CN214427286U - Liquid transfer device for electrochemical luminescence detection equipment - Google Patents

Liquid transfer device for electrochemical luminescence detection equipment Download PDF

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CN214427286U
CN214427286U CN202120279844.XU CN202120279844U CN214427286U CN 214427286 U CN214427286 U CN 214427286U CN 202120279844 U CN202120279844 U CN 202120279844U CN 214427286 U CN214427286 U CN 214427286U
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detection
pipette
reagent
pipetting device
magnetic
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杨志伟
刘铮
胡春苗
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Suzhou Yilai Biotechnology Co ltd
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Suzhou Yilai Biotechnology Co ltd
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Abstract

The application discloses move liquid device for electrochemiluminescence detection equipment, this move liquid device includes: a longitudinal mobile seat mounted to the support longitudinally translatably; and the vertical moving seat can be vertically arranged on the longitudinal moving seat in a vertically up-and-down moving mode and is provided with at least one liquid transferring device pointing downwards to the pretreatment device.

Description

Liquid transfer device for electrochemical luminescence detection equipment
Technical Field
The application relates to the field of test detection, in particular to a liquid transfer device for an electrochemiluminescence detection device.
Background
Electrochemical-luminescence (ECL) detection technology has been widely used in detection work in various technical fields such as biology, medicine, pharmacy, clinic, environment, food, immunity, nucleic acid hybridization analysis and industrial analysis. Moreover, the current immunoassay system based on the electrochemical luminescence detection technology has a relatively mature product. For example, WO 2017/129803 a1 discloses an electrochemiluminescence method and apparatus for detecting an analyte in a liquid sample. However, the conventional ECL detection device has the defects of complex structure, high cost, influence on detection accuracy due to repeated cleaning and the like in practical application. Particularly, in the conventional scheme, various reagents are sequentially injected into the reaction chamber according to a program, so that liquid feeding and discharging are complicated and pollution among the reagents is easily caused.
In order to solve the above drawbacks at least to a certain extent, the applicant of the present application has previously proposed a solution: CN 111198181 a, which is a solution more around the improvement of the detection method, and in this application, more around the specific structure of the ECL detection device and its operation process, more specific improvements are proposed compared with the above-mentioned prior application, so as to make the ECL suitable for a wider application scenario, such as emergency department, treatment department, food safety, inspection and quarantine, etc., which is a technical problem to be solved in the field.
SUMMERY OF THE UTILITY MODEL
In view of the above, the present application proposes a solution for electrochemiluminescence detection, which can improve the efficiency of reagent transfer and reduce the mutual contamination of reagents, at least to some extent.
According to the present application, there is provided a pipetting device for an electrochemiluminescence detection apparatus, the pipetting device comprising: a longitudinal mobile seat mounted to the support longitudinally translatably; and the vertical moving seat can be vertically arranged on the longitudinal moving seat in a vertically up-and-down moving mode and is provided with at least one liquid transferring device pointing downwards to the pretreatment device.
Preferably, the pipetting device has a plurality of pipettes, and each pipette corresponds in the longitudinal direction to a respective reagent container or reagent buffer.
Preferably, the plurality of pipettes are arranged spaced apart from each other in the lateral direction to reciprocate in the vertical direction simultaneously or independently of each other.
Preferably, the pipette is connected with an actuating device to cause the pipette to aspirate liquid into the pipette or to discharge liquid in the pipette to the outside.
Preferably, the actuation means is pneumatic.
Preferably, a permanent magnet is provided on the holder, the permanent magnet being arranged adjacent to the pipette.
Preferably, the pipetting device comprises an auxiliary longitudinal moving seat which is positioned below the longitudinal moving seat and adjacent to the pipettor, and the permanent magnet is fixedly arranged on the auxiliary longitudinal moving seat.
Preferably, the auxiliary longitudinal moving seat has a working position approaching the pipette forward and a retreating position away from the pipette backward, in the working position, the permanent magnet is adjacent to or attached to the pipette, and in the retreating position, the permanent magnet is away from the pipette.
Preferably, the auxiliary longitudinal moving seat is provided with a plurality of through grooves which are open towards the front and extend in the vertical direction, and each through groove is provided with the permanent magnet.
Preferably, each channel has a shape that matches a corresponding pipette.
According to the technical scheme of this application, move liquid device and be used for drawing the liquid sample that awaits measuring to each reagent container in from the sample vessel to move the liquid in the reagent holding chamber 161 of each reagent container in proper order, thereby promote feed liquor and flowing back efficiency and reduce the degree of reagent pollution.
Additional features and advantages of the present application will be described in detail in the detailed description which follows.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate an embodiment of the invention and, together with the description, serve to explain the invention. In the drawings:
fig. 1 is a perspective view of an electrochemiluminescence detection apparatus according to a preferred embodiment of the present application, viewed (partially) from an oblique front side, wherein a part of a cover member or the like is omitted.
Fig. 2 is a schematic perspective view of an electrochemiluminescence detection apparatus according to a preferred embodiment of the present application, viewed (partially) from an oblique rear side.
FIG. 3 is a schematic view showing the structure of a detecting unit in an electrochemiluminescence detecting apparatus according to a preferred embodiment of the present application.
FIG. 4 is a schematic diagram of the arrangement of the buffer, the pretreatment device and the detection device in the electrochemiluminescence detection apparatus according to the preferred embodiment of the present application.
Fig. 5, 8 and 11 are exploded schematic views of the arrangement shown in fig. 4.
Fig. 6 and 7 are perspective views of the pretreatment device.
Fig. 9 and 10 are perspective views of a reagent vessel according to a preferred embodiment of the present application.
FIG. 12 is a partially schematic view of a pipetting device in an electrochemiluminescence detection apparatus according to a preferred embodiment of the present application.
Fig. 13 to 15 are schematic views of the condition that the pipetting device is at different positions relative to the temporary storage device and the pretreatment device in the electrochemiluminescence apparatus according to the preferred embodiment of the present application.
FIG. 16 is a schematic view showing the arrangement of a detecting means in an electrochemiluminescence apparatus according to a preferred embodiment of the present application.
Fig. 17 is a partially enlarged schematic view of the detecting device in fig. 16.
Detailed Description
The technical solutions of the present application will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
As mentioned above, the present application is an improvement proposed by the applicant on CN 111198181 a, which is more about the specific structure of the ECL detection apparatus and the operation process thereof, and particularly, the present application performs specific structural design, such as modularization, on each component of the electrochemiluminescence detection apparatus, so that each component can also constitute an independent product theme, and the applicant performs patent layout about different themes in order to fully protect the innovation scheme. The technical contents disclosed in the prior application can be referred or referred to on the basis of the detection method. All the technical solutions of the previous applications can therefore be incorporated into the present application, while also naturally being able to achieve and obtain all the technical advantages and effects described in the previous applications.
For example, in the technical solution of the present application, a process of preparing a detected target complex sample (in the detected target complex sample, a complex including a label, a detected target or a control thereof, and magnetic particles) by a pretreatment device using a liquid sample to be detected is isolated from a detection step of performing electrochemiluminescence detection after mixing a luminescent agent and the detected target complex sample in a detection cell, and is not performed in the same working vessel or working space. Therefore, the problem of cross contamination in the conventional scheme can be avoided, and the requirements and difficulty for flushing and/or cleaning are greatly reduced.
The technical scheme of the application is also applicable to the detection field of various biochemical projects, including but not limited to: thyroid function detection, anemia detection, hormone detection, down's screening detection at the early stage of pregnancy, detection of various tumor markers, detection of cardiac markers, bone markers, detection of markers of various infectious diseases, autoimmune detection and the like. For example, the detected target may be, but is not limited to: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, hepatitis B core antibody, hepatitis C antibody, AIDS virus antibody, syphilis serum specific antibody, cardiac troponin, c-reactive protein, N-terminal brain natriuretic peptide precursor, procalcitonin, etc. Thus, depending on the assay situation, the sample processing can be performed by using a sandwich method, a competition method or a bridging method, using a pre-processing device and a pipetting device, so as to obtain a corresponding complex sample of the target complex to be detected, which may include a complex of the label, the target to be detected (e.g., in the sandwich method) or a control thereof (e.g., in the competition method), and the magnetic particles. The magnetic particles can be magnetic iron oxide particles with the particle size of 100nm-50um, and can be coated with streptavidin. The target substance may be a product obtained by modifying the target substance, for example, the target substance is free thyroxine (FT4), and the control substance may be obtained by modifying one amine group of the target substance with biotin.
In the technical scheme of the present application, the pretreatment device and the pipetting device can physically separate the sample treatment process and the detection during the electrochemical luminescence from each other (the "physical separation" means that the tool, vessel, area or space for performing the sample treatment step and the tool, vessel, area or space for performing the detection step (especially, the detection cell) are different and are separated from each other to avoid mutual interference), so the technical scheme of the present application can realize a step-by-step ECL detection mode, rather than an integrated ECL detection mode in which the sample liquid continuously flows into the reaction cell or the detection cell in the conventional ECL detection scheme.
In the technical solution of the present application, a specific implementation manner is proposed in the aspect of the structure of the detection device, and the improvements include but are not limited to: the arrangement mode of the electrode component, the arrangement mode of the magnetic component, the relation between the magnetic field and the electric field, the encapsulation and temperature control of the reagent, the structure of the pipetting device and the like. This will be explained in detail below. These improvement points can be protected as independent technical solutions.
Detection equipment for electrochemiluminescence
According to an aspect of the present application, there is provided a detection apparatus for electrochemiluminescence, the detection apparatus comprising: a rack, a buffer device 12, a pretreatment device 13, a pipetting device 14 and a detection device 15, as shown in fig. 1 to 3.
The frame forms the basic part of the whole detection equipment and provides a mounting base for other devices, components or structures. As shown in fig. 1, the housing may be divided to include a base 10 and a support 11 provided on the base 10. The term "disposed" in this application may be taken to mean either a direct or indirect arrangement, either a fixed arrangement or a movable arrangement. The base 10 is generally a bottom portion of the housing and the support 11 is generally an upper portion extending from the base 10, both of which may provide a mounting base for other devices, components or structures, and the base 10 and/or the support 11 may be selected as the mounting base according to specific operating requirements during design and manufacture.
The buffer device 12 is arranged on the machine frame, for example on the base 10, and may be arranged fixedly or also movably. The buffer device 12 has a sample buffer 101 for removably arranging a sample container containing a liquid sample to be tested. The buffer is usually arranged in front of the entire inspection apparatus, in particular the base 10, so that the direction from the buffer to the inspection apparatus is defined as the direction from front to back. It should be noted that the terms of orientation such as front-back, left-right, up-down, longitudinal, transverse and the like in the description of the present application are only used for convenience of description of the relative positional relationship between the devices or components, and do not limit the scope of protection of the present application.
The preprocessing unit 13 is located at the rear side of the buffer unit 12 and is preferably mounted on the base 10 of the rack so as to be longitudinally movable back and forth. The pre-treatment device comprises a reagent container arrangement 102 for removably arranging at least one reagent container. The liquid sample to be detected and each reagent in the reagent container are reacted and/or cleaned by utilizing the liquid-transfering device and the pretreatment device which are described below to work together, so that the detected target compound combined with the magnetic particles can be finally obtained by utilizing the liquid sample to be detected.
A pipetting device 14 is fixedly or movably arranged on the support 11 of the frame and above the pretreatment device 13, as shown in fig. 1, 2 and 9, the pipetting device and the pretreatment device have a degree of freedom of relative horizontal movement back and forth along the longitudinal direction, and the pipetting device is provided with a pipettor (not shown) which can move up and down and is used for sucking and discharging liquid, and the pipettor is matched with the pretreatment device to work for obtaining the detected target compound body combined with the magnetic particles by using the liquid sample to be detected.
The detection device 15 is located on the rear side of the pipetting device 14 and comprises a detection cell 151, an optical detector 152, an electrode assembly 153 and a magnetic assembly 154. The detection cell is used for accommodating the detected target compound combined with the magnetic particles; the electrode assembly 153 provides a direct current electric field for the detection cell; the magnetic assembly 154 is used to provide a magnetic field for the detection cell to hold the detected target complex bound with magnetic particles; the optical detector 152 is used for performing optical detection under photochemical reaction to obtain required data information.
The above description is the basic configuration of the detection apparatus or detection instrument for photochemical emission according to the present application and the basic operation thereof. It can be understood that, in the technical scheme of the application, the pretreatment process and the luminescence detection process of the liquid sample to be detected are separated from each other, so that the requirements and the difficulty of detection precision on flushing and/or cleaning can be greatly reduced. On the basis, the technical scheme of the application also particularly recognizes the correlation between the electric field and the magnetic field in the detection device, and further structurally provides a further improvement scheme. This and other specific improvements will be described in detail below.
First, look at the buffer.
Temporary storage device
The buffer device 12 can have various configurations, for example, in the form of a test tube holder, or can be formed as a module arranged in a fixed manner in front of the base, as shown in fig. 1 and 4, on which a plurality of sample buffers 101 can be arranged. By designing the device under test as modular, interchangeability can be provided to reduce maintenance and repair costs.
Thus, a liquid sample to be tested may be placed in a sample container (e.g., a test tube) after sampling thereof is completed. Before the detection equipment of the application is used for carrying out electrochemiluminescence detection, the sample container is arranged at the sample temporary storage part of the temporary storage device, and then the sample is extracted by other devices to carry out the detection process. After the test is completed, the sample container may be removed and replaced with another sample container. The sample container can be written with relevant information in various forms, such as patient information, and the like, and can adopt a form of a common two-dimensional code.
The sample buffer portion 101 of the buffer device 12 may be one or more, which may be designed according to specific application conditions. When there are a plurality of sample buffers, the sample buffers are preferably arranged laterally left and right so as to be able to process a plurality of different liquid samples to be tested simultaneously or process a plurality of different liquid samples to be tested separately. Preferably, as shown in fig. 4, the plurality of sample buffers are formed as a plurality of recesses 104 arranged in a transverse direction.
Third, pretreatment device
In the pretreatment device, the liquid sample pretreatment device and the liquid transfer device work together to realize sample treatment of the liquid sample to be detected, so that the detected target compound sample is obtained by a sandwich method or a competition method.
In the present application, the liquid sample to be tested includes various biological samples, such as various tissue treatment or body fluids obtainable from the human or other animal body, in particular blood, serum, plasma, urine, saliva, sweat, semen, milk, cerebrospinal fluid or any derivatives thereof.
According to one embodiment, obtaining the sample of the detected target complex using a sandwich method during the sample processing comprises: mixing: mixing the liquid sample to be detected with a first reagent with a luminescent marker, a second reagent with a magnetic marker capable of being combined with magnetic particles and a third reagent with magnetic particles to obtain a detected target compound sample, wherein the detected target compound sample is provided with a sandwich type compound body comprising the luminescent marker, the detected target and the magnetic marker combined with the magnetic particles; and a cleaning step: and under the condition of applying a magnetic field, washing away impurities which are not combined with the magnetic particles in the detected target compound sample by using a washing agent.
The sample of the target complex to be tested obtained in this way forms a so-called "sandwich. The target substance (such as antigen) to be detected is combined with the luminescent label and the magnetic particle (or magnetic bead) by means of specific combination with the double antibody. In the subsequent detection process, the complex body combined with the magnetic particles can be captured by using a magnetic field, and then impurities which are not combined with the magnetic particles in the detected target compound sample are washed away by using a washing agent, so that the complex body combined with the magnetic particles is reserved. In order to achieve this, in the solution of the present application, an improved solution is proposed with respect to the arrangement and design of the magnetic field, which will be explained below. Furthermore, detection of electrochemiluminescence may be achieved using luminescent labels in a subsequent detection step.
The above-described manner of obtaining a complex by the sandwich method is generally applicable to a case where a target to be detected has a plurality of binding sites, for example, an antigen having two or more binding sites.
According to another embodiment, obtaining the sample of the detected target complex by a competition method during the sample processing comprises: mixing: mixing the liquid sample to be detected with a first reagent with a luminescent marker and a second reagent with a magnetic marker capable of being combined with magnetic particles, and then mixing with a third reagent with magnetic particles to obtain a detected target compound sample, wherein the detected target compound sample is provided with an immune complex comprising the luminescent marker, a detected target control substance and the magnetic marker combined with the magnetic particles; and a cleaning step: and under the condition of applying a magnetic field, washing away impurities which are not combined with the magnetic particles in the detected target compound sample by using a washing agent.
In the mixing step, the detected target in the liquid sample to be detected and the detected target control substance combined with the magnetic label in the second reagent are combined with the luminescent label in the first reagent in a competitive manner, and then combined with the magnetic particles (coated with streptavidin for example) in the third reagent, so as to form a detected target complex sample. However, unlike the sandwich method, an immune complex including a luminescent label, a detection target control substance, and a magnetic label bound to a magnetic particle is present in the detection target complex sample. Similarly, the target compound sample to be detected may be washed away impurities that do not bind to the magnetic particles with a washing agent under the application of a magnetic field, thereby retaining the immunocomplexes of the magnetic labels bound to the magnetic particles. Furthermore, detection of electrochemiluminescence may be achieved using luminescent labels in a subsequent detection step. In this embodiment, the level of the parameter of the target substance to be detected in the sample is indirectly reflected by the level of the parameter of the control substance to be detected.
In the mixing process, preferably, the mixing step further comprises a heat preservation standing process after mixing, wherein in the heat preservation standing process, the temperature range is 0-50 ℃, preferably 20-40 ℃, and more preferably 35-38 ℃, and the standing duration is 0-30 minutes. However, the technical scheme of the application is not limited to this, and different parameter ranges such as temperature and time can be selected according to different detection conditions. By selecting the above temperature and/or time, the reaction can be allowed to proceed sufficiently to allow the complex or immune complex to be prepared more sufficiently. In order to control the temperature, the present invention proposes a modification of the pretreatment device 13 in which a temperature control device for bringing the reagent container stored in the reagent container arrangement unit 102 into a predetermined temperature range is provided. This will be explained below.
Preferably, the washing step is carried out at least once, preferably 3 to 5 times, in order to achieve a good washing result, so as not to cause unacceptable interference with the detection result. In the washing step, the washing solution used may be, for example, PBS buffer, NaHCO buffer, Tris buffer, borate buffer, TEAA buffer, or the like. The cleaning solution may be contained in the reagent container in advance as a part of the reagent.
The sample processing steps are described in detail above. After obtaining the sample of the detected target compound, the sample is transferred to a detection pool of a detection device for detection. The pretreatment device for the above-described electrochemiluminescence detection is described in detail below. As shown in fig. 4, 5 to 7, the pretreatment device for electrochemiluminescence detection includes a pretreatment device body 131, and at least one reagent vessel arranging part 102 for removably arranging a reagent vessel 16 containing a reagent is provided on the pretreatment device body 131.
The pretreatment device body 131 constitutes a basic configuration of the pretreatment device, and has a different structure and a different selection manner, for example, the pretreatment device body 131 may be a rectangular parallelepiped as a whole, or may be another disc-shaped, etc., and the reagent container arrangement portion 102 may have a recessed hole structure which is independent from or adjacently communicated with each other, so as to temporarily arrange the reagent containers on the reagent container arrangement portion 102, and after completion of the operation, remove the reagent containers from the reagent container arrangement portion 102, thereby replacing other reagent containers.
In addition, different reagent containers may be used in combination with different reagent container arrangement portions 102, which may be selected according to different application conditions. For example, the reagent container arrangement portion 102 may be one, or may be plural as shown in fig. 6 and 7, and the plural reagent container arrangement portions extend longitudinally in parallel with each other and each is formed with plural concave holes 105 arranged longitudinally, and each corresponds to a respective sample buffer portion in the longitudinal direction. In the embodiment shown in fig. 6 and 7, one channel is formed per reagent container arrangement part 102, and therefore a plurality of reagent container arrangement parts are formed as reagent processing mechanisms of a plurality of channels, each of which can perform individual processing of a reagent, respectively, and also can perform a large number of reagent processing operations in synchronization.
As described above, in order to ensure the progress of each reaction process in the reagent processing process, it is preferable that the pretreatment device body 131 is provided with a temperature control device for bringing the reagent vessel disposed in the reagent vessel disposition part 102 into a suitable temperature range. The temperature control device can keep the temperature of the reagent container disposed on the reagent container disposing part of the pretreatment device body 131 within a suitable temperature range, can keep the temperature lower than room temperature, can keep the temperature higher than room temperature as required, and can keep the temperature within a predetermined range within a predetermined time range.
The temperature control device preferably includes a temperature sensor, a heater, and a controller. The temperature sensor is disposed on the pretreatment device body 131 for sensing the temperature of the reagent vessel disposition part 102. The heater is disposed on the pretreatment device body 131 and at a position away from the temperature sensor, and heats the reagent container disposing part 102. The controller is connected with the temperature sensor and the heater and is used for sending a control signal for heating or not heating to the heater according to the temperature value of the reagent container arrangement part sensed by the temperature sensor.
Therefore, when the temperature sensor senses that the temperature of the reagent vessel arrangement portion 102 is lower than a predetermined value, the controller controls the heater to start heating up until the temperature of the reagent vessel arrangement portion 102 is within a predetermined range. In this way, the temperature of the reagent vessel arrangement 102 can be maintained within a suitable temperature range, thereby facilitating the progress of the relevant reactions during the mixing and washing processes.
The temperature sensor may be a conventional temperature sensor, such as a patch temperature sensor. According to different temperature sensors, the temperature sensors can be arranged at different positions on the pretreatment device body 131, and preferably, as shown in fig. 6, at least one hole structure 132 is arranged on the pretreatment device body 131, and the temperature sensors are detachably arranged in the hole structure 132, so that the temperature sensors are deeply arranged inside the pretreatment device body 131 to obtain more accurate temperature data. The well structure 132 preferably extends in a lateral direction so as to open into each reagent container arrangement 102 to enable detection of the temperature at each reagent container arrangement 102.
The heater may be in the form of an electric heating plate, a heating fluid, or the like, and for example, a heating plate (not shown) may be provided as the heater on the bottom side of the pretreatment device body 131. The controller can be a single chip microcomputer, an industrial personal computer, a control chip and other different controllers with built-in temperature control programs. Preferably, the plurality of heaters are provided for heating the respective reagent container arrangement parts, or the plurality of heaters are provided for heating the respective concave holes 105 of the respective reagent container arrangement parts.
As shown in fig. 6 and 7, the pretreatment device body 131 is a single modular member in which a plurality of reagent container arrangement parts are integrated, but the present application is not limited thereto, and the pretreatment device body 131 may be an assembly in which a plurality of reagent container arrangement parts are detachably joined.
As described above, the reagent vessel 16 is removably disposed on the reagent vessel disposition portion of the pretreatment device (as shown in fig. 9 and 10), and a pipetting device may be disposed above and a detection device disposed on the rear side. These subjects will be described in detail one by one hereinafter. In a preferred embodiment, as shown in fig. 6 and 7, a base plate 121 is integrally disposed or mounted on the rear side of the pretreatment device body 131, and the base plate 121 provides a mounting base for the detection device. This will be described in detail below in connection with the detection device. The reagent vessel will be explained first.
Fourth, reagent container
The present application also provides a reagent container 16 for use with the pretreatment device described above. The reagent vessels 16 can have different configurations, for example, the reagent vessels 16 can be individual test tube pieces, but preferably, the reagent vessels 16 can be designed with a plurality of longitudinally arranged receiving chambers 161. Thus, a plurality of reagent containers 16 of different reagents may be provided simultaneously for one liquid sample to be tested.
The preferred reagent container provided by the present application is described with emphasis in conjunction with fig. 9 and 10.
As shown in FIGS. 9 and 10, a reagent vessel 16 according to a preferred embodiment of the present invention may be used in the above-described electrochemiluminescence detection apparatus provided herein, particularly in cooperation with a pretreatment device. The reagent contained in each containing cavity 161 of the reagent container 16 may be different according to the liquid sample to be tested and the target object thereof, and the design may be selected according to the specific application.
As shown in fig. 9, the reagent vessel 16 includes a reagent vessel body 160 having an upper surface 162, the reagent vessel body 160 extending in a longitudinal direction and having a plurality of reagent accommodating chambers 161 arranged in the longitudinal direction, each of the reagent accommodating chambers 161 being formed with an opening portion 163 in the upper surface 162.
The reagent vessel body 160 may be made of a suitable material, and may typically be integrally made of a plastic material and meet the relevant hygienic or aseptic requirements. Each reagent holding chamber 161 is formed with a respective opening 163 in the upper surface 162 to allow a corresponding reagent to be placed into or removed from the reagent holding chamber 161.
The upper surface 162 may have various forms, for example, it may be designed with a step structure having unevenness, but is preferably designed as a plane extending horizontally to facilitate integral injection molding. The opening 163 may be open to the outside atmosphere, for example, in a biological laboratory condition in a clean environment; however, when the operation is performed in an environment where clean conditions are not ideal, it is preferable that a membrane member enclosing at least one opening 163 of the reagent holding chamber 161 is provided on the upper surface 162, so that the reagent can be previously enclosed in the reagent holding chamber 161 where it is located to provide a protective effect. When the reagent holding chamber has a plurality of reagent holding chambers, the opening of one or more of the reagent holding chambers may be selectively sealed, or the openings of all the reagent holding chambers may be sealed.
The membrane may be a plastic film to facilitate packaging and facilitate puncturing and penetration of a pipette (described below) into the reagent holding chamber. The membrane may be plural, each enclosing an opening portion of a respective reagent holding chamber; but preferably, the membrane-like member is one, which is disposed on the upper surface 162 while enclosing the opening portions of the plurality of reagent holding chambers.
As shown in fig. 9 and 10, the reagent container body 160 includes: a top plate 164 and a connecting plate 165, the top plate 164 being formed with the upper surface 162, the reagent holding chamber 161 being located on the lower side of the top plate 164; the connecting plate 165 is fixedly disposed under the top plate 164 and connected between the reagent holding chambers 161. Through the design of the top plate 164 and the connecting plate 165, a plurality of reagent holding chambers 161 can be integrated together, while obtaining relatively good overall structural strength. The top plate 164 and the connecting plate 165 may have various relative positional relationships therebetween, such as a parallel arrangement, etc., but preferably, as shown in fig. 9, the top plate 164 extends horizontally in the longitudinal direction and the connecting plate 165 extends vertically in the longitudinal direction. Therefore, on the one hand, the integral injection molding manufacturing is facilitated, and on the other hand, the connecting plate 165 is utilized to play a role in positioning.
Preferably, a stopper structure is provided on the lower side of the top plate 164 adjacent to the reagent holding chamber 161. The limiting structure may include the connecting plate 165, or other structures may be used as the limiting structure. By providing the limiting structure, after the reagent container 16 is arranged on the pretreatment device, the reagent container can be ensured to be positioned at an accurate and reliable position relative to the pretreatment device, so as to be beneficial to subsequent operations. For example, the above-described limiting structure may limit the freedom of the reagent container to translate back and forth in the longitudinal direction, for which purpose at least one limiting plate 166 extending downwardly from the top plate 164 and arranged laterally is preferably provided; furthermore, the freedom in the transverse direction can be limited by the cooperation of the web 165 with the longitudinal grooves on the pretreatment device. Therefore, the above-mentioned position-limiting structure can preferably play the role of position limitation and positioning at the same time, as shown in fig. 10.
As shown in fig. 10, a schematic view of a single reagent container, but it will be appreciated that in other embodiments, the single reagent containers shown in fig. 10 may be combined into a reagent container assembly. This can be selected and applied according to different working condition application occasions. Alternatively, it is preferable that a plurality of reagent containers shown in fig. 10 are combined with each other into a single member, and each reagent holding chamber 161 of the single member or the above-described reagent container assembly corresponds one-to-one to each concave hole 105 of the reagent container arrangement portion of the pretreatment apparatus.
The structure of the reagent vessel and its cooperation with the pretreatment apparatus are described in detail above. The pipetting device is described below with emphasis.
Liquid transfer device
The pipetting device 14 is used for taking a liquid sample to be tested from the sample container arranged on the buffer device into each reagent container of the reagent container arrangement part 102 of the reagent container arranged on the pretreatment device, sequentially pipetting the liquid sample into the reagent accommodating chamber 161 of each reagent container (performing the mixing treatment and/or the washing treatment), and finally pipetting the obtained compound sample of the target object into the detection cell for detection.
The pipetting device 14 is mounted on the frame 11 or base 10 of the rack and above the pretreatment device 13 for facilitating pipetting operations, as shown in fig. 1, 12 to 15. In addition, the pipetting device and the pretreatment device have relative freedom of horizontal movement in the longitudinal direction, so that the reagent accommodating cavities of different positions of the reagent containers arranged on the pretreatment device can be operated.
According to different embodiments, the pretreatment device 3 can be designed to be translatable in the longitudinal direction and/or the pipetting device can be designed to be translatable in the longitudinal direction, but in any case, the pipetting device is provided with a pipettor (not shown) which can move up and down and is used for sucking and discharging liquid, and the pipettor is matched with the pretreatment device to realize the sucking and the transferring of the liquid between different positions so as to obtain a detected target compound body combined with magnetic particles by using the detected liquid sample and finally provide the detected target compound body to the detection pool of the detection device.
According to a preferred embodiment of the present application, as shown in fig. 12-15, the pipetting device 14 comprises: a longitudinal moving base 141 and a vertical moving base 142. The longitudinal moving seat 141 is longitudinally translatably mounted to the bracket 11; the vertical moving seat 142 is vertically and vertically movably disposed on the longitudinal moving seat 141 and provided with at least one pipette pointing downward to the pretreatment device.
Through the arrangement of the longitudinal moving seat 141 and the vertical moving seat 142, the pipettes mounted on the vertical moving seat 142 can be provided with the degrees of freedom of longitudinal forward and backward translation and vertical up and down translation. In a further preferred embodiment, the pipettor may also be provided with freedom to translate laterally on the vertical motion mount 142, thereby providing the pipettor with translational freedom in three dimensions for more convenient working of the corresponding reagent holding chamber. The movement is typically referred to as translation, but in certain preferred embodiments, rotational freedom may also be provided to the pipettor, for example, using a robotic arm.
The pipette may be one, but preferably, the pipette device 14 has a plurality of pipettes, and each pipette corresponds to a respective reagent container or reagent container arrangement in the longitudinal direction. Thus, a plurality of pipettes, for example arranged at a distance from one another in the transverse direction, can be operated simultaneously or independently of one another in order to be moved back and forth in the vertical direction simultaneously or independently of one another. Pipettes may also take various forms, such as pipette forms, syringe forms, and the like.
As described above, the pipette may extract the liquid reagent in the reagent holding chamber from the reagent holding chamber or inject the liquid such as after washing into the reagent holding chamber, and thus the actuation means is connected to the pipette so that the pipette sucks the liquid into the pipette or discharges the liquid in the pipette to the outside. The actuator may take many forms, for example, the movement of the liquid may be performed manually, similar to a dropper; preferably, however, the control of the liquid can be achieved by means of pneumatic means, using positive and negative pressure.
As described above, in the washing step, it is necessary to wash away impurities in the sample of the target compound to be detected, which are not bound to the magnetic particles, with a washing agent under application of a magnetic field. To achieve this, as shown in fig. 12, a permanent magnet 103 is provided on the frame, and the permanent magnet 103 is disposed adjacent to the pipette. Due to the adjacent arrangement of the two, when the pipette is under the action of the magnetic field of the permanent magnet 103 during operation, the composite sample with the bound magnetic particles (such as magnetic beads) is adsorbed to the inner side surface of the side wall of the pipette facing the permanent magnet during the liquid moving process, and impurities without bound magnetic particles are washed away along with the liquid flowing process.
In the solution of the present application, since the pipettor generally has a freedom of movement, in order to better enable the permanent magnet 103 to work with the pipettor, preferably, as shown in fig. 12, the pipetting device 14 includes an auxiliary longitudinal moving seat 143 below the longitudinal moving seat 141 and adjacent to the pipettor, and the permanent magnet 103 is fixedly disposed on the auxiliary longitudinal moving seat 143. By disposing the pipette on the auxiliary longitudinal moving seat 143, the permanent magnet 103 can be allowed to approach or separate from the pipette. For example, the auxiliary longitudinal moving seat 143 has an operating position in which the permanent magnet 103 is adjacent to or in abutment with the pipette and a retracted position in which the permanent magnet 103 is away from the pipette, in which it approaches forward to the pipette and in which it moves backward away from the pipette. Of course, the present application is not limited thereto, and for example, the permanent magnet 103 may also be provided with a translational degree of freedom in the vertical direction and/or the lateral direction, and a rotational degree of freedom may also be increased. The specific setting mode can be selected and designed according to the relative position relation between the liquid suction device and the liquid suction device in the application working condition.
In order to arrange the permanent magnet 103 and the pipette, as shown in fig. 12, a plurality of through grooves 144 opened toward the front and extending in the vertical direction are provided on the auxiliary longitudinal moving base 143, and the permanent magnet 103 is provided in each through groove 144. Thus, in the above-mentioned working position state, each pipette may extend downward from the vertical moving seat 142 to pass through the respective through slot 144, and then contact the permanent magnet 103 in each through slot 144; and in the remote position state, the pipettor can be far away from the through groove in the longitudinal direction. To facilitate a mating relationship between pipettes and the channels, each channel 144 preferably has a shape that matches a corresponding pipettor.
The structural features of the pipetting device and its course of action are described in detail above. And finally, the pipetting device pipettes the obtained compound sample of the detected target object into the detection pool for detection. The most central detection means is explained in detail below.
Sixth, detection device
And transferring the detected target compound sample to a detection cell, and performing detection operation, wherein the detection operation comprises applying a direct current electric field effect on the detection cell. Specifically, the detected target compound sample and the luminescent agent are injected into the detection cell simultaneously or sequentially or pre-mixed with each other, and then the electrochemical luminescence detection is performed after the direct current electric field is applied. The luminescent agent can be Tripropylamine (TPA), triethylamine, tributylamine, diisopropylethylamine, n-butyldiethanolamine, etc.
In the detection cell, the luminescent agent and the detected target compound sample generate electrochemical reaction under the action of a direct current electric field. For example, in the electrochemical process of obtaining electrons provided by tripropylamine in bipyridyl ruthenium as a luminescent marker, photons are released, and the parameter level of a detected target compound complex or immune complex is obtained by detecting the light intensity. With respect to the specific process of the electrochemical reaction, the present application is not specifically described, and reference may be made to the above-mentioned related documents.
Preferably, in the detection operation, the magnetic field is applied to the detection cell before the application of the dc electric field and the dc electric field is applied after the application of the magnetic field is cancelled. In this way, the complex or immune complex bound with the magnetic particles can be immobilized to obtain a good detection effect in the detection process of applying the direct current electric field. However, the magnetic field is cancelled when the electric field is applied, so that the electromagnetic interference of the magnetic field on the electric field is avoided, and the detection precision is further influenced.
In the technical scheme of this application, because the separation design of sample processing step and detection step, therefore the function of testing cell mainly focuses on the detection, compares with traditional scheme, and the structure of testing cell can be simplified by great extent in this application technical scheme. Therefore, in a preferred case, the electrode generating the dc electric field may be disposed outside the detection cell and not in direct contact with the detected target compound sample. Moreover, the electrode is arranged outside the detection cell, so that the detection cell provided with the electrode can be maintained and repaired conveniently; and the electrode is not in direct contact with the detected target compound sample, so that the pollution problem in the detection process is reduced, and the dependence on the service life of the electrode and the cleaning and/or flushing degree is reduced.
6.1 magnetic field generating device
In order to realize the magnetic field, an electromagnet mode can be adopted. In embodiments employing electromagnets, the adjustment of the magnetic field may be achieved by adjusting relevant parameters of the electromagnet (e.g., current, voltage, etc.). According to another preferred embodiment, instead of an electromagnet, a permanent magnet can be used, because: in the development process, the inventor of the present application finds that, in the embodiment using the electromagnet, in addition to generating the required magnetic field, the electromagnet generates an additional electric field in the detection cell, and the additional electric field and the predetermined electric field generated by the electrode generate additional interference, which affects the normal proceeding of the electrochemiluminescence reaction under the action of the predetermined electric field.
Furthermore, the inventors of the present application have also found that the magnetic field interferes with the dc electric field generated by the electrode assembly, and therefore, preferably, in order to avoid adverse effects of the magnetic field on the progress of the electrochemiluminescence reaction, the magnetic field of the magnetic assembly is optionally designed to not interfere, at least to a partial extent, with the dc electric field of the electrode assembly. Specifically, when a magnetic field is required to keep the detected target compound combined with the magnetic beads fixed, the magnetic field can normally exert a magnetic field effect on the detection cell; when performing an electrochemiluminescence reaction, the magnetic field may be selected to reduce its magnetic flux or field strength such that the magnetic field does not interfere, at least to some extent, with the dc electric field of the electrode assembly. In other words, the influence of the magnetic field on the detection cell is different between when the electrochemiluminescence reaction is not performed and when the electrochemiluminescence reaction is performed, and particularly, the influence of the magnetic field generated by the magnetic member is smaller when the electrochemiluminescence reaction is performed.
As mentioned above, in the embodiment of the electromagnet, this can be conveniently achieved by controlling the relevant parameters of the electromagnet, but with the consequent adverse effects of the additional electric field introduced by the electromagnet. For this reason, the present application also proposes an alternative design for how to achieve a magnetic field when the magnetic assembly is a permanent magnet, as described in detail below.
As shown in fig. 16 and 17, according to a preferred embodiment of the present application, the detecting means includes a detecting cell 151, an optical detector 152, an electric field generating means including an electrode assembly 153, and a magnetic field generating means including a magnetic assembly 154. The detection cell is fixedly or movably arranged on the frame and is used for receiving the detected target compound sample; the optical detector is movably arranged on the rack and positioned above the detection pool; the electrode assembly is arranged outside the detection cell and adjacent to the detection cell and used for providing a direct current electric field for the space in the detection cell; the magnetic assembly is a permanent magnet and is arranged outside the detection cell, the magnetic field of the magnetic assembly optionally being designed such that it does not interfere, at least to a partial extent, with the direct current field of the electrode assembly.
The measuring cell 151 may include a measuring cell body (not labeled) and a reaction chamber (not labeled) supported by the measuring cell body, as shown in fig. 16 and 17, wherein the measuring cell body constitutes a main structure of the measuring cell 151, and the reaction chamber is specifically used for accommodating a composite sample of a target object to be measured and performing an electrochemiluminescence reaction in the reaction chamber. After the target complex sample is placed in the detection cell 151 (in the reaction chamber), the complex bound with magnetic particles or magnetic beads is first kept fixed by the magnetic assembly 154 under the action of a magnetic field, for example, in the preferred embodiment of the present invention, the complex bound with magnetic particles or magnetic beads is gathered at the bottom of the reaction chamber of the detection cell under the action of the magnetic assembly located below the detection cell; and then, an electric field is applied to the detection cell by using the electrode assembly 153, so that an electrochemiluminescence reaction occurs under the action of a direct current electric field, and the luminescence condition is detected by the optical detector 151 in the luminescence process, so as to obtain final detection result data.
In the solution of the applicant's prior application document, it has been proposed: it is advantageous to eliminate the magnetic field generated by the magnetic assembly when performing electrochemiluminescence detection. However, both the magnetic field generated by the magnetic assembly and the dc electric field generated by the electrode assembly are necessary for the detection device. As mentioned above, in order to avoid the drawbacks of magnetic components in the form of electromagnets, permanent magnets may be used in the preferred solution of the present application. However, for permanent magnets, unlike the solutions of the previous applications, the present application proposes a solution for controlling the magnetic field strength of the magnetic assembly at the detection cell (in particular the reaction chamber) within a reasonable range, so as to achieve a desired balance between efficiency of operation, realisability of the solution and technical effect.
Specifically, in the preferred embodiment of the present application, the magnetic field of the magnetic component need not be completely canceled, but the magnetic field strength of the magnetic component 154 at the detection cell is designed to be no greater than 50 gauss, preferably no greater than 30 gauss, and more preferably between 10 and 20 gauss, when the optical detector 152 detects the electrochemiluminescence reaction.
This is mainly achieved in two ways.
According to one embodiment, the magnetic assembly 154 is adjustable from the detection cell, having a proximal position closer to the detection cell where it is located when the optical detector 152 is not detecting the electrochemiluminescence reaction, and a distal position further from the detection cell; the magnetic assembly is located at the remote location when the optical detector 152 detects the electrochemiluminescence reaction.
The distance between the magnetic assembly 154 and the detection cell may be a distance in the longitudinal direction or a distance in the transverse direction, but is preferably a distance in the height direction in the vertical direction as shown in fig. 16 and 17. That is, the magnetic assembly 154 is located below the detection cell 151 and is provided to the base 10 of the housing to be movable up and down to reciprocate between the adjacent position and the distant position. In particular, when the complexes with bound magnetic particles or beads are held stationary by a magnetic element, the magnetic element may be brought into proximity with the detection cell, in which case the magnetic field strength of the magnetic element 154 at the detection cell is greater than 200 gauss, preferably greater than 500 gauss, more preferably greater than 800 gauss, more preferably greater than 1000 gauss, more preferably between 800 and 1300 gauss; after the fixation is completed, the magnetic assembly is far away from the detection cell and is in a far position before or during the electrochemical luminescence reaction, so that the magnetic field intensity of the magnetic assembly at the detection cell is adjusted to a preset low degree, and the adverse effect of the magnetic field on the direct current electric field can be reduced to an acceptable degree.
This embodiment is to adjust the magnetic field strength of the magnetic assembly by adjusting the distance.
According to another embodiment (not shown), a movable shield is disposed between the magnetic assembly and the detection cell, the shield having a shielding position between the magnetic assembly and the detection cell and a non-shielding position away from the magnetic assembly and the detection cell, wherein the shield is in the non-shielding position when the optical detector 152 is not detecting the electrochemiluminescence reaction; the shield is in the shielded position when the optical detector 152 detects the electrochemiluminescence reaction. The shield may be made of an electromagnetic shielding material, such as conductive rubber, conductive coating, or the like.
The shielding member can be movably arranged between the magnetic assembly and the detection cell in various ways, so that the magnetic assembly can be fixedly arranged on the machine frame; or the shielding part can be rotatably arranged on the frame to switch between the shielding position and the non-shielding position. When the shielding piece is positioned at the non-shielding position, the magnetic assembly can be used for keeping the complex combined with the magnetic particles or the magnetic beads fixed; after the fixing is finished, the shielding part is moved to the shielding position before or during the electrochemical luminescence reaction, so that the magnetic field intensity of the magnetic component at the detection cell is shielded to a preset low degree, and the adverse effect of the magnetic field on the direct current electric field can be reduced to an acceptable degree. As for the value of the magnetic field strength, reference may be made to the above-described embodiments.
The detection cell 151 may be plural, and each of one or more detection cells may have a plurality of reaction chambers. Therefore, the plurality of detection cells are arranged at intervals in the lateral direction while corresponding to the reagent container arrangement portion of the pretreatment device in the longitudinal direction, thereby forming a multi-channel detection device.
The magnetic assembly may be plural corresponding to the detection cells, and the plural magnetic assemblies may be configured to move up and down synchronously or individually so that each magnetic assembly corresponds to a respective detection cell.
In addition, as shown in FIG. 3, the optical detector 152 is at least one, and has the freedom of transverse translation and/or longitudinal translation to selectively perform photochemical detection on the reaction chamber of one detection cell.
The arrangement of the magnetic assembly is described in detail above. In addition, the electrode assembly 153 is also a core component of the detection apparatus. The electric field generating device for forming a direct current electric field is described in detail below.
6.2 apparatus for generating electric field
As shown in fig. 5, 16 and 17, the electric field generating device of the detecting apparatus for electrochemiluminescence includes: a base plate 121, the base plate 121 being fixedly or movably disposed on the frame; a mounting plate 155, the mounting plate 155 being detachably mounted on the base plate 121, the mounting plate 155 being provided with an electrode interface 156 and a circuit board 157 electrically connected to the electrode interface 156; and an electrode assembly 153, wherein the electrode assembly 153 is removably disposed on the electrode interface 156 and is located below the detection cell of the detection device.
The base plate 121 may be fixed or movable or may be directly or indirectly disposed to the frame and provides a mounting base for the test cells 151. Preferably, as shown in fig. 17, the preprocessing unit is used as a base plate 121 at the rear portion.
The mounting plate 155 is detachably provided on the base plate 121 to provide a mounting base for the electrode assembly 153, and thus the mounting plate 155 is provided with an electrode interface 156 for inserting the electrode assembly 153 and a circuit board 157 electrically connected to the electrode interface, as shown in fig. 16.
The electrode assembly 153 is removably inserted into the electrode port 156 and is positioned below the sensing cell 151. Thus, upon completion of assembly, base plate 121, electrode assembly 153, and detection cell 151 form a "sandwich" laminate structure from bottom to top. Since the electrode assembly 153 is located under the cell 151, the electrode assembly can be brought closer to the cell to provide a direct current electric field to the reaction chamber of the cell. Also, the mounting plate 155 provides a pluggable design of the electrode assembly 153 by the arrangement of the electrode interface 156, thereby not only facilitating the installation and removal of the electrode assembly 153, but also advantageously facilitating the pluggable design when the electrode assembly is damaged or needs to be replaced according to the operating conditions. Meanwhile, the interchangeability of the electrode assembly is favorably improved. The wiring board 157 may be electrically connected to an external controller or power source to provide a controllable electrical signal to the electrode assembly 153 via the wiring board 157 to generate the respective dc electric fields.
To facilitate the plugging and unplugging of the electrode assembly 153, as shown in fig. 17, the electrode assembly 153 includes a plug part 1531 and a holding part 1532, the plug part is plugged into the electrode interface 156 in a pluggable manner, and the holding part 1532 protrudes from the base plate 121. Therefore, when the operator inserts the electrode assembly 153 into the electrode interface 156, the operator can hold the holding portion 1532 to insert or remove the insertion portion 1531 into or from the electrode interface. Meanwhile, after the electrode assembly is inserted into the electrode port, since the grip portion 1532 protrudes from the base plate 121, it is very convenient for an operator to pull out the electrode assembly. The electrode assembly 153 may be a conventional electrode assembly to enable the generation of an electric dc field.
The base plate 121 includes a mounting portion 1211 and a supporting portion 1212 higher than the mounting portion 1211, the mounting plate 155 is disposed on the mounting portion 1211, and the electrode assembly 153 is inserted into the electrode interface 156 from the rear side to the front side on the supporting portion 1212. As shown in fig. 17, since the base plate 121 includes the stepped portion, i.e., the mounting portion 1211 and the supporting portion 1212 higher than the mounting portion, the electrode interface 156 is substantially flush with the upper surface of the supporting portion 1212. In other words, the mounting portion 1211 provides a mounting space for the mounting plate 155, which facilitates the positioning of the mounting plate, on the one hand, and avoids interference with the mounting space for the detection cell, on the other hand.
Preferably, as shown in fig. 17, a groove 1213 is provided on the upper surface of the support 1212, and the electrode assembly 153 is dropped into the groove 1213 to be inserted into the electrode interface 156. By the arrangement of the groove 1213, at least a portion of the electrode assembly 153 falls into the groove 1213, thereby avoiding damage to the electrode assembly from the upper components. It is further preferred that the thickness of the electrode assembly 153 is not greater than the depth of the groove 1213 to provide better protection for the electrode assembly.
As described above, the supporting portion 1212 is detachably supported by the cell, which is located above the electrode assembly 153, so as to conveniently provide a dc electric field to the cell. It is further preferred that the electrode assembly and the reaction chamber of the upper detection cell are aligned with each other in the height direction. As shown, the detecting cells 151 and the corresponding electrode assemblies 153 are multiple and respectively correspond to each other.
As shown in fig. 16 and 17, a magnetic assembly 154 is provided under the supporting portion 1212 to be movable up and down, and the magnetic assembly, the electrode assembly, and the sensing cells are aligned with each other in a vertical direction. In this embodiment, the variation of the magnetic field can be controlled by the up-and-down movement of the magnetic assembly. This point has already been described in detail above and will therefore be omitted here.
Preferably, as shown in fig. 17, the support portion 1212 is provided with a through hole 1214 extending vertically, and the permanent magnet of the magnetic assembly 154 has a degree of freedom to move up and down in the through hole 1214. Due to the through hole, when the permanent magnet of the magnetic assembly moves upwards and approaches the detection cell, the permanent magnet can approach the detection cell more, so that a stronger magnetic field is applied to the magnetic particles in the detection cell. Preferably, as shown in fig. 17, a through hole 1214 is formed at the groove 1213, thereby achieving that the permanent magnet of the magnetic assembly, the electrode assembly, and the sensing cell correspond to each other in the height vertical direction.
The electric field generating device is described in detail above. The technical solution of the present application will be described below with reference to an example of the detection process to facilitate understanding of the technical solution of the present application.
Seventh, example of detection Process
First, a sample container containing a liquid sample to be measured is placed in a sample buffer of a buffer. At this time, the temperature is preferably controlled to 37 ℃.
Then, the liquid sample to be detected is pipetted into the reagent accommodating cavity of the reagent container by using a pipettor of the pipetting device to mix with different reagents according to a predetermined sequence, and a warm bath standing and/or washing treatment is performed at a predetermined temperature (e.g. 37 ℃) in the middle to remove the complex without the magnetic particles or magnetic beads, so as to finally obtain the detected target complex with the magnetic particles.
Subsequently, the target complex particles to be detected, to which the magnetic particles are bound, are transferred to (the reaction chamber of) the detection cell by a pipette using the electrochemiluminescence reaction solution as a medium. Firstly, moving a magnetic assembly upwards to approach a detection pool, keeping for 30-60 s, and then enabling a detected target compound combined with magnetic particles to be attracted to the bottom under the action of a magnetic field; then the magnetic component is controlled to move downwards to be far away from the detection pool; then the optical detector is moved to the upper part of the detection cell (the reaction cavity of the detection cell) and is aligned with the detection cell and then moves downwards to form a light-tight closed space with the detection cell; in this case, the electrode assembly is energized to start an electrochemiluminescence reaction, and is detected by the optical detector.
And finally, after the detection is finished, processing the data obtained by the optical detector to obtain a detection result. After the detection is finished, the detection cell needs to be cleaned for the next detection procedure.
As described above, in the technical solution of the present application, numerous improvements have been made with respect to the prior applications, such as a pretreatment device, a pipetting device, an electric field generating device, a magnetic field generating device, and the like. These devices, as a constituent of an electrochemiluminescence detection apparatus, may be of modular design or as separate distributed products, which are therefore explained in detail separately in the description of the present application and subject matter described above may be patented. In addition, the above detection process examples are only used as an exemplary illustration, and parameters, reagents, steps and the like can be adaptively adjusted according to different specific working conditions, so that the present application is not limited, and the adjustments are within the scope of the present application.
The preferred embodiments of the present application have been described in detail above, but the present application is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present application within the technical idea of the present application, and these simple modifications all belong to the protection scope of the present application.
It should be noted that, in the foregoing embodiments, various features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described in the present application.
In addition, any combination of the various embodiments of the present application can be made, and the same should be considered as the disclosure of the present invention as long as the combination does not depart from the spirit of the present application.

Claims (10)

1. Pipetting device (14) for an electrochemiluminescence detection apparatus, characterized in that the pipetting device comprises:
a longitudinal mobile seat (141), the longitudinal mobile seat (141) being mounted to the support (11) so as to be longitudinally translatable; and
a vertical moving seat (142), wherein the vertical moving seat (142) can be vertically arranged on the longitudinal moving seat (141) in a vertically up-and-down moving mode and is provided with at least one pipette pointing downwards to the pretreatment device.
2. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 1, characterized in that the pipetting device (14) has a plurality of pipettes and each pipette corresponds in longitudinal direction to a respective reagent container or reagent buffer.
3. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 1, characterized in that the plurality of pipettes are arranged spaced apart from each other in the lateral direction to be reciprocated in the vertical direction simultaneously or each independently.
4. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 1, characterized in that an actuating device is connected to the pipette in order to cause the pipette to aspirate liquid into the pipette or to discharge liquid in the pipette to the outside.
5. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 4, characterized in that the actuating device is a pneumatic device.
6. Pipetting device (14) for an electrochemiluminescence detection apparatus according to any of claims 1-5, characterized in that the holder (11) is provided with a permanent magnet (103), which permanent magnet (103) is arranged adjacent to the pipette.
7. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 6, characterized in that the pipetting device (14) comprises an auxiliary longitudinal moving seat (143) located below the longitudinal moving seat (141) and adjacent to the pipettor, the permanent magnet (103) being fixedly arranged on the auxiliary longitudinal moving seat (143).
8. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 7, characterized in that the auxiliary longitudinal moving seat (143) has an operating position in which the permanent magnet (103) is adjacent to or in abutment with the pipette and a retracted position in which the permanent magnet (103) is remote from the pipette, in forward proximity to the pipette and in rearward direction away from the pipette.
9. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 8, characterized in that the auxiliary longitudinal movable holder (143) is provided with a plurality of through slots (144) opening to the front and extending in a vertical direction, each through slot (144) being provided with the permanent magnet (103) therein.
10. Pipetting device (14) for an electrochemiluminescence detection apparatus according to claim 9, characterized in that each channel (144) has a shape matching a corresponding pipette.
CN202120279844.XU 2021-02-01 2021-02-01 Liquid transfer device for electrochemical luminescence detection equipment Active CN214427286U (en)

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