Patent Application
20230333093
This application claims the benefit of priority to Chinese Patent Application No. 202210388780.6, entitled “SAMPLE ANALYZER AND PLATELET COUNTING METHOD,” and filed on Apr. 14, 2022, the contents of which are incorporated herein by reference.
This disclosure relates to the field of in vitro diagnostics and, in particular, to a sample analyzer and a platelet counting method.
Platelet count is an important test item for clinical diagnosis and treatment of platelet (PLT) decrease-related diseases caused by various reasons. When the platelet count of a patient is lower than 20×10{circumflex over ( )}9/L, it is conventionally believed that platelet transfusion must be given to the patient, otherwise, the patient will be at risk of life-threatening bleeding. A platelet count threshold of 20×10{circumflex over ( )}9/L is a medical decision level for prophylactic platelet transfusion in clinical practices.
In recent years, there has been a trend to reduce prophylactic platelet transfusion in clinical practices, because the risk of random bleeding has not increased significantly after the threshold is lowered from 20×10{circumflex over ( )}9/L to 10×10{circumflex over ( )}9/L. Studies have shown that if clinicians have sufficient confidence in the reliability of platelet counts for evaluating the risk of bleeding, the medical decision level for prophylactic platelet transfusion can be lowered to 5×10{circumflex over ( )}9/L. In order to ensure the correctness and safety of clinical diagnosis, the platelet count should be both precise and accurate. Thus, accurate counting of platelets has important clinical significance.
For existing blood cell counting instruments, an impedance method is generally used for platelet counting. However, interferences from abnormal blood samples may lead to inaccurate results of platelet counting based on the impedance method, resulting in a clinical diagnosis error. For this reason, flow cytometry is used in some blood cell counting instruments for platelet counting, which eliminates the interferences mentioned above. However, for this purpose, it is necessary to additionally provide a special optical platelet testing channel for counting platelets, which not only increases the cost of clinical tests, but also leads to a significant increase in the volume and complexity of the instruments.
Thus, there is a need to obtain accurate platelet counting results at a cost as low as possible to assist in clinical diagnosis.
Thus, the object of the disclosure is to provide a sample analyzer and a corresponding platelet counting method, which can improve the accuracy of platelet counting without increasing the detection cost as much as possible.
In order to achieve the above object of the disclosure, a first aspect of the disclosure firstly provides a sample analyzer, including:
In the sample analyzer provided in the first aspect of the disclosure, two platelet counting results, namely, the first platelet counting result and the second platelet counting result, are obtained at a low cost through a testing channel based on impedance method and a hemolysis optical testing channel, and the first platelet counting result and/or the second platelet counting result are/is selectively outputted according to the result of determining whether the first platelet counting result is unreliable due to the abnormality of the test blood sample, thereby ensuring the accuracy of platelet counting results for abnormal samples.
A second aspect of the disclosure provides another sample analyzer, including:
In the sample analyzer provided in the second aspect of the disclosure, accurate platelet counting results can be obtained through a testing channel based on impedance method combined with an existing hemolysis optical testing channel, and an additional dedicated optical testing channel is used for platelet retest only when the platelet counting result is unreliable, so that the accuracy of platelet counts for abnormal samples can be improved with little overall increase in test cost.
A third aspect of the disclosure provides a corresponding platelet counting method, including:
The platelet counting method according to the third aspect of the disclosure is particularly applicable to the sample analyzer according to the first aspect of the disclosure.
For the features and advantages of the sample analysis method according to the third aspect of the disclosure, reference can be made to the foregoing description of the sample analyzer according to the first aspect of the disclosure.
A fourth aspect of the disclosure provides a corresponding platelet counting method, including:
The platelet counting method according to the fourth aspect of the disclosure is particularly applicable to the sample analyzer according to the second aspect of the disclosure.
For the features and advantages of the sample analysis method according to the fourth aspect of the disclosure, reference can be made to the foregoing description of the sample analyzer according to the second aspect of the disclosure.
A fifth aspect of the disclosure further provides a platelet counting method for use in a hematology analyzer, the platelet counting method including:
In the platelet counting method provided in the fifth aspect of the disclosure, it is possible to determine whether to directly obtain and output the third platelet counting result for the test blood sample according to the determination of whether the platelet optical measurement of the hematology analyzer is activated.
The embodiments of the disclosure will be described below clearly and completely with reference to the accompanying drawings. Obviously, the embodiments described are merely some, rather than all, of the embodiments of the disclosure. Based on the embodiments of the disclosure, all the other embodiments which would have been obtained by those of ordinary skill in the art without any creative efforts shall fall within the scope of protection of the disclosure.
The inventors of the disclosure have recognized that during counting platelets by an impedance method, an abnormity of a blood sample may lead to an inaccurate platelet counting result for the blood sample. For example, if microcytes or red blood cell fragments are present in the blood sample, since the microcytes and the red blood cell fragments are similar in size to platelets, the microcytes and the red blood cell fragments may be erroneously recognized as the platelets during counting, resulting in a high platelet count. If large platelets are present in the blood sample, since the large platelets are similar in volume to red blood cells, the large platelets may be erroneously recognized as the red blood cells during counting, resulting in a low platelet count. If platelet aggregation is present in the blood sample, many platelets may aggregate into one cell, resulting in a low platelet count. All the above situations will lead to inaccurate platelet count, and in turn lead to incorrect clinical diagnosis.
In view of the limitation of platelet counting based on the impedance method, an optical platelet testing channel is usually added in the industry to count platelets, so as to eliminate the above interferences from an abnormal sample. However, adding an optical platelet testing channel requires additional clinical test costs, and the volume and complexity of the instrument will also increase significantly.
On this basis, the disclosure provides a technical solution of obtaining an accurate platelet counting result at a cost as low as possible.
Referring to
The sampling device 110 may have a pipette (e.g., a sampling needle) with a pipette nozzle, and may have a drive portion that is configured to drive the pipette to quantitatively aspirate the test blood sample through the pipette nozzle. For example, the sampling needle is driven by the drive portion to move into a sample container holding the blood sample to aspirate the test blood sample.
The sample preparation device 120 is configured to prepare a first test sample containing a first part of the test blood sample and a diluent, and to prepare a second test sample containing a second part of the test blood sample, a hemolysis reagent for hemolyzing red blood cells, and a first stain reagent. Optionally, the sample preparation device 120 may be further configured to prepare a third test sample containing a third part of the test blood sample, a diluent and a second stain reagent.
In some embodiments, the sample preparation device 120 may have at least one reaction cell and a reagent supply device (not shown in the figures). The at least one reaction cell is configured to receive the test blood sample aspirated by the sampling device 110, and the reagent supply device supplies treatment reagents (including the diluent, the hemolysis reagent, the first stain reagent, the second stain reagent, etc.) to the at least one reaction cell, so that the test blood sample aspirated by the sampling device 110 is mixed, in the reaction cell, with the treatment reagents supplied by the reagent supply device, so as to prepare the test samples (including the first test sample and the second test sample).
In a specific example, the at least one reaction cell may include a first reaction cell and a second reaction cell, and the reagent supply device may include a first reagent supply portion and a second reagent supply portion. The sampling device 110 is configured to respectively dispense part of the aspirated test blood sample to the first reaction cell and the second reaction cell. The first reagent supply portion is configured to supply the diluent to the first reaction cell, so that a first part of the test blood sample that is dispensed to the first reaction cell is mixed and reacts with the diluent so as to prepare the first test sample. The second reagent supply portion is configured to supply the hemolysis reagent and the first stain reagent to the second reaction cell, so that a second part of the test blood sample that is dispensed to the second reaction cell is mixed and reacts with the hemolysis reagent and the first stain reagent so as to prepare the second test sample.
The hemolysis reagent herein is configured to lyse red blood cells in blood to break the red blood cells into fragments, with the morphology of white blood cells substantially unchanged. The first stain reagent may be a stain reagent configured to achieve leukocyte differential, for example, a stain reagent that can be used to achieve differential of leukocytes in a blood sample into at least three leukocyte subpopulations (monocytes, lymphocytes and neutrophils), or a stain reagent that can be used to recognize basophils and/or nucleated red blood cells in a blood sample.
In some embodiments, the hemolysis reagent may include at least one of alkyl glycosides, triterpenoid saponins and steroidal saponins, and the first stain reagent may include a membrane-specific dye or a mitochondria-specific dye. For more embodiments of the hemolysis reagent and the first stain reagent provided in the disclosure, reference can be made to PCT patent application WO 2019/206300 A1 submitted by the applicant and filed on 26 Apr. 2019, which is incorporated herein by reference in its entirety.
Optionally, the at least one reaction cell may further include a third reaction cell, and the reagent supply device may further include a third reagent supply portion. The sample collection device 110 is further configured to respectively dispense part of the aspirated test blood sample to the third reaction cell. The third reagent supply portion is configured to supply the diluent and the second stain reagent to the third reaction cell, so that a third part of the test blood sample that is dispensed to the third reaction cell is mixed and reacts with the diluent and the second stain reagent so as to prepare a third test sample. The diluent herein is configured to spheroidize cells and has a staining promoting effect, and the second stain reagent is different from the first stain reagent and is a stain reagent that can be used to recognize platelets in a blood sample.
The testing device 130 includes an optical testing device 131 and an impedance testing device 132. The optical testing device 131 is configured to test the second test sample prepared by the sample preparation device 120 so as to obtain optical information of the second test sample (which is also referred to as a hemolysis optical testing channel), and is optionally configured to test the third test sample prepared by the sample preparation device 120 so as to obtain optical information of the third test sample (which is also referred to as an optical platelet testing channel). The impedance testing device 132 is configured to test the first test sample prepared by the sample preparation device 120 so as to obtain electronic information of the first test sample (which is also referred to as an impedance testing channel).
The impedance testing device 132 includes a first flow chamber and a detection component, the first flow chamber being configured to allow the first test sample to pass through, and the detection component being configured to obtain electronic information as the first test sample passes through the first flow chamber.
In an embodiment of the impedance testing device 132, the impedance testing device 132 is configured as a sheath flow impedance testing device. As shown in
The optical testing device 131 includes a second flow chamber, a light source and an optical detector, the second flow chamber being configured to allow the second test sample to pass through, the light source being configured to irradiate the second test sample as the second test sample passes through the second flow chamber with a light, and the optical detector being configured to detect optical information generated by the second test sample after the second test sample is irradiated with the light as it passes through the second flow chamber. Optionally, the second flow chamber is further configured to allow the third test sample to pass through, the light source is further configured to irradiate the third test sample as the third test sample passes through the second flow chamber with light, and the optical detector is configured to detect the optical information generated by the third test sample after the third test sample is irradiated with the light as it passes through the second flow chamber.
In an embodiment of the optical testing device 131, as shown in
The controller 140 includes a processor and a storage medium that stores a computer program. The controller 140 is configured to control, when the computer program is executed by the processor, the impedance testing device 132 and the optical testing device 131 to test the first test sample and the second test sample (and optionally the third test sample), so as to obtain and output a platelet counting result for the test blood sample.
In some embodiments, as shown in
Specific processes of obtaining and outputting the platelet counting result by means of the controller 140 of the sample analyzer provided according to the disclosure will be described below with reference to
In some embodiments, as shown in
It should be understood that step S100 and step S110 can be performed simultaneously or successively, which is not specifically limited in the disclosure.
It should be understood that in the disclosure, the second platelet counting result PLT-W or PLT-H is obtained using an existing hemolysis optical testing channel, such as a leukocyte differential counting channel or a nucleated red blood cell testing channel, rather than adding a special optical platelet testing channel as in the prior art. Since a blood routine test typically includes at least a platelet test based on an impedance method and a leukocyte differential, obtaining the first platelet counting result and the second platelet counting result basically has no increase in test cost.
In the disclosure, when the first platelet counting result PLT-I (i.e., the platelet counting result based on the impedance method) is determined to be reliable, the controller 140 may output the first platelet counting result PLT-I or the second platelet counting result PLT-W or PLT-H; and when the first platelet counting result is determined to be unreliable due to the first abnormality of the test blood sample, the controller 140 may further determine whether the second platelet counting result PLT-H is unreliable due to a second abnormality of the test blood sample or output the second platelet counting result PLT-W. Herein, the first abnormality and the second abnormality may be different from each other or may be the same.
In some embodiments, as shown in
In this case, the controller 140 may be further configured to, in step S130, perform
Further, as shown in
Studies have shown that the first platelet counting result PLT-I is unreliable when an interference from abnormal particles, such as microcytes, large-volume fragments (fragments with a volume greater than a predetermined value), large platelets, minimal-volume fragments (fragments with a volume less than a predetermined value) or platelet aggregation, etc., is present in the test blood sample. Furthermore, PLT-H is calculated from the electronic information of the first test sample and the optical information of the second test sample, and is thus similarly affected by the interference from abnormal particles. Particularly, when the platelet aggregation and/or at least a predetermined quantity of minimal-volume fragments is present in the test blood sample, PLT-H is unreliable. However, the third platelet counting result PLT-O is substantially not affected by the interference from abnormal particles. Thus, in the case where the first platelet counting result PLT-I of the test blood sample is unreliable, based on the further determination of whether the second platelet counting result PLT-H is reliable, it is possible to directly output the second platelet counting result PLT-H or trigger the test for the third platelet counting result PLT-O, thereby ensuring the accuracy of the platelet counting result for the abnormal sample.
In some other embodiments as an alternative to the embodiment shown in
In this case, the controller 140 may be further configured to, in step S130, perform step S135 of outputting the second platelet counting result PLT-W when the first platelet counting result PLT-I is determined to be unreliable due to the first abnormality of the test blood sample.
Further, as shown in
Studies have shown that the first platelet counting result PLT-I is unreliable when an interference from particles, such as microcytes, large-volume fragments, large platelets, minimal-volume fragments or platelet aggregation, etc., is present in the test blood sample, but the second platelet counting result PLT-W obtained based only on the optical information of the second test sample containing the test blood sample will not be affected by these abnormal interferences. Thus, in the case where PLT-I is unreliable, PLT-W may be outputted directly; and in the case where PLT-I is reliable, either or both of PLT-I and PLT-W may be outputted, thereby ensuring the accuracy of the platelet counting result for the abnormal sample.
In some other embodiments as an alternative to the embodiment shown in
PLT-H is calculated from the electronic information of the first test sample and the optical information of the second test sample, and is thus affected by interferences from abnormal particles. Particularly, when platelet aggregation and/or at least a predetermined quantity of minimal-volume fragments is present in the test blood sample, PLT-H is unreliable. However, the third platelet counting result PLT-O is substantially not affected by interferences from abnormal particles. Thus, in the case where the second platelet counting result PLT-H of the test blood sample is unreliable, the test for the third platelet counting result PLT-O is triggered, thereby ensuring the accuracy of the platelet counting result for the abnormal sample.
Further, in the embodiment shown in
As described above, the sample abnormality that leads to the first platelet counting result PLT-I being unreliable may include at least one of: presence of microcytes, large-volume fragments, large platelets, minimal-volume fragments and platelet aggregation in the test blood sample. The sample abnormality that leads to the second platelet counting result PLT-H, which is obtained based on the electronic information of the first test sample and the optical information of the second test sample, being unreliable may include at least one of: presence of platelet aggregation in the test blood sample, and presence of at least a predetermined quantity of fragments in the test blood sample that have a volume less than a predetermined value.
Specific processes of determining whether a sample abnormality is present in the test blood sample by means of the controller 140 will be described below with reference to
Studies have shown that microcytes, red blood cell fragments (including large-volume fragments and minimal-volume fragments), large platelets and platelet aggregation may lead to an abnormality in the platelet volume distribution histogram obtained based on the impedance method, especially lead to an abnormality of particle information distribution in a specific region of the platelet volume distribution histogram.
On this basis, in some embodiments, as shown in
For example, the controller 140 may be further configured to perform the steps of:
As shown in
In a specific example, if the ratio H1/H2>M, where M represents a preset threshold, which may be, for example, a fixed constant, it can be determined that the particle information distribution in the specific region W is abnormal, and thus it can be determined that a sample abnormality which leads to PLT-I being unreliable is present in the test blood sample; and if the ratio H1/H2≤M, it can be determined that the particle information distribution in the specific region W is normal, and thus it can be determined that no sample abnormality which leads to the PLT-I being unreliable is present in the test blood sample.
Alternatively or additionally, in some other embodiments, the controller 140 may be further configured to, in step S120, perform the steps of:
For example, the preset threshold may be 70 fL, and when the mean corpuscular volume obtained based on the electronic information of the first test sample is lower than 70 fL, it is indicated that many microcytes are present in the test blood sample, which may result in falsely high PLT-I of the test blood sample, that is, it is indicated that a sample abnormality that leads to PLT-I being unreliable is present in the test blood sample.
Alternatively or additionally, in yet some other embodiments, the controller 140 may be further configured to determine whether platelet aggregation is present in the test blood sample based on the optical information of the second test sample, so as to determine whether a sample abnormality that leads to the first platelet counting result PLT-I being unreliable is present in the test blood sample.
In some embodiments, as shown in
Studies have shown that when an interference from minimal-volume fragments or platelet aggregation, etc., is present in the blood sample, the particle information distribution in the specific region in the second platelet volume distribution histogram is abnormal. Thus, it is possible to determine whether the particle information distribution in the specific region in the second platelet volume distribution histogram is abnormal so as to determine whether a sample abnormality that leads to PLT-H being unreliable is present in the test blood sample.
In a specific example, the controller 140 may be further configured to perform the steps of:
For example, if a ratio of the first area to the sum of the first area and the second area is greater than a preset threshold, or a ratio of the second area to the sum of the first area and the second area is less than the preset threshold, it can be determined that the particle information distribution in the specific region of the second platelet volume distribution histogram is abnormal, and thus it can be determined that a sample abnormality that leads to PLT-H being unreliable is present in the test blood sample.
When PLT-H is interfered, there will be significantly more particles in a small-volume region, and thus particle distribution information in the small-volume region will be abnormal. Thus, it can be determined whether PLT-H is interfered based on the abnormal distribution in the small-volume region.
As shown in
Assuming that N is a preset threshold, if A1/(A1+A2)>N or A2/(A1+A2)<N, it can be determined that the particle information distribution in the specific region of the second platelet volume distribution histogram is abnormal, and thus it can be determined that a sample abnormality that leads to PLT-H being unreliable is present in the corresponding test blood sample.
Alternatively, in some other embodiments, the controller 140 may be further configured to, when determining whether the second platelet counting result PLT-H is unreliable due to the abnormality of the test blood sample, perform the steps of determining whether platelet aggregation is present in the test blood sample based on the optical information of the second test sample.
In the embodiments of the disclosure, the second platelet counting result PLT-H or PLT-W is calculated from the optical information of the second test sample after being subjected to hemolysis and staining. Different from obtaining an optical platelet count by means of adding a special optical platelet testing channel as in the prior art, the second platelet counting result may be obtained using an existing hemolysis optical platelet testing channel in the disclosure.
On this basis, in some embodiments, the controller 140 may be further configured to obtain a leukocyte differential result and/or a leukocyte counting result and/or an immature granulocyte test result for the test blood sample based on the optical information of the second test sample. For example, in an example, the controller 140 may classify leukocytes into at least neutrophils, lymphocytes and monocytes based on the optical information of the second test sample.
Alternatively, in some other embodiments, the controller 140 may be further configured to recognize basophilic granulocyte and/or nucleated red blood cells in the test blood sample based on the optical information of the second test sample.
The disclosure further provides a platelet counting method. As shown in
In some embodiments, as shown in
Further, in the embodiment shown in
In some alternative embodiments, as shown in
Further, in the embodiment shown in
In some embodiments, the platelet counting method may further include: obtaining a leukocyte differential result and/or a leukocyte counting result and/or an immature granulocyte test result for the test blood sample based on the optical information of the second test sample.
The disclosure further provides another platelet counting method. As shown in
In some embodiments, the platelet counting method may further include: obtain a leukocyte differential result and/or a leukocyte counting result and/or an immature granulocyte test result for the test blood sample based on the optical information of the second test sample.
The platelet counting methods provided in the disclosure are particularly applicable to the sample analyzers provided in the disclosure. For the advantages and more embodiments of the platelet counting methods provided in the disclosure, reference can be made to the forgoing description of the sample analyzers, which will not be repeated herein.
Another aspect of the disclosure further provides a platelet counting method for use in a hematology analyzer. As shown in
The platelet optical measurement herein is a non-hemolysis optical test channel separately and specifically configured to carry out a platelet test in the hematology analyzer. When the hematology analyzer is provided with the non-hemolysis optical test channel, if a predetermined testing mode of the test blood sample originally includes a platelet optical measurement, the third platelet counting result obtained based on the platelet optical measurement is directly outputted, and the platelet counting method mentioned above is performed only when the predetermined testing mode of the test blood sample does not include the platelet optical measurement.
It should be noted that the term “first/second/third” in the embodiments of the disclosure is only used to distinguish similar objects, and does not represent specific order for the objects. It may be understood that “first/second/third” may be interchanged for specific order or chronological order when allowed.
The features or combinations thereof mentioned above in the description, accompanying drawings, and claims can be combined with each other arbitrarily or used separately as long as they are meaningful within the scope of the disclosure and do not contradict each other. The advantages and features described for the sample analyzers provided in the disclosure are applicable in a corresponding manner to the platelet counting methods provided in the disclosure, and vice versa. The foregoing description merely relates to the preferred embodiments of the disclosure, and is not intended to limit the scope of patent of the disclosure. All equivalent variations made by using the content of the specification and the accompanying drawings of the disclosure from the concept of the disclosure, or the direct/indirect applications of the contents in other related technical fields all fall within the scope of patent protection of the disclosure.
| Number | Date | Country | Kind |
|---|---|---|---|
| 202210388780.6 | Apr 2022 | CN | national |
