenizing chamber hemispheroids, the size of the outlet at the lower part of the liquid collecting port is adjustable, and the liquid flowing out of the valve body can be ensured to be dripped on the liquid homogenizing chamber hemispheroids in a liquid drop form.

The liquid outlet area consists of a collecting tank and a telescopic liquid outlet interface. The collecting tank is arranged below the liquid homogenizing chamber and communicated with the liquid homogenizing chamber, and mixed liquid drops passing through the hemispherical body of the liquid homogenizing chamber are collected and stored. The liquid outlet interface is a telescopic interface, and slide rails are machined at two side ends of the liquid outlet interface and are used for being connected with the cuvette. A handle for controlling the telescopic liquid outlet interface is also processed in the liquid outlet area at the lower part of the chip. A sealing bottom cover for sealing the bottom surface of the whole chip is processed at the bottom of the chip in a matching way.

Above-mentioned technical scheme is preferred, every divides the appearance passageway can combine with dividing the liquid mouth, continues to divide into three branch appearance passageway by a subdivision, and a chip can divide 9 branch appearance passageways promptly, and the functional part below the connection branch appearance passageway is even a pair of increase, can form 9 kinds of mixed liquids, connects 9 cuvettes all. The main channel and the sample separation channel are subjected to hydrophobic surface treatment by adopting plasma treatment. The cavity and hemispherical body of the mixing area are all treated by hydrophobic surface.

In the above technical solution, preferably, the split column is on a central line of the liquid splitting port channel; the 2 small split columns are arranged on two sides of the rear part of the split columns. The diversion island is in a shuttle shape, and the tip of the diversion island at the front part and the tip of the island at the tail part are both positioned on the central line of the liquid diversion port channel. The middle and rear parts of the split islands are processed into the shape of a concave at the middle part at the opening parts of the split channels opposite to the two sides.

According to the technical scheme, preferably, the size of the outlet at the lower part of the liquid collecting port can be adjusted by using the liquid drops with different diameters and sizes, and the liquid drops in each liquid collecting port are prevented from falling out and being replaced by the protective screen.

The technical scheme of the invention has the following main beneficial effects.

(1) Evenly split. The design of the liquid separating port evenly divides the reagent passing through the main pipeline into 3 parts through the vertexes of the two triangles, and the reagent enters three sample injection channels respectively.

(2) The solution was mixed rapidly. The design of the liquid collecting port can drop the mixed liquid in the valve in the form of water drops, so that the reaction rate of the whole device is controlled. The mixed solution is dropped on the hemispheres at intervals in the form of water drops, so that the mixed solution can be ensured to form countless finer water drops, and the water drops are mixed to obtain fully mixed solution. And the whole mixing area is coated with a hydrophobic material, so that adhesion of surface solution is avoided.

(3) A unique liquid outlet interface. The liquid outlet interface is designed to be similar to a Type-C interface commonly used by a current mobile phone, so that the liquid outlet interface can be directly connected into the cuvette, different reagents directly flow into the cuvette after being mixed by the chip, the transferring step is omitted, and the waste of the reagents is maximally reduced. And the design of the slide rails is added at the two ends of the liquid outlet interface, the liquid outlet interface is retracted into the chip when the liquid outlet interface is idle and covered by the cover, so that pollution caused by contact with the outside can be effectively avoided.

Drawings

Fig. 1 is a schematic diagram of a front view structure of the present invention.

Fig. 2 is a right-view schematic structure of the present invention.

Fig. 3 is a schematic diagram of the front and right-side view of a valve body according to the present invention.

FIG. 4 is a schematic diagram of the present invention in use with a cuvette.

Fig. 5 is a schematic top view of a liquid homogenizing chamber according to the present invention.

Fig. 6 is a schematic structural view of a liquid separating port according to the present invention.

FIG. 7 is a schematic cross-sectional view of a dispensing port according to the present invention.

Fig. 8 is a schematic top view of a shunting island according to the present invention.

Fig. 9 is a schematic front view of a liquid collecting port according to the present invention.

In the figure: 1. a sample inlet; 2. a sample storage pool; 3. a main channel; 4. a liquid separating port; 5. a sample separation channel; 6. a valve cavity; 7. a liquid collecting port; 8. a liquid homogenizing chamber; 9. a support frame; 10. a slide rail; 11. a collecting tank; 12. a handle; 13. a liquid outlet interface; 14. square holes; 15. a valve body; 16. reagent opening and closing; 17. a knob; 18. sealing the bottom cover; 19. a cuvette; 20. a convex liquid head; 21. a shunt bar; 22. a small shunt column; 23. a liquid separation sharp corner; 24. a middle sample separation channel; 25. sample separating channels on two sides; 26. a shunt island tip; 27. a shunt island; 28. a concave surface in the middle; 29. island tail tip; 30. a chip holder; 31. dropping liquid beads; 32. and a protective screen.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

Referring to the shape structure of fig. 1 and 9, a multichannel microfluidic chip combined with a cuvette is composed of a diversion area, a mixing area and a liquid outlet area. The method is characterized in that: the whole chip is in a cuboid thick sheet shape. The components are vertically arranged at the longest side of the cuboid, fixed by a chip bracket 30, and are sequentially processed from the top end into a diversion area, a mixing area and a liquid outlet area.

The diversion area comprises a sample inlet 1 at the top end, a cylindrical sample storage pool 2 below the sample inlet 1, a main channel 3 communicated below the sample storage pool 2, a liquid diversion port 4 and a sample diversion channel 5. The main channel 3 is connected with 3 sample separating channels 5 through the liquid separating opening 4, and the 3 sample separating channels 5 are arranged in parallel, vertically and equidistantly after the liquid separating opening 4 separates liquid. The width dimension of the liquid separation port 4 is consistent with the width of the main channel 3, and the channel depth dimension of the liquid separation port 4 is smaller than the depth dimension of the main channel 3. In the channel of the tap 4, there are 1

tap

21 and 2 small taps 22 for tapping, or 1 tap island 27. Two triangular liquid separation sharp angles 23 are processed between the 3 sample separation channels 5 of the liquid separation port 4, namely between the 2 sample separation channels 25 on two sides and the 1 sample separation channel 24. The design of the flow dividing functional part of the liquid dividing port 4 is that the sample liquid of the main channel 3 is accurately and uniformly divided under the constant sample feeding flow rate or the stable acceleration state according to the optimal size parameter simulated by a computer. The sample liquid passes through two triangular split corners 23, divides the sample liquid passing through the main channel 3 into 3 parts, and enters three sample separating channels 5 respectively.

The mixing zone comprises a cylindrical valve cavity 6, a liquid collecting port 7 and a liquid homogenizing chamber 8, wherein each sample separating channel 5 is horizontally processed on the same horizontal plane, and the liquid collecting port 7 is arranged at the outlet of the lower bottom of the valve cavity 6, and the liquid homogenizing chamber 8 is arranged below the liquid collecting port 7. The valve cavity 6 is matched with the valve body 15; the valve body 15 is a cylinder and can rotate in a closed manner in the valve cavity 6. The valve body 15 is of a hollow bottle-shaped structure, a top sealing cover is processed into a fixed knob 17, and a reagent opening and closing opening 16 is processed at the center of the knob 17. A through square hole 14 is processed on the side wall of the middle part of the valve body 15, and the size of the square hole 14 is consistent with the size of the interface between the sample separation channel 5 and the valve cavity 6, and is consistent with the size of the valve cavity 6 and the size of the liquid collecting port 7. The reagent opening and closing port 16 is located at the top of the whole valve body, and is mainly used for adding heavy metal ion solution, and other reagent solutions can be added according to detection requirements. The square hole 14 is a square hole formed on the side surface of the valve body 15, and is mainly used for connecting the interior of the valve body 15 with the sample separation channel 5 and the liquid collecting port 7. Because the whole valve body 15 has only one square hole, when the square hole is not aligned with the sample separating channel 5, one section of the sample separating channel 5 is closed, and a part of gas exists, so that the solution cannot flow down. The whole valve body 15 is hollow, so that a certain volume is provided, and the solution entering the valve body 15 through the sample inlet 1 and the sample dividing channel 5 can be temporarily stored. The liquid collecting port 7 is a round table-shaped through passage with a large upper part and a small lower part, and the lower part is communicated with the liquid homogenizing chamber 8. The liquid homogenizing chamber 8 is composed of a cavity and a hemispherical body, and the hemispherical body is overhead at the lower part of the liquid homogenizing chamber 8 by a supporting frame 9. The processing position of the liquid collecting port 7 is arranged right above the hemispheroids of the liquid homogenizing chamber 8, the size of the outlet at the lower part of the liquid collecting port 7 is adjustable, and the liquid flowing out of the valve body 15 can be ensured to drop on the hemispheroids of the liquid homogenizing chamber 8 in a liquid drop mode. The main components of the liquid homogenizing chamber 8 are a hemisphere, which is used for sputtering liquid drops, a supporting frame 9 and a cuboid cavity, wherein the supporting frame 9 is used for supporting the hemisphere. The design of the liquid collecting port 7 can drop the mixed liquid in the valve body 15 in the form of water drops, so that the reaction rate of the whole device is controlled. The mixed solution is dropped on the hemispheres of the liquid homogenizing chamber 8 at intervals in the form of water drops, so that the mixed solution can be ensured to form countless finer water drops, and the water drops are mixed to obtain fully mixed solution. And the whole mixing area is coated with a hydrophobic material, so that adhesion of surface solution is avoided. The mixing zone is located in the middle lower part of the whole chip, the collecting tank 11 and the upper section of the liquid outlet port 13.

The liquid outlet area consists of a collecting tank 11 and a telescopic liquid outlet port 13. The collecting tank 11 is arranged below the liquid homogenizing chamber 8 and is communicated with the liquid homogenizing chamber 8, and mixed liquid drops passing through the hemispheres of the liquid homogenizing chamber 8 are collected and stored. The liquid outlet interface 13 is a telescopic interface, and slide rails 10 are processed at two side ends of the liquid outlet interface 13 and are used for being connected with a cuvette 19. A handle 12 for controlling the telescopic liquid outlet 13 is also arranged in the liquid outlet area at the lower part of the chip. A sealing bottom cover 18 is formed on the bottom of the chip to seal the entire bottom surface of the chip. The liquid outlet interface 13 is designed to be similar to a Type-C interface commonly used in the current electronic product, so that the liquid outlet interface 13 can be directly connected into the cuvette 19, different reagents are mixed through a chip, and the mixed reagents directly flow into the cuvette 19 after reaction, so that the transfer step is omitted, and the waste of the reagents is reduced to the greatest extent. And the design of the slide rails is added at the two ends of the liquid outlet interface 13, the liquid outlet interface 13 is retracted into the chip when the liquid outlet interface is idle, and the liquid outlet interface is covered by the sealing bottom cover 18, so that pollution caused by contact with the outside can be effectively avoided. The sealing bottom cover 18 functions to cover the bottom of the chip and prevent contamination of the liquid outlet port 13. Because the liquid outlet 13 is designed to be telescopic, the liquid outlet 13 needs to be retracted after use, and then the sealing bottom cover 18 is covered, so that the chip mixing area can be sealed.

According to the invention, 3 reagents for specific detection of heavy metals are added into 3 valve bodies 15, and sample liquid for heavy metal ions to be detected is added into the sample inlet 1, so that heavy metal detection experiments can be completed. The multi-channel microfluidic chip for heavy metal ion detection is provided, and the functional integration of the heavy metal sample pretreatment device in sample introduction, flow division, reagent addition and mixing is solved. Meanwhile, 3 heavy metal ion reagents with certain concentrations are added into 3 valve bodies 15, and living cell suspension is added into the sample inlet 1, so that the invention can be used for finishing cytotoxicity experiments. For a living cytotoxicity experiment, the chip provided by the invention is more suitable for the living cytotoxicity experiment with high heavy metal ion toxicity or high concentration content.

In the above technical scheme, each sample separation channel 5 can be combined with the liquid separation port 4, and is continuously subdivided into three sample separation channels 5, namely, one chip can divide 9 sample separation channels 5, functional components below the connecting sample separation channels 5 are increased uniformly and correspondingly, 9 reagents can be mixed, and 9 cuvettes are connected. The main channel 3 and the sample separation channel 5 are subjected to hydrophobic surface treatment by adopting plasma treatment. The cavity and hemispherical body of the mixing area are all treated by hydrophobic surface. For example: polytetrafluoroethylene (PTFE) coating.

In the above technical solution, the dividing rail 21 is on the central line of the channel of the liquid dividing opening 4, and the convex liquid head 20 is divided into 2 parts in a head-on manner. The 2 small split columns 22 are arranged on both sides of the rear portion thereof. The diversion island 27 is in a shuttle shape, and the diversion island tip 26 at the front part and the island tip 29 at the tail part are both positioned on the central line of the channel of the liquid diversion opening 4. The middle rear part of the split island 27 is formed with a middle concave surface 28 at the opening facing the two side split channels 25. The central concave surface 28 functions to direct the separated liquid into the central sample channel 24.

In the above technical solution, the size of the outlet at the lower part of the liquid collecting port 7 can be adjusted by the liquid drop beads 31 with different diameters placed in the liquid collecting port 7, and the liquid drop beads 31 in each liquid collecting port 7 are prevented from falling out and being replaced by the protective screen 32.

Finally, it is noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention.

Claims

1. A multichannel microfluidic chip combined with a cuvette consists of a diversion area, a mixing area and a liquid outlet area; the method is characterized in that: the whole chip is in a cuboid thick sheet shape; each functional component of a diversion area, a mixing area and a liquid outlet area is processed from the top end in sequence by vertically placing the longest side of the cuboid;

the flow dividing region comprises a sample inlet at the top end, a cylindrical sample storage pool below the sample inlet, a main channel communicated with the lower part of the sample storage pool, a liquid dividing port and a sample dividing channel; the main channel is connected with 3 sample separating channels through the liquid separating port, and the 3 sample separating channels are arranged in parallel, vertically and equidistantly after liquid separation of the liquid separating port; the width dimension of the liquid separation port is consistent with the width of the main channel, and the depth dimension of the liquid separation port is smaller than that of the main channel; 1 split column and 2 small split columns or 1 split island for splitting are processed in the channel of the liquid splitting port; two triangular liquid separation sharp angles are processed between 3 sample separation channel openings of the liquid separation port, namely, between 2 sample separation channel openings on two sides and 1 middle sample separation channel opening;

the mixing zone comprises a cylindrical valve cavity horizontally processed on the same horizontal plane and a liquid collecting port at the bottom outlet of the valve cavity, and a liquid homogenizing chamber below the liquid collecting port; the valve cavity is matched with the valve body; the valve body is a cylinder and can rotate in a closed manner in the valve cavity; the inside of the valve body is of a hollow bottle-shaped structure, the top sealing cover is processed into a fixed knob, and a reagent opening and closing opening is processed at the circle center of the knob; a through square hole is formed in the side wall of the middle part of the valve body, the size of the square hole is consistent with the size of an interface of the sample separation channel and the valve cavity, and the square hole is consistent with the size of the valve cavity and the size of the liquid collecting opening correspondingly, and the sizes are the same; the liquid collecting port is a round table-shaped through channel with a large upper part and a small lower part, and the lower part is communicated with the liquid homogenizing chamber; the liquid homogenizing chamber consists of a cavity and a hemispherical body, and the hemispherical body is overhead at the lower part of the liquid homogenizing chamber by a support frame; the processing position of the liquid collecting port is arranged right above the liquid homogenizing chamber hemispheroids, the size of the outlet at the lower part of the liquid collecting port is adjustable, and the liquid flowing out of the valve body can be ensured to drop on the liquid homogenizing chamber hemispheroids in a liquid drop form;

the liquid outlet area consists of a collecting tank and a telescopic liquid outlet interface; the collecting tank is arranged below the liquid homogenizing chamber, is communicated with the liquid homogenizing chamber, and is used for collecting and storing mixed liquid drops passing through the hemispherical body of the liquid homogenizing chamber; the liquid outlet interface is a telescopic interface, and slide rails are processed at two side ends of the liquid outlet interface and are used for being connected with the cuvette; a handle for controlling the telescopic liquid outlet interface is also processed in the liquid outlet area at the lower part of the chip; a sealing bottom cover for sealing the bottom surface of the whole chip is processed at the bottom of the chip in a matching way.

2. A multi-channel microfluidic chip for use with a cuvette as claimed in claim 1, wherein: each sample separation channel can be combined with the liquid separation port, and is continuously divided into three sample separation channels, namely, one chip can be divided into 9 sample separation channels, functional components below the sample separation channels are connected to be increased uniformly and correspondingly, 9 mixed liquids can be formed, and 9 cuvettes are connected; the main channel and the sample separation channel are subjected to hydrophobic surface treatment by adopting plasma treatment; the cavity and hemispherical body of the mixing area are all treated by hydrophobic surface.

3. A multi-channel microfluidic chip for use with a cuvette as claimed in claim 1, wherein: the diversion fence is arranged on the central line of the liquid diversion port channel; the 2 small shunt columns are respectively arranged at two sides of the rear part of the small shunt columns; the shunt island is in a shuttle shape, and the tip of the shunt island at the front part and the tip of the island at the tail part are both positioned on the central line of the liquid-separating port channel; the middle and rear parts of the split islands are provided with middle concave surfaces at the openings of the split channels opposite to the two sides.

4. A multi-channel microfluidic chip for use with a cuvette as claimed in claim 1, wherein: the size of the outlet at the lower part of the liquid collecting port can be adjusted by using the liquid drops with different diameters and sizes, and the liquid drops in each liquid collecting port are prevented from falling out and being replaced by using the protective screen plate.