WO2021249543A1

WO2021249543A1 - Liquid detection pool and liquid analysis system

Info

Publication number: WO2021249543A1
Application number: PCT/CN2021/099734
Authority: WO
Inventors: 陈思
Original assignee: 杭州准芯生物技术有限公司
Priority date: 2020-06-12
Filing date: 2021-06-11
Publication date: 2021-12-16
Also published as: CN111650389A

Abstract

A liquid detection pool and a liquid analysis system. The liquid detection pool comprises a body (11), the body (11) having an inlet (12); a quantifying cavity (21) provided in the body (11) and communicated with the inlet (12) by means of a first channel (31); a communicating cavity (41) provided in the body (11) and communicated with the quantifying cavity (21) by means of a second channel (32), wherein the position of the quantifying cavity (21) is lower than the positions of the communicating cavity (41) and the inlet (12); and a gas-liquid separation membrane (62) used for isolating the communicating cavity (41) from the outside, a gas in the communicating cavity (41) being suitable for penetrating through the gas-liquid separation membrane (62).

Description

Liquid detection cell and liquid analysis system

Cross-references to related applications

This application requires the priority of the Chinese patent application number "2020105377781" submitted by Hangzhou Zhunxin Biotechnology Co., Ltd. on June 12, 2020, with the title of "Liquid Detection Cell and Liquid Analysis System".

Technical field

This application relates to liquid detection, in particular to liquid detection pools and liquid analysis systems.

Background technique

In various types of analysis, samples and multiple reagents need to be added to the mixing chamber, such as a test tube. These samples can be human and animal samples, such as whole blood, plasma, serum, urine, saliva, feces, cerebrospinal fluid or lavage fluid, wax-sealed tissues and sections, tissue homogenates, and can also be plants, including traditional Chinese medicine, food Raw materials, processed foods, meats, beverages and alcoholic beverages, and raw materials and semi-finished products obtained in the beverage manufacturing process. It can also be cell culture or virus culture. The types of components analyzed include minerals, inorganic substances, organic substances, nucleic acid DNA, RNA, protein or fat.

At present, liquid detection mainly uses microfluidic centrifugal discs. The discs are provided with a quantitative cavity, a quantitative cavity and a waste liquid chamber. The quantitative liquid enters the quantitative cavity for detection and is finally discharged into the waste liquid chamber. This scheme has many shortcomings, such as:

1. The quantitative cavity and the quantitative cavity contain gas, which affects the accuracy of liquid quantification and detection;

2. It is necessary to set up a waste liquid chamber, which increases the structural complexity and volume accordingly.

Summary of the invention

In order to solve the above-mentioned shortcomings in the prior art solutions, the present application provides a liquid detection cell with accurate quantification and simple structure.

According to the liquid detection cell of the present application, the liquid detection cell includes a body with an inlet; the liquid detection cell further includes:

A quantitative cavity, the quantitative cavity is arranged in the body and communicates with the inlet through a first channel;

A communication cavity, the communication cavity is arranged in the body and communicates with the quantitative cavity through a second channel; the position of the quantitative cavity is lower than that of the communication cavity and the inlet;

A gas-liquid separation membrane, the gas-liquid separation membrane is used to isolate the communication cavity from the outside, and the gas in the communication cavity is suitable for permeating the gas-liquid separation membrane.

According to the liquid analysis system of the present application, the liquid analysis system includes a chip having a cover and a casing; the liquid analysis system further includes:

A storage device, the storage device adopts the above-mentioned liquid detection pool, and the liquid detection pool is in communication with the inside of the chip.

The liquid analysis system of the present application has a simple structure and a small volume; the gas-liquid separation membrane is used to achieve isolation from the outside world without the need for a waste liquid chamber, which reduces the structural complexity and volume; and the gas-liquid separation membrane is used to achieve the quantitative measurement of the gas in the chamber. Discharge improves the accuracy of liquid quantification and correspondingly improves the accuracy of subsequent liquid detection; the detection flux is high; there are multiple quantification chambers in a detection cell, and the detection of different parameters of the same liquid is performed at the same time.

Description of the drawings

Figure 1 is a cross-sectional view of the liquid detection pool of this application;

Figure 2 is a cross-sectional view of the liquid detection cell of the present application.

detailed description

Figures 1-2 and the following description describe alternative implementations of this application to teach those skilled in the art how to implement and reproduce this application. In order to teach the technical solutions of this application, some conventional aspects have been simplified or omitted. Those skilled in the art should understand that variations or substitutions derived from these embodiments will fall within the scope of the present application. Those skilled in the art should understand that the following features can be combined in various ways to form multiple variations of the present application. Therefore, this application is not limited to the following alternative embodiments, but only by the claims and their equivalents.

Example 1:

Figure 1-2 schematically shows a cross-sectional view of a liquid detection cell according to an embodiment of the present application. As shown in Figure 1-2, the liquid detection cell includes:

If the body 11 is made of plastic material, the body 11 has an inlet 12, which is suitable for liquid to enter;

The quantitative cavity 21 has a certain volume, and the quantitative cavity is arranged in the body and communicates with the inlet through the first channel 31;

The communicating cavity 41, the communicating cavity 41 is arranged in the body 11, and communicates with the quantitative cavity 21 through the second channel 32; the position of the quantitative cavity 21 is lower than that of the communicating cavity 41 and the inlet 12 ；

A gas-liquid separation membrane 62, the gas-liquid separation membrane 62 is used to isolate the communicating cavity 41 from the outside air, and the gas in the communicating cavity 41 is suitable for permeating the gas-liquid separation membrane 62; In the gas-liquid separation membrane, the gas in each of the channels 31-32, the quantitative chamber 21 and the communication chamber 41 is discharged through the gas-liquid separation membrane.

In order to improve the detection throughput, in an embodiment of the present application, the quantitative chamber has two or more, which are respectively connected with the inlet and the communication chamber, and the same liquid enters the multiple quantitative chambers for detection, and simultaneously detects the volume of multiple liquids. Parameters.

In order to improve analysis efficiency, in an embodiment of the present application, the number of the inlet and the quantitative cavity are the same, and the inlet, the quantitative cavity, and the communicating cavity constitute detection channels, and the detection channels are isolated.

In order to reduce the processing difficulty and cost of the liquid detection cell, in an embodiment of the present application, at least one of the quantitative cavity, the first channel, the communication cavity, and the second channel is formed in the following manner:

The body is provided with a groove, and the closing member is used to close the groove.

In order to reduce the processing difficulty and improve the processing efficiency, in an embodiment of the present application, the communicating cavity, the gas-liquid separation membrane and the closing member are arranged in sequence from the inside to the outside, and there is a gap between the gas-liquid separation film and the closing member. The gap is connected to the outside world.

In order to smoothly discharge the gas escaping from the gas-liquid separation membrane, in an embodiment of the present application, the body further has an exhaust groove, the gap is in communication with the exhaust groove, and a closing member closes a part of the exhaust groove , The part of the exhaust groove communicates with the outside; the position of the exhaust groove is higher than the position of the communication cavity.

In order to improve the processing efficiency and reduce the manufacturing cost, in an embodiment of the present application, the same sealing member is used to form the quantitative cavity and the communicating cavity, and to close a part of the exhaust groove.

In order to reduce processing difficulty and improve quantitative accuracy, in an embodiment of the present application, the quantitative cavity is formed in the following manner:

The main body has a penetrating part, and the front and back sides of the main body are respectively provided with closing parts for closing the penetrating part to form a closed space.

Example 2:

An application example of the liquid detection cell according to Embodiment 1 of the present application.

In this application example, as shown in Figure 1-2, the body is made of plastic; the upper side has two inlets 12 at both ends in the length direction; the lower side has two right-angle ends, and the right-angle end is adjacent to the volumetric cavity with a determined volume. (V-shaped detection cavity) 21. The quantitative cavity is: the main body has a penetrating part, and the front and rear sides of the main body are respectively provided with closing parts, thereby forming a closed space-the quantitative cavity; the main body has a communicating cavity 41, specifically: the main body The body 11 has a through part, the front side of the main body has a closing member 61, and the rear side has a gas-liquid separation membrane 62, thereby forming a closed space-quantification chamber; A channel 31, and a second channel 32 for communicating the quantitative cavity 21 and the communicating cavity 41. The first and second channels are: the front side of the body has a groove, and the closing member 61 closes the groove, thereby forming an elongated shape The first channel and the second channel are arranged up and down adjacent to the edge of the body, and the second channel is arranged up and down, from the outside to the inside, the first channel, the dosing chamber and the second channel are arranged in sequence; from top to bottom, the inlet, The first channel and the quantitative cavity are arranged in sequence, and the communication cavity, the second channel and the quantitative cavity are arranged in sequence; the upper part of the communication cavity on the rear side of the main body has an exhaust groove 51, and the closing member closes the part of the exhaust groove; the front side of the main body is closed The parts are the same PP film, fixed once, used to form the quantitative cavity, the communication cavity, the first channel and the second channel; the sealing part on the back side is the same PP film, fixed once, used to form the quantitative cavity and the communication cavity, and seal it There is a gap between the PP membrane on the back side and the gas-liquid separation membrane, so that the gas that escapes the gas-liquid separation membrane enters the exhaust groove through the gap, and finally enters the outside air.

The working mode of the above-mentioned liquid detection pool is:

The liquid enters the body through two inlets, passes through the first channel downwards, and then enters the quantitative cavity;

After the liquid fills the dosing cavity, it flows upwards, passes through the second channel and then enters the communication cavity;

In the above liquid feeding process, the gas in the first channel, the quantitative chamber, the second channel and the communicating chamber pass through the gas-liquid separation membrane, enter the gap between the gas-liquid separation membrane and the PP membrane, and then enter the exhaust groove, and finally Into the atmosphere.

Example 3:

According to the application example of the liquid detection pool of Embodiment 1 of the present application, the difference from Embodiment 2 is:

1. The body has only one inlet, which is connected to multiple quantitative cavities through multiple channels, and multiple quantitative cavities are connected to only one communicating cavity through multiple channels;

2. The quantitative cavity is formed as follows: the body has a groove (the side wall and the bottom wall of the groove are both part of the body), and the closing member closes the opening of the groove;

3. There is no need to provide a closure member on the outside of the gas-liquid separation membrane, and no need to set an exhaust groove.

Example 4:

An application example of the liquid detection cell according to Embodiment 2 of the present application in a liquid analysis system.

In this application example, the liquid analysis system includes a liquid detection tank, and further includes:

A frame, which is used to carry components such as chips and guide rails;

A carrier, the carrier is arranged on the frame and is suitable for carrying a chip; for example, the bottom end of the carrier is two V-shaped detection grooves, suitable for the two V-shaped quantitative cavities of the chip Insertion and fixation;

A fixed plate, the fixed plate has a first through hole and a third through hole, and is arranged on the guide rail by a sliding member; when the fixed plate is in the working position, from top to bottom, the third through hole and the The first groove (first matching portion) of the linkage part of the chip on the carrier (with the safety pin removed) corresponds up and down;

A guide rail, the guide rail is horizontally arranged at the top end of the frame and extends along the front-to-rear direction;

A first motor, the first motor is fixed on the fixed plate, and drives the connecting member to move up and down, thereby driving the moving member to move up and down;

A connecting piece, the upper part of the connecting piece is on the upper side of the fixed plate, the lower part passes through the first through hole of the fixed plate, and is connected with the moving part on the lower side of the fixed plate;

A moving part, the moving part is arranged on the lower side of the fixed plate, and the upper side of the chip moves up and down under the drive of the connecting part;

A second motor, the second motor is fixed on the fixing plate, and the encoder is connected with the rotation shaft of the second motor, and is used to determine the position of the rotation shaft of the second motor;

The transmission member passes through the third through hole, and the transmission member is driven by the second motor; when the fixed plate is in the working position, the key (second mating portion) at the bottom end of the transmission member is in contact with the The first groove of the linkage part of the chip is matched; in the vertical direction, the bottom end position of the transmission member is not lower than the height of the first groove, and not higher than the height of the top end of the linkage part; when the fixing When the plate moves forward along the guide rail, the bottom end of the transmission member moves forward in the second groove of the cover body and snaps into the first groove; when the fixed plate moves along the guide rail When moving backward, the bottom end of the transmission member is sequentially moved out of the first groove and the second groove, so that the detected chip is taken out and a new chip is installed;

A guide, at least two cylindrical guides are fixed on the upper end of the moving part;

Guide holes, guide holes matching the number of the guide pieces are provided on the fixing plate, and are suitable for the passage of the guide pieces;

The chip includes a cover, a housing, a first base, a second base, and a liquid detection pool arranged from top to bottom;

A housing, the housing has a cylindrical channel, a plurality of liquid cavities are arranged around the cylindrical channel, and are respectively used for accommodating samples and reagents, and the bottom of the liquid cavity has outlets distributed along the outer side of the cylindrical channel, such as On concentric circles or non-same circles, each outlet has a film that closes the liquid cavity; the housing has a closing piece that closes multiple liquid cavities from the upper part, and the closing piece has a through hole that communicates with the inside of the liquid cavity and is suitable for adding samples Wait;

A safety pin, the safety pin has a horizontal part, the length of the horizontal part is greater than the length of the second groove, that is, the horizontal part extends outside the second groove, and is suitable for the operator to pull out the safety pin; the edge of the horizontal part The two opposite sides extending in the length direction have strip-shaped protrusions extending outward, such as at the bottom end of the two sides (the left and right sides of the horizontal part, not the upper and lower sides and the front and rear sides) Or the middle part has a strip-shaped protrusion that extends continuously or intermittently along the length direction; the two side parts have a first set of grooves suitable for the end of the elastic part to be inserted into, such as Vertical grooves or inclined grooves extending up and down; the width of the end of the horizontal part becomes smaller, which is suitable for inserting into the first groove of the linkage part; in order to be beautiful and prevent dust from falling into the cylindrical channel, The upper end of the end portion also has a sheet-like protrusion extending outward and along the length direction; in order to facilitate the extraction of the safety pin, the top end of the sheet-like protrusion further has a plurality of strips extending perpendicular to the length direction (ie, the width direction). Protrusions; the horizontal part adopts a non-solid hollow structure; a safety pin fixed in the second groove prevents downward movement of the housing, and the sheet-like protrusion covers the top end of the linkage part;

The cover is located on the upper side of the housing and closes the through hole at the upper end of the housing, such as by inserting a protrusion into the through hole to seal, so that the liquid cavity in the housing becomes a closed environment; There is a second groove, the second groove extends to the cylindrical channel; the linkage part of the rotating body of the first base passes through the cylindrical channel, and the upper end is in the second groove; the second groove The two opposite walls of the groove have opposite wings, and the distance between the two wings is smaller than the width of the second groove; the second groove is suitable for the strip-shaped protrusion to be locked in, and the two wings block The strip-shaped protrusion moves upward, that is, prevents the housing from moving downward. The horizontal part is inserted between the two wing parts; the side parts of the two wing parts facing the safety pin respectively have suspended elastic parts, For example, the elastic part processed on the wing part, in the free state, the distance between the two opposite elastic parts is smaller than the width of the part with the strip-shaped protrusion of the horizontal part, when the horizontal part is inserted into the second When in the groove, the gradually smaller width of the horizontal part passes between the two elastic parts, and the distance between the two elastic parts is gradually enlarged, and finally it snaps into the first of the two side parts. Group groove

The first base has a fifth through hole, a second opening, and a third opening. The bottom end of the first base has a concentric first opening and a first set of openings surrounding the fifth through hole. The second group of openings and the eighth opening of the through holes are concentric or not on the same circumference. The upper end of the second group of openings has a hollow tip-shaped protrusion, which is suitable for puncturing the film and inserting into the outlet at the lower end of the liquid cavity; A base has a plurality of separated fourth channels for communicating with the first group of openings and the second group of openings respectively, so that the first group of openings correspond to the liquid cavity one by one, and the internal communication, the first opening and the eighth opening Communication; the inner diameter of the channel is small, so that the liquid in the liquid cavity cannot flow autonomously to the first set of outlets only by its own gravity; the first base also has a second opening and a third opening, which are connected to the The eighth outlet is connected; the lower end of the first base has a fifth groove, such as a circular groove, and the fifth through hole is in the fifth groove;

A multi-channel directional valve, the multi-channel directional valve includes a rotating body, and the rotating body includes:

The linkage part, the rotating disk and the hollow rotating part with the central axis collinear from top to bottom; the linkage part passes through the fifth through hole and is in the cylindrical channel; the linkage part is in the second groove The upper end of the part has a first groove; in order to cooperate with the transmission member, preferably, in the extension direction of the horizontal second groove, the width of the first groove becomes larger: the rotating disk includes a larger radius (larger than the fifth The first part of the through hole) and the second part with a smaller radius, the first part and the second part are accommodated in the fifth groove; the upper end of the rotating disk has a fourth opening, and the inside of the rotating disk has a fifth channel and the inside of the rotating part. Connected; when the rotating disk rotates, the fourth opening is respectively communicated with the first opening and the first group of openings, which realizes the selective communication of the first opening and the first group of openings, which means that the inside of the rotating part is selectively connected with the liquid cavity Connected

The second base, the lower end of the second base has the mixing tank, and the cross-sectional area of the mixing tank gradually increases from bottom to top; the second base on the upper part of the mixing tank has a sixth through hole, and the upper end has a surrounding first A circular groove with six through holes; a rubber O-ring is sleeved on the rotating part and is in the circular groove to achieve a seal between the rotating part and the mixing tank; the circular groove has an annular protrusion on the periphery, the The second part is in the space enclosed by the annular protrusion and the second base, the first part is blocked by the annular protrusion; the annular protrusion is in the fifth groove, and the rotating disk is in the fifth groove and the annular protrusion, In the space enclosed by the second base; the rotating member extends through the sixth through hole into the mixing tank, and the distance between the bottom end of the rotating member and the bottom wall of the mixing tank is less than 1mm, such as 0.5mm; the first outside the mixing tank The lower end of the second base has a fifth opening, the fifth opening is provided with a filter membrane, and the second base has a third channel for connecting the mixing tank and the fifth opening;

A temperature control unit, the temperature control unit adopts a metal material and is sleeved outside the mixing tank in a ring shape, the inner wall matches the outer wall (convex curved surface) of the mixing tank, and an electric heating body is arranged in the temperature control unit ; The bottom end of the mixing tank extends to the lower side of the temperature control unit; the cold end of the TEC refrigerator is attached to the temperature control unit, and the hot end is attached to the radiator; the airflow generated by the fan sweeps the radiator;

An air pump, which is connected to the fifth opening;

The liquid detection cell includes a body; the body has a convex sixth opening and a convex seventh opening respectively communicating with the V-shaped quantitative cavity; the sixth opening and the seventh opening are inserted into the flexible material in the fourth groove, and Communicate with the second opening and the third opening;

Before the formal inspection, the distance between the housing and the first base is greater than zero, and the second set of openings are not connected to the liquid chamber; at the same time, since the safety pin is inserted into the first groove of the linkage part, the housing Can't move down

A light source, which emits light of multiple wavelengths;

A first selection module, the first selection module is configured to select excitation lights of different wavelengths from the light of multiple wavelengths, and the excitation lights are respectively incident into the quantitative cavity in the detection groove;

A second selection module, the second selection module is used to select emitted light of different wavelengths from the light emitted in the quantitative cavity;

A detector, which converts the emitted light of different wavelengths into electrical signals;

An incident optical fiber, the incident optical fiber transmits the light emitted by different light sources into the quantitative cavity, and the output end of the incident optical fiber is fixed on the V-shaped groove;

The exit fiber transmits the light in the quantitative cavity to different detectors, and the input end of the exit fiber is fixed on the V-shaped groove.

The working mode of the above-mentioned mixing system includes a preparation phase, a mixing phase, a conveying phase, and a detection phase; the preparation phase includes the following steps:

(A1) Push the fixed plate backward, and the fixed plate moves backward along the guide rail;

Pull out the safety pin on the chip. The safety pin is separated from the first groove and the second groove of the cover. The distance between the housing and the first base is greater than zero. The liquid channel, such as the fourth channel, is not connected to the liquid cavity in the casing, and then the chip is placed on the carrier on the lower side of the fixed plate, and the two V-shaped grooves of the carrier carry the two V-shaped quantitative cavities of the storage device;

(A2) Pull the fixed plate forward, and the fixed plate moves forward along the guide rail;

The transmission member passing through the fixed plate moves forward in a direction parallel to the extension direction of the guide rail, and the bottom end of the transmission member moves forward in the second groove, thereby snapping into the multi-channel selection The first groove on the upper end of the linkage part of the valve, so that the second motor drives the linkage part and the rotating disk to rotate through the transmission member;

(A3) The first motor rotates to drive the moving part to move down, thereby pushing the cover to move down. The lowered housing and the fixed first base are buckled together, and the second set of openings enters the outlet of the liquid chamber , Puncture the film to make the liquid channel in the first base communicate with the liquid cavity in the housing;

The mixing stage includes the following steps:

The second motor uses the transmission member to drive the linkage part, the rotating disk and the rotating member to rotate, and uses the encoder to position, so that the fourth opening on the rotating disk selectively communicates with the first group of openings; in this state, the liquid chamber is selected It is in communication with the second set of openings, the first set of openings, the fourth opening, the channel in the rotating disc and the rotating part, and the mixing tank. However, due to the resistance of the narrow channel, the liquid cannot flow out of the liquid chamber to the liquid chamber by gravity alone. The first group of openings; at the same time, the liquid in the liquid cavity that is not in communication with the fourth opening cannot flow out to the first group of openings by relying solely on its own gravity;

When the air pump works, the gas in the mixing tank is discharged from the third channel and the fifth opening in sequence, and the mixing tank becomes negative pressure; the liquid in the liquid cavity sequentially breaks through and passes through the second set of openings, the channel in the first base, The first set of openings, the fourth opening, the fifth channel and the inner channel of the rotating member enter the mixing tank, so that multiple liquids (samples and reagents) are selectively drawn from the liquid cavity and mixed in the mixing tank;

During the reaction process of the mixed liquid in the mixing tank, the temperature control unit maintains the set temperature of the mixed liquid through the heater and the refrigerator;

The ultrasonic oscillating device is used to realize the full mixing of the liquid in the mixing tank.

The delivery stage includes the following steps:

The second motor drives the linkage part to rotate, and through the positioning of the encoder, the fourth opening on the rotating rotating disk is connected to the first opening;

Gas is injected into the mixing tank through the air pump and the fifth opening. The liquid level in the mixing tank is positive, and the mixed liquid in the mixing tank is forced to pass through the hollow rotating member, the fifth channel, the fourth opening, and the first The opening, the fourth channel, and the eighth opening enter the V-shaped quantitative cavity in the liquid detection tank through the second opening and the third opening, and the specific method is as follows:

In the above liquid feeding process, the gas in the first channel, the quantitative chamber, the second channel and the communicating chamber pass through the gas-liquid separation membrane, enter the gap between the gas-liquid separation membrane and the PP membrane, and then enter the exhaust groove, and finally Into the atmosphere;

The detection stage includes the following steps:

(B1) The excitation light of different wavelengths emitted by multiple light sources is injected into each quantitative cavity through the incident optical fiber, and the first switching module is used to make part of the excitation light output by different light sources enter the quantitative cavity respectively; through the second switching module, The emitted light in different quantitative cavities enters the detector to receive, and the parameters of the sample are obtained after analysis;

The electric heating plate is used to increase the temperature of the liquid in the dosing chamber, and the air flow generated by the fan is used to reduce the temperature of the liquid in the dosing chamber, so that the liquid in the dosing chamber maintains a set temperature.

Example 5:

An application example of the liquid analysis system according to Embodiment 4 of the present application in fluorescent quantitative PCR.

In this application example, the liquid analysis system includes:

A chip, the chip comprising a cover, a housing, a first base, a second base, and a liquid detection pool arranged from top to bottom;

A housing with a cylindrical channel in the housing, a plurality of liquid cavities are arranged around the cylindrical channel, and are respectively used for accommodating samples and reagents, and the bottom of the liquid cavity has concentric circles distributed along the central axis of the cylindrical channel Each outlet has a film that closes the liquid cavity; the housing has a closure piece that closes multiple liquid cavities from the upper part, and the closure piece has a through hole that communicates with the inside of the liquid cavity and is suitable for adding samples, etc.;

A safety pin, the safety pin has a horizontal part, the length of the horizontal part is greater than the length of the second groove, that is, the horizontal part extends outside the second groove, and the operator pulls out the safety pin; the edge of the horizontal part The two opposite sides extending in the length direction have strip-shaped protrusions extending outward, such as at the bottom end of the two sides (the left and right sides of the horizontal part, not the upper and lower sides and the front and rear sides) Or the middle part has a strip-shaped protrusion that extends continuously or intermittently along the length direction; the two side parts have a first set of grooves suitable for the end of the elastic part to be inserted into, such as The vertical groove or the inclined groove extending in the up and down direction; the width of the end of the horizontal part becomes smaller, which is suitable for being inserted into the first groove of the linkage part; the upper end of the end has an outward and along the length In order to facilitate the extraction of the safety pin, the top of the sheet-shaped protrusion further has a plurality of protrusions extending perpendicular to the length direction (ie, the width direction); the horizontal part adopts a non-solid hollow structure ；

The first base has a fifth through hole, a second opening, and a third opening. The bottom end of the first base has a concentric first opening and a first set of openings surrounding the fifth through hole. The second group of openings and the eighth opening of the through holes are concentric, and the upper end of the second group of openings has a hollow tip-shaped protrusion, which is suitable for puncturing the film and inserting into the outlet at the lower end of the liquid cavity; the first base has A plurality of isolated fourth channels are used to connect the first group of openings and the second group of openings respectively, so that the first group of openings correspond to the liquid cavity in one-to-one communication, and the first opening and the eighth opening are connected; the inner diameter of the channel is relatively small Small, so that the liquid in the liquid cavity cannot flow to the first set of outlets by its own gravity alone; the upper end of the first base also has a ninth opening and a tenth opening, and the eighth opening and the first opening pass through the first base. The channel in the seat is connected, the ninth opening and the second opening are connected through the channel in the first base, and the tenth opening and the third opening are connected through the channel in the first base; the upper end of the first base has an annular protrusion, The second group of openings, the eighth opening, the ninth opening, and the tenth opening are located in the third groove surrounded by the annular protrusion; one side of the connecting piece has a "Y"-shaped groove, which is inverted in the third groove. In the groove, a "Y"-shaped channel isolated from the outside is formed between the eighth opening, the ninth opening and the tenth opening; the second opening and the third opening are set in the fourth groove at the lower end of the first base, and rotate Outside the rotation radius of the disc, there is a flexible material in the fourth groove; the lower end of the first base has a fifth groove, and the fifth through hole is in the fifth groove;

The linkage part, the rotating disk and the hollow rotating part with the central axis collinear from top to bottom; the linkage part passes through the fifth through hole and is in the cylindrical passage; the linkage part is in the second groove The upper end of the part has a first groove; in the extension direction of the horizontal second groove, the width of the first groove becomes larger: in this application example, the linkage part is cylindrical and has two grooves with different widths The rotating disk includes a first part with a larger radius (larger than the fifth through hole) and a second part with a smaller radius. The first and second parts are accommodated in the fifth groove; the upper end of the rotating disk has a fourth opening, which rotates There is a fifth channel inside the disk that communicates with the interior of the rotating part; when the rotating disk rotates, the fourth opening is respectively communicated with the first opening and the first group of openings, so that the first opening and the first group of openings can be selectively connected. That is to realize that the inside of the rotating part is selectively connected with the liquid cavity; the end of the horizontal part is inserted into the first groove of the linkage part: firstly insert the groove with the larger width, then insert the groove with the smaller width, and fix it in The safety pin in the second groove prevents the housing from moving downward, and the sheet-like protrusion covers the top end of the linkage part;

The second base, the lower end of the second base has a mixing tank, the cross-sectional area of the mixing tank gradually increases from bottom to top; the second base at the upper part of the mixing tank has a sixth through hole, and the upper end has a sixth through hole. The circular groove of the hole; the rubber O-ring is sleeved on the rotating part and is in the circular groove to realize the seal between the rotating part and the mixing tank; the circular groove has an annular protrusion on the periphery, and the second part is in the In the space enclosed by the annular protrusion and the second base, the first part is blocked by the annular protrusion; the annular protrusion is in the fifth groove, the rotating disk is in the fifth groove and the annular protrusion, and the second base In the enclosed space; the rotating part extends into the mixing tank through the sixth through hole, and the distance between the bottom end of the rotating part and the bottom wall of the mixing tank is less than 1mm, such as 0.5mm; the second base outside the mixing tank A convex-shaped fifth opening is provided at the lower end, a filter membrane is provided at the fifth opening, and a third channel is provided in the second base for connecting the mixing tank and the fifth opening;

An air pump, which is connected to the fifth opening;

The storage device (liquid detection pool) includes a main body and a film. The main body has a V-shaped quantitative cavity, and the film is attached to both sides of the main body; the main body has a convex sixth opening and a convex seventh opening respectively communicating with the quantitative cavity; The sixth opening and the seventh opening are inserted into the flexible material in the fourth groove and communicate with the second opening and the third opening;

Before the formal inspection, the distance between the housing and the first base is greater than zero, and the second set of openings are not connected to the liquid chamber; at the same time, since the safety pin is inserted into the groove of the linkage part, the housing cannot be lowered. shift;

A frame, the frame is used to carry the chip, the fixing plate and other components;

A carrier, the carrier is arranged on the frame and is suitable for carrying the chip; the bottom end of the carrier is two V-shaped detection grooves, which is suitable for the two V-shaped quantitative cavities of the storage device Insertion and fixation;

A fixed plate, the fixed plate has a third through hole and a first through hole, and is arranged on the guide rail by a sliding member; when the fixed plate is in the working position, the third through hole and the chip on the carrier (The safety pin is unplugged) the first groove corresponds up and down;

Transmission member, the transmission member passes through the third through hole, and the transmission member is driven by the second motor; when the fixed plate is in the working position, the bottom end of the transmission member is clamped into the first groove; Corresponding to the first groove, in the horizontal direction, the width from one end to the other end of the bottom end of the transmission member becomes larger; in the vertical direction, the position of the bottom end of the transmission member is not lower than the first The height of a groove, and not higher than the height of the top of the linkage part; when the fixed plate moves forward along the guide rail, the bottom end of the transmission member moves forward in the second groove and Clamp into the first groove; when the fixed plate moves backward along the guide rail, the bottom end of the transmission member moves out of the first groove and the second groove in turn, so as to take out the detected chip , And load a new chip;

A first motor, the first motor is fixed on the fixing plate;

A connecting plate, the upper part of the connecting plate is on the upper side of the fixed plate and has a second through hole (rectangular through hole), and the lower part passes through the first through hole of the fixed plate and is fixedly connected to the movable plate on the lower side of the fixed plate;

The eccentric wheel is arranged in the second through hole, and the rotating shaft of the first motor is connected to the eccentric wheel; the rotating eccentric wheel drives the connecting plate to move up and down: When the bottom wall of the through hole rotates, the connecting plate and the moving plate are driven to move down, and when the eccentric wheel rotates against the top wall of the second through hole, the connecting plate and the moving plate are driven to move;

A moving plate, the moving plate is arranged on the lower side of the fixed plate, and the upper side of the chip has a fourth through hole suitable for the transmission member to pass through;

A guide, at least two cylindrical guides are fixed on the upper end of the moving plate;

A guide part, the guide part is arranged on the upper side of the fixed plate, and the guide part is adapted to pass through the guide hole and the inside of the guide part, so as to limit the moving plate to only move up and down perpendicular to the guide part;

The first selection module and the second selection module are shared, and the first selection module includes:

A rotating part, the rotating part having installation positions distributed in a concentric circle around the rotation axis;

A third motor, the third motor drives the rotating member to rotate;

Multiple groups of detection units, each group of detection units includes:

A transmitting module and a detecting module, the transmitting module and the detecting module are respectively fixed on the installation position; the light source, the collimating lens group and the filter are respectively arranged in the transmitting module, the collimating lens group, the filter and The detector is arranged in the detection module; when the emission module that rotates with the rotating member corresponds to the incident optical fiber, the adjacent detection module corresponds to the emission optical fiber; the emission modules of each group of detection units emit excitation light of different wavelengths;

An incident optical fiber, the incident optical fiber transmits the light emitted by the light sources in different emission modules into the quantitative cavity, and the output end of the incident optical fiber is fixed on the V-shaped groove;

The exit fiber transmits the light in the quantitative cavity to different detection modules, and the input end of the exit fiber is fixed on the V-shaped groove; through rotation, the different detection units correspond to the incident fiber and the exit fiber, respectively, That is, the excitation light of different wavelengths enters the quantitative cavity through the incident fiber, and the fluorescence of different wavelengths excited in the quantitative cavity is sent to the detection module through the exit fiber to be received; in this embodiment, four groups of detection units are used to make four different wavelengths The excitation light is incident into the two quantitative cavities respectively, and the fluorescence of different wavelengths emitted from the quantitative cavity is received by the detection module respectively.

The working method of the liquid mixing system of this application example includes a preparation phase, a mixing phase, a conveying phase, and a detection phase; the preparation phase includes the following steps:

Pull out the safety pin on the chip. The safety pin is separated from the first groove and the second groove of the cover. The distance between the housing and the first base is greater than zero. The liquid channel and the liquid cavity in the casing are not connected, and then the chip is placed on the carrier on the lower side of the fixed plate, and the two V-shaped grooves of the carrier carry the two V-shaped quantitative cavities of the storage device;

The transmission member passing through the fixed plate moves forward in a direction parallel to the extending direction of the guide rail, and the bottom end of the transmission member moves forward in the second groove, thereby snapping into the multi-channel selection The first groove on the upper end of the linkage part of the valve, so that the second motor drives the rotation of the linkage part through the transmission member;

(A3) The first motor rotates, driving the eccentric wheel to rotate against the bottom wall of the second through hole of the connecting plate, pushing the connecting plate down, thereby pushing the moving plate and the cover to move down, and the moving shell and the fixed part are not fixed. The movable first base is buckled together, and the second set of openings enters the outlet of the liquid cavity, puncturing the film, so that the liquid channel in the first base communicates with the liquid cavity in the housing;

The mixing stage includes the following steps:

The second motor uses the transmission member to drive the linkage part, the rotating disk and the rotating member to rotate, and uses the encoder to position, so that the fourth opening on the rotating disk selectively communicates with the first group of openings; in this state, the liquid chamber is selected It is in communication with the second set of openings, the first set of openings, the fourth opening, the channel in the rotating disc and the rotating part, and the mixing tank. However, due to the resistance of the narrow channel, the liquid cannot flow out of the liquid cavity to the liquid chamber by gravity alone. The first group of openings; at the same time, the liquid in the liquid cavity that is not in communication with the fourth opening cannot flow out to the first group of openings by relying solely on its own gravity;

There are magnetic beads (stirring bars) in the mixed liquid, the magnetic beads are adsorbed by an electromagnet, and the magnetic beads are concentrated at the bottom of the mixing tank; an ultrasonic oscillator is used to disperse the concentrated magnetic beads.

The delivery stage includes the following steps:

Gas is injected into the mixing tank through the air pump and the fifth opening. The liquid level in the mixing tank is positive, and the mixed liquid in the mixing tank is forced to pass through the hollow rotating member, the fifth channel, the fourth opening, and the first The opening, the fourth channel and the eighth opening, and then enter the quantitative cavity in the storage device through the ninth opening, the tenth opening, the second opening, and the third opening;

The detection stage includes the following steps:

(B1) The third motor drives the rotating member to rotate, so that the detection units of different groups correspond to the incident optical fiber and the output optical fiber, respectively. The excitation light of different wavelengths output by each emission module is injected into the quantitative cavity through the incident optical fiber, and the quantitative cavity The light emitted from the inside is respectively transmitted to each detection module through the output fiber, and the parameters of the sample are obtained after analysis;

The benefits achieved according to the embodiments of the present application are:

1. Automatic buckle;

After adding the sample, pull out the safety pin, use the combination of the first motor, the connecting unit and the moving part, and use the moving part that moves downward to push the housing down, the housing and the first base are buckled together, and the internal flow path is connected. It realizes the automatic buckle, and does not affect the rotation of the inner parts of the multi-channel selector valve, without manual pressing, is automatic, time-consuming, and accurate;

The design of the guide part and the guide hole connected with the moving part ensure the downward translation of the housing, improve the stability and accuracy of the fit between the housing and the first base, that is, accurately and reliably realize the internal liquid The conduction of the flow path;

2. Simple structure;

The mobile platform of this patent application: the combination of the fixed plate, the sliding part and the horizontal guide rail realizes the automatic buckling of the housing and the first base, and at the same time realizes the accurate connection and disconnection between the transmission part and the chip, and facilitates the insertion of the chip And take out

3. High work efficiency;

The cover has a second groove extending to the rotating part, which is suitable for inserting and pulling out the safety pin and realizes the safety function; on the other hand, it is suitable for the bottom end of the transmission part to move back and forth in the second groove; When moving in the forward direction, the bottom end of the transmission member passes through the second groove first, and then cooperates with the rotating member to drive the multi-channel selector valve to work; when moving in the reverse direction, the bottom end of the transmission member moves out of the rotating member and the first Two grooves, so as to take out the used chips and put in new chips, the coordination is fast and accurate, without manual alignment;

4. Good working performance;

The design with different widths of the first mating part and the corresponding design with different widths of the second mating part help the transmission part to cooperate with the rotating part and fit closely, and improve the positioning accuracy of the multi-channel directional valve.

Example 6:

According to the application example of the liquid analysis system in the embodiment 4 of the present application in the fluorescent quantitative PCR, the difference from the embodiment 5 is:

1. The openings at the bottom of each liquid cavity are distributed in non-concentric circles, and the openings in the first group are also distributed in non-concentric circles.

2. An annular groove is arranged on the periphery of the sixth through hole, and the sealing member is in the annular groove and is sleeved outside the rotating member.

3. The end of the horizontal part of the safety pin far from the end inserted into the first groove has a vertical part. When the safety pin is inserted into the second groove, the vertical part is exposed, which is convenient for the operator to grasp and pull.

4. The first switching module uses a combination of multiple mirrors to combine the excitation light with different wavelengths output by the multiple emission modules. The combined light is coupled into the emission fiber, and the incident fiber is split into each quantitative cavity. ; By switching the power supply of the light source to realize the selective incidence of light of different wavelengths into the quantitative cavity;

The output fibers corresponding to each quantitative cavity are combined, and then divided into multiple beams by an optical beam splitter. The optical beam splitter uses a combination of a mirror and a transflective mirror, and the detection module is placed on each optical path after the beam splitting; An optical switch is provided on the optical fiber to realize the switching function; compared with the switching of embodiment 5, no moving parts are used, which improves the operational stability and reliability.

The above-mentioned embodiment illustrates that the second channel and the communicating cavity are separately provided, of course, they can also be shared. The highest part of the second channel is used as the communicating cavity; the core purpose of the communicating cavity is to establish a gas communicating channel with the outside world, and the first in the body The gas in the channel, the quantitative cavity and the second channel is discharged to the outside through the communicating cavity.

Claims

A liquid detection pool, the liquid detection pool includes a body with an inlet; the feature is that the liquid detection pool further includes:

A quantitative cavity, the quantitative cavity is arranged in the body and communicates with the inlet through a first channel;

A communication cavity, the communication cavity is arranged in the body and communicates with the quantitative cavity through a second channel; the position of the quantitative cavity is lower than that of the communication cavity and the inlet;

A gas-liquid separation membrane, the gas-liquid separation membrane is used to isolate the communication cavity from the outside, and the gas in the communication cavity is suitable for permeating the gas-liquid separation membrane.
The liquid detection cell according to claim 1, wherein the quantitative cavity has two or more, which are respectively connected with the inlet and the communicating cavity.
The liquid detection cell according to claim 2, wherein the number of the inlet and the quantitative cavity are the same, and the inlet, the quantitative cavity and the communicating cavity form a detection channel, and the detection channels are isolated.
The liquid detection cell according to claim 3, wherein at least one of the quantitative cavity, the first channel, the communication cavity, and the second channel is formed in a manner as follows:

The body is provided with a groove, and the closing member is used to close the groove.
The liquid detection cell according to claim 4, wherein the communication cavity, the gas-liquid separation membrane and the closing member are arranged in sequence from the inside to the outside, and there is a gap between the gas-liquid separation film and the closing member, and the gap Connect with the outside world.
The liquid detection cell according to claim 5, characterized in that: the body further has an exhaust groove, the gap is in communication with the exhaust groove, a closing member closes a part of the exhaust groove, and the exhaust groove The part of the air tank communicates with the outside.
7. The liquid detection cell according to claim 6, wherein the position of the exhaust groove is higher than the position of the communication cavity.
The liquid detection cell according to claim 5 or 6, characterized in that: the quantitative cavity and the communicating cavity are formed by the same sealing member, and a part of the exhaust groove is closed.
The liquid detection cell according to any one of claims 1-8, wherein the quantitative cavity is formed in:

The main body has a penetrating part, and the front and back sides of the main body are respectively provided with closing parts for closing the penetrating part to form a closed space.
A liquid analysis system, the liquid analysis system includes a chip, the chip has a cover and a casing; the feature is that the liquid analysis system further includes:

A storage device, the storage device adopts the liquid detection pool according to any one of claims 1-9, and the liquid detection pool is in communication with the inside of the chip.