JP6770985B2 - Blood test system and method - Google Patents

Description

This document relates to systems and methods for examining the properties of blood samples, such as an automated thromboelastometry system for point-of-care total blood coagulation analysis.

Hemostasis is the reaction of the human body to vascular injury and bleeding. Hemostasis means the concomitant action of platelets with a large number of blood coagulation proteins (or coagulation factors), which results in the formation of blood clots followed by bleeding arrest.

Various methods have been introduced to form sufficient clots and to assess the ability of blood to determine the stability of the clot. While common laboratory tests, such as platelet measurements or fibrin concentration measurements, provide information on whether the components tested are available in sufficient amounts, some of these tests are physiological conditions. Under the circumstances, it may not be possible to determine whether the components tested work properly. For example, in point-of-care situations (eg, at the surgical site during surgery), other laboratory tests act on plasma, thereby imposing additional preparatory steps and additional time beyond the preferred time. There is.

Another group of tests that assess the ability of blood to form sufficient clots is known as the "viscoelastic method." In at least some viscoelastic methods, clot stiffness (or other parameters dependent on it) can be measured over a period of time, for example, from the formation of first fibrin fibers to the dissolution of clots by the fibrin lysis phenomenon. Be measured. Clot hardness is a functional parameter that contributes to hemostasis in vivo, as the clot must resist blood pressure and shear stress at the vascular injury or incision location. In many cases, clot hardness can be derived from a number of related processes, including coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activation, and fibrin-platelet interactions. To isolate and test for specific functions of platelets, fibrinogen, and other factors in a blood sample, reagent compounds can be mixed with the blood sample, whereby certain constants in the blood sample. Activates or suppresses ingredients.

Some of the systems for testing the properties of a blood sample, which will be understood to contain a derivative of blood such as blood or plasma, as used herein. Embodiments include a control console configured to test blood samples to provide a point of care total blood coagulation analysis. For example, the system is used as an automated thromboelastometry system to provide detailed and rapid results of blood coagulation properties in response to the receipt of one or more blood samples mixed with various reagents. it can.

In some embodiments, the thromboelastometry system comprises a reusable analyzer console and one or more single-use components configured to correspond to the console. In one example, to operate a thromboelastometry system, the user is prompted by the user interface of the analyzer console to initiate a large number of blood and reagent transfer and mixing operations. The analyzer console then automatically performs the test (without further requiring user interaction with the analyzer console or the blood sample) using a qualitative graphical display and quantitative parameters. Then, the result is displayed on the graphical display. Such analysis provides information on the entire mechanism of hemostasis, such as clot time, clot morphology, clot stability, and lysis. In addition, such information is quickly output from the user interface of the system to indicate reliability of the patient's blood characteristics at the point of care (eg, while the patient is undergoing surgery in the operating room). Yes, and can provide quick results.

In one embodiment, the control console for measuring the coagulation properties of the blood sample is (i) the control unit housing, (ii) a user interface coupled to the control unit housing to project the coagulation properties of the blood sample. And (UI) include a plurality of individual thromboelastometry measurement modules housed within the control unit housing. Each measurement module of the plurality of individual thromboelastometry measurement modules includes a shaft configured to receive a probe for testing the blood sample using a probe cup device. Each individual measurement module of the plurality of individual thromboelastometry measurement modules is said to be independent of the rotation of the shaft of all the other individual measurement modules of the plurality of individual thromboelastometry measurement modules. Includes a dedicated actuating unit that rotates each shaft of the measurement module.

Such a control console for measuring the coagulation properties of a blood sample may optionally include one or more of the following features: In some embodiments, the actuating unit comprises a stepper motor. The stepper motor may optionally include a threaded drive shaft. In various embodiments, the actuating unit also includes a sliding unit. The sliding unit may have a threaded collar that is screw-engaged to the threaded drive shaft of the motor, whereby the motor transforms the sliding unit into a straight line. Can be driven. In certain embodiments, the actuating unit also includes a spring wire. In some such embodiments, due to the spring wire extending between the sliding unit and the shaft, the linear transformation of the sliding unit may result in a rotational movement of the shaft.

In various embodiments of the control console for measuring the coagulation properties of a blood sample, the actuating unit further comprises a magnet that attracts the spring wire to the sliding unit. The spring wire may be magnetically attracted to the curved surface of the sliding unit. If desired, the actuating unit may include a sensor configured to detect the position of the sliding unit. In some embodiments, the sensor comprises a Hall effect sensor. In various embodiments, the actuating unit may include one or more moving end sensors configured to detect a movement limit of the sliding unit. The control console may include one or more vibration sensors housed within the control unit housing. In some embodiments, each individual measurement module of the plurality of individual thromboelastometry measurement modules comprises one or more vibration sensors.

In certain embodiments of the control console for measuring the coagulation properties of a blood sample, each individual measurement module of the plurality of individual thromboelastometry measurement modules is for evaluating a charge coupling element (CCD) component. Includes evaluation unit. In some embodiments, the evaluation unit (i) receives the luminance distribution data from the CCD, (ii) generates CCD calibration data based on the luminance distribution data, and (iii) the CCD calibration. The data may be configured to be compared with real-time measured CCD luminance distribution data. In some embodiments, each individual measurement module of the plurality of individual thromboelastometry measurement modules may further include a heater configured to heat the cup in the probe cup device.

In another embodiment, the method for evaluating the CCD component of a thromboerastometry analysis system is performed by one or more processors of the thromboelastometry analysis system or one or more processors of a separate AD module. .. The method receives brightness distribution data from the CCD, generates CCD calibration data (where the CCD calibration data is generated based on the brightness distribution data from the CCD), and said. This includes comparing the CCD calibration data with the real-time measured CCD brightness distribution data (where the thromboelastometry analysis system is performing the thromboelastometry analysis). In some embodiments, the luminance distribution data from the CCD represents individual luminance distribution data from a plurality of individual pixels of the CCD.

Such a method for evaluating the CCD component of a thromboelastometry analysis system performed by one or more processors of the thromboelastometry analysis system or one or more processors of a separate AD module is optionally. It may include one or more of the following features: In some embodiments, the method further comprises determining the position of the falling or rising edge of the luminance distribution data from the CCD.

In another embodiment, the method of controlling the accuracy of the thromboelastometry analysis system is performed by one or more processors of the thromboelastometry analysis system or one or more processors of a separate AD module. .. The method receives vibration data indicating the detection level of vibration of the thromboelastometry analysis system, compares the received vibration data with an allowable threshold, and receives the vibration data larger than the allowable threshold. Includes generating vibration error indications accordingly.

Such methods of controlling the accuracy of the thromboelastometry analysis system may optionally include one or more of the following features: In some embodiments, the method provides position indication data indicating the position of the sliding unit detected relative to the operating unit of the thromboelastometry analysis system to one or more processors of the thromboelastometry analysis system. Including receiving at. In certain embodiments, the method also comprises comparing the received position indication data with one or more permissible thresholds by one or more processors of the thromboelastometry analysis system. In various embodiments, the method is said by one or more processors of the thromboelastometry analysis system and based on comparison of one or more tolerance thresholds with the received position indication data. It also includes generating position error indications in response to the received position indication data that is greater than one or more permissible thresholds.

In another embodiment, the method of controlling the accuracy of the thromboerastometry analysis system is performed by one or more processors of the thromboelastometry analysis system, or by one or more processors of a separate AD module. To. The method receives position indication data indicating the position of the sliding unit detected with respect to the operating unit of the thromboelastometry analysis system, and compares the received position indication data with one or more allowable thresholds. And (based on the comparison of the one or more permissible thresholds with the received position indication data), depending on the received position indication data greater than the one or more permissible thresholds. Includes generating position error indications.

Such methods of controlling the accuracy of a thromboelastometric analysis system may optionally include one or more of the following features: In some embodiments, the position indication data comprises one or more signals from one or more moving end sensors indicating whether the sliding unit is located at the desired movement limit position. .. In certain embodiments, the position indication data indicates the real-time position of the sliding unit as it moves linearly back and forth along a linear path, one or more from one or more sensors. Contains 10 signals.

Some or all of the embodiments described herein may provide one or more of the following advantages: First, some embodiments of the thromboelastometry system described herein are configured with independent operating units of multiple inspection and measurement channels for individual modules or channels. .. For example, in some embodiments, the thromboelastometry system comprises four modules or channels, each of which has an independent operating unit. Therefore, the operation of each inspection and measurement module can be controlled independently of other inspection and measurement modules. In addition, the use of independent actuation units for each of the multiple inspection and measurement modules provides a module design that, in some situations, benefits the maintenance performance of the system.

Second, the actuation unit of some embodiments of the thromboelastometry system comprises a position-controllable rotary actuator (eg, a stepper motor coupled to a programmable stepper motor control system, or a feedback encoder. , And another type of suitable rotary actuator coupled to the control system). The use of position controllable actuators (eg, motors) is advantageous in allowing programmable actuation patterns. In addition, in some embodiments, the stepper motor allows the rotary thromboelastometry system to operate more accurately than some other type of motor. Moreover, in some embodiments, the stepper motor enhances isolation from certain external error factors such as vibration.

Third, some embodiments of the thromboelastometry system are configured with firmware for self-evaluation and calibration of the CCD (charge coupling element) component of the thromboelastometry inspection system. Therefore, in some cases, measurement inaccuracies are reduced or eliminated. In some such embodiments, the functionality of each individual pixel of the CCD is verified prior to performing a thromboelastometry test. As a result, the invariance of the performance of the thromboelastometry system is enhanced.

Fourth, some embodiments of the thromboelastometry system are configured with additional firmware to monitor and evaluate the functional aspects of the rotary thromboelastometry operation and detection system. The firmware. For example, in some embodiments, vibrations that may distort the measurement signal are detected and used to manage the thromboelastometry system. In addition, some embodiments include sensors that detect the movement and position of the moving end of the rotary thromboelastometry actuation system. These systems, which monitor and evaluate the functional aspects of the rotary thromboelastometry operation and detection system, provide a robust measurement system and enhance the quality of the measurement (eg, the accuracy of the thromboelastometry measurement). And / or increase precision).

Details of one or more embodiments of the invention will be revealed in the accompanying drawings and in the following detailed description. Other features, objectives, and advantages of the present invention will become apparent from the detailed description and drawings, and from the claims.

FIG. 1 is a perspective view of an exemplary thromboelastometry system according to some embodiments. FIG. 2 is an example of a graphic that quantifies clot stiffness during clot formation, as calculated and displayed by the thromboelastometry system of FIG. FIG. 3 is a schematic view illustrating an exemplary rotary thromboelastometry detection system unit of the thromboelastometry system of FIG. FIG. 4 shows an exemplary activation and detection module (also referred to herein as “AD module” or “ADM”) for the individual thromboelastometry measurement channels of the thromboelastometry system of FIG. It is a perspective view. FIG. 5 is an enlarged perspective view of an exemplary AD module of FIG. FIG. 6 is an enlarged perspective view of an operating unit of an exemplary AD module of FIG. FIG. 7 is an enlarged perspective view of a sliding portion of the operating unit of FIG. FIG. 8 is a flow chart of an exemplary CCD evaluation process that can be used with the thromboelastometry system of FIG. FIG. 9 is a flow chart of another CCD evaluation process that can be used with the thromboelastometry system of FIG. FIG. 10 is a flow chart of the process of controlling the quality of thromboelastometry measurements that can be used with the thromboelastometry system of FIG. FIG. 11 is a flow chart of the process of controlling the quality of another thromboelastometry measurement that can be used with the thromboelastometry system of FIG.

Similar reference symbols in the various figures indicate similar elements.

Referring to FIG. 1, some embodiments of an exemplary blood test system 100 include a blood analyzer console 110 as well as a graphical user interface 120 coupled to the blood analyzer console 110. In the illustrated embodiment, the blood test system 100 is a thromboelastometry system configured to measure the blood coagulation properties of a large number of blood samples. An example of such a thromboelastometry system 100 is the Rotem (ROTEM®) delta thromboelastometry system available from Tem International Geembeher, which has its headquarters in Munich, Germany. Thromboelastography and thromboelastography continuously plot clot stiffness during clot formation (eg, related to coagulation factors and inhibitors, platelets, and fibrin) and subsequent fibrin lysis. It is based on measuring the elasticity of blood by recording.

An exemplary thromboerastometry system 100 performs in vitro blood diagnostics, especially in point-of-care settings (eg, in surgical settings when the patient is in surgery and in preparation for surgery). It is advantageous. In addition, the thromboelastometry system 100 can be used as a laboratory-installed total blood coagulation analysis system. The thromboelastometry system 100 provides quantitative and qualitative indications of the coagulation status of blood samples.

In some embodiments, the graphical display displayed on the graphical user interface 120 is a variety of blood diagnostic results (eg, one or more plots, numerical data or measurement results, sometimes referred to as TEMograms). , Or a combination thereof), and the various blood diagnostic results may explain the interaction between components such as coagulation factors and inhibitors, fibrinogens, platelets and the fibrinolytic system. For example, with reference to FIG. 2, in some embodiments, the graphical user interface 120 provides the clot hardness recorded continuously as a diagram as a graphical display 200 during clot formation. FIG. 2 is an example of a graphic 200, for example, during which analysis is being performed, the graphic is calculated and displayed by the thromboelastometry system 100, thereby quantifying the hardness of the thrombus during clot formation. Will be done. In some embodiments, during clot formation, a plurality of such graphical displays 200 related to thrombus hardness are simultaneously displayed on the graphical user interface 120.

Further referring to FIG. 1, in some embodiments, the analyzer console 110 houses a hardware device and a subsystem that controls the operation of the thromboelastometry system 100. For example, the analyzer console 110 houses one or more processors and a memory device capable of storing the operating system and other executable commands. In some embodiments, the executable command, when executed by the one or more processors, includes analysis of blood test result data indicating blood coagulation properties, and output via user interface 120. The operation is configured to be performed by the system 100.

In some embodiments, the analyzer console 110 also houses various internal subsystems, includes various electronic connection receivers (not shown), and includes cartridge ports (not shown). The various electronic connection receivers are not limited to these, but include one or more USB ports, Ethernet® ports (eg, RJ45), VGA connectors, sub-D9 connectors (RS232), and the like. Such network and device connectors may be included. Such connection receivers may be located at the rear of the analyzer console 110 or at other convenient locations on the analyzer console 110. For example, in some embodiments, one or more USB ports may be located on or near the front of the analyzer console 110. The USB ports so arranged may provide user convenience for storing data on a memory stick, for example. In some embodiments, the thromboelastometry system 100 operates using wireless communication methods such as, but not limited to, Wi-Fi, Bluetooth®, NFC, RF, IR, and the like. It is configured as follows.

Further referring to FIG. 1, in some embodiments, the graphical user interface 120 is in graphical and / or textual form to assist the user during preparation of a blood sample for examination by the thromboerastometry system 100. It is also used to convey user commands. If desired, the graphical user interface 120 is coupled to the analyzer console 110 and is a touch screen display. This allows the user, for example, to enter information and select menu items. In some embodiments, the graphical user interface 120 is fixedly attached to the analyzer console 110. In certain embodiments, the graphical user interface 120 is rotatable and / or otherwise position adjustable or removable with respect to the analyzer console 110.

The blood test system 100 may include a keyboard 130 and / or other types of user input devices such as a mouse, touchpad, trackball, and the like. In some embodiments, the thromboelastometry system 100 also includes an external barcode reader. Such external barcode readers are not limited to these, but are simple one-dimensional or two-dimensional bar code input (entry) of data such as blood sample data, user identifiers, patient identifiers, normal values, and the like. Can be smoothed. Alternatively or additionally, the thromboelastometry system 100 may include a reader configured to read near-field communication tags, RFID tags, and the like. In some embodiments, even if a computer data network (eg, intranet, internet, LAN, etc.) is used so that the remote device can receive and / or input information from the thromboelastometry system 100. Good.

The illustrated thromboelastometry system 100 also includes a pipette 160 for an electronic system. The pipette 160 of the system allows the user to conveniently distribute a measured volume of liquid (such as blood or reagents) during the process of preparing a pre-test blood sample. In some embodiments, the pipette 160 of the system is a semi-automatic software controlled device. For example, in some embodiments, the pipette 160 of the system automatically draws the desired amount of liquid from one container, after which the user can dispense the desired amount of liquid into another container. ..

In some embodiments, the operation of the blood test system 100 comprises using one or more reagents 170 that are mixed with a blood sample prior to performing thromboelastometry. For example, reagent 170 may comprise compounds such as, but not limited to, CaCl2, ellagic acid or phospholipids, tissue factor, heparinase, polybrene, cytochalasin D, tranexamic acid, and combinations thereof. it can. In some embodiments, the thromboelastometry system 100 provides user instructions (eg, via a graphical user interface 120) for mixing a particular reagent 170 with the blood sample using the pipette 160 of the system. Will do.

The thromboelastometry analyzer console 110 also includes one or more individual thromboelastometry measurement stations 180 (sometimes also referred to herein as "channels" or "measurement modules"). The illustrated embodiment of the thromboelastometry system 100 includes four individual thromboelastometry measurement stations 180 (ie, four channels or four measurement modules).

As further described below, each thromboelastometry measurement station 180 includes a cup holder in which the user places a sample cup containing blood and reagents while preparing for a thromboelastometry test. In some embodiments, the cup holder is attached with a heating system, whereby the sample is warmed to near body temperature (eg, 37 ± 1.0 ° C.) and maintained at that temperature. Can be done.

As further described below, in some embodiments, each thromboelastometry measurement station 180 includes a pin or probe that may be detachably placed within a cup containing the sample to be inspected. There is a gap between the probe and the cup. In some embodiments, the shaft and probe are swung back and forth by less than about 10 ° (in both directions), preferably about 3 ° to 6 ° (in both directions), or otherwise. The method is to rotate. The swing of the shaft and the probe may have the same amplitude in both rotation directions. The sway is measured and the sway is reduced as the blood / reagent mixture begins to harden due to thrombolysis. By measuring such fluctuations over a period of time with the thromboelastometry measurement station 180, the results of thromboelastometry are produced.

Also with reference to FIG. 3, an exemplary rotary thromboelastometry actuation and detection system 300 that may be present within each thromboelastometry measurement station 180 (measurement module) is schematically shown. In some embodiments, the shaft 310 of the actuation and detection system 300 can engage the single-use probe 138 to perform rotary thromboelastometry on the blood sample contained within the single-use cup 136. .. In FIG. 3, the probe 138 and cup 136, as a whole, are shown in the longitudinal cross section for easy viewing and comprehension of the exemplary rotary thromboelastometry actuation and detection system 300. In some embodiments, the probe 138 has an outer diameter of about 6 mm and the cup 136 has an inner diameter of about 8 mm. However, the dimensions of the cup 136 and probe 138 can be increased or decreased as appropriate.

In this particular embodiment, the typically exemplary rotary thromboelastometry actuation and detection system 300 includes a base plate 302, a shaft 310, a bearing 312, a mirror 314, a reaction spring wire 320, a light source 330, and a detection. Includes a vessel 340 (eg, charge coupling element (CCD), etc.). The single-use cup 136 can be lifted (eg, by the user) as indicated by arrow 318, whereby the tip position of the shaft 310 enters the hole 139 of the probe 138 and is detachable from the probe 138. Will be combined with. The bearing 312 is engaged with the base plate 302 and the shaft 310 to cause a rotational movement of the shaft 310 with respect to the base plate 302. The spring wire 320 is coupled to the shaft 310 and the induced movement of the spring wire 320 (as driven by a motor as further described below) is indicated by arrow 316 (both rotation directions). The shaft 310 can be guided to swing back and forth by less than 10 °, preferably by about 3 ° to about 6 ° (in both directions of rotation). The mirror 314 is coupled to the shaft 310. The light source 330 is configured to illuminate the mirror 314, which can be reflected from the mirror 314 towards the detector 340 (in a direction corresponding to the direction of rotation of the shaft 310). Therefore, the operation of probe 138 is detected by an optical detection system (eg, detector 340). It should be understood that other configurations of the rotary thromboelastometry actuation and detection system 300 are also envisioned within this disclosure.

As the blood in the cup 136 begins to coagulate, the amplitude of movement of the shaft 310 begins to decrease (as detected by the reflection of light rays from the mirror 314 to the detector 340). During coagulation, the fibrin skeleton of blood creates a mechanical elastic bond (along with platelets) between the surface of cup 136 and the surface of probe 138. Thus, ongoing coagulation steps induced by the addition of one or more of the activators (eg, reagents) can be observed and quantified.

The motion data detected by the detector 340 is analyzed by an algorithm running on the analyzer console 110 to process and confirm the thromboelastometry results. This system is not limited to these, but is limited to clot time, clot formation time, alpha angle, amplitude, maximum clot hardness, dissolution start time, dissolution time, dissolution index (%), and maximum dissolution. Facilitates various thromboelastometric parameters such as (%). Thus, for suitable medical intervention, various deficiencies in the patient's hemostatic state can be identified and various deficiencies in the patient's hemostatic state can be explained. At the end of the inspection step, the cup 136 may be lowered from the probe 138 to disengage the shaft 310.

Further referring to FIG. 1, the analyzer console 110 corresponds to one or more individual thromboelastometry measurement stations 180 (eg, one-to-one) with one or more rotary thromboelastometry operations. And can accommodate the detection module (AD module) 400. Such a rotary thromboelastometry AD module 400 can be operated, for example, like the exemplary rotary thromboelastometry actuation and detection system 300 described above with reference to FIG.

With reference to FIG. 4, the individual rotary thromboelastometry AD module 400 can generally include a housing 410 and a shaft 420. The shaft 420 can be detachably coupled to a single-use probe (eg, probe 138 in FIG. 3) to perform thromboelastography and / or thromboelastography, as described above. .. That is, as previously described, the shaft 420 is rotatably swung back and forth by less than 10 ° (in both directions of rotation), preferably by about 3 ° to about 6 ° (in both directions of rotation). Can be

With reference to FIG. 5, an enlarged view of the rotary thromboelastometry AD module 400 makes the main components of the AD module 400 easy to see. For example, the rotary thromboelastometry AD module 400 includes a housing 410 (including three housing portions 410a, 410b, and 410c), a shaft 420, an actuating unit 430, a spring wire 440, an LED450, a CCD460, and a print. Includes substrate (PCB) assembly 470.

In some embodiments, the housing 410 includes a cover 410a, a substrate 410b, and a back cover 410c. The housing 410 includes other components of the AD module 400, except for a portion of the shaft 420 that projects beyond the substrate 410b so that the shaft 420 can engage the single-use probe. Therefore, in some embodiments, the AD module 400 is a discrete module that can be removed and replaced as a unit.

The rotary thromboelastometry AD module 400 also includes a shaft 420. In the illustrated embodiment, the shaft 420 includes a bearing 422 and a mirror 424. When the AD module 400 is assembled, the bearing 422 is fixedly coupled to the substrate 410b. Therefore, the shaft 420 can rotate freely with respect to the substrate 410b. The mirror 424 is attached to the shaft 420 and is configured to reflect the light from the LED 450 towards the CCD 460. As the shaft 420 swings during a rotary thromboelastometry test, the orientation of the mirror 424 (due to the mirror 424 attached to the shaft 420) swings accordingly. Therefore, during a rotary thromboelastometry test, the light from the LED 450 will be reflected (and towards the CCD 460) from the mirror 424 at an angle that changes as the shaft 420 swings.

The rotary thromboelastometry AD module 400 also includes an actuating unit 430. The actuating unit 430 (discussed in more detail below with reference to FIG. 6) provides propulsion to rotate and swing the shaft 420.

In the illustrated embodiment, the spring wire 440 connects between the actuating unit 430 and the shaft 420. In other words, the actuating unit 430 drives the spring wire 440, and the spring wire 440 transmits the propulsive force from the actuating unit 430 to the shaft 420.

The rotary thromboelastometry AD module 400 also includes an LED 450. In some embodiments, the LED 450 is fixedly mounted on the PCB assembly 470, and the PCB assembly is fixedly mounted on the housing 410. The LED 450 emits light that is steadily oriented in the direction of the mirror 424. In some embodiments, one or more lenses are used with the LED 450.

The light from the LED 450 is reflected from the mirror 424 in the direction of the CCD 460. The CCD460 includes a plurality of pixels arranged along the plane of the CCD460 (for example, arranged substantially linearly). Therefore, as the shaft 420 rotates, the light reflected from the mirror 424 scans across the surface of the CCD 460. By detecting the position of a particular pixel on the CCD460 that receives the LED light, other properties related to the angular position and the rotation angle of the shaft 420 can be measured. In some embodiments, other types of photodetectors (other than CCD detectors) are used in place of or in addition to CCD460.

The rotary thromboelastometry AD module 400 also includes a PCB assembly 470. The PCB assembly 470 includes electronic devices and circuit elements, which are used for the operation of the rotary thromboelastometry AD module 400. In a particular embodiment, the PCB assembly 470, which includes an executable code stored therein, receives the brightness distribution data from the CCD and generates CCD calibration data based on the brightness distribution data. The evaluation unit is configured to compare the CCD calibration data with the CCD calibration data measured in real time. In some embodiments, the PCB assembly 470 includes a microprocessor, a motor driver, a fuse, an integrated circuit, and the like. The PCB assembly 470 includes, but is not limited to, one or more types of sensors such as vibration sensors, acceleration sensors, Hall effect sensors, moving end detectors, proximity sensors, optical sensors, microswitches and the like. It may be included.

With reference to FIG. 6, an exemplary actuating unit 430 of the rotary thromboelastometry AD module 400 is shown in an enlarged view for easy viewing of actuating unit components. In the illustrated embodiment, the actuating unit 430 includes a motor 432, a sliding unit 434, and a sliding guide member 438. The motor 432 is installed on the sliding guide member 438. The sliding unit 434 is slidably engaged with the sliding guide member 438. The motor 432 is engaged with the sliding unit 434, which allows the motor 432 to provide propulsion to the sliding unit 434, as further described below.

The exemplary actuation unit 430 is designed to provide a number of operational benefits. For example, as will be more apparent from the description below, the actuating unit 430 is small, lightweight, resistant to external vibrations, mechanically precise, electronically mounted, highly controllable, and It can be positioned repeatedly and is durable.

In some embodiments, the motor 432 is a stepper motor. Thus, in some such embodiments, the motor 432 can be programmed and controlled to rotate and operate in a predetermined manner. That is, in some embodiments, the motor 432 is operated according to selected parameters including, but not limited to, parameters such as rotational speed, rotation speed, acceleration, deceleration, direction, and the like. Can be programmed as. Such factors may be programmed in the memory of the rotary thromboelastometry AD module 400 or the analyzer console 110. Therefore, the various working curves for the motor 432 can be easily selected and / or adjusted as desired. In some embodiments, all rotary thromboelastometry AD modules 400 are programmed to operate with the same working curve. In other embodiments, the one or more rotary thromboelastometry AD modules 400 are operated with different operating curves as compared to the one or more other rotary thromboelastometry AD modules 400. Is programmed.

The motor 432 includes a drive shaft 433. In some embodiments, the drive shaft 433 is a lead screw. The male screw of the feed screw may be screwed to the position where the inside of the sliding unit 434 is threaded. In some such embodiments, the drive shaft 433 is a precisely threaded feed screw, which facilitates accurate and smooth control of the sliding unit 434. When the drive shaft 433 and the sliding unit 434 are screwed together, the rotation of the motor 432 becomes a linear movement of the sliding unit 434. That is, as the drive shaft 433 of the motor 432 rotates, the sliding unit 434 moves slidably in the sliding guide member 438. When the rotation direction of the motor 432 is reversed (for example, clockwise with respect to the counterclockwise direction), the linear direction of the sliding unit 434 with respect to the sliding guide member 438 is reversed accordingly.

Also with reference to FIG. 7, an example of the sliding unit 434 is shown in an enlarged perspective view for easy viewing of the sliding unit components. The sliding unit 434 includes a curved member 435, a threaded collar 436, a spring wire holding magnet 437, a sliding unit holding magnet 439, a spring wire mounting member 452, and a sliding body 454. The threaded collar 436 and curved member 435 are attached to the sliding body 454. The spring wire holding magnet 437 is attached to the curved member 435. The spring wire mounting member 452 is engaged with the curved member 435 and the sliding body 454. The sliding unit holding magnet 439 is attached to the sliding guide member 438 and is magnetically coupled to the sliding body 454.

The curved member 435 has a curved surface formed in contact with the spring wire 440 (see FIG. 5). When the curved member 435 linearly moves back and forth in the sliding guide member 438, the contact region between the spring wire 440 and the curved side surface of the curved member 435 is adjusted in position. The configuration transforms the linear motion of the curved member 435 into a smooth rotational motion of the spring wire 440 (along with the shaft 420 acting as a axis of rotation).

The spring wire holding magnet 437 attracts the spring wire 440, whereby the spring wire 440 keeps in contact with the curved side surface of the curved member 435 while the sliding unit 434 moves back and forth. .. Further, in some embodiments, the spring wire holding magnet 437 is used with a Hall effect sensor mounted on the PCB assembly 470 (see FIG. 5) so that the position of the sliding unit 434 can be monitored electronically. ..

The threaded collar 436 has a female thread that is complementary to the male thread on the drive shaft 433 of the motor 432. Therefore, the threaded collar 436 is constrained in rotation due to its engagement with the sliding body 454, and when the drive shaft 433 rotates, it moves linearly along the longitudinal direction of the drive shaft 433 of the motor 432. To do. When the threaded collar 436 moves straight, the sliding body 454 and the curved member 435 also move linearly (due to the threaded collar 436 being attached to the sliding body 454). Since the sliding unit holding magnet 439 is attached to the sliding guide member 438 and magnetically coupled to the sliding body 454, when the sliding body 454 moves back and forth with respect to the sliding guide member 438, the sliding guide member 438 On the other hand, it helps to accurately maintain the sliding body 454 in a close driving relationship.

Since the spring wire mounting member 452 is coupled to the sliding body 454, it is useful for mechanically engaging the spring wire 440 (see FIG. 5) with the sliding unit 434. Therefore, the spring wire mounting member 452 facilitates mechanical connection between the spring wire 440 and the sliding unit 434 (in addition to the above-mentioned magnetic coupling between the spring wire 440 and the spring wire holding magnet 437). To. Further, in some embodiments, the spring wire mounting member 452 includes an external feature used for detecting the movement or moving end of the sliding unit 434. For example, in some embodiments, the spring wire mounting member 452 comprises one or more protrusions that can be detected by a sensor mounted on the PCB assembly 470. Optical sensors, proximal sensors, mechanical sensors, and the like may be used to detect the position of the spring wire attachment member 452 in a defined manner.

Referring to FIG. 8, in some embodiments, one or more processors of the thromboelastometry system 100 (see FIG. 1) are configured to perform the CCD evaluation process 800. In certain embodiments, the CCD evaluation process 800 is performed in one or more processors of the individual AD modules (eg, in one or more processors of the PCB assembly 470 of the AD module 400 according to the example; FIG. 4 and 5) Can be executed. In some such embodiments, each individual measurement module of the thromboelastometry system 100 may include one or more processors configured to perform the CCD evaluation process 800. With the CCD evaluation process 800, in some cases the inaccuracy of thromboelastometry measurements can be reduced or eliminated. As a result, the performance (eg, accuracy and precision) of the thromboelastometry system 100 may be more consistent.

In step 810, one or more processors of the thromboelastometry system or AD module receive the CCD luminance distribution data. In some embodiments, a plurality of pixels of the CD of the AD module are activated using a light source (eg, LED450 of the AD module according to the example; see FIG. 5). The data generated and obtained by the plurality of pixels is received by the one or more processors.

In step 820, one or more processors of the thromboelastometry system or AD module generate CCD calibration data using the CCD luminance distribution data received in step 810. In some embodiments, this is done by evaluating the position of the falling or rising edges of the luminance distribution data from the CCD. The falling edge or rising edge of the luminance distribution data may also be referred to herein as a "side surface".

In step 830, one or more processors of the thromboelastometry system or AD module compare the calibration data generated in step 820 with the real-time measured CCD luminance data. In some embodiments, the real-time CCD evaluation process of step 830 is iteratively performed (circulated) while the thromboelastometry system is being operated. For example, in some embodiments, the cycle time of the running real-time CCD evaluation process 830 is less than about 200 mm / s. In some embodiments, a running real-time CCD evaluation process 830 is for adapting the calibration-derived sample to the currently measured position of the falling or rising edge (or brightness distribution side) of the luminance distribution data. It is an optimization process.

Referring to FIG. 9, in some embodiments, one or more processors of the thromboelastometry system 100 (see FIG. 1) or AD module are configured to perform a two-step CCD evaluation process 900. .. The two-step CCD evaluation process 900 includes a booted CCD evaluation process 910 and a running real-time CCD evaluation process 920. With the two-step CCD evaluation process 900, the inaccuracy of thromboelastometry measurements can be reduced or eliminated in some cases. As a result, the overall performance (eg, accuracy and precision) consistency of the individual AD modules and thromboelastometry system 100 may be enhanced.

In some embodiments, the first step of the two-step CCD evaluation process 900 is to generate calibration data in the form of fitted samples (data points). This is done by starting with step 911 and evaluating the best luminance distribution aspect at startup of the thromboelastometry system 100. At each inspection position on the CCD, each optical signal distribution is analyzed to determine whether the pixel is OK or not OK. As an example, some pixels of the CCD may be considered problematic due to lack of performance due to contamination in the CCD.

In some embodiments, the state of the CCD pixels is analyzed by performing a binomial moving average over the entire light dispersion curve and comparing the resulting values with the measured data. For each pixel, the pixel is considered problematic in some embodiments if the difference between the binomial moving average over the entire dispersion curve and the pixel measurement is greater than the threshold. Conversely, if the difference between the binomial moving average over the entire variance curve and the pixel measurement is less than the threshold, then the pixel is considered acceptable.

In step 912, the data associated with each pixel is stored in the buffer. That is, since all CCDs are analyzed in step 911, a map of the disturbed pixels may be calculated by storing the positions of all the disturbed pixels in the buffer. The data is also used as input data to the running real-time CCD evaluation process 920.

In step 913, the position of the CCD with the least concentration of problematic pixels is determined as the optimal position for calculating the CCD evaluation algorithm. The shaft mirror (see FIG. 4) is then rotatably arranged so that the LED light reflected from the mirror is directed to the optimum position of the CCD.

In step 914, the luminance distribution curve measured at the optimum position is then filtered to remove outlier errors of the luminance distribution curve measured at the optimum position. In some embodiments, the filtering process is applied to linearly approximate the outlier portion of the luminance distribution curve. This step is configured to solve problems caused, for example, by some dirt that darkens the portion of the CCD. Most of these stains are generally noticeable as wide, conspicuous areas (outlier errors) where the illumination is significantly lower than normal. In some embodiments, this step uses an algorithm that includes two steps. In the first step, the curve is sampled using a fixed step width to search for anomalous outliers to be corrected. In the second stage, the start point of the outlier is acquired and the end point of the outlier is searched. This step is performed by approximating the slope of the luminance distribution curve. The algorithm estimates that the closest non-problematic point is within the region of this slope extension. Observing the shape of a typical CCD luminance distribution curve and the error obtained from dirt on the CCD, the outliers should only increase the value of the points. This algorithm has a low memory footprint and some more complex filter nuclei and FF
It moves faster than the T approach.

In step 915, a part of the accurate falling edge or rising edge (side surface) of the luminance distribution data is extracted from the filtered data of step 914. The algorithm is designed to robustly detect the exact end of filtered outliers of a given luminance distribution.

In some embodiments, when starting from the minimum value, the search algorithm is designed to find the latest possible event that better matches the searched value. Since the luminance distribution data curve is rising, the latest possible event is at the desired position with high probability. This custom-made algorithm is extremely fast and reliable for a low memory footprint.

In step 916, the extracted luminance distribution sides are then smoothed and sampled. In some embodiments, this is done by applying very little noise to the sides and bringing the result closer to the curve fit model. A cubic spline with sufficient complement points is superior to a typical polynomial or linear interpolation, which exhibits good performance only when the curve has a normal shape, because it can approximate a nonlinear curve well enough.

In steps 917 and 918, samples with a fixed step width are extracted as the final calibration step and stored in the buffer. This substantially reduces the memory footprint and facilitates real-time evaluation, as fewer comparison operations are performed.

The boot CCD evaluation process 910 is complete when the buffer containing the problematic pixel position is nearly filled (step 912) and the buffer containing the sample for real-time ray position evaluation is almost filled (step 918).

While the thromboelastometry system 100 is in operation, the running real-time CCD evaluation process 920 is repeated (circularly). For example, in some embodiments, the cycle time of the running real-time CCD evaluation process 920 is about 50 mm / sec. The running real-time CCD evaluation process 920 is an optimization process for adapting the calibration-derived sample to the currently measured luminance distribution aspect.

In step 921, the sample from step 918 is compared and fitted to the target position by the interval based algorithm. The algorithm evaluates a sample in the middle of the interval. The section includes a feasible destination position on the left side. In some embodiments, the first interval (space) is the total CCD pixel range. The algorithm then determines whether the desired position is on the right or left side of the desired position (which is feasible because the luminance distribution is monotone). ). That is, if any pixel is larger than the center right side, a new right side boundary is determined. The currently evaluated position then serves as a new right or left boundary for a new interval that equally divides the explored CCD pixel range. This scheme is repeated until the interval (space) is long enough to achieve its purpose. This first rapid fit algorithm further reduces the total time required to fit the sample to the measured curve. The algorithm requires only about 10 iterations to accurately find the desired position within a range of about 10 pixels. The algorithm is superior in speed to the more common minimum averaging method used after this rapid fit.

In step 922, an accurate weighted convergence is performed to fit the sample as favorably as possible. This is done by calculating the average of the absolute distances between all the samples and the portion of the luminance distribution curve that corresponds to that absolute distance. Since each pixel has information about the pixel state (no problem or problem) in the memory, the sample to compare with the problem pixel can be ignored. This makes it more robust than the typical approach of not ignoring known bad pixels.

In step 923, the position of the sample (CCD pixel position, buffer position) on the X-axis of the ray position is determined and sent to the software.

Referring to FIG. 10, the AD module error detection process 1000 is a cyclic process that can be performed by the processor of the thromboelastometry measurement system. The AD module error detection process 1000 may be performed to evaluate parameters that may indicate the cause of the thromboelastometry operation and detection system error.

In step 1010, the error detection process 1000 of the AD module is started. The AD module error detection process 1000 can be performed simultaneously with the thromboelastometry measurement process.

In step 1020, the processor of the thromboerastometry measurement system receives data related to the amount of vibration detected that can affect the accuracy and precision of the thromboelastometry measurement data from the AD module. In some embodiments, the vibration is measured by a ball-based sensor that is a component of the AD module (eg, placed on a PCB inside the housing of the AD module). In some embodiments, other types of sensors such as one or more accelerometers, piezoelectric sensors, displacement sensors, velocity sensors, etc. are used for vibration detection.

In step 1030, the processor compares the received vibration data with one or more thresholds. If the vibration data received is greater than the threshold, the processor will generate vibration-related error indications in step 1040.

In step 1050, the processor of the thromboelastometry measurement system relates to the detected position of the moving component of the AD module that may affect the accuracy or precision of the thromboelastometry measurement data from the AD module. Receive data to do. For example, the position indicating data is not limited to these, but may include moving end data, rotation position data, linear conversion position data, and the like, and a combination thereof. In some embodiments, a moving end switch, which is a component of the AD module (eg, located on a PCB in the housing of the AD module), is used to detect the absolute position of the AD module actuating unit. .. In some embodiments, the moving end switch is in the form of an optical sensor or proximity sensor, limit switch, and the like. In some embodiments, a Hall effect sensor (eg, located on a PCB in the housing of the AD module), which is a component of the AD module, is used to generate position indication data. Other types of sensors that provide position indication data may be used.

In step 1060, the processor compares the received data associated with the detection position of the moving component of the AD module with one or more thresholds. If the received data is greater than the threshold, the processor will generate a position error indication in step 1070. The process 1000 loops back to step 1020 and the process 1000 is repeated.

With reference to FIG. 11, the process flow chart describes the AD module measurement loop 1100 and the thromboelastometry measurement and evaluation loop 1150 in considerable detail. The processes 1100 and 1150 include steps to control the operation of the thromboelastometry system 100 (see FIG. 1) to enhance error detection and accuracy of the thromboelastometry system.

During thromboelastometry measurements, processes 1100 and 1150 are used to manage and evaluate key items in real time. For example, vibrations that can distort the measurement signal are managed and evaluated. In addition, the quality of motion of the rotary thromboelastometry operation and detection system is controlled and evaluated using Hall effect sensors. In addition, the accuracy of the rotary thromboelastometry operation and movement of the detection system is controlled and evaluated using one or more moving end sensors. In addition, the quality of the measurement signal is evaluated. By combining the vibration, motion quality, and motion accuracy with the ray position, the processor of the thromboelastometry system can determine the current quality of the measurement signal, analyze the cause of the distortion, and be responsive. High measurement can be adopted.

In some embodiments, the measurement loop 1100 of the AD module is performed at about 50 mm / s. In certain embodiments, the AD module measurement loop 1100 is part of a normal measurement routine in the AD module.

Steps 1104 and 1106 relate to the position of the LED rays of the AD module. For example, in some embodiments, ray positions are detected and evaluated.

Steps 1108 to 1114 relate to the evaluation of the vibration. In some embodiments, the vibration is measured by a ball-based sensor (eg, placed on a PCB in the housing of the AD module) that is a component of the AD module. In some embodiments, other types of sensors such as one or more accelerometers, piezoelectric sensors, displacement sensors, velocity sensors, etc. are used for vibration detection. The data obtained that need to be evaluated are vibrational events over time. A typical evaluation algorithm may be limited to allow only a given amount of vibrational events over a given time. If the limit is exceeded, an error message will be sent to the processor running the thromboelastometry measurement software.

Steps 116 to 1120 evaluate a rotary thromboelastometry actuation and detection system that is monitored using a Hall effect sensor (eg, located on a PCB in the housing of the AD module) that is part of the AD module. including. The measured data provide the characteristics of the actual movement of the system. In some embodiments, the evaluation algorithm may be performed to compare the measured motion with the theoretical motion to be performed by the rotary thromboelastometry actuation and detection system. For example, the sum of the absolute differences or squares differences between theory and reality is a good algorithm when properly optimized. When the threshold amount of difference is detected, an error message is sent to the processor running the thromboelastometry measurement software (step 1122).

Steps 1124 and 1126 include an assessment of the absolute moving position of the rotary thromboelastometry actuation and detection system. A terminal switch (eg, placed on a PCB in the housing of the AD module), which is a component of the AD module, is used to detect the absolute position of the operating unit with the accuracy of the substep (stepper motor). .. In some embodiments, the terminal switch is in the form of an optical sensor, or proximity sensor, limit switch, or the like. Statistical data that collects deviations from said optimal position is used to determine if it is working as expected. If the actual position differs significantly from the desired position with respect to the time threshold amount, an error message is sent to the processor running the thromboerastomy measurement software (step 1122).

In step 1122, the data collected for the quality of operation from steps 1116 to 1126 can be used to fully assess the quality of operation of the rotary thromboelastometry operation and detection system. In some embodiments, the evaluation can be achieved at low cost and in a small space as compared to, for example, using an external encoder that monitors the stepper motor.

Now let us turn to the description of the thromboelastometry measurement and evaluation loop 1150. Steps 1154 to 1158 relate to a thromboelastometry measurement process, such as performed by a processor running the thromboelastometry measurement software.

Steps 1160 and 1162 describe the evaluation of errors sent by process 1100 by the AD module. Further errors sent by the AD module after the position has been evaluated may be used by a processor running the thromboelastometry measurement software to interpret currently known errors. The type and frequency of errors are evaluated by the software and an error message is presented to the user if it is as frequent as it needs to be communicated to the user or if it is important enough to be communicated to the user. In some embodiments, the AD is performed by a processor that runs the thromboelastometry measurement software that conveys additional information that causes the error and facilitates further improvements in hardware, electronics, and firmware. Module errors may be associated with measurement errors.

Many embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the scope of the invention. Therefore, other embodiments are within the scope of the following claims.

Claims (19)

An actuation and detection module for a blood coagulation measurement system, said module.
A rotatable shaft extending from the actuation and detection module, the rotatable shaft engaged with the single-use probe and configured to rotate the single-use probe.
An actuating unit mechanically coupled to the rotatable shaft that is programmable to cause rotation of the rotatable shaft according to predetermined actuating parameters and is a sliding unit that includes a spring wire holding magnet. Te, the spring wire holding magnet is a magnet to attract the spring wire magnetically during linear movement of the slide unit on the surface of the sliding unit, and operating unit including the sliding unit,
One or more processors that communicate with the actuating unit, comprising one or more processors that control the operation of the actuating unit.
Activation and detection module. The actuating unit comprises a stepper motor.
The operation and detection module according to claim 1. The stepper motor includes a threaded drive shaft.
The sliding unit comprises a threaded collar that is engaged with the threaded drive shaft so that the stepper motor can drive the sliding unit in a linear motion.
The operation and detection module according to claim 2. The linear movement of the sliding unit causes rotation of the shaft by the spring wire extending between the sliding unit and the shaft.
The operation and detection module according to claim 3. The spring wire is magnetically attracted to the curved surface of the sliding unit.
The operation and detection module according to claim 1. The actuating unit further comprises a sensor configured to detect the position of the sliding unit.
The operation and detection module according to claim 3. The sensor comprises a Hall effect sensor.
The operation and detection module according to claim 6. The actuating unit further comprises one or more moving end sensors configured to detect the movement limit of the sliding unit.
The operation and detection module according to claim 3. The operating parameters are present in the group consisting of rotational speed, rotational speed, acceleration, deceleration, and direction.
The operation and detection module according to claim 1. The actuation parameters are programmed in the memory of the actuation and detection module.
The operation and detection module according to claim 1. Includes multiple separate thromboelastometry measurement modules
Each individual measurement module of a plurality of individual thromboelastometry measurement modules includes an evaluation unit for evaluating charge coupling element (CCD) components.
The evaluation unit (i) receives the brightness distribution data from the CCD, (ii) generates CCD calibration data based on the brightness distribution data, and (iii) the CCD calibration data is measured in real time. Constructed to compare with data,
The operation and detection module according to claim 1. A system for measuring the coagulation properties of a blood sample.
A control console that includes a user interface for displaying the coagulation properties of blood samples,
One or a plurality of the actuation and detection modules according to claim 1 attached to the control console, each of the actuation and detection modules operating independently in communication with the control console. Alternatively, the operation and detection modules are provided.
A system for measuring the coagulation properties of blood samples. The actuation and detection module is a discrete module that can be removed and replaced independently of the control console as a unit.
The system for measuring the coagulation characteristics of the blood sample according to claim 12. With additional control unit housing
One or more vibration sensors are housed in the control unit housing.
The system for measuring the coagulation characteristics of the blood sample according to claim 12. Each of the one or more actuation and detection modules comprises one or more vibration sensors.
The system for measuring the coagulation characteristics of the blood sample according to claim 12. The operating parameters are programmed in the memory of the control console.
The system for measuring the coagulation characteristics of the blood sample according to claim 12. Further equipped with a user interface coupled to the control console
The user interface is configured to select an actuation curve for the actuation unit.
The system for measuring the coagulation characteristics of the blood sample according to claim 12. The user interface is configured to adjust the actuation curve of the actuation unit.
The system for measuring the coagulation properties of the blood sample according to claim 17. Further equipped with a user interface coupled to the control console
The user interface is configured to receive the operating parameters from the user.
The system for measuring the coagulation characteristics of the blood sample according to claim 12.