• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    This determination method comprises the steps of providing a reaction cuvette (2) containing a blood sample (33) and a ferromagnetic ball (11) placed on a raceway (9) provided in the bottom of the reaction cuvette ( 2), subjecting the ball (11) to a magnetic field so as to move the ball along the raceway (9) in oscillatory motion, exposing the blood sample to an incident light beam (36), detecting a light beam (38) transmitted through the reaction cuvette (2) and from the incident light beam (36) to provide a measurement signal, performing a first processing of the measurement signal to provide a first signal representative of the variation of at least one physical quantity representative of the movement of the ball (11), performing a second processing of the measurement signal so as to provide a second signal representative of the variation of at least one pro In the optical sample of the blood sample, determine a first value of the clotting time of the blood sample from the first signal, and determine a second value of the clotting time of the blood sample from the second signal.
    公开号:FR3030048A1
    申请号:FR1462423
    申请日:2014-12-15
    公开日:2016-06-17
    发明作者:Alain Rousseau；Norbert Brutt；Bertrand Guyon
    申请人:Immunodiagnostic Systems France SA；
    IPC主号:
    专利说明:

    [0001] The present invention relates to a method and a device for determining the coagulation time of a blood sample to be analyzed, and a reaction cuvette. EP 0 325 874 discloses a reaction cuvette for determining the coagulation time of a blood sample to be analyzed. For this purpose, the bottom of the reaction bowl comprises a curvilinear raceway whose concavity is directed upwards, on which a ferromagnetic ball is able to be placed and driven in motion. EP 0 325 874 further discloses a method for determining the coagulation time, comprising the following steps: - introducing the blood sample to be analyzed into the reaction cuvette, - placing a ferromagnetic ball on the running track of the cuvette. reaction vessel, - subjecting the ferromagnetic ball to a magnetic field so as to move the ferromagnetic ball along the raceway in oscillatory motion, - exposing the blood sample to be analyzed to an incident light beam configured to be substantially tangent to the ferromagnetic ball when it is at the lowest point of the raceway, 20 - detecting at least one light beam transmitted through the reaction vessel and from the incident light beam so as to provide a measurement signal representative of the variation of the amplitude and / or the frequency of the movement of the ferromagnetic ball, and - determine the coagulation of the blood sample to be analyzed from the measurement signal. However, when the variation of the amplitude and / or the frequency of the movement of the ferromagnetic ball is not due to an increase in the viscosity of the blood sample to be analyzed, but on the contrary to the presence of air bubbles and / or impurities in the blood sample, the coagulation time determined by such a determination method is then incorrect, which affects the reliability of such a determination method. The present invention aims to remedy this disadvantage. The technical problem underlying the invention consists in particular in providing a method and a device for determining the coagulation time of a blood sample to be analyzed which make it possible to reliably and economically determine the coagulation time. For this purpose, the present invention relates to a method for determining the coagulation time of a blood sample to be analyzed, comprising the steps of: providing a reaction cuvette containing the blood sample to be analyzed, the reaction cuvette comprising a bottom defining a concave raceway whose concavity is directed upwards, - placing a ferromagnetic ball on the raceway of the reaction vessel, - subjecting the ferromagnetic ball to a magnetic field so as to move the ball ferromagnetic along the raceway according to oscillatory movement, - exposing the blood sample to be analyzed to an incident light beam configured to be at least partially obscured by the ferromagnetic ball during at least part of its oscillatory movement along the runway, 15 - detecting at least one light beam transmitted through the reaction bowl ion and derived from the incident light beam so as to provide a measurement signal, - perform a first processing of the measurement signal so as to provide a first signal representative of the variation of at least one physical quantity representative of the movement of the ferromagnetic ball - performing a second processing of the measurement signal so as to provide a second signal representative of the variation of at least one optical property of the blood sample to be analyzed; - determining a first value of the coagulation time of the sample blood to be analyzed from the first signal, and - determine a second value of the clotting time of the blood sample to be analyzed from the second signal. Such a determination method makes it possible to quantify the coagulation time according to two different methods, which makes it possible to secure the results obtained. Indeed, in case of premature termination of the movement of the ferromagnetic ball 30 due to the presence for example of an air bubble or impurities in the blood sample to be analyzed, the comparison of the first and second determined values allows to identify a difference between the two determined coagulation time values. An operator can then take into account only the second determined value which is less influenced by the stopping of the ferromagnetic ball, or else repeat the test to ensure a correct measurement of the coagulation time. The determination method according to the present invention makes it possible to obtain two independent measurements of the coagulation time, and thus to make reliable the coagulation time measurements. According to an embodiment of the determination method, the measurement signal provided is obtained by sampling a continuous signal at regular intervals, the duration of an interval being preferably less than 15 ms, for example from order of 10 ms or 4 ms. According to an embodiment of the determination method, the first processing of the measurement signal is carried out such that the first signal supplied corresponds to the difference between a high envelope and a low envelope of the measurement signal. According to another embodiment of the invention, the processing unit is configured such that the first signal supplied corresponds to a sliding average of the difference between the high envelope and the low envelope of the measurement signal, and more specifically a sliding average of the difference between the high envelope and the low envelope of the measurement signal over a predetermined set of values of the difference between the high envelope and the low envelope of the measurement signal, for example twelve, corresponding to successive measurement or sampling instants, or a predetermined slip interval. Advantageously, each value of the first signal for a given measurement or sampling instant is determined as a sliding average of a predetermined set of values of the difference between the high envelope and the low envelope of the measurement signal Sm corresponding to successive measurement or sampling instants preceding the respective measurement or sampling instant. Preferably, each value of the first signal for a given measurement or sampling instant is determined as a sliding average of the last values of the difference between the high envelope and the low envelope of the measurement signal, for example last twelve values of the difference between the high envelope and the low envelope of the measurement signal. According to an embodiment of the determination method, the upper envelope of the measurement signal is determined by connecting the local maximums 30 of the measurement signal, and the low envelope of the measurement signal is determined by connecting the local minimums of the measurement signal. measurement signal. According to an embodiment of the determination method, the at least one physical quantity representative of the movement of the ferromagnetic ball is the amplitude and / or the frequency of the movement of the ferromagnetic ball. According to an embodiment of the determination method, the step of determining the first value of the coagulation time of the blood sample to be analyzed comprises a step of providing a base signal corresponding to a sliding average of first signal, for example on a predetermined slip interval or on a set of values of the first signal corresponding to successive measurement or sampling instants, the first value of the coagulation time of the blood sample to be analyzed being determined at from the basic signal. According to an embodiment of the determination method, each value of the basic signal for a given measurement or sampling instant is determined as a sliding average of a set of values of the first signal corresponding to measurement instants or successive sampling in a time interval whose limits are defined by reference to the given measurement or sampling instant. For example, each value of the base signal for a given measurement or sampling instant is determined as a sliding average of a set of values of the first signal corresponding to measurement or sampling times within a time interval. advantageously between 8 and 12 seconds and is for example about 10 seconds, preceding the given measurement or sampling time. According to another embodiment of the determination method, each value of the basic signal for a given measurement or sampling instant is determined as a sliding average of a set of values including the value of the first signal to the given measurement or sampling instant and all the values of the first signal corresponding to measurement or sampling instants preceding the respective measurement or sampling instant. According to an embodiment of the determination method, the step of determining the first value of the coagulation time of the blood sample to be analyzed comprises a step of determining the point of intersection between the first signal and a percentage. predetermined value of the basic signal, the first value of the coagulation time of the blood sample to be analyzed being the time value corresponding to the determined intersection point. According to an embodiment of the determination method, the predetermined percentage of the basic signal is between 30 and 60%. According to an embodiment of the determination method, the second processing of the measurement signal is carried out such that the second signal supplied corresponds to an averaged high envelope of the measurement signal. According to an embodiment of the determination method, the processing unit 5 is configured such that the second signal supplied corresponds to a sliding average of the upper envelope of the measurement signal, and more specifically a running average of the upper envelope of the measurement signal on a predetermined set of values of the upper envelope, for example twelve, corresponding to successive measurement or sampling instants, or on a predetermined slip interval. Advantageously, each value of the second signal for a given measurement or sampling instant is determined as a sliding average of a predetermined set of values of the upper envelope corresponding to successive measurement or sampling instants preceding the instant given measurement or sampling. Preferably, each value of the second signal for a given measurement or sampling instant is determined as a sliding average of the last values of the upper envelope, for example the last twelve values of the upper envelope. According to an embodiment of the determination method, the step of determining the second value of the coagulation time of the blood sample to be analyzed comprises a step of determining the maximum slope of the second signal, the second value of time of coagulation of the blood sample to be analyzed being the time corresponding to said maximum slope. According to an embodiment of the determination method, the latter comprises a step of comparing the determined first and second values of the coagulation time. According to an embodiment of the determination method, the latter further comprises a step of adjusting the light intensity of the incident light beam as a function of an initial value of the measurement signal. According to an embodiment of the determination method, the reaction vessel is provided such that the raceway has its lowest point substantially at its center. According to an embodiment of the determination method, the initial value of the measurement signal corresponds to a position of the ferromagnetic ball substantially at the lowest point of the raceway.
    [0002] According to an embodiment of the determination method, the latter further comprises a step of adjusting, during an initial phase of the determination method, at least one parameter representative of the magnetic field to which the ferromagnetic ball is subjected according to initial values of the measurement signal. According to an embodiment of the determination method, the at least one parameter representative of the magnetic field to which the ferromagnetic ball is subjected is adjusted according to the initial values of the first signal. According to one embodiment of the determination method, the at least one parameter representative of the magnetic field is the period and / or the intensity of the magnetic field to which the ferromagnetic ball is subjected.
    [0003] According to an embodiment of the determination method, the excitation frequency of the magnetic field is close to the natural frequency of the oscillatory movement of the ferromagnetic ball. According to an embodiment of the determination method, the magnetic field is generated by means of a magnetic field generation system shifted transversely to the general direction of extension of the raceway. Such an arrangement of the magnetic field generation system makes it possible to arrange the emission element vertically close to the bottom of the reaction vessel so as to reduce the distance separating the incident light beam and the bottom of the reaction vessel, and this without being hindered by the presence of the magnetic field generation system. This further results in a decrease in the amount of reagents and blood sample to be introduced into the reaction cuvette to perform each test, and therefore costs associated with each test. According to one embodiment of the determination method, the magnetic field generation system is arranged at least partly facing a wall of the reaction vessel extending substantially parallel to the raceway, and for example facing a longitudinal wall of the reaction bowl. According to one embodiment of the determination method, the magnetic field generation system comprises a first and a second electromagnet disposed respectively close to the ends of the raceway. The first and second electromagnets are for example arranged on the same side of the raceway. According to one embodiment of the determination method, the magnetic field can be adjusted by varying, for example, the deviations and / or the length of the electrical pulses applied to the coils of the electromagnets.
    [0004] According to an embodiment of the determination method, the determination device is configured such that, when the reaction bowl is received in the receiving housing and the ferromagnetic ball is at the lowest point of the path of rolling, the ferromagnetic ball occultly occult the incident light beam. According to an embodiment of the determination method, the transmitted light beam is detected by means of a detection element located substantially in the axis of the incident light beam. According to an embodiment of the determination method, the incident light beam is emitted by means of a transmitting element. The emission element and the detection element are for example arranged substantially in the axis of the raceway. The present invention furthermore relates to a device for determining the coagulation time of a blood sample to be analyzed, the determination device comprising: a reception housing in which a reaction dish containing the blood sample is intended to be received; to analyze and a ferromagnetic ball, the reaction cup delimiting a concave raceway whose concavity is directed upwards and on which the ferromagnetic ball 20 is placed; a magnetic field generation system configured to generate a magnetic field capable of moving the ferromagnetic ball along the race in an oscillatory motion when the reaction cuvette is received in the receiving housing, a transmitting element configured to emit an incident light beam towards the blood sample to be analyzed when the reaction bowl is received in the housing of r ception, the incident light beam being configured to be at least partly obscured by the ferromagnetic ball during at least part of its movement along the raceway, - a detection element configured to detect at least one light beam transmitted through the reaction vessel and from the incident light beam and to output a measurement signal, and - a processing unit configured to: - perform a first processing of the measurement signal so as to provide a first representative signal the variation of at least one physical quantity representative of the movement of the ferromagnetic ball, 3030048 8 - performing a second processing of the measurement signal so as to provide a second signal representative of the variation of at least one optical property of the blood sample to be analyzed, - determine a first value of the coagulation time of the blood sample to be analyzed from the first signal, and - determining a second value of the clotting time of the blood sample to be analyzed from the second signal. According to one embodiment of the determination device, the magnetic field generating system is shifted transversely relative to the general direction of extension of the raceway. According to one embodiment of the invention, the detection element is located substantially in the axis of the incident light beam. According to one embodiment of the invention, the raceway has its lowest point substantially in its center.
    [0005] According to one embodiment of the determination device, the ferromagnetic ball and the raceway are configured such that, when the ferromagnetic ball is at the lowest point of the raceway, the ferromagnetic ball occultly partially the incident light beam. According to one embodiment of the invention, the occultation rate of the incident light beam varies between a minimum value corresponding to a position of the ferromagnetic ball at the lowest point of the raceway and a maximum value corresponding to a position of the ferromagnetic ball furthest from the lowest point of the raceway, the minimum value being for example between 5 and 10%.
    [0006] According to one embodiment of the invention, the detection element is a photodetector, such as a photodiode. According to one embodiment of the invention, the emission element is a light-emitting diode. According to one embodiment of the invention, the determination device comprises a ferromagnetic ball intended to be placed in the bottom of the reaction cuvette. According to one embodiment of the invention, the determination device comprises a loading system configured to load and unload reaction cuvettes into and out of the reaction housing. The loading system 35 advantageously comprises a linear actuator, which may for example comprise an electric motor step by step.
    [0007] The present invention further relates to a reaction cuvette adapted for carrying out the method according to the invention, the reaction cuvette comprising: a receptacle configured to contain a biological fluid to be analyzed, the receptacle comprising: lower part having a bottom defining a concave raceway whose concavity is directed upwards, the raceway having its lowest point substantially at its center and being intended to guide an oscillatory movement of a ferromagnetic ball, 10 - an upper part delimiting an introduction opening, - first attachment means configured to hook the reaction cuvette to a first adjacent reaction cuvette in a first attachment direction, and - second attachment means configured to hook the reaction cuvette to a second adjacent reaction cuvette according to a second directio n hook which is substantially perpendicular to the first attachment direction, the reaction cup being characterized in that the width of the lower portion of the receptacle transversely to the general direction of extension of the raceway is less than the width of the upper part of the receptacle transversely to the direction of extension of the raceway, and in that the raceway is shifted transversely to a median longitudinal plane of the upper part of the receptacle. As a result, the raceway is closer to a first longitudinal wall of the reaction vessel than a second longitudinal wall of the reaction vessel opposite to said first longitudinal wall. Such a configuration of the reaction cuvette makes it possible to measure coagulation time in a reduced reaction volume, for example less than 90 μl, and thus to reduce the quantity of sample taken and also the quantity of reagents. used. This results in a significant decrease in costs associated with each test performed. In addition, in the context of immunological measurements using magnetic particles, such a configuration of the reaction cuvette ensures positioning of a magnet or electromagnet, during the washing operations of the magnetic particles, as close as possible to the reaction zone of the magnet. the reaction cuvette (placing it substantially in contact with the longitudinal wall of the reaction vessel 3030048 closest to the race), and therefore an optimum magnetic attraction of the magnetic particles against a longitudinal wall of the reaction cuvette, This makes it possible to avoid any risk of removal of a portion of the magnetic particles bound to the analyte to be quantified out of the reaction cuvette with the washing solution. In addition, in the context of further immunological measurements using magnetic particles, such a configuration of the reaction cuvette ensures positioning of an optical reading element as close as possible to the reaction zone of the reaction cuvette, and therefore of the results. accurate and reliable measurement.
    [0008] According to one embodiment of the invention, the upper part of the receptacle is flared in the direction of the insertion opening. According to one embodiment of the invention, the lower part of the receptacle is of substantially parallelepipedal shape and is elongated in the general direction of extension of the raceway.
    [0009] According to one embodiment of the invention, the first attachment means comprise at least one attachment tongue directed downwards and extending from an upper edge of the upper part of the receptacle. According to one embodiment of the invention, the reaction bowl comprises a notch formed on an upper edge of the upper part of the receptacle opposite to the upper edge from which the hooking tab extends, the hooking tab. a reaction cuvette being intended to cooperate with the notch of an adjacent reaction cuvette in the first attachment direction. According to one embodiment of the invention, the second hooking means 25 comprise a first hook open upwards and a second hook open downwards, the first hook open upwards being configured to engage with the second hook. open hook downwardly of an adjacent reaction bowl, the first and second hooks being formed on a base of the reaction bowl, along two opposite edges and orthogonal to the upper edge 30 from which extends the tongue of the reaction bowl; hooking. According to one embodiment of the invention, the raceway has the shape of a cylinder portion with a radius of between 8 and 10 mm. In any case, the invention will be better understood with the aid of the following description with reference to the appended schematic drawing showing, by way of nonlimiting examples, one embodiment of this determination device and of this trough. reaction.
    [0010] Figure 1 is a perspective view of a reaction cuvette according to the invention. Figure 2 is a cross-sectional perspective view of the reaction cup of Figure 1.
    [0011] Figure 3 is a longitudinal sectional view of the reaction cuvette of Figure 1 equipped with a ferromagnetic ball. Figure 4 is a cross-sectional view of the reaction cuvette of Figure 1 equipped with a ferromagnetic ball. Figures 5 to 8 are perspective views of a coagulation time determining device according to the invention equipped with a reaction cuvette and in different operating positions. Figure 9 is a schematic sectional view showing the relative arrangement between a magnetic field generating system of the determining device of Figure 5 and a reaction cup equipping said determination device. Figures 10 to 13 are partial views in longitudinal section of the determination device of Figure 5 showing different positions occupied by a ferromagnetic ball placed on a raceway of the reaction bowl.
    [0012] Figure 15 is a diagram showing the evolution of the amplitude of a measurement signal as a function of time. Figure 16 is a diagram showing the evolution of the amplitude of the low and high envelopes of the measurement signal as a function of time. Figure 17 is a diagram showing the evolution of the gap between the high and low envelopes of the measurement signal and the change in a predetermined percentage of a base signal determined from the gap between the envelopes high and low of the measurement signal. Figure 18 is a diagram showing the evolution of the amplitude of a high averaged envelope of the measurement signal as a function of time.
    [0013] Figures 1 to 4 show a unitary plastic reaction vessel 2 which is transparent to the light beams. The reaction cup 2 comprises a receptacle 3 configured to contain a biological fluid to be analyzed, such as a blood sample. The receptacle 3 for example has a height of the order of 22 mm and may for example contain up to 600 u.1_ of biological fluid to be analyzed.
    [0014] The receptacle 3 comprises a lower portion 4 and an upper portion 5 extending the lower portion 4. The lower portion 4 is of substantially parallelepipedal shape and has for example a length of the order of 8 mm and a width of the order 3 mm. The lower part 4 comprises two longitudinal walls 5 6a, 6b parallel to each other, two transverse walls 7a, 7b parallel to each other and a bottom 8. The bottom 8 defines a concave raceway 9 whose concavity is directed upwards. The raceway 9 is elongated in the longitudinal direction of the lower portion 4 of the receptacle 3 and has its lowest point substantially at its center. The raceway 9 is intended to guide an oscillatory movement of a ferromagnetic ball 11. The raceway 9 may for example be curvilinear and be substantially V-shaped, or as can be seen in FIG. a cylinder portion. According to the embodiment shown in the figures, the raceway 9 is delimited by two lateral rails 12, 13 15 formed in the bottom 8 of the lower part 4 of the receptacle 3. These two lateral rails 12, 13 allow more particularly guide the oscillating movement of the ferromagnetic ball 11 in the reaction bowl 2. The upper part 5 of the receptacle 3 flares away from the bottom 8 and defines an insertion opening 14. The upper part 5 has, for example 20 a general frustoconical shape. The upper portion 5 comprises two longitudinal walls 15a, 15b parallel to each other, and two transverse walls 16a, 16b connecting the longitudinal walls 15a, 15b therebetween, the longitudinal walls 15a, 15b and the transverse walls 16a, 16b delimiting the opening of In the embodiment shown in the figures, the upper portion 5 further comprises a connecting wall 17 connecting the longitudinal walls 6b, 15b, the connecting wall 17 being inclined relative to the longitudinal walls 6b, 15b . According to this embodiment of the invention, the longitudinal walls 6a, 15a are coplanar while the longitudinal walls 6b, 15b are parallel and offset with respect to each other.
    [0015] The transverse direction D1 is defined as the direction orthogonal to the longitudinal walls 6a, 6b and the longitudinal direction D2 as the direction orthogonal to the transverse walls 7a, 7b. The plane P1 is also defined as the median longitudinal plane of the upper part 5 of the receptacle 3, the plane P2 as the median longitudinal plane of the lower part 4 of the receptacle 3, and the plane P3 as the median transverse plane P3 of the receptacle. (see Figures 3 and 4).
    [0016] As can be seen more particularly in FIGS. 2 and 4, the width of the lower part 4 of the receptacle 3 perpendicular to the general direction of extension of the raceway 9, that is to say in the direction D1 , is less than the width of the upper part 5 of the receptacle 3 perpendicular to the direction of extension of the raceway 9, that is to say in the direction Dl. In addition, the lower portion 4 of the receptacle 3, and more particularly the raceway 9, is shifted transversely relative to the median longitudinal plane P1 of the upper portion 5 of the receptacle 3. Therefore, the raceway 9 is closer of the longitudinal wall 6a of the lower part 4 than 10 of the longitudinal wall 6b. According to the embodiment shown in the figures, the reaction bowl 2 further comprises a first finishing wall 18 extending in the extension of the longitudinal wall 6a opposite the insertion opening 14, and a second finishing wall 19 extending in the extension of the longitudinal wall 15b opposite the introduction opening 14. The reaction bowl 2 also comprises a catching tongue 21 directed downwards and extending from an upper longitudinal edge 22 of the upper part 5 of the receptacle 3. The reaction bowl 2 further comprises a notch 23 formed on an upper longitudinal edge 24 of the upper part 5 opposite the upper longitudinal edge 22. The notch 23 is of dimensions adapted to those of the latching tongue 21 so that the latching tongue 21 of a reaction bowl 2 is intended to cooperate with the notch 23 of a cubicle. adjacent reaction vette 2 in the direction D1 to effect the attachment of two adjacent reaction cuvettes 2.
    [0017] In addition, the reaction bowl 2 comprises a base 25 in the lower part, in which are formed along two opposite edges parallel to the direction D1, a first projection 26 forming a first hook open upwards and a second overflow 27 forming a second hook open downward. The first upwardly open hook is configured to engage the second downwardly open hook 2 of an adjacent reaction cup 2 in the direction D2 to hook two adjacent reaction cuvettes 2. Thanks to the structure of the latching tongue 21 and the first and second projections 26, 27, it is possible to hook reaction cups 2 to each other in two orthogonal directions, manually or automatically, to form plates. In addition, the overhangs 26, 27 make it possible to have overall dimensions of the reaction cups 2 which are substantially the same in their upper parts 5 and in their lower parts 4 so that the cups are assembled together. Reaction 2 is a flat plate. This makes it possible to order the reaction cuvettes 2 to store them in a simple, compact manner, while at the same time making it easy to detach a reaction cuvette 5 from the corresponding plate. Figures 5 to 13 show a determination device 31 configured to determine the coagulation time of a blood sample to be analyzed. The determining device 31 comprises a receiving housing 32 in which is intended to receive a reaction cuvette 2 containing the blood sample to be analyzed 33 and a ferromagnetic ball 11 placed on the raceway 9. The determination device 31 also comprises a magnetic field generation system 34 configured to generate a magnetic field 15 able to move the ferromagnetic ball 11 along the raceway 9 according to oscillatory movement when the reaction bowl 2 is received in the receiving housing 32. The excitation frequency of the magnetic field generated by the magnetic field generation system 34 is advantageously close to the natural frequency of the oscillatory movement of the ferromagnetic ball 11, and is for example 20 of the order of 3.125 Hz (period of the order of 320 ms). The determining device 31 is configured such that the magnetic field generation system 34 is shifted transversely to the general direction of extension of the raceway 9 when the reaction bowl 2 is received in the receiving housing 32 More particularly, the determining device 31 is configured such that the magnetic field generating system 34 is disposed at least partly facing a longitudinal wall, and for example the longitudinal wall 6b, of the receptacle 3 when the reaction cuvette 2 is received in the receiving housing 32.
    [0018] The magnetic field generation system 34 advantageously comprises two electromagnets 34a, 34b disposed respectively close to the ends of the raceway 9 and on the same side of the raceway 9, when the reaction bowl 2 is received in the housing. The magnetic field generated by the magnetic field generation system 34 can be advantageously adjusted by varying, for example, the deviations and / or the length of the electrical pulses applied to the coils of the electromagnets 34a, 34b. The determining device 31 further comprises a transmitting element 35 configured to emit an incident light beam 36 towards the blood sample to be analyzed 33 when the reaction cuvette 2 is received in the receiving housing 32. emission element 36 may for example be a light emitting diode. According to the embodiment shown in the figures, the determining device 31 is configured such that when the reaction cup 2 is received in the receiving housing 32 and the ferromagnetic ball 11 is at the lowest point of the 9, the ferromagnetic ball 11 partly obscures the incident light beam 36 (see Figures 10 and 12). According to one embodiment of the invention, the occultation rate of the incident light beam 36 varies between a minimum value corresponding to a position of the ferromagnetic ball 11 at the lowest point of the raceway 9 (see FIG. 10 and 12) and a maximum value corresponding to a position of the ferromagnetic ball 11 furthest from the lowest point of the raceway 9 (see FIGS. 11 and 13), the minimum value being for example between 5 and 10%.
    [0019] The determining device 31 further comprises a sensing element 37 configured to detect at least one transmitted light beam 38 through the reaction dish 2 and issuing from the incident light beam 36, and to output a measurement signal SM. FIG. 15 shows the evolution of the amplitude of an example of a measurement signal SM as a function of time, and more particularly the evolution of the relative luminous intensity of an example of a measurement signal SM as a function of the time. The detection element 37 may for example be a photodetector, such as a photodiode. According to the embodiment shown in the figures, the detection element 37 is located substantially in the axis of the incident light beam 36.
    [0020] Thus, according to the embodiment shown in the figures, the emission and detection elements are arranged on either side of the ends of the raceway 9 when the reaction bowl 2 is received in the receiving housing 32. According to one embodiment of the invention, the measurement signal SM is obtained by sampling a continuous signal at regular intervals, the duration of an interval, that is to say between two instants of time. sampling, being for example of the order of 10 ms. The determining device 31 also comprises a processing unit 39. As shown in particular in FIG. 5, the processing unit 39 can be arranged close to the receiving housing 32. Nevertheless, the processing unit 39 could also be remote from the measurement area. The processing unit 39 is more particularly configured to: - perform a first processing of the measurement signal SM so as to provide a first signal S1 representative of the variation of at least one physical quantity representative of the movement of the ferromagnetic ball 11 the at least one physical quantity representative of the movement of the ferromagnetic ball 11 being, for example, the amplitude and / or the frequency of the movement of the ferromagnetic ball 11, 15 - performing a second processing of the measurement signal SM so as to provide a second signal S2 representative of the variation of at least one optical property of the blood sample to be analyzed 33, the at least one optical property of the blood sample to be analyzed 33 being, for example, the absorbance of the sample test 33, 20 - determine a first value t1 of the coagulation time of the blood sample to be analyzed from the first signal S1, and - d end a second value t2 of the clotting time of the blood sample to be analyzed from the second signal S2. According to one embodiment of the invention, the processing unit 39 is configured so that the first signal 51 supplied corresponds to the difference between a high envelope and a low envelope of the measurement signal SM. The upper envelope of the measurement signal is determined by connecting the local maximums of the measurement signal SM, while the low envelope of the measurement signal is determined by connecting the local minimums of the measurement signal SM. FIG. 16 represents the evolution of the amplitude of the low and high envelopes EB and EH as a function of time, and more particularly the evolution of the relative light intensity of the low and high envelopes EB and EH as a function of time. According to another embodiment of the invention, the processing unit 39 is configured such that the first signal S1 provided corresponds to a sliding average of the difference between the high envelope and the low signal envelope. measuring device SM on a predetermined set of values of the difference between the high envelope and the low envelope of the measurement signal SM, for example twelve, corresponding to successive measurement or sampling instants. Preferably, each value of the first signal S1 for a given measurement or sampling instant is determined as a sliding average of the last values of the difference between the high envelope and the low envelope of the measurement signal SM, by example of the last twelve values of the difference between the high envelope and the low envelope of the measurement signal SM. According to one embodiment of the invention, the processing unit 39 is configured to provide a base signal corresponding to a sliding average of the first signal S1 over a predetermined slip interval. More particularly, each value of the base signal for a given measurement or sampling instant is determined as a sliding average of a set of values of the first signal S1 corresponding to measurement or sampling times within a range of time whose limits are defined by reference to the given measurement or sampling instant. For example, the time interval is 10 seconds, and precedes, for each value of the basic signal, the respective given measurement or sampling time. According to another embodiment of the determination method, each value of the basic signal for a given measurement or sampling instant is determined as a sliding average of a set of values including the value of the first signal 51 to the respective given measurement or sampling instant and all the values of the first signal 51 corresponding to measurement or sampling instants preceding the respective measurement or sampling instant. According to one embodiment of the invention, the processing unit 39 is configured to determine the point of intersection Pi between the first signal 51 and a third signal S3 corresponding to a predetermined percentage of the basic signal, the first value t1 of the clotting time of the blood sample to be analyzed determined by the processing unit 39 then being the instant corresponding to the point of intersection Pi determined. According to one embodiment of the invention, the third signal is between 30 and 60% of the basic signal. FIG. 17 represents the evolution of the amplitude of the first and third signals 51, S3 as a function of time, and more particularly the evolution of the relative light intensity of the first and third signals 51, S3 as a function of time. It should be noted that the predetermined percentage of the base signal can be programmed according to the tests to be performed, and for example depending on the reaction volume of the reaction cuvettes used.
    [0021] According to one embodiment of the invention, the processing unit 39 is configured such that the second signal S2 supplied corresponds to an averaged high envelope of the measurement signal SM. For example, the processing unit 39 is configured such that the second signal S2 provided corresponds to a sliding average of the upper envelope of the measurement signal on a predetermined set of values of the upper envelope, for example twelve , corresponding to successive measurement or sampling instants. Preferably, each value of the second signal S2 for a given measurement or sampling instant is determined as a sliding average of the last values of the upper envelope, for example the last twelve values of the upper envelope. FIG. 18 represents the evolution of the amplitude of the high averaged envelope as a function of time, and more particularly the evolution of the relative luminous intensity of the high averaged envelope as a function of time. According to one embodiment of the invention, the processing unit 39 is configured to determine the maximum slope Pm of the second signal S2, the second value t2 of the coagulation time of the blood sample to be analyzed, determined by the unit treatment 39 being then the moment corresponding to said maximum slope. According to one embodiment of the invention, the determining device 31 comprises an optical lens 41 disposed in the path of the incident light beam and configured to collimate the incident light beam 36. The determining device 31 further comprises loading 42 configured to load and unload reaction cuvettes 2 into and out of the reaction housing. The charging system 42 advantageously comprises a linear actuator, which may for example comprise an electric motor 43, such as an electric stepper motor. The determining device 31 furthermore advantageously comprises a first and a second element or body 44a, 44b respectively delimiting first and second housing portions 32a, 32b. The first and second members 44a, 44b are movably mounted relative to one another between a loading or unloading position (see FIG. 5) in which the first and second members 44a, 44b are spaced apart. on the other side and allow the reaction bowl 2 to move to the first and second housing portions 32a, 32b, and a measuring position in which the first and second members 44a, 44b are brought closer together. on the other side and delimit the reception housing 32.
    [0022] A method for determining the coagulation time of a blood sample to be analyzed using the determining device 31 will now be described. Such a determination method comprises the following steps: - providing a reaction cuvette 2 containing the blood sample to be analyzed 33, - placing a ferromagnetic ball 11 on the raceway 9 of the reaction cuvette 2, 10 - placing the reaction vessel 2 in the receiving housing 32 of the determining device 31, - generating a magnetic field using the magnetic field generation system 34 so as to move the ferromagnetic ball 11 along the raceway 9 according to oscillatory movement, the magnetic field being generated by sequentially feeding the coils of the two electromagnets 34a, 34b one after the other, - emitting an incident light beam 35 towards the blood sample to be analyzed 33 using of the transmitting element 36, detecting, for example every 20 ms, a light beam 38 transmitted through the reaction bowl 2 and coming from the incident light beam 36 with the aid of the detection element 37 so as to provide a measurement signal SM; - perform a first processing of the measurement signal SM with the aid of the processing unit 39 so as to provide a first signal S1 representative of the variation in particular of the amplitude of the movement of the ferromagnetic ball 11, 25 - performing a second processing of the measurement signal SM by means of the processing unit 39 so as to provide a second signal S2 representative of the variation, in particular, of the absorbance of the blood sample to be analyzed 33, - determining, using the treatment unit 39, a first value t1 of the coagulation time of the blood sample to be analyzed from the first signal 30 if, - determining with the aid of the processing unit 39 a second value t2 of the coagulation time of the blood sample to be analyzed from the second signal S2, and - comparing the first and second values t1, t2 determined from the coagulation time.
    [0023] According to an embodiment of the determination method, the latter further comprises a step consisting in regulating, and more precisely in controlling, the light intensity of the incident light beam 36 as a function of an initial value of the signal of SM measurement corresponding to a position of the ferromagnetic ball 5 substantially at the lowest point of the raceway 9. These provisions allow to control the light intensity of the incident light beam 36 on the initial absorbance of the sample blood to be analyzed, and for example to increase said light intensity if the blood sample to be analyzed is initially very absorbent, or vice versa, and in particular to have a reference signal as high as possible, without risk of saturation. According to an embodiment of the determination method, the latter further comprises a step of adjusting, and more precisely of controlling, during an initial phase of the determination method, for example of the order of 1 to 2 seconds at from the initiation of the movement of the ferromagnetic ball, at least one parameter representative of the magnetic field to which the ferromagnetic ball 11 is subjected as a function of the initial values of the measurement signal SM, and more particularly as a function of the initial values of the first signal 51. The at least one parameter representative of the magnetic field may, for example, be the period and / or the intensity of the magnetic field generated by the magnetic field generation system 34. These arrangements make it possible to optimize the oscillation of the ferromagnetic ball. 11 depending on the initial viscosity of the blood sample to be analyzed 33, and thus for example to avoid shocks of the ferromagnetic ball 11 against the walls of the reaction bowl 2, or, conversely, to prevent the maximum amplitude of the ferromagnetic ball 11 is insufficient.
    [0024] FIG. 14 shows a determination device 31 according to a second embodiment of the invention which differs from that shown in FIGS. 5 to 13 essentially in that the loading system 42 and the receiving housing 2 are respectively adapted for charging and receiving an assembly or block comprising a plurality of reaction cuvettes 2 'connected to each other.
    [0025] The various reaction cuvettes 2 'of such an assembly or block are, for example, integrally molded from a plastics material. The reaction cuvettes 2 'are advantageously arranged adjacent so that their longitudinal walls are parallel to each other. The reaction cuvettes 2 'are for example connected to each other at their upper part by lateral connection portions 45a, 45b.
    [0026] As goes without saying, the invention is not limited to the embodiments of this determination device and of this reaction bowl, described above as examples, it encompasses all the contrary. variants of embodiment.
    权利要求:
    Claims (12)
    [0001]
    REVENDICATIONS1. A method for determining the coagulation time of a blood sample to be analyzed, comprising the steps of: - providing a reaction cuvette (2) containing the blood sample to be analyzed (33), the reaction cuvette (2) comprising a bottom (8) delimiting a concave raceway (9) whose concavity is directed upwards, - placing a ferromagnetic ball (11) on the raceway (9) of the reaction bowl (2), - subjecting the ball ferromagnetic (11) to a magnetic field so as to move the ferromagnetic ball along the raceway (9) according to oscillatory movement, - expose the blood sample to be analyzed to an incident light beam (36) configured to be at least part obscured by the ferromagnetic ball (11) during at least part of the oscillatory movement of the ferromagnetic ball along the raceway (9), - detecting at least one light beam (38) transmitted through the reaction cuvette (2) and coming from the incident light beam (36) so as to provide a measurement signal (SM), - performing a first processing of the measurement signal (SM) so as to provide a first signal (S1) representative of the variation of at least one physical quantity representative of the movement of the ferromagnetic ball (11), - performing a second processing of the measurement signal (SM) so as to provide a second signal (S2) representative of the variation of at least one optical property of the blood sample to be analyzed, - determining a first value (t1) of the coagulation time of the blood sample to be analyzed from the first signal, and - determining a second value (t2) of the coagulation of the blood sample to be analyzed from the second signal. 30
    [0002]
    2. Determination method according to claim 1, in which the first processing of the measurement signal (SM) is carried out in such a way that the first signal (S1) supplied corresponds to the difference between a high envelope and a low signal envelope. Measurement (SM). 35 3030048 23
    [0003]
    The method of determining according to claim 1 or 2, wherein the step of determining the first value (t1) of the coagulation time of the blood sample to be analyzed comprises a step of providing a base signal corresponding to a sliding average of the first signal (S1), the first value of the coagulation time of the blood sample to be analyzed being determined from the base signal.
    [0004]
    The method of determining according to any one of claims 1 to 3, wherein the second processing of the measurement signal (SM) is performed such that the second signal (S2) provided corresponds to a running average of the high envelope of the measurement signal.
    [0005]
    The method of determining according to claim 4, wherein the step of determining the second value (t2) of the clotting time of the blood sample to be analyzed comprises a step of determining the maximum slope of the second signal (S2 ), the second value (t2) of the coagulation time of the blood sample to be analyzed being the time corresponding to said maximum slope.
    [0006]
    6. A method of determination according to any one of claims 1 to 5, which comprises a step of comparing the determined first and second values (t1, t2) of the coagulation time.
    [0007]
    The method of determining according to any one of claims 1 to 6, which further comprises a step of adjusting the light intensity of the incident light beam (36) according to an initial value of the measurement signal.
    [0008]
    8. Determination method according to any one of claims 1 to 7, which further comprises a step of adjusting, during an initial phase of the determination method, at least one parameter representative of the magnetic field to which the ferromagnetic ball is subjected ( 11) according to the initial values of the measuring signal (SM).
    [0009]
    9. Device for determining (31) the coagulation time of a blood sample to be analyzed, the determination device comprising: - a receiving housing (32) in which is intended to receive a reaction bowl (2) containing a blood sample to be analyzed (33) and a ferromagnetic ball (11), the reaction bowl (2) delimiting a concave raceway (9) whose concavity is directed upwards and on which the ferromagnetic ball is placed (11), - a magnetic field generation system (34) configured to generate a magnetic field capable of moving the ferromagnetic ball (11) along the raceway (9) in oscillatory motion when the reaction bowl (2) ) is received in the receiving housing, - a transmitting element (35) configured to emit an incident light beam (36) towards the blood sample to be analyzed (33) when the reaction bowl (2) is received in the receiving housing (32), the incident light beam (36) being configured to be at least partially obscured by the ferromagnetic ball (11) during at least a portion of the movement of the ball ferromagnetic along the raceway (9), - a detection element (37) configured to detect at least one light beam (38) transmitted through the reaction vessel (2) and from the incident light beam (36) and to output a measurement signal (SM), and - a processing unit (39) configured to: - perform a first processing of the measurement signal (SM) so as to provide a first signal (S1) representative of the variation of at least one physical quantity representative of the movement of the ferromagnetic ball (11), - performing a second processing of the measurement signal (SM) so as to provide a second signal representative of the variation of at least one optical property of the sample n blood to be analyzed, - determining a first value (t1) of the coagulation time of the blood sample to be analyzed from the first signal, and - determining a second value (t2) of the clotting time of the blood sample to analyze from the second signal.
    [0010]
    The determining device (31) according to claim 9, wherein the magnetic field generating system (34) is offset transversely to the general direction of extension of the raceway (9).
    [0011]
    Determination device (31) according to claim 9 or 10, which is configured such that when the reaction cuvette (2) is received in the receiving housing (32) and the ferromagnetic ball (11) located at the lowest point of the race (9), the ferromagnetic ball (11) partly obscures the incident light beam (36).
    [0012]
    12. Reaction cuvette (2) adapted for carrying out the method according to one of claims 1 to 8, the reaction cuvette (2) comprising: a receptacle (3) configured to contain a biological fluid to be analyzed; , the receptacle (3) comprising: - a lower part (4) comprising a bottom (8) delimiting a concave raceway (9) whose concavity is directed upwards, the rolling path (9) having its point the lowest substantially at its center and being intended to guide an oscillatory movement of a ferromagnetic ball (11), - an upper part (5) delimiting an insertion opening (14), - first attachment means configured to hooking the reaction cuvette (2) to a first adjacent reaction cuvette in a first hooking direction (D1), and - second hooking means configured to hook the reaction cuvette (2) to a second cuvette adjacent reaction e according to a second attachment direction (D2) which is substantially perpendicular to the first attachment direction (D1), the reaction cuvette (2) being characterized in that the width of the lower part (4) of the receptacle (3) transverse to the general direction of extension of the raceway (9) is less than the width of the upper part (5) of the receptacle (3) transversely to the direction of extension of the rolling path (9), and in that the raceway (9) is shifted transversely to a median longitudinal plane (P1) of the upper part (5) of the receptacle (3).
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    同族专利:
    公开号 | 公开日
    EP3234596B1|2020-08-12|
    FR3030048B1|2016-12-23|
    EP3234596A1|2017-10-25|
    US20170370905A1|2017-12-28|
    ES2829583T3|2021-06-01|
    WO2016097536A1|2016-06-23|
    RU2017123908A3|2019-04-01|
    CN107003297B|2019-08-20|
    RU2724335C2|2020-06-23|
    CN107003297A|2017-08-01|
    KR20170094408A|2017-08-17|
    JP2017538941A|2017-12-28|
    JP6696985B2|2020-05-20|
    BR112017011174A2|2018-02-27|
    CA2968490A1|2016-06-23|
    MX2017007791A|2018-01-11|
    RU2017123908A|2019-01-17|
    US10605801B2|2020-03-31|
    AU2015366041A1|2017-06-22|
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    法律状态:
    2015-10-30| PLFP| Fee payment|Year of fee payment: 2 |
    2016-06-17| PLSC| Publication of the preliminary search report|Effective date: 20160617 |
    2016-07-29| TP| Transmission of property|Owner name: DIAGNOSTICA STAGO, FR Effective date: 20160622 |
    2016-10-13| PLFP| Fee payment|Year of fee payment: 3 |
    2017-11-16| PLFP| Fee payment|Year of fee payment: 4 |
    2019-09-20| PLFP| Fee payment|Year of fee payment: 6 |
    2020-09-17| PLFP| Fee payment|Year of fee payment: 7 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1462423A|FR3030048B1|2014-12-15|2014-12-15|METHOD AND DEVICE FOR DETERMINING THE COAGULATION TIME OF A BLOOD SAMPLE AND REACTION CUP|FR1462423A| FR3030048B1|2014-12-15|2014-12-15|METHOD AND DEVICE FOR DETERMINING THE COAGULATION TIME OF A BLOOD SAMPLE AND REACTION CUP|
    CN201580068082.6A| CN107003297B|2014-12-15|2015-12-09|For determining the method and apparatus and reaction vessel of the setting time of blood sample|
    RU2017123908A| RU2724335C2|2014-12-15|2015-12-09|Method and apparatus for determining the blood sample coagulation time, as well as a reaction tray|
    KR1020177019343A| KR20170094408A|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and a reaction cuvette|
    CA2968490A| CA2968490A1|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction vessel|
    BR112017011174-8A| BR112017011174A2|2014-12-15|2015-12-09|method and device for determining the clotting time of a blood sample and a reaction vessel|
    US15/535,696| US10605801B2|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction cuvette|
    PCT/FR2015/053399| WO2016097536A1|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction vessel|
    JP2017532633A| JP6696985B2|2014-12-15|2015-12-09|Method and apparatus for determining the clotting time of a blood sample, and reaction cuvette|
    MX2017007791A| MX2017007791A|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction vessel.|
    EP15825613.1A| EP3234596B1|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction vessel|
    ES15825613T| ES2829583T3|2014-12-15|2015-12-09|Procedure and device for determining the clotting time of a blood sample, and reaction cuvette|
    AU2015366041A| AU2015366041B2|2014-12-15|2015-12-09|Method and device for determining the coagulation time of a blood sample, and reaction vessel|
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