Patent Application
20100260391
The present invention relates to a blood fluidity measurement system and a blood fluidity measurement method.
In recent years, along with increasing awareness of health, blood fluidity has been paid attention as a health barometer. The fluidity is also called as the degree of smoothness, and it means that the higher the fluidity or the smoothness, the better in health.
As a method for investigating the above blood fluidity, it has been known that, as described for example in Patent Document 1, blood is allowed to pass through a filter with fine grooves, and the time required for passing through the filter is measured. Further, it is also possible for the method of Patent Document 1 to grasp visually the blood fluidity by observing with a camera blood cells passing through the filter using a filter substrate made of a transparent glass.
Patent Document 1: Japanese Patent No. 2685544
However, with the method described in Patent Document 1, it is required to measure the time taken for a prescribed amount of blood to fully pass through a filter, and the measurement takes a lot of time.
The present invention has been achieved in consideration of the above issue, and it is an object of the invention to provide a blood fluidity measurement system and a blood fluidity measurement method, which can measure the blood fluidity in a short time.
To solve the above-described issue, the invention described in claim 1 is a blood fluidity measurement system to measure the aforesaid blood fluidity by flowing blood in a channel, wherein the blood fluidity measurement system is provided with a means of taking a picture of blood flow in the above channel, and a detection means for the state of blood flow to detect the state of blood flow in the above channel, as blood fluidity, from an image obtained by the above means of a taking picture.
The invention described in claim 2 is a blood fluidity measurement system described in claim 1, wherein the above channel has a plurality of gates formed with a narrower width than a blood cell size, the above means of taking a picture takes a picture of blood flow at an exit area of at least one of the above gates, and the above detection means for the state of blood flow detects the state of blood flow at the above exit area, as blood fluidity.
The invention described in claim 3 is a blood fluidity measurement system described in claim 2, wherein the above detection means for the state of blood flow detects motions of blood cells in blood at the above exit area, and then, obtains the speed vector of the aforesaid blood cells as the above state of blood flow.
The invention described in claim 4 is a blood fluidity measurement system described in claim 2, wherein the above detection means for the state of blood flow detects a boundary as a line between a portion containing blood cells and a portion without a blood cell among the above exit areas, and then, obtains an angle between the aforesaid line and a center line of the above gate, as the above state of blood flow.
The invention described in claim 5 is a blood fluidity measurement system described in claim 2, wherein the above detection means for the state of blood flow recognizes the both areas of a portion containing blood cells and a portion without a blood cell among the above exit areas by different colors of each area, and obtains an area ratio of the aforesaid both areas as the above state of blood flow.
The invention described in claim 6 is a blood fluidity measurement system described in any one of claims 3 to 5, wherein the blood fluidity measurement system is provided with a conversion means, which converts the above state of blood flow into the time required for the prescribed amount of blood passing through the above gate, transformability of a blood cell, or viscosity of blood.
The invention described in claim 7 is a blood fluidity measurement system described in claim 1, wherein the above channel has a stress change area, which affects blood existing in the interior, and the above means of taking a picture takes a picture of the blood flow in front of and behind the above change area in the direction of the blood flow.
The invention described in claim 8 is a blood fluidity measurement system described in claim 7, wherein the above channel has a small size channel, whose internal size is smaller than a blood cell size, and large size channels, which are arranged in front of and behind the above small size channel in the direction of the blood flow and have a larger cross section than that of the aforesaid small size channel, and the above change area is a joining part between the above small size channel and the above large size channel.
The invention described in claim 9 is a blood fluidity measurement system described in claim 7 or claim 8, wherein the above detection means for the state of blood flow obtains, as the above state of blood flow, at least one of blood speed, blood direction, and a degree of aggregation of blood cells in front of and behind the above change area.
The invention described in claim 10 is a blood fluidity measurement system described in any one of claims 7 to 9, wherein, by joining the first substrate having fine grooves on its surface and the second substrate having a flat surface part and making a close contact with the surface of the first substrate, the above channel is a space formed by the above fine groove and the above flat surface part.
The invention described in claim 11 is a blood fluidity measurement system described in any one of claims 7 to 9, wherein, by joining or pressure bonding the first substrate, in which a plurality of hollows, each of which hollows has an inflow entrance at one end and an outflow exit at the other end, are arranged side by side, has fine grooves communicating with the above hollows each other at wall parts, which divide the above hollows each other in the direction almost perpendicular to a straight line between the above inflow entrance and the above outflow exit, and the second substrate having a flat surface part and making a close contact with the surface of the above first substrate, the above channels are spaces formed by the above hollows and the above fine grooves.
The invention described in claim 12 is a blood fluidity measurement method, wherein the blood fluidity measurement method measures blood fluidity using the blood fluidity measurement system described in any one of claims 1 to 11.
According to the invention described in claim 1, since there are provided a means of taking a picture, which takes a picture of blood flow in a channel, and a detection means for the state of blood flow to detect as blood fluidity the state of blood flow in the above channel from an image obtained by the means of a taking picture, the blood fluidity can be detected at any time, if the image is timely taken by the above means of taking a picture. Therefore, compared to a conventional case, in which the time taken for a prescribed amount of blood to fully pass through a filter was measured, the blood fluidity can be measured in a short time.
According to the invention described in claim 2, since there are provided a means of taking a picture, which takes a picture of blood flow at an exit area of a gate, and a detection means for the state of blood flow to detect as blood fluidity the state of blood flow at the above exit area from an image obtained by the means of a taking picture, the blood fluidity can be detected at any time, if the image is timely taken by the above means of tatting a picture. Therefore, compared to the conventional case, in which the time taken for a prescribed amount of blood to fully pass through a filter was measured, the blood fluidity can be measured in a short time.
According to the invention described in claim 6, since there is provided a conversion means which converts the above state of blood flow into the time required for the prescribed amount of blood passing through a gate, transformability of a blood cell, or viscosity of blood, the state of blood flow, such as the above-described speed vector, angle, and area ratio, can be converted to other representative parameters showing the blood fluidity such as the time required to pass through the gate, transformability of a blood cell, or viscosity of blood, whereby a broader range of blood diagnosis can be conducted.
According to the invention described in claim 7, since the channel has the stress change area, which affects blood existing in the interior, and the means of taking a picture takes a picture of blood flow in front of and behind the above change area in the direction of the blood flow, the state of blood flow can be detected at positions where aggregation is likely to occur. Therefore, the various aspects of the state of blood flow can be detected.
According to the invention described in claim 8, a channel is arranged in a small size channel, whose inner size is smaller than a blood cell size, and in front of and behind the small size channel in the direction of the blood flow, and has a large size channel, whose cross section is larger than that of the aforesaid small size channel, and a change area is a joining part between the small size channel and the large size channel. Therefore, the above channel reproduces a stress change area of blood in a blood vessel in a pseudo manner, whereby the state of blood flow can be detected in front of and behind the change area.
a is a partial top view of a gate according to an embodiment of the present invention, and
a is a still picture in moving images of blood flow in case where healthy blood is flowed, and
a is a still picture in moving images of blood flow in case where blood having a low degree of health is flowed, and
a is a figure showing an example in case where angle θ regarding healthy blood is determined, and
b a figure showing an example in case where angle θ regarding blood having a low degree of health is determined.
a is a figure showing an example in case where an area ratio R regarding healthy blood is determined, and
a is a plan,
Embodiments of the present invention will hereinafter be described with reference to figures.
First, regarding the blood fluidity measurement system according to the present invention, an outline of a constitution thereof will be described.
Further, the blood fluidity measurement system 1 not only introduces blood to the filter 2 as it is, but also is provided with a plurality of solution bottles 12 connected to a channel through a mixer 3 for the purpose of introducing blood to the filter 2 after mixing the blood with other solutions such as a physiological salt solution, and a physiological active substance. Blood and others, which are introduced to the filter 2, are designed so that the desired amount of blood and others are flowed, by controlling a pump 4 with a differential pressure controlling part 5 to regulate differential pressure in front of and behind the filter 2. The mixer 3, the pump 4, a valve of the inlet 10, and the diagnosis part 8 are integrated and controlled by a sequence control part 9. Above each part of the blood fluidity measurement system 1 may be arranged in an integrated fashion as one apparatus, or may be arranged as individual devices connected with each other.
Next, of the constituent elements of the above-described blood fluidity measurement system 1, major ones will be detailed.
The filter 2 is provided with apertures 23 composed of a group of fine channels between a silicon single crystal substrate 21 and a glass flat board 22, as shown in a cross section of
The opening 23 owned by the filter 2 is, as shown in
The TV camera 6 is, for example, a digital CCD camera, and a high-speed camera with a flame rate of 3,000 fps (frame per second) having enough resolution to take moving images of blood flow. The above TV camera 6 is arranged at the upper part of the filter 2, and takes pictures, from a side of the glass flat board 22, of blood flow passing through the opening 23. The extent of taking a picture may, as shown in
The image processing part 7 is provided with an analytical means such as a CPU or a memory means such as a semiconductor memory, and is electrically connected with the TV camera 6. The image processing part 7 processes moving pictures of blood flow obtained by the TV camera 6, and detects, as blood fluidity, the state of blood flow at the exit area C of the gate 30. The specific states of blood flow detected by the above image processing part 7 indicate a speed vector V of blood cells, an angle θ showing a direction of a boundary between a portion containing blood cells and a portion without a blood cell, and the area ratio R of the above both portions. However, the image processing part 7 can detect, as the state of blood flow, at least one change in a blood speed, a direction of blood flow, and a degree of aggregation of blood cells in front of and behind the change area H. The image processing part 7 is arranged to detects at least one of these states of blood flow depending on the degree of definition of moving pictures of blood, and, in an embodiment of the present invention, it is made to detect the speed vector V. The detected state of blood flow is designed to be displayed on a display, which is not illustrated.
A diagnosis part 8 is provided with a conversion means 81, which converts the state of blood flow detected by the image processing part 7 into other fluidity parameters, in addition to an analytical means such as a CPU or a memory means such as a semiconductor memory, and is electrically connected with the image processing part 7. The specific fluidity parameters converted from the state of blood flow indicate the time required for the prescribed amount of blood passing through the gate 30, transformability of a blood cell, or viscosity of blood. The conversion means 81 has, for example, a conversion table as shown in
Next, a blood fluidity measurement method via the blood fluidity measurement system 1 according to an embodiment of the present invention will be described.
First, steps until a step of taking a picture of blood flow after blood is flowed in the filter 2 will be described.
First, blood for measurement is charged into the inlet 10, and at the same time, a physiological salt solution or others is added to a solution bottle 12, as needed. Then, blood and a physiological salt solution or others (hereinafter, referred to as blood) are flowed to the filter 2 by putting differential pressure on the filter 2, and at the same time, pictures of blood flow passing through the gate 30 are taken by the TV camera 6.
At this time, for example, if differential pressure of 10 to 30 cmAq is put on the filter 2, it takes 30 to 180 seconds for blood of 100 μl to flow. Therefore, the speed of blood flowing 7,854 gates 30 having a cross section of 6.4 μm×4.5 μm shown in
Examples of moving pictures of blood flow taken in this way are shown in
Next, a process, in which images of moving pictures of blood flow are processed to investigate the fluidity, will be described. This process is executed following steps shown in
First, each of frames in moving pictures of blood flow is sampled, and a frame to be processed is set (S1). Then, one of the gates 30 to be inspected is similarly set (S2).
After that, the state of blood flow at the exit area C of the gate 30 is measured (S3). At this step, the states of blood flow of different types are measured for each of cases where behavior of blood cells at the exit area C can be captured or not, based on a frame rate of the TV camera 6.
In case where the behavior can be captured, that is, as an embodiment of the present invention, identical blood cell can be recognized in successive frames at the exit area C, as the state of blood flow, the speed vector of a blood cell can be determined. The method for determining the above speed vector can be a method for making a two-dimensional speed map of blood cells as described, for example, in Japanese Patent Applications No. 2001-264318 or No. 2006-223761, or can be other methods. However, since at least two successive frames are required to determine the speed vector, the aforesaid speed vector can be determined by a cycle including step S5, which will be described later, in which similar processing on another one frame is carried out.
Examples of the speed vector thus determined are shown in
The above-described speed vectors can at any time be determined, if at least two frames of moving pictures of blood flow are taken by the TV camera 6. Therefore, it is not necessary to measure the time of the prescribed amount of blood passing through a filter as is the conventional method, resulting in enabling in the measurement to be completed in a short time.
After completion of the above-described measurement of the state of blood flow (S3 of
Next, a conversion processing of the state of blood flow, in which a statistical processing was completed, is carried out (S7). This processing is executed by the conversion means 81, with which the diagnosis part 8 is provided. The conversion means 81 converts the speed vector determined as the state of blood flow to other fluidity parameters such as the time required for the blood passing through the gate 30, transformability of a blood cell, or viscosity of blood. This conversion is executed with reference to conversion data owned by the conversion means 81.
With such conversion means 81, the speed vector V as the state of blood flow can be converted to other representative parameters showing the blood fluidity such as the time required for the blood passing through a gate, transformability of a blood cell, or viscosity of blood, whereby a broader range of blood diagnosis can be conducted.
Lastly, the diagnosis part 8 makes a diagnosis of the states of blood flow or fluidity parameters converted from the states of blood flow (S8). In case where this diagnosis is made of the fluidity parameters, the degree of health of blood is judged based on criteria owned by the diagnosis part 8. In case where this diagnosis is made of the states of blood flow, that is, the speed vector V, it may be judged that when for example the angle of the speed vector V is zero degree, blood is healthy, and the larger the angle, the lower the degree of health. At this time, each of angles of a plurality of blood cells may be evaluated, or one representative blood cell may be evaluated.
As stated above, according to blood the fluidity measurement system 1 according to an embodiment of the present invention, the above system is provided with the image processing part 7, which detects the state of blood flow in the aforesaid channel (the exit area C) as fluidity of blood using the TV camera 6, which takes a picture of blood flow in a channel (the exit area C of at least one of gates 30) and images obtained by the TV camera 6. So, the speed vectors can at any time be determined as the state of blood flow, if at least two frames of moving pictures of blood flow are taken by the TV camera 6. Therefore, it is not necessary to measure the time of the prescribed amount of blood passing through a filter as is the conventional method, resulting in enabling in the measurement to be completed in a short time.
Further, since the above system is provided with the conversion means 81, the speed vector V as the state of blood flow can be converted to other representative parameters showing the blood fluidity such as the time required for the blood passing through a gate, transformability of a blood cell, or viscosity of blood, whereby a broader range of blood diagnosis can be conducted.
Subsequently, the first modified example of the blood fluidity measurement system 1 will be described. Any constituent element similar to the above embodiment will be denoted by the same reference numerals, and their descriptions will be omitted.
A blood fluidity measurement system 1A is, as shown in
A blood fluidity measurement method via the above blood fluidity measurement system 1A will be described.
First, steps until a step of taking a picture of blood flow after blood is flowed in the filter 2 are similar to those described in the above-described embodiment. However, in this modified example, even if the speed of blood flowing the gate 30 is 2.46 to 14.7 μm/ms, which is the same as that of the above-described embodiment, because of the frame rate of the TV camera 6A being small as 30 fps, blood advances as much as 81.9 to 491 μm (=(2.46 to 14.7)/30×103) during taking one frame by this TV camera 6A. Since this distance is longer than the length of 31.5 μm in the outflow direction at the exit area C, an identical blood cell cannot be recognized in successive frames.
Next, a process, in which images of moving pictures of blood flow are processed to investigate the fluidity, will be described. This process is executed following steps shown in
First, each of frames in moving pictures of blood flow is sampled, and a frame to be processed is set (S1). Then, one of the gates 30 to be inspected is similarly set (S2).
After that, the state of blood flow at the exit area C of the gate 30 is measured (S3). In this modified example, as stated above, an identical blood cell cannot be recognized in successive frames at the exit area C. In such a case, the angle θ showing a direction of a boundary between a portion containing blood cells and a portion without a blood cell among the exit areas C, or the area ratio R of the above both portions can be determined as the state of blood flow. If the parameters are the angle θ or the area ratio R, the above parameters can be determined from one piece of still picture, that is, one frame of moving pictures, as described below.
The Angle θ is determined as follows: first, by executing enhancement or a binary processing of a boundary between a portion containing blood cells and a portion without a blood cell on the exit area C of an image, an approximate line of the boundary is determined. For this purpose, conventional methods such as the minimum square method and the linear Hough method may be used. Then, from a slope of the straight line thus obtained, an angle between a center line of the gate 30, which is a reference line, and the aforesaid straight line is calculated as the angle θ to be determined.
If the blood is healthy, the angle θ thus determined is close to zero, as shown in
The area ratio R is determined in the following way: first, a binary processing for different colors is carried out for the exit area C of an image. This process is carried out based mainly on difference of color density. With this processing, as shown in
In place of the above-described area ratio R, a representative length L may be determined as the state of blood flow. As the representative length L, a lower side of a portion containing blood cells, that is, L1 or L3 shown in
It is possible to determine at any time the above-described angle θ and area ratio R, if at least one frame of the moving pictures of blood flow is taken by the TV camera 6. Therefore, it is not necessary to measure the time of the prescribed amount of blood passing through a filter as is the conventional method, resulting in enabling in the measurement to be completed in a short time.
After completion of the above-described measurement of the state of blood flow (S3 of
Next, a conversion processing of the state of blood flow, in which a statistical processing was completed, is carried out (S7). This processing is executed by the conversion means 81, with which the diagnosis part 8 is provided. The conversion means 81 converts at least one of the angle θ and area ratio R determined as the state of blood flow to other fluidity parameters such as the time required for the blood passing through the gate 30, transformability of a blood cell, or viscosity of blood. This conversion is executed with reference to conversion table owned by the conversion means 81, as shown for example in
With such the conversion means 81, the angle θ and area ratio R as the state of blood flow can be converted to other representative parameters showing the blood fluidity such as the time required for the blood passing through a gate, transformability of a blood cell, or viscosity of blood, whereby a broader range of blood diagnosis can be conducted.
Lastly, the diagnosis part 8 makes a diagnosis of the states of blood flow or fluidity parameters converted from the states of blood flow (S8). In case where this diagnosis is made of the fluidity parameters, the degree of health of blood is judged based on criteria owned by the diagnosis part 8. For the state of blood flow, the diagnosis is made as follows: with regard to the angle θ, it may be judged that when for example its value is zero degree, blood is healthy, and the larger the angle, the lower the degree of health. With regard to the area ratio R, it may simply be that the smaller the ratio, the lower the degree of health, or it may be judged by using a ratio between the area ratio R of healthy blood and the area ratio R of blood to be inspected. However, in case where a ratio with healthy blood is used, it is necessary that the exit area C has the same region for both measurements. With regard to the representative length L, a judgment can be made in the similar manner to the area ratio R.
As stated above, according to the blood fluidity measurement system 1A, the angle θ and area ratio R as the state of blood flow can at any time be determined as the state of blood flow, if at least one frame of moving pictures of blood flow is taken by the TV camera 6A. Therefore, it is not necessary to measure the time of the prescribed amount of blood passing through a filter as is the conventional method, resulting in enabling in the measurement to be completed in a short time.
Further, since the above system is provided with the conversion means 81, the angle θ and area ratio R as the state of blood flow can be converted to other representative parameters showing the blood fluidity such as the time required for the blood passing through a gate, transformability of a blood cell, or viscosity of blood, whereby a broader range of blood diagnosis can be conducted.
Subsequently, a blood fluidity measurement system 1B as the second modified example of the blood fluidity measurement system 1 will be described. Any constituent element similar to the above embodiment will be denoted by the same reference numerals, and their descriptions will be omitted.
The blood fluidity measurement system 1B is, as shown in
The microchip 2B is, as shown in
The glass flat board 20B is formed in a flat board fashion, and covers an interior surface (the upper surface of
The base board 21B has hollow parts 210B and 211B at each end, and a plurality of grooves 212B and others between the above hollow parts 210B and 211B.
Of these hollow parts, the hollow part 210B has a pass-through opening 210Ba communicating with the inlet 10 at bottom surface, and forms an upstream side collection part 22B, which collects blood, between the hollow part 210B and the glass flat board 20B.
Similarly, the hollow part 211B has the a pass-through opening 211Ba communicating with the discharge part 11 at bottom surface, and forms a downstream side collection part 23B, which collects blood, between the hollow part 211B and the glass flat board 20B.
A plurality of grooves 212B and others are arranged so as to be extended parallel to a direction between the hollow part 210B and the hollow part 211B (in the X direction given in the figure), and is in a state that they are divided by a terrace part 213B, which is extended in the above-described X direction. These plurality of grooves 212B and others are alternately communicated with the hollow part 210B or the hollow part 211B, and with this configuration, an upstream side blood circuit 24B which allows blood to flow from the upstream side collection part 22B, and a downstream side blood circuit 25B which allows blood to flow from the downstream side collection part 23B are formed under the glass flat board 20B.
On the upper end of the terrace part 213B, as shown in
The channel 26B is arranged in the inner area A of the gate 215B, whose inner size is smaller than a blood cell size, and in front of and behind the inner area A in the Y direction, and has the entrance area B and the exit area C located upstream and downstream of the gate 215B whose cross section is larger than that of the aforesaid inner area A. In addition, the joining part between the inner area A and the entrance area B, and the joining part between the inner area A and the exit area C are the stress change area H, which affects blood existing in the interior of the channel 26B. Namely, it is assumed that the change in stress is caused by an existence of the inner area A of the gate 215B through which a blood cell is unable to pass without being deformed. The inner size of the gate 215B is preferably about 1 μm to about 10 μm, and more preferably about 5 μm to about 10 μm.
In such microchip 2B, blood introduced from the inlet 10 is collected in the upstream collection part 22B, and after passing through the channel 26B and the downstream side blood circuit 25B from the upstream side blood circuit 24B, the blood is collected in the downstream side collection part 23B to be discharged from a discharge part 11. In more detail, as shown in
The region that the TV camera 6B takes a picture includes the inner area A, the entrance area B, and the exit area C of the gate 215B. However, the TV camera 6B may take at least a picture of blood flow in front of and behind the change area H in the Y direction. Namely, the region of taking a picture may be a region including at least a joining part between the inner area A and the entrance area B, or a joining part between the inner area A and the exit area C. The above TV camera 6B is, in other points, constituted in a similar manner to that of the TV camera 6 in the above-described embodiment, but it may have a low frame rate similarly to the first modified example of the embodiment.
Next, the blood fluidity determined by the blood fluidity measurement system 1B will be exemplified. The measurement method of the fluidity is carried out in a similar manner to that of the above-described embodiment or the first modified example of the embodiment.
As described above, according to the blood fluidity measurement system 1B, similar effects to those of the above-described embodiment and the first modified example thereof are naturally obtained, and further, since the channel 26B has the stress change area H, which affects blood in the channel, and the TV camera 6B takes a picture of blood flow in front of and behind the change area H in the Y direction, the state of blood flow can be detected at positions where aggregation is likely to occur. Therefore, the various aspects of the state of blood flow can be detected.
The channel 26B is arranged in the inner area A of the gate 215B, whose inner size is smaller than a blood cell size, and in front of and behind the inner area A in the Y direction, and has the entrance area B and the exit area C located upstream and downstream of the gate 215B, whose cross section is larger than that of the aforesaid inner area A, and the change area H is a joining part between the inner area A and the entrance area B or the exit area C. Therefore, the channel 26B reproduces a stress change area of blood in a blood vessel in a pseudo manner, whereby the state of blood flow can be detected in front of and behind the change area.
In the second modified example of the above-described embodiment, both of the joining part between the inner area A and the entrance area B and the joining part between the inner area A and the exit area C are designated as the stress change area H, but the joining part between the channel 26B and the upstream side blood circuit 24 or the downstream side blood circuit 25 may be designated as the aforesaid change area H.
Further, in other points, the present invention is not limited to the above-described embodiment and the modified examples thereof, and naturally it can appropriately be modified.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2007-306969 | Nov 2007 | JP | national |
| 2008-175489 | Jul 2008 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP2008/069528 | 10/28/2008 | WO | 00 | 5/25/2010 |
