CN110579598A - Optical signal detection device, system and method - Google Patents
Optical signal detection device, system and method Download PDFInfo
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- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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Abstract
The application provides a device for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte, comprising: at least one set of first light sources, each set of first light sources comprising at least two first light sources that can be controlled to illuminate the reaction zone under first and second illumination conditions, respectively; at least one first optical signal detector for detecting a first optical signal detection value pair of the reaction region under a first illumination condition and a second optical signal detection value under a second illumination condition; and an optical signal correction value determining unit for performing predetermined processing on the first optical signal detection value pair; and determining an optical signal correction value of the reaction zone based on the predetermined processing result, the second optical signal detection value and the optical signal value correlation function. By using the device, the influence of the position error of the reaction area on the accuracy of the detection result can be eliminated.
Description
Technical Field
The present application relates generally to the field of specific substance detection, and more particularly, to methods, devices and systems for detecting optical signal values in reaction zones of reaction carriers after reaction with an analyte.
Background
In recent years, due to abuse of long-term pesticides, hormones and antibiotics, the food safety problem of China is more and more serious, at present, the mainstream food safety detection is mainly carried out by returning to the mouth of a special department under a food and drug administration, large-scale liquid phase, mass spectrum or liquid-mass joint inspection is carried out, a plurality of large-scale desktop gold-labeled detectors are assisted, professional operators are required to complete the detection, the period for obtaining results is long, and the detection cannot be applied to on-site timely detection.
With the improvement of the living standard of people, the family health self-test is more and more important for modern people, but the current mainstream early pregnancy and ovulation monitoring adopts a visual inspection method or disposable pen type qualitative measurement, and the body indexes cannot be quantitatively monitored in the family environment for a long time.
The test paper is suitable for rapid detection at present, can be stored at normal temperature and is widely applied, and particularly, the colloidal gold test paper can be rapidly popularized to the fields of food safety and home health self-testing due to low cost and high detection speed and batch production and manufacturing.
The principle of the test paper for detecting the specific substance is that a labeled reactant capable of reacting with the specific substance is arranged in a reaction area of the test paper, after a sample to be detected is added into the test paper, the specific substance in the sample to be detected can gradually enter the reaction area to react with the labeled reactant, optical signal changes, such as changes of color depth and fluorescence intensity, can be formed in the reaction area after the reaction, and due to the fact that a functional relation exists between the optical signal changes and the concentration of the specific substance to be detected, the method can be used for detecting the content of the specific substance.
The current technology mainly includes the following three ways for judging the change of the optical signal of the test paper. The first method is to use a test paper with color change, and make qualitative or semi-quantitative judgment by observing the color depth of a detection line of a reaction area on the test paper through human eyes. The second method is to use an image sensor as a detection element to photograph the color change of the test paper, and then use image recognition to make qualitative or quantitative judgment. The third method is to use the principle of reflection of light, receive a reflected light signal using a photoelectric sensor as a photoelectric receiving device, and perform determination using the intensity of the received light signal.
However, in the first technical solution, the interference of the test paper artifact is large, and the judgment error of different people or people without experience on the result is large, so that the method can be only used for qualitative or semi-quantitative judgment. In addition, the fluorescent test strip cannot be manually judged.
In the second technical scheme, the control system is complex, an optical lens is required for imaging, and the imaging quality directly influences result judgment, so that a good optical device is required to be used, the cost is high, and the cost advantage of the colloidal gold test paper is offset to a certain extent. In addition, the whole scheme has large volume and cannot be miniaturized.
in the third technical solution, the device can be designed as a micro-instrument due to low implementation cost and simple structure, however, the device has the problems of test paper background interference, and sample color interference and position error of a reaction area (such as a color development strip) have great influence on the accuracy and stability of the detection result. In addition, due to the limitation of the production process of the test paper, the position error of the color development strip cannot be completely eliminated, the color of the sample in the field of food safety detection is different, the color of the sample cannot be effectively removed through the test paper sample pad, and then the interference of the color of the sample on the measurement cannot be eliminated, so that the scheme cannot realize effective quantitative determination.
Disclosure of Invention
In view of the above, the present application provides a method, device and system for detecting an optical signal value in a predetermined reaction region of a reaction carrier after reaction with an analyte. By using the method, the device and the system, the influence of test strip background interference, sample color interference and/or reaction area position error on the accuracy of the detection result can be eliminated.
according to an aspect of the present application, there is provided an apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reacting with an analyte, comprising: at least one set of first light sources, each set of first light sources comprising at least two first light sources that can be controlled separately to illuminate the same reaction zone of the reaction carrier under first and second illumination conditions; at least one first optical signal detector for detecting a first optical signal detection value pair of the reaction zone under the first illumination condition and a second optical signal detection value under the second illumination condition; and an optical signal correction value determining unit for performing predetermined processing on the first optical signal detection value pair; and determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and a corresponding optical signal value correlation function, wherein the optical signal value correlation function is used for reflecting the functional relation between the optical signal correction value after the position error correction and the predetermined processing result and the second optical signal detection value, and the first illumination condition comprises that two groups of light sources which are respectively composed of the first light sources in each group of the first light sources according to a specified rule are respectively illuminated, and the second illumination condition comprises that the light sources related to the light sources forming the first illumination condition are illuminated.
Optionally, in one example of the above aspect, the second illumination condition includes illumination by a light source group including at least a light source selected from the two groups of light sources.
Optionally, in one example of the above aspect, the second illumination condition includes illumination by all of the at least two first light sources.
Alternatively, in one example of the above aspect, the predetermined processing includes difference processing or ratio processing.
Optionally, in one example of the above aspect, the apparatus may further include a detection parameter setting unit for setting a detection start time, a detection off time, and a detection interval period of the first optical signal detector according to a property of a specific substance to be detected and a label on the reaction carrier; a timer; and the timing trigger unit is connected with the timer and used for triggering the timer to start timing after the reaction carrier enters a detection ready state.
optionally, in one example of the above aspect, the first light source is a light source having a full wavelength range or a specific wavelength range.
Optionally, in one example of the above aspect, the first light source is a fluorescence excitation light source, and the first optical signal detector has a filter characteristic matching a wavelength of the excited fluorescence.
optionally, in one example of the above aspect, the at least two first light sources are positioned so as to be located on both sides of the reaction area of the standard reaction carrier when the standard reaction carrier is in a ready-to-detect state.
optionally, in one example of the above aspect, the positions of the at least two first light sources are arranged so as to be symmetrically located on both sides of the reaction area of a standard reaction carrier when the standard reaction carrier is in a ready-to-detect state.
Optionally, in an example of the above aspect, the apparatus may further include: and the temperature sensor is used for detecting temperature data when the reaction carrier is in a detection state.
alternatively, in one example of the above-described aspect, the optical signal value correlation function is generated based on history data of a predetermined processing result, history data of the second optical signal detection value, and history data of a corresponding optical signal detection reference value; and/or the light signal value correlation function is associated with the model of the first light signal detector, the first and second illumination conditions.
optionally, in an example of the above aspect, the apparatus may further include: at least one second optical signal detector for detecting a third optical signal detection value of the non-reaction area of the reaction carrier under a third illumination condition, and the optical signal correction value determining unit further includes: a background correction module for acquiring the second optical signal detection value after background correction based on the second optical signal detection value, the third optical signal detection value and corresponding illumination conditions, and the optical signal correction value determination unit is configured to: determining an optical signal correction value of the reaction zone after position error correction based on the predetermined processing result, the corrected second optical signal detection value and the corresponding optical signal value correlation function; or the optical signal correction value determining unit is further used for determining the optical signal correction value of the reaction area after background correction based on the determined optical signal correction value of the predetermined reaction area after position error correction, the third optical signal detection value and the corresponding irradiation condition.
Optionally, in one example of the above aspect, the second illumination condition and the third illumination condition are the same.
optionally, in one example of the above aspect, the second illumination condition and the third illumination condition are provided by the same light source or by different light sources.
Optionally, in one example of the above aspect, the first optical signal detector and the second optical signal detector are implemented using the same optical signal detector.
Optionally, in an example of the above aspect, the apparatus may further include: a specific substance content determination unit for determining the content of the specific substance based on the determined optical signal correction value.
Optionally, in an example of the above aspect, the apparatus may further include: and the communication unit is used for data communication between the specific substance content determination unit and the upper computer.
Optionally, in an example of the above aspect, the specific substance content determination unit is disposed in an upper computer or a cloud server, and the apparatus may further include: and the communication unit is used for data communication between the optical signal correction value determination unit and the specific substance content determination unit.
Optionally, in an example of the above aspect, the apparatus may further include: a controller for controlling illumination of the respective light sources, detection of the respective light signal detectors, data communication between the respective components in the apparatus, and/or data communication between the components in the apparatus and the outside.
Optionally, in one example of the above aspect, the specific substance includes one of: toxins, antibiotics, pesticides or hormones.
According to another aspect of the present application, there is provided an apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reacting with an analyte, including: at least one set of first light sources, each set of first light sources for illuminating the same reaction zone of the reaction carrier under first illumination conditions; at least one first optical signal detector for detecting a first optical signal detection value of the reaction zone under the first illumination condition; at least one set of second light sources, each set of second light sources for illuminating the same non-reaction zone of the reaction carrier under second illumination conditions; at least one second optical signal detector for detecting a second optical signal detection value of the non-reaction area of the reaction carrier under the second irradiation condition, and an optical signal correction value determining unit for determining an optical signal correction value of the reaction area after background correction based on the first optical signal detection value, the second optical signal detection value and the corresponding irradiation condition.
optionally, in one example of the above aspect, the at least one first set of light sources and the at least one second set of light sources are implemented using the same light source, and the same light source is arranged as an area located between the at least one first optical signal detector and the at least one second optical signal detector.
optionally, in one example of the above aspect, the at least one set of first light sources and the at least one set of second light sources are positioned so as to be directly above the reaction region and the non-reaction region of the standard reaction carrier, respectively, when the standard reaction carrier is in a ready-to-detect state.
Optionally, in one example of the above aspect, the first optical signal detector and the second optical signal detector are implemented using the same optical signal detector.
Optionally, in an example of the above aspect, the apparatus may further include: a specific substance content determination unit for determining the content of the specific substance based on the determined optical signal correction value.
optionally, in an example of the above aspect, the apparatus may further include: and the communication unit is used for data communication between the specific substance content determination unit and the upper computer.
Optionally, in an example of the above aspect, the specific substance content determination unit is disposed in an upper computer or a cloud server, and the apparatus may further include: and the communication unit is used for data communication between the optical signal correction value determination unit and the specific substance content determination unit.
optionally, in an example of the above aspect, the apparatus may further include: a controller for controlling illumination of the respective light sources, detection of the respective light signal detectors, data communication between the respective components in the apparatus, and/or data communication between the components in the apparatus and the outside.
Optionally, in one example of the above aspect, the specific substance includes one of: toxins, antibiotics, pesticides or hormones.
According to another aspect of the present application, there is provided a system for detecting the content of a specific substance in an analyte, comprising: a reaction carrier; a device for detecting an optical signal value in a predetermined reaction region of the reaction carrier after the reaction with the analyte as described above; and a specific substance content determination unit for determining the content of the specific substance based on the determined optical signal correction value.
optionally, in an example of the above aspect, the system may further include an upper computer for presenting a specific substance content detection result to a user and/or controlling the operation of the apparatus, the operation of the specific content determining unit, and the operation between the apparatus and the specific substance content determining unit.
Optionally, in an example of the above aspect, the specific content determining unit may be implemented in the apparatus, a cloud server, or the upper computer.
according to another aspect of the present application, there is provided a method for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte, comprising: detecting a first optical signal detection value pair of a reaction area of the reaction carrier under a first illumination condition and a second optical signal detection value under a second illumination condition, wherein the first illumination condition comprises that two groups of light sources which are formed by first light sources in each group of first light sources according to a specified rule are respectively illuminated, and the second illumination condition comprises that the light sources related to the light sources forming the first illumination condition are illuminated; performing predetermined processing on the first optical signal detection value pair; and determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and a corresponding optical signal value correlation function, wherein the optical signal value correlation function is used for reflecting the functional relation between the optical signal correction value after the position error correction and the predetermined processing result and the second optical signal detection value.
Optionally, in an example of the above aspect, the method may further include: detecting a third optical signal detection value of the non-reaction area of the reaction carrier under a third irradiation condition; and acquiring the second optical signal detection value after background correction based on the second optical signal detection value, the third optical signal detection value and corresponding illumination conditions, and determining the optical signal correction value of the reaction zone based on the predetermined processing result, the second optical signal detection value and a corresponding optical signal value correlation function comprises: and determining the optical signal correction value of the reaction area after the position error correction based on the preset processing result, the second optical signal detection value after the background correction and the corresponding optical signal value correlation function.
optionally, in an example of the above aspect, the method may further include: detecting a third optical signal detection value of the non-reaction area of the reaction carrier under a third irradiation condition; and determining the optical signal correction value of the reaction area after background correction based on the optical signal correction value of the reaction area after position error correction, the third optical signal detection value and the corresponding irradiation condition.
According to another aspect of the present application, there is provided a method for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte, comprising: detecting a first optical signal detection value of a reaction area of the reaction carrier under a first irradiation condition; and detecting a second optical signal detection value of the non-reaction area of the reaction carrier under a second irradiation condition, and acquiring an optical signal correction value of the reaction area after background correction based on the first optical signal detection value, the second optical signal detection value and the corresponding irradiation condition.
drawings
A further understanding of the nature and advantages of the present disclosure may be realized by reference to the following drawings. In the drawings, similar components or features may have the same reference numerals.
FIG. 1 shows a block diagram of a system for detection of the amount of a specific substance in an analyte according to the application;
FIG. 2 shows a schematic of a test strip according to the present application;
FIG. 3 is a block diagram showing an optical signal detection apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte according to a first embodiment of the present application;
Fig. 4A shows a schematic diagram of one example of an arrangement of a first light source and a first optical signal detector according to a first embodiment of the present application;
FIG. 4B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 4A with respect to the regions in the test strip;
fig. 5 shows a flow chart of a method for determining an optical signal value correlation function according to a first embodiment of the present application;
FIG. 6 shows a flow chart of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a first embodiment of the present application;
FIG. 7 is a block diagram showing an optical signal detection apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte according to a second embodiment of the present application;
Fig. 8A shows a schematic diagram of one example of an arrangement of a light source and a light signal detector according to a second embodiment of the present application;
FIG. 8B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 8A with respect to a region in a test strip;
FIGS. 8C and 8D are schematic diagrams illustrating the relative positional relationship of another exemplary arrangement of a light source and a light signal detector relative to an area in a test strip according to the present application;
fig. 9A shows a schematic diagram of another example of an arrangement of a light source and a light signal detector according to a second embodiment of the present application;
FIG. 9B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 9A with respect to a region in a test strip;
Fig. 10A shows a schematic diagram of another example of an arrangement of a light source and a light signal detector according to a second embodiment of the present application;
FIG. 10B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 10A with respect to a region in a test strip;
FIG. 11 shows a flow chart of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a second embodiment of the present application;
FIG. 12 is a flow chart illustrating a process for obtaining background corrected optical signal correction values for a reaction zone based on first and second optical signal detection values according to the present application;
FIG. 13 is a block diagram showing an optical signal detection apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte according to a third embodiment of the present application;
Fig. 14A shows a schematic diagram of one example of an arrangement of a light source and a light signal detector according to a third embodiment of the present application;
FIG. 14B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 14A with respect to the regions in the test strip;
FIG. 15 shows a flowchart of an example of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a third embodiment of the present application;
FIG. 16 shows a flow chart of another example of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to the third embodiment of the present application;
Fig. 17 is a schematic external shape diagram showing an example of a concrete implementation of an optical signal detection apparatus for detecting an optical signal value in a reaction region of a reaction carrier after a reaction with an analyte according to the fourth embodiment of the present application;
FIG. 18 illustrates an exploded view of the internal structure of the specific implementation example shown in FIG. 17; and
Fig. 19 is an exploded view showing an internal structure of another specific implementation example of the optical signal detection apparatus for detecting an optical signal value in the reaction region of the reaction carrier after the reaction with the analyte according to the fifth embodiment of the present application.
detailed description of the preferred embodiments
The subject matter described herein will now be discussed with reference to example embodiments. It should be understood that these embodiments are discussed only to enable those skilled in the art to better understand and thereby implement the subject matter described herein, and are not intended to limit the scope, applicability, or examples set forth in the claims. Changes may be made in the function and arrangement of elements discussed without departing from the scope of the disclosure. Various examples may omit, substitute, or add various procedures or components as needed. For example, the described methods may be performed in an order different from that described, and various steps may be added, omitted, or combined. In addition, features described with respect to some examples may also be combined in other examples.
As used herein, the term "include" and its variants mean open-ended terms in the sense of "including, but not limited to. The term "based on" means "based at least in part on". The terms "one embodiment" and "an embodiment" mean "at least one embodiment". The term "another embodiment" means "at least one other embodiment". The terms "first," "second," and the like may refer to different or the same object. Other definitions, whether explicit or implicit, may be included below. The definition of a term is consistent throughout the specification unless the context clearly dictates otherwise.
As used herein, the term "coupled" means either a direct mechanical, communication, or electrical connection between the two components, or an indirect mechanical, communication, or electrical connection through intermediate components. The term "electrically connected" means that electrical communication can be made between two components for data/information exchange. Likewise, the electrical connection may refer to a direct electrical connection between two components, or an indirect electrical connection through an intermediate component. The electrical connection may be achieved in a wired manner or a wireless manner.
fig. 1 shows a block diagram of a system for detecting the content of a specific substance in an analyte according to the present application (hereinafter referred to as specific substance content detecting system 1).
As shown in fig. 1, the specific substance content detecting system 1 includes a reaction carrier 10. The reaction carrier 10 has a reaction zone and a non-reaction zone. In the reaction area of the reaction carrier 10, a labeled reactant capable of reacting with a specific substance to be measured is provided. The labeling reactant is not disposed in the non-reaction region of the reaction carrier 10. Since the principle of the present application is to detect the value of an optical signal, all reaction carriers that produce a change in an optical signal after reacting with an analyte can be applied, and examples of the reaction carrier 10 can include any test strip or reagent card for detecting a large molecule or small molecule chemical substance, including but not limited to test strips prepared by the competitive method or sandwich method. Examples of the test paper may include, for example, a colloidal gold test paper, a fluorescent test paper, a dry chemical test paper, and the like. Examples of reagent cards may include, for example, microfluidic reagent cards and the like. FIG. 2 shows a schematic of a test strip according to the present application. In the test paper shown in FIG. 2, 2 reaction regions, i.e., regions where the display band 1 and the color development band 2 are located, are shown. In general, the reaction zone may be configured to have a prescribed size. The area of the test strip other than the reaction area is a non-reaction area, for example, a blank area of the test strip in fig. 2.
The specific substance content detection system 1 may further include an optical signal detection device 20. The optical signal detection device 20 is used for detecting the optical signal correction value of the reaction area of the reaction carrier after the labeled reactant in the reaction carrier reacts with the substance to be detected. The structure and operation of the optical signal detection device 20 will be described in detail below with reference to fig. 3 to 18.
The specific substance content detection system 1 may further include a specific substance content determination unit 30. The specific substance content determination unit 30 is electrically connected to the optical signal detection device 20, and is configured to receive the detected optical signal correction value of the reaction region from the optical signal detection device 20, and determine the content of the specific substance in the analyte based on the detected optical signal correction value of the reaction region. For example, the specific substance content determination unit 30 may determine the specific substance content corresponding to the detected optical signal correction value based on the correspondence between the optical signal value and the specific substance content. The correspondence may be, for example, a correspondence table between the optical signal value and the specific substance content, or a variation curve between the optical signal value and the specific substance content, or a functional relationship between the optical signal value and the specific substance content. For example, the specific substance content determining unit 30 may determine the specific substance content by table look-up or calculation (e.g., mathematical solution). In the present application, the specific substance is a chemical substance to be detected, such as a macromolecular or small molecule compound, for example, the specific substance may include one of the following: toxins, antibiotics, pesticides or hormones.
the specific substance content determination unit 30 and the optical signal detection device 20 may communicate with each other in a wired or wireless manner. Examples of the wired communication may be, for example, an optical fiber, a coaxial line, and the like. Examples of such wireless communication may be, for example, bluetooth, WiFi, microwave, etc.
The specific substance content detection system 1 may further include an upper computer 40. The upper computer 40 is electrically connected with the specific substance content determination unit 30, and is used for receiving the determined specific substance content from the specific substance content determination unit 30 and presenting the detection result of the specific substance content to the user. Examples of the upper computer 40 may include, but are not limited to, a mobile phone, a PC, a tablet, a single chip, a server, or the like, for example. In addition, the upper computer 40 may also control the operation of the optical signal detection device 20, the operation of the specific substance content determination unit 30, and the operation (e.g., interactive operation) between the optical signal detection device and the specific substance content determination unit 30.
In the present application, the specific substance content determining unit 30 may be implemented in the form of a software module or a hardware module. The specific substance content determination unit 30 may be implemented in, for example, a cloud server, or may be included in the optical signal detection device 20 or the upper computer 40.
The optical signal detecting device 20 may further include a temperature sensor for detecting temperature data when the reaction carrier is in a detection state. In the present application, the detected temperature data may be used to select a corresponding curve of the concentration of the specific substance as a function of the optical signal value, i.e. a curve characterizing the correspondence between the optical signal value and the content of the specific substance as described above.
first embodiment
The optical signal detection device is designed according to the theoretical position of the reaction carrier in the ready state, and actually, various factors can cause the position of the reaction area to have an error with the theoretical position during detection, such as design errors and assembly errors of the test paper or reagent reaction area during production, the difference between the actual position and the theoretical position of the reaction area caused by the difference, and the slight position difference of the test paper card relative to the device caused by the force applied when the detection device is inserted into the reagent card. These cause a deviation between the detected value of the optical signal and the actual value of the optical signal. Therefore, in the scheme of the application, the reaction area is irradiated by light sources at different positions, the same photosensitive element is used for detection, two optical signals are obtained, the correlation exists between the operation result of the two optical signals, the optical signal detection value and the real optical signal value, the correlation is found out through multiple tests, namely, the functional relation is determined, then the optical signal values at the different positions of the target test paper or reagent and the detection value are obtained, and the detection value is brought into the functional relation, so that the position errors caused by various reasons are corrected.
fig. 3 shows a block diagram of an optical signal detection device 20 for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a first embodiment of the present application.
As shown in fig. 3, the optical signal detection device 20 may include at least one set of first light sources 210, each set including at least two first light sources. At least two first light sources of each set of first light sources may be controlled separately to illuminate the same reaction area of the reaction carrier, e.g. the colored strip 1 in fig. 2, under the first illumination condition and the second illumination condition. Further, in the present application, each set of first light sources illuminates a different reaction zone, such as one set of first light sources (such as light sources 1404 and 1405 in FIG. 14A) illuminating color stripe 1 and another set of first light sources (such as light sources 1408 and 1409 in FIG. 14A) illuminating color stripe 2. Further, for convenience of illustration, a group of first light sources is shown in fig. 3 as an example. In other examples of the present application, two or more sets of first light sources may be included.
In one example of the present application, the number of first light sources included in each group of first light sources may be an even number, such as 2, 4, 6, etc. Typically, the number of first light sources in each group of first light sources is 2. Furthermore, in one example of the present application, the positions of the at least two first light sources of each set of first light sources are arranged so as to be located on both sides of the reaction area of the standard reaction carrier when the standard reaction carrier is in the ready-to-detect state, for example, above or below both sides of the reaction area of the standard reaction carrier, that is, projections of the arrangement positions of the at least two light sources on the reaction area of the standard reaction carrier are located on both sides of the reaction area. Preferably, the positions of the at least two first light sources are arranged such that they are symmetrically located on both sides of the reaction zone when the standard reaction carrier is in the ready-to-detect state. As shown in fig. 4A, the first light source group includes three groups of first light sources, and each group of first light sources is symmetrically arranged on both sides of one color rendering stripe, for example, as shown in fig. 4B, the first light sources 404 and 405 are symmetrically arranged on both sides of the color rendering stripe 1. In the present application, the standard reaction carrier means a reaction carrier free from design errors and assembly errors, and insertion errors due to insufficient insertion of the standard reaction carrier into the optical signal detection apparatus are not generated even when the optical signal detection is performed using the standard reaction carrier.
In another example of the present application, the number of first light sources included in each group of first light sources may also be an odd number, such as 3, 5, 7, etc. In this case, one first light source of the group of first light sources is arranged above (e.g., directly above) the color development strip, and the remaining even number of first light sources are symmetrically arranged on both sides of the color development strip.
In the present application, the first illumination condition includes that two groups of light sources composed of respective first light sources of the at least two first light sources according to a specified rule are respectively illuminated. The specified rule is that the two groups of light sources are composed to generate light source signals with different angles for the same reaction zone. For example, assuming that each set of first light sources includes 2n first light sources, the two sets of light sources in the first illumination condition are respectively composed of k first light sources, and the positions of the two sets of light sources are symmetrical with respect to the color development band, where k is equal to or less than n. Further, assuming that each set of first light sources includes 2n +1 first light sources, the two sets of light sources in the first illumination condition are respectively composed of k +1 first light sources, and likewise, the positions of the two sets of light sources are symmetrical with respect to the color development band. The second illumination condition includes illumination by a light source selected from the first light sources, and these light sources should be associated with the above-mentioned light sources for forming the first illumination condition, that is, the light source illumination angle, the illumination distance, the light source type, and the like, that is, the second illumination condition is associated with the first illumination condition. For example, if the first illumination condition is to be illuminated by two light sources arranged symmetrically with respect to the reaction zone (when the standard reaction carrier is in the ready-for-detection state), the second illumination condition may be to select a light source having a similar arrangement to the light source forming the first illumination condition, i.e., to select the other two light sources arranged symmetrically with respect to the reaction zone to be illuminated. Preferably, the second illumination condition may include illumination by a light source group including at least a light source selected from the two groups of light sources. For example, the light source group in the second illumination condition may be composed of the above 2k light sources, of a light source selected from the above 2k light sources, of the above 2k light sources and other light sources, or of a light source selected from the above 2k light sources and other light sources. Preferably, the second illumination condition comprises illumination by all of the at least two first light sources.
The optical signal detection device 20 may include at least one first optical signal detector 220 for detecting a first optical signal detection value pair under a first illumination condition and a second optical signal detection value under a second illumination condition of the reaction area of the reaction carrier after the reaction with the analyte. Here, the first optical signal detection value pair is an optical signal detection value pair composed of two optical signal detection values obtained under the irradiation of the two sets of light sources in the first irradiation condition. In the present application, one first optical signal detector 220 may be provided for each set of first light sources 210. In the present application, the first light source group 210 and the first optical signal detector 220 may also be collectively referred to as a first optical signal detection unit, as shown in fig. 3.
For example, assume that each set of first light sources 210 consists of two first light sources 210-1, 210-2. The first illumination condition means that the first light sources 210-1 and 210-2 are turned on to individually illuminate, and then the corresponding light signal detection values detected by the first light signal detector 220 are used to form a first light signal detection value pair. The second illumination condition is that both the first light sources 210-1 and 210-2 are turned on to illuminate and then the corresponding light signal detection value is detected by the first light signal detector 220 as the second light signal detection value.
In the present application, the first light source 210 and the first optical signal detector 220 may be arranged on the same plane, for example, on the same Printed Circuit Board (PCB), as shown in fig. 18. Fig. 4A shows a schematic diagram of one example of an arrangement of a first light source and a first optical signal detector according to a first embodiment of the present application. FIG. 4B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 4A with respect to the regions in the test strip.
in fig. 4A, three sets of first light sources and three first light signal detectors are shown, wherein the first light sources 404 and 405 constitute a set of first light sources, and the first light signal detector 401 is used to detect light signal values under illumination conditions formed by the set of first light sources 404 and 405. The first light sources 406 and 407 constitute a set of first light sources, and the first light signal detector 402 is configured to detect light signal values under illumination conditions formed by the set of first light sources 406 and 407. The first light sources 408 and 409 constitute a set of first light sources, and the first light signal detector 403 is used to detect light signal values under the illumination conditions formed by the set of first light sources 408 and 409. In addition, each set of light sources is used to illuminate the same reaction area of the reaction carrier, e.g., one color development band of the test strip shown in FIG. 2.
The positional relationship of the first light sources 404 and 405 and the first optical signal detector 401 with respect to the color development band to be detected is shown in fig. 4B. As shown in fig. 4B, the first optical signal detector 401 is located above, preferably directly above, the color development band, and the first light sources 404 and 405 are symmetrically arranged on both sides of the color development band, specifically, above both sides of the color development band on which projections of the arrangement positions of the first light sources 404 and 405 on the reaction regions of the reaction carrier 10 are located.
In the present application, the first light source 210 emits light with a desired wavelength, and after the light is irradiated onto the test paper, the light is detected by the optical signal detector 220. In one example of the present application, the first light source 210 may be a full wavelength range or a specific wavelength range light source, for example, an LED lamp, wherein a green LED lamp with a high signal response value is preferred.
The first optical signal detector 220 functions to convert an optical signal in the reaction region into an electrical signal, thereby detecting the intensity of the optical signal. Examples of the first optical signal detector may include a photodiode, a color sensor, a phototransistor, a monochromatic light sensor. The first optical signal detector 220 preferably uses a photodiode if the size and cost of the optical signal detecting device 20 are taken into consideration.
In the present application, when the reaction carrier (e.g., a fluorescent test paper) needs to be detected based on fluorescence, the first light source 210 may be a fluorescence excitation light source, and the first optical signal detector 220 has a filtering characteristic matching the wavelength of the excited fluorescence. For example, the first light source having a corresponding wavelength may be obtained by disposing a filter of a specific wavelength on a light source optical path of a general light source (i.e., a light source emitting white light), or a specific light source capable of emitting fluorescent light may be used. Furthermore, preferably, a filter may be further disposed on the optical path of the fluorescent light source in order to filter stray light. In addition, a filter matched to the wavelength of the excited fluorescence may be added to the detection optical path of the first optical signal detector 220, and a narrow-band filter with better filtering effect is preferred.
The optical signal detection device 20 may further include an optical signal correction value determination unit 230. The optical signal correction value determining unit 230 is electrically connected to the first optical signal detector 220, and is configured to receive the detected optical signal detection value from the first optical signal detector 220 and process the received optical signal detection value to obtain an optical signal correction value. Specifically, the optical signal correction value determining unit 230 performs predetermined processing on the first optical signal detection value pair received from the first optical signal detector 220; and determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and the corresponding optical signal value correlation function. Here, the optical signal value correlation function is used to reflect a functional relationship between the optical signal correction value after the position error correction and the predetermined processing result and the second optical signal detection value. In the present application, the predetermined processing includes difference processing or ratio processing. The difference processing is to perform subtraction on two optical signal detection values in the first optical signal detection value pair. The ratio processing means calculating a ratio of two optical signal detection values in the first optical signal detection value pair. In addition, the optical signal correction value determining unit 230 may be implemented in an upper computer or a server, but thus data transmission is relatively slow and the error probability is increased, so that the present optical signal detecting apparatus includes it inside the apparatus.
In the present application, for a fixed optical signal detector and illumination conditions, the optical signal value correlation function may be obtained by performing a plurality of tests by adjusting the position of the reagent card in the optical signal detection device a plurality of times to obtain a corresponding optical signal detection value and an optical signal reference value, and then performing analysis (e.g., curve fitting) or the like to find the correlation between the optical signal reference value and the predetermined processing result and the second optical signal detection value. Furthermore, the corresponding optical signal value correlation function may also be obtained by setting different first and second illumination conditions and/or different optical signal detector types. In the present application, the optical signal reference value may be obtained using a reliable reference detection method or instrument, for example, using a large dedicated instrument. And the optical signal detection value can be obtained by various types of optical signal detectors available on the market.
In this application, it is noted that the light signal value correlation function is correlated with the model number of the light signal detector, the first illumination condition, and the second illumination condition. The light signal value correlation function changes whenever any one of the light signal detector model, the first and second illumination conditions changes. Further, the irradiation conditions may be determined by the number of light sources, the irradiation positions of the light sources, the kinds of the light sources, and the like.
fig. 5 shows a flow chart of a method for determining an optical signal value correlation function according to a first embodiment of the present application.
as shown in fig. 5, in step S510, first light signal detection value pairs of the same reaction region (for example, display color band 1) detected by a light signal detector of a predetermined model under irradiation of light sources respectively in a light source pair at set positions are detected. Then, in step S520, predetermined processing is performed on the acquired first optical signal detection value pair to acquire a predetermined processing result. Next, in step S530, a second optical signal detection value detected by the optical signal detector of the predetermined model under the light source-to-illumination is acquired. In step S540, a reference value of the optical signal under the light source versus illumination is obtained using a reliable method or instrument.
After the predetermined processing result, the second optical signal detection value, and the corresponding optical signal reference value are acquired as above, it is determined whether the predetermined number of trials has been reached at step S550. When the number of times of the predetermined test is not reached, the position of the reaction carrier (reagent card) in the optical signal detection apparatus is finely adjusted in step S560, and then the process returns to step S510, and the above-described detection process is performed again for the reaction carrier whose position has been finely adjusted. After the predetermined number of trials is reached, in step S570, an optical signal value association function corresponding to the predetermined model of optical signal detector is determined based on the acquired predetermined processing result, the second optical signal detection value, and the corresponding optical signal reference value. In the above manner, the light signal value correlation function corresponding to the predetermined model of the light signal detector under the first and second illumination conditions can be obtained. Further, in the present application, it is also possible to acquire the corresponding optical signal value correlation function by adjusting the model number of the optical signal detector, the first and second illumination conditions, and the like, respectively.
In one example of the present application, the optical signal value correlation function may be stored in the optical signal detection apparatus 20, for example, in the optical signal detection apparatus 20 in the form of a mapping table, i.e., the optical signal value correlation function is in a mapping relationship with the model number, the first and/or the second illumination condition of the first optical signal detector 220 used in the optical signal detection apparatus 20. Accordingly, the optical signal detection device 20 may comprise a storage unit for storing the optical signal correlation function. In another example of the present application, the optical signal value correlation function may also be stored in an external server, for example in the form of a mapping table. The optical signal correction value determining unit 230 is electrically connected to an external server in a wired or wireless manner to acquire a corresponding optical signal value correlation function from the external server when necessary.
In another example of the present application, the optical signal detection apparatus 20 may further include an optical signal value correlation function generation unit that generates the optical signal value correlation function based on history data of a predetermined processing result, history data of the second optical signal detection value, and history data of a corresponding optical signal detection reference value.
In an example of the present application, the optical signal correction value determining unit 230 may further include an optical signal preprocessing module (not shown) for performing a predetermined process on the first optical signal detection value pair. For example, the optical signal preprocessing module may be implemented using a subtractor or a ratio calculator. The optical signal correction value determining unit 230 may further include an optical signal correction value determining module (not shown) for determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and the corresponding optical signal value correlation function. Here, the optical signal correction value determining unit 230 and/or its components may be implemented by a device having a calculation capability, for example, a processor, a microprocessor, a single chip microcomputer, a DSP, an FPGA, or a digital circuit unit having a calculation capability.
optionally, the optical signal detection device 20 may further include a communication unit 240. Examples of the communication unit 240 may include a bluetooth device, a USB device, Zigbee, an infrared unit, a WIFI device, or the like. When the specific substance content determination unit 30 is provided in the optical signal detection device 20, the communication unit 240 is provided between the specific substance content determination unit 30 and the upper computer 40, for enabling data communication between the specific substance content determination unit 30 and the upper computer 40. When the specific substance content determining unit 30 is provided in the upper computer 40 or the server, the communication unit 240 is provided between the optical signal correction value determining unit 230 and the specific substance content determining unit 30, and is configured to implement data communication between the optical signal correction value determining unit 230 and the specific substance content determining unit 30.
With the optical signal detection apparatus, when optical signal detection is performed for a single reaction region, light sources at different angles are provided for the same reaction region by disposing at least two light sources in different regions, detection is performed with the same optical signal detector to obtain two optical signals, then a difference or ratio operation result of the two signals is calculated, and a predetermined optical signal detection value, an optical signal correction value (i.e., the optical signal reference value described above), and a correlation between the difference or ratio operation result (i.e., the optical signal value correlation function) are used to determine an optical signal correction value, thereby correcting a position error of the reaction region.
Optionally, the optical signal detection apparatus 20 may further include a timer 250 and a detection parameter setting unit 260. The timer 250 is used for timing after the reaction carrier 10 enters the ready state for detection. The detection parameter setting unit 260 is used for setting the detection start time, the detection stop time and the detection interval period of the optical signal detector according to the specific substance to be detected and the properties of the label on the reaction carrier 10. For example, the detection parameter setting unit 260 sets the detection start time, the detection off time, and the detection interval period of the first optical signal detector 220.
further, optionally, the optical signal detection device 20 may further include a timing trigger unit 270 connected to the timer 250. The timing triggering unit 270 is used for triggering the timer 250 to start timing after the reaction carrier 10 enters the detection ready state. For example, when the reaction carrier 10 (e.g., reagent strip) is placed in the optical signal detection device 20, e.g., when a test paper is inserted, the timing trigger unit 270 triggers the timer 250 to start timing. The implementation form of the timing trigger unit 270 may include, but is not limited to, a mechanical trigger unit (e.g., a micro switch), an optoelectronic trigger unit (e.g., a photoelectric sensor), and a magnetic trigger unit (e.g., a hall element). By using the timing trigger unit 270 and combining the detection start time, the detection stop time and the detection interval period of the optical signal detector set by the detection parameter setting unit 260, the optical signal detection apparatus 20 can be applied to reagents with different reaction times, thereby realizing detection of different specific substances.
In one example of the present application, the illumination control for the first light source 210 and the light signal detection by the first light signal detector 220 may be artificially controlled. For example, the first light source 210 and the first optical signal detector may be operated by manually turning on power switches of the first light source 210 and the first optical signal detector 220.
in another example of the present application, the optical signal detection apparatus 20 may further include a controller (not shown in the figure) electrically connected to each light source and each optical signal detector of the optical signal detection apparatus 20, and configured to control the irradiation of each light source and the detection of each optical signal detector. In addition, the controller may be electrically connected to other components of the optical signal detection device 20 for controlling data communication between the respective components of the optical signal detection device 20 and/or data communication between the components of the optical signal detection device 20 and the outside. In the present application, the controller may be implemented by a processor, a microprocessor, a single chip, a DSP, an FPGA, or other digital circuit units with processing capability.
Fig. 6 shows a flow chart of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a first embodiment of the present application.
As shown in fig. 6, in step S610, a first optical signal detection value pair under a first illumination condition and a second optical signal detection value under a second illumination condition of a reaction area of a reaction carrier reacted with an analyte are detected. Next, in step S620, a predetermined process is performed on the first optical signal detection value pair to obtain a predetermined process result. Then, in step S630, an optical signal correction value of the reaction zone after the position error correction is determined based on the predetermined processing result and the detected second optical signal detection value and using the corresponding optical signal value correlation function.
optionally, in an example of the present application, before step S630, the method may further include: the corresponding optical signal value correlation function is determined from the mapping table based on the model number of the first optical signal detector 220 used in the optical signal detection apparatus 20, the first and second illumination conditions. For example, in one example, the mapping table may be stored in the optical signal detection apparatus 20. In another example, the mapping table may be stored in an external server. In this case, the optical signal detection apparatus 20 may acquire the corresponding optical signal value correlation function from the external server based on the model number of the first optical signal detector 220 used in the optical signal detection apparatus 20, the first and second illumination conditions.
Optionally, in an example of the present application, the method may further include: the at least two first light sources 210 are controlled to illuminate the predetermined reaction area of the reaction carrier 10 according to the first and second illumination conditions.
Optionally, in an example of the present application, the method may further include: determining the content of the specific substance based on the determined optical signal correction value.
Second embodiment
Fig. 7 shows a block diagram of an optical signal detection device 20' for detecting an optical signal correction value in a reaction area of a reaction carrier after reaction with an analyte according to a second embodiment of the present application. The embodiment shown in fig. 7 is an improvement to the optical signal detection device 20 shown in fig. 3.
The optical signal detecting device 20' shown in fig. 7 is different from that of fig. 3 in that each of at least one set of first light sources is controlled to irradiate the reaction region of the reaction carrier only under the first irradiation condition, and the first irradiation condition in the present embodiment is different from that in the first embodiment. In addition, at least one set of second light sources 210 'and at least one second light signal detector 220' are added in fig. 7. Further, the optical signal correction value determination unit 230' shown in fig. 7 is different from the optical signal correction value determination unit 230 in fig. 3. The other elements in fig. 7 are identical to the corresponding elements shown in fig. 3. For simplicity of description, only the differences will be described below, and the same elements will not be described again.
As shown in FIG. 7, the optical signal detecting device 20' includes at least one set of first light sources 210, each set of first light sources being used to irradiate the same reaction area of the reaction carrier 10 under the first irradiation condition. Here, each of the at least one set of first light sources 210 may include one or more first light sources. In the case where each set of the first light sources 210 includes a plurality of first light sources, the plurality of first light sources are used to illuminate the same color development band (i.e., the same reaction region). In the present application, each of the first light source groups 210 corresponds to one color development band (i.e., one reaction region) for irradiating the corresponding reaction region of the reaction carrier 10, e.g., the color development bands 1, 2, etc., under the first irradiation condition. In the present embodiment, the first illumination condition refers to an illumination condition in which a single light source group consisting of a first light source selected from the first light source group 210 individually illuminates. The at least one first optical signal detector 220 is used for detecting a first optical signal detection value of the reaction area after the reaction with the object to be detected under the first irradiation condition.
The optical signal detection device 20 ' may further comprise at least one set of second light sources 210 ' and at least one second optical signal detector 220 '. Each of the at least one set of second light sources 210' is used to illuminate the same non-reaction area of the reaction carrier 10 under a second illumination condition. Here, each set of second light sources 210' may include one or more second light sources for illuminating the same non-reaction region (i.e., the same blank area of the test strip). The at least one second light source 210 'may also include a plurality of second light source sets, each second light source set 210' corresponds to a non-reaction region for irradiating the corresponding non-reaction region of the reaction carrier 10, such as a blank region of the test strip, under the second irradiation condition. Accordingly, at least one second optical signal detector 220' is used to detect a second optical signal detection value of the corresponding non-reaction area of the reaction carrier 10 under the second illumination condition. Here, one second optical signal detector 220 'may be provided for each set of second light sources 210'. The second illumination condition in the present embodiment refers to an illumination condition in which a single light source group composed of the second light sources in each group of the second light sources 210' is illuminated according to a predetermined rule, unlike the second illumination condition in the first embodiment.
then, the optical signal correction value determining unit 230' determines the optical signal correction value of the background-corrected reaction region based on the first and second optical signal detection values and the corresponding irradiation conditions (i.e., the first and second irradiation conditions in the present embodiment).
In one example of the present application, the first light source group 210 and the second light source group 210 'may be implemented with different light sources, and the at least one first light signal detector 220 and the at least one second light signal detector 220' may be implemented with different light signal detectors, for the same reaction region, for example, the color development strip 1. Fig. 8A shows a schematic diagram of one example of an arrangement of a light source and a light signal detector according to a second embodiment of the present application. FIG. 8B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 8A with respect to the regions in the test strip. As shown in fig. 8A and 8B, the first light source 804 and the second light source 806 are positioned so as to be located directly above the reaction region (colored band 1) and the non-reaction region (test strip blank region) of the standard reaction carrier when the standard reaction carrier is in the ready-to-detect state, respectively, and the first optical signal detector 801 and the second optical signal detector 802 are positioned so as to be located directly above the reaction region (colored band 1) and the non-reaction region (test strip blank region) when the reaction carrier 10 is in the ready-to-detect state, respectively. In the present application, the first optical signal detector 801 and the second optical signal detector 802 may be disposed at other suitable positions. In fig. 8B, a second light source 806 and a corresponding second optical signal detector 802 are shown as being disposed directly above the non-reaction region (blank region of the test paper) between the colored band 1 and the colored band 2. In other examples of the present application, the second light source 806 and the corresponding second light signal detector 802 may be disposed directly above the non-reaction region (blank region of the test paper) outside the color development bands 1 and 2, for example, directly above the left side regions of all the color development bands (color development bands 1 and 2), as in fig. 8C, or directly above the right side regions of all the color development bands (color development bands 1 and 2), as in fig. 8D.
in one example of the present application, the first light source group 210 and the second light source group 210 'may be implemented with the same light source, and the at least one first light signal detector 220 and the corresponding at least one second light signal detector 220' may be implemented with different light signal detectors, for the same reaction region, for example, the color development strip 1. The same light source is positioned to be located in the area between the first light signal detector 220 and the second light signal detector 220'. Fig. 9A shows a schematic diagram of another example of an arrangement of a light source and a light signal detector according to a second embodiment of the present application. FIG. 9B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 9A with respect to the regions in the test strip.
In one example of the present application, the first light source group 210 and the second light source group 210 'may be implemented with different light sources, and the at least one first light signal detector 220 and the corresponding at least one second light signal detector 220' may be implemented with the same light signal detector, for the same reaction region, for example, the color development strip 1. The position of the same optical signal detector is arranged so as to be above the reaction area (colored strip 1) of the standard reaction carrier when the standard reaction carrier is in a ready-to-detect state, or at any position above the standard reaction carrier. Fig. 10A shows a schematic diagram of another example of an arrangement of a light source and a light signal detector according to the second embodiment of the present application. FIG. 10B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 10A with respect to the regions in the test strip.
Fig. 11 shows a flow chart of a method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte according to a second embodiment of the present application.
As shown in fig. 11, in step S1110, a first optical signal detection value of the reaction area of the reaction carrier 10 reacted with the analyte under the first irradiation condition is detected. Wherein the first illumination condition is provided by a corresponding first light source. Next, in step S1120, a second optical signal detection value of the non-reaction region of the reaction carrier 10 under the second irradiation condition is detected. Wherein the second illumination condition is provided by a corresponding second light source. Then, in step S1130, a light signal correction value of the reaction region after the background correction is determined based on the first light signal detection value and the second light signal detection value and the corresponding irradiation conditions (i.e., the first irradiation condition and the second irradiation condition mentioned in the second embodiment).
FIG. 12 is a flow chart illustrating a process for determining a background corrected optical signal correction value for a reaction zone based on first and second optical signal detection values according to the present application.
As shown in fig. 12, in step S1131, it is determined whether the first irradiation condition and the second irradiation condition are the same. If the first illumination condition and the second illumination condition are different, the second optical signal detection value is converted into an optical signal detection value under the same illumination condition as the first illumination condition in step S1133. For example, assuming that the first illumination condition is illumination with 2 light sources of the same model and the second illumination condition is illumination with a light source of the same model among 1 first illumination condition, the second light signal detection value is multiplied by 2 as the converted light signal detection value. Further, more preferably, when considering that the illumination conditions are the same, factors that influence the illumination conditions, such as the illuminance of the light source, the angle of the light source, and the like, may also be considered. Then, in step S1135, the converted second optical signal detection value is subtracted from the first optical signal detection value as an optical signal correction value of the background-corrected reaction region.
When the first and second irradiation conditions are the same as a result of the determination in S1131, the second optical signal detection value is subtracted from the first optical signal detection value in step S1135, and the result is used as the optical signal correction value of the reaction region after the background correction.
optionally, in another example of the present application, the method for detecting an optical signal value in a reaction area of a reaction carrier after reacting with an analyte may further include: controlling at least one set of first light sources 210 to irradiate the reaction area of the reaction carrier 10 according to the first irradiation condition; and controlling at least one set of second light sources 210' to irradiate the non-reaction region of the reaction carrier 10 according to the second irradiation condition.
Optionally, in another example of the present application, the method may further include: determining the content of the specific substance based on the determined optical signal correction value.
With the optical signal detecting apparatus and method shown in fig. 7-12, by adding a second light source and/or a second optical signal detecting apparatus for detecting an optical signal value of a non-reaction region (i.e., a background region of a reaction carrier), and subtracting the second optical signal detection value from the first optical signal detection value of the reaction region, it is possible to eliminate the influence of the optical signal generated by the background region of the reaction carrier (reagent strip or test paper) and/or non-reacted reactants and/or samples after reaction, i.e., the influence of the background optical signal, thereby making the detected optical signal correction value of the reaction region more accurate.
Third embodiment
Fig. 13 shows a block diagram of an optical signal detection device 20 ″ for detecting an optical signal correction value in a reaction area of a reaction carrier after reaction with an analyte according to a third embodiment of the present application. The embodiment shown in fig. 13 is an improvement of the optical signal detection device 20 shown in fig. 3.
Compared to fig. 3, the optical signal detection device 20 ″ shown in fig. 13 differs in that at least one set of second light sources 210 'and at least one second optical signal detector 220' are added. Further, the optical signal correction value determination unit 230 ″ shown in fig. 13 is different from the optical signal correction value determination unit 230 in fig. 3. The other elements in fig. 13 are identical to the corresponding elements shown in fig. 3. For simplicity of description, only the differences will be described below, and the same elements will not be described again.
The first light source group 210 in fig. 13 is identical to the first light source group in fig. 3 and will not be described again. The at least one first optical signal detector 220 detects a first optical signal detection value pair of the corresponding reaction region after the reaction with the analyte under the first illumination condition and a second optical signal detection value under the second illumination condition. Here, the first and second irradiation conditions in the present embodiment are similar to those described in the first embodiment. The structure and function of the at least one set of second light sources 210' in fig. 13 are identical to those of the at least one set of second light sources in fig. 7. The at least one second optical signal detector 220' is used for detecting a third optical signal detection value of the non-reaction area of the reaction carrier 10 under a third illumination condition. Here, the third illumination condition in the present embodiment is similar to the second illumination condition described in the second embodiment, and may be provided by the first light source group or by a separate second light source group.
in one example of the present application, the background signal of the optical signal value of the reaction region may be subtracted, and then the position error of the reaction region may be corrected. Specifically, the optical signal correction value determination unit 230 ″ is configured to perform predetermined processing on the first optical signal detection value pair to obtain a predetermined processing result. Next, the optical signal correction value determining unit 230 ″ acquires the second optical signal detection value after background correction based on the second optical signal detection value and the third optical signal detection value. In one example of the present application, the above-described correction function may be implemented using a background correction module. Then, the optical signal correction value determining unit 230 ″ determines the optical signal correction value of the reaction region after the position error correction based on the predetermined processing result, the background-corrected second optical signal detection value, and the corresponding optical signal value correlation function.
In another example of the present application, the position error of the reaction region may be corrected for the optical signal value of the reaction region before background signal subtraction. Specifically, the optical signal correction value determining unit 230 ″ may perform a predetermined process on the first optical signal detection value pair of the reaction zone to obtain a predetermined process result, and determine the second optical signal detection value of the reaction zone subjected to the position error correction based on the predetermined process result, the second optical signal detection value, and the corresponding optical signal value correlation function. Further, the optical signal correction value determining unit 230 ″ is further configured to obtain the optical signal correction value of the reaction region after the background correction based on the determined optical signal correction value of the reaction region after the position error correction, the third optical signal detection value, and the corresponding irradiation conditions (i.e., the second irradiation condition and the third irradiation condition).
In the present application, the optical signal correction value determining unit 230 ″ may be implemented by a processor, a microprocessor, a single chip, a DSP, an FPGA, or other digital circuit units with processing capability.
Fig. 14A shows a schematic diagram of one example of an arrangement of a light source and a light signal detector according to a third embodiment of the present application. FIG. 14B shows a schematic diagram of the relative positional relationship of the example arrangement of FIG. 14A with respect to the regions in the test strip. In fig. 14A, 2 display bands and one blank area of the test strip are shown, along with corresponding 2 sets of first light sources (1404,1405,1408 and 1409) and one set of second light sources (1406 and 1407).
Fig. 15 shows a flowchart of an example of a method for detecting an optical signal correction value in a reaction area of a reaction carrier after reaction with an analyte according to a third embodiment of the present application.
As shown in FIG. 15, in step S1510, a first light signal detection value pair under a first illumination condition and a second light signal detection value under a second illumination condition of a corresponding reaction zone of a reaction carrier are detected by at least one first light signal detector. In step S1520, predetermined processing is performed on the first optical signal detection value pair of the reaction zone to obtain a predetermined processing result, and then, in step S1530, an optical signal correction value of the reaction zone subjected to the position error correction is determined based on the predetermined processing result for the reaction zone, the second optical signal detection value, and the corresponding optical signal value correlation function.
Next, in step S1540, a third optical signal detection value of the corresponding non-reaction area of the reaction carrier under a third irradiation condition is detected by at least one second optical signal detector.
then, in step S1550, a light signal correction value of the reaction region subjected to background correction is determined based on the determined light signal correction value of the reaction region subjected to position error correction, the third light signal detection value, and the corresponding irradiation conditions (i.e., the second irradiation condition and the third irradiation condition). For example, if the second irradiation condition is the same as the third irradiation condition, the light signal correction value of the non-reaction region is subtracted from the light signal correction value of the reaction region as the light signal correction value of the reaction region after the background correction. And if the second irradiation condition is different from the third irradiation condition, converting the optical signal correction value of the non-reaction area into the converted optical signal correction value of the non-reaction area under the same irradiation as the second irradiation condition, and then subtracting the converted optical signal correction value of the non-reaction area from the optical signal correction value of the reaction area to be used as the optical signal correction value of the reaction area after background correction.
Fig. 16 shows a flowchart of another example of a method for detecting an optical signal correction value in a reaction area of a reaction carrier after reaction with an analyte according to the third embodiment of the present application.
As shown in FIG. 16, in step S1610, a first light signal detection value pair under a first illumination condition and a second light signal detection value under a second illumination condition of the corresponding reaction area of the reaction carrier are detected by at least one first light signal detector. In step S1620, a predetermined process is performed on the first optical signal detection value pair of the reaction region to obtain a predetermined process result. In step S1630, a third optical signal detection value of the non-reaction area of the reaction carrier under a third illumination condition is detected by at least one second optical signal detector. In step S1640, a second optical signal detection value of the reaction region after the background correction is determined based on the second optical signal detection value of the reaction region, the third optical signal detection value of the non-reaction region, and the corresponding illumination conditions (i.e., the second illumination condition and the third illumination condition). The determination process of the second optical signal detection value after background correction can be referred to the determination process described above with reference to fig. 12. Then, in step S1650, an optical signal correction value of the reaction region after the position error correction is determined based on the predetermined processing result for the reaction region, the background-corrected second optical signal detection value, and the corresponding optical signal value correlation function.
further, similar to the methods shown in fig. 6 and 11, the methods shown in fig. 15 and 16 may also include a corresponding control process and a specific substance content determination process. And will not be described in detail herein.
The system for detecting the content of a specific substance in an analyte, the apparatus for detecting a correction value of an optical signal in a reaction area of a reaction carrier after reacting with the analyte, and the method according to the present application are described above with reference to fig. 1 to 16.
The device for detecting a modification value of an optical signal in a reaction area of a reaction carrier after reaction with an analyte according to the present application is further described below using a specific implementation example.
Fourth embodiment
fig. 17 is a schematic external shape diagram showing an example of a specific implementation of an optical signal detection apparatus 1700 for detecting an optical signal correction value in a predetermined reaction region of a reaction carrier after a reaction with an analyte according to the fourth embodiment of the present application. As shown in fig. 17, the optical signal detection apparatus 1700 includes an indicator lamp 1701, a USB charging port 1702, a power button 1703, a body 1704, and a cap 1705.
Fig. 18 shows an exploded view of the internal structure of the specific implementation example shown in fig. 17. As shown in fig. 18, the optical signal detection apparatus 1700 may include an optical signal detection unit 1712 composed of an optical source and an optical signal detector. Here, the light source and the light signal detector in the light signal detection unit 1712 may take various combinations as described above with reference to fig. 3, 7, and 13.
The optical signal detection apparatus 1700 may further include a bluetooth module 1711 for data communication between the optical signal detection apparatus 1700 and the outside. Here, the bluetooth module 1711 may be replaced with various other types of communication units.
the optical signal detection apparatus 1700 may further include a processor 1713, configured to process each optical signal detection value detected by the optical signal detection unit 1712. For example, the processor 1713 may implement the functions of the optical signal correction value determination unit described above. Further, the processor 1713 may also perform the functions of the specific substance content determination unit and/or the controller described above.
optical signal detection apparatus 1700 may further include a micro switch 1714. Here, the microswitch 1714 may realize the function of the timer counting triggering unit described above. The optical signal detection apparatus 1700 may further include a USB charging port 1715 and a power switch 1716.
Further, in the specific implementation example shown in fig. 18, the bluetooth module 1711, the optical signal detection unit 1712, the processor 1713, the micro switch 1714, the USB charging port 1715, and the power switch 1716 are arranged on the same printed circuit board 1710. In other examples of the present application, the modules or units may not necessarily be arranged on the same printed circuit board,
In addition, the optical signal detection apparatus 1700 may further be provided with a structural support 1709 for fixing the printed circuit board 1710 on the structural support 1709 through a positioning hole and a snap. In addition, the structural support 1709 may also be provided with a reagent card receiving space for receiving a reagent card 1708. In addition, the structural support 1709 may be optionally provided with a battery receiving space for receiving the lithium battery 1707. The lithium batteries 1707 are secured within corresponding recesses of the structural support 1709, for example, by an adhesive process. When charging is required, the lithium battery 1707 is charged through the USB charging port 1705.
In addition, the optical signal detection apparatus 1700 may further include a light shielding member disposed on the structural support 1709 for eliminating stray light interference and interference between the detection units from affecting the detection result. For example, a light shield is provided between the reagent card 1708 and the PCB 1710. Specifically, the light-shielding member is disposed, for example, at a position corresponding to the light source and the optical signal detector on the PCB 1710.
In performing the assay, the reagent card 1708 may be inserted 1709 into the reagent card receiving space and accurately positioned. Upon detection of the reagent card being inserted in place (i.e., the reaction carrier is in a ready-for-assay state), micro switch 1704 is triggered to start timing using a timing function provided in processor 1703, thereby completing the detection of the light signal value at each time period of the reaction.
The processor 1703 may obtain relevant measurement data in response to the instruction and report the measurement data to the upper computer, or may control each component in the optical signal detection apparatus 1700 to perform a corresponding function and sum up the obtained data.
The device can be used for detecting test paper with color change after reaction with an object to be detected, so as to detect the content of the object to be detected.
fifth embodiment
fig. 19 is an exploded view showing an internal structure of another specific implementation example of the optical signal detection apparatus for detecting the optical signal correction value in the predetermined reaction region of the reaction carrier after the reaction with the analyte according to the fifth embodiment of the present application. Fig. 19 is a modification of the specific implementation example shown in fig. 18, except that the light source is changed to a fluorescence excitation light source, and the detection element is changed to a detection element capable of detecting excited fluorescence, for example, a filter for a specific wavelength is provided on a light source optical path of a general light source (i.e., a light source emitting white light), so that a first light source (e.g., a fluorescence excitation light source) having a corresponding wavelength can be implemented, and a filter is provided on an optical path of the optical signal detector 220, and optical signal value detection (e.g., optical signal detection for a fluorescence test paper) for the corresponding wavelength is performed. As shown in fig. 19, a filter matched with the excited fluorescent light source may be added at a position corresponding to the optical signal detector 220 of the light shielding member 1911, and the filter is used for wavelength filtering of light emitted from the light source. And a filter can be added below the light source to filter stray light. The optical signal detection device shown in fig. 19 can be applied to optical signal detection of a fluorescent test paper or a fluorescent reagent card.
Sixth embodiment
And (3) detecting the performance of the instrument:
The basis for making a quantitative determination is the precision of the system measurement, which is usually characterized by the CV value of multiple measurements.
The CV values of the parallel wells were verified by using the apparatus to measure colloidal gold control cards of different concentrations and a reference measurement was made using a bench top gold standard (Wakery HR201 gold standard) measurement on the same control cards. Specific experimental protocols and data are as follows:
And testing by using prepared quality control cards with the concentration gradient of 5mIU/ml,25mIU/ml and 45mIU/ml for two batches, wherein 10 quality control cards are arranged at each batch concentration point, and 20 quality control cards are arranged at each concentration point, and the CV value statistics is carried out by respectively measuring the obtained measured value of each time. A typical set of experimental data statistics is listed as follows:
according to the data, the precision of the scheme detection result without background deduction and position correction is poor, only qualitative and semi-quantitative determination can be carried out, the measured CV value is greatly improved after the background deduction of the system, and the measured CV value is further improved after the position correction; the CV value of the data after the position correction and the background deduction correction is further optimized. Therefore, the conclusion can be drawn that the quantitative determination can be carried out, the background subtraction method can overcome batch background difference of the NC membrane, and the position correction method can overcome position error of the quality control card strip, so that the CV value of the detection result is obviously improved; by simultaneously applying the two methods, the CV value is smaller, namely the detection result is more stable, and the CV value reaches or approaches the level of a desktop gold-labeled analyzer.
The optical signal detection device according to the present application can be applied to detection in various fields such as the field of food safety, the medical field, the environmental field, and the like, and in the field of food safety, the optical signal detection device according to the present application can be used, for example, for applications for detecting the content of toxins, antibiotics, pesticides, hormones, or the like.
Specifically, the optical signal detection device can be used for detecting the content of toxins, antibiotics, pesticides or hormones in human or animal body fluid (urine, blood, milk, saliva, tears) or food (meat, milk, eggs, grains, tea, fruits and vegetables) or feed.
The optical signal detection device according to the present application may be manufactured as a portable micro device, for example, a device having a length, width, and height of 13 × 3 × 2.2cm or less and a weight of 220g or less.
In addition, the optical signal detection device can be used for home detection, such as home quantitative or qualitative detection, and can be used for rapid detection, such as rapid quantitative or qualitative detection, due to its portability and rapidity.
The detailed description set forth above in connection with the appended drawings describes exemplary embodiments but does not represent all embodiments that may be practiced or fall within the scope of the claims. The term "exemplary" used throughout this specification means "serving as an example, instance, or illustration," and does not mean "preferred" or "advantageous" over other embodiments. The detailed description includes specific details for the purpose of providing an understanding of the described technology. However, the techniques may be practiced without these specific details. In some instances, well-known structures and devices are shown in block diagram form in order to avoid obscuring the concepts of the described embodiments.
The previous description of the disclosure is provided to enable any person skilled in the art to make or use the disclosure. Various modifications to the disclosure will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other variations without departing from the scope of the disclosure. Thus, the disclosure is not intended to be limited to the examples and designs described herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (31)
1. an apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte, comprising:
At least one set of first light sources, each set of first light sources comprising at least two first light sources that can be controlled separately to illuminate the same reaction zone of the reaction carrier under first and second illumination conditions;
At least one first optical signal detector for detecting a first optical signal detection value pair of the reaction zone under the first illumination condition and a second optical signal detection value under the second illumination condition; and
An optical signal correction value determining unit configured to perform predetermined processing on the first optical signal detection value pair; and determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and the corresponding optical signal value correlation function,
Wherein the optical signal value correlation function is used for reflecting the functional relation between the optical signal correction value after the position error correction and the predetermined processing result and the second optical signal detection value, an
Wherein the first illumination condition comprises two groups of light sources respectively consisting of the first light sources in each group of the first light sources according to a specified rule, and the second illumination condition comprises illumination by the light sources associated with the light sources forming the first illumination condition.
2. The apparatus of claim 1, wherein the second illumination condition comprises illumination by a set of light sources comprising at least a light source selected from the two sets of light sources.
3. the apparatus of claim 2, wherein the second illumination condition comprises illumination by all of the at least two first light sources.
4. The apparatus of claim 1, wherein the predetermined process comprises a difference process or a ratio process.
5. The apparatus of claim 1, further comprising:
a detection parameter setting unit for setting a detection start time, a detection stop time and a detection interval period of the first optical signal detector according to the properties of the specific substance to be detected and the label on the reaction carrier;
A timer; and
And the timing trigger unit is connected with the timer and used for triggering the timer to start timing after the reaction carrier enters a detection ready state.
6. The apparatus of claim 1, wherein the first light source is a light source having a full wavelength range or a specific wavelength range.
7. The apparatus of claim 1, wherein the first light source is a fluorescence excitation light source and the first optical signal detector has a filter characteristic matching a wavelength of the excited fluorescence.
8. The apparatus of claim 1, wherein the at least two first light sources are positioned so as to be located on both sides of a reaction zone of a standard reaction carrier when the standard reaction carrier is in a ready-to-detect state.
9. The apparatus of claim 8, wherein the at least two first light sources are positioned so as to be symmetrically located on both sides of the reaction zone of a standard reaction carrier when the standard reaction carrier is in a ready-to-detect state.
10. The apparatus of claim 1, further comprising:
And the temperature sensor is used for detecting temperature data when the reaction carrier is in a detection state.
11. The apparatus according to claim 1, wherein the optical signal value correlation function is generated based on history data of a predetermined processing result, history data of the second optical signal detection value, and history data of the corresponding optical signal detection reference value; and/or
The light signal value correlation function is correlated with the model of the first light signal detector and the first and second illumination conditions.
12. The apparatus of claim 1, further comprising:
At least one second optical signal detector for detecting a third optical signal detection value under a third illumination condition with the non-reaction area of the reaction carrier, an
the optical signal correction value determining unit further includes: a background correction module for obtaining the second optical signal detection value after background correction based on the second optical signal detection value, the third optical signal detection value and corresponding illumination conditions, an
The optical signal correction value determination unit is configured to: determining an optical signal correction value of the reaction zone after position error correction based on the predetermined processing result, the corrected second optical signal detection value and the corresponding optical signal value correlation function; or
The optical signal correction value determination unit is further configured to: and determining the optical signal correction value of the reaction area after background correction based on the determined optical signal correction value of the reaction area after position error correction, the third optical signal detection value and the corresponding irradiation condition.
13. The apparatus of claim 12, wherein the second illumination condition and the third illumination condition are the same.
14. The apparatus of claim 13, wherein the second illumination condition and the third illumination condition are provided by the same light source or by different light sources.
15. The apparatus of claim 12, wherein the first optical signal detector and the second optical signal detector are implemented using the same optical signal detector.
16. an apparatus for detecting an optical signal value in a reaction region of a reaction carrier after reaction with an analyte, comprising:
at least one set of first light sources, each set of first light sources for illuminating the same reaction zone of the reaction carrier under first illumination conditions;
At least one first optical signal detector for detecting a first optical signal detection value of the reaction zone under the first illumination condition;
at least one set of second light sources, each set of second light sources for illuminating the same non-reaction zone of the reaction carrier under second illumination conditions;
At least one second optical signal detector for detecting a second optical signal detection value of the non-reaction region of the reaction carrier under the second illumination condition, an
and the optical signal correction value determining unit is used for determining the optical signal correction value of the reaction area based on the first optical signal detection value, the second optical signal detection value and the corresponding irradiation condition.
17. the apparatus of claim 16, wherein the at least one first set of light sources and the at least one second set of light sources are implemented using the same light source, and the same light source is arranged as a region between the at least one first optical signal detector and the at least one second optical signal detector.
18. The apparatus of claim 16, wherein the at least one set of first light sources and the at least one set of second light sources are positioned so as to be directly above a reaction zone and a non-reaction zone of a standard reaction carrier, respectively, when the standard reaction carrier is in a ready-to-detect state.
19. The apparatus of claim 16, wherein the first optical signal detector and the second optical signal detector are implemented using the same optical signal detector.
20. The apparatus of claim 1, 12 or 16, further comprising:
A specific substance content determination unit for determining the content of the specific substance based on the determined optical signal correction value.
21. The apparatus of claim 20, further comprising:
And the communication unit is used for data communication between the specific substance content determination unit and the upper computer.
22. The apparatus of claim 20, wherein the specific substance content determination unit is provided in an upper computer or a cloud server, and the apparatus further comprises:
And the communication unit is used for data communication between the optical signal correction value determination unit and the specific substance content determination unit.
23. the apparatus of any of claims 1-22, further comprising:
A controller for controlling illumination of the respective light sources, detection of the respective light signal detectors, data communication between the respective components in the apparatus, and/or data communication between the components in the apparatus and the outside.
24. The device of any one of claims 1-22, wherein the specific substance comprises one of:
Toxins, antibiotics, pesticides or hormones.
25. A system for detecting the amount of a specific substance in an analyte, comprising:
A reaction carrier;
the device of any one of claims 1-19, 23, or 24; and
A specific substance content determination unit for determining the content of the specific substance based on the determined optical signal correction value.
26. The system of claim 25, further comprising:
And the upper computer is used for presenting a detection result of the content of the specific substance to a user and/or controlling the operation of the device, the operation of the content determining unit of the specific substance and the operation between the device and the content determining unit of the specific substance.
27. The system of claim 26, wherein the specific content determining unit is implemented in the device, a cloud server, or the host computer.
28. A method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte, comprising:
detecting a first optical signal detection value pair of a reaction area of the reaction carrier under a first illumination condition and a second optical signal detection value under a second illumination condition, wherein the first illumination condition comprises that two groups of light sources which are formed by first light sources in each group of first light sources according to a specified rule are respectively illuminated, and the second illumination condition comprises that the light sources related to the light sources forming the first illumination condition are illuminated;
Performing predetermined processing on the first optical signal detection value pair; and
Determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and the corresponding optical signal value correlation function,
the optical signal value correlation function is used for reflecting the functional relation between the optical signal correction value after the position error correction and the preset processing result and the second optical signal detection value.
29. The method of claim 28, further comprising:
Detecting a third optical signal detection value of the non-reaction area of the reaction carrier under a third irradiation condition;
Acquiring the second optical signal detection value after background correction based on the second optical signal detection value, the third optical signal detection value and corresponding illumination conditions, and
determining an optical signal correction value of the reaction zone after the position error correction based on the predetermined processing result, the second optical signal detection value and the corresponding optical signal value correlation function comprises:
And determining an optical signal correction value of the reaction zone after the position error correction based on the preset processing result, the corrected second optical signal detection value and the corresponding optical signal value correlation function.
30. The method of claim 28, further comprising:
Detecting a third optical signal detection value of the non-reaction area of the reaction carrier under a third irradiation condition; and
And determining the optical signal correction value of the reaction area after background correction based on the optical signal correction value of the reaction area after position error correction, the third optical signal detection value and the corresponding irradiation condition.
31. A method for detecting an optical signal value in a reaction area of a reaction carrier after reaction with an analyte, comprising:
Detecting a first optical signal detection value of a reaction area of the reaction carrier under a first irradiation condition;
Detecting a second optical signal detection value of the non-reaction region of the reaction carrier under a second irradiation condition, an
And determining an optical signal correction value of the reaction area after background correction based on the first optical signal detection value, the second optical signal detection value and corresponding irradiation conditions.
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| WO2021212594A1 (en) * | 2020-04-21 | 2021-10-28 | 杭州博日科技有限公司 | Optical path calibration method and device for pcr instrument and pcr instrument |
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