BLOOD CHARACTERISTICS EVALUATION APPARATUS, BLOOD CHARACTERISTICS EVALUATION METHOD, AND PROGRAM

Abstract

To provide a new method for evaluating the characteristics of blood.SOLUTION: A blood characteristic evaluation device of an embodiment comprises: a control unit; a measurement unit; and a calculation unit. The control unit causes a foaming phenomenon in a blood sample. The measurement unit measures the state of foaming in the blood sample. The calculation unit calculates an index indicating the tendency of coagulation of the blood sample based on a result of measurement of the state of foaming in the blood sample.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The embodiments disclosed in the present specification and drawings relate to a blood characteristic evaluation device, a blood characteristic evaluation method, and a program. [Background technology]

[0002] There are known technologies that evaluate the characteristics of a patient's blood and use them to formulate treatment plans and procedures, etc. For example, depending on the patient, coagulation and fibrinolysis abnormalities may occur during procedures using a cardiopulmonary bypass, or acute thrombus formation may occur during drug-eluting stent (DES) placement, but by evaluating the characteristics of the blood, it is possible to consider how to deal with these situations in advance. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-154036 Summary of the Invention [Problem to be solved by the invention]

[0004] One of the problems to be solved by the embodiments disclosed in this specification and the drawings is to provide a new method for evaluating blood characteristics. However, the problems to be solved by the embodiments disclosed in this specification and the drawings are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described below can also be positioned as other problems. [Means for solving the problem]

[0005] The blood characteristic evaluation device of the embodiment includes a control unit, a measurement unit, and a calculation unit. The control unit causes a foaming phenomenon in a blood sample. The measurement unit measures the foaming state in the blood sample. The calculation unit calculates an index showing the coagulation tendency of the blood sample based on the measurement result of the foaming state in the blood sample. [Brief explanation of the drawings]

[0006] [Figure 1] FIG. 1 is a diagram showing an example of the configuration of a blood characteristic evaluation apparatus according to the first embodiment. [Figure 2] FIG. 2 is a diagram showing an example of the configuration of a flow channel according to the first embodiment. [Figure 3] FIG. 3 is a diagram illustrating an outline of processing by the processing circuit according to the first embodiment. [Figure 4] FIG. 4 is a diagram showing an example of the evaluation of characteristics of a blood sample according to the first embodiment. [Figure 5] FIG. 5 is a flowchart showing an example of processing by the processing circuit of the blood characteristic evaluation apparatus according to the first embodiment. [Figure 6] FIG. 6 is a diagram showing an example of the configuration of a flow channel according to the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0007] Hereinafter, embodiments of a blood characteristic evaluation device, a blood characteristic evaluation method, and a program will be described in detail with reference to the accompanying drawings.

[0008] (First embodiment) 1 is a diagram showing an example of the configuration of a blood characteristic evaluation device 1 according to a first embodiment. For example, the blood characteristic evaluation device 1 includes a memory 11, a processing circuit 12, a light source 13, a camera 14, a microscope 15, and a sample holder 16a.

[0009] Memory 11 is realized by, for example, a semiconductor memory element such as a RAM (Random Access Memory), a flash memory, a hard disk, an optical disk, etc. For example, memory 11 stores a program that enables circuits included in blood characteristic evaluation apparatus 1 to realize their functions.

[0010] The processing circuit 12 controls the overall operation of the blood characteristic evaluation apparatus 1 by executing a control function 12a, a measurement function 12b, a calculation function 12c, and an output function 12d. The control function 12a is an example of a control unit. The measurement function 12b is an example of a measurement unit. The calculation function 12c is an example of a calculation unit. The output function 12d is an example of an output unit.

[0011] For example, the processing circuitry 12 reads out from the memory 11 and executes a program corresponding to the control function 12a to control the flow of the blood sample in the channel provided in the sample holder 16a. The control function 12a also generates a foaming phenomenon in the blood sample. The processing circuitry 12 reads out from the memory 11 and executes a program corresponding to the measurement function 12b to control the operations of the light source 13, the camera 14, and the microscope 15 to measure the foaming state in the blood sample. The processing circuitry 12 also reads out from the memory 11 and executes a program corresponding to the calculation function 12c to evaluate the characteristics of the blood sample based on the measurement results of the foaming state. The processing circuitry 12 also reads out from the memory 11 and executes a program corresponding to the output function 12d to output the evaluation results obtained by the calculation function 12c. Details of the processes performed by the control function 12a, the measurement function 12b, the calculation function 12c, and the output function 12d will be described later.

[0012] The light source 13, the camera 14, and the microscope 15 are an example of a measurement device for measuring the foaming state in a blood sample. Note that Fig. 1 is merely an example, and various modifications are possible for the method of measuring the foaming state in a blood sample.

[0013] The light source 13 is a light emitting device that assists in taking pictures with the camera 14. For example, the light source 13 is an electronic flash device that emits light under the control of the processing circuit 12 when taking pictures with the camera 14.

[0014] The camera 14 photographs the blood sample in the sample holder 16a. Specifically, the camera 14 photographs an area of ​​the blood sample where foaming is occurring under the control of the processing circuit 12. Note that multiple frames of images may be continuously captured of the area where foaming is occurring. In other words, the camera 14 may capture moving images. The blood characteristic evaluation device 1 may also include a high-speed camera as the camera 14.

[0015] For example, by emitting light from light source 13 in synchronization with the timing of foaming, foaming can be photographed by camera 14. In this case, in order to photograph any timing in the process from foaming to defoaming, any delay time (delay) may be added to the timing of light emission from light source 13. Alternatively, light source 13 may be caused to emit light continuously in synchronization with the timing of foaming, and multiple foaming states may be photographed continuously by camera 14.

[0016] The microscope 15 optically magnifies the area of ​​the blood sample where the foaming phenomenon is occurring. The camera 14 takes an image through the microscope 15, thereby capturing a magnified image of the area where the foaming phenomenon is occurring.

[0017] In the blood characteristic evaluation device 1 shown in Fig. 1, each processing function is stored in the form of a computer-executable program in memory 11. Processing circuitry 12 is a processor that realizes the function corresponding to each program by reading and executing the program from memory 11. In other words, the processing circuitry 12 in a state in which a program has been read has the function corresponding to the read program.

[0018] Although FIG. 1 illustrates a single processing circuit 12 that implements the control function 12a, measurement function 12b, calculation function 12c, and output function 12d, the processing circuit 12 may be configured using a combination of multiple independent processors, with each processor executing a program to implement the functions. Furthermore, the processing functions of the processing circuit 12 may be implemented by distributing or integrating them as appropriate across a single or multiple processing circuits. Furthermore, the processing circuit 12 may implement its functions using a processor in an external device connected via a network. For example, the processing circuit 12 implements each function shown in FIG. 1 by reading and executing a program corresponding to each function from the memory 11 and using a group of servers (cloud computing) connected to the blood characteristic evaluation device 1 via a network as a computational resource.

[0019] The above describes an example of the configuration of the blood characteristic evaluation device 1 according to this embodiment. With this configuration, the blood characteristic evaluation device 1 provides a new method for evaluating the characteristics of blood.

[0020] Specifically, the control function 12a causes a foaming phenomenon in the blood sample. The measurement function 12b measures the foaming state in the blood sample. The calculation function 12c evaluates the characteristics of the blood sample based on the measurement results. The foaming phenomenon is sensitive to differences in properties of the blood sample, such as viscoelasticity, surface tension, and composition. Therefore, the processing circuit 12 can accurately evaluate the characteristics of the blood sample by measuring the foaming state. The processing circuit 12 can also easily evaluate the characteristics of the blood sample without requiring complicated processes.

[0021] First, the control of the blood sample by the control function 12a will be described with reference to Fig. 2. Fig. 2 is a diagram showing an example of the configuration of a flow path according to the first embodiment. The control function 12a causes the blood sample to flow within the flow path shown in Fig. 2, and also causes a foaming phenomenon in a part of the blood sample.

[0022] As shown in FIG. 2, the sample holder 16a has a flow path for the blood sample. Specifically, the sample holder 16a has a groove on its surface, a tunnel-shaped internal space, a tube, or the like as a flow path for the blood sample. For example, the flow path can be formed in the sample holder 16a by photolithography, etching, laser processing, cutting, or other machining processes, casting, or a 3D printer. While the material of the sample holder 16a is not particularly limited, it is desirable for it to be made of a material with high transmittance, at least near the area where the foaming phenomenon occurs in the blood sample. For example, the sample holder 16a may be made of glass or an acrylic resin such as PMMA (Polymethyl Methacrylate) near the area where the foaming phenomenon occurs in the blood sample. Using a material with high transmittance enables optical measurement of the foaming phenomenon, as described below.

[0023] For example, the control function 12a causes the blood sample to flow into the flow path F11 shown in Fig. 2. The blood sample may be untreated blood collected from a patient, or may be treated blood. Treated blood is, for example, blood (plasma) from which blood cells have been removed.

[0024] For example, the blood sample may be stored in a syringe barrel (not shown) equipped with a syringe and plunger, and the control function 12a may control the flow rate and flow velocity of the blood sample flowing into the flow path F11 by controlling the operation of the plunger relative to the syringe.

[0025] The control function 12a may perform pretreatment on the blood sample before flowing into the flow path F11. For example, the control function 12a adjusts the number of blood cells in the blood sample to a predetermined value before flowing into the flow path F11. For example, the control function 12a measures the number of blood cells in the blood sample using a blood cell counter and dilutes the blood sample with a diluent so that the number of blood cells per unit volume becomes a predetermined value. The diluent may be, but is not limited to, physiological saline, phosphate buffer, citrate buffer, or an aqueous or non-aqueous solution containing various additives such as proteins, sugars, calcium, magnesium, and other metal ions. The blood cell counter may also be configured to be connected before flowing into the flow path F11. For example, the control function 12a stirs the blood sample before flowing into the flow path F11. That is, the control function 12a stirs the blood sample prior to measurement to maintain uniform distribution of blood cells in the blood sample. These pretreatments make it possible to standardize the measurement conditions and further improve the accuracy of blood evaluation.

[0026] The control function 12a may also perform pretreatment to suppress coagulation within the flow path. For example, the control function 12a adds a factor to suppress coagulation to the blood sample at any time before the inflow of the blood sample begins, such as at the time of blood collection. The control function 12a can use, as the factor to suppress coagulation, anticoagulants such as sodium citrate, EDTA (Ethylene-Diamine-Tetraacetic Acid), warfarin, heparin, low-molecular-weight heparin, factor IIa inhibitor, and factor Xa inhibitor. Additionally, the control function 12a can use any factor that inhibits or reduces blood coagulation as the factor to suppress coagulation. Furthermore, if sodium citrate or EDTA is used as a factor to suppress coagulation in advance, calcium may be replenished before measurement to restore coagulation properties.

[0027] 2, the flow path F11 branches into a flow path F12 and a flow path F13. That is, the blood sample flowing through the flow path F11 is divided into the flow paths F12 and F13. The flow path F12 is an example of a first flow path. The flow path F13 is an example of a second flow path.

[0028] The control function 12a causes a foaming phenomenon in the blood sample in the flow path. For example, the control function 12a causes a foaming phenomenon by applying thermal energy to the blood sample from a heating portion of the sample holder 16a. For example, the sample holder 16a has a heater H11 as a heating portion at a position corresponding to region R11 in FIG. 2. As an example, the heater H11 is an electrothermal conversion element such as cobalt silicide (CoSi2). In this case, the control function 12a controls the power supply to the electrothermal conversion element to boil a portion of the blood sample, thereby causing a foaming phenomenon. For example, the control function 12a causes a foaming phenomenon in the blood sample flowing through region R11 of the flow path F12 by applying thermal energy to the blood sample from the heater H11.

[0029] More specifically, when heating is performed using an electrothermal transducer, film boiling occurs at the interface. That is, the moment the blood sample reaches its heating limit temperature, multiple bubbles are generated at the interface between the electrothermal transducer and the blood sample, and they coalesce and grow rapidly. At this time, the pressure inside the bubbles acts as an impulse, and the pressure becomes particularly high at the moment of foaming. The bubbles begin to grow due to this force, but they continue to grow due to the inertia of the blood sample even after the bubble pressure disappears, so that at the time of maximum foaming, they are already in a negative pressure state. Therefore, the time from foaming to its disappearance is short, and the impact of the foaming phenomenon on the blood sample is small. In other words, by generating the foaming phenomenon through film boiling, control function 12a can further improve the accuracy of blood evaluation.

[0030] It is also possible to generate the foaming phenomenon by a method other than adding thermal energy. For example, a piezoelectric element can be provided at a position corresponding to region R11 in Figure 2 to generate ultrasonic waves, and the foaming phenomenon can be generated by pressure fluctuations caused by the ultrasonic waves. In other words, the control function 12a can generate the foaming phenomenon at the position corresponding to region R11 by using any foaming-inducing element such as an electrothermal conversion element or a piezoelectric element.

[0031] The measurement function 12b measures the foaming state in the blood sample. For example, the measurement function 12b controls the operation of the light source 13, the camera 14, and the microscope 15 to capture an image of the region R11 where the foaming phenomenon is occurring. That is, while the measurement function 12b operates the light source 13 to emit light, it causes the camera 14 to capture an image of the region R11 magnified through the microscope 15. Furthermore, the measurement function 12b measures the foaming state based on the captured image of the region R11.

[0032] For example, the control function 12a applies a pulse voltage to the electrothermal conversion element to generate bubbles in the blood sample. The measurement function 12b captures an image of the region R11 after a given delay time (delay) has elapsed since the application of the pulse voltage by the control function 12a. The delay time is adjusted, for example, according to the standard time required for bubbles generated in the blood sample to reach their maximum size after the application of the pulse voltage to the electrothermal conversion element.

[0033] Alternatively, the measurement function 12b may control the camera 14 to continuously capture images of the region R11 for a predetermined period after the application of the pulse voltage by the control function 12a. For example, the measurement function 12b continuously emits light from the light source 13 in synchronization with the timing of bubble generation, and continuously captures multiple images of the bubble generation state with the camera 14. For example, the measurement function 12b continuously captures multiple images at a predetermined frame rate for a standard period from when bubbles are generated in the blood sample by the application of the pulse voltage until they disappear. Note that the control function 12a can also repeatedly generate and destroy bubbles by continuously applying the pulse voltage multiple times. Furthermore, the measurement function 12b can repeatedly capture images of the bubble generation state at a predetermined timing after the application of the pulse voltage. That is, the control function 12a periodically generates and destroys bubbles, and the measurement function 12b synchronizes the emission of light from the light source 13 and the capture of images with the camera 14 with this cycle, thereby repeatedly capturing images of the bubble generation state in the same phase. In other words, the measurement function 12b can perform stop-motion photography using strobe photography.

[0034] Then, the measurement function 12b measures the foaming state based on the image of the region R11. For example, the measurement function 12b measures the size of bubbles generated in the region R11 as the foaming state. Note that the bubble size is not particularly limited as long as it is information indicating the size of the bubbles. For example, the bubble size may be the diameter, circumferential length, area, volume, number of pixels, etc. of the bubbles.

[0035] Note that bubbles on the image are not necessarily circular and may be distorted relative to a circle. In such cases, the measurement function 12b can, for example, identify the long and short axes of the bubbles and use the long and short axes as the bubble size. Furthermore, if multiple images of region R11 are captured, the measurement function 12b can, for example, identify the image with the largest bubble size and use the bubble size in the identified image as the measurement result of the foaming state. Alternatively, the measurement function 12b can use a statistical value, such as the average value of the bubble sizes measured based on each of the multiple images, as the measurement result of the foaming state.

[0036] The measurement function 12b may also be configured to exclude outliers from the measurement results of the foaming state. For example, the measurement function 12b measures the bubble size of each of multiple bubbles generated by multiple heating cycles, or of some of the multiple bubbles. Alternatively, electrothermal conversion elements may be arranged in series or in parallel in different flow paths, and multiple bubbles may be generated by applying voltage to the multiple electrothermal conversion elements at the same time or at different times, and the bubble size of each may be measured. The measurement function 12b then excludes outliers from the measured values ​​of the multiple bubbles. For example, the measurement function 12b sets a predetermined standard deviation as a threshold and identifies and excludes outliers by comparing the measured values ​​with the standard deviation. In this case, the calculation function 12c evaluates the characteristics of the blood sample based on the measurement results after excluding the outliers, thereby further improving the accuracy of the evaluation.

[0037] As shown in FIG. 2, the control function 12a also allows a blood coagulation-related factor to flow into the flow path F14. The blood coagulation-related factor is a component or substance related to blood coagulation. Examples of the blood coagulation-related factor include heparin, EDTA, sodium citrate, coumarin derivatives (e.g., warfarin or dicoumarol), tissue factor pathway inhibitor (TFPI), antithrombin III, lupus anticoagulant, nematode anticoagulant peptide (NAPc2), active site-blocked factor VIIa (factor VIIai), factor IXa inhibitor, factor Xa inhibitor (fondaparinux, idraparinux, DX-9065a, and razaxan). Anticoagulant factors and coagulation inhibitors include anticoagulants such as razaxaban (DPC906), inhibitors of factor Va and factor VIIIa (including activated protein C (APC) and soluble thrombomodulin), thrombin inhibitors (including hirudin, bivalirudin, argatroban, and ximelagatran), C1 esterase inhibitors, and heparin cofactor 2; and fibrinolytic factors and their inhibitors, such as plasminogen, t-PA, pro-urokinase, PAI-1, and u-PA. Hereinafter, heparin will be described as an example of a blood coagulation-related factor. For example, control function 12a causes a heparin solution containing a predetermined concentration of heparin as a blood coagulation-related factor to flow into flow path F14.

[0038] As shown in FIG. 2, flow paths F13 and F14 merge to form flow path F15. That is, the blood sample flowing through flow path F13 and the heparin solution flowing through flow path F15 are mixed and flow through flow path F15. Hereinafter, a blood sample mixed with a blood coagulation-related factor such as a heparin solution will also be referred to as a mixed sample. Flow path F14 is an example of a third flow path. Flow path F15 is also an example of a fourth flow path. Note that a configuration may be provided at the point where flow paths F13 and F14 merge, allowing the blood sample and the heparin solution to be sufficiently mixed before reaching region R12. While not limited thereto, for example, a flow path long enough for mixing may be provided, or the flow path may be configured to meander to promote mixing.

[0039] As in the case of region R11, control function 12a generates a foaming phenomenon in region R12 of the mixed sample flowing through flow path F15. For example, sample holder 16a includes heater H12 as a heating portion at a position corresponding to region R12 in FIG. 2. Control function 12a applies thermal energy from heater H12 to the mixed sample, thereby generating a foaming phenomenon in the mixed sample flowing through region R12 of flow path F15. Measurement function 12b also measures the foaming state in the mixed sample. For example, measurement function 12b captures an image of region R12 where a foaming phenomenon is occurring and measures the bubble size based on the image. Note that while FIG. 1 shows only one measurement device consisting of light source 13, camera 14, and microscope 15, blood characteristic evaluation device 1 may include such a measurement device for each of region R11 and region R12.

[0040] For example, the measurement function 12b approximately simultaneously measures the foaming state in the blood sample flowing through flow path F12 and the foaming state in the mixed sample flowing through flow path F15. Specifically, the control function 12a approximately simultaneously applies thermal energy to regions R11 and R12 to cause a foaming phenomenon. The measurement function 12b also approximately simultaneously captures images of regions R11 and R12. Based on these images, the measurement function 12b can then measure the bubble sizes in the blood sample and the mixed sample at approximately the same time.

[0041] Here, the measurement function 12b may repeatedly measure the foaming state in the mixed sample while changing the blood coagulation-related factor. For example, after a solution containing a predetermined concentration of heparin is introduced into the flow path F14 and the foaming state is measured, the control function 12a introduces a solution with a different heparin concentration or a solution containing a different type of anticoagulant factor into the flow path F14, and the measurement function 12b measures the foaming state in the mixed sample again.

[0042] For example, the measurement function 12b acquires a measurement result X0 of the foaming state in the blood sample, as shown in Fig. 3. The measurement result X0 is, for example, the bubble size measured for the blood sample flowing through the flow path F12. Fig. 3 is a diagram showing an overview of the processing of the processing circuit 12 according to the first embodiment.

[0043] Furthermore, the measurement function 12b acquires a measurement result of the foaming state of a mixed sample obtained by mixing a blood sample and heparin. For example, the measurement function 12b acquires a measurement result X1 of the foaming state of a mixed sample obtained by mixing a blood sample and a heparin solution L11 containing heparin. The heparin concentration and flow rate of the heparin solution L11 are adjusted so that the heparin concentration in the mixed sample of the blood sample and the heparin solution L11 becomes C1. Next, the measurement function 12b acquires a measurement result X2 of the foaming state of a mixed sample obtained by mixing the blood sample and a heparin solution L12 containing heparin. The heparin concentration and flow rate of the heparin solution L12 are adjusted so that the heparin concentration in the mixed sample of the blood sample and the heparin solution L12 becomes C2. Next, the measurement function 12b acquires a measurement result X3 of the foaming state of a mixed sample obtained by mixing the blood sample and a heparin solution L13 containing heparin. The heparin concentration and flow rate of the heparin solution L13 are adjusted so that the heparin concentration in the mixed sample of the blood sample and the heparin solution L13 becomes C3. Note that the concentration C2 is higher than the concentration C1, and the concentration C3 is higher than the concentration C2. The calculation function 12c then evaluates the characteristics of the blood sample based on the measurement results X0 to X3.

[0044] Here, the process of evaluating the characteristics of a blood sample by the calculation function 12c will be described with reference to Fig. 4. Fig. 4 is a diagram showing an example of the evaluation of the characteristics of a blood sample according to the first embodiment. Fig. 4 shows two examples of blood samples: blood B1 collected from patient P1 and blood B2 collected from patient P2. The horizontal axis of Fig. 4 indicates the heparin concentration. The vertical axis of Fig. 4 indicates the measured bubble size.

[0045] On the horizontal axis of FIG. 4, "without heparin" indicates the measurement result X0. That is, "without heparin" represents the bubble size measured for the blood sample flowing through flow path F12. Heparin "C1" represents the measurement result X1 of the foaming state of the mixed sample obtained by mixing heparin solution L11 with the blood sample so that the heparin concentration becomes C1. Heparin "C2" represents the measurement result X2 of the foaming state of the mixed sample obtained by mixing heparin solution L12 with the blood sample so that the heparin concentration becomes C2. Heparin "C3" represents the measurement result X3 of the foaming state of the mixed sample obtained by mixing heparin solution L13 with the blood sample so that the heparin concentration becomes C3. If heparin has been added to the blood sample as a pretreatment to suppress coagulation in the flow path, the amount of heparin added in the pretreatment may be taken into account when plotting FIG. 4.

[0046] As shown in Figure 4, blood B1 and blood B2 differ in their responsiveness to heparin. Specifically, blood B1 has a strong tendency for bubble size to increase with increasing heparin concentration. Here, while bubble size decreases as the viscoelasticity of a liquid increases, blood B1 has a strong tendency for viscoelasticity to decrease with increasing heparin concentration, and can be said to be blood with a high tendency to clot. On the other hand, blood B2 has a small change in bubble size with respect to heparin concentration, and can be said to be blood with a low tendency to clot.

[0047] The calculation function 12c can evaluate the characteristics of each blood sample based on such responsiveness to heparin. For example, the calculation function 12c obtains a regression equation for the plot (scatter plot) of blood B1 shown in FIG. 4 and calculates its slope. Similarly, the calculation function 12c calculates the slope of the regression equation for the plot of blood B2. The slope of such a regression equation is an example of an index showing the coagulation tendency of a blood sample.

[0048] Here, the calculation function 12c may evaluate the characteristics of each blood sample taking into account the number of blood cells in the blood sample. For example, the calculation function 12c calculates an index showing the coagulation tendency of the blood sample based on the measurement result of the foaming state and the number of blood cells in the blood sample.

[0049] For example, the calculation function 12c first calculates the slope of the regression equation between heparin concentration and bubble size. Then, the calculation function 12c corrects the calculated slope according to the blood cell count and calculates a value as an index indicating the coagulation tendency of the blood sample. For example, it is generally known that the higher the blood cell count, the higher the viscosity of blood. Therefore, if the responsiveness to heparin is the same, the higher the blood cell count, the more likely the blood flow is to be stagnant and the higher the possibility of coagulation. Therefore, the calculation function 12c corrects the slope calculated from the regression equation so that it becomes higher the higher the blood cell count, and calculates a value as an index indicating the coagulation tendency of the blood sample.

[0050] Output function 12d outputs the evaluation results obtained by calculation function 12c. For example, output function 12d displays the evaluation results on a display device connected to blood characteristic evaluation device 1. The display device may be, for example, a liquid crystal display, a CRT (Cathode Ray Tube) display, a touch panel, or other display. For example, output function 12d displays numerical values, graphs, etc. indicating the slope of the regression equation calculated by calculation function 12c.

[0051] The output function 12d may display an error range in addition to displaying the evaluation result. For example, the output function 12d displays the slope of the regression equation between heparin concentration and bubble size as the evaluation result obtained by the calculation function 12c. Furthermore, the output function 12d displays an error range for the slope. In this case, the error range can be calculated according to the magnitude of the error that occurs when approximating multiple plots such as those shown in FIG. 4 with the regression equation. The output function 12d may display the error range graphically using error bars or the like, or may display it as text.

[0052] In addition to displaying the evaluation results, the output function 12d can output the evaluation results of the calculation function 12c in various ways. That is, the output function 12d directly or indirectly provides the evaluation results of the calculation function 12c to a user, such as a doctor. For example, the output function 12d may control a projector to project the evaluation results of the calculation function 12c onto an arbitrary plane. The output function 12d may also print out the evaluation results. The output function 12d may also notify the user of the evaluation results by voice or the like. The output function 12d may also transmit the evaluation results to an external server and store them. For example, the output function 12d registers the evaluation results in a system such as a Hospital Information System (HIS). In this case, the user can access the system at will and refer to the evaluation results.

[0053] Next, an overview of a series of processes performed in the blood characteristic evaluation apparatus 1 will be described with reference to FIG. 5. FIG. 5 is a flowchart showing an example of processes performed by the processing circuit 12 of the blood characteristic evaluation apparatus 1 according to the first embodiment. Steps S101, S102, S104, and S105 correspond to the control function 12a. Step S103 corresponds to the measurement function 12b. Step S106 corresponds to the calculation function 12c. Step S107 corresponds to the output function 12d.

[0054] First, the processing circuit 12 starts the flow of the blood sample and heparin into the flow paths of the sample holder 16a (step S101). For example, the processing circuit 12 starts the flow of the blood sample into the flow path F11 and the flow of heparin into the flow path F14 substantially simultaneously.

[0055] Next, the processing circuit 12 causes a foaming phenomenon in each sample (step S102). For example, the processing circuit 12 applies thermal energy to the blood sample flowing through flow path F12 to cause a foaming phenomenon. The processing circuit 12 also applies thermal energy to the mixed sample flowing through flow path F15 to cause a foaming phenomenon.

[0056] Next, the processing circuitry 12 measures the foaming state (step S103). For example, the processing circuitry 12 controls the light source 13, the camera 14, and the microscope 15 to capture an image of the area where the foaming phenomenon is occurring. For example, the processing circuitry 12 captures images of the areas R11 and R12 shown in FIG. 2. The processing circuitry 12 also measures the bubble size based on the captured image.

[0057] Next, the processing circuit 12 determines whether or not to continue the measurement (step S104), and if it does (Yes in step S104), changes the heparin concentration (step S105) and proceeds again to step S102. For example, the processing circuit 12 causes heparin solution L11 to flow into flow path F14 and performs measurement, then changes the sample to be flowed into flow path F14 to heparin solution L12 and proceeds again to step S102.

[0058] On the other hand, if the measurement is not to be continued (No in step S104), the processing circuitry 12 evaluates the characteristics of the blood sample based on the measurement results of the foaming state (step S106). For example, the processing circuitry 12 obtains a regression equation between the heparin concentration and the bubble size, and calculates the slope of the regression equation as an index showing the coagulation tendency of the blood sample. The processing circuitry 12 then outputs the evaluation results of the blood sample and ends the process (step S107).

[0059] As described above, according to the first embodiment, the control function 12a causes a foaming phenomenon in a blood sample. The control function 12a also causes a foaming phenomenon in a mixed sample obtained by mixing the blood sample with a blood coagulation-related factor. The measurement function 12b measures the foaming state in the blood sample and the foaming state in the mixed sample. The calculation function 12c evaluates the characteristics of the blood sample based on the measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. In other words, the blood characteristic evaluation device 1 according to the first embodiment provides a new method for evaluating the characteristics of blood.

[0060] Here, the foaming phenomenon is sensitive to differences in the characteristics of blood samples, and blood characteristic evaluation device 1 can accurately evaluate the characteristics of a blood sample based on the measurement results of the foaming state. Furthermore, as shown in Figure 5, no time-consuming steps are required before the characteristics of a blood sample can be evaluated, and no special measuring device that is expensive to manufacture is required. In other words, blood characteristic evaluation device 1 can easily evaluate the characteristics of a blood sample.

[0061] Another known method for evaluating blood involves detecting changes in the electrical resistance of a piezoresistance element. Specifically, by detecting the deflection of a flexible element such as a piezoresistance element as electrical resistance, it is possible to evaluate the viscoelasticity and other properties of a blood sample. However, the physical variations measured in this method are minute and difficult to measure. For example, implementing this method requires a probe with a fine and complex configuration. Furthermore, the probe itself may affect the viscoelasticity distribution. In contrast, the blood characteristic evaluation device 1 according to the first embodiment accurately evaluates the characteristics of a blood sample based on the measurement results of the foaming state, and can easily perform the evaluation without requiring a special probe or the like.

[0062] Furthermore, according to the first embodiment, the calculation function 12c evaluates the characteristics of the blood sample by calculating an index indicating the coagulation tendency of the blood sample. Furthermore, the output function 12d outputs the index calculated by the calculation function 12c. A user who receives such an index can make decisions regarding the use of blood coagulation-related factors such as heparin, for example, when formulating a treatment plan or a procedure. For example, in a procedure using an artificial heart-lung machine or a drug-eluting stent (DES) placement procedure, the user can determine the necessity, type, and amount of blood coagulation-related factors based on the evaluation results from the blood characteristic evaluation device 1.

[0063] As shown in FIG. 2, the control function 12a causes the blood sample to flow into the first and second flow paths and causes the blood coagulation-related factors to flow into the third flow path. The control function 12a also causes foaming in the blood sample flowing through the first flow path and in the mixed sample flowing through the fourth flow path formed by the merging of the second and third flow paths. Therefore, the blood characteristic evaluation device 1 according to the first embodiment can measure the foaming state in the blood sample and the foaming state in the mixed sample in parallel. In other words, the blood characteristic evaluation device 1 according to the first embodiment can evaluate the characteristics of the blood sample in a shorter time.

[0064] The control function 12a may control the flow rate according to the timing at which the measurement function 12b measures the foaming state. For example, the control function 12a applies a pulse voltage to the electrothermal transducer to cause a foaming phenomenon, and then reduces or stops the flow rate in the flow path after a predetermined delay time. For example, the control function 12a controls the flow in the flow path so that the flow rate is equal to or lower than a certain value. Furthermore, the measurement function 12b measures the foaming state at approximately the same timing as the control function 12a reduces or stops the flow rate. By reducing or stopping the flow rate during measurement in this way, errors in bubble size and the like can be suppressed, enabling more accurate evaluation of the characteristics of the blood sample.

[0065] Furthermore, while FIG. 2 shows one flow path F11 for introducing a blood sample and one flow path F14 for introducing a blood coagulation-related factor, the blood characteristic evaluation device 1 may include multiple of these flow paths. Furthermore, the multiple flow paths can be merged in any combination. The blood characteristic evaluation device 1 can simultaneously evaluate blood characteristics under different conditions. For example, the blood characteristic evaluation device 1 allows blood coagulation-related factors with different concentrations and types to flow into each of the multiple flow paths F14, and merges the flow path F11 for introducing a blood sample into each of the flow paths F14. The blood characteristic evaluation device 1 can simultaneously perform measurements under different conditions downstream of each of the multiple flow paths F14.

[0066] (Second embodiment) In the first embodiment described above, an example of a flow path for flowing a sample is shown in FIG. 2. In the second embodiment, a modified example of the flow path will be described. The blood characteristic evaluation device 1 according to the second embodiment has a configuration similar to that of the blood characteristic evaluation device 1 shown in FIG. 1, but differs in that it includes a sample holder 16b shown in FIG. 2 instead of the sample holder 16a. FIG. 6 is a diagram showing an example of the configuration of a flow path according to the second embodiment. Hereinafter, the same reference numerals will be used to designate the same components as those described in the first embodiment, and further description will be omitted.

[0067] The sample holder 16b can be manufactured using the same materials and methods as the sample holder 16a. For example, the control function 12a causes a blood sample to flow into the flow path F21 shown in FIG. 6, causing a foaming phenomenon in a portion of the blood sample flowing through the flow path F21. For example, the sample holder 16b includes a heater H21 as a heating portion at a position corresponding to the region R21 in FIG. 6. The control function 12a applies thermal energy from the heater H21 to the blood sample, causing a foaming phenomenon in the blood sample flowing through the region R21 of the flow path F21. For example, the control function 12a applies thermal energy to a position corresponding to the region R21 in FIG. 2, causing a foaming phenomenon. The flow path F21 is an example of a first flow path.

[0068] Furthermore, the control function 12a causes a blood coagulation-related factor to flow into the flow path F22. Hereinafter, heparin will be described as an example of a blood coagulation-related factor. For example, the control function 12a causes a heparin solution containing a predetermined concentration of heparin as the blood coagulation-related factor to flow into the flow path F22. The flow path F22 is an example of a second flow path.

[0069] As shown in FIG. 6, flow paths F21 and F22 merge to form flow path F23. That is, a mixed sample, which is a mixture of a blood sample flowing through flow path F21 and a heparin solution flowing through flow path F22, flows through flow path F23. Flow path F23 is an example of a third flow path. As in the case of region R21, control function 12a causes a foaming phenomenon in the mixed sample in region R22. For example, sample holder 16a includes heater H22 as a heating portion at a position corresponding to region R22 in FIG. 6. Then, control function 12a applies thermal energy from heater H22 to the mixed sample, thereby causing a foaming phenomenon in the mixed sample flowing through region R22 of flow path F23.

[0070] The measurement function 12b measures the foaming state in the blood sample and the foaming state in the mixed sample. For example, the measurement function 12b captures an image of the region R21 where foaming occurs and measures the size of bubbles in the blood sample based on the image. The measurement function 12b also captures an image of the region R22 where foaming occurs and measures the size of bubbles in the mixed sample based on the image.

[0071] The bubbles generated in region R21 disappear in a short time. In particular, when the foaming phenomenon occurs due to film boiling, the time required for the bubbles to disappear is short. However, it is preferable to provide a certain distance between region R21 and region R22 so that the bubbles generated in region R21 do not remain and are measured in region R22.

[0072] Here, the processing circuit 12 can repeatedly measure the foaming state in the mixed sample in region R22 while changing the blood coagulation-related factor. For example, after measuring the foaming state by flowing a solution containing a predetermined concentration of heparin into flow path F22, the processing circuit 12 flows a solution with a different heparin concentration or a solution containing a different type of anticoagulation factor into flow path F22 and measures the foaming state again.

[0073] Alternatively, the processing circuit 12 can perform measurements by changing blood coagulation-related factors at a position downstream of region R22. For example, the control function 12a causes a heparin solution L21 containing heparin to flow into flow path F22. The heparin concentration and flow rate of the heparin solution L21 are adjusted so that the heparin concentration in the mixed sample of the blood sample and the heparin solution L21 becomes C1. In this case, the measurement function 12b can measure the foaming state in the mixed sample having the concentration C1 in region R22.

[0074] Furthermore, the control function 12a causes a heparin solution L22 containing heparin to flow into a flow path F24 (not shown). Here, the flow path F24 is configured to merge with the flow path F23. The heparin concentration and flow rate of the heparin solution L22 are adjusted so that the heparin concentration in the mixed sample of the mixed sample flowing through the flow path F23 and the heparin solution L22 becomes C2. In this case, the measurement function 12b can measure the foaming state in the mixed sample having the concentration C2 in a flow path F25 (not shown) where the flow paths F23 and F24 merge. The flow path F24 is an example of a second flow path. The flow path F25 is an example of a third flow path.

[0075] Similarly, the control function 12a causes a heparin solution L23 containing heparin to flow into a flow path F26 (not shown). Here, the flow path F26 is configured to merge with the flow path F25. The heparin concentration and flow rate of the heparin solution L23 are adjusted so that the heparin concentration in the mixed sample of the mixed sample and the heparin solution L23 flowing through the flow path F25 becomes C3. In this case, the measurement function 12b can measure the foaming state in the mixed sample with the concentration C3 in a flow path F27 (not shown) where the flow paths F25 and F26 merge. The flow path F26 is an example of a second flow path. The flow path F27 is an example of a third flow path.

[0076] That is, the control function 12a causes a heparin solution to flow into each of the multiple second flow paths, and causes a foaming phenomenon in each of the multiple mixed samples flowing through multiple third flow paths formed by the merging of the first flow path and one or more second flow paths. Furthermore, the measurement function 12b measures the foaming state in the mixed sample in each of the multiple third flow paths, such as flow path F23, flow path F25, and flow path F27. Here, the measurement function 12b can also approximately simultaneously measure the foaming state in the blood sample in flow path F21, the foaming state in the mixed sample in flow path F23, the foaming state in the mixed sample in flow path F25, and the foaming state in the mixed sample in flow path F27. That is, the blood characteristic evaluation device 1 can simultaneously evaluate blood characteristics under different conditions.

[0077] As described above, according to the second embodiment, the control function 12a causes the blood sample to flow into the first flow path and the blood coagulation-related factor to flow into the second flow path. The control function 12a also causes foaming in the blood sample flowing through the first flow path and in the mixed sample flowing through the third flow path formed by the merging of the first and second flow paths. The measurement function 12b also measures the foaming state in the blood sample and the foaming state in the mixed sample.

[0078] The calculation function 12c then evaluates the characteristics of the blood sample based on the measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. That is, the blood characteristic evaluation device 1 according to the second embodiment can provide a new method for evaluating blood characteristics. Furthermore, like the first embodiment, the blood characteristic evaluation device 1 according to the second embodiment can evaluate blood characteristics simply and accurately. Furthermore, as shown in FIG. 6, the sample holder 16b is configured with fewer flow paths than the sample holder 16a. That is, the blood characteristic evaluation device 1 according to the second embodiment enables blood characteristics to be evaluated more simply.

[0079] (Third embodiment) Although the first and second embodiments have been described above, the present invention may be embodied in various different forms other than the above-described embodiments.

[0080] For example, in the above-described embodiment, the bubble size is measured based on an image of an area where a bubbling phenomenon occurs. However, the embodiment is not limited to this.

[0081] For example, the measurement function 12b can measure the size of bubbles based on the amount of light transmitted through the area where the bubbling phenomenon is occurring. For example, the measurement function 12b irradiates the area where the bubbling phenomenon is occurring with light from the light source 13, and measures the amount of transmitted light using a camera 14 or a light-receiving element (not shown). Here, since the light absorption rate within bubbles is lower than in blood samples or mixed samples, if there are large bubbles in the light path, the amount of transmitted light will increase. Therefore, the measurement function 12b can measure the size of bubbles according to the amount of transmitted light.

[0082] As another example, the measurement function 12b can measure the size of bubbles based on the amount of light reflected from the area where the bubbling phenomenon is occurring. For example, the measurement function 12b irradiates the area where the bubbling phenomenon is occurring with light from the light source 13 and measures the amount of reflected light using the camera 14 or a light-receiving element (not shown). Here, the light reflected from the area where the bubbling phenomenon is occurring refers to light reflected from the interface between the blood sample or mixed sample and the bubbles. In other words, if there is a large bubble in the light path, the interface will also be large, and the amount of reflected light will increase. Therefore, the measurement function 12b can measure the size of bubbles according to the amount of reflected light.

[0083] Alternatively, the measurement function 12b can measure bubble size based on the change over time (time profile) in the amount of transmitted light or the amount of reflected light. For example, the amount of transmitted light begins to increase after foaming begins, reaches a peak, and then gradually decreases and returns to the state before foaming. That is, in the change over time in the amount of transmitted light, the time from when the amount of transmitted light begins to increase until it returns to its original value corresponds to the length of time from foaming to defoaming. Also, typically, the larger the bubble, the longer the time from foaming to defoaming. Thus, the measurement function 12b can measure bubble size by acquiring the change over time in the amount of transmitted light and measuring the time from when the amount of transmitted light begins to increase until it returns to its original value, the length of time until it reaches its peak, etc. Similarly, the measurement function 12b can measure bubble size based on the change over time in the amount of reflected light.

[0084] The change in the amount of transmitted light or the amount of reflected light over time may be obtained by measuring the amount of light for one bubbling event, or by measuring the amount of light for multiple bubbling events. In the former method, the measurement function 112b measures the change in the amount of light over time, for example, by continuously or repeatedly measuring the amount of light while continuously or repeatedly emitting light from the light source 13 for one bubbling event. On the other hand, in the latter method, the measurement function 112b obtains the change in the amount of light over time by performing multiple measurement sets, each of which measures the amount of light one or more times for one bubbling event, with different delay times between bubbling and the light amount measurement. In this case, the measurement function 112b can synchronize the timing of the light emission of the light source 13 and the light amount measurement by causing the light source 13 to emit light in accordance with the delay time between bubbling and the light amount measurement.

[0085] In the above-described embodiment, the bubble size is measured as the foaming state. However, the embodiment is not limited to this. For example, the measurement function 12b may measure the bubble shape as the foaming state. Here, there is a correlation between the bubble shape and the characteristics of the blood sample, and the calculation function 12c can evaluate the characteristics of the blood sample based on the measurement results of the bubble shape. For example, the higher the viscosity, the more suppressed the bubble deformation is, and the more likely the bubbles are to become spherical. Therefore, the calculation function 12c can calculate the viscosity of the blood sample based on the measurement results of the bubble shape.

[0086] As another example, the measurement function 12b may measure the discharge characteristics due to foaming as the foaming state. Specifically, the control function 12a heats the blood sample in a hollow member such as a nozzle. This causes film boiling of a portion of the blood sample, generating pressure within the member and discharging the blood sample. Here, the measurement function 12b measures the discharge characteristics, such as the amount and speed of the blood sample being discharged, as the foaming state. It is also possible to measure the discharge characteristics due to foaming for mixed samples in the same way.

[0087] In the above-described embodiment, the case where the blood sample is stirred prior to measurement has been described. However, the blood characteristic evaluation device 1 may first measure the foaming state without stirring, and then determine whether or not the blood sample needs to be stirred based on the measurement result.

[0088] Specifically, first, the control function 12a causes a foaming phenomenon in an unagitated blood sample. Next, the measurement function 12b measures the foaming state in the blood sample. Next, the calculation function 12c calculates the variance (dispersion) of the measurement results of the foaming state. Here, if the variance is smaller than a threshold, the control function 12a determines that agitation of the blood sample is unnecessary. In other words, if the variance is smaller than the threshold, the calculation function 12c performs a characteristic evaluation of the blood sample based on the measurement results of the foaming state in the unagitated blood sample. By this processing, if agitation is unnecessary, the agitation step can be omitted, and the characteristics of the blood sample can be evaluated in a shorter time.

[0089] On the other hand, if the variation is greater than the threshold, the control function 12a determines that the blood sample needs to be stirred. In other words, if the variation is smaller than the threshold, the control function 12a stirs the blood sample, causing a foaming phenomenon in the stirred blood sample. Furthermore, the measurement function 12b measures the foaming state in the blood sample. Then, the calculation function 12c evaluates the characteristics of the blood sample based on the measurement results of the foaming state in the stirred blood sample. This process ensures that the measurement conditions are consistent, further improving the accuracy of the evaluation.

[0090] In the above-described embodiment, the characteristics of a blood sample are evaluated by calculating an index indicating the coagulation tendency of the blood sample. However, the embodiment is not limited to this. For example, the calculation function 12c may evaluate the characteristics of the blood sample by calculating an index other than the index indicating the coagulation tendency of the blood sample. As an example, the calculation function 12c may calculate the viscosity, viscoelasticity, surface tension, composition, etc. of the blood sample as an index other than the index indicating the coagulation tendency of the blood sample.

[0091] For example, it is known that the higher the viscosity of a liquid, the smaller the size of the bubbles that form in the liquid. Therefore, the calculation function 12c can calculate the viscosity based on the bubble size as an evaluation result of the characteristics of the blood sample.

[0092] For example, the calculation function 12c generates correspondence information in advance that associates viscosity with bubble size. For example, the control function 12a causes a liquid sample with a known viscosity to flow into the flow path shown in FIG. 2 or FIG. 6. The measurement function 12b causes a foaming phenomenon in the liquid sample. The calculation function 12c generates correspondence information by associating the bubble size in the liquid sample with the known viscosity, and stores the correspondence information in the memory 11. Then, when the foaming state in the blood sample is measured, the calculation function 12c can calculate the viscosity of the blood sample based on the correspondence information read from the memory 11.

[0093] For example, in the above-described embodiment, the slope of the regression equation between heparin concentration and bubble size was described as an example of an index indicating the clotting tendency of a blood sample. However, the embodiment is not limited to this. For example, the calculation function 12c may calculate a statistical value, such as a variance value, for bubble size when the heparin concentration is changed, and use the statistical value as an index indicating the clotting tendency of the blood sample. Furthermore, since there is a correlation between clotting tendency and bubble size, the calculation function 12c may calculate a value corresponding to bubble size as an index indicating the clotting tendency of the blood sample.

[0094] Furthermore, in the above-described embodiment, a case has been described in which both the foaming state in a blood sample and the foaming state in a mixed sample obtained by mixing a blood sample with a blood coagulation-related factor are measured, but it is also possible to omit either of these steps.

[0095] For example, the control function 12a omits the process of causing foaming in the mixed sample and causes foaming only in the blood sample. The measurement function 12b measures the foaming state in the blood sample. The calculation function 12c evaluates the characteristics of the blood sample based on the measurement results of the foaming state in the blood sample. For example, the calculation function 12c can calculate an index such as viscosity according to the size of bubbles, or an index showing the coagulation tendency of the blood sample. The calculation function 12c may calculate the index by referring to a lookup table according to the number of blood cells.

[0096] Furthermore, for example, the control function 12a omits the process of generating a foaming phenomenon in the blood sample and generates a foaming phenomenon only in the mixed sample. The measurement function 12b measures the foaming state in the mixed sample. The calculation function 12c evaluates the characteristics of the blood sample based on the measurement results of the foaming state in the mixed sample. For example, the calculation function 12c can calculate an index such as viscosity according to the size of bubbles, or an index showing the coagulation tendency of the blood sample. For example, when the foaming state is measured for multiple mixed samples with different heparin concentrations, the calculation function 12c can calculate the slope of the regression equation between the heparin concentration and the bubble size.

[0097] The term "processor" used in the above description refers to a circuit such as a CPU, a graphics processing unit (GPU), an application specific integrated circuit (ASIC), or a programmable logic device (e.g., a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), or a field programmable gate array (FPGA)). When the processor is a CPU, for example, the processor realizes its function by reading and executing a program stored in a memory circuit. On the other hand, when the processor is an ASIC, for example, instead of storing a program in a memory circuit, the function is directly incorporated into the processor circuit as a logic circuit. Note that each processor in the embodiments is not limited to being configured as a single circuit, but may be configured as a single processor by combining multiple independent circuits to realize its function. Furthermore, multiple components in each figure may be integrated into a single processor to realize its function.

[0098] 1, a single memory 11 is described as storing programs corresponding to each processing function of the processing circuit 12. However, the embodiment is not limited to this. For example, a configuration may be adopted in which multiple memories 11 are distributed and the processing circuit 12 reads corresponding programs from individual memories 11. Furthermore, instead of storing programs in the memory 11, the programs may be directly embedded in the circuitry of the processor. In this case, the processor realizes the functions by reading and executing the programs embedded in the circuitry.

[0099] The components of each device according to the above-described embodiments are conceptual and functionally independent, and are not necessarily physically configured as shown in the drawings. In other words, the specific form of distribution and integration of each device is not limited to that shown in the drawings, and all or part of each device can be functionally or physically distributed and integrated in any unit depending on various loads, usage conditions, etc. Furthermore, all or any part of the processing functions performed by each device can be realized by a CPU and a program analyzed and executed by the CPU, or can be realized as hardware using wired logic.

[0100] The blood characteristic evaluation method described in the above-described embodiment can be realized by executing a prepared program on a computer such as a personal computer or a workstation. This program can be distributed via a network such as the Internet. This program can also be recorded on a non-transitory computer-readable recording medium such as a hard disk, flexible disk (FD), CD-ROM, MO, or DVD, and executed by being read from the recording medium by a computer.

[0101] According to at least one of the embodiments described above, a new technique for evaluating the characteristics of blood can be provided.

[0102] Although several embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, modifications, and combinations of embodiments can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims.

[0103] With respect to the above embodiment, the following supplementary notes are disclosed as one aspect and optional features of the invention.

[0104] (Appendix 1) a control unit that causes a foaming phenomenon in the blood sample; a measuring unit that measures the foaming state in the blood sample; a calculation unit that calculates an index showing the coagulation tendency of the blood sample based on the measurement result of the foaming state in the blood sample; A blood characteristic evaluation device comprising: (Appendix 2) the control unit causes a foaming phenomenon in the blood sample and in a mixed sample obtained by mixing the blood sample with a blood coagulation-related factor; the measuring unit measures the foaming state in the blood sample and the foaming state in the mixed sample, The calculation unit may calculate the index based on measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. (Appendix 3) The control unit allowing the blood sample to flow into the first flow path and the second flow path; allowing the blood coagulation-related factor to flow into a third flow path; The foaming phenomenon may be caused in the blood sample flowing through the first flow path and the mixed sample flowing through a fourth flow path formed by joining the second flow path and the third flow path. (Appendix 4) The measurement unit may substantially simultaneously measure the foaming state in the blood sample flowing through the first flow path and the foaming state in the mixed sample flowing through the fourth flow path. (Appendix 5) The control unit flowing the blood sample into a first flow path; allowing the blood coagulation-related factor to flow into a second flow path; The foaming phenomenon may be caused in the blood sample flowing through the first flow path and the mixed sample flowing through a third flow path formed by joining the first flow path and the second flow path. (Appendix 6) The control unit may cause the blood coagulation-related factor to flow into each of the plurality of second flow paths, and may cause the foaming phenomenon in each of the plurality of mixed samples flowing through the plurality of third flow paths formed by the merging of the first flow path and one or more of the second flow paths. (Appendix 7) The blood coagulation-related factor may be heparin. (Appendix 8) The control unit may cause the foaming phenomenon by applying thermal energy. (Appendix 9) The calculation unit may calculate the index based on the measurement result and the number of blood cells in the blood sample. (Appendix 10) The control unit may cause the foaming phenomenon in the blood sample after adjusting the number of blood cells to a predetermined value. (Appendix 11) The control unit may cause the foaming phenomenon to occur in the blood sample after stirring. (Appendix 12) the control unit causes the foaming phenomenon in the blood sample in an unagitated state, the measuring unit measures the foaming state in the blood sample, the calculation unit calculates a variation in the measurement results of the foaming state, When the variation is smaller than a threshold value, the calculation unit calculates the index based on a measurement result of a foaming state in the blood sample in an unstirred state; If the variation is greater than a threshold value, the control unit may further perform agitation of the blood sample, thereby causing the foaming phenomenon in the agitated blood sample. (Appendix 13) the measurement unit measures the foaming state in the blood sample and excludes outliers from the foaming state measurement results; The calculation unit may calculate the index based on the measurement results after excluding outliers. (Appendix 14) further comprising an output unit that displays the indicator; The output unit may display an error range of the index together with the index. (Appendix 15) The measuring unit may measure a bubble size as the foaming state. (Appendix 16) The measuring unit may measure the bubble size based on an image of the region where the bubbling phenomenon occurs, the amount of light transmitted through the region, or the amount of light reflected from the region. (Appendix 17) The measuring unit may measure the bubble size based on a change over time in the amount of transmitted light or the amount of reflected light. (Appendix 18) The measuring section may measure a discharge characteristic due to bubbling as the bubbling state. (Appendix 19) a control unit for causing foaming in a mixed sample obtained by mixing a blood sample and a blood coagulation-related factor; a measuring unit that measures the foaming state in the mixed sample; a calculation unit that evaluates the characteristics of the blood sample based on the measurement result of the foaming state in the mixed sample; A blood characteristic evaluation device comprising: (Appendix 20) The calculation unit may calculate, as the evaluation, an index indicating the coagulation tendency of the blood sample. (Appendix 21) the control unit causes a foaming phenomenon in the blood sample and the mixed sample, the measuring unit measures the foaming state in the blood sample and the foaming state in the mixed sample, The calculation unit may calculate the evaluation based on measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. (Appendix 22) A foaming phenomenon is caused in the blood sample, measuring the foaming state in the blood sample; Calculating an index showing the coagulation tendency of the blood sample based on the measurement result of the foaming state in the blood sample. A method for evaluating blood characteristics, comprising: (Appendix 23) causing foaming in a mixed sample obtained by mixing a blood sample with a blood coagulation-related factor; measuring the foaming state in the mixed sample; The characteristics of the blood sample are evaluated based on the measurement result of the foaming state in the mixed sample. A method for evaluating blood characteristics, comprising: (Appendix 24) A program that causes a computer to execute each component of the blood characteristic evaluation device. [Explanation of symbols]

[0105] 1. Blood Characterization Device 11. Memory 12 Processing circuit 12a Control Functions 12b Measurement Function 12c Calculation Function 12d output function 13 Light source 14 Camera 15. Microscope 16a Sample holder 16b Sample holder

Claims

1. a control unit for generating a foaming phenomenon in a blood sample and a mixed sample obtained by mixing the blood sample with a blood coagulation-related factor; a measurement unit for measuring the foaming state in the blood sample and the foaming state in the mixed sample, a calculation unit that calculates a single index that indicates the coagulation tendency of the blood sample based on the measurement results of the foaming state in the blood sample and the foaming state in the mixed sample; A blood characteristic evaluation device comprising:

2. The control unit is flowing the blood sample into a first flow path and a second flow path; allowing the blood coagulation-related factor to flow into a third flow path; 2. The blood characteristic evaluation device according to claim 1, wherein the foaming phenomenon is caused in the blood sample flowing through the first flow path and in the mixed sample flowing through a fourth flow path formed by joining the second flow path and the third flow path.

3. 3. The blood characteristic evaluation device according to claim 2, wherein the measurement unit substantially simultaneously measures a foaming state in the blood sample flowing through the first flow path and a foaming state in the mixed sample flowing through the fourth flow path.

4. The control unit is flowing the blood sample into a first flow path; allowing the blood coagulation-related factor to flow into a second flow path; 2. The blood characteristic evaluation device according to claim 1, wherein the foaming phenomenon is caused in the blood sample flowing through the first flow path and in the mixed sample flowing through a third flow path formed by joining the first flow path and the second flow path.

5. 5. The blood characteristic evaluation device according to claim 4, wherein the control unit causes the blood coagulation-related factor to flow into each of the second flow paths, and causes the foaming phenomenon in each of the mixed samples flowing through a third flow path formed by joining the first flow path and one or more of the second flow paths.

6. 6. The blood characteristic evaluation device according to claim 1, wherein the blood coagulation-related factor is heparin.

7. 7. The blood characteristic evaluation device according to claim 1, wherein the control unit causes the bubbling phenomenon by application of thermal energy.

8. 8. The blood characteristic evaluation device according to claim 1, wherein the calculation unit calculates the index based on the measurement result and the number of blood cells in the blood sample.

9. 9. The blood characteristic evaluation device according to claim 1, wherein the control unit causes the foaming phenomenon to occur in the blood sample after the number of blood cells has been adjusted to a predetermined value.

10. The blood characteristic evaluation device according to claim 1 , wherein the control unit causes the foaming phenomenon to occur in the blood sample after stirring.

11. the measurement unit measures the foaming state in the blood sample and excludes outliers from the foaming state measurement results; 11. The blood characteristic evaluation device according to claim 1, wherein the calculation unit calculates the index based on the measurement results after excluding outliers.

12. An output unit that displays the indicator is further provided, The blood characteristic evaluation apparatus according to any one of claims 1 to 11, wherein the output section displays an error range of the index together with the index.

13. The blood characteristic evaluation device according to claim 1 , wherein the measurement unit measures a bubble size as the foaming state.

14. 14. The blood characteristic evaluation device according to claim 13, wherein the measurement unit measures the bubble size based on an image of a region where the bubbling phenomenon is occurring, an amount of light transmitted through the region, or an amount of light reflected from the region.

15. The blood characteristic evaluation device according to claim 14 , wherein the measurement unit measures the bubble size based on a change over time in the amount of transmitted light or the amount of reflected light.

16. The blood characteristic evaluation device according to claim 1 , wherein the measurement unit measures ejection characteristics due to bubbling as the bubbling state.

17. causing a foaming phenomenon in a blood sample and a mixed sample obtained by mixing the blood sample with a blood coagulation-related factor; measuring the foaming state in the blood sample and the foaming state in the mixed sample, respectively; A single index showing the coagulation tendency of the blood sample is calculated based on the measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. A method for evaluating blood characteristics, comprising:

18. causing a foaming phenomenon in a blood sample and a mixed sample obtained by mixing the blood sample with a blood coagulation-related factor; measuring the foaming state in the blood sample and the foaming state in the mixed sample, respectively; A single index showing the coagulation tendency of the blood sample is calculated based on the measurement results of the foaming state in the blood sample and the foaming state in the mixed sample. A program that causes a computer to execute each process.

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