An electrochemiluminescence detection device and a method of use

Abstract

The present invention discloses an electrochemiluminescence detection device, belonging to the field of electrochemiluminescence detection. The device includes a light detection module, at least two reaction modules, a first optical fiber, and a spectrometer. The spectrometer is connected to the light detection module through the first optical fiber. Each reaction module includes a light-emitting container and a second optical fiber. The second optical fiber is connected to the light-emitting container. The spectrometer is connected to the second optical fiber of each reaction module. Through the above design, one light detection module can detect the optical signals in multiple light-emitting containers, and the utilization rate of the light detection module is high; the entire electrochemiluminescence detection device has a simpler structure and lower cost. The present invention also relates to a method for using the above electrochemiluminescence detection device.

Description

Technical Field

[0001] The present invention relates to the field of electrochemiluminescence detection, and particularly to an electrochemiluminescence detection device and a method for using the electrochemiluminescence detection device. Background Art

[0002] Electrochemiluminescence reaction is a specific chemiluminescence reaction initiated electrochemically on the surface of a working electrode in a luminescence container. The conjugate of antigen-antibody complex and ruthenium pyridine undergoes an oxidation-reduction reaction excited by voltage under the action of tripropylamine, releasing photons. This process occurs repeatedly on the electrode surface, generating photons repeatedly to increase the intensity of the optical signal. The number of photons generated during the reaction process can be collected and processed by a light detection module, and by detecting the intensity of the optical signal generated during the electrochemiluminescence process, the detection of the concentration of the substance to be measured is achieved.

[0003] In existing electrochemiluminescence immunoassay analyzers, in order to improve the detection speed, multiple luminescence containers are usually installed, and the light detection module corresponds to each luminescence container one by one, that is, one light detection module only detects the photons generated by the electrochemiluminescence reaction in one luminescence container. Therefore, multiple light detection modules are also installed. However, within one detection cycle, the light detection module is only in the powered-on working state for a short time and is in the powered-off state for a long time, which results in a very low utilization rate of the light detection module. Coupled with the high price of the light detection module, using multiple light detection modules will increase the cost of the instrument. Summary of the Invention

[0004] In order to overcome the deficiencies of the prior art, one of the purposes of the present invention is to provide an electrochemiluminescence detection device with a high utilization rate of the light detection module and low cost.

[0005] In order to overcome the deficiencies of the prior art, the second purpose of the present invention is to provide a method for using an electrochemiluminescence detection device with a high utilization rate of the light detection module and low cost.

[0006] One of the purposes of the present invention is achieved by adopting the following technical solutions:

[0007] An electrochemiluminescence detection device includes a light detection module, at least two reaction modules, a first optical fiber, and a beam splitter. The beam splitter is connected to the light detection module through the first optical fiber. Each reaction module includes a luminescence container and a second optical fiber. The second optical fiber is connected to the luminescence container, and the beam splitter is connected to the second optical fiber of each reaction module.

[0008] Further, within the same time, only one of the luminescence containers of at least two reaction modules is in the luminescence stage.

[0009] Further, each of the reaction modules further includes a control switch, which is located between the optical splitter and the light-emitting container, and the control switch controls the on / off of the second optical fiber optical path.

[0010] Further, the control switch is a mechanical optical switch or an electro-optic effect optical switch.

[0011] Further, the optical detection module is a vacuum electronic device, and the optical detection module converts the weak electrochemiluminescence optical signal into an electrical signal.

[0012] The second object of the present invention is achieved by the following technical solution:

[0013] A method for using any one of the above-mentioned electrochemiluminescence detection devices includes the following steps:

[0014] Electrode activation: Continuously fill at least two light-emitting containers with an electrochemiluminescence co-reactant solution.

[0015] Sample injection: Inject the pretreated sample to be tested into at least two light-emitting containers, and fill in the co-reactant solution as the luminescent substrate.

[0016] Electrochemical reaction: The electrode provides the voltage required for the electrochemical reaction. The conjugate of the antigen-antibody complex and ruthenium pyridine undergoes an oxidation-reduction reaction excited by the voltage under the action of the co-reactant solution, releasing photons. Due to the sequence, at the same time, only one light-emitting container is in the light-emitting stage. When an electrochemiluminescence reaction occurs in any one of the light-emitting containers to generate an optical signal, the optical signal is transmitted through the second optical fiber, the optical splitter, and the first optical fiber to the optical detection module for detection, and the optical detection module detects the photons generated by at least two light-emitting containers.

[0017] Electrode cleaning: Fill the light-emitting container with an electrochemistry reaction cleaning solution to rinse the residual reaction substances in the container, providing a clean environment for the next measurement.

[0018] Further, when the light-emitting container is in the non-light-emitting stage, the control switch controls the disconnection of the second optical fiber optical path of the light-emitting container.

[0019] Further, the optical detection module is only in the powered-on working state during the electrochemistry reaction step.

[0020] Further, the method for using the electrochemiluminescence detection device further includes a calibration and quality control step, and the calibration and quality control step is before the electrode activation step. The calibration and quality control step is specifically: Since all the light-emitting containers commonly use one optical detection module, at least two of the reaction modules are calibrated and quality controlled through the optical detection module.

[0021] Further, in the calibration and quality control step, the prerequisite for primary calibration and quality control is that the consistency of the multiple light-emitting containers is relatively good.

[0022] Compared with the prior art, the electrochemiluminescence detection device of the present invention further includes a spectroscope, which is connected to the light detection module through a first optical fiber. Each reaction module includes a light-emitting container and a second optical fiber. The second optical fiber is connected to the light-emitting container, and the spectroscope is connected to the second optical fiber of each reaction module. Through the above design, one light detection module can detect the optical signals in multiple light-emitting containers, and the utilization rate of the light detection module is high; the overall structure of the electrochemiluminescence detection device is simpler and the cost is lower. Description of the Drawings

[0023] Figure 1 is a schematic structural diagram of the electrochemiluminescence detection device of the present invention;

[0024] Figure 2 is a time proportion distribution diagram of a complete measurement cycle of electrochemiluminescence detection.

[0025] In the figure: 10, light detection module; 20, first interface; 30, first optical fiber; 40, spectroscope; 50, reaction module; 51, control switch; 52, second optical fiber; 53, second interface; 54, light-emitting container. Detailed Embodiments

[0026] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0027] It should be noted that when a component is referred to as being "fixed to" another component, it can be directly on the other component or there may also be another intermediate component through which it is fixed. When a component is considered to be "connected" to another component, it can be directly connected to the other component or there may be another intermediate component at the same time. When a component is considered to be "disposed on" another component, it can be directly disposed on the other component or there may be another intermediate component at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are only for the purpose of illustration.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs. The terms used in the description of the present invention herein are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0029] As Figure 1 shown, the electrochemiluminescence detection device of the present invention includes a light detection module 10, a first interface 20, a first optical fiber 30, a spectroscope 40, and a plurality of reaction modules 50.

[0030] The light detection module 10 is a vacuum electronic device that converts weak electrochemiluminescence light signals into electrical signals.

[0031] The first interface 20 is installed on the light detection module 10.

[0032] One end of the first optical fiber 30 is connected to the first interface 20, and the other end is connected to the spectroscope 40.

[0033] The spectroscope 40 is used to collect the optical signals transmitted in the second optical fibers 52 corresponding to a plurality of channel light-emitting containers 54 into a first optical fiber 30 connected to the light detection module 10. The spectroscope 40 selects the corresponding number of spectroscopic channels according to the number of light-emitting containers 54 to be connected.

[0034] The number of reaction modules 50 is plural. In this embodiment, the number of reaction modules 50 is two. Each reaction module 50 includes a control switch 51, a second optical fiber 52, a second interface 53, and a light-emitting container 54. The second interface 53 is installed on the light-emitting container 54. One end of the second optical fiber 52 is connected to the spectroscope 40, and the other end is connected to the second interface 53. The control switch 51 is installed on the second optical fiber 52 to control the on / off of the optical path of the second optical fiber 52. The control switch 51 is a mechanical optical switch or an electro-optic effect optical switch. The purpose of the control switch 51 is to disconnect the optical path of the second optical fiber 52 of the light-emitting container 54 in the non-light-emitting stage to avoid background noise interference and achieve more accurate measurement. When a light-emitting container 54 generates an optical signal, the background noise generated by the remaining light-emitting containers 54 is small and can be ignored, and the reaction module 50 may not need to be provided with a control switch 51.

[0035] When using an electrochemiluminescence detection device, the process of one measurement in the luminescence container 54 of the electrochemiluminescence detection device includes four steps. The first step is the electrode activation process, in which an electrochemiluminescence co-reactant solution is continuously filled into the luminescence container 54, and the main component of the co-reactant solution is tripropylamine. The purpose of electrode activation is to eliminate the oxide film on the surface of the reaction container electrode and provide the electrode surface conditions required for the reaction. The second step is to inject the sample. In this process, the pretreated sample to be tested is injected into the luminescence container 54, and the co-reactant solution is filled as the luminescence substrate. The third step is the electrochemical reaction process. At this stage, the electrode provides the voltage required for the electrochemical reaction. The conjugate of the antigen-antibody complex and ruthenium pyridine generates an oxidation-reduction reaction under the action of tripropylamine under the excitation of the voltage, releasing photons. The light detection module 10 is only in the powered-on working state at this stage. The fourth step is electrode cleaning. In this process, an electrochemical reaction cleaning solution is filled into the luminescence container 54 to rinse the residual reaction substances in the container, providing a clean environment for the next measurement.

[0036] In the electrochemical reaction process step, due to the sequence of timing, only one luminescence container 54 is in the luminescence stage at the same time, and the remaining luminescence containers 54 are in the other three non-luminescence stages. When an electrochemiluminescence reaction occurs in a certain luminescence container 54 to generate a light signal, the control switch 51 on the corresponding second optical fiber 52 is in the conducting state, and the light signal is transmitted from the second optical fiber 52, the optical splitter 40, and the first optical fiber 30 to the light detection module 10 for detection. At this time, due to the sequence of timing, the remaining luminescence containers 54 are in the other three non-luminescence stages. Considering that there may be background noise interference, the control switches 51 corresponding to the remaining luminescence containers 54 are in the open state to achieve more accurate measurement. If the background noise generated by the remaining luminescence containers 54 is small and can be ignored when a light signal is generated in a luminescence container 54, the optical control switch 51 of the second optical fiber 52 can be removed, and this design also falls within the protection scope of this patent.

[0037] When the luminescence containers 54 of the remaining reaction modules 50 are in the luminescence stage, the working process is as described above.

[0038] Please continue to refer to Figure 2, a complete measurement cycle within the luminescent container 54 includes four processes: electrode activation, sample injection, electrochemiluminescence reaction, and electrode cleaning. Among them, the purpose of electrode activation is to provide specified surface conditions on the working electrode, and the time accounts for approximately 11.13% of the entire measurement cycle. Sample injection is to enable the streptavidin magnetic microparticles conjugated with antigens or antibodies to adsorb onto the electrode surface, and the time accounts for approximately 59.17% of the entire measurement cycle. After applying a specific voltage, an electrochemiluminescence reaction occurs, and the photon detection module 10 collects the photons generated during the reaction process for detection, and the time accounts for approximately 3.80% of the entire measurement cycle. After the reaction ends, the flow channels and electrodes within the luminescent container 54 are rinsed with a cleaning solution to prepare for the next measurement, and the time accounts for approximately 25.90% of the entire measurement cycle. Within one measurement cycle, the photon detection module 10 is only powered on to detect optical signals during the electrochemiluminescence reaction stage, and is in a power-off state at other times. Moreover, due to the sequential nature of the instrument, there will be no situation where all photon detection modules 10 detect luminescence simultaneously. Therefore, by using the electrochemiluminescence detection device designed in this patent, with a single photon detection module 10 corresponding to multiple-channel luminescent containers 54, the number of photon detection modules 10 used can be reduced while ensuring the high throughput of the instrument, and the working time of a single photon detection module 10 can be increased to 3.80% × N, where N is the number of luminescent containers 54 corresponding to a single photon detection module 10. This improves the usage efficiency of the photon detection module 10 and reduces the instrument cost.

[0039] In addition, in order to ensure the accuracy and stability of the electrochemiluminescence detection device during detection, it is necessary to calibrate and quality control the device before detection. Especially in the case of multiple channels, it is necessary to calibrate and quality control each channel separately. Since all the luminescent containers 54 of the electrochemiluminescence detection device designed in this patent share a single photon detection module 10, under the premise of good consistency of the luminescent containers 54, only one calibration and quality control are required, which greatly reduces the complexity of calibration and quality control and reduces the consumption of calibration products and quality control products.

[0040] The present invention also relates to a method for using the above-mentioned electrochemiluminescence detection device, including the following steps:

[0041] Electrode activation: Continuously fill at least two luminescent containers 54 with an electrochemiluminescence co-reactant solution;

[0042] Sample injection: Inject the pretreated sample to be measured into at least two luminescent containers 54, and fill in a co-reactant solution as a luminescent substrate;

[0043] Electrochemical reaction: The electrode provides the voltage required for the electrochemical reaction. The conjugate of the antigen-antibody complex and ruthenium pyridine undergoes an oxidation-reduction reaction excited by the voltage under the action of the co-reactant solution, releasing photons. Due to the sequence, at the same time, only one luminescent container 54 is in the luminescent stage. When an electrochemical luminescence reaction occurs in any one of the luminescent containers 54 to generate a light signal, the light signal is transmitted through the second optical fiber 52, the optical splitter 40, and the first optical fiber 30 to the light detection module 10 for detection. The light detection module 10 detects the photons generated by at least two luminescent containers 54;

[0044] Electrode cleaning: The electrochemical reaction cleaning solution is filled into the luminescent container 54 to rinse the residual reaction substances in the container, providing a clean environment for the next measurement.

[0045] When the luminescent container 54 is in the non-luminescent stage, the control switch 51 controls the second optical fiber 52 where the luminescent container 54 is located to be in an open circuit state. The light detection module 10 is only in the powered-on working state during the electrochemical reaction step.

[0046] The method of using the electrochemical luminescence detection device further includes a calibration and quality control step. The calibration and quality control step is before the electrode activation step. Specifically, since all the luminescent containers 54 share one light detection module 10, the light detection module 10 performs a calibration and quality control on at least two reaction modules 50 once. The premise of one calibration and quality control is that the consistency of multiple luminescent containers 54 is relatively good.

[0047] One light detection module 10 of the present application can detect the light signals in multiple luminescent containers 54, and the utilization rate of the light detection module 10 is high; the entire electrochemical luminescence detection device has a simpler structure and lower cost.

[0048] The above embodiments only represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can be made. These are all equivalent modifications and evolutions based on the essence of the present invention to the above embodiments, and these all belong to the protection scope of the present invention.

Claims

1. A method for using an electrochemiluminescence detection device, characterized in that, The electrochemical luminescence detection device includes a light detection module, at least two reaction modules, a first optical fiber, and a spectroscope. The spectroscope is connected to the light detection module through the first optical fiber. Each reaction module includes a luminescence container and a second optical fiber. The second optical fiber is connected to the luminescence container. The spectroscope is connected to the second optical fiber of each reaction module. At the same time, only one of the luminescence containers of at least two reaction modules is in the luminescence stage. The usage method of the electrochemical luminescence detection device includes the following steps: Electrode activation: Continuously fill the electrochemical luminescence co-reactant solution into the luminescence container. Sample injection: Inject the pretreated sample to be measured into at least two luminescence containers, and fill in the co-reactant solution as the luminescence substrate. Electrochemical reaction: The electrode provides the voltage required for the electrochemical reaction. The conjugate of the antigen-antibody complex and ruthenium pyridine undergoes an oxidation-reduction reaction excited by the voltage under the action of the co-reactant solution, releasing photons. Due to the sequence, at the same time, only one luminescence container is in the luminescence stage. When an electrochemical luminescence reaction occurs in any luminescence container to generate a light signal, the light signal is transmitted through the second optical fiber, the spectroscope, and the first optical fiber to the light detection module for detection. The light detection module detects the photons generated by at least two luminescence containers. Electrode cleaning: Fill the electrochemical reaction cleaning solution into the luminescence container to rinse the residual reaction substances in the container, providing a clean environment for the next measurement.

2. The method for using an electrochemiluminescence detection device according to claim 1, characterized in that: When the luminescence container is in the non-luminescence stage, the control switch controls the disconnection of the optical path of the second optical fiber of the luminescence container in the non-luminescence stage.

3. The method for using an electrochemiluminescence detection device according to claim 1, characterized in that: The light detection module is only in the powered-on working state during the electrochemical reaction step.

4. The method for using an electrochemiluminescence detection device according to claim 1, characterized in that: The usage method of the electrochemical luminescence detection device further includes a calibration and quality control step. The calibration and quality control step is before the electrode activation step. The calibration and quality control step is specifically: Since all luminescence containers commonly use one light detection module, at least two reaction modules are calibrated and quality controlled through the light detection module.

5. The method for using an electrochemiluminescence detection device according to claim 4, characterized in that: In the calibration and quality control step, the prerequisite for one calibration and quality control is that the consistency of multiple luminescence containers is relatively good.

6. The method for using an electrochemiluminescence detection device according to claim 1, characterized in that: Each reaction module further includes a control switch. The control switch is located between the spectroscope and the luminescence container. The control switch controls the on-off of the optical path of the second optical fiber.

7. The method for using an electrochemiluminescence detection device according to claim 6, characterized in that: The control switch is a mechanical optical switch or an electro-optic effect optical switch.

8. The method for using an electrochemiluminescence detection device according to claim 1, characterized in that: The light detection module is a vacuum electron device. The light detection module converts the weak electrochemical luminescence light signal into an electrical signal.

Images