CN115824965A - Flow type fluorescence detection liquid path system - Google Patents

Flow type fluorescence detection liquid path system Download PDF

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Publication number
CN115824965A
CN115824965A CN202211527387.7A CN202211527387A CN115824965A CN 115824965 A CN115824965 A CN 115824965A CN 202211527387 A CN202211527387 A CN 202211527387A CN 115824965 A CN115824965 A CN 115824965A
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China
Prior art keywords
module
quantitative
sampling device
sample
sheath
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CN202211527387.7A
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Chinese (zh)
Inventor
武林
管海兵
随从亚
方剑秋
钟春梅
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Hangzhou Depth Bio Tech Co ltd
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Hangzhou Depth Bio Tech Co ltd
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Priority to CN202211527387.7A priority Critical patent/CN115824965A/en
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Abstract

The invention discloses a flow-type fluorescence detection liquid path system and a flow-type fluorescence detection liquid path method, which aim to overcome the problems of low detection efficiency and low device utilization rate in the prior art and comprise a flow chamber, a sheath liquid providing module, a sampling device, a first quantitative module, a second quantitative module, a first valve group and a second valve group, wherein the sheath liquid providing module is connected to a sheath liquid inlet, the first quantitative module and the second quantitative module through the first valve group, the first quantitative module is connected to a sample inlet and the sampling device through the second valve group, and the second quantitative module is connected to the sample inlet and the sampling device through the second valve group.

Description

Flow type fluorescence detection liquid path system
Technical Field
The invention belongs to a biological detection technology, and particularly relates to a flow type fluorescence detection liquid path system.
Background
Flow-type fluorescence detection, also known as suspension array, liquid phase chip, etc. The principle of the technology is that a fluorescent coding microsphere is taken as a core, microneedle molecules on the fluorescent coding microsphere can be specifically combined with biomolecules to achieve the effect of fluorescently labeling the biomolecules, the labeled biomolecules are subjected to laser analysis, and then a series of processing is performed on optical signals generated by the laser analysis to obtain a visual diagnosis result.
The invention of China with the prior publication number of CN215574651U discloses a flow-type fluorescence detection liquid path system, which utilizes the fluorescence detection technology and comprises a flow chamber, a sampling device, a cleaning device, a sheath liquid pump and a sample pump, and realizes the flow regulation of media (comprising a sample and sheath liquid) in a pipeline by controlling various valves, thereby realizing the flow of sample suction, sample pushing, detection and cleaning.
However, the existing liquid path system is not perfect, and has the following problems: (1) In the process of detecting a sample by the liquid path system, the sampling device, the cleaning device, the sheath liquid pump and the flow chamber are respectively in an idle state in different degrees, so that the problem of low utilization rate of components in the liquid path system is caused; (2) When a plurality of samples are continuously detected, the liquid path system can only detect the plurality of samples one by one, and only after the last sample is detected, the liquid path system can start the detection of the next sample, which causes the problem of low detection efficiency.
Disclosure of Invention
In order to overcome the defects and problems in the prior art, the invention provides a flow type fluorescence detection liquid path system.
In order to achieve the purpose, the invention adopts the following technical scheme:
a flow-through fluorescence detection fluid circuit system, comprising:
a flow cell comprising a sample inlet, a sheath fluid inlet, and a waste fluid outlet;
a sheath fluid providing module for providing a sheath fluid to the sheath fluid inlet, the first dosing module and the second dosing module;
a sampling device for providing a sample to the first and second quantification modules;
the first quantitative module is used for sucking and cleaning sheath liquid of the first quantitative module and the sampling device through the sheath liquid supply module and is also used for sucking a sample quantitatively through the sampling device;
the second quantitative module is used for sucking and cleaning sheath liquid of the second quantitative module and the sampling device through the sheath liquid supply module and also used for sucking a sample quantitatively through the sampling device;
the sheath liquid supply module is connected to the sheath liquid inlet, the first quantitative module and the second quantitative module through the first valve group;
and the second quantitative module is connected with the sample inlet and the sampling device through the second valve group.
Preferably, the first valve group comprises a third shut-off valve, and the sheath fluid supply module is connected to the first dosing module through the third shut-off valve.
Preferably, the first valve group comprises a fourth shut-off valve, and the sheath fluid supply module is connected to the second quantitative module through the fourth shut-off valve.
Preferably, the first valve group comprises a fifth shutoff valve, and the sheath fluid inlet is connected to the sheath fluid supply module through the fifth shutoff valve.
Preferably, the second valve set comprises a first multiplex valve, and the first quantitative module is connected to the sample inlet and the sampling device through the first multiplex valve.
Preferably, the second valve set comprises a second multiplex valve, and the second quantitative module is connected to the sample inlet and the sampling device through the second multiplex valve.
Preferably, the first multi-way valve and the second multi-way valve are both three-way valves.
Preferably, the first quantitative module comprises two first flow ports, the first valve group and the second valve group are respectively connected to the two first flow ports, the second quantitative module comprises two second flow ports, and the first valve group and the second valve group are respectively connected to the two second flow ports.
Preferably, the waste liquid collector is connected to the waste liquid outlet through the sixth stop valve.
On the other hand, the invention also provides a detection method adopting the flow-type fluorescence detection liquid path system, which adopts the liquid path system and comprises the following steps:
detection flow using a first quanta module: the first quantitative module quantitatively absorbs a sample through the sampling device, the first quantitative module pushes the sample to the flow chamber, the fluorescence detector detects the concentration of an analyte in the sample from the first quantitative module on the flow chamber, and the first quantitative module absorbs sheath liquid through the sheath liquid providing module and cleans the first quantitative module and the sampling device through the sheath liquid;
detection procedure using a second quantification module: the second quantitative module absorbs a sample quantitatively through the sampling device, the second quantitative module pushes the sample to the flow chamber, the fluorescence detector detects the concentration of an analyte in the sample from the second quantitative module on the flow chamber, and the second quantitative module absorbs sheath liquid through the sheath liquid providing module and cleans the second quantitative module and the sampling device through the sheath liquid;
the detection process using the first dosing module and the detection process using the second dosing module are performed simultaneously, and if the first dosing module pushes the sample to the flow chamber, the second dosing module draws the sheath fluid through the sheath fluid providing module and cleans the first dosing module and the sampling device through the sheath fluid.
Preferably, the method further comprises the following steps:
if the second quantitative module pushes the sample to the flow chamber, the first quantitative module absorbs the sheath liquid through the sheath liquid providing module and cleans the first quantitative module and the sampling device through the sheath liquid.
Preferably, the method further comprises the following steps:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber, the second quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid.
Preferably, the method further comprises the following steps:
if the fluorescence detector detects the concentration of the analyte in the sample from the second quantitative module on the flow chamber, the first quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid.
Preferably, the method further comprises the following steps:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber, the first quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid.
Preferably, the method further comprises the following steps:
and if the fluorescence detector detects the concentration of the analyte in the sample from the second quantitative module on the flow chamber, the second quantitative module absorbs the sheath fluid through the sheath fluid supply module and cleans the second quantitative module and the sampling device through the sheath fluid.
Compared with the prior art, the invention has the outstanding and beneficial technical effects that:
(1) In the invention, the first quantitative module and the second quantitative module share the sampling device, the flow chamber and the sheath fluid providing module, thereby greatly improving the use efficiency of each device in the fluid path system and simplifying the structure of the fluid path system under the condition of ensuring the requirements of sampling, pushing, measuring and cleaning.
(2) In the invention, the first quantitative module and the second quantitative module alternately use the sampling device, the flow chamber and the sheath fluid providing device, on one hand, the first quantitative module and the second quantitative module respectively and independently sample, and corresponding devices are cleaned before sampling, so that the problem of mutual pollution of samples in a detection process using the first quantitative module and samples in a detection process using the second quantitative module is avoided, on the other hand, when the first quantitative module pushes and samples, the second quantitative module can clean and sample, for example, when the first quantitative module pushes samples to the flow chamber, the second quantitative module can clean the second quantitative module and the sampling device, so that the utilization rate of each device in the fluid path system is greatly improved, and in actual use, the fluid path system has higher efficiency when detecting a plurality of groups of samples (such as repeated experiments and control actual samples).
(3) In the invention, the control on the flow and the flow direction of media (including samples and sheath fluid) in the liquid path system is realized by controlling the first valve group and the second valve group, and the working reliability of the liquid path system is ensured.
Drawings
FIG. 1 is a schematic diagram of a fluid path system in accordance with an embodiment of the present invention;
FIG. 2 is a schematic structural diagram of a fluid path system in accordance with another embodiment of the present invention;
in the figure: the device comprises a waste liquid collecting module 1, a waste liquid collecting module 2, a sampling device 3, a sheath liquid providing module 3, a flow chamber 4, a first quantitative module 5, a second quantitative module 6, a first multi-way valve 7, a second multi-way valve 8, a third shut-off valve 9, a fourth shut-off valve 10, a fifth shut-off valve 11, a sixth shut-off valve 12, a seventh multi-way valve 13, a eighth shut-off valve 14, a ninth shut-off valve 15, a tenth shut-off valve 16, an eleventh shut-off valve 17, a sampling needle 21, a sampling port 22, a sample inlet 41, a sheath liquid inlet 42, a waste liquid outlet 43, a first flow channel port 51 and a second flow channel port 61.
Detailed Description
To facilitate understanding of those skilled in the art, the present invention is further described below in conjunction with the accompanying drawings and the specific embodiments.
As shown in fig. 1 and 2, the present invention provides a flow-type fluorescence detection fluid path system for detecting a liquid-phase sample, which includes a flow chamber, a sheath fluid providing module, a sampling device, a first quantitative module, a second quantitative module, a first valve group, a second valve group, a waste fluid collecting module, and a sixth shut-off valve. All the components of the liquid path system are connected together by adopting pipelines so as to form the liquid path system. The sampling device has a sampling port through which the sample enters the fluid path system.
The first quantitative module and the second quantitative module share the same sampling device, the same sheath liquid providing module and the same flow chamber, and in use, the first quantitative module and the second quantitative module can alternately use the sampling device, the sheath liquid providing module and the flow chamber, so that the problem that the sampling device, the sheath liquid providing module and the flow chamber are vacant is solved, and the utilization rate of the sampling device is greatly improved.
Before use, a sample is arranged on a sampling device with a sampling port, and sheath liquid is arranged on a sheath liquid supply module.
The use of the present fluid path system includes the use of a first dosing module and the use of a second dosing module. When the first quantitative module is used, the first quantitative module is controlled to sequentially suck and push samples, the fluorescence detector measures optical signals of the samples on the flow chamber, the concentration of analytes in the samples in the liquid path system is calculated according to the fluorescence intensity and the sample pushing amount of the samples, the purpose of quantitative detection is achieved, and finally the first quantitative module is controlled to suck sheath liquid to clean the first quantitative module and the sampling device. Similarly, when the second quantitative module is used, the second quantitative module is controlled to sequentially suck and push samples, the fluorescence detector measures the optical signal of the sample on the flow chamber, and the concentration of the analyte in the sample in the liquid path system is calculated according to the optical signal intensity and the sample pushing amount of the sample.
For ease of understanding, the present embodiment explains the technical terms described above.
And (3) sample suction: the first quantification module/the second quantification module absorbs the sample by the sampling device.
Sample pushing: the first/second dosing module pushes the sample in the first/second dosing module into the flow chamber.
And (3) sample measurement: the fluorescence detector optically detects the sheath fluid-sample flow flowing through the flow cell to determine the concentration of the analyte in the sample.
Sample suction amount: the first quantitative module/the second quantitative module sucks the sample amount in the first quantitative module/the second quantitative module when the sample is sucked.
Sample pushing amount: the first dosing module/second dosing module pushes the amount of sample in the flow chamber when pushing the sample.
Sample(s)
The sample is in a liquid phase and includes an analyte and a fluorescent coded sphere.
Any analyte present in a sample capable of specific reaction can be detected using the present embodiment. Some analytes may be detected using the present fluid path system, for example, the analytes may include proteins, polypeptides, enzymes, hormones, antibodies, target nucleic acid fragments, and other bioactive substances capable of specifically reacting with the fluorescent-encoded microspheres, and the analytes are widely present in whole blood, serum, plasma, urine, and saliva.
The fluorescent-coded microsphere is a microsphere with a fluorescent marker and a molecular probe, and the shape of the microsphere is spherical, the particle size is generally between 1 nanometer and 500 micrometers, and in the embodiment, the particle size is preferably between 5.5 and 5.6 micrometers. The surface or the interior of the microsphere is loaded with a fluorescent marker, which is also called fluorescent molecule, and can trigger stronger optical signals under weaker laser stimulation. For example, fluorescent labels may include molecular phycoerythrin, fluorescein isothiocyanate, 7-amino-4-methylcoumarin, and the like. The molecular probe can be specifically combined with the analyte, so that the fluorescent coding microspheres are marked on the analyte, and the marked analyte can be captured by the fluorescence detector in the flow chamber to obtain an image of an optical signal.
Flow cell
The flow chamber belongs to a core device in a liquid path system, and the quality of the flow chamber directly influences the fluorescence detection result of the fluorescence detector on the marked analyte. The flow cell is made of a transparent and chemically stable material such that laser light emitted by the laser emitter and an optical signal reflected by the labeled analyte can pass through the flow cell. The transparent and chemically stable material is typically glass. The flow chamber comprises a sample inlet through which a sample of the first dosing module or a sample provided by the second dosing module can enter the conduit inside the flow chamber. The axis of the sample inlet is located on the axis of the flow cell inner conduit such that a sample entering the flow cell inner conduit from the sample inlet can flow along the axis of the flow cell inner conduit. The flow chamber further comprises a sheath fluid inlet through which a sheath fluid provided by the sheath fluid providing module can enter the conduit inside the flow chamber. The sheath fluid inlet is positioned on the side surface of the inner pipeline of the flow chamber, so that the sheath fluid entering the inner pipeline of the flow chamber from the sheath fluid inlet wraps the sample from the periphery of the sample, and the sheath fluid forces the sample to keep flowing on the axis of the inner pipeline of the flow chamber. The flow cell further includes a waste outlet for discharging waste fluid within the flow cell internal conduit, the waste fluid being a sheath fluid-sample flow detected by the laser detector. In addition to the above-described flow cell configuration, other specific configurations of flow cells will be apparent to those skilled in the art of biological testing from a review of the well-known art.
Sheath fluid providing module
The sheath liquid providing module of the liquid path system is provided with sheath liquid, and the sheath liquid providing module can provide the sheath liquid to the flowing chamber, the first quantitative module and the second quantitative module. In use, sheath fluid flowing from the sheath fluid module to the flow chamber is used to entrain a sample, sheath fluid flowing from the sheath fluid module to the first dosing module is used to clean the first dosing module and the sampling device, and sheath fluid flowing from the sheath fluid module to the second dosing module is used to clean the second dosing module and the sampling device. In one embodiment, the sheath fluid providing module includes a cavity for storing the sheath fluid, and the flow chamber, the first dosing module and the second dosing module are respectively connected to the cavity. In one embodiment, the sheath fluid providing module includes a sheath fluid pump for delivering sheath fluid to facilitate delivery of the sheath fluid to the flow chamber, the first dosing module and the second dosing module.
Sampling device
The sampling device is particularly intended to be a sampling device for use in biological testing. A sample can be provided on the sampling device, which can collect the sample and can provide the collected sample to the first and second quantification modules. Since the sample is in a liquid phase, the sample is usually placed in a container such as a test tube, a beaker, or the like, and the sampling device is placed in the container so that the sampling device can suck the sample. In one embodiment, the sampling device includes a sampling needle having a unitary construction in the form of a needle tube, the opening of the container being generally sealed with a septum, and the sampling needle being capable of piercing the septum and inserting into the container to aspirate a sample from the container. In order to facilitate the penetration of the septum by the sampling needle, one end of the sampling needle may be made sharp and the sampling port may be provided at the sharp end of the sampling needle.
First quantity module
The first quantitative module is used for quantitatively sucking or pushing a medium, and the medium can be a sample or sheath fluid.
In a specific embodiment, the first quantitative module includes a quantitative pump, the quantitative pump refers to a hydraulic pump with a constant volume of a medium discharged by one rotation of a pump shaft, the specific structure of the quantitative pump is known in the prior art, and the volume of the medium sucked or pushed by the first quantitative module can be calculated by counting the rotation number of the pump shaft of the quantitative pump. In one embodiment, the first dosing module includes two first port ports, a first valve group coupled to one of the first port ports and a second valve group coupled to the other of the first port ports, such that control of the first and second valve groups is independent of and does not interfere with each other.
In another embodiment, the first dosing module comprises a cavity having a known volume, and wherein, in use, the first dosing module is capable of filling the cavity with a medium or draining the medium filling the cavity, and also of drawing or pushing the medium in the empire amount. In another particular embodiment, the first dosing module further comprises a hydraulic pump for delivering the medium for the purpose of sucking or pushing the medium by the first dosing module.
Second dosing module
The function and the specific structure of the second quantitative module are consistent with those of the first quantitative module, the second quantitative module comprises two second flow openings, and the first valve group and the second valve group are respectively connected to the two second flow openings. The difference is that, in use, the first dosing module and the second dosing module are an alternative to the use of the sampling device, the sheath fluid providing module and the flow chamber. For example, when the first quantitative module sucks a sample through the sampling device, the second quantitative module sucks sheath fluid through the sheath fluid supply module.
First valve group
The first valve group is used as a control device between the sheath liquid providing module and the sheath liquid inlet, between the sheath liquid providing module and the first quantitative module, and between the sheath liquid providing module and the second quantitative module. In this embodiment, the sheath liquid providing module is connected to the sheath liquid inlet through a pipeline, and the first valve set is disposed on the pipeline between the sheath liquid providing module and the sheath liquid inlet and used for opening and closing the pipeline between the sheath liquid providing module and the sheath liquid inlet; the first valve group is also arranged on the pipeline between the sheath liquid providing module and the first quantitative module and is used for opening and closing the pipeline between the sheath liquid providing module and the first quantitative module; the sheath liquid providing module is connected with the second quantitative module through a pipeline, and the first valve group is further arranged on the pipeline between the sheath liquid providing module and the second quantitative module and used for opening and closing the pipeline between the sheath liquid providing module and the second quantitative module.
In one embodiment, as shown in fig. 1, the first valve set comprises a third shut-off valve, the third shut-off valve is disposed on a pipeline between the sheath fluid providing module and the sheath fluid inlet, the sheath fluid providing module is connected to the sheath fluid chamber through the third shut-off valve, and the third shut-off valve is controlled to independently control the on-off between the sheath fluid providing module and the sheath fluid chamber. In a specific embodiment, the first valve group further includes a fourth shut-off valve, the fourth shut-off valve is disposed on a pipeline between the sheath liquid providing module and the sheath liquid inlet, the sheath liquid providing module is connected to the first quantitative module through the fourth shut-off valve, and the fourth shut-off valve is controlled to independently control on/off between the sheath liquid providing module and the first quantitative module. In a specific embodiment, the first valve group further comprises a fifth shutoff valve, the fifth shutoff valve is arranged on a pipeline between the sheath liquid providing module and the second quantitative module, the sheath liquid providing module is connected to the second quantitative module through the fifth shutoff valve, and the fifth shutoff valve is controlled to independently control the on-off between the sheath liquid providing module and the second quantitative module.
As shown in fig. 2, in another embodiment, the first valve group includes a seventh multi-way valve, the seventh multi-way valve is disposed on a pipeline between the sheath fluid providing module and the first quantitative module, the sheath fluid providing module is connected to the first quantitative module through the seventh multi-way valve, the seventh multi-way valve is further disposed on a pipeline between the sheath fluid providing module and the second quantitative module, the sheath fluid providing module is further connected to the second quantitative module through the seventh multi-way valve, and the on/off between the sheath fluid providing module and the second quantitative module can be controlled through the seventh multi-way valve, thereby simplifying the structure of the first valve group. The multi-way valve refers to a valve with a plurality of channel ports, the seventh multi-way valve can be a three-way valve with three channel ports, the sheath fluid providing module, the first quantitative module and the second quantitative module are respectively connected to the three channel ports of the seventh multi-way valve, and in use, if the sheath fluid providing module and the first quantitative module are connected through the seventh multi-way valve, the sheath fluid providing module and the second quantitative module are disconnected through the seventh multi-way valve; if the seventh multi-way valve is connected with the sheath liquid providing module and the second quantitative module, the sheath liquid providing module and the first quantitative module are disconnected by the seventh multi-way valve, so that the sheath liquid providing module can be used by the first quantitative module and the second quantitative module alternately by controlling the seventh multi-way valve.
Second valve group
The second set of valves acts as a control means between the sampling device and the first dosing module, between the sampling device and the second dosing module, between the first dosing module and the flow chamber, and between the second dosing module and the flow chamber. In the embodiment, the sampling device is connected with the first quantitative module through a pipeline, and the second valve group is arranged on the pipeline between the sampling device and the first quantitative module and is used for opening and closing the pipeline between the sampling device and the first quantitative module; the sampling device is also connected with the second quantitative module through a pipeline, and the second valve group is also arranged on the pipeline between the sampling device and the second quantitative module and used for opening and closing the pipeline between the sampling device and the second quantitative module; the first quantitative module is also connected with the flow chamber through a pipeline, and the second valve group is also arranged on the pipeline between the first quantitative module and the flow chamber and used for opening and closing the pipeline between the first quantitative module and the flow chamber; the second quantitative module is connected with the flow chamber through a pipeline, and the second valve group is also arranged on the pipeline between the second quantitative module and the flow chamber and used for opening and closing the pipeline between the second quantitative module and the flow chamber.
As shown in fig. 1, in a specific embodiment, the first valve group includes a first multi-way valve, the first multi-way valve is disposed on a pipeline between the sampling device and the first dosing module, the sampling device is connected to the first dosing module through the first multi-way valve, the first multi-way valve is further disposed on a pipeline between the first dosing module and the flow chamber, the first dosing module is connected to the flow chamber through the first multi-way valve, and the on/off between the sampling device and the first dosing module and the on/off between the first dosing module and the flow chamber can be controlled by controlling the first multi-way valve, so that the structure of the first valve group is simplified. The first multi-way valve may be a three-way valve having three ports, the sampling device, the first dosing module and the flow chamber being connected to the three ports of the first multi-way valve respectively, the first multi-way valve disconnecting the first dosing module and the flow chamber in use if the first multi-way valve switches the sampling device and the first dosing module on; if the first multi-way valve conducts the first quantitative module and the flow chamber, the first multi-way valve disconnects the sampling device and the first quantitative module, and therefore the sampling device and the flow chamber can be used for alternately using the first quantitative module by controlling the first multi-way valve. In a specific embodiment, the second valve group further comprises a second multi-way valve, the second multi-way valve is arranged on a pipeline between the sampling device and the second quantitative module, the sampling device is connected to the second quantitative module through the second multi-way valve, the second multi-way valve is further arranged on a pipeline between the second quantitative module and the flow chamber, the second quantitative module is connected to the flow chamber through the second multi-way valve, and the on-off between the sampling device and the second quantitative module and the on-off between the second quantitative module and the flow chamber can be controlled by controlling the second multi-way valve, so that the structure of the first valve group is simplified. The second multi-way valve can be a three-way valve and is provided with three passage ports, the sampling device, the second quantitative module and the flow chamber are respectively connected to the three passage ports of the second multi-way valve, and in use, if the sampling device and the second quantitative module are connected through the second multi-way valve, the second quantitative module and the flow chamber are disconnected through the second multi-way valve; if the second multi-way valve is connected with the second quantitative module and the flow chamber, the second multi-way valve is disconnected with the sampling device and the second quantitative module, so that the sampling device and the flow chamber can be alternately used by controlling the second multi-way valve. In addition, the effect that the first quantitative module and the second quantitative module alternately use the sampling device and the flow chambers can be achieved by controlling the first multi-way valve and the second multi-way valve.
In another embodiment, as shown in fig. 2, the first valve set includes an eighth shut-off valve, the eighth shut-off valve is disposed on a pipeline between the sampling device and the first dosing module, the sampling device is connected to the first dosing module through the eighth shut-off valve, and the eighth shut-off valve is controlled to independently control the on-off between the sampling device and the first dosing module. In another embodiment, the second valve group comprises a ninth shut-off valve, the ninth shut-off valve is arranged on a pipeline between the sampling device and the second quantitative module, the sampling device is connected to the second quantitative module through the ninth shut-off valve, and the on-off between the sampling device and the second quantitative module can be independently controlled by controlling the ninth shut-off valve. In another embodiment, the first valve group comprises a tenth shutoff valve, the tenth shutoff valve is arranged on a pipeline between the first dosing module and the flow chamber, the first dosing module is connected to the flow chamber through the tenth shutoff valve, and the tenth shutoff valve is controlled to independently control the connection and disconnection between the first dosing module and the flow chamber. In another embodiment, the second valve set further comprises an eleventh shutoff valve, the eleventh shutoff valve is arranged on a pipeline between the second dosing module and the flow chamber, the second dosing module is connected to the flow chamber through the eleventh shutoff valve, and the second dosing module and the flow chamber can be independently controlled to be opened or closed by controlling the eleventh shutoff valve.
Waste liquid collecting module
The waste liquid collection module refers in particular to a container for collecting waste liquid of biological type. Waste fluid refers to the sheath fluid-sample stream after detection is complete. By collecting the waste liquid in the waste liquid collecting module, personal injury, environmental pollution and social harm caused by the potentially pathogenic and harmful waste liquid are avoided.
Sixth shutoff valve
And the sixth shut-off valve is used as a control device between the waste liquid outlet and the waste liquid collecting module. The sixth shutoff valve sets up on the pipeline between waste liquid export and waste liquid collection module, and the waste liquid export passes through the sixth shutoff valve to be connected on waste liquid collection module, but the break-make between flow room and the waste liquid collection module of independent control through controlling the sixth shutoff valve.
Fluorescence detector (not shown in the figure)
The fluorescence detector is generally disposed near the flow cell, and includes a laser emitter and a detector, the laser emitter is configured to emit laser light into the flow cell, the sample entrained by the sheath fluid emits optical signals such as fluorescence, side-scattered light, and forward scattering under excitation of the laser light, and the detector can capture an image of the optical signals. The fluorescence detector used in this embodiment is not different from the prior art, and the specific structure of the fluorescence detector including the laser emitter and the detector can be clearly and completely known by those skilled in the art of biological detection.
Detection method
The invention also provides a detection method of the flow-type fluorescence detection liquid path system, which is implemented by adopting the liquid path system and is used for detecting the concentration of an analyte in a sample. The detection method comprises a detection process using a first quantitative module and a detection process using a second quantitative module. The detection process using the first quantitative module indicates that the liquid path system uses the first quantitative module in a sample detection process. The detection process using the second quantitative module means that the second quantitative module is used in one sample detection process of the liquid path system.
The detection process using the first quantitative module specifically includes:
step1: the first multi-way valve disconnects the first quantitative module and the flow chamber, the first multi-way valve connects the first quantitative module and the sampling device, the first quantitative module quantitatively sucks a sample through the sampling device, and the sample is stored in the first quantitative module;
step2: the first multi-way valve disconnects the first quantitative module and the sampling device, the first multi-way valve conducts the first quantitative module and the flow chamber, and the first quantitative module pushes the sample to the flow chamber;
and step3: the first multi-way valve disconnects the first quantitative module and the sampling device, the first multi-way valve connects the first quantitative module and the flow chamber, the sheath fluid providing module pushes the sheath fluid into the flow chamber, and the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber;
and 4, step 4: the first multi-way valve disconnects the first quantitative module and the flow chamber, the first quantitative module and the sampling device are connected through the first multi-way valve, the sheath liquid is sucked by the first quantitative module through the sheath liquid supply module, and the first quantitative module and the sampling device are cleaned through the sheath liquid.
Similarly, the detection process using the second quantitative module specifically includes:
a) The second multi-way valve disconnects the second quantitative module and the flow chamber, the second multi-way valve connects the second quantitative module and the sampling device, the second quantitative module quantitatively absorbs the sample through the sampling device, and the sample is stored in the second quantitative module;
b) The second multi-way valve disconnects the second quantitative module and the sampling device, the second multi-way valve connects the second quantitative module and the flow chamber, and the second quantitative module pushes the sample to the flow chamber;
c) The second multi-way valve disconnects the second quantification module and the sampling device, the second multi-way valve connects the second quantification module and the flow chamber, the sheath fluid providing module pushes the sheath fluid into the flow chamber, and the fluorescence detector detects the concentration of the analyte in the sample from the second quantification module on the flow chamber;
d) The second multi-way valve disconnects the second quantitative module and the flow chamber, the second multi-way valve connects the second quantitative module and the sampling device, and the second quantitative module sucks the sheath liquid through the sheath liquid supply module and cleans the second quantitative module and the sampling device through the sheath liquid.
In the detection method, the detection process using the first quantitative module and the detection process using the second quantitative module are executed simultaneously, so that the liquid path system can detect two/kinds of samples simultaneously, and the detection efficiency is greatly improved.
Since the first quantitative module and the second quantitative module share the sheath fluid supply module, the flow chamber and the sampling device, in order to avoid the problem of contamination between samples, the first quantitative module and the second quantitative module are required to alternately use the sheath fluid supply module, the flow chamber and the sampling device.
To this end, in a specific embodiment, the detection method further includes:
if first ration module when with sample propelling movement to mobile room, the sheath liquid is provided the module through the sheath liquid to second ration module and absorbs sheath liquid and washs first ration module and sampling device through the sheath liquid. At this time, when the first quantitative module solely uses the flow chamber, the second quantitative module solely uses the sheath fluid supply module and the sampling device.
Similarly, if the second quantitative module pushes the sample to the flow chamber, the first quantitative module absorbs the sheath liquid through the sheath liquid providing module and cleans the first quantitative module and the sampling device through the sheath liquid. At this time, when the second quantitative module uses the flow chamber alone, the first quantitative module uses the sheath fluid supply module and the sampling device alone.
In a specific embodiment, the detection method further includes:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber, the second quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid. At this time, when the first quantitative module uses the flow chamber alone, the second quantitative module uses the sheath fluid supply module and the sampling device.
Similarly, if the fluorescence detector detects the analyte concentration in the sample from the second quantitative module on the flow chamber, the first quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid. At this time, when the second quantitative module solely uses the flow chamber, the first quantitative module uses the sheath fluid supply module and the sampling device.
In addition, the efficiency of the detection process using the first quantitative module and the efficiency of the detection process using the second quantitative module are improved. In a specific embodiment, the detection method further includes:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber, the first quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid.
Further, if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module on the flow chamber, the first quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the first quantitative module and the sampling device through the sheath fluid, and the second quantitative module absorbs the sheath fluid through the sheath fluid providing module and cleans the second quantitative module and the sampling device through the sheath fluid.
Similarly, in a specific embodiment, the detection method further includes:
and if the fluorescence detector detects the concentration of the analyte in the sample from the second quantitative module on the flow chamber, the second quantitative module absorbs the sheath fluid through the sheath fluid supply module and cleans the second quantitative module and the sampling device through the sheath fluid.
Further, if the fluorescence detector detects the concentration of the analyte in the sample from the second quantitative module on the flow chamber, the second quantitative module sucks the sheath fluid through the sheath fluid supply module and cleans the second quantitative module and the sampling device through the sheath fluid, and the first quantitative module sucks the sheath fluid through the sheath fluid supply module and cleans the first quantitative module and the sampling device through the sheath fluid.
In summary, in order to more clearly understand the beneficial effects of the above-mentioned detection method, the following describes in detail the procedure of detecting the analyte concentration in the sample by the detection method:
step1: placing the sampling device into a test tube filled with a sample, switching a first multi-way valve to conduct the sampling device and a first quantitative module, and sucking the sample by the first quantitative module through the sampling device for a second;
step2: the first multi-way valve is switched to conduct a first quantitative module and a flow chamber, the second multi-way valve is switched to conduct a sampling device and a second quantitative module, the first quantitative module pushes a sample, the sample pushing time of the first quantitative module is b seconds, a sheath liquid providing module provides sheath liquid into the flow chamber, the sheath liquid providing time is c seconds, a sample flow wrapped by the sheath liquid is formed in the flow chamber, a fluorescence detector detects the sample flow wrapped by the sheath liquid, the second quantitative module sucks the sheath liquid through the sheath liquid providing module to clean the second quantitative module and the sampling device, the time for cleaning the second quantitative module and the sampling device by the sheath liquid is d seconds, the sampling device is placed into another test tube filled with the sample, the second quantitative module sucks the sample through the sampling device, the sample sucking time of the second quantitative module is e seconds, c is larger than b, the sheath liquid can flush the flow chamber after the fluorescence detection is finished, the flow chamber can be used subsequently, and c is not smaller than the sum of d and e, so that the second quantitative module can push the sample immediately after the flow chamber is cleaned;
step3: the second multi-way valve is switched to be communicated with the second quantitative module and the flow chamber, the fourth cut-off valve is switched to be communicated with the sheath liquid providing module and the first quantitative module, the second quantitative module pushes samples, the sample pushing time of the second quantitative module is f seconds, the sheath liquid providing module provides sheath liquid into the flow chamber, the sheath liquid providing time is g seconds, a sample flow wrapped by the sheath liquid is formed in the flow chamber, the fluorescence detector performs fluorescence detection on the sample flow wrapped by the sheath liquid, the first quantitative module sucks the sheath liquid through the sheath liquid providing module to clean the first quantitative module and the sampling device, the time for cleaning the first quantitative module and the sampling device by the sheath liquid is h seconds, g is larger than f, and g is not smaller than the sum of h and a.
Therefore, the steps 1 to 3 can be iterated to alternately detect a plurality of groups of samples, so that the detection efficiency of the plurality of groups of samples is greatly improved.
The invention shown and described herein may be practiced in the absence of any element or elements, limitation or limitations, which is specifically disclosed herein. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, and it is recognized that various modifications are possible within the scope of the invention. It should therefore be understood that although the present invention has been specifically disclosed by various embodiments and optional features, modification and variation of the concepts herein described may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
The contents of the articles, patents, patent applications, and all other documents, and any electronic information mentioned or cited herein, which is useful in the present application, are incorporated by reference as if fully set forth herein, and for any portion of this disclosure, are specifically set forth. The applicants reserve the right to incorporate into this application any and all information and material from such articles, patents, patent applications, or other documents as part of the disclosure of this patent specification.

Claims (10)

1. A flow-through fluorescence detection fluid path system, comprising:
a flow cell (4) comprising a sample inlet (41), a sheath fluid inlet (42), and a waste fluid outlet (43); a sheath fluid supply module (3) for supplying a sheath fluid to the sheath fluid inlet (42), the first dosing module (5) and the second dosing module (6);
a sampling device (2) for providing a sample to a first dosing module (5) and a second dosing module (6);
the first quantitative module (5) is used for sucking and cleaning the sheath liquid of the first quantitative module (5) and the sampling device (2) through the sheath liquid providing module (3) and is also used for sucking a sample quantitatively through the sampling device (2);
the second quantitative module (6) is used for sucking and cleaning the sheath liquid of the second quantitative module (6) and the sampling device (2) through the sheath liquid providing module (3) and is also used for sucking the sample quantitatively through the sampling device (2);
the sheath liquid providing module (3) is connected to the sheath liquid inlet (42), the first quantitative module (5) and the second quantitative module (6) through the first valve group;
and the second valve group is used for connecting the first quantitative module (5) to the sample inlet (41) and the sampling device (2), and the second quantitative module (6) is connected to the sample inlet (41) and the sampling device (2).
2. A flow-type fluorescence detection fluid path system according to claim 1, wherein the first valve set comprises a third shut-off valve (9), the sheath fluid providing module (3) is connected to the first dosing module (5) through the third shut-off valve (9), the first valve set comprises a fourth shut-off valve (10), and the sheath fluid providing module (3) is connected to the second dosing module (6) through the fourth shut-off valve (10).
3. A flow-through fluorescence detection fluid circuit system according to claim 1, wherein the second valve set comprises a first multiplex valve (7), and the first quantitative module (5) is connected to the sample inlet (41) and the sampling device (2) via the first multiplex valve (7).
4. A flow-through fluorescence detection fluid circuit system according to claim 1 or 3, wherein the second valve set comprises a second multiplex valve (8), and the second quantification means (6) is connected to the sample inlet (41) and the sampling device (2) via the second multiplex valve (8).
5. A flow-type fluorescence detection fluid circuit system according to claim 1, wherein the first quantitative module (5) comprises two first flow ports (51), the first valve set and the second valve set are respectively connected to the two first flow ports (51), the second quantitative module (6) comprises two second flow ports (61), and the first valve set and the second valve set are respectively connected to the two second flow ports (61).
6. A flow-type fluorescence detection fluid path system according to claim 1, further comprising a waste liquid collector and a sixth shut-off valve (12), wherein the waste liquid collector is connected to the waste liquid outlet (43) through the sixth shut-off valve (12).
7. A detection method of a flow-type fluorescence detection fluid path system, characterized in that the fluid path system of any one of claim 1 to claim 6 is adopted, and the method comprises:
detection procedure using a first quantification module (5): the first quantitative module (5) quantitatively absorbs a sample through the sampling device (2), the first quantitative module (5) pushes the sample to the flow chamber (4), the fluorescence detector detects the concentration of an analyte in the sample from the first quantitative module (5) on the flow chamber (4), and the first quantitative module (5) absorbs sheath liquid through the sheath liquid providing module (3) and cleans the first quantitative module (5) and the sampling device (2) through the sheath liquid;
detection procedure using a second quantification module (6): the second quantitative module (6) sucks a sample quantitatively through the sampling device (2), the second quantitative module (6) pushes the sample to the flow chamber (4), the fluorescence detector detects the concentration of an analyte in the sample from the second quantitative module (6) on the flow chamber (4), and the second quantitative module (6) sucks sheath liquid through the sheath liquid providing module (3) and cleans the second quantitative module (6) and the sampling device (2) through the sheath liquid;
the detection process of the first quantitative module (5) and the detection process of the second quantitative module (6) are executed simultaneously, and if the first quantitative module (5) pushes the sample to the flow chamber (4), the second quantitative module (6) sucks the sheath fluid through the sheath fluid providing module (3) and cleans the first quantitative module (5) and the sampling device (2) through the sheath fluid.
8. The detection method according to claim 7, further comprising:
if second ration module (6) when with sample propelling movement to flow room (4), first ration module (5) provide module (3) through the sheath liquid and absorb sheath liquid and wash first ration module (5) and sampling device (2) through the sheath liquid.
9. The detection method according to claim 7, further comprising:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module (5) on the flow chamber (4), the second quantitative module (6) sucks the sheath fluid through the sheath fluid providing module (3) and cleans the first quantitative module (5) and the sampling device (2) through the sheath fluid.
10. A detection method using a flow-type fluorescence detection fluid circuit system according to any one of claims 7 to 9, further comprising:
if the fluorescence detector detects the concentration of the analyte in the sample from the first quantitative module (5) on the flow chamber (4), the first quantitative module (5) sucks the sheath fluid through the sheath fluid providing module (3) and cleans the first quantitative module (5) and the sampling device (2) through the sheath fluid.
CN202211527387.7A 2022-11-30 2022-11-30 Flow type fluorescence detection liquid path system Pending CN115824965A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211527387.7A CN115824965A (en) 2022-11-30 2022-11-30 Flow type fluorescence detection liquid path system

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211527387.7A CN115824965A (en) 2022-11-30 2022-11-30 Flow type fluorescence detection liquid path system

Publications (1)

Publication Number Publication Date
CN115824965A true CN115824965A (en) 2023-03-21

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Country Status (1)

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