Patent Grant
11022558
This application is based upon and claims priority to Chinese Patent Application No. 201710627022.4, filed on Jul. 27, 2017 the entire contents of which are incorporated herein by reference.
The present invention relates to the technical field of medical instruments, and particularly to a coagulation analyzer and a coagulation analysis method.
With the development of medical instruments and biotechnology, and the progress made in the basic theory of hemostasis and thrombosis and the application thereof, automatic coagulation analyzers have been developed rapidly and widely used in the diagnosis and treatment process.
The leading international coagulation device manufacturers such as Sysmex, Werfen, and Stago dominate the mainstream market. Chinese manufacturers such as Succeeder, Precil, Rayto and so on also launched coagulation analyzer products. Generally, there are three approaches to the testing of blood coagulation, namely, coagulation, immunonephelometry, and colorimetry. Based on the reaction principle of the immunoturbidimetry and colorimetry, optical method is usually used by the manufacturers for the testing. For the coagulation approach, two methods are mainly used by the leading manufacturers, i.e. magnetic bead (which refers to magnetically drivable particle in the context of the present invention) method and optical method. These two methods have their own advantages and disadvantages. Currently, the optical method is dominant in the market. However, during the test of coagulation items, when interferents of hemolysis, jaundice, and lipemia etc. occur in the sample, the measurement result of the optical method will be affected. The magnetic bead method uses magnetic force to drive a demagnetized steel bead (magnetically drivable particle) to move in the sample. When the sample clots, the movement of the demagnetized steel bead stops, gradually. A steel bead particle displacement sensing device (usually a magnetic displacement sensing) is used to sense the movement of the demagnetized steel bead and calculate the clot time. By doing so, the optical interference of hemolysis, jaundice, and lipemia to the coagulation test can be avoided.
For the magnetic bead based instruments, the items of coagulation approach are tested by the magnetic bead method, the items of immunoturbidimetry and the colorimetry approaches are tested by the optical method. For optical method based instruments, the items of the coagulation, immunoturbidimetry, and colorimetry approaches are tested by the optical method.
Because the magnetic bead based instrument should be equipped with magnetic bead method test channel and optical method test channel at the same time, the instrument is more complex and the challenges for reliability are more. Each testing analysis cup is provided with a magnetic bead, resulting in an increased cost of consumables for an individual test. For the items tested by immunoturbidimetry approach (for example, D-DIMER, FDP, etc.) and the items tested by colorimetry approach (for example, anti-thrombin III, etc.), the disadvantages of using the analysis cup with magnetic bead of the magnetic bead based instrument are more obvious. Increased amount of reagents are required, so the cost for customers is further increased. Moreover, the magnetic bead affects the mixing effect, and thus reduces the accuracy of measurement.
The coagulation analyzer and the coagulation analysis method provided by the present invention use a sample interference analysis module to determine whether an interferent in the sample has effect on the test results of the coagulation items in the optical coagulation analysis channel. If the interferent in the sample has no effect on the test results, the optical coagulation analysis module is used to perform the measurement and report the test result. If the interferent in the sample has effect on the test results, a test transfer module is used to transfer the test to a magnetic coagulation analysis module to perform the measurement and report the test result.
For the coagulation test samples in the hospital, merely a few samples are interfered samples, and most of the samples are the normal samples, so the method of the present invention effectively reduces the frequency of use of the magnetic coagulation analysis module. For example, in a hospital where about 40 samples are tested in a day, the magnetic coagulation analysis module is merely used about once or twice, thus compared with the magnetic bead based instrument, the cost is reduced while the situation where an accurate result cannot be reported by the optical method based instrument as a result of the occurrence of lipemia, jaundice, and hemolysis in the samples and thus affecting the follow-up treatment can be avoided. Moreover, most of the tests of the present invention are accomplished by the optical method, so the characteristics of low cost, high accuracy, and high reliability of the optical method based instruments are kept.
In the magnetic bead instruments, when the items of immunoturbidimetry (for example, d-dimer, FDP, etc.), and the items of colorimetry (for example, anti-thrombin III, etc.) are tested, the optical method test channel is used to perform the measurement and the analysis cup with magnetic bead is still used, namely, the analysis cup with magnetic bead is used even if the magnetic bead test channel is not used. The analysis cup is designed with a space reserved for the movement of the magnetic bead, so the magnetic bead occupies the space in the analysis cup, thereby limiting the design for operations such as adding sample, mixing etc. For example, the design for adding sample needs to consider the collision between the sample adding probe and the magnetic bead, and the design of mixing also needs to consider the effects of the magnetic bead. Moreover, when the cup with magnetic bead is used for optical measurement, the optical path needs to avoid the magnetic bead, so that the amount of reagent used and the design of optical path are both affected.
The optical coagulation analysis module of the coagulation analyzer of the present invention uses an analysis cup without particle, thereby reducing the cost of analysis cup and reagent, while the design in aspects of mixing, and loading of the analysis cup is easier and more reliable. The magnetic coagulation analysis module uses an analysis cup with particle, so the advantage of anti-sample-interference of magnetic bead method in the test of the coagulation items is maintained. The interfered sample can be transferred to the magnetic analysis module to be tested. In the hospital where about 40 samples are tested in a day, the magnetic module is merely used once or twice, so most of the samples are tested in the optical coagulation analysis module, and the analysis cup used is the analysis cup without particle, thereby greatly improving the economic efficiency of the test while keeping the advantage of anti-interference of the magnetic bead method.
In order to overcome the drawbacks and deficiencies of the above-mentioned prior art, based on the above-mentioned design principles, the present invention provides a coagulation analyzer including:
an optical coagulation analysis module which uses an analysis cup without particle for an optical coagulation analysis;
a sample interference analysis module for analyzing an effect of a sample interference on the optical coagulation analysis, and determining a coagulation test affected by the sample interference;
a magnetic coagulation analysis module which uses an analysis cup with a magnetically drivable particle for a magnetic coagulation analysis; and
a test transfer module for transferring the coagulation test affected by the sample interference to the magnetic coagulation analysis module.
The coagulation analyzer uses the sample interference analysis module to determine whether the interferent in the sample has effect on the coagulation test result of the optical coagulation analysis module. If the interferent in the sample has no effect on the coagulation test result, the optical coagulation analysis module is used to perform the coagulation analysis and report the test result. If the interferent in the sample has effect on the coagulation test result, the test transfer module is used to transfer the test to the magnetic coagulation analysis module to perform the coagulation analysis and report the coagulation test result.
Since the optical coagulation analysis module uses an analysis cup without particle, the cost of the analysis cup and the reagent is reduced, and the design in aspects of mixing, and loading of the analysis cup is easier and more reliable. Since the magnetic coagulation analysis module uses the analysis cup with particle, the advantage of the anti-sample-interference of the magnetic bead method in the test of the coagulation items is maintained. The interfered sample can be transferred to the magnetic analysis module to be tested. In the hospital where about 40 samples are tested in a day, the magnetic module is used about once or twice, so most of the samples are tested in the optical coagulation analysis module, and the analysis cup used is the analysis cup without particle, thereby greatly improving the economic efficiency of the test, while keeping the advantage of anti-interference of the magnetic bead method.
In a preferred implementation, the sample interference analysis module using an optical analysis method includes a first light source component, a first light reception component, and a sample interference data processing unit. The first light reception component collects optical signals of a transmitted light or a scattered light of a sample or a mixture of the sample and a reagent irradiated by the first light source component. The sample interference data processing unit determines whether the interferent in the sample has effect on a part of or a whole coagulation test of the optical coagulation analysis module.
In a preferred implementation, the optical coagulation analysis module includes a second light source component and a second light reception component. The second light reception component collects optical signals of the transmitted light or the scattered light of the sample or the mixture of the sample and the reagent irradiated by the second light source component to complete the optical coagulation test of the sample.
Preferably, a light source of the first light source component and the second light source component is a light source device such as a halogen lamp, a semiconductor laser, or an LED light source etc.
In a preferred implementation, the first light source component and the second light source component are the same component.
In a preferred implementation, the first light reception component and the second light reception component are the same component.
In a preferred implementation, the magnetic coagulation analysis module includes a magnetic drive component and a particle displacement sensing component. The magnetic drive component drives the magnetically drivable particle to displace. The particle displacement sensing component detects a movement of the magnetically drivable particle and complete the coagulation test of the sample. The magnetic drive module drives the magnetically drivable particle to move regularly. The particle displacement sensing component detects the movement of the particle. When the clot occurs, a change of the movement of the particle is detected to complete the coagulation test of the sample. The particle displacement sensing component may use an optical displacement sensing, a magnetic displacement sensing, or other detection means that can capture the change of the movement of the particle driven by magnetic force. Preferably, magnetic displacement sensing is used.
In a preferred implementation, the magnetically drivable particle may be pre-loaded into the analysis cup to be provided to the coagulation analyzer, or be automatically loaded into the analysis cup by the coagulation analyzer. Preferably, the magnetically drivable particle is demagnetized steel bead.
In a preferred implementation, the coagulation analyzer further includes a reagent placing module for placing coagulation analysis reagents. For example, the reagent of coagulation test such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), anti-thrombin III (AT-III), FDP, D-DIMER, Protein C, Protein C, cleaning solution, coagulation factor etc. When the reagent needs to be kept stable in the instrument, the reagent placing module may further include a cooling component for maintaining a low temperature storage condition for the reagent. Preferably, the low temperature is ranged from 10° C.-15° C.
In a preferred implementation, the test transfer module includes a liquid transfer module including one or more liquid transfer components. The liquid transfer component completes the operation of transferring the coagulation test to the magnetic coagulation analysis module by a liquid transfer operation of the sample and/or reagent and/or the mixture of the sample and the reagent.
In a preferred implementation, the test transfer module includes an analysis cup transfer module including one or more analysis cup transfer components. The analysis cup transfer component completes the operation of transferring the coagulation test to the magnetic coagulation analysis module by a transfer operation of the analysis cup.
In a preferred implementation, the test transfer module may also transfer the interference sample to a position where the magnetic coagulation analysis module is enabled to perform the measurement. The magnetic coagulation analysis module may be separately equipped with a liquid transfer device to suck the interference sample and then transfer to the analysis cup with magnetic bead.
In a preferred implementation, the analysis cup without particle and the analysis cup with the magnetically drivable particle have different geometrical structural characteristics.
Generally, plasma samples are used in the coagulation tests, sometimes with the occurrence of interferents of hemolysis, jaundice, lipemia etc. As shown in
An optical interference recognition is performed on the coagulation sample or the mixture of sample and reagent (which are collectively referred as the to-be-recognized sample). Preferably, the to-be-recognized sample is irradiated by lights with a plurality of wavelengths ranged from 300 nm-800 nm in the recognition to detect a transmitted light intensity or a scattered light intensity of the to-be-recognized sample (preferably, transmitted light intensity). The presence of interferents, which can affect the coagulation test in the to-be-recognized sample, is determined by the optical interference recognition.
Preferably, the specific optical interference recognition method includes selecting a sample having no effect on the coagulation test result (including a sample without optical interference and a sample with a low content of the optical interferent which is insufficient to affect the coagulation test result); measuring a transmitted light intensity or scattered light intensity in a normal condition without interference; calculating characteristic values such as transmittivity, absorbance value, or scattered light intensity value; counting a distribution of eigenvalues and setting a threshold. After the to-be-recognized sample is irradiated by the light source, the light reception component acquires an intensity signal of the transmitted light or the scattered light and calculates the eigenvalues such as transmittivity, absorbance value, or the scattered light intensity value. If the eigenvalue exceeds the pre-set threshold, it is determined that the sample interference has an effect on the coagulation test.
The optical interference recognition is completed by the sample interference analysis module. The sample interference analysis module and the optical coagulation analysis module may be a common module, i.e., sharing all module components, different modules that share a part of components (e.g., light source component), or independent modules that do not share any component. Specifically, the optical interference recognition of the to-be-recognized sample may be realized in the optical coagulation measurement position of the optical coagulation analysis module by using the analysis cup without particle. Specifically, the optical interference recognition may be performed in the specific optical interference recognition position by using the sample in the original sample tube, directly. Specifically, the optical interference recognition of the sample or the mixture of sample and reagent (collectively referred as the to-be-recognized sample) in the analysis cup may be performed in the specific optical interference recognition position.
The coagulation test unaffected by sample interference is performed in the optical coagulation analysis channel and the test results are reported. If the coagulation test is determined to be affected by the sample interference, the test is transferred to the magnetic coagulation analysis channel by the test transfer device to perform the measurement and report the test results. The magnetic coagulation analysis module uses the magnetic force to drive the movement of a macroscopic steel bead particle. The particle movement itself is unaffected by the interferents. The movement of the driven macroscopic steel bead particle may be sensed by the particle displacement sensing component, and the magnetic displacement sensing is generally preferred, so the magnetic coagulation analysis module is also unaffected by the optical interferents in the sample.
A coagulation analysis method provided by the present invention specifically includes the following steps:
(1) performing an optical interference recognition for a sample or a mixture of the sample and a reagent in a sample interference analysis module;
(2) determining whether an interferent in the sample has an effect on a test result of coagulation items of an optical coagulation analysis channel;
(3) using the optical coagulation analysis channel of an optical coagulation analysis module to perform a measurement and report the test result if the interferent in the sample has no effect on the test result.
(4) using a test transfer module to transfer the test to a magnetic coagulation analysis channel of a magnetic coagulation analysis module to perform the measurement and report the test result if the interferent in the sample has effect on the test result.
In a preferred implementation, the optical coagulation analysis channel uses an analysis cup without particle.
In a preferred implementation, the magnetic coagulation analysis channel uses an analysis cup with magnetically drivable particle.
In a preferred implementation, the magnetically drivable particle may be pre-loaded into the analysis cup to be provided to the magnetic coagulation analysis module, or automatically loaded into the analysis cup by the coagulation analyzer. The magnetically drivable particle is a demagnetized steel bead.
In a preferred implementation, the optical interference recognition includes determining whether the optical interference has effect on the coagulation test by detecting the optical signals of transmitted light or the scattered light after the sample or the mixture of sample and reagent is irradiated by a light source optical signal.
In a preferred implementation, the test transfer module includes a liquid transfer module including one or more liquid transfer components. The liquid transfer component completes the operation of transferring the coagulation test to the magnetic coagulation analysis channel of the magnetic coagulation analysis module by a liquid transfer operation of the sample and/or the reagent and/or the mixture of the sample and the reagent.
In a preferred implementation, the test transfer module includes an analysis cup transfer module including one or more analysis cup transfer components. The analysis cup transfer component completes the operation of transferring the coagulation test to the magnetic coagulation analysis channel of the magnetic coagulation analysis module by a transfer operation of the analysis cup.
In a preferred implementation, the optical coagulation analysis channel includes at least a light source component and a light reception component. The light reception component collects the optical signals of the transmitted light or the scattered light of the sample or the mixture of the sample and the reagent irradiated by the light source component to complete the coagulation test of the sample.
In a preferred implementation, the magnetic coagulation analysis channel includes a magnetic drive component and a particle displacement sensing component. The magnetic drive component drives the magnetically drivable particle to displace. The particle displacement sensing component detects a movement state of the particle and complete the coagulation test of the sample.
In a preferred implementation, the mixture of the sample and the reagent is a mixture of the sample and coagulation test reagent or a mixture of sample and a buffer solution. Preferably, the buffer solution is normal saline.
In
In
In
In
In
In
In order to make the objectives, technical solutions, and advantages of the present invention more clear, the present invention will be described herein in detail hereinafter with reference to the drawings and embodiments. It should be understood that the specific embodiments described hereinafter are merely intended to explain the present invention, rather than limit the present invention.
One of the embodiments of the present invention is shown in
As shown in
The coagulation analyzer uses the sample interference analysis module to determine whether the interferent in the sample has effect on the coagulation test result of the optical coagulation analysis module. If the interferent in the sample has no effect on the coagulation test result, the optical coagulation analysis module is used to perform the coagulation analysis and report the test result. If the interferent in the sample has effect on the coagulation test result, the test transfer module is used to transfer the test to the magnetic coagulation analysis module to perform the coagulation analysis and report the test results.
In the embodiment, module 5 is the common module of the optical coagulation analysis module and the sample interference analysis module which share all module components. Module 5 has a thermostatic control, and the center temperature is preferably set at 37° C.
In the embodiment, incubation module 2 which only has an incubation function is separately provided. The analysis cup placing position area of incubation module 2 has a constant temperature incubation function, and the center temperature is preferably set at 37° C.
Sample tube 10 containing the sodium citrate anticoagulated plasma sample after centrifugation is stored in sample tube placing module 11.
In the embodiment, the effects of interference on the coagulation test is determined during the coagulation test.
Analysis cup transfer module 1 transfers the analysis cups without particle in analysis cup placing module 3 to respective analysis cup placing position area on incubation module 2. As shown in
In step 52, the effects of the sample interferent is determined according to the optical signals of the mixture of sample and reagent. Preferably, the specific determination algorithm includes selecting more than 100 samples having no effect on the coagulation test result (including samples without optical interference and samples with a low content of the optical interferent which is insufficient to affect the coagulation test result); measuring the transmitted light intensity of the mixture of sample and reagent in normal sate without effects; calculating the absorbance values; counting the distribution of the absorbance values and setting the threshold. When the sample is tested, after the mixture of sample and reagent in the analysis cup to be recognized is irradiated by the light source component, the light reception component acquires the intensity signal of the transmitted light and calculates the absorbance value. If the absorbance value exceeds the preset threshold, it is determined that there is a risk that the sample interference affects the coagulation test. In the embodiment, preferably, the absorbance value within 3 seconds after the sample and reagent are mixed is selected, so as to avoid the effects of the blood clotting response.
In the embodiment, liquid transfer module 8 is the test transfer module. For a coagulation test being determined to have sample interference, as shown in
As shown in
Another embodiment of the present invention is shown in
According to the embodiment shown in
More than 100 samples having no effect on the coagulation test result (including samples without optical interference and samples with a low content of the optical interferent which is insufficient to affect the coagulation test result) are selected to measure the transmitted light intensity in the normal sate without effects, then the absorbance value is calculated, the distribution of the absorbance value is counted, and the threshold is set. When the sample is tested, after the to-be-recognized sample tube is irradiated by the light source component, the light reception component acquires the transmitted light intensity signal and calculates the absorbance value. If the absorbance value exceeds the preset threshold, it is determined that there is a risk that the sample interference affects the coagulation test.
In the embodiment, liquid transfer module 8 is the test transfer module. For the coagulation test being determined to have sample interference, liquid transfer module 8 transfers the coagulation test to magnetic coagulation analysis module 7 to complete the coagulation analysis and report the test result. The coagulation test that is not transferred to the magnetic coagulation analysis module 7 is completed in the common module 15 of optical coagulation analysis module and incubation module and the test results are reported. In the embodiment, the optical coagulation analysis module and the incubation module completely share the same module, and no incubation module that only has incubation function is separately provided.
The analysis cup transfer module 1 not only can be used to automatically transfer the analysis cup 21 without particle, and manually transfer the analysis cup with magnetically drivable particle from module 6 to module 7, but also can be used to automatically transfer the analysis cup 21 without particle and the analysis cup 29 with magnetically drivable particle.
Another embodiment of the present invention is shown in
In the embodiment, module 5 is the common module of optical coagulation analysis module and sample interference analysis module which share all module components. Module 5 has a thermostatic control, and the center temperature is preferably set at 37° C.
Analysis cup transfer module 1 transfers the analysis cups without particle in analysis cup placing module 3 to respective analysis cup placing position at the module 5. As shown in
In step 59, the effects of the sample interferent are determined according to the optical signals of the mixture of sample and buffer solution. Preferably, the specific determination algorithm includes selecting more than 100 samples having no effect on the coagulation test result (including samples without optical interference and samples with a low content of the optical interferent which is insufficient to affect the coagulation test result); measuring the transmitted light intensity of the mixture of sample and buffer solution in normal state without effect; calculating the absorbance value, counting the distribution of the absorbance value, and setting the threshold. When the sample is tested, after the mixture of sample and buffer solution in the analysis cup to be recognized is irradiated by the light source component, the light reception component acquires the transmitted light intensity signal and calculates the absorbance value. If the absorbance value exceeds the preset threshold, it is determined that there is a risk that the sample interference affects the coagulation test.
In the embodiment, analysis cup transfer module 1 is the test transfer module. For the coagulation test being determined to have the sample interference, analysis cup transfer module 1 transfers the analysis cup without particle of the coagulation test to the magnetic coagulation analysis module 7. Magnetically drivable particle automatic loading module 16 adds the magnetically drivable particle to the analysis cup as shown in step 62 of
In the embodiment, incubation module 2 that only has an incubation function is separately provided. The analysis cup placing area of incubation module 2 has a constant temperature incubation function, and the center temperature is preferably set at 37° C.
The above-mentioned embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modification, equivalent, combination, and improvement derived within the spirit and principle of the present invention shall fall within the scope of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201710627022.4 | Jul 2017 | CN | national |
| Number | Name | Date | Kind |
|---|---|---|---|
| 20080044912 | Yamamoto | Feb 2008 | A1 |
| 20150044780 | Kurz | Feb 2015 | A1 |
| Number | Date | Country |
|---|---|---|
| 201720925726.5 | Jul 2017 | CN |
| Number | Date | Country | |
|---|---|---|---|
| 20190033221 A1 | Jan 2019 | US |
