WO2021077591A1 - Microfluidic chip and in vitro test system - Google Patents

Microfluidic chip and in vitro test system Download PDF

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Publication number
WO2021077591A1
WO2021077591A1 PCT/CN2019/126900 CN2019126900W WO2021077591A1 WO 2021077591 A1 WO2021077591 A1 WO 2021077591A1 CN 2019126900 W CN2019126900 W CN 2019126900W WO 2021077591 A1 WO2021077591 A1 WO 2021077591A1
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WIPO (PCT)
Prior art keywords
cavity
microfluidic chip
quantitative
waste liquid
microchannel
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PCT/CN2019/126900
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French (fr)
Chinese (zh)
Inventor
白孟斌
万惠芳
冷杰
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广州万孚生物技术股份有限公司
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Publication of WO2021077591A1 publication Critical patent/WO2021077591A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409Moving fluids with specific forces or mechanical means specific forces centrifugal forces

Definitions

  • This application relates to the field of in vitro diagnostic technology, such as a microfluidic chip and an in vitro detection system.
  • In Vitro Diagnosis belongs to the medical and biological industry, which refers to taking blood, body fluids, tissues and other samples from the human body, and using in vitro testing reagents, instruments, etc. to test and verify the samples in order to prevent diseases , Diagnosis, treatment testing, late-stage observation, health evaluation, genetic disease prediction, etc.
  • In vitro diagnosis is divided into three categories: biochemical diagnosis, immunodiagnosis and molecular diagnosis according to methodology, as well as point-of-care testing (POCT) differentiated from biochemical, immunological and molecular diagnosis.
  • PCT point-of-care testing
  • Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with a specific substrate, and then quantitatively detects the concentration of the target through an instrument to calculate certain biochemical indicators of the human body.
  • Traditional biochemical diagnosis needs to be tested on a large-scale biochemical analyzer, which leads to high reagent consumption and insufficient flexibility.
  • the general dry-type biochemical POCT diagnosis method has a low test throughput, and generally only one or a few tests can be tested at a time. Samples, one or several items.
  • Microfluidics technology can integrate basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes on the chip, automatically completing the entire analysis process, greatly improving the detection efficiency, and at the same time It has the advantages of miniaturization and automation, so it is more and more widely used in the field of POCT.
  • the embodiments of the present application provide a microfluidic chip capable of improving sample processing efficiency and an in vitro detection system containing the microfluidic chip.
  • a microfluidic chip has a separation and quantification unit, the separation and quantification unit includes a sample addition cavity, a first connecting microchannel, a quantification cavity, a first waste liquid cavity, an overflow microchannel, and a second waste The liquid cavity;
  • the sample loading cavity has a sample hole;
  • the quantitative cavity communicates with the sample cavity through the first connecting microchannel;
  • the first waste liquid cavity and the quantitative The cavity is in communication;
  • the second waste liquid cavity is in communication with the quantitative cavity through the overflow microchannel;
  • the separation and quantification unit has a proximal end close to the center of rotation during centrifugation;
  • the sample adding cavity Body is closer to the proximal end than the dosing cavity;
  • the dosing cavity is closer to the proximal end than the first waste liquid cavity; when the dosing cavity is filled with liquid, excess liquid
  • the second waste liquid cavity can enter the second waste liquid cavity through the overflow microchannel, and the overall distance of the second waste liquid cavity from the proximal
  • An in vitro detection system includes the microfluidic chip described in the above-mentioned embodiment and a detection mechanism, the detection mechanism is in communication with the quantitative cavity, and the detection mechanism is configured to detect a sample in the quantitative cavity.
  • Figure 1 Figure 1 and Figure 3 are schematic diagrams of the front, back and side of a microfluidic chip according to an embodiment of the application;
  • FIG. 4 and 5 are schematic diagrams of the front and back structures of the centrifugal tray matching the microfluidic chip shown in FIG. 1, respectively;
  • Fig. 6 is a schematic diagram of assembling the microfluidic chip shown in Fig. 1 and the centrifugal tray shown in Fig. 4;
  • Figure 7-1, Figure 7-2 and Figure 7-3 are schematic diagrams of the flow of the microfluidic chip shown in Figure 1 to separate and quantify the sample solution, and Figure 7-2-1 is a partial enlarged schematic diagram;
  • Figure 8-1 and Figure 8-2 are schematic diagrams of the detection process using the microfluidic chip shown in Figure 1 respectively.
  • microfluidic chip 11: proximal end, 12: card connection part; 13: chip body, 14: transparent cover film, 15: mounting groove;
  • 100 Separation and quantitative unit
  • 110 Sample loading chamber
  • 111 Sample loading hole
  • 112 First air vent
  • 120 First connecting micro flow channel
  • 130 Quantitative chamber
  • 140 First waste liquid chamber
  • 150 overflow micro channel
  • 160 second waste liquid cavity
  • 170 liquid outlet micro channel
  • 171 permeation hole
  • 172 capillary channel
  • 172a, 172b and 172c are different positions of the capillary channel
  • 173 the fourth connecting micro channel
  • 180 the quality control chamber
  • 190 the second connecting micro channel
  • 191 the second vent hole
  • 200 the third connecting micro channel;
  • an embodiment of the present application provides a microfluidic chip 10 having a separation and quantification unit 100.
  • the separation and quantification unit 100 includes a sample loading cavity 110, a first connecting micro flow channel 120, a quantification cavity 130, a first waste liquid cavity 140, an overflow micro flow channel 150, and a second waste liquid cavity 160, each cavity
  • the structure of the communicating device is formed in cooperation with the micro flow channel.
  • the sample loading cavity 110 has a sample loading hole 111.
  • the sample solution can be added into the sample adding cavity 110 from the sample adding hole 111.
  • the quantitative cavity 130 communicates with the sample adding cavity 110 through the first connecting microfluidic channel 120.
  • the quantification cavity 130 is configured to realize the quantification of the solution to be tested.
  • the first waste liquid cavity 140 is in communication with the quantitative cavity 130.
  • the first waste liquid cavity 140 is configured to be filled with excess sample solution and separated fixed impurity precipitation.
  • the second waste liquid cavity 160 communicates with the quantitative cavity 130 through the overflow microchannel 150.
  • the second waste liquid cavity 160 is configured to be filled with excess sample solution.
  • the separation and quantitative unit 100 has a proximal end 11 close to the center of rotation during centrifugation.
  • the sample loading cavity 110 is closer to the proximal end 11 than the quantitative cavity 130 is.
  • the quantitative cavity 130 is closer to the proximal end 11 than the first waste liquid cavity 140.
  • the sample solution After adding the sample solution to the sample adding cavity 110, by rotating and centrifuging, the sample solution can enter the quantitative cavity 130 and the first waste liquid cavity 140 through the first connecting microchannel 120, and gradually fill up the first waste liquid.
  • the excess sample solution overflows into the second waste liquid cavity 160 through the overflow microchannel 150, and the solid impurities in the sample solution can be separated from the solution to be tested by centrifugation ( For example, the blood cells in the whole blood sample are separated from the serum (plasma), and solid impurities are centrifuged to precipitate into the first waste liquid cavity 140, and the solution to be tested remains in the quantitative cavity 130 near the proximal end 11. So as to realize the separation and quantification of the sample solution.
  • a detection mechanism can be used to detect the quantitative solution to be tested in the quantitative cavity 130.
  • the microfluidic chip 10 needs only one centrifugation after adding the sample solution to separate and quantify the impurities in the sample solution and the target solution to be tested, without excessive centrifugation operations, so the operation is simple, and the waiting time is short. The efficiency of processing is significantly improved.
  • the sample injection hole 111 is closer to the proximal end 11 than the connection position of the sample injection cavity 110 and the first connecting microfluidic channel 120, so as to prevent the sample solution from flowing back from the sample injection hole 111 during centrifugation. .
  • the sample loading cavity 110 further has a first vent 112, and the first vent 112 is closer to the proximal end 11 than the connection position of the sample loading cavity 110 and the first connecting microfluidic channel 120.
  • the air in the sample adding cavity 110 can be effectively discharged in time during sample loading, so as to ensure the smooth progress of sample loading.
  • connection between the sample loading cavity 110 and the first connecting microfluidic channel 120 is in the shape of a funnel, which is more conducive to introducing the sample solution in the sample loading cavity 110 to the quantitative measurement via the first connecting microfluidic channel 120.
  • the cavity 130 In the cavity 130.
  • the microfluidic chip 10 further includes a quality control cavity 180.
  • the quality control cavity 180 communicates with the second waste liquid cavity 160, and the quality control cavity 180 is farther from the proximal end 11 than the second waste liquid cavity 160.
  • the sample solution entering the second waste liquid cavity 160 will flow in after the quantitative cavity 130 is filled with the sample, and the excess sample solution will flow into the mass away from the proximal end 11 in the second waste liquid cavity 160.
  • the control cavity 180 by observing whether there is liquid in the quality control cavity 180, it can be determined whether the quantitative cavity 130 is filled with the sample solution.
  • the microfluidic chip 10 further includes a second connecting microfluidic channel 190 connected to the second waste liquid cavity 160, and the second connecting microfluidic channel 190 is from an end connected to the second waste liquid cavity 160. It gradually extends toward the proximal end 11, and a second vent 191 is provided at the other end.
  • the second vent 191 By arranging the second vent 191 on the side of the second waste liquid cavity 160 close to the proximal end 11, when the sample solution overflows into the second waste liquid cavity 160, the second waste liquid cavity can be removed in time. The air in 160 is discharged to ensure the smooth progress of overflow.
  • the microfluidic chip 10 further includes a third connecting microfluidic channel 200, and the first waste liquid cavity 140 is in communication with the quantitative cavity 130 through the third connecting microfluidic channel 200.
  • the third connecting micro flow channel 200 By providing the third connecting micro flow channel 200, the first waste liquid cavity 140 and the quantitative cavity 130 can be separated, and impurities deposited in the first waste liquid cavity 140 are prevented from entering the quantitative cavity 130.
  • the microfluidic chip 10 further includes a microfluidic channel 170 for liquid discharge.
  • One end of the liquid outlet microchannel 170 communicates with the quantitative cavity 130, and the other end has a permeation hole 171.
  • the liquid outlet microchannel 170 is configured to lead the quantitatively measured solution in the quantitative cavity 130 from the permeation hole 171 to the detection mechanism.
  • the liquid outlet microchannel 170 includes a capillary channel 172.
  • One end of the capillary channel 172 is connected to the third connecting micro channel 200, and the other end is provided with a permeation hole 171.
  • the capillary flow channel 172 gradually extends from the end connected to the third connecting micro flow channel 200 in a direction close to the proximal end 11 and then extends in a direction away from the proximal end 11 after being bent.
  • the position of the bending apex of the capillary flow channel 172 is closer to the proximal end 11 than the connection position of the quantitative cavity 130 and the first connecting micro flow channel 120.
  • the "valve" is closed, and the sample solution to be tested will not break through the bent apex of the capillary flow channel 172. Permeate from the permeation hole 171; in the subsequent detection, under the action of the capillary force of the capillary channel 172, combined with low-speed centrifugation, the solution to be tested quantitatively in the quantitative cavity 130 will be siphoned along the capillary channel 172 It keeps moving forward and can seep from the permeable hole 171 to be detected.
  • the liquid outlet microchannel 170 further includes a fourth connecting microchannel 173.
  • One end of the fourth connecting micro channel 173 is connected to the third connecting micro channel 200, and the other end is connected to the capillary channel 172.
  • the fourth connecting micro flow channel 173 it is more convenient to introduce the quantitative solution to be measured in the quantitative cavity 130 into the capillary flow channel 172 during detection.
  • the fourth connecting microfluidic channel 173 gradually extends from the end connected to the third connecting microfluidic channel 200 toward the proximal end 11 to be connected to the capillary channel 172.
  • the sample solution will not break through the bent apex of the capillary flow channel 172, and the capillary flow channel 172 can act as a "valve" to close
  • the solution to be tested in the quantitative cavity 130 will continue to advance along the capillary flow channel 172 under the action of the hair suction force, and break through the bending apex of the capillary flow channel 172 Position, the "valve” is opened, and under the action of the siphon, the solution to be tested continues to advance and seeps out through the penetration hole 171 to the detection mechanism to be detected.
  • the capillary flow channel 172 is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling detection process more stable and reliable, while simplifying the chip assembly process, which is beneficial reduce manufacturing cost.
  • each microfluidic chip 10 is provided with a separation and quantification unit 100.
  • the microfluidic chip 10 can have a fan-shaped structure as a whole, but is not limited to a fan-shaped structure, and can be installed on a centrifuge tray and other devices to realize single item detection of samples.
  • the microfluidic chip 10 also has a clamping part 12 for mounting on a centrifugal device.
  • the clamping part 12 is clamped on an external centrifugal tray and other devices, and has the functions of positioning and stable assembly.
  • the clamping portion 12 may be located at but not limited to the proximal end 11 of the microfluidic chip 10.
  • the microfluidic chip 10 includes a chip body 13 and a transparent cover film 14 covering the chip body 13.
  • the chip body 13 and the transparent cover film 14 cooperate to form various cavity structures and flow channel structures.
  • the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 13, as shown in FIG. 2, each hole is opened on the back of the chip body 13, and each cavity structure and flow channel
  • the groove of the structure is opened on the front surface of the chip body 13, and subsequently covered and sealed on the front surface of the chip body 11 by a transparent cover film 12 to complete the packaging of the cavity structure and the flow channel structure, forming a complete cavity structure and Runner structure.
  • the transparent cover film 14 can be, but is not limited to, transparent tape or transparent pressure-sensitive adhesive. It cooperates with the chip body 13 to form the entire microfluidic chip 10, which is simple to assemble and does not need to use complicated and expensive ultrasonic welding technology. It can be directly bonded. , Can significantly reduce production costs. It can be understood that, in other examples, the microfluidic chip 10 may also be formed by welding with a relatively high-cost ultrasonic welding technology, or be integrally formed with a 3D printing technology.
  • the present application also provides an in vitro detection system, which includes the above-mentioned microfluidic chip 10 and a detection mechanism.
  • the detection mechanism communicates with the quantitative cavity 130 through a penetration hole 171, and the detection mechanism is configured to detect a sample in the quantitative cavity 130.
  • the detection mechanism is a dry chemical test paper.
  • the dry chemical test paper includes a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer.
  • the reaction indicator layer contains a reaction reagent and an indicator reagent capable of reacting with the target substance in the sample to be tested, and the diffusion layer passes through The injection port faces the permeation hole 171.
  • the detection mechanism is not limited to dry chemical test paper, and may also be various other test paper strips or reactors.
  • the microfluidic chip 10 is provided with installation grooves 15 around the permeation hole 171 of the separation and quantitative unit 100, and the detection mechanism is embedded in each installation groove 15.
  • the in vitro detection system further includes a centrifugal tray 20 for installation on a centrifugal device.
  • the centrifugal tray 20 is provided with a mounting position 21 for placing the microfluidic chip 10.
  • the middle part of the centrifugal tray 20 has a rotating mounting part 22.
  • the centrifugal tray 20 is provided with at least one observation hole for observing the status of the microfluidic chip 10 and/or the detection result at the installation position 21.
  • the centrifugal tray 20 is provided with a detection hole 23 corresponding to the detection mechanism, and is provided with a quality control hole 24 for observing the state of the quality control cavity 180.
  • microfluidic chip shown in FIG. 1 and the centrifugal tray shown in FIG. 4 as an example to detect whole blood samples, the separation and quantification of the sample solution and the detection process will be described in detail below.
  • a plurality of microfluidic chips 10 can be installed on the centrifugal tray 20, and a corresponding number of microfluidic chips 10 can be installed according to the requirements of the test items and samples. For vacancies, blank microfluidic chips 10 can be used to fill in Ensure the basic balance at each position of the centrifugal tray 20.
  • the process of separating and quantifying whole blood samples by the microfluidic chip 10 can be referred to but not limited to the following:
  • a whole blood sample is added to the sample loading cavity 110 through the sample loading hole 111, the centrifuge tray 20 is installed on a detection device with a centrifugal function, the device is turned on, and the centrifuge tray 20 is rotated.
  • the centrifugation progresses, the whole blood sample in the sample loading chamber 110 enters the quantitative chamber 130 and the first waste liquid chamber 140 through the first connecting microchannel 120, and the excess whole blood The blood sample enters the quality control cavity 180 and the second waste liquid cavity 160 through the overflow microchannel 150.
  • a whole blood sample is detected in the quality control cavity 180, it indicates that the quantitative cavity 13 is filled with whole blood. sample.
  • the centrifugal force is greater than the capillary during high-speed centrifugation (such as 4000-6000 rpm).
  • the whole blood sample solution will only enter the section 172a of the capillary flow channel 172, and will not break through the bending apex 172b of the capillary flow channel 172 and flow to the section 172c.
  • the blood cells in the whole blood sample filled in the quantitative cavity 130 will be separated from the serum (plasma) and deposited in the first waste liquid cavity 140, thereby realizing whole blood Separation and quantification of samples.
  • the process of using the microfluidic chip 10 to detect whole blood samples can be referred to but not limited to the following:
  • the rotation of the centrifuge tray 20 is suspended, and the serum (plasma) in the quantification chamber 130 will be quantified by the capillary flow channel 172.
  • the capillary flow channel 172 continues to advance along the capillary channel 172 and break through the bending apex 172b of the capillary channel 172.
  • the device is centrifuged at a low speed (such as 1000-2500 rpm), and the serum (plasma) flows from the 172c section of the capillary channel 172.
  • the permeation hole 171 seeps out, and under the siphon action, the serum (plasma) in the quantitative cavity 130 is continuously discharged until all is emptied for detection.
  • microfluidic chip By adopting the form of separating the microfluidic chip and the centrifugal tray, multiple microfluidic chips can be freely assembled on a centrifugal tray to realize the free collocation of test items and test samples, which is beneficial to improve the overall flexibility of the in vitro test system.

Abstract

Disclosed are a microfluidic chip (10) and an in vitro test system comprising the microfluidic chip (10). After a sample solution has been added to a sample addition cavity (110) of a microfluidic chip (10), spin centrifugation is performed, such that the sample solution enters, and gradually fills, a dosing cavity (130) and a first waste liquid cavity (140) by means of a first microfluidic connecting channel (120). Excess sample solution overflows into a second waste liquid cavity (160) by means of a microfluidic overflow channel (150). In the invention, centrifugation is performed on a sample solution to separate solid impurities from a solution under test, such that the solid impurities are sedimented in the first waste liquid cavity (140) by centrifugation while the solution under test remains in the dosing cavity (130) at an end close to the center, thereby realizing separation and dosing of the sample solution.

Description

微流控芯片及体外检测系统Microfluidic chip and in vitro detection system
本申请要求在2019年10月21日提交中国专利局、申请号为201911001358.5的中国专利申请的优先权,该申请的全部内容通过引用结合在本申请中。This application claims the priority of a Chinese patent application filed with the Chinese Patent Office with application number 201911001358.5 on October 21, 2019. The entire content of this application is incorporated into this application by reference.
技术领域Technical field
本申请涉及体外诊断技术领域,例如涉及一种微流控芯片及体外检测系统。This application relates to the field of in vitro diagnostic technology, such as a microfluidic chip and an in vitro detection system.
背景技术Background technique
体外诊断行业(In Vitro Diagnosis,IVD)属于医药生物行业,是指将血液、体液、组织等样本从人体中取出,使用体外检测试剂、仪器等对样本进行检测与校验,以便对疾病进行预防、诊断、治疗检测、后期观察、健康评价、遗传疾病预测等。体外诊断按照方法学分为生化诊断、免疫诊断和分子诊断三大类,以及从生化、免疫和分子诊断中分化出来的床旁快速诊断(Point-of-Care Testing,POCT)。干化学反应是生化诊断的一种,是利用生化试剂与特定的底物反应,再通过仪器定量检测出标的物浓度,推算出人体的某些生化指标。传统生化诊断需要在大型生化仪上进行检测,由此导致试剂消耗多、灵活性不够等情况;一般的干式生化POCT诊断方式则在测试通量上较低,一般一次只能测验一个或几个样本、一个或几个项目。微流控芯片技术(Microfluidics)能把生物、化学、医学分析过程的样品制备、反应、分离、检测等基本操作单元集成在芯片上,自动完成分析全过程,极大的提高了检测效率,同时具有小型化、自动化等优点,因而在POCT领域中应用越来越广泛。In Vitro Diagnosis (IVD) belongs to the medical and biological industry, which refers to taking blood, body fluids, tissues and other samples from the human body, and using in vitro testing reagents, instruments, etc. to test and verify the samples in order to prevent diseases , Diagnosis, treatment testing, late-stage observation, health evaluation, genetic disease prediction, etc. In vitro diagnosis is divided into three categories: biochemical diagnosis, immunodiagnosis and molecular diagnosis according to methodology, as well as point-of-care testing (POCT) differentiated from biochemical, immunological and molecular diagnosis. Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with a specific substrate, and then quantitatively detects the concentration of the target through an instrument to calculate certain biochemical indicators of the human body. Traditional biochemical diagnosis needs to be tested on a large-scale biochemical analyzer, which leads to high reagent consumption and insufficient flexibility. The general dry-type biochemical POCT diagnosis method has a low test throughput, and generally only one or a few tests can be tested at a time. Samples, one or several items. Microfluidics technology (Microfluidics) can integrate basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes on the chip, automatically completing the entire analysis process, greatly improving the detection efficiency, and at the same time It has the advantages of miniaturization and automation, so it is more and more widely used in the field of POCT.
在生化检测领域中,以美国的Abaxis公司为代表,率先开发了用于生化检测的微流控芯片,国内如天津微纳芯、成都斯马特等都有类似微流控芯片开发。传统产品的芯片对全血样本的定量与分配过程,往往需要将全血的分离和血清的定量过程分开,因此需要进行多次的离心分离和定量,使得样本处理的时间比较长,导致检测时间过于延长。In the field of biochemical testing, Abaxis of the United States took the lead in the development of microfluidic chips for biochemical testing. Domestic companies such as Tianjin Micronanochip and Chengdu Smart have similar microfluidic chip development. The process of quantification and distribution of whole blood samples with traditional products often requires separation of whole blood and serum quantification. Therefore, multiple centrifugation and quantification are required, which makes the sample processing time longer and leads to detection time. Too extended.
发明内容Summary of the invention
本申请实施例提供一种能够提高样本处理效率的微流控芯片和含有该微流 控芯片的体外检测系统。The embodiments of the present application provide a microfluidic chip capable of improving sample processing efficiency and an in vitro detection system containing the microfluidic chip.
一种微流控芯片,具有分离定量单元,所述分离定量单元包括加样腔体、第一连接微流道、定量腔体、第一废液腔体、溢流微流道和第二废液腔体;所述加样腔体具有加样孔;所述定量腔体通过所述第一连接微流道与所述加样腔体连通;所述第一废液腔体与所述定量腔体连通;所述第二废液腔体通过所述溢流微流道与所述定量腔体连通;所述分离定量单元具有在离心时靠近旋转中心的近心端;所述加样腔体较所述定量腔体靠近所述近心端;所述定量腔体较所述第一废液腔体靠近所述近心端;当所述定量腔体中填满液体后,多余的液体能够经由所述溢流微流道进入所述第二废液腔体,所述第二废液腔体整体距离所述近心端的距离大于或等于所述定量腔体距离所述近心端的距离。A microfluidic chip has a separation and quantification unit, the separation and quantification unit includes a sample addition cavity, a first connecting microchannel, a quantification cavity, a first waste liquid cavity, an overflow microchannel, and a second waste The liquid cavity; the sample loading cavity has a sample hole; the quantitative cavity communicates with the sample cavity through the first connecting microchannel; the first waste liquid cavity and the quantitative The cavity is in communication; the second waste liquid cavity is in communication with the quantitative cavity through the overflow microchannel; the separation and quantification unit has a proximal end close to the center of rotation during centrifugation; the sample adding cavity Body is closer to the proximal end than the dosing cavity; the dosing cavity is closer to the proximal end than the first waste liquid cavity; when the dosing cavity is filled with liquid, excess liquid The second waste liquid cavity can enter the second waste liquid cavity through the overflow microchannel, and the overall distance of the second waste liquid cavity from the proximal end is greater than or equal to the distance between the quantitative cavity and the proximal end .
一种体外检测系统,包括上述实施例所述的微流控芯片和检测机构,所述检测机构与所述定量腔体连通,所述检测机构设置为检测所述定量腔体内的样本。An in vitro detection system includes the microfluidic chip described in the above-mentioned embodiment and a detection mechanism, the detection mechanism is in communication with the quantitative cavity, and the detection mechanism is configured to detect a sample in the quantitative cavity.
附图说明Description of the drawings
图1、图2和图3分别为本申请一实施例的微流控芯片的正面、背面和侧面示意图;Figure 1, Figure 2 and Figure 3 are schematic diagrams of the front, back and side of a microfluidic chip according to an embodiment of the application;
图4和图5分别为与图1所示微流控芯片相匹配的离心托盘的正面和背面结构示意图;4 and 5 are schematic diagrams of the front and back structures of the centrifugal tray matching the microfluidic chip shown in FIG. 1, respectively;
图6为图1所示微流控芯片与图4所示离心托盘的组装示意图;Fig. 6 is a schematic diagram of assembling the microfluidic chip shown in Fig. 1 and the centrifugal tray shown in Fig. 4;
图7-1、图7-2和图7-3分别为图1所示微流控芯片实现对样本溶液的分离和定量的流程示意图,图7-2-1为局部放大示意图;Figure 7-1, Figure 7-2 and Figure 7-3 are schematic diagrams of the flow of the microfluidic chip shown in Figure 1 to separate and quantify the sample solution, and Figure 7-2-1 is a partial enlarged schematic diagram;
图8-1和图8-2分别为使用图1所示微流控芯片的检测流程示意图。Figure 8-1 and Figure 8-2 are schematic diagrams of the detection process using the microfluidic chip shown in Figure 1 respectively.
附图标记说明如下:The reference signs are explained as follows:
10:微流控芯片,11:近心端,12:卡接部;13:芯片本体,14:透明盖膜,15:安装槽;10: microfluidic chip, 11: proximal end, 12: card connection part; 13: chip body, 14: transparent cover film, 15: mounting groove;
100:分离定量单元,110:加样腔体,111:加样孔,112:第一透气孔,120:第一连接微流道,130:定量腔体,140:第一废液腔体,150:溢流微流道,160:第二废液腔体,170:出液微流道,171:渗透孔,172:毛细流道,172a、172b和172c分别为毛细流道的不同位置,173:第四连接微流道,180:质控腔体, 190:第二连接微流道,191:第二透气孔,200:第三连接微流道;100: Separation and quantitative unit, 110: Sample loading chamber, 111: Sample loading hole, 112: First air vent, 120: First connecting micro flow channel, 130: Quantitative chamber, 140: First waste liquid chamber, 150: overflow micro channel, 160: second waste liquid cavity, 170: liquid outlet micro channel, 171: permeation hole, 172: capillary channel, 172a, 172b and 172c are different positions of the capillary channel, 173: the fourth connecting micro channel, 180: the quality control chamber, 190: the second connecting micro channel, 191: the second vent hole, 200: the third connecting micro channel;
20:离心托盘,21:安装位,22:旋转安装部,23:检测孔,24:质控孔。20: Centrifugal tray, 21: Mounting position, 22: Rotating mounting part, 23: Inspection hole, 24: Quality control hole.
具体实施方式Detailed ways
需要说明的是,当元件被称为“设于”另一个元件,它可以直接在另一个元件上或者也可以存在居中的元件。当一个元件被认为是“连接”、“连通”另一个元件,它可以是直接连接到另一个元件或者可能同时存在居中元件。It should be noted that when an element is referred to as being "disposed on" another element, it can be directly on the other element or a central element may also exist. When an element is considered to be "connected" or "connected with" another element, it can be directly connected to the other element or a central element may exist at the same time.
除非另有定义,本文所使用的所有的技术和科学术语与属于本申请的技术领域的技术人员通常理解的含义相同。本文中在本申请的说明书中所使用的术语只是为了描述具体的实施例的目的,不是旨在于限制本申请。本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field of this application. The terminology used in the specification of the application herein is only for the purpose of describing specific embodiments, and is not intended to limit the application. The term "and/or" as used herein includes any and all combinations of one or more related listed items.
请结合图1和图2,本申请一实施例提供了一种微流控芯片10,其具有分离定量单元100。分离定量单元100包括加样腔体110、第一连接微流道120、定量腔体130、第一废液腔体140、溢流微流道150和第二废液腔体160,各腔体与微流道配合构成连通器的结构。1 and FIG. 2, an embodiment of the present application provides a microfluidic chip 10 having a separation and quantification unit 100. The separation and quantification unit 100 includes a sample loading cavity 110, a first connecting micro flow channel 120, a quantification cavity 130, a first waste liquid cavity 140, an overflow micro flow channel 150, and a second waste liquid cavity 160, each cavity The structure of the communicating device is formed in cooperation with the micro flow channel.
加样腔体110具有加样孔111。样本溶液可自加样孔111加入至加样腔体110中。定量腔体130通过第一连接微流道120与加样腔体110连通。定量腔体130设置为实现待测溶液的定量。第一废液腔体140与定量腔体130连通。第一废液腔体140设置为填装多余的样本溶液和分离后的固定杂质沉淀等。第二废液腔体160通过溢流微流道150与定量腔体130连通。第二废液腔体160设置为填装多余的样本溶液。The sample loading cavity 110 has a sample loading hole 111. The sample solution can be added into the sample adding cavity 110 from the sample adding hole 111. The quantitative cavity 130 communicates with the sample adding cavity 110 through the first connecting microfluidic channel 120. The quantification cavity 130 is configured to realize the quantification of the solution to be tested. The first waste liquid cavity 140 is in communication with the quantitative cavity 130. The first waste liquid cavity 140 is configured to be filled with excess sample solution and separated fixed impurity precipitation. The second waste liquid cavity 160 communicates with the quantitative cavity 130 through the overflow microchannel 150. The second waste liquid cavity 160 is configured to be filled with excess sample solution.
在本实施例中,分离定量单元100具有在离心时靠近旋转中心的近心端11。加样腔体110较定量腔体130靠近近心端11。定量腔体130较第一废液腔体140靠近近心端11。当定量腔体130中填满液体后,多余的液体能够经由溢流微流道150进入第二废液腔体160,第二废液腔体160整体距离近心端11的距离大于或等于定量腔体130距离近心端11的距离。In this embodiment, the separation and quantitative unit 100 has a proximal end 11 close to the center of rotation during centrifugation. The sample loading cavity 110 is closer to the proximal end 11 than the quantitative cavity 130 is. The quantitative cavity 130 is closer to the proximal end 11 than the first waste liquid cavity 140. When the dosing cavity 130 is filled with liquid, the excess liquid can enter the second waste liquid cavity 160 through the overflow microchannel 150, and the overall distance of the second waste liquid cavity 160 from the proximal end 11 is greater than or equal to the amount The distance between the cavity 130 and the proximal end 11.
在向加样腔体110中加入样本溶液后,通过旋转离心,样本溶液可经由第一连接微流道120进入定量腔体130和第一废液腔体140中,并逐渐填满第一废液腔体140和定量腔体130,多余的样本溶液经由溢流微流道150溢流进入第二废液腔体160中,通过离心可以将样本溶液中的固体杂质等与待测溶液分离(例 如将全血样本中的血细胞与血清(血浆)分离),固体杂质等被离心沉淀至第一废液腔体140中,待测溶液留在靠近于近心端11的定量腔体130中,从而实现对样本溶液的分离和定量。需要检测时,可以使用检测机构对定量腔体130中定量的待测溶液进行检测。After adding the sample solution to the sample adding cavity 110, by rotating and centrifuging, the sample solution can enter the quantitative cavity 130 and the first waste liquid cavity 140 through the first connecting microchannel 120, and gradually fill up the first waste liquid. In the liquid cavity 140 and the quantitative cavity 130, the excess sample solution overflows into the second waste liquid cavity 160 through the overflow microchannel 150, and the solid impurities in the sample solution can be separated from the solution to be tested by centrifugation ( For example, the blood cells in the whole blood sample are separated from the serum (plasma), and solid impurities are centrifuged to precipitate into the first waste liquid cavity 140, and the solution to be tested remains in the quantitative cavity 130 near the proximal end 11. So as to realize the separation and quantification of the sample solution. When detection is needed, a detection mechanism can be used to detect the quantitative solution to be tested in the quantitative cavity 130.
该微流控芯片10在加入样本溶液后只需要一次离心就可以实现样本溶液中杂质和目标待测溶液的分离和定量,无需过多的离心操作,因而操作简便,需要等待的时间短,样本处理的效率显著提高。The microfluidic chip 10 needs only one centrifugation after adding the sample solution to separate and quantify the impurities in the sample solution and the target solution to be tested, without excessive centrifugation operations, so the operation is simple, and the waiting time is short. The efficiency of processing is significantly improved.
在一个示例中,加样孔111较加样腔体110与第一连接微流道120的连接位置更靠近近心端11,这样可以避免在离心操作时,样本溶液自加样孔111倒流出去。In an example, the sample injection hole 111 is closer to the proximal end 11 than the connection position of the sample injection cavity 110 and the first connecting microfluidic channel 120, so as to prevent the sample solution from flowing back from the sample injection hole 111 during centrifugation. .
在一个示例中,加样腔体110还具有第一透气孔112,第一透气孔112较加样腔体110与第一连接微流道120的连接位置更靠近近心端11。通过设置第一透气孔112,在加样时,可以及时有效地将加样腔体110中的空气排出,保证加样的顺利进行。In an example, the sample loading cavity 110 further has a first vent 112, and the first vent 112 is closer to the proximal end 11 than the connection position of the sample loading cavity 110 and the first connecting microfluidic channel 120. By arranging the first vent 112, the air in the sample adding cavity 110 can be effectively discharged in time during sample loading, so as to ensure the smooth progress of sample loading.
在一个示例中,加样腔体110与第一连接微流道120的连接处呈漏斗状,这样更有利于将加样腔体110中的样本溶液经由第一连接微流道120导入至定量腔体130中。In one example, the connection between the sample loading cavity 110 and the first connecting microfluidic channel 120 is in the shape of a funnel, which is more conducive to introducing the sample solution in the sample loading cavity 110 to the quantitative measurement via the first connecting microfluidic channel 120. In the cavity 130.
在其中一个实施例中,该微流控芯片10还包括质控腔体180。质控腔体180与第二废液腔体160连通,质控腔体180较第二废液腔体160远离近心端11。进入第二废液腔体160中的样本溶液是在定量腔体130中充满样本后才会流入的,多余的样本溶液在第二废液腔体160中会流入至远离近心端11的质控腔体180中,通过观察质控腔体180中有无液体,即可判断定量腔体130中是否填满样本溶液。In one of the embodiments, the microfluidic chip 10 further includes a quality control cavity 180. The quality control cavity 180 communicates with the second waste liquid cavity 160, and the quality control cavity 180 is farther from the proximal end 11 than the second waste liquid cavity 160. The sample solution entering the second waste liquid cavity 160 will flow in after the quantitative cavity 130 is filled with the sample, and the excess sample solution will flow into the mass away from the proximal end 11 in the second waste liquid cavity 160. In the control cavity 180, by observing whether there is liquid in the quality control cavity 180, it can be determined whether the quantitative cavity 130 is filled with the sample solution.
在一个示例中,该微流控芯片10还包括与第二废液腔体160连通的第二连接微流道190,第二连接微流道190自与第二废液腔体160连接的一端逐渐向靠近近心端11的方向延伸,并在另一端设有第二透气孔191。通过在第二废液腔体160的靠近近心端11的一侧设置第二透气孔191,可以在样本溶液溢流至第二废液腔体160中时,及时将第二废液腔体160中的空气排出,保证溢流的顺利进行。In an example, the microfluidic chip 10 further includes a second connecting microfluidic channel 190 connected to the second waste liquid cavity 160, and the second connecting microfluidic channel 190 is from an end connected to the second waste liquid cavity 160. It gradually extends toward the proximal end 11, and a second vent 191 is provided at the other end. By arranging the second vent 191 on the side of the second waste liquid cavity 160 close to the proximal end 11, when the sample solution overflows into the second waste liquid cavity 160, the second waste liquid cavity can be removed in time. The air in 160 is discharged to ensure the smooth progress of overflow.
在一个示例中,微流控芯片10还包括第三连接微流道200,第一废液腔体 140通过第三连接微流道200与定量腔体130连通。通过设置第三连接微流道200,可以将第一废液腔体140与定量腔体130隔开,避免第一废液腔体140中沉积的杂质进入定量腔体130中。In an example, the microfluidic chip 10 further includes a third connecting microfluidic channel 200, and the first waste liquid cavity 140 is in communication with the quantitative cavity 130 through the third connecting microfluidic channel 200. By providing the third connecting micro flow channel 200, the first waste liquid cavity 140 and the quantitative cavity 130 can be separated, and impurities deposited in the first waste liquid cavity 140 are prevented from entering the quantitative cavity 130.
在一个示例中,该微流控芯片10还包括出液微流道170。出液微流道170的一端与定量腔体130连通,另一端具有渗透孔171。出液微流道170设置为将定量腔体130中定量的待测溶液自渗透孔171导出至检测机构中。In an example, the microfluidic chip 10 further includes a microfluidic channel 170 for liquid discharge. One end of the liquid outlet microchannel 170 communicates with the quantitative cavity 130, and the other end has a permeation hole 171. The liquid outlet microchannel 170 is configured to lead the quantitatively measured solution in the quantitative cavity 130 from the permeation hole 171 to the detection mechanism.
在一示例中,出液微流道170包括毛细流道172。毛细流道172的一端与第三连接微流道200连接,另一端设有渗透孔171。示例性的,毛细流道172自与第三连接微流道200连接的一端逐渐向靠近近心端11的方向延伸并弯折后向远离近心端11的方向延伸。毛细流道172的弯折顶点位置较定量腔体130与第一连接微流道120的连接位置处更靠近近心端11。通过设置毛细流道172,毛细流道172可以起到“阀门”的作用,在样本溶液的分离和定量时,“阀门”关闭,待测样本溶液不会突破毛细流道172的弯折顶点而从渗透孔171渗透出;在后续检测时,在毛细流道172的毛细力的作用下,配合低速离心,定量在定量腔体130中的待测溶液会在虹吸作用下,沿毛细流道172不断前进,并可自渗透孔171渗出被检测。In an example, the liquid outlet microchannel 170 includes a capillary channel 172. One end of the capillary channel 172 is connected to the third connecting micro channel 200, and the other end is provided with a permeation hole 171. Exemplarily, the capillary flow channel 172 gradually extends from the end connected to the third connecting micro flow channel 200 in a direction close to the proximal end 11 and then extends in a direction away from the proximal end 11 after being bent. The position of the bending apex of the capillary flow channel 172 is closer to the proximal end 11 than the connection position of the quantitative cavity 130 and the first connecting micro flow channel 120. By setting the capillary flow channel 172, the capillary flow channel 172 can function as a "valve". When the sample solution is separated and quantified, the "valve" is closed, and the sample solution to be tested will not break through the bent apex of the capillary flow channel 172. Permeate from the permeation hole 171; in the subsequent detection, under the action of the capillary force of the capillary channel 172, combined with low-speed centrifugation, the solution to be tested quantitatively in the quantitative cavity 130 will be siphoned along the capillary channel 172 It keeps moving forward and can seep from the permeable hole 171 to be detected.
在一个示例中,该出液微流道170还包括第四连接微流道173。第四连接微流道173的一端与第三连接微流道200连接,另一端与毛细流道172连接。通过设置第四连接微流道173,可以在检测时,更便于将定量腔体130中定量的待测溶液导入至毛细流道172中。可选地,第四连接微流道173自与第三连接微流道200连接的一端逐渐向靠近近心端11的方向延伸以与毛细流道172连接。In an example, the liquid outlet microchannel 170 further includes a fourth connecting microchannel 173. One end of the fourth connecting micro channel 173 is connected to the third connecting micro channel 200, and the other end is connected to the capillary channel 172. By providing the fourth connecting micro flow channel 173, it is more convenient to introduce the quantitative solution to be measured in the quantitative cavity 130 into the capillary flow channel 172 during detection. Optionally, the fourth connecting microfluidic channel 173 gradually extends from the end connected to the third connecting microfluidic channel 200 toward the proximal end 11 to be connected to the capillary channel 172.
在样本溶液的离心分离和定量时,由于离心力大于毛细流道172内的毛吸力,样本溶液不会突破毛细流道172的弯折顶点,该毛细流道172即可起到“阀门”的关闭作用,后续在检测时,在低速离心的情况下,存在定量腔体130内的待测溶液就会在毛吸力的作用下沿毛细流道172不断前进,并突破毛细流道172的弯折顶点位置,“阀门”打开,在虹吸作用下,待测溶液继续前进并经渗透孔171渗出至检测机构被检测。During the centrifugal separation and quantification of the sample solution, since the centrifugal force is greater than the hair suction in the capillary flow channel 172, the sample solution will not break through the bent apex of the capillary flow channel 172, and the capillary flow channel 172 can act as a "valve" to close In the subsequent detection, under the condition of low-speed centrifugation, the solution to be tested in the quantitative cavity 130 will continue to advance along the capillary flow channel 172 under the action of the hair suction force, and break through the bending apex of the capillary flow channel 172 Position, the "valve" is opened, and under the action of the siphon, the solution to be tested continues to advance and seeps out through the penetration hole 171 to the detection mechanism to be detected.
通过毛细流道172来作为控制样本与检测机构接触反应的阀门,可以代替传统的水溶性膜或阀门等延时打开机构,使进样检测过程更加稳定可靠,同时简化了芯片组装工艺,有利于降低生产成本。The capillary flow channel 172 is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling detection process more stable and reliable, while simplifying the chip assembly process, which is beneficial reduce manufacturing cost.
在一个示例中,各微流控芯片10上设有一个分离定量单元100。该微流控芯片10整体上可呈但不限于扇形的结构,可以安装在离心托盘等装置上,实现对样本的单项目检测。In an example, each microfluidic chip 10 is provided with a separation and quantification unit 100. The microfluidic chip 10 can have a fan-shaped structure as a whole, but is not limited to a fan-shaped structure, and can be installed on a centrifuge tray and other devices to realize single item detection of samples.
在一个示例中,微流控芯片10上还具有用于安装在离心设备上的卡接部12。卡接部12卡接在外接的离心托盘等装置上,具有定位和稳定装配的功能。In an example, the microfluidic chip 10 also has a clamping part 12 for mounting on a centrifugal device. The clamping part 12 is clamped on an external centrifugal tray and other devices, and has the functions of positioning and stable assembly.
在一个示例中,该卡接部12可位于但不限于微流控芯片10的近心端11。In an example, the clamping portion 12 may be located at but not limited to the proximal end 11 of the microfluidic chip 10.
如图3所示,在一个示例中,微流控芯片10包括芯片本体13和覆盖在芯片本体13上的透明盖膜14。芯片本体13与透明盖膜14配合形成各腔体结构和流道结构。示例性的,各腔体结构和流道结构的沟槽等均预形成在芯片本体13上,如图2所示,各孔均开口在芯片本体13的背面,而各腔体结构和流道结构的沟槽则开口在芯片本体13的正面,后续通过透明盖膜12覆盖并密封在芯片本体11的正面即可形成完成对腔体结构和流道结构的封装,形成完整的腔体结构和流道结构。As shown in FIG. 3, in an example, the microfluidic chip 10 includes a chip body 13 and a transparent cover film 14 covering the chip body 13. The chip body 13 and the transparent cover film 14 cooperate to form various cavity structures and flow channel structures. Exemplarily, the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 13, as shown in FIG. 2, each hole is opened on the back of the chip body 13, and each cavity structure and flow channel The groove of the structure is opened on the front surface of the chip body 13, and subsequently covered and sealed on the front surface of the chip body 11 by a transparent cover film 12 to complete the packaging of the cavity structure and the flow channel structure, forming a complete cavity structure and Runner structure.
透明盖膜14可以是但不限于透明胶带或者透明压敏胶等,其与芯片本体13配合构成整个微流控芯片10,装配简单,无需使用复杂、昂贵的超声焊接技术,直接粘接即可,可以显著降低制作成本。可理解,在其他示例中,微流控芯片10也可以采用成本较高的超声焊接技术焊接形成,或者采用3D打印技术一体成型。The transparent cover film 14 can be, but is not limited to, transparent tape or transparent pressure-sensitive adhesive. It cooperates with the chip body 13 to form the entire microfluidic chip 10, which is simple to assemble and does not need to use complicated and expensive ultrasonic welding technology. It can be directly bonded. , Can significantly reduce production costs. It can be understood that, in other examples, the microfluidic chip 10 may also be formed by welding with a relatively high-cost ultrasonic welding technology, or be integrally formed with a 3D printing technology.
本申请还提供了一种体外检测系统,其包括上述微流控芯片10和检测机构,检测机构通过渗透孔171与定量腔体130连通,检测机构设置为检测定量腔体130内的样本。The present application also provides an in vitro detection system, which includes the above-mentioned microfluidic chip 10 and a detection mechanism. The detection mechanism communicates with the quantitative cavity 130 through a penetration hole 171, and the detection mechanism is configured to detect a sample in the quantitative cavity 130.
在一个示例中,检测机构为干化学试纸。示例性的,干化学试纸包括支撑层和在支撑层上依次层叠设置的反应指示层和扩散层,反应指示层中含有能够与待测样本中目标物质反应的反应试剂和指示试剂,扩散层通过进样口面向于渗透孔171。可理解,在其他示例中,检测机构也不限于干化学试纸,也可以是各类其他试纸条或者反应器等。In one example, the detection mechanism is a dry chemical test paper. Exemplarily, the dry chemical test paper includes a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer. The reaction indicator layer contains a reaction reagent and an indicator reagent capable of reacting with the target substance in the sample to be tested, and the diffusion layer passes through The injection port faces the permeation hole 171. It can be understood that in other examples, the detection mechanism is not limited to dry chemical test paper, and may also be various other test paper strips or reactors.
在一个示例中,如图2所示,微流控芯片10围绕分离定量单元100的渗透孔171设有安装槽15,检测机构镶嵌在各安装槽15中。In an example, as shown in FIG. 2, the microfluidic chip 10 is provided with installation grooves 15 around the permeation hole 171 of the separation and quantitative unit 100, and the detection mechanism is embedded in each installation groove 15.
在一个示例中,如图4、图5和图6所示,该体外检测系统还包括用于安装在离心设备上的离心托盘20。离心托盘20上设有用于放置微流控芯片10的安 装位21。In an example, as shown in Figs. 4, 5, and 6, the in vitro detection system further includes a centrifugal tray 20 for installation on a centrifugal device. The centrifugal tray 20 is provided with a mounting position 21 for placing the microfluidic chip 10.
示例性的,该离心托盘20的中部具有旋转安装部22。安装位21有多个,多个安装位21围绕旋转安装部22设置。Exemplarily, the middle part of the centrifugal tray 20 has a rotating mounting part 22. There are multiple mounting positions 21, and the multiple mounting positions 21 are arranged around the rotating mounting portion 22.
在一示例中,该离心托盘20在安装位21设有至少一个用于观察微流控芯片10状态和/或检测结果的观察孔。例如在图示的示例中,该离心托盘20对应于检测机构设有检测孔23,并设有用于观察质控腔体180状态的质控孔24。In an example, the centrifugal tray 20 is provided with at least one observation hole for observing the status of the microfluidic chip 10 and/or the detection result at the installation position 21. For example, in the illustrated example, the centrifugal tray 20 is provided with a detection hole 23 corresponding to the detection mechanism, and is provided with a quality control hole 24 for observing the state of the quality control cavity 180.
以下以图1所示的微流控芯片和图4所述的离心托盘对全血样本进行检测为例,对样本溶液的分离和定量以及检测过程进行详细的说明。该离心托盘20上可安装多个微流控芯片10,可根据检测项目需求和样本需求安装相应数量的微流控芯片10,对于缺位情况,可使用空白的微流控芯片10填补,以保证离心托盘20各位置处的基本平衡。Taking the microfluidic chip shown in FIG. 1 and the centrifugal tray shown in FIG. 4 as an example to detect whole blood samples, the separation and quantification of the sample solution and the detection process will be described in detail below. A plurality of microfluidic chips 10 can be installed on the centrifugal tray 20, and a corresponding number of microfluidic chips 10 can be installed according to the requirements of the test items and samples. For vacancies, blank microfluidic chips 10 can be used to fill in Ensure the basic balance at each position of the centrifugal tray 20.
微流控芯片10实现对全血样本的分离和定量过程可参考但不限于如下:The process of separating and quantifying whole blood samples by the microfluidic chip 10 can be referred to but not limited to the following:
如图7-1所示,将全血样本经由加样孔111加入至加样腔体110中,将离心托盘20安装至具有离心功能的检测设备上,开启设备,转动离心托盘20。As shown in FIG. 7-1, a whole blood sample is added to the sample loading cavity 110 through the sample loading hole 111, the centrifuge tray 20 is installed on a detection device with a centrifugal function, the device is turned on, and the centrifuge tray 20 is rotated.
如图7-2所示,随着离心的进行,加样腔体110中的全血样本经由第一连接微流道120进入定量腔体130和第一废液腔体140中,多余的全血样本经由溢流微流道150进入质控腔体180和第二废液腔体160中,当检测到质控腔体180中有全血样本时,说明定量腔体13中填充满全血样本。如图7-2-1所示,由于毛细流道172的弯折顶点位置较定量腔体130的最上方更靠近于近心端11,在高速离心(如4000-6000rpm)时,离心力大于毛细流道172中毛吸力,全血样本溶液只会进入毛细流道172的172a段,而不会突破毛细流道172的弯折顶点172b而流至172c段。As shown in Figure 7-2, as the centrifugation progresses, the whole blood sample in the sample loading chamber 110 enters the quantitative chamber 130 and the first waste liquid chamber 140 through the first connecting microchannel 120, and the excess whole blood The blood sample enters the quality control cavity 180 and the second waste liquid cavity 160 through the overflow microchannel 150. When a whole blood sample is detected in the quality control cavity 180, it indicates that the quantitative cavity 13 is filled with whole blood. sample. As shown in Figure 7-2-1, since the bending apex of the capillary channel 172 is closer to the proximal end 11 than the top of the quantitative cavity 130, the centrifugal force is greater than the capillary during high-speed centrifugation (such as 4000-6000 rpm). With the hair suction in the flow channel 172, the whole blood sample solution will only enter the section 172a of the capillary flow channel 172, and will not break through the bending apex 172b of the capillary flow channel 172 and flow to the section 172c.
如图7-3所示,继续离心过程,填装在定量腔体130中的全血样本中血细胞会与血清(血浆)分离被沉积在第一废液腔体140中,进而实现了全血样本的分离和定量。As shown in Figure 7-3, continuing the centrifugation process, the blood cells in the whole blood sample filled in the quantitative cavity 130 will be separated from the serum (plasma) and deposited in the first waste liquid cavity 140, thereby realizing whole blood Separation and quantification of samples.
使用该微流控芯片10实现对全血样本的检测过程可参考但不限于如下:The process of using the microfluidic chip 10 to detect whole blood samples can be referred to but not limited to the following:
如图8-1和图8-2所示,在全血样本定量结束后,暂停转动离心托盘20,定量在定量腔体130中的血清(血浆)会在毛细流道172的毛吸力的作用下不断沿着毛细流道172前进,并突破毛细流道172的弯折顶点172b处,优选地,开启设备低速离心(如1000-2500rpm),血清(血浆)从毛细流道172的172c段 自渗透孔171渗出,在虹吸作用下,定量腔体130中的血清(血浆)不断排出直至全部排空而被检测。As shown in Figure 8-1 and Figure 8-2, after the quantification of the whole blood sample is completed, the rotation of the centrifuge tray 20 is suspended, and the serum (plasma) in the quantification chamber 130 will be quantified by the capillary flow channel 172. Continue to advance along the capillary channel 172 and break through the bending apex 172b of the capillary channel 172. Preferably, the device is centrifuged at a low speed (such as 1000-2500 rpm), and the serum (plasma) flows from the 172c section of the capillary channel 172. The permeation hole 171 seeps out, and under the siphon action, the serum (plasma) in the quantitative cavity 130 is continuously discharged until all is emptied for detection.
通过采用微流控芯片与离心托盘相分离的形式,一个离心托盘上可自由装配多个微流控芯片,实现对检测项目和检测样本的自由搭配,有利于整体提高体外检测系统的灵活性。By adopting the form of separating the microfluidic chip and the centrifugal tray, multiple microfluidic chips can be freely assembled on a centrifugal tray to realize the free collocation of test items and test samples, which is beneficial to improve the overall flexibility of the in vitro test system.

Claims (21)

  1. 一种微流控芯片,具有分离定量单元,所述分离定量单元包括加样腔体、第一连接微流道、定量腔体、第一废液腔体、溢流微流道和第二废液腔体;所述加样腔体具有加样孔;所述定量腔体通过所述第一连接微流道与所述加样腔体连通;所述第一废液腔体与所述定量腔体连通;所述第二废液腔体通过所述溢流微流道与所述定量腔体连通;A microfluidic chip has a separation and quantification unit, the separation and quantification unit includes a sample addition cavity, a first connecting microchannel, a quantification cavity, a first waste liquid cavity, an overflow microchannel, and a second waste The liquid cavity; the sample loading cavity has a sample hole; the quantitative cavity communicates with the sample cavity through the first connecting microchannel; the first waste liquid cavity and the quantitative The cavity is in communication; the second waste liquid cavity is in communication with the quantitative cavity through the overflow microchannel;
    所述分离定量单元具有在离心时靠近旋转中心的近心端;所述加样腔体较所述定量腔体靠近所述近心端;所述定量腔体较所述第一废液腔体靠近所述近心端;当所述定量腔体中填满液体后,多余的液体能够经由所述溢流微流道进入所述第二废液腔体,所述第二废液腔体整体距离所述近心端的距离大于或等于所述定量腔体距离所述近心端的距离。The separation and quantitative unit has a proximal end closer to the center of rotation during centrifugation; the sample loading cavity is closer to the proximal end than the quantitative cavity; the quantitative cavity is closer to the first waste liquid cavity Close to the proximal end; when the quantitative cavity is filled with liquid, the excess liquid can enter the second waste liquid cavity through the overflow microchannel, and the second waste liquid cavity as a whole The distance from the proximal end is greater than or equal to the distance between the quantitative cavity and the proximal end.
  2. 如权利要求1所述的微流控芯片,其中,所述加样孔较所述加样腔体与所述第一连接微流道的连接位置更靠近所述近心端。The microfluidic chip of claim 1, wherein the sample injection hole is closer to the proximal end than the connection position of the sample injection cavity and the first connecting microfluidic channel.
  3. 如权利要求1所述的微流控芯片,其中,所述加样腔体还具有第一透气孔,所述第一透气孔较所述加样腔体与所述第一连接微流道的连接位置更靠近所述近心端。The microfluidic chip of claim 1, wherein the sample loading cavity further has a first vent hole, and the first vent hole is larger than the gap between the sample loading cavity and the first connecting microfluidic channel. The connection position is closer to the proximal end.
  4. 如权利要求1所述的微流控芯片,其中,所述加样腔体与所述第一连接微流道的连接处呈漏斗状。The microfluidic chip of claim 1, wherein the connection between the sample loading cavity and the first connecting microfluidic channel is in the shape of a funnel.
  5. 如权利要求1所述的微流控芯片,还包括质控腔体,所述质控腔体与所述第二废液腔体连通,所述质控腔体较所述第二废液腔体远离所述近心端。The microfluidic chip of claim 1, further comprising a quality control cavity, the quality control cavity is in communication with the second waste liquid cavity, and the quality control cavity is smaller than the second waste liquid cavity. The body is far away from the proximal end.
  6. 如权利要求1所述的微流控芯片,还包括与所述第二废液腔体连通的第二连接微流道,所述第二连接微流道自与所述第二废液腔体连接的一端逐渐向靠近所述近心端的方向延伸,并在另一端设有第二透气孔。The microfluidic chip according to claim 1, further comprising a second connection microchannel connected to the second waste liquid chamber, the second connection microchannel being separated from the second waste liquid chamber One end of the connection gradually extends toward the proximal end, and a second vent is provided at the other end.
  7. 如权利要求1~6中任一项所述的微流控芯片,还包括第三连接微流道,所述第一废液腔体通过所述第三连接微流道与所述定量腔体连通。The microfluidic chip according to any one of claims 1 to 6, further comprising a third connecting microfluidic channel, and the first waste liquid cavity is connected to the quantitative cavity through the third connecting microfluidic channel. Connected.
  8. 如权利要求7所述的微流控芯片,还包括出液微流道,所述出液微流道的一端与所述定量腔体连通,另一端具有渗透孔。8. The microfluidic chip according to claim 7, further comprising a liquid outlet microchannel, one end of the liquid outlet microchannel is in communication with the quantitative cavity, and the other end has a permeation hole.
  9. 如权利要求8所述的微流控芯片,其中,所述出液微流道包括毛细流道,所述毛细流道的一端与所述第三连接微流道连接,另一端设有所述渗透孔;The microfluidic chip according to claim 8, wherein the liquid outlet microchannel comprises a capillary channel, one end of the capillary channel is connected to the third connecting microchannel, and the other end is provided with the Penetration hole
    所述毛细流道自与所述第三连接微流道连接的一端逐渐向靠近所述近心端的方向延伸并弯折后向远离所述近心端的方向延伸;所述毛细流道的弯折顶点 位置较所述定量腔体与所述第一连接微流道的连接位置处更靠近所述近心端。The capillary flow channel gradually extends from the end connected to the third connecting micro flow channel in a direction close to the proximal end and is bent and then extends in a direction away from the proximal end; bending of the capillary flow channel The apex position is closer to the proximal end than the connection position of the quantitative cavity and the first connecting microfluidic channel.
  10. 如权利要求9所述的微流控芯片,其中,所述出液微流道还包括第四连接微流道,所述第四连接微流道的一端与所述第三连接微流道连接,另一端与所述毛细流道连接。The microfluidic chip according to claim 9, wherein the liquid outlet microchannel further comprises a fourth connecting microchannel, and one end of the fourth connecting microchannel is connected to the third connecting microchannel , The other end is connected with the capillary flow channel.
  11. 如权利要求10所述的微流控芯片,其中,所述第四连接微流道自与所述第三连接微流道连接的一端逐渐向靠近所述近心端的方向延伸以与所述毛细流道连接。The microfluidic chip according to claim 10, wherein the fourth connecting microfluidic channel gradually extends from an end connected to the third connecting microfluidic channel toward the proximal end to communicate with the capillary Runner connection.
  12. 如权利要求1~6及8~11中任一项所述的微流控芯片,其中,各所述微流控芯片上设有一个所述分离定量单元。The microfluidic chip according to any one of claims 1 to 6 and 8 to 11, wherein each of the microfluidic chips is provided with one separation and quantification unit.
  13. 如权利要求12所述的微流控芯片,其中,所述微流控芯片上还具有用于安装在离心设备上的卡接部。The microfluidic chip according to claim 12, wherein the microfluidic chip further has a clamping part for mounting on a centrifugal device.
  14. 如权利要求13所述的微流控芯片,其中,所述卡接部位于所述近心端。The microfluidic chip according to claim 13, wherein the clamping part is located at the proximal end.
  15. 一种体外检测系统,包括如权利要求1~14中任一项所述的微流控芯片和检测机构,所述检测机构与所述定量腔体连通,所述检测机构设置为检测所述定量腔体内的样本。An in vitro detection system, comprising the microfluidic chip according to any one of claims 1-14 and a detection mechanism, wherein the detection mechanism is in communication with the quantitative cavity, and the detection mechanism is configured to detect the quantitative The sample inside the cavity.
  16. 如权利要求15所述的体外检测系统,还包括用于安装在离心设备上的离心托盘,所述离心托盘上设有用于放置所述微流控芯片的安装位。The in vitro detection system according to claim 15, further comprising a centrifugal tray for installation on a centrifugal device, and an installation position for placing the microfluidic chip is provided on the centrifugal tray.
  17. 如权利要求16所述的体外检测系统,其中,所述离心托盘的中部具有旋转安装部,所述安装位有多个,多个所述安装位围绕所述旋转安装部设置。The in vitro detection system according to claim 16, wherein the center of the centrifugal tray has a rotating mounting part, there are a plurality of the mounting positions, and the plurality of mounting positions are arranged around the rotating mounting part.
  18. 如权利要求16所述的体外检测系统,其中,所述离心托盘在所述安装位设有至少一个用于观察所述微流控芯片状态和/或检测结果的观察孔。The in vitro detection system according to claim 16, wherein the centrifugal tray is provided with at least one observation hole in the installation position for observing the state of the microfluidic chip and/or the detection result.
  19. 如权利要求15所述的体外检测系统,其中,所述检测机构为干化学试纸。The in vitro detection system according to claim 15, wherein the detection mechanism is a dry chemical test paper.
  20. 如权利要求19所述的体外检测系统,其中,所述干化学试纸包括支撑层和在所述支撑层上依次层叠设置的反应指示层和扩散层,所述反应指示层中含有能够与待测样本中目标物质反应的反应试剂和指示试剂,所述扩散层通过所述进样口面向于所述渗透孔。The in vitro detection system according to claim 19, wherein the dry chemical test paper comprises a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer, and the reaction indicator layer contains The reaction reagent and indicator reagent for the reaction of the target substance in the sample, and the diffusion layer faces the permeation hole through the injection port.
  21. 如权利要求15~20中任一项所述的体外检测系统,其中,所述微流控芯片围绕所述分离定量单元的渗透孔设有安装槽,所述检测机构镶嵌在各所述安装槽中。The in vitro detection system according to any one of claims 15 to 20, wherein the microfluidic chip is provided with mounting grooves surrounding the permeation hole of the separation and quantitative unit, and the detection mechanism is embedded in each of the mounting grooves. in.
PCT/CN2019/126900 2019-10-21 2019-12-20 Microfluidic chip and in vitro test system WO2021077591A1 (en)

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CN114433259B (en) * 2021-12-24 2023-12-26 广州万孚生物技术股份有限公司 Homogeneous phase test micro-fluidic chip and detection system
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CN114509323A (en) * 2022-02-24 2022-05-17 含光微纳科技(太仓)有限公司 Centrifugal micro-fluidic whole blood separation plasma structure

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2002895A1 (en) * 2007-06-04 2008-12-17 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
EP2128614A1 (en) * 2008-05-14 2009-12-02 Samsung Electronics Co., Ltd. Microfluidic device containing lyophilized reagent therein and analyzing method using the same
US20110085950A1 (en) * 2009-10-08 2011-04-14 Samsung Electronics Co., Ltd. Centrifugal force based microfluidic system and bio cartridge for the microfluidic system
CN103464230A (en) * 2013-09-25 2013-12-25 中国科学院长春光学精密机械与物理研究所 Centrifugal whole blood analysis micro-fluidic chip, preparation method as well as application method thereof
CN105652023A (en) * 2016-01-09 2016-06-08 深圳市贝沃德克生物技术研究院有限公司 Comprehensive detection equipment for multiple serum markers
CN205347420U (en) * 2015-12-07 2016-06-29 中国科学院苏州生物医学工程技术研究所 Full -automatic nucleic acid extraction and PCR increase micro -fluidic chip

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2002895A1 (en) * 2007-06-04 2008-12-17 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
EP2128614A1 (en) * 2008-05-14 2009-12-02 Samsung Electronics Co., Ltd. Microfluidic device containing lyophilized reagent therein and analyzing method using the same
US20110085950A1 (en) * 2009-10-08 2011-04-14 Samsung Electronics Co., Ltd. Centrifugal force based microfluidic system and bio cartridge for the microfluidic system
CN103464230A (en) * 2013-09-25 2013-12-25 中国科学院长春光学精密机械与物理研究所 Centrifugal whole blood analysis micro-fluidic chip, preparation method as well as application method thereof
CN205347420U (en) * 2015-12-07 2016-06-29 中国科学院苏州生物医学工程技术研究所 Full -automatic nucleic acid extraction and PCR increase micro -fluidic chip
CN105652023A (en) * 2016-01-09 2016-06-08 深圳市贝沃德克生物技术研究院有限公司 Comprehensive detection equipment for multiple serum markers

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