Description
Title of Invention
ELECTRICAL CHARACTERISTIC MEASURING DEVICE
Technical Field
[0001]
The present technology relates to an electrical characteristic measuring
device that measures electrical characteristics of blood. More particularly, the
10 present technology relates to a technology for chronologically measuring electrical
characteristics of blood and acquiring information such as coagulability of the blood
or the like.
Background Att
15 [0002]
Anti-platelet aggregation agents or anti-coagulant agents are
prophylactically administered to patients or healthy persons susceptible to
thrombosis. Examples of the patients susceptible to thrombus formation include
patients with diabetes, arteriosclerosis, cancer, heatt disease and respiratory disease;
20 perioperative patients; and patients taking immunosuppressants. Also, examples of
the healthy persons susceptible to thrombus include pregnant women and elderly
people. As the anti-platelet aggregation agents, acetylsalicylic acid and the like arc
used; and as the anti-coagulant agents, warfarin, heparin, activated blood coagulation
factor Xa inhibitors, direct thrombin inhibitors, and the like are used.
25 [0003]
The prophylactic administration of anti-platelet aggregation agents and anticoagulant
agents against thrombosis has the side effect that an excessively high
administered dose increases bleeding risk. In order to obtain a sufficient
prophylactic effect while inhibiting this side effect, an administration management
30 becomes important in which blood coagulability of an administered subject is timely
evaluated, and the drug and dose to be administered are appropriately selected and
SP349572WOOO
2/26
detenn ined.
[0004]
A method for a blood coagulability test for managing drug administration
includes the prothrombin time-international normalized ratio (PT-INR), the activated
5 partial thromboplastin time (APTT), and the like. Also, a method for a platelet
aggregation test includes adding a substance that induces aggregation of platelet to
platelet rich plasma (PRP) obtained by centrifuging blood, and measuring a change
in transmitted light levels or absorbance associated with the aggregation to determine
good or poor in aggregation capacity.
10 [0005]
Recently, there is also proposed a technique of acquiring information on
blood coagulation system based on a dielectric constant of blood (See Patent
Literatures I and 2). For example, in the blood coagulation system analyzers
disclosed in Patent Literatures I and 2, blood to be analyzed is retained in a container
15 provided with electrodes through which voltage is applied to the blood, and an
alternating current is applied to the electrodes thereby to measure a complex
dielectric constant. These analyzers analyze the obtained complex dielectric
constant spectrum according to a predetermined algorithm thereby to evaluate
enhancement or reduction of blood coagulability such as a blood coagulation time.
20 [0006]
Also, an example of the sample container used for measuring electrical
characteristics of a liquid sample such as blood includes a sample cartridge provided
with a narrowed portion between opposing two electrodes in order to inhibit a
chemical reaction and interface polarization on a contact surface with the electrodes
25 (See Patent Literature 3).
30
Patent Literature
[0007]
[Patent Literature I]
[Patent Literature 2]
Citation List
JP 201 0-181400A
JP 2012-194087 A
SP349572WOOO
3/26
[Patent Literature 3] JP 20 l2-52906A
Summary of Invention
Technical Problem
5 [0008]
However, known blood coagulability tests such as PT-INR and APTT
substantially evaluate only bleeding risk associated with reduction in blood
coagulability caused by excess administration of anti-coagulant agents, and cannot
evaluate thrombus risk associated with enhancement in blood coagulability. Also,
10 the existing platelet aggregation test using PRP may require a centrifugation process.
This may cause platelet to be activated during this process, thereby inhibiting
accurate test results fi·om being obtained. Fmthermore, the operation is complicated.
[0009]
On the contrary, the method of measuring a dielectric constant of blood
15 disclosed in Patent Literatures I to 3 can simply and accurately evaluate information
on blood coagulability and the like. However, even in this method, the
measurement data may be changed by the influence of blood sedimentation.
[0010]
Therefore, the present disclosure has a main object to provide an electrical
20 characteristic measuring device that can accurately measure electrical characteristics
of blood.
25
30
Solution to Problem
[00 I I]
An electrical characteristic measuring device according to the present
disclosure includes a rotating mechanism that rotates a sample container to be filled
with blood to be measured, to any angle, and a measurement unit that applies a
voltage between a pair of electrodes installed in the sample container, and
chronologically measures electrical characteristics of the blood.
With regard to the electrical characteristic measuring device, the rotating
mechanism may intermittently rotate the sample container.
SP349572WOOO
4/26
In addition, the rotating mechanism can alternate between forward rotation
and reverse rotation.
On the other hand, the measurement unit can apply an alternating voltage
between the pair of electrodes, and measure one or both of impedance and a
5 dielectric constant of the blood.
The sample container may include a tubular container body made of
insulating material, a first electrode that is made of conductive material and blocks
one end of the container body, and a second electrode that is made of conductive
material and is arranged so as to be in contact with the blood.
10 In this case, the other end of the container body is blocked by the second
electrode, and a space constituted by the first electrode, the second electrode and the
container body is filled with the blood.
In addition, the second electrode may be provided with a blood injection
hole.
15 Moreover, the sample container can be made of conductive material and
include a stopper that is fitted into the blood injection hole.
Here, the stopper can be a screw stopper.
In addition, the stopper may be provided with a vent.
The sample container can be arranged in a manner that a rotation axis of the
20 sample container is parallel to or forms a tilt angle of 45° or less with respect to an
installation surface.
25
In addition, the electrical characteristic measuring device may include an
analysis unit that analyzes an action of a blood coagulation system on the basis of the
electrical characteristics of the blood measured in the measurement unit.
Advantageous Effects of Invention
[00 12]
According to the present disclosure, the influence of blood sedimentation
can be reduced, thereby enabling electrical characteristics of blood to be accurately
30 measured.
SP349572WOOO
5/26
Brief Description of Drawings
[00 13]
[FIG. I] FIG. I is a diagram illustrating a schematic configuration of an electrical
characteristic measuring device according to a first embodiment of the present
5 disclosure.
[FIG. 2] FIG. 2 is an exploded perspective view illustrating a configuration example
of a sample container 2 illustrated in FIG. I.
[FIG. 3] A, B, C and D are a plan view, a side view, a bottom plan view and a crosssectional
view, respectively, of the sample container 2 illustrated in FIG. 2.
10 [FIG. 4] FIG. 4 is a diagram illustrating a configuration example of a stopper 24
provided with a vent, and A, B, C and D are a plan view, a side view, a bottom plan
view and a cross-sectional view along a-a line indicated in C, respectively.
[FIG. 5] FIG. 5 is a diagram illustrating a configuration example of a container holder
33 illustrated in FIG. I.
15 [FIG. 6] FIG. 6 is a diagram illustrating an arrangement example of a sample
container in an electrical characteristic measuring device according to a second
embodiment of the present disclosure.
[FIG. 7] FIG. 7 is a dielectric spectrum of blood m which elevated blood
sedimentation is not observed.
20 [FIG. 8] FIG. 8 is data at 760kHz in the dielectric spectrum illustrated in FIG. 7.
[FIG. 9] FIG. 9 is a dielectric spectrum of blood in which blood sedimentation is
significant.
[FIG. 10] FIG. 10 is data at 760kHz in the dielectric spectrum illustrated in FIG. 9.
[FIG. II] FIG. II is data at I 0.7 MHz in the dielectric spectrum illustrated in FIG. 9.
25 (FIG. 12] FIG. 12 is a dielectric spectrum measured while rotating the blood in which
blood sedimentation is significant.
30
[FIG. 13] FIG. 13 is data at 760 kHz in the dielectric spectrum illustrated in FIG. 12.
[FIG. 14] FIG. 14 is data at 10.7 MHz in the dielectric spectrum illustrated in FIG. 12.
Description of Embodiments
[00 14]
SP349572WOOO
6/26
Hereinafter, embodiments for carrying out the present disclosure will be
described in detail with reference to the accompanying drawings. It is noted that
the present disclosure is not limited to the embodiments described blow.
Description will be provided in the following order.
5 I. First Embodiment
(Example of electrical characteristic measuring device including sample container
rotating mechanism)
2. Second Embodiment
(Example of electrical characteristic measuring device including sample container
10 attached in tilted manner)
[0015]

First, an electrical characteristic measuring device according to a first
embodiment of the present disclosure will be described. As described above,
15 measurement results of electrical characteristics of blood can be influenced by blood
sedimentation. Also, it is repmied that a dielectric constant of uncoagulated blood
is changed by blood sedimentation (K. Asami, T. Hanai, Colloid and Polymer
Science, vol. 270, 1992, p. 78-84). However, it is not known what influence the
blood sedimentation has in a blood coagulation test performed using a dielectric
20 constant, and it has not been studied how such influence can be eliminated.
[00 16]
For this reason, in order to perform more accurate measurement in an
electrical characteristic measuring device for blood, such as a dielectric coagulometer,
it may be necessary to employ a method being fi·ee fi·om the influence of blood
25 sedimentation, or to isolate the influence by blood sedimentation according to an
algorithm for correction. However, such techniques have not been established.
Furthermore, evaluation of blood sedimentation itself is also useful in the medical
field, and it is desired to develop a device that can measure blood coagulation while
evaluating blood sedimentation.
30 [0017]
Therefore, the electrical characteristic measuring device according to the
SP349572WOOO
7/26
present embodiment is configured to rotate a sample container to be filled with blood
to be measured, so that the influence by blood sedimentation is inhibited. FIG. I is
a diagram illustrating a schematic configuration of the electrical characteristic
measuring device according to the present embodiment. As illustrated in FIG. I, an
5 electrical characteristic measuring device I according to the present embodiment
includes: a rotating mechanism 3 that rotates a sample container 2 to be filled with
blood I 0 to be measured, to any angle; and a measurement unit 4 that
chronologically measures electrical characteristics of the blood I 0 filled in the
sample container 2.
10 [0018]
[Sample Container 2]
The sample container 2 has a configuration in which the measured blood I 0
does not leak, and desirably has a configuration in which impedance mismatches are
as small as possible in order to enable high-frequency measurement. FIG. 2 and
15 FIG. 3 are each a diagram illustrating a configuration example of the sample
container 2 illustrated in FIG. I, and FIG. 4 is a diagram illustrating a configuration
example of a stopper 24 illustrated in FIG. 2. The sample container 2 may include a
pair of or at least two pairs of electrodes, and can contain the blood I 0 to be
measured. Specifically, the sample container 2 can be configured such that both
20 ends of a tubular container body 21 as illustrated in FIG. 2 and FIG. 3 arc blocked
with a pair of electrodes 22 and 23.
[0019]
Here, a material of the container body 21 is not particularly limited as long
as it is insulated. Examples thereof may include a hydrophobic and insulating
25 polymer, copolymer and blend polymer such as polypropylene, polymethyl
methacrylate, polystyrene and polytetrafluoroethylene. Also, the container body 21
may be obtained by coating the surface of a tubular body made of a predetermined
material with these hydrophobic and insulating polymers and the like. It is noted
that the shape of the container body 21 may be, other than a round tube illustrated in
30 FIG. 2, a polygonal tube having a cross section of a triangle, a rectangle, or a polygon
with more corners.
SP349572WOOO
8/26
[0020]
On the other hand, a material of the electrodes 22 and 23 is not particularly
limited as long as it is a conductive material having less influence on blood. Since a
stable oxidized thin film is naturally formed in the atmosphere, titanium or titanium
5 alloy, or aluminum or aluminum alloy is suitable. Fmthermore, a contact region
221 for electrically connecting with the measurement unit 4 may be installed in the
electrode 22 that blocks a bottom end of the container body 21. The contact region
221 can be formed, for example, in a concave shape on the central portion of the
outer surface of the electrode 22. This enables stable electrical connection even
10 while the sample container 2 is rotated.
[0021]
Fmthermore, the electrode 23 that blocks an upper end of the container body
21 may include, in the container, a blood injection hole 231 through which the blood
I 0 to be measured is injected. In this case, the sample container 2 is preferably
15 provided with the stopper 24 that intrudes into and blocks the blood injection hole
231. This can inhibit the blood I 0 from leaking out from the blood injection hole
231. A material of the stopper 24 is not particularly limited as long as it is a
conductive material having less influence on blood. From a similar reason to for
the above-described electrodes 22 and 23, titanium or titanium alloy, or aluminum or
20 aluminum alloy is suitable.
[0022]
The stopper 24 may also be a screw stopper which can enhance sealing
properties. Also, when air remains in the sample container 2, measurement
accuracy can deteriorate, and measurement safety can be impaired. Therefore, a
25 vent 241 for releasing remained air may be formed to the stopper 24. The shape of
the vent 241 is not particularly limited. An example thereof may include a reversed
L shape constituted by a lateral hole and a vettical hole as illustrated in FIG. 4. This
enables efficient release of air while inhibiting leakage of liquid.
30
[0023]
It is noted that as illustrated in FIG. 3D, a surface on the blood I 0 side of the
electrode 23 is preferably inclined toward the blood injection hole 231. This allows
5
SP349572WOOO
9/26
air remained in the sample container 2 to gather around the blood injection hole 231
when the electrode 22 side is arranged to face downward. Accordingly, the
remained air can be surely released.
[0024]
The angle of this tilted surface installed in the electrode 23 is not
pmticularly limited, and is preferably approximately 140 to 160° when an untilled
planar state is assumed to be 180°. As the angle of the tilted surface is closer to a
plane (180°), the effect of releasing remained air becomes smaller. On the other
hand, when the angle of the tilted surface becomes an acute angle, a difference of the
10 inter-electrode distance becomes larger between the center and the outer edge,
causing a formed electric field to become non-uniform. Specifically, the center
portion with a long distance between the electrode 22 and the electrode 23 has a
weak electric field, and as becoming closer to the outer edge, the distance between
the electrode 22 and the electrode 23 increases thereby causing an electric filed to
15 become stronger. As a result, the outer edge having a stronger electric field has
higher measurement sensitivity, and in this position, a slight change (blood
sedimentation and the like) in the blood 10 have greater influence on measurement
results.
20
[0025]
Furthermore, a notch 232 may be installed in a flange portion of the
electrode 23, so that a screw may be tightened using a jig or the like that engages
with this notch 232. This can inhibit idle running of the sample container 2, enables
smooth screw tightening, and ftuthermore, can easily accomplish an automatic screw
tightening mechanism by robot actions.
25 [0026]
It is noted that the sample container used in the electrical characteristic
measuring device according to the present embodiment is not limited to the
configuration illustrated in FIGS. 2 to 4, and two or more pairs of electrodes may be
installed. Also, for example, the electrodes may be integrated with the container
30 body 21. However, when the sample container 2 is configured to be disposable, the
electrode pairs are preferably an independent detachable member.
--------------------
SP3,l9572WOOO
10/26
[0027]
Furthermore, the electrode 23 may not be provided with the blood injection
hole 231, and may also be configured such that, for example, an injection needle is
pierced into inner air from the outer surface of the container body 21 to inject the
5 blood I 0. In this case, the portion through which the injection needle has
penetrated may be blocked with grease or the like in order to seal the container.
Still furthermore, there can also be used a sample cartridge disclosed in Patent
Literature 3 which has been proposed by the present inventor. However, from the
viewpoint of handling properties, it is preferred to use the sample container 2
10 provided with the blood injection hole 231 in the electrode 23 illustrated in FIGS. 2
and 3.
[0028]
[Rotating Mechanism 3]
The rotating mechanism 3 includes, for example, a rotor 32 including a
15 container holder 33 attached thereto, and a motor 31 that rotates the rotor 32. FIG. 5
is a diagram illustrating a configuration example of the container holder 33
illustrated in FIG. I. A method of attaching the sample container 2 to the rotating
mechanism 3 is not pmticularly limited. For example, as illustrated in FIG. 5, the
sample container 2 can be arranged such that a rotation axis thereof becomes parallel
20 to an installation surface.
[0029]
In this case, the electrode 22 is connected with the measurement unit 4 via a
sliding contact probe 336 and the like, and the electrode 23 is connected with the
measurement unit 4 via a rotation connection member 332 and a sliding contact
25 probe 331. It is noted that the rotation connection member 332 and the sliding
contact probe 331 are fixed to a slide mechanism-mounted base 334, thereby
enabling their positions to be adjusted.
[0030]
A gear 333 is attached to the rotation connection member 332, so that the
30 rotation connection member 332 is rotated to any angle when a motor drives the gear
333. Furthermore, a leading end of the rotation connection member 332 has a shape
SP349572WOOO
I 1/26
similar to that of a driver being fitted into the groove formed on the head of a screw
inserted into the electrode 23. Accordingly, rotation of the rotation connection
member 332 causes the whole sample container 2 containing the electrode 23 and the
electrode 22 to be rotated.
5 [003 I]
Fmthermore, in order to surely bring the rotation connection member 332
into contact with the electrode 23 and obtain a favorable contact state, a spring 335
that assists a pressing force may also be provided between the rotation connection
member 332 and the base 334. Such a configuration can maintain a favorable
10 contact state even during rotation, thereby enabling stable measurement.
[0032]
[Measurement Unit 4]
The measurement unit 4 applies a voltage between a pair of electrodes
installed in the sample container 2, and chronologically measures electrical
15 characteristics of the blood !0. A configuration of the measurement unit 4 is not
particularly limited, and may be appropriately determined according to the electrical
characteristics to be measured. For example, when an alternating voltage is applied
between a pair of electrodes to measure impedance and dielectric constants of the
blood I 0, an impedance analyzer and a network analyzer can also be used as the
20 measurement unit 4.
[0033]
[Analysis Unit 6]
Fwthermore, the electrical characteristic measuring device according to the
present embodiment may include an analysis unit 6 that analyzes the action of a
25 blood coagulation system based on the electrical characteristics of the blood I 0
measured in the measurement unit 4. The analysis unit 6, for example, determines
coagulability and an elevated blood sedimentation level of the blood I 0 based on a
complex dielectric constant spectrum and its fi·equency dispersion of the blood I 0
measured in the measurement unit 4.
30 [0034]
A method for the determination is not particularly limited, and an example
SP349572WOOO
12/26
thereof includes the method disclosed in Patent Literatures I and 2 and proposed by
the present inventor. A specific example thereof includes the determination based
on a difference in the complex dielectric constant spectrum measured in the
coagulation process between the blood added with substances activating or
5 inactivating thrombocytes and the blood without being added with these substances.
[0035]
[Operation]
Next, operation of the electrical characteristic measuring device according
to the present embodiment will be described. When electrical characteristics of the
10 blood I 0 are measured using the electrical characteristic measuring device according
to the present embodiment, the sample container 2 is firstly filled with the blood 10
to be measured. At that time, for example, while the electrode 22 is insetted into
the container body 21 to block the bottom end, the electrode 23 is not fully inserted,
and is inserted to a degree that allows a space larger than an injected volume of the
15 blood I 0 to be provided.
[0036]
In this state, the blood 10 is injected through the blood injection hole 23 I,
and the stopper 24 is fitted into the blood injection hole 231 as necessary.
Thereafter, the electrode 23 is pressed into the container body 2 I. Accordingly, air
20 remained in the container can be easily released without allowing the blood I 0 to
leak out.
[0037]
Next, the sample container 2 is attached to the container holder 33, and the
electrodes 22 and 23 are connected with the measurement unit 4. Then, the blood
25 I 0 is electrically measured while the sample container is rotated to any angle by the
rotating mechanism 3. At this time, a rotation pattern of the sample container is not
particularly limited. Although continuous rotation may be possible, the sample
container is preferably intermittently rotated so that measurement is performed while
it is not rotated, fi·om the viewpoint of the stability of electrical connection.
30 [0038]
The rotation of the sample container 2 may be unidirectional, or may
SP349572WOOO
13/26
alternate between forward rotation and reverse rotation. However, the stopper 24
having a screw shape preferably rotates in a direction that the screw is tightened.
Also, the rotation angle of the intermittent rotation is most suitably, but not limited to,
180°, and may be other than 180°.
5 [0039]
At this time, the measurement unit 4 chronologically measures electrical
characteristics such as a complex dielectric constant and a frequency dispersion
thereof, starting from when an order to initiate measurement is received or when
power is input. For example, in order to measure the complex dielectric constant of
10 the blood 10, the measurement unit 4 applies an alternating voltage between the
electrode 22 and the electrode 23, and measures impedance at predetermined
intervals. A method of calculating a complex dielectric constant fi·om the measured
impedance is not patticularly limited, and any known function and relational formula
may be used.
15 [0040]
Also, the complex dielectric constant can be converted into complex
impedance, complex admittance, complex capacitance, complex conductance and the
like, through simple conversion of an electrical quantity. Information obtained by
analyzing these convetted results is equivalent to information obtained by analyzing
20 the complex dielectric constant.
[0041]
Thereafter, the analysis unit 6 determines coagulability and an elevated
blood sedimentation level of the blood I 0 as necessary. Also, the determination
results in the analysis unit 6 and the measurement results in the measurement unit 4
25 can be output to a printer (not shown) for printing, and can be output to a display
apparatus (not shown) for displaying.
[0042]
The electrical characteristic measurmg device according to the present
embodiment chronologically measures electrical characteristics of blood while the
30 sample container is rotated by the rotating mechanism. Therefore, the influence of
blood sedimentation can be reduced compared to in existing methods. This enables
SP349572WOOO
14/26
electrical characteristics of blood to be accurately measured.
[0043]
Fwthermore, the electrical characteristic measuring device according to the
present embodiment can evaluate an elevated degree of blood sedimentation without
5 adopting other methods, thereby saving time and labor for conducting a test. A
simple evaluation method of the contribution degree of erythrocytes to enhanced
coagulation has not existed. However, the use of the electrical characteristic
measuring device according to the present embodiment enables such evaluation.
10
[0044]
Specifically, centrifugation or the like is used to adjust specimen samples
having different hematocrit values, and blood coagulation is dielectrically measured.
As the hematocrit value increases,· the blood coagulation time becomes shmter.
Furthermore, as this decrease rate is higher, the contribution of erythrocytes to
enhanced blood coagulation is higher. At this time, for evaluation of the decrease
15 rate, a negative tilt of a liner equation may be simply used, or a fitting parameter
obtained by more accurately fitting in a certain function expression may be used.
[0045]
Also, since the method using centrifugation takes time and labor, a simple
evaluation method may also be used in which the contribution of erythroc)1es to
20 enhanced blood coagulation is estimated fi·mn a diftcrence in the blood coagulation
time of the whole blood of a blood specimen used as it is, between when measured
while inhibiting blood sedimentation and when measured without inhibiting blood
sedimentation. However, in such a case, since the above-described difference is
affected by the occurrence level of blood sedimentation, correction may be necessary
25 based on the elevated degree of blood sedimentation.
[0046]
It is noted that this elevated degree of blood sedimentation can be quantified
with a peak of the dielectric constant change by blood sedimentation, which occurs
around several kHz to several hundred kHz and is observed in the dielectric blood
30 sedimentation measurement without inhibiting blood sedimentation.
[0047]
SP349572WOOO
15/26
As described above, the electrical characteristic measuring device according
to the present embodiment accomplishes a new blood coagulation measurement
method that can evaluate risk of thrombosis. Accordingly, even a specimen of a
patient having significant elevated blood sedimentation due to various factors such as
5 infections can be accurately evaluated for blood coagulability. In addition, since a
patient having high risk of thrombosis is considered to have a certain fundamental
disease in many cases, the present disclosure is a technology that is important in
clinical applications.
[0048]
10 <2. Second Embodiment>
Next, an electrical characteristic measuring device according to a second
embodiment of the present disclosure will be described. In the above-described
first embodiment, both ends of the container body are blocked with a pair of
electrodes. However, the present disclosure is not limited to this configuration, and
15 one of the pair of electrodes may be installed so as to be in contact with blood as
long as the other blocks one end of the container body. That is, the sample
container may be an open system in which the upper end is not blocked.
[0049]
FIG. 6 is a diagram illustrating an arrangement example of the sample
20 container in the electrical characteristic measuring device according to the present
embodiment. It is noted that in FIG. 6, components other than the sample container
20 and the measurement unit 4 are omitted for simplification of the diagram. As
illustrated in FIG. 6, the sample container 20 being an open system is used in the
electrical characteristic measuring device according to the present embodiment.
25 [0050]
[Sample Container 20]
In the sample container 20, a bottom end of the container body 21 is blocked
with the electrode 22, while an upper end of the container body ·21 is open.
Furthermore, an electrode 25 is installed so as to be in contact with the blood I 0 to
30 be measured. These electrodes 22 and 25 are each connected with the measurement
unit 4 via a cable or the like.
l
SP349572WOOO
16/26
[0051]
[Operation]
In the electrical characteristic measuring device according to the present
embodiment, the sample container 20 is installed so as to tilt to a degree that the
5 blood I 0 does not spill. The angle may be appropriately set depending on an
injected amount of the blood I 0. For example, the sample container 20 can be
installed such that the rotation axis has a tilt angle of 45° or less with respect to an
installation surface. Then, electrical characteristics of blood are chronologically
measured while the sample container is rotated at any angle by the rotating
10 mechanism, in a similar manner to the above-described first embodiment.
[0052]
Accordingly, the sample container can have a configuration in which sealing
is not necessary while the influence of blood sedimentation is eliminated. As a
result, for example, blood can be easily injected, thereby improving workability. It
15 is noted that the configuration, action and effect other than the above of the electrical
characteristic measuring device according to the present embodiment are similar to
those of the above-described first embodiment.
[0053]
Additionally, the present technology may also be configured as below.
20 (I)
An electrical characteristic measuring device including:
a rotating mechanism that rotates a sample container to be filled with blood
to be measured, to any angle; and
a measurement unit that applies a voltage between a pair of electrodes
25 installed in the sample container, and chronologically measures electrical
characteristics of the blood.
(2)
The electrical characteristic measuring device according to (I),
wherein the rotating mechanism intermittently rotates the sample container.
30 (3)
The electrical characteristic measuring device according to (I) or (2),
"· 3.·.·····/~
~/
SP349572WOOO
17/26
wherein the rotating mechanism alternates between forward rotation and
reverse rotation.
(4)
The electrical characteristic measuring device according to any one of (I) to
5 (3),
10
wherein the measurement unit applies an alternating voltage between the
pair of electrodes, and measures one or both of impedance and a dielectric constant
ofthe blood.
(5)
The electrical characteristic measuring device according to any one of (I) to
(4),
wherein the sample container includes
a tubular container body made of insulating material,
a first electrode that is made of conductive material and blocks one
15 end of the container body, and
20
25
a second electrode that is made of conductive material and ts
arranged so as to be in contact with the blood.
(6)
The electrical characteristic measuring device according to (5),
wherein the other end of the container body is blocked by the second
electrode, and
wherein a space constituted by the first electrode, the second electrode and
the container body is filled with the blood.
(7)
(8)
The electrical characteristic measuring device according to (5) or (6),
wherein the second electrode is provided with a blood injection hole.
The electrical characteristic measuring device according to (7),
wherein the sample container is made of conductive material and includes a
30 stopper that is titled into the blood injection hole.
(9)
(I 0)
5
(II)
(I 0),
SP349572WOOO
18/26
The electrical characteristic measuring device according to claim 8,
wherein the stopper is a screw stopper.
The electrical characteristic measuring device according to (8),
wherein the stopper is provided with a vent.
The electrical characteristic measuring device according to any one of (I) to
wherein the sample container is arranged in a manner that a rotation axis of
10 the sample container is parallel to or forms a tilt angle of 45° or less with respect to
an installation surface.
15
20
(12)
The electrical characteristic measuring device according to any one of (I) to
(II), fmiher including:
an analysis unit that analyzes an action of a blood coagulation system on the
basis of the electrical characteristics ofthe blood measured in the measurement unit.
[Example]
[0054]
Hereinafter, effects of the present disclosure will be specifically described.
In the present embodiment, the effect of inhibiting blood sedimentation was
confirmed using sample blood of healthy persons and patients having significant
blood sedimentation.
[0055]
25 (!)Blood Collection
Using a vacuum blood collection tube in which sodium citrate was treated
as an anti-coagulant agent, blood was collected from each of healthy persons and
patients having significant blood sedimentation to obtain a specimen blood.
[0056]
30 (2) Dielectric Measurement
To the specimen blood that was thermally insulated at 37"C, 0. 25 M
SP349572WOOO
19/26
aqueous calcium chloride solution was added at a concentration of85 ~tL per I mL of
blood immediately before the statt of measurement, to initiate a blood coagulation
reaction. Then, measurement was performed for 60 minutes under the conditions of
a measurement temperature of 37°C, a measurement fi·equency range of 40 to I I 0
5 MHz, and a measurement interval of one minute.
[0057]
An apparatus having a configuration illustrated in FIG. I was used for the
measurement. Specifically, an impedance analyzer ( 4294A) manufactured by
Agilent Technologies Inc. was used as the measurement unit 4. Then, a probe kit
10 ( 4294 lA) was connected to the impedance analyzer ( 4294A), and a rebuilt highfi-
equency coaxial conversion adapter (a conversion adapter from SMA to APC7) was
fmther connected to a leading end of the probe kit.
[0058]
One of the electrodes 22 and 23 of the sample container 2 was connected
15 with an inner conductor of the rebuilt coaxial adapte1; and the other was contactconnected
with an outer conductor of the rebuilt adapter. This enabled broadband
measurement containing a high-fi·equency range. Then, measurement was
performed while the sample container 2 was rotated to 180° in forward and reverse
directions by motor drive. It is noted that although the probe kit (42941A) was
20 twisted at I 80° and straightened back every time the sample container 2 was rotated,
no influence was exerted on the measurement.
[0059]
FIG. 7 is a dielectric spectrum of the blood in which elevated blood
sedimentation is not observed, and FIG. 8 is the data at 760 kHz. Also, FIG. 9 is a
25 dielectric spectrum of the blood in which elevated blood sedimentation is significant,
FIG. I 0 is the data at 760 kHz, and FIG. I I is the data at I 0. 7 MHz. Furthermore,
FIG. 12 is a dielectric spectrum measured while rotating the blood in which elevated
blood sedimentation is significant, FIG. I 3 is the data at 760 kHz, and FIG. 14 is the
data at I 0. 7 MHz.
30 (0060]
As illustrated in FIG. 7 and FIG. 8, in the blood in which elevated blood
·.--..-. ;;;J--v····· ffiii/
SP319572WOOO
20/26
sedimentation is not observed, peak (i) by rouleaux formation of erythrocytes is
firstly observed, and thereafter peak (ii) by blood coagulation is obtained. In this
case, the time when peak (ii) is provided can be defined as a "blood coagulation
time".
5 [0061 l
On the other hand, as illustrated in FIG. 9, when blood sedimentation is
significant, the peak of the change in a dielectric constant by blood sedimentation
appears in several kHz to several hundred kHz. Also, as illustrated in FIG. 10, the
dielectric constant at 760 kHz decreases after the first peak attributable to rouleaux of
10 erythrocytes is observed, and the second peak related to blood coagulation becomes
difficult to distinguish.
[0062]
On the contrary, FIGS. II to 14 arc data obtained by measuring a blood
sedimentation process while repeating forward rotation and reverse rotation at an
15 angle of 180° every one minute to inhibit blood sedimentation. These data arc
results of the measurement performed with the same blood specimen as for the data
illustrated in FIGS. 9 and I 0 on the same experiment day. The comparison between
the both data enables the effect of inhibiting the blood sedimentation by the rotation
of the sample container 2 to be studied.
20 [0063]
Specifically, the peak appearing due to blood sedimentation observed in the
range of several kHz to several hundred kHz in the dielectric spectrum illustrated in
FIG. 9 disappeared in the dielectric spectrum illustrated in FIG. 12. Also, in the
dielectric constant at 760 kHz illustrated in FIG. 13, the peak (i) by rouleaux of
25 erythrocytes was relatively suppressed, and the peak (ii) by blood coagulation was
able to be clearly distinguished.
[0064]
Furthermore, data around I 0 MHz can be used to evaluate a blood
coagulation time and the like. When comparing the dielectric constant at I 0.7 MHz
30 between the result measured while inhibiting blood sedimentation by the rotation of
the sample container 2 (FIG. 14) and the result measured without the rotation (FIG.
SP349572WOOO
21/26
II), the step-like change by blood coagulation occurs for a shorter time when
measured while rotating the sample container 2. That is, the blood coagulation time
is shmter when measured while inhibiting blood sedimentation by the rotation of the
sample container 2 than when measured without the rotation. This phenomenon
5 was almost commonly observed with minor differences even in other specimens in
which blood sedimentation is significant.
[0065]
Furthermore, the use of these data also enables evaluation of an elevated
blood sedimentation degree. As described above, when blood sedimentation occurs,
10 an increase in a dielectric constant is observed in the range of several kHz to several
hundred kHz, and the amount of this increase can be used as an index of blood
sedimentation. Furthermore, when measurement is performed without adding
calcium to a specimen blood, blood coagulation does not occur, thereby enabling
only the influence of blood sedimentation to be measured.
15 [0066]
20
25
The above results clearly show that according to the present disclosure, the
influence of blood sedimentation can be reduced, and electrical characteristics of
blood can be accurately measured.
Reference Signs List
[0067]
electrical characteristic measuring device
2,20 sample container
3 rotating mechanism
4 measurement unit
5 constant temperature bath
6 analysis unit
10 blood
21 container body
30 22,23,25 electrode
24 stopper
SP349572WOOO
22/26
31 motor
32 rotor
33 container holder
221 contact region
5 231 blood injection hole
232 notch
241 vent
331, 336contact probe
332 rotation connection member
10 333 gear
334 base
335 spnng
SP349572WOOO
23/26
CLAIMS
Claim 1
An electrical characteristic measuring device comprising:
a rotating mechanism that rotates a sample container to be filled with blood
5 to be measured, to any angle; and
a measurement unit that applies a voltage between a pair of electrodes
installed in the sample container, and chronologically measures electrical
characteristics of the blood.
10 Claim 2
15
20
Claim 3
The electrical characteristic measuring device according to claim 1,
wherein the rotating mechanism intermittently rotates the sample container.
The electrical characteristic measuring device according to claim I,
wherein the rotating mechanism alternates between forward rotation and
reverse rotation.
Claim 4
The electrical characteristic measuring device according to claim I,
wherein the measurement unit applies an alternating voltage between the
pair of electrodes, and measures one or both of impedance and a dielectric constant
of the blood.
25 Claim 5
The electrical characteristic measuring device according to claim I,
wherein the sample container includes
a tubular container body made of insulating material,
a first electrode that is made of conductive material and blocks one
30 end of the container body, and
a second electrode that 1s made of conductive material and is
SP349572WOOO
24/26
arranged so as to be in contact with the blood.
Claim 6
The electrical characteristic measuring device according to claim 5,
5 wherein the other end of the container body is blocked by the second
electrode, and
wherein a space constituted by the first electrode, the second electrode and
the container body is filled with the blood.
10 Claim 7
15
20
25
Claim 8
The electrical characteristic measuring device according to claim 6,
wherein the second electrode is provided with a blood injection hole.
The electrical characteristic measuring device according to claim 7,
wherein the sample container is made of conductive material and includes a
stopper that is fitted into the blood injection hole.
Claim 9
The electrical characteristic measuring device according to claim 8,
wherein the stopper is a screw stopper.
Claim I 0
Claim II
The electrical characteristic measuring device according to claim 8,
wherein the stopper is provided with a vent.
The electrical characteristic measuring device according to claim I,
wherein the sample container is arranged in a manner that a rotation axis of
30 the sample container is parallel to or forms a tilt angle of 45° or less with respect to
an installation surface.
5
SP349572WOOO
25/26
Claim 12
The electrical characteristic measuring device according to claim I, fwther
comprising:
an analysis unit that analyzes an action of a blood coagulation system on the
basis of the electrical characteristics of the blood measured in the measurement unit.