阅读说明：本技术 血液净化装置和血液净化方法 (Blood purification device and blood purification method ) 是由 长野敬 北川寿美子 菊池俊秋 野口智弘 于 2020-01-29 设计创作，主要内容包括：本发明提供一种能够确认磁性颗粒是否从血液中分离并去除的血液净化装置等。血液净化装置(1A)包括供血液(10)流经的主流路(20),通过磁力回收血液(10)中所含的磁性颗粒的磁性提取部(30)(磁性提取部件),和用于检测血液(10)中磁性颗粒的存在的至少一个磁性传感器(40)。磁性颗粒在其外周部的至少一部分中具有能被能够捕获血液(10)中的特定物质的被分离成分捕获物质所改性的改性部。(The invention provides a blood purification device and the like capable of confirming whether magnetic particles are separated from blood and removed. A blood purification device (1A) is provided with a main channel (20) through which blood (10) flows, a magnetic extraction unit (30) (magnetic extraction means) which recovers magnetic particles contained in the blood (10) by magnetic force, and at least one magnetic sensor (40) which detects the presence of the magnetic particles in the blood (10). The magnetic particles have, in at least a part of the outer periphery thereof, a modified portion capable of being modified by a substance capable of capturing a specific substance in blood (10) and being separated into components.)

1. A blood purification device comprising:

a main flow path for blood flow;

a magnetic extraction means for recovering magnetic particles contained in the blood by magnetic force; and

at least one magnetic sensor capable of detecting the presence of said magnetic particles in said blood,

the magnetic particles have, in at least a part of the outer periphery thereof, a modified portion capable of being modified by a substance capable of capturing a specific substance in the blood,

the magnetic extraction means purifies blood by extracting the specific substance from blood by recovering the magnetic particles having captured the specific substance.

2. The blood purification apparatus according to claim 1, wherein at least one of the magnetic sensors is provided at a later stage of the magnetic extraction means.

3. The blood purification apparatus according to claim 2, wherein the magnetic sensor is provided in a preceding stage of the magnetic extraction means.

4. A blood purification device according to any one of claims 1 to 3, comprising:

a first channel selection member that is disposed in the main channel at a stage preceding the magnetic extraction member and selects a destination of the blood;

a second channel selection member that is disposed downstream of the magnetic extraction member in the main channel and selects a destination of the blood; and

a return flow path provided between the first flow path selection member and the second flow path selection member.

5. The blood purification apparatus according to claim 4, wherein a magnetic sensor is provided in the main channel at a stage subsequent to the second channel selection member.

6. The blood purification apparatus according to claim 4 or 5, further comprising:

a control section connected to the magnetic sensor, the first flow path selection member, and the second flow path selection member,

the control portion controls at least one of the first flow path selection member and the second flow path selection member in response to an output of the magnetic sensor.

7. The blood purification apparatus according to any one of claims 1 to 6, wherein the magnetic sensor is a magnetoresistive element that is disposed outside the flow path and does not come into contact with the blood.

8. The blood purification apparatus according to any one of claims 1 to 6, wherein the magnetic sensor is a coil-type sensor that is disposed outside the flow path and does not come into contact with the blood.

9. The blood purification device according to any one of claims 1 to 6, wherein the magnetic sensor is a Hall sensor that is disposed outside the flow path and does not come into contact with the blood.

10. The blood purification apparatus according to any one of claims 1 to 9,

the magnetic extraction means has magnetic field generation means for generating a magnetic field for recovering the magnetic particles,

the magnetic field generating member is disposed outside the flow path at a position not in contact with the blood.

11. The blood purification device according to any one of claims 1 to 10, wherein the temperature of the entire device is maintained at a constant temperature or within a specific temperature range.

12. The blood purification apparatus according to any one of claims 1 to 11, further comprising a verification section for determining whether the magnetic sensor is functioning properly.

13. A method for purifying blood, wherein,

causing blood containing magnetic particles modified by a substance for trapping a component to be separated which can trap a specific substance in the blood to flow into a main channel through which the blood can flow,

recovering at least a portion of the magnetic particles contained in the blood by means of a magnetic extraction means capable of generating a magnetic field,

detecting whether the magnetic particles remain in the blood after recovering at least a part of the magnetic particles by the magnetic extraction means by at least one magnetic sensor capable of detecting the presence of the magnetic particles.

Technical Field

The present disclosure relates to a blood purification apparatus and a blood purification method. .

The present application claims priority based on japanese patent application special application 2019-.

Background

As a method for removing disease-causing pathogenic substances from blood, methods using centrifugation, membrane separation, adsorption column separation, and the like are known. Further, a blood purification device is known which recovers magnetic particles by utilizing magnetism by mixing fine particles (magnetic particles) which have magnetism and can adsorb pathogenic substances in blood into blood (for example, see patent document 1).

Documents of the prior art

Patent document

Patent document 1: japanese patent No. 4485380

Disclosure of Invention

However, in the conventional blood purification apparatus using magnetic particles, the mechanism for confirming that the magnetic particles have been removed is insufficient, and there is a risk that the magnetic particles may remain in the purified blood.

Therefore, there is a problem that the purified blood cannot be safely returned to the body.

Accordingly, an object of the present disclosure is to provide a blood purification apparatus and a blood purification method capable of confirming separation and removal of magnetic particles from blood.

The technique according to the present disclosure includes the following aspects.

[1] A blood purification device comprising:

a main flow path for blood flow;

a magnetic extraction means for recovering magnetic particles contained in the blood by magnetic force; and

at least one magnetic sensor capable of detecting the presence of said magnetic particles in said blood,

the magnetic particles have, in at least a part of the outer periphery thereof, a modified portion capable of being modified by a substance capable of capturing a specific substance in the blood,

the magnetic extraction means purifies blood by extracting the specific substance from blood by recovering the magnetic particles having captured the specific substance.

[2] The blood purification apparatus according to [1], wherein at least one of the magnetic sensors is provided at a later stage of the magnetic extraction means.

[3] The blood purification apparatus according to [2], wherein the magnetic sensor is provided at a preceding stage of the magnetic extraction means.

[4] The blood purification apparatus according to any one of [1] to [3], comprising:

a first channel selection member that is disposed in the main channel at a stage preceding the magnetic extraction member and selects a destination of the blood;

a second channel selection member that is disposed downstream of the magnetic extraction member in the main channel and selects a destination of the blood; and

a return flow path provided between the first flow path selection member and the second flow path selection member.

[5] The blood purification apparatus according to [4], wherein a magnetic sensor is provided in the main channel at a stage subsequent to the second channel selection member.

[6] The blood purification apparatus according to [4] or [5], wherein,

further comprising: a control section connected to the magnetic sensor, the first flow path selection member and the second flow path selection member,

the control portion controls at least one of the first flow path selection member and the second flow path selection member in response to an output of the magnetic sensor.

[7] The blood purification apparatus according to any one of [1] to [6], wherein the magnetic sensor is a magnetoresistive element that is disposed outside the channel and does not come into contact with the blood.

[8] The blood purification apparatus according to any one of [1] to [6], wherein the magnetic sensor is a coil-type sensor that is disposed outside the flow path and does not come into contact with the blood.

[9] The blood purification apparatus according to any one of [1] to [6], wherein the magnetic sensor is a Hall sensor that is disposed outside the channel and does not come into contact with the blood.

[10] The blood purification apparatus according to any one of [1] to [9], wherein the magnetic extraction member has a magnetic field generation member for generating a magnetic field for recovering the magnetic particles, and the magnetic field generation member is disposed at a position outside the channel where the magnetic field generation member does not contact the blood.

[11] The blood purification apparatus according to any one of [1] to [10], wherein the temperature of the entire apparatus is maintained at a constant temperature or within a specific temperature range.

[12] The blood purification apparatus according to any one of [1] to [11], further comprising a verification unit for determining whether or not the magnetic sensor is operating correctly.

[13] A method for purifying blood, wherein,

causing blood containing magnetic particles modified by a substance for trapping a component to be separated which can trap a specific substance in the blood to flow into a main channel through which the blood can flow,

recovering at least a portion of the magnetic particles contained in the blood by means of a magnetic extraction means capable of generating a magnetic field,

detecting whether the magnetic particles remain in the blood after recovering at least a part of the magnetic particles by the magnetic extraction means by at least one magnetic sensor capable of detecting the presence of the magnetic particles.

According to the present disclosure, a technique for confirming separation and removal of magnetic particles from blood may be provided.

Drawings

Fig. 1A is a schematic diagram schematically illustrating the configuration of a top view of a blood purification apparatus 1A according to a first embodiment of the present disclosure.

Fig. 1B is a schematic diagram schematically showing another configuration of the blood purification apparatus 1A according to the first embodiment of the present disclosure.

Fig. 2A is a schematic diagram schematically illustrating a configuration of a plan view of a blood purification apparatus 1B according to a second embodiment of the present invention.

Fig. 2B is a schematic diagram schematically showing another configuration of a blood purification apparatus 1B according to a second embodiment of the present invention.

Fig. 3A is a schematic diagram schematically showing a configuration of a plan view of a blood purification apparatus 1C according to a third embodiment of the present invention.

Fig. 3B is a schematic diagram schematically showing another configuration of a blood purification apparatus 1C according to a third embodiment of the present disclosure.

Fig. 4A is a schematic diagram schematically illustrating a configuration of a plan view of a blood purification apparatus 1D according to a fourth embodiment of the present invention.

Fig. 4B is a schematic diagram schematically illustrating another configuration of a blood purification apparatus 1D according to a fourth embodiment of the present disclosure.

Fig. 5A is a schematic diagram schematically illustrating a configuration of a plan view of a blood purification apparatus 1E according to a fifth embodiment of the present invention.

Fig. 5B is a schematic diagram schematically illustrating another configuration of a blood purification apparatus 1E according to a fifth embodiment of the present disclosure.

Fig. 6A is a schematic diagram schematically showing the structure of a plan view of a blood purification apparatus 1F according to a sixth embodiment of the present invention.

Fig. 6B is a schematic diagram schematically showing another structure of a blood purification apparatus 1F according to a sixth embodiment of the present invention.

Detailed Description

Hereinafter, embodiments in which the technology according to the present disclosure can be implemented will be described in detail with reference to the accompanying drawings. In the drawings used in the following description, a characteristic portion may be shown enlarged for convenience, and a dimensional ratio or the like of each constituent member is not limited to that shown in the drawings.

[ blood purification device ]

(first embodiment)

Fig. 1A and 1B are plan views showing the configuration of a blood purification apparatus 1A according to a first embodiment of the present disclosure. In the present embodiment, a case where the path through which blood flows does not include the return channel will be described as an example.

As illustrated in fig. 1A, the blood purification apparatus 1A includes: a main channel 20 through which blood 10 flows, a magnetic extraction unit 30 (magnetic extraction means) for collecting magnetic particles contained in blood 10, and a magnetic sensor 40 and a magnetic sensor 41 for detecting the presence of magnetic particles in blood 10.

The blood purification apparatus 1A further includes a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

The magnetic extraction portion 30, the magnetic sensor 40, and the magnetic sensor 41 are disposed in contact with the main channel 20. The magnetic sensor 40 and the magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1A, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is two, and may be one or three or more.

The blood 10 containing the magnetic particles flows into the main channel 20 from the connection port 2. After the magnetic particles contained in the blood 10 are collected by the magnetic extraction unit 30, the magnetism of the blood 10 is measured by the magnetic sensor 40, and as a result, it is possible to determine whether or not the magnetic particles are contained in the blood 10. Subsequently, the blood 10 passes through the filter 50, and it is determined whether the blood 10 contains magnetic particles by the magnetic sensor 41. Then, the blood 10 having passed through the filter 50 flows out from the connection port 3.

The filter 50 can capture magnetic particles contained in the blood 10 and foreign substances contained in the blood 10, etc., which are not removed by the magnetic extraction section 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, the magnetic particles can be collected from blood by taking out the magnetic particles into a channel connected to the main channel 20, or by collecting the magnetic particles with a collecting unit provided on the inner wall of the main channel 20.

The magnetic extraction section 30 may have a magnetic field generating means (not shown) for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40 and the magnetic sensor 41 can detect the presence of magnetic particles by detecting a leakage magnetic field generated by magnetic particles in blood flowing through the main channel 20.

Preferably, the magnetic sensor 40 and the magnetic sensor 41 are disposed outside the main channel 20 and do not contact the blood 10. Since the magnetic sensor 40 and the magnetic sensor 41 do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40 and the magnetic sensor 41, known magnetic sensors, for example, a coil type sensor, a hall sensor, or an element using magnetic resistance can be used. It is possible to determine whether or not the blood 10 flowing through the main channel 20 contains magnetic particles using the magnetic measurement values indicated by the magnetic sensor 40 and the magnetic sensor 41.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passing magnetic particles using the induction coil. The coil type sensor has an advantage of easy setup.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element is an element utilizing a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensor 40 and the magnetic sensor 41 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

When it is determined from the measurement values of the magnetic sensor 40 and/or the magnetic sensor 41 that the blood 10 does not contain magnetic particles, the blood flowing out of the connection port 3 can be safely returned into the body.

Further, based on the measurement value of the magnetic sensor 41, it is possible to determine whether or not the blood 10 having passed through the filter 50 contains magnetic particles, and to return the blood 10 into the body more safely.

In this case, for example, by comparing the measurement values of the magnetic sensor 40 and the magnetic sensor 41 with a specific reference value (for example, a reference value relating to safety for the human body), it is possible to determine whether or not the blood 10 contains magnetic particles in an amount harmful to the human body.

Further, a signal for controlling an artificial heart lung device described later may be output from the magnetic sensor 41. According to this configuration, for example, it can be confirmed that the magnetic particles have been sufficiently separated and removed from the blood before the purified blood is returned into the body.

< blood transfusion pump >

The blood purification apparatus 1A may include a blood transfer pump (not shown) for extracting blood from the outside of the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1A, blood 10 containing magnetic particles modified with a substance to be separated and capturing a specific substance in the blood is introduced into the main channel 20 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

The first embodiment of the present disclosure has been explained in detail above, but the technique according to the present disclosure is not limited to the first embodiment, and various modifications and changes can be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the first embodiment, in the blood purification apparatus 1A, the entire apparatus can be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus 1A may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

Further, as illustrated in fig. 1B, the blood purification apparatus 1A may further include: and a verification unit 90 for determining whether or not the magnetic sensors 40 and 41 are operating correctly. For example, the verification unit 90 is connected to the magnetic sensors 40 and 41, and can determine whether or not the magnetic sensors 40 and 41 are operating correctly based on an output (magnetic value of blood) from the magnetic sensors. At this time, the verification unit 90 may determine the operation of the magnetic sensors 40 and 41 by comparing the outputs from the magnetic sensors 40 and 41 with a specific reference value, for example. As an example, when the outputs from the magnetic sensors 40, 41 are included in a certain range, the verification section 90 may determine that the magnetic sensors 40, 41 are operating correctly. As another example, the verification section 90 may determine that the magnetic sensors 40, 41 are not operating correctly when the outputs from the magnetic sensors 40, 41 exceed a certain upper limit value or fall below a certain lower limit value.

The verification section 90 may be realized by, for example, a circuit element capable of comparing the output from the magnetic sensor with a specific reference value, and may be realized by a combination of a general-purpose arithmetic device (microprocessor) and an appropriate software program. The configuration of the authentication portion 90 is not limited to the above.

The blood purification apparatus 1A is connected to the magnetic sensors 40 and 41, and may further include a control unit 80 (for example, fig. 1B) that determines whether or not the blood 10 contains magnetic particles based on an output of the magnetic sensors. The control unit 80 can check the operating state of the magnetic sensors 40 and 41 determined by the verification unit 90. Thus, the control unit 80 as a safety circuit can check the operation state of the magnetic sensors 40 and 41, and as a result, the control unit 80 can accurately determine whether or not the blood 10 contains magnetic particles.

The control unit 80 may be realized by, for example, a circuit element capable of comparing output values from one or more magnetic sensors with each other, an output value from a magnetic sensor with a specific reference value, or the like, or may be realized by combining a general-purpose arithmetic device (microprocessor) and an appropriate software program. The configuration of the control section is not limited to the above.

The authentication section 90 and the control section 80 may be realized individually by using a plurality of devices, or may be integrated into one device.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components. The specific method for capturing a specific component in blood by a substance to be separated and captured by a component to be separated is not particularly limited, and for example, a chemical bond (molecular biological bond, electric bond (van der waals force, polar attraction, intermolecular force, coulomb force), adsorption, steric structure capture, or the like can be used. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself. Further, the magnetic particles may be embedded in the particulate-formed substance captured by the separated component.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1A is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purification apparatus 1A can extract a specific substance from blood to purify the blood. The blood purifying apparatus 1A may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1A may purify blood taken from an animal in advance without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

(second embodiment)

Fig. 2A and 2B are plan views showing the configuration of a blood purification apparatus 1B according to a second embodiment of the present disclosure. In the present embodiment, a case where the channel through which blood flows includes a return channel will be described as an example.

As illustrated in fig. 2A, the blood purification apparatus 1B includes: a main channel 20, a main channel 21, and a main channel 22 through which blood 10 taken out of the body flows; a magnetic extraction unit 30 (magnetic extraction means) for recovering magnetic particles contained in the blood 10; a magnetic sensor 40 for detecting the presence of magnetic particles in the blood 10, and a magnetic sensor 41. The blood purification apparatus 1B further includes: the return channel 23 for returning the blood 10 is a first channel selection part 61 (first channel selection member) for selecting a destination (flow direction) of the blood, and a second channel selection part 62 (second channel selection member) for selecting a destination of the blood. The blood purification apparatus 1B further includes: a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

The magnetic extraction unit 30 and the magnetic sensor 40 are disposed in contact with the main channel 20, and the magnetic sensor 41 is disposed in contact with the main channel 22. The magnetic sensor 40 and the magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1B, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is two, and may be one or three or more.

In the main channel 20, the first channel selector 61 is disposed at the front stage of the magnetic extractor 30, and the second channel selector 62 is disposed at the rear stage of the magnetic extractor 30. In the blood purification apparatus 1B, the first channel selector 61 and the second channel selector 62 can be operated manually, for example. As another example, the actions of the first flow path selecting section 61 (flow path selector) and the second flow path selecting section 62 (flow path selector) may be controlled by using an appropriate actuator or the like. The first flow path selector 61 and the second flow path selector 62 are, for example, three-way valves.

First, the first channel selector 61 is operated to communicate the main channel 21 with the main channel 20, and the second channel selector 62 is operated to communicate the main channel 20 with the return channel 23. The main flow path 20 and the main flow path 22 are shut off. Subsequently, the blood 10 containing the magnetic particles flows into the main channel 21 from the connection port 2.

After the blood 10 containing the magnetic particles flows from the connection port 2, the first channel selection part 61 is operated to communicate the main channel 20 with the return channel 23. At this time, the second channel selector 62 continues to put the main channel 20 and the return channel 23 in a state of communicating with each other.

The blood 10 circulates through the main channel 20 and the return channel 23. During this time, the magnetic particles are recovered by the magnetic extraction portion 30, and the magnetism generated by the blood 10 is measured by the magnetic sensor 40.

When it is determined that the blood 10 flowing through the main channel 20 contains magnetic particles based on the measurement value indicated by the magnetic sensor 40, the first channel selector 61 and the second channel selector 62 continue to bring the main channel 20 and the return channel 23 into communication with each other. When the blood 10 containing the magnetic particles flows back in the main channel 20 and the return channel 23, the magnetic particles contained in the blood 10 are collected by the magnetic extraction unit 30.

When it is determined that the blood 10 flowing through the main channel 20 does not contain magnetic particles based on the measurement value indicated by the magnetic sensor 40, the first channel selection unit 61 operates the second channel selection unit 62 to communicate the main channel 20 with the main channel 22 while continuing to communicate the main channel 20 with the return channel 23.

Then, the blood 10 flows into the main flow path 22 and passes through the filter 50. After the magnetic sensor 41 determines whether or not the blood 10 contains magnetic particles, the blood 10 flowing through the main channel 22 flows out from the connection port 3.

When it is determined from the measurement values of the magnetic sensor 40 and/or the magnetic sensor 41 that the blood 10 does not contain magnetic particles, the blood flowing out of the connection port 3 can be safely returned to the body. Further, based on the measurement value of the magnetic sensor 41, it can be determined whether or not the blood 10 after passing through the filter 50 contains magnetic particles, and the blood 10 can be returned to the body more safely.

Further, a signal for controlling an artificial heart lung device described later may be output from the magnetic sensor 41. According to this configuration, it can be confirmed that the magnetic particles have been sufficiently separated and removed from the blood before the purified blood is returned into the body.

The filter 50 can capture magnetic particles contained in the blood 10 and foreign substances contained in the blood 10, etc., which cannot be removed by the magnetic extraction unit 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, magnetic particles can be recovered from blood by: the magnetic particles are taken out into a flow path connected to the main flow path 20, or the magnetic particles are collected by a collecting unit provided on the inner wall of the main flow path 20.

The magnetic extraction section 30 may have a magnetic field generating means (not shown) for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40 can detect the presence of magnetic particles by detecting a leakage magnetic field generated by magnetic particles in blood flowing through the main channel 20. The magnetic sensor 41 can detect the presence of magnetic particles by detecting a leakage magnetic field generated by magnetic particles in blood flowing through the main channel 22.

Preferably, the magnetic sensor 40 is disposed outside the main channel 20, and the magnetic sensor 41 is disposed outside the main channel 22 so as not to contact the blood 10. Since the magnetic sensor 40 and the magnetic sensor 41 do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40 and the magnetic sensor 41, known magnetic sensors, for example, a coil type sensor, a hall sensor, or an element using a magnetic resistance can be used. It is possible to determine whether or not the blood 10 flowing through the main channel 20 contains magnetic particles from the magnetic measurement values indicated by the magnetic sensor 40 and the magnetic sensor 41.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passed magnetic particles by the induction coil. The coil type sensor has an advantage of easy installation.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element utilizes a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensor 40 and the magnetic sensor 41 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

< blood transfusion pump >

The blood purification apparatus 1B may be connected to a blood pump (not shown) capable of flowing blood. Blood delivery pumps may be used, for example, to withdraw blood from outside the body or to circulate blood withdrawn from outside the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1B, blood 10 containing magnetic particles modified with a substance to be separated and capable of capturing a specific substance in the blood is introduced into the main flow paths 20, 21, and 22 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

The second embodiment of the technique of the present disclosure has been described above in detail, but the technique according to the present disclosure is not limited to the second embodiment, and various modifications and changes can be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the second embodiment, in the blood purification apparatus 1B, the entire apparatus can be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

Further, as illustrated in fig. 2B, the blood purification apparatus 1B may further include: and a verification unit 90 for determining whether or not the magnetic sensors 40 and 41 are operating correctly. For example, the verification unit 90 is connected to the magnetic sensors 40 and 41, and can determine whether or not the magnetic sensors are operating correctly based on the output (magnetic value of blood) from the magnetic sensors. For example, the authentication unit 90 according to the second embodiment may be configured in the same manner as the authentication unit 90 according to the first embodiment.

The blood purification apparatus 1B may be connected to the magnetic sensors 40 and 41, and may further include a controller 80 (for example, fig. 2B) that determines whether or not the blood 10 contains magnetic particles based on an output of the magnetic sensors. The control unit 80 can check the operating state of the magnetic sensors 40 and 41 determined by the verification unit 90. For example, the control unit 80 of the second embodiment may be configured in the same manner as the control unit 80 of the first embodiment described above. Thus, the control unit 80 as a safety circuit can confirm the operation of the magnetic sensors 40 and 41, and thereby can accurately determine whether or not the blood 10 contains magnetic particles.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components. The specific method for capturing a specific component in blood by a substance to be separated and captured by a component to be separated is not particularly limited, and for example, a chemical bond (molecular biological bond, electric bond (van der waals force, polar attraction, intermolecular force, coulomb force), adsorption, steric structure capture, or the like can be used. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1B is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purifying apparatus 1B can purify blood by extracting a specific substance from blood. The blood purifying apparatus 1B may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1B may purify blood taken in advance from an animal without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

(third embodiment)

Fig. 3A and 3B are plan views showing the configuration of a blood purification apparatus 1C according to a third embodiment of the present disclosure. In the present embodiment, a case where the channel through which blood flows includes the return channel and the return channel is zigzag will be described as an example.

As illustrated in fig. 3A, the blood purification apparatus 1C includes: a main channel 20, a main channel 21, and a main channel 22 through which blood 10 flows; a magnetic extraction unit 30 (magnetic extraction means) for recovering magnetic particles contained in the blood 10; and a magnetic sensor 40 for detecting the presence of magnetic particles in the blood 10 and a magnetic sensor 41. The blood purification apparatus 1C further includes: the return channel 23 for returning the blood 10, a first channel selector 61 (first channel selector member) for selecting a channel, and a second channel selector 62 for selecting a channel. The blood purification apparatus 1C further includes: a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

The magnetic extraction unit 30 and the two magnetic sensors 40 and 40 are disposed in contact with the main channel 20, and the magnetic sensor 41 is disposed in contact with the main channel 22. Two magnetic sensors 40, 40 and a magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1C, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is three, and one or two or four or more magnetic sensors may be provided.

In the blood purification apparatus 1C, for example, in a side view of the main channel 20, two magnetic sensors 40 and 40 provided in the main channel 20 are attached in a state of being offset from the axis of the magnetic extraction unit 30. Further, the two magnetic sensors 40, 40 are also mounted in a state of being off-axis from each other. In this way, the two magnetic sensors 40, 40 are configured not to be affected by the magnetic field generated by the magnetic extraction section 30.

In the blood purification apparatus 1C, by providing two magnetic sensors 40, the magnetism of the blood 10 can be measured more accurately by using two measurement values of the two magnetic sensors 40, 40. Further, with this configuration, malfunction of the magnetic sensor 40 is less likely to occur, and the measurement accuracy of the magnetic sensor 40 can be improved.

In the main channel 20, the first channel selector 61 is disposed at the front stage of the magnetic extractor 30, and the second channel selector 62 is disposed at the rear stage of the magnetic extractor 30. In the blood purification apparatus 1C, the first channel selector 61 and the second channel selector 62 can be operated manually, for example. As another example, the operations of the first flow path selecting portion 61 and the second flow path selecting portion 62 may be controlled by using an appropriate actuator or the like. The first flow path selector 61 and the second flow path selector 62 are, for example, three-way valves.

First, the first channel selector 61 is operated to communicate the main channel 21 with the main channel 20, and the second channel selector 62 is operated to communicate the main channel 20 with the return channel 23. Subsequently, the blood 10 containing the magnetic particles flows into the main channel 21 from the connection port 2.

After the blood 10 containing the magnetic particles flows from the connection port 2, the first channel selection part 61 is operated to communicate the main channel 20 with the return channel 23. At this time, the second channel selector 62 continues to put the main channel 20 and the return channel 23 in a state of communicating with each other.

The blood 10 circulates through the main channel 20 and the return channel 23. During this time, the magnetic particles are recovered by the magnetic extraction portion 30, and the magnetism generated by the blood 10 is measured by the magnetic sensor 40.

When it is determined that the blood 10 flowing through the main channel 20 contains magnetic particles based on the measurement value indicated by the magnetic sensor 40, the first channel selector 61 and the second channel selector 62 continue to bring the main channel 20 and the return channel 23 into communication with each other. When the blood 10 containing the magnetic particles flows back in the main channel 20 and the return channel 23, the magnetic particles contained in the blood 10 are collected by the magnetic extraction unit 30.

When it is determined that the blood 10 flowing through the main channel 20 does not contain magnetic particles based on the measurement value indicated by the magnetic sensor 40, the first channel selection unit 61 operates the second channel selection unit 62 to communicate the main channel 20 with the main channel 22 while continuing to communicate the main channel 20 with the return channel 23.

Then, the blood 10 flows into the main flow path 22 and passes through the filter 50. After the magnetic sensor 41 determines whether or not the blood 10 contains magnetic particles, the blood 10 flowing through the main channel 22 flows out from the connection port 3.

When it is determined from the measurement values of the magnetic sensor 40 and/or the magnetic sensor 41 that the blood 10 does not contain magnetic particles, the blood flowing out of the connection port 3 can be safely returned to the body. Further, based on the measurement value of the magnetic sensor 41, it can be determined whether or not the blood 10 after passing through the filter 50 contains magnetic particles, and the blood 10 can be returned to the body more safely.

Further, a signal for controlling an artificial heart lung device described later may be output from the magnetic sensor 41. According to this configuration, it can be confirmed that the magnetic particles have been sufficiently separated and removed from the blood before the purified blood is returned into the body.

The filter 50 can capture magnetic particles contained in the blood 10 and foreign substances contained in the blood 10, etc., which cannot be removed by the magnetic extraction unit 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, magnetic particles can be recovered from blood by: the magnetic particles are taken out into a flow path connected to the main flow path 20, or the magnetic particles are collected by a collecting unit provided on the inner wall of the main flow path 20.

The magnetic extraction section 30 may have a magnetic field generating means (not shown) for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40 and the magnetic sensor 41 can detect the presence of magnetic particles by detecting a leakage magnetic field generated by magnetic particles in blood flowing through the main channel 20.

Preferably, the magnetic sensor 40 is disposed outside the main channel 20, and the magnetic sensor 41 is disposed outside the main channel 22 so as not to contact the blood 10. Since the magnetic sensor 40 and the magnetic sensor 41 do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40 and the magnetic sensor 41, known magnetic sensors, for example, a coil type sensor, a hall sensor, or an element using a magnetic resistance can be used. It is possible to determine whether or not the blood 10 flowing through the main channel 20 contains magnetic particles from the magnetic measurement values indicated by the magnetic sensor 40 and the magnetic sensor 41.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passed magnetic particles by the induction coil. The coil type sensor has an advantage of easy installation.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element utilizes a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensor 40 and the magnetic sensor 41 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

< blood transfusion pump >

The blood purification apparatus 1C may be connected to a blood delivery pump capable of flowing blood. Blood delivery pumps may be used, for example, to withdraw blood from outside the body or to circulate blood withdrawn from outside the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1C, blood 10 containing magnetic particles modified with a substance to be separated and capable of capturing a specific substance in the blood is introduced into the main flow paths 20, 21, and 22 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

Although the third embodiment of the present disclosure has been described in detail above, the technique according to the present disclosure is not limited to the third embodiment, and various modifications and changes may be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the third embodiment, the entire device of the blood purification device 1C may be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

Further, as illustrated in fig. 3B, the blood purification apparatus 1C may further include: and a verification unit 90 for determining whether or not the magnetic sensors 40, 41 are operating correctly. For example, the verification unit 90 is connected to the magnetic sensors 40, and 41, and can determine whether or not the magnetic sensors 40, and 41 are operating correctly based on an output (magnetic value of blood) from the magnetic sensors. For example, the verification unit may be configured in the same manner as the verification unit 90 of the first embodiment.

The blood purification apparatus 1C may be connected to the magnetic sensors 40, and 41, and may further include a controller 80 (for example, fig. 3B) that determines whether or not the blood 10 contains magnetic particles based on an output of the magnetic sensors. The control unit 80 can check the operating state of the magnetic sensors 40, and 41 determined by the verification unit 90. For example, the control unit 80 of the third embodiment may be configured in the same manner as the control unit 80 of the first embodiment. Thus, the control unit 80 as a safety circuit can confirm the operation of the magnetic sensors 40, and 41, and thereby can accurately determine whether or not the blood 10 contains magnetic particles.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components. The specific method for capturing a specific component in blood by a substance to be separated and captured by a component to be separated is not particularly limited, and for example, a chemical bond (molecular biological bond, electric bond (van der waals force, polar attraction, intermolecular force, coulomb force), adsorption, steric structure capture, or the like can be used. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself. Further, the magnetic particles may be embedded in the particulate-formed substance captured by the separated component.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1C is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purifying apparatus 1C can purify blood by extracting a specific substance from blood. The blood purifying apparatus 1C may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1C may purify blood taken from an animal in advance without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

(fourth embodiment)

Fig. 4A and 4B are plan views showing the configuration of a blood purification apparatus 1D according to a fourth embodiment of the present disclosure. In the present embodiment, a case will be described as an example where the flow path through which blood flows does not include the return flow path and the blood purification apparatus 1D includes the control unit 80 for processing the measurement value of the magnetic sensor.

As illustrated in fig. 4A, the blood purification apparatus 1D includes: a main channel 20 through which blood 10 flows; a magnetic extraction unit 30 (magnetic extraction means) for recovering magnetic particles contained in the blood 10; and a magnetic sensor 40, a magnetic sensor 41, a magnetic sensor 42 for detecting the presence or absence of magnetic particles in the blood 10; a magnetic particle mixing section 70 for mixing magnetic particles into the blood 10; and a control section 80 for processing the measurement value of the magnetic sensor. The blood purification apparatus 1D further includes: a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

As illustrated in fig. 4B, the blood purification apparatus 1D may include at least one of a magnetic sensor 42a and a magnetic sensor 42B for detecting the presence of magnetic particles in the blood 10. Although both the magnetic sensor 42a and the magnetic sensor 42B are shown in fig. 4B as specific examples, the blood purification apparatus 1D may include only the magnetic sensor 42B.

The magnetic particle mixing unit 70 is provided at a stage preceding the magnetic extraction unit 30, and mixes the magnetic particles into the blood 10 taken out of the body. However, the magnetic particle mixing section 70 may not necessarily be included in a part of the blood purification apparatus 1D, and may be provided outside the blood purification apparatus 1D.

In the specific example shown in fig. 4A and 4B, the magnetic sensor 42a, and the magnetic sensor 42B are disposed at the front stage of the magnetic extraction section 30. The magnetic sensors 42 and 42a may be disposed at a later stage of the magnetic particle mixing section 70. The magnetic sensor 42b may be disposed in a stage before the magnetic particle mixing section 70.

The magnetic sensor 42(42a) can measure the magnetism exhibited by blood after mixing magnetic particles into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42(42a) may be used as a reference value after the magnetic particles are put (hereinafter, may be referred to as "first reference value").

The magnetic sensor 42b can measure the magnetism exhibited by the blood itself before the magnetic particles are mixed into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42b may be used as a reference value (hereinafter, may be referred to as "second reference value") before the magnetic particles are thrown.

The magnetic extraction portion 30, the magnetic sensor 40, and the magnetic sensor 41 are disposed in contact with the main channel 20. The magnetic sensor 40 and the magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1D, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is two, and may be one or three or more.

The control section 80 is connected to, for example, the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42, and an artificial heart-lung device (not shown) (fig. 4A). The control section 80 may also be connected to the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42B, and the artificial heart-lung device (not shown) as illustrated in fig. 4B. For example, signals from the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensor 42 are input to the control section 80. Signals from the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, and the magnetic sensor 42B may be input to the control section 80 (fig. 4B). Further, as an example, the control portion 80 may be configured to be able to output a signal to the artificial heart lung device. However, the control section 80 may not necessarily be directly connected to the magnetic sensors 40, 41, 42a, 42b and the artificial heart lung device. For example, the control unit 80 may receive as input data of measurement values measured by the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42b, and the like.

Blood 10 containing magnetic particles flows into the main channel 20 from the connection port 2, and the magnetic particles are collected by the magnetic extraction unit 30. Subsequently, after the blood 10 has passed through the filter 50, the magnetism of the blood is measured by the magnetic sensor 41.

As a specific example, the control section 80 may perform a process of comparing the magnetism (first reference value) indicated by the blood containing the magnetic particles measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensor 40. In this case, the control section 80 may output, for example, the result of the processing to an appropriate display device or the like. The control unit 80 may output a signal for controlling the operation of the artificial heart lung machine based on a result of comparing the difference between the magnetism of the blood containing the magnetic particles measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensor 41 with a specific reference value (or a range of the reference value).

For example, the control unit 80 controls whether or not the blood 10 is allowed to flow to the artificial heart lung device based on the result of comparing the first reference value measured by the magnetic sensor 42(42a) with the magnetism of the blood measured by the magnetic sensor 41.

For example, when the magnetism of blood measured by the magnetic sensor 41 is decreased to a certain reference value or more compared to the first reference value (i.e., when the magnetic particles are captured by the magnetic extraction part 30 and thus the amount of the magnetic particles in the blood is sufficiently decreased), the control part 80 may flow the blood 10 to the cardiopulmonary bypass device.

On the other hand, the control unit 80 may control the blood 10 not to flow to the artificial heart lung device when it is determined that the amount of the magnetic particles in the blood is not sufficiently reduced. Specifically, for example, when the magnetism of blood measured by the magnetic sensor 41 is higher than a first reference value, the control section 80 may control the artificial heart lung device or the like in such a manner that the flow of blood 10 into the artificial heart lung device is stopped. Further, for example, when the difference between the first reference value and the magnetism of the blood measured by the magnetic sensor 41 is not included in the range of the specific reference value (for example, it is smaller than the specific reference value), the control section 80 may control the artificial heart lung device or the like in such a manner that the flow of the blood 10 into the artificial heart lung device is stopped. Thus, the control portion 80 can prevent, for example, blood 10 containing magnetic particles in an amount outside a specific reference value range from flowing into the artificial heart lung device. For example, the reference value may be appropriately determined from the viewpoint of safety to the human body or the like (the same applies to the embodiment described later).

As another specific example, the control section 80 may perform a process of comparing the magnetism (second reference value) shown by the blood itself without the magnetic particles measured by the magnetic sensor 42b and the magnetism of the blood measured by the magnetic sensor 40. In this case, the control section 80 may output, for example, the result of the processing to an appropriate display device or the like.

For example, the control unit 80 may control whether or not the blood 10 is caused to flow to the artificial heart lung device based on a result of comparing the second reference value measured by the magnetic sensor 42b with the magnetism of the blood measured by the magnetic sensor 41.

For example, when the magnetism of blood measured by the magnetic sensor 41 is equal to or less than a second reference value (when the amount of magnetic particles in the blood is sufficiently reduced), the control portion 80 causes the blood 10 to flow to the artificial heart lung device.

On the other hand, the control section 80 controls the artificial heart lung device so that, for example, when the magnetism of the blood measured by the magnetic sensor 41 is larger than the second reference value, the flow of the blood 10 into the artificial heart lung device is stopped. The control section 80 may also control the artificial heart lung device such that, for example, when the difference between the second reference value and the magnetism of the blood measured by the magnetic sensor 41 is not included in the range of the specific reference value (for example, when it is larger than the specific reference value), the flow of the blood 10 into the artificial heart lung device is stopped. Thus, the control portion 80 can prevent, for example, blood 10 containing magnetic particles in an amount outside a specific reference value range from flowing into the artificial heart lung device.

As described above, the control unit 80 may control whether or not the blood 10 is to be flowed to the artificial heart lung device, based on the result of comparing the magnetism of the blood measured by the magnetic sensor 41 with the first reference value measured by the magnetic sensor 42 (magnetic sensor 42a) or the second reference value measured by the magnetic sensor 42 b. As an example, as described above, the control part 80 controls whether or not to allow the blood 10 to flow into the artificial heart lung device, depending on whether or not the difference between the magnetism of the blood measured by the magnetic sensor 41 and the first reference value or the difference between the magnetism of the blood measured by the magnetic sensor 41 and the second reference value is included in a specific range.

In the blood purification apparatus 1D, the control unit 80 is provided, whereby the magnetism of the blood 10 can be measured more accurately, and it can be confirmed that the magnetic particles have been sufficiently separated from the blood and removed before the purified blood is returned to the body.

The filter 50 can capture magnetic particles, foreign substances contained in the blood 10, and the like that are not removed by the magnetic extraction unit 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, the magnetic particles can be collected from blood by taking out the magnetic particles into a channel connected to the main channel 20, or by collecting the magnetic particles with a collecting unit provided on the inner wall of the main channel 20.

The magnetic extraction section 30 may have a magnetic field generating means (not shown) for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42b can detect the presence of magnetic particles by detecting a leakage magnetic field generated by the magnetic particles in the blood flowing through the main channel 20.

Preferably, the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42(42a), and the magnetic sensor 42b are disposed outside the main channel 20 and do not contact the blood 10. Since the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensor 42 do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a) and 42b, known magnetic sensors, for example, coil sensors, hall sensors, and elements using magnetic resistance can be used. Whether or not the blood 10 flowing through the main channel 20 contains magnetic particles can be determined by using the magnetic measurement values indicated by the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42 b. The magnetic sensors 40, 41 and 42(42a), 42b may be the same type of magnetic sensor or different types of magnetic sensors.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passing magnetic particles using the induction coil. The coil type sensor has an advantage of easy setup.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element is an element utilizing a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensors 40, 41, and 42(42a), 42b may have a member capable of shielding a magnetic field, such as a magnetic shield layer. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

< blood transfusion pump >

The blood purification apparatus 1D may include a blood transfer pump (not shown) for extracting blood from the outside of the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1D, the blood 10 containing the magnetic particles modified with the substance captured by the separated component that can capture the specific substance in the blood is flowed into the main channel 20 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

Although the fourth embodiment of the present disclosure has been described in detail above, the technique according to the present disclosure is not limited to the fourth embodiment, and various modifications and changes may be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the fourth embodiment, the entire device of the blood purification device 1D can be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

As shown in fig. 4A and 4B, blood purification apparatus 1D further includes verification unit 90 for determining whether or not magnetic sensors 40, 41, 42(42a) and 42B are operating correctly. For example, the verification section 90 is connected to the magnetic sensors 40, 41, 42(42a), and 42b, and can determine whether the magnetic sensors 40, 41, 42(42a), and 42b are operating correctly or not from the output (magnetic value of blood) from the magnetic sensors. For example, the verification unit may be configured in the same manner as the verification unit 90 in the first embodiment.

The blood purification apparatus 1D may further include a controller 80 connected to the magnetic sensors 40, 41, 42(42a), and 42b, and determining whether or not the blood 10 contains magnetic particles based on the outputs of the magnetic sensors. The control section 80 can confirm the operation states of the magnetic sensors 40, 41, 42(42a) and 42b determined by the verification section 90. For example, the control unit 80 of the third embodiment may be configured in the same manner as the control unit 80 of the first embodiment. Thus, the control unit 80 as a safety circuit can check the operation states of the magnetic sensors 40, 41, 42(42a) and 42b, and as a result, can accurately determine whether or not the blood 10 contains magnetic particles.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components.

The specific method for capturing a specific component in blood by a substance to be separated and captured by a component to be separated is not particularly limited, and for example, a chemical bond (molecular biological bond, electric bond (van der waals force, polar attraction, intermolecular force, coulomb force), adsorption, steric structure capture, or the like can be used. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself. Further, the magnetic particles may be embedded in the particulate-formed substance captured by the separated component.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1D is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purification apparatus 1D can extract a specific substance from blood to purify the blood. The blood purifying apparatus 1D may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1D may purify blood taken from an animal in advance without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

(fifth embodiment)

Fig. 5A and 5B are plan views showing the configuration of a blood purification apparatus 1E according to a fifth embodiment of the present disclosure. In the present embodiment, a case will be described as an example where the blood purification apparatus 1E has a control unit 80 having a return channel as a channel through which blood flows and an operation channel selection unit.

As illustrated in fig. 5A, the blood purification apparatus 1E includes a main channel 20, a main channel 21, and a main channel 22 through which blood 10 flows; a magnetic extraction unit 30 (magnetic extraction means) for recovering magnetic particles contained in the blood 10; and a magnetic sensor 40, a magnetic sensor 41, a magnetic sensor 42 for detecting the presence or absence of magnetic particles in the blood 10; a magnetic particle mixing section 70 for mixing magnetic particles into the blood 10; and a control section 80 for processing the measurement value of the magnetic sensor. Further, the blood purification apparatus 1E further includes: the return channel 23 for returning the blood 10, a first channel selector 61 (first channel selector member) for selecting a channel, and a second channel selector 62 (second channel selector member) for selecting a channel. Further, the blood purification apparatus 1E further includes: a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

As illustrated in fig. 5B, the blood purification apparatus 1E may include at least one of a magnetic sensor 42a and a magnetic sensor 42B for detecting the presence of magnetic particles in the blood 10. Although both the magnetic sensor 42a and the magnetic sensor 42B are shown in fig. 5B as specific examples, the blood purification apparatus 1E may include only the magnetic sensor 42B.

The magnetic particle mixing section 70 is provided at a stage preceding the magnetic extraction section 30 and mixes the magnetic particles into the blood 10. However, the magnetic particle mixing section 70 may not be provided in the blood purification apparatus 1E, or may be provided outside the blood purification apparatus 1E.

In the specific example shown in fig. 5A and 5B, the magnetic sensor 42a, and the magnetic sensor 42B are disposed at the front stage of the magnetic extraction section 30. The magnetic sensors 42 and 42a may be disposed at a later stage of the magnetic particle mixing section 70. The magnetic sensor 42b may be disposed in a stage before the magnetic particle mixing section 70.

The magnetic sensor 42(42a) can measure the magnetism exhibited by blood after mixing magnetic particles into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42(42a) may be used as a reference value (hereinafter, referred to as "first reference value") after the magnetic particles are put in.

The magnetic sensor 42b can measure the magnetism exhibited by blood itself that did not contain magnetic particles before the magnetic particles were mixed into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42b may be used as a reference value (hereinafter, referred to as "second reference value") before the magnetic particles are thrown.

The first flow path selector 61 and the second flow path selector 62 are, for example, three-way solenoid valves. Not limited to this, the first channel selector 61 and the second channel selector 62 may be realized by, for example, an appropriate structure (for example, an actuator, a valve, or the like) that can select a blood channel by a control signal output from the controller 80.

The magnetic extraction portion 30, the magnetic sensor 40, and the magnetic sensor 41 are disposed in contact with the main channel 20. The magnetic sensor 40 and the magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1E, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is two, and may be one or three or more.

The control section 80 is connected (fig. 5A) to the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42, the first flow path selecting section 61, the second flow path selecting section 62, and the artificial heart lung device (not shown). The control portion 80 may also be connected to the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42B, the first flow path selecting portion 61, the second flow path selecting portion 62, and the artificial heart lung device (not shown) as illustrated in fig. 5B. For example, signals from the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensor 42 are input to the control section 80. Signals from the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, and the magnetic sensor 42B may be input to the control section 80 (fig. 5B). Further, as an example, the control portion 80 may be configured to be able to output signals to the first flow path selecting portion 61, the second flow path selecting portion 62, and the artificial heart lung device. However, the control section 80 may not necessarily be directly connected to the magnetic sensors 40, 41, 42a, 42b and the artificial heart lung device. For example, the control unit 80 may receive as input data of measurement values measured by the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42b, and the like.

First, the control section 80 outputs a signal to the first channel selection section 61, and operates the first channel selection section 61 to communicate the main channel 21 with the main channel 20. Further, the control section 80 outputs a signal to the second channel selecting section 62, operates the second channel selecting section 62 to communicate the main channel 20 and the return channel 23, and shuts off the main channel 20 and the main channel 22. Thereby, the blood 10 containing the magnetic particles flows into the main channel 21 from the connection port 2.

After the blood 10 containing the magnetic particles flows from the connection port 2, the control section 80 operates the first channel selection section 61 to communicate the main channel 20 and the return channel 23. At this time, the second channel selector 62 continues to put the main channel 20 and the return channel 23 in a state of communicating with each other.

The blood 10 circulates through the main channel 20 and the return channel 23. During this time, the magnetic particles are recovered by the magnetic extraction portion 30, and the magnetism generated by the blood 10 is measured by the magnetic sensor 40.

As a specific example, the control section 80 may perform a process of comparing the magnetism (first reference value) indicated by the blood containing the magnetic particles measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensor 40. In this case, the control section 80 may output, for example, the result of the processing to an appropriate display device or the like. The control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 based on a result of comparison between the first reference value measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensor 40.

For example, when the magnetism of blood measured by the magnetic sensor 40 decreases to a certain reference value or more as compared with the first reference value (that is, when the magnetic particles are captured by the magnetic extraction unit 30 and the amount of magnetic particles in blood sufficiently decreases), the control unit 80 controls at least one of the first channel selection unit 61 and the second channel selection unit 62, for example, so that the main channel 20 and the main channel 22 communicate with each other. Specifically, the control section 80 outputs, for example, a signal to the second channel selection section 62, and operates the second channel selection section 62 to communicate the main channel 20 and the main channel 22. At this time, the control unit 80 continues the state in which the first channel selection unit 61 causes the main channel 20 and the return channel 23 to communicate with each other. Then, the blood 10 flows into the main flow path 22 and passes through the filter 50.

On the other hand, the control section 80 may control at least one of the first channel selection section 61 and the second channel selection section 62 so as to maintain the state in which the main channel 20 and the return channel 23 communicate when it is determined that the amount of magnetic particles in the blood is not sufficiently reduced. Specifically, for example, when the magnetism of blood measured by the magnetic sensor 40 is higher than the first reference value measured by the magnetic sensor 42(42a), at least one of the first flow path selection part 61 and the second flow path selection part 62 is controlled to continue the state in which the main flow path 20 and the return flow path 23 are communicated. Further, for example, the control section 80 may control at least one of the first channel selection section 61 and the second channel selection section 62 in such a manner as to maintain a state in which the main channel 20 and the return channel 23 communicate when the difference between the first reference value and the magnetism of blood measured by the magnetic sensor 40 is not included in the range of the specific reference value (for example, it is smaller than the specific reference value). The first channel selection portion 61 and the second channel selection portion 62 continue to bring the main channel 20 and the return channel 23 into a state of communicating with each other in response to a control signal from the control portion 80. Thus, the control section 80 can prevent, for example, blood 10 containing magnetic particles in an amount outside a specific reference value range from flowing into the main channel 22.

As another specific example, the control section 80 may perform a process of comparing the magnetism (second reference value) shown by the blood itself without the magnetic particles measured by the magnetic sensor 42b and the magnetism of the blood measured by the magnetic sensor 40. For example, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 based on a result of comparing the second reference value measured by the magnetic sensor 42b with the magnetism of blood measured by the magnetic sensor 40.

Specifically, for example, when the magnetism of blood measured by the magnetic sensor 40 is equal to or less than the second reference value (when the amount of magnetic particles in blood sufficiently decreases), the control portion 80 may perform the following processing. That is, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 so that the main channel 20 and the main channel 22 communicate with each other. The control section 80 outputs, for example, a signal to the second channel selection section 62, and operates the second channel selection section 62 to communicate the main channel 20 and the main channel 22. At this time, the control unit 80 continues the state in which the first channel selection unit 61 communicates the main channel 20 and the return channel 23. Then, the blood 10 flows into the main flow path 22 and passes through the filter 50.

On the other hand, the control section 80 may control at least one of the first channel selection section 61 and the second channel selection section 62 in such a manner as to maintain a state in which the main channel 20 and the return channel 23 are communicated when, for example, the magnetism of blood measured by the magnetic sensor 40 is larger than the second reference value (i.e., the amount of magnetic particles in the blood is not sufficiently reduced). For example, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 so as to maintain the state in which the main channel 20 and the return channel 23 are communicated when the difference between the second reference value and the magnetism of blood measured by the magnetic sensor 40 is not within the range of a specific reference value (for example, when the difference is larger than a certain reference value). The first channel selector 61 and the second channel selector 62 continue to bring the main channel 20 and the return channel 23 into a state of communication with each other in response to a control signal from the control section 80. Thus, the control section 80 can prevent, for example, blood 10 containing magnetic particles in an amount outside a specific reference value range from flowing into the main channel 22.

As described above, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 based on the result of comparing the magnetism of the blood measured by the magnetic sensor 40 with the first reference value measured by the magnetic sensor 42 (magnetic sensor 42 a). The controller 80 may control at least one of the first channel selector 61 and the second channel selector 62 based on the magnetic properties of the blood measured by the magnetic sensor 40 and the second reference value measured by the magnetic sensor 42b or the result of comparison. For example, as described above, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 according to whether or not the difference between the magnetism of blood measured by the magnetic sensor 40 and the first reference value or the difference between the magnetism of blood measured by the magnetic sensor 40 and the second reference value is included in a specific range. Thus, the control unit 80 can control the flow of blood based on the measurement result of each magnetic sensor.

Further, the control unit 80 may determine whether or not the blood 10 flowing through the main channel 22, that is, the blood 10 having passed through the filter 50 contains magnetic particles, based on the magnetism of the blood measured by the magnetic sensor 41 and the magnetism (first reference value) indicated by the blood containing the magnetic particles measured by the magnetic sensor 42(42 a). For example, if the magnetism of the blood measured by the magnetic sensor 41 is reduced by a certain reference value or more from the first reference value, the control unit 80 determines that the magnetic particles contained in the blood 10 after passing through the filter 50 have been sufficiently reduced. Further, for example, when the difference between the magnetism of blood measured by the magnetic sensor 41 and the first reference value is included in a specific range (for example, when the difference is large at a certain reference value or more), it can be determined that the magnetic particles included in the blood 10 after passing through the filter 50 are sufficiently reduced.

Similarly, the control unit 80 may determine whether or not the blood 10 flowing through the main channel 22, that is, the blood 10 having passed through the filter 50 contains magnetic particles, based on the magnetism of the blood measured by the magnetic sensor 41 and the magnetism (second reference value) indicated by the blood containing magnetic particles measured by the magnetic sensor 42 b. For example, if the magnetism of blood measured by the magnetic sensor 41 is equal to or less than the second reference value, the control unit 80 determines that the magnetic particles contained in the blood 10 after passing through the filter 50 are sufficiently reduced. Further, for example, when the difference between the magnetism of blood measured by the magnetic sensor 41 and the second reference value is included in a specific range (for example, when the difference is a certain reference value or less), the control section 80 may determine that the magnetic particles included in the blood 10 after passing through the filter 50 are sufficiently reduced.

When the control unit 80 determines that the blood 10 flowing through the main channel 22 does not contain magnetic particles (or the magnetic particles are sufficiently reduced), the state in which the main channel 20 and the main channel 22 are continuously communicated is continued. In this case, the blood 10 flows out from the connection port 3. On the other hand, when it is determined that the blood 10 flowing through the main channel 22 contains magnetic particles (or the magnetic particles are not sufficiently reduced), the control section 80 may output a signal for controlling the operation of the artificial heart lung apparatus. For example, the control section 80 may control the artificial heart lung device to stop the flow of blood 10 into the artificial heart lung device. At this time, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 to block the main channel 22 and the return channel 23 and switch to a state in which the main channel 20 and the return channel 23 communicate with each other. Thus, the control part 80 can prevent the blood 10 containing the magnetic particles from flowing into the artificial heart lung device.

In this blood purification apparatus 1E, the control unit 80 operates the first channel selection unit 61 and the second channel selection unit 62 based on the measurement values of the magnetic sensor 40 and the magnetic sensors 42(42a), 42b, and the like, so that the magnetic particles can be sufficiently separated and removed from the blood before the purified blood is returned to the body.

The filter 50 can trap magnetic particles, foreign substances contained in the blood 10, and the like, which cannot be removed by the magnetic extraction section 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, the magnetic particles can be collected from blood by taking out the magnetic particles into a channel connected to the main channel 20, or by collecting the magnetic particles with a collecting unit provided on the inner wall of the main channel 20.

The magnetic extraction section 30 may have a magnetic field generating means (not shown) for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42b can detect the presence of magnetic particles by detecting a leakage magnetic field generated by the magnetic particles in the blood flowing through the main channel 20.

Preferably, the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a) and 42b are disposed outside the main channel 20 and do not contact the blood 10. Since the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42b do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a) and 42b, known magnetic sensors, for example, coil sensors, hall sensors, and elements using magnetic resistance can be used. Whether or not the blood 10 flowing through the main channel 20 contains magnetic particles can be determined by using the magnetic measurement values indicated by the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42 b. The magnetic sensors 40, 41 and 42(42a), 42b may be the same type of magnetic sensor or different types of magnetic sensors.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passing magnetic particles using the induction coil. The coil type sensor has an advantage of easy setup.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element is an element utilizing a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensors 40, 41, and 42(42a), 42b may have a member capable of shielding a magnetic field, such as a magnetic shield layer. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

< blood transfusion pump >

The blood purification apparatus 1E may be connected to a blood delivery pump capable of flowing blood. Blood delivery pumps may be used, for example, to withdraw blood from outside the body or to circulate blood withdrawn from outside the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1E, the blood 10 containing the magnetic particles modified with the substance for capturing the separated component capable of capturing the specific substance in the blood is introduced into the main flow paths 20, 21, and 22 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

Although the fifth embodiment of the present disclosure has been described in detail above, the technique according to the present disclosure is not limited to the fifth embodiment, and various modifications and changes may be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the fifth embodiment, the entire device of the blood purification device 1E may be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

As shown in fig. 5A and 5B, blood purification apparatus 1E further includes verification unit 90 for determining whether or not magnetic sensors 40, 41, 42(42a) and 42B are operating correctly. For example, the verification section 90 is connected to the magnetic sensors 40, 41, 42(42a), and 42b, and can determine whether the magnetic sensors 40, 41, 42(42a), and 42b are operating correctly or not from the output (magnetic value of blood) from the magnetic sensors. For example, the verification unit may be configured in the same manner as the verification unit 90 in the first embodiment.

The blood purification apparatus 1E may further include a control unit connected to the magnetic sensors 40, 41, 42(42a), and 42b, and determining whether or not the blood 10 contains magnetic particles based on the outputs of the magnetic sensors. The control section 80 can confirm the operation states of the magnetic sensors 40, 41, 42(42a) and 42b determined by the verification section 90. Thus, the control unit 80 as a safety circuit can check the operation states of the magnetic sensors 40, 41, 42(42a) and 42b, and as a result, can accurately determine whether or not the blood 10 contains magnetic particles.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components. The specific method for capturing a specific component in blood by a substance to be separated into components is not particularly limited, and for example, chemical bonds (molecular biological bonds, electric bonds (van der waals force, polar attraction, intermolecular force, coulomb force), adsorption, steric structure capture, and the like can be suitably used. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself. Further, the magnetic particles may be embedded in the particulate-formed substance captured by the separated component.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1E is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purification apparatus 1E can extract a specific substance from the blood to purify the blood. The blood purification apparatus 1E may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1E may purify blood taken from an animal in advance without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

(sixth embodiment)

Fig. 6A and 6B are plan views showing the configuration of a blood purification apparatus 1F according to a sixth embodiment of the present disclosure. In the present embodiment, a case where the blood purification apparatus 1F has a zigzag-shaped return channel and a control unit 80 for operating the channel selection unit is provided is taken as an example.

As shown in fig. 6A, the blood purification apparatus 1F includes a main channel 20, a main channel 21, and a main channel 22 through which blood 10 flows; a magnetic extraction unit 30 (magnetic extraction means) for recovering magnetic particles contained in the blood 10; and two magnetic sensors 40, 41, 42 for detecting the presence or absence of magnetic particles in the blood 10; a magnetic particle mixing section 70 for mixing magnetic particles into the blood 10; and a control section 80 for processing the measurement value of the magnetic sensor. Further, the blood purification apparatus 1F further includes: the return channel 23 for returning the blood 10, a first channel selector 61 (first channel selector member) for selecting a channel, and a second channel selector 62 (second channel selector member) for selecting a channel. Further, the blood purification apparatus 1F further includes: a filter 50, a connection port (inlet) 2, and a connection port (outlet) 3.

As illustrated in fig. 6B, the blood purification apparatus 1F may include at least one of a magnetic sensor 42a and a magnetic sensor 42B for detecting the presence of magnetic particles in the blood 10. Although both the magnetic sensor 42a and the magnetic sensor 42B are shown in fig. 6B as specific examples, the blood purification apparatus 1F may include only the magnetic sensor 42B.

In the blood purification apparatus 1F, two magnetic sensors 40 and 40 are provided in the main channel 20. The magnetic sensor 40 is configured to be less susceptible to the magnetic field generated by the magnetic extraction section 30. With this configuration, the magnetic sensor 40 can more accurately determine the magnetism of the blood 10.

In the blood purification apparatus 1F, for example, in a side view of the main channel 20, two magnetic sensors 40 and 40 provided in the main channel 20 are attached in a state of being offset from the axis of the magnetic extraction unit 30. Further, the two magnetic sensors 40 and 40 are also attached in a state of being off-axis from each other. In this way, the two magnetic sensors 40 and 40 are arranged so as to be less susceptible to the magnetic field generated by the magnetic extraction unit 30.

In this blood purification apparatus 1F, by providing two magnetic sensors 40, the magnetism of the blood 10 can be measured more accurately by using two measurement values of the two magnetic sensors 40, 40. Further, with this configuration, the magnetic sensor 40 is less likely to malfunction, and the measurement accuracy of the magnetic sensor 40 can be improved.

The magnetic particle mixing section 70 is provided at a stage preceding the magnetic extraction section 30 and mixes the magnetic particles into the blood 10. However, the magnetic particle mixing section 70 may not be provided in the blood purification apparatus 1F, or may be provided outside the blood purification apparatus 1F.

The magnetic sensors 42, 42a, 42b are disposed at the front stage of the magnetic extraction unit 30. The magnetic sensors 42 and 42a may be disposed at a later stage of the magnetic particle mixing section 70. The magnetic sensor 42b may be disposed in a stage before the magnetic particle mixing section 70.

The magnetic sensor 42(42a) can measure the magnetism exhibited by blood after mixing magnetic particles into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42(42a) may be used as a reference value (hereinafter, referred to as "first reference value") after the magnetic particles are put in.

The magnetic sensor 42b can measure the magnetism exhibited by blood itself that did not contain magnetic particles before the magnetic particles were mixed into the blood. In this case, for example, the magnetic value measured by the magnetic sensor 42b may be used as a reference value (hereinafter, referred to as "second reference value") before the magnetic particles are thrown.

The first flow path selector 61 and the second flow path selector 62 are, for example, three-way solenoid valves. Not limited to this, the first channel selector 61 and the second channel selector 62 may be realized by, for example, an appropriate structure (for example, an actuator, a valve, or the like) that can select a blood channel by a control signal output from the controller 80.

The magnetic extraction portion 30, the magnetic sensor 40, and the magnetic sensor 41 are disposed in contact with the main channel 20. The magnetic sensor 40 and the magnetic sensor 41 are provided at the subsequent stage of the magnetic extraction section 30. In blood purification apparatus 1F, the number of magnetic sensors provided at the subsequent stage of magnetic extraction unit 30 is three, and may be one, two, or four or more.

The control section 80 is connected (fig. 6A) to the two magnetic sensors 40, the magnetic sensor 41, the magnetic sensor 42, the first flow path selecting section 61, the second flow path selecting section 62, and the artificial heart lung device (not shown). The control portion 80 may also be connected to the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42B, the first flow path selecting portion 61, the second flow path selecting portion 62, and the artificial heart lung device (not shown) as illustrated in fig. 6B. For example, signals from the two magnetic sensors 40, the magnetic sensor 41, and the magnetic sensor 42 are input to the control section 80. Signals from the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, and the magnetic sensor 42B may be input to the control section 80 (fig. 6B). Further, as an example, the control portion 80 may be configured to be able to output signals to the first flow path selecting portion 61, the second flow path selecting portion 62, and the artificial heart lung device. However, the control section 80 may not necessarily be directly connected to the magnetic sensor 41 and the artificial heart lung device. For example, the control unit 80 may receive as input data of measurement values measured by the magnetic sensor 40, the magnetic sensor 41, the magnetic sensor 42a, the magnetic sensor 42b, and the like.

First, the control section 80 outputs a signal to the first channel selection section 61, and operates the first channel selection section 61 to communicate the main channel 21 with the main channel 20. Further, the control section 80 outputs a signal to the second channel selecting section 62, operates the second channel selecting section 62 to communicate the main channel 20 and the return channel 23, and shuts off the main channel 20 and the main channel 22. Thereby, the blood 10 containing the magnetic particles flows into the main channel 21 from the connection port 2.

After the blood 10 containing the magnetic particles flows from the connection port 2, the control section 80 operates the first channel selection section 61 to communicate the main channel 20 and the return channel 23. At this time, the second channel selector 62 continues to put the main channel 20 and the return channel 23 in a state of communicating with each other.

The blood 10 circulates through the main channel 20 and the return channel 23. During this time, the magnetic particles are recovered by the magnetic extraction portion 30, and the magnetism generated by the blood 10 is measured by the magnetic sensors 40, 40.

As a specific example, the control section 80 may perform a process of comparing the magnetism (first reference value) indicated by the blood containing the magnetic particles measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensors 40, 40. In this case, the control section 80 may output, for example, the result of the processing to an appropriate display device or the like. The control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 based on a result of comparison between the first reference value measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensors 40 and 40.

For example, when it is determined that one or both of the magnetism of the blood measured by the two magnetic sensors 40, 40 is greater than the first reference value measured by the magnetic sensor 42(42a), the control portion 80 may control the first channel selection portion 61 and the second channel selection portion 62 to continue the state in which the main channel 20 and the return channel 23 are communicated with each other. Further, for example, when it is determined that the difference between the first reference value measured by the magnetic sensor 42(42a) and one or both of the magnetism of the blood measured by the two magnetic sensors 40, 40 is not included in the specific reference value range (for example, when the difference is smaller than a certain reference value, or the like), the control section 80 may control the first channel selection section 61 and the second channel selection section 62 to continue the state in which the main channel 20 and the return channel 23 are communicated with each other

As another specific example, the control section 80 may perform a process of comparing the magnetism (second reference value) shown by the blood itself without the magnetic particles measured by the magnetic sensor 42b and the magnetism of the blood measured by the magnetic sensors 40, 40. The controller 80 may control at least one of the first channel selector 61 and the second channel selector 62 based on a result of comparison between the second reference value and the magnetism of the blood measured by the magnetic sensors 40 and 40.

Specifically, for example, when one or both of the magnetism of the blood measured by the two magnetic sensors 40 and 40 is larger than the second reference value measured by the magnetic sensor 42b, the control unit 80 may control the first channel selection unit 61 and the second channel selection unit 62 so as to continue the state in which the main channel 20 and the return channel 23 are communicated. For example, when it is determined that the difference between the second reference value measured by the magnetic sensor 42b and one or both of the magnetic properties of the blood measured by the two magnetic sensors 40 and 40 is not within the range of the specific reference value (for example, when the difference is larger than a certain reference value), the control unit 80 may control the first channel selection unit 61 and the second channel selection unit 62 so as to continue the state in which the main channel 20 and the return channel 23 are communicated with each other.

On the other hand, the control section 80 may perform the following processing when it is determined that the blood 10 flowing through the main channel 20 does not contain magnetic particles (or the magnetic particles are sufficiently reduced) based on the magnetism of the blood measured by one or both of the two magnetic sensors 40, 40 and the first reference value measured by the magnetic sensor 42(42 a). That is, in this case, the control unit 80 outputs a signal to the second channel selecting unit 62, for example, and operates the second channel selecting unit 62 so that the main channel 20 and the main channel 22 communicate with each other. At this time, the control portion 80 may control the first channel selection portion 61 to continue the state in which the main channel 20 and the return channel 23 are communicated with each other. Then, the blood 10 flows into the main flow path 22 and passes through the filter 50. For example, the control unit 80 may operate the second channel selection unit 62 to communicate the main channel 20 and the main channel 22 when it is determined that the difference between the first reference value measured by the magnetic sensor 42(42a) and one or both of the magnetic properties of the blood measured by the two magnetic sensors 40, 40 is included in a specific range (for example, when the difference is larger than the reference value).

Further, the control section 80 may execute the following processing when it is determined that the blood 10 flowing through the main channel 20 does not contain magnetic particles (or the magnetic particles are sufficiently reduced) based on the magnetism of the blood measured by one or both of the two magnetic sensors 40, 40 and the second reference value measured by the magnetic sensor 42 b. That is, in this case, the control unit 80 outputs a signal to the second channel selecting unit 62, for example, and operates the second channel selecting unit 62 so that the main channel 20 and the main channel 22 communicate with each other. At this time, the control portion 80 may control the first channel selection portion 61 to continue the state in which the main channel 20 and the return channel 23 are communicated with each other. Then, the blood 10 flows into the main flow path 22 and passes through the filter 50. For example, the control unit 80 may operate the second channel selection unit 62 to communicate the main channel 20 and the main channel 22 when it is determined that the difference between the second reference value measured by the magnetic sensor 42b and one or both of the magnetic properties of the blood measured by the two magnetic sensors 40, 40 is included in a specific range (for example, when the difference is larger than the reference value).

Further, the control section 80 may determine whether or not the blood 10 flowing through the main channel 22 contains magnetic particles (or whether or not the magnetic particles are sufficiently reduced) based on the magnetism of the blood measured by the magnetic sensor 41 and the magnetism (first reference value) exhibited by the blood itself containing the magnetic particles measured by the magnetic sensor 42(42 a). Further, the control unit 80 may determine whether or not the blood 10 flowing through the main channel 22 contains magnetic particles (or whether or not the magnetic particles are sufficiently reduced) based on the magnetism of the blood measured by the magnetic sensor 41 and the magnetism of the blood itself containing the magnetic particles measured by the magnetic sensor 42 b.

Specifically, for example, when the magnetism of blood measured by the magnetic sensor 41 is higher than a first reference value, the control portion 80 may determine that the magnetic particles are not sufficiently reduced. Further, for example, when the difference between the first reference value and the magnetism of blood measured by the magnetic sensor 41 is not included in the range of the specific reference value (for example, a case where the difference is smaller than the reference value), the control portion 80 may determine that the magnetic particles are not sufficiently reduced.

Likewise, for example, when the magnetism of blood measured by the magnetic sensor 41 is higher than the second reference value, the control portion 80 may determine that the magnetic particles are not sufficiently reduced. Further, for example, when the difference between the second reference value and the magnetism of blood measured by the magnetic sensor 41 is not included in the range of the specific reference value (for example, a case where the difference is larger than the reference value), the control portion 80 may determine that the magnetic particles are not sufficiently reduced.

For example, the control unit 80 may compare the first reference value measured by the magnetic sensor 42(42a) with the magnetism of blood measured by the magnetic sensor 40, and output the result to a display device or the like. For example, the control unit 80 may compare the second reference value measured by the magnetic sensor 42b with the magnetism of blood measured by the magnetic sensor 40, and output the result to a display device or the like.

The control unit 80 may output a signal for controlling the operation of the artificial heart lung device when it has been determined that the magnetic particles are not sufficiently reduced based on the first reference value measured by the magnetic sensor 42(42a) and the magnetism of the blood measured by the magnetic sensor 41. Similarly, when the control unit 80 determines that the magnetic particles are not sufficiently reduced based on the second reference value measured by the magnetic sensor 42b and the magnetism of the blood measured by the magnetic sensor 41, a signal for controlling the operation of the artificial heart lung device may be output. In this case, for example, the control section 80 may control the artificial heart lung device to stop the flow of the blood 10 into the artificial heart lung device. At this time, the control unit 80 may control at least one of the first channel selection unit 61 and the second channel selection unit 62 to block the main channel 22 and the return channel 23 and switch to a state in which the main channel 20 and the return channel 23 communicate with each other. Thus, the control part 80 can prevent the blood 10 containing the magnetic particles from flowing into the artificial heart lung device.

In this blood purification apparatus 1F, since the control unit 80 operates the first channel selection unit 61 and the second channel selection unit 62 based on the measurement values of the two magnetic sensors 40 and the magnetic sensors 42(42a) and 42b, the measurement accuracy of the magnetic sensor 40 can be improved, and the magnetic particles can be sufficiently separated and removed from the blood before the purified blood is returned to the body.

The filter 50 can trap magnetic particles, foreign substances contained in the blood 10, and the like, which cannot be removed by the magnetic extraction section 30.

< magnetic extraction means >

The magnetic extraction unit 30 can recover magnetic particles from blood flowing through the main channel 20 by magnetic force, and can extract a specific substance captured by the magnetic particles from the blood.

As the magnetic extraction unit 30, a known device, for example, a magnetic separator described in patent document 1 can be used.

For example, the magnetic particles can be collected from blood by taking out the magnetic particles into a channel connected to the main channel 20, or by collecting the magnetic particles with a collecting unit provided on the inner wall of the main channel 20.

The magnetic extraction section 30 may have a magnetic field generating means for generating a magnetic field. The magnetic particles are recovered from the blood 10 flowing through the main channel 20 by the magnetic field. The magnetic field generating member may be, for example, a permanent magnet, a variable flux magnet, or an induced magnetic field.

The magnetic extraction section 30 may have a member capable of shielding a magnetic field, such as a magnetic shield layer or the like. This can suppress or prevent a leakage magnetic field from the magnetic extraction unit 30.

Preferably, the magnetic field generating member is disposed outside the main channel 20 and does not contact the blood 10. Since the magnetic field generating member does not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

< magnetic sensor >

The magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42b can detect the presence of magnetic particles by detecting a leakage magnetic field generated by the magnetic particles in the blood flowing through the main channel 20.

Preferably, the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a) and 42b are disposed outside the main channel 20 and do not contact the blood 10. Since the magnetic sensors 40, 41, 42(42a) and 42b do not contact the blood 10, coagulation of the blood 10 can be suppressed, and mixing of foreign substances can be suppressed.

As the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a) and 42b, known magnetic sensors, for example, coil sensors, hall sensors, and elements using magnetic resistance can be used. Whether or not the blood 10 flowing through the main channel 20 contains magnetic particles can be determined by using the magnetic measurement values indicated by the magnetic sensor 40, the magnetic sensor 41, and the magnetic sensors 42(42a), 42 b. The magnetic sensors 40, 41 and 42(42a), 42b may be the same type of magnetic sensor or different types of magnetic sensors.

When a sample containing magnetic particles passes through the induction coil, the coil-type sensor measures and detects the magnetic field of the passing magnetic particles using the induction coil. The coil type sensor has an advantage of easy setup.

The hall sensor detects a magnetic field by the hall effect, and has an advantage of being inexpensive and easy to install.

The magnetoresistive element is an element utilizing a phenomenon in which resistance changes under the influence of a magnetic field, and includes an anisotropic magnetoresistive effect (AMR) element, a Giant Magnetoresistive (GMR) element, a Tunnel Magnetoresistive (TMR) element, and the like. The GMR element and the TMR element have advantages in that temperature change and change with time are small, and sensitivity (MR ratio) is large.

The magnetic sensors 40, 41, and 42(42a), 42b may have a member capable of shielding a magnetic field, such as a magnetic shield layer. This makes it possible to prevent problems such as erroneous detection due to the influence of the magnetic field generated from the magnetic extraction section 30.

< blood transfusion pump >

The blood purification apparatus 1F may be connected to a blood delivery pump capable of flowing blood. Blood delivery pumps may be used, for example, to withdraw blood from outside the body or to circulate blood withdrawn from outside the body. Alternatively, a blood transfer pump provided outside in addition to the blood purification apparatus of the present disclosure may be used.

For example, in the blood purification apparatus 1F, blood 10 containing magnetic particles modified with a substance to be separated and capable of capturing a specific substance in the blood is flowed into the main flow paths 20, 21, and 22 through which the blood 10 can flow. Further, at least a part of the magnetic particles contained in the blood 10 is collected by the magnetic extraction unit 30 that can generate a magnetic field. Then, by the magnetic sensors 40, 41 capable of detecting the presence of the magnetic particles, it is detected whether or not the magnetic particles remain in the blood after at least a part of the magnetic particles have been collected by the magnetic extraction portion 30.

Although the sixth embodiment of the present disclosure has been described in detail above, the technique according to the present disclosure is not limited to the sixth embodiment, and various modifications and changes may be made within the scope of the gist of the present disclosure recited in the patent claims.

For example, in the sixth embodiment, the entire device of the blood purification device 1F may be maintained at a constant temperature or within a specific temperature range. For example, the blood purification apparatus may be provided with an exterior material covering the entire apparatus and composed of a heat insulating material or the like. For example, by keeping the entire apparatus at a constant temperature, the measurement value of the magnetic sensor becomes stable. Further, it is preferable that the entire blood purification apparatus is maintained at the same temperature as the body temperature. For example, the blood purification apparatus may further have: a temperature sensor (not shown) for detecting an internal temperature of the exterior material; and a heating unit (not shown) such as a heater for heating the inside of the external material based on a signal from the control unit. This stabilizes the measurement value of the magnetic sensor and maintains the quality of the blood flowing through the blood purification apparatus for a long period of time.

As shown in fig. 6A and 6B, blood purification apparatus 1F further includes verification unit 90 for determining whether or not magnetic sensors 40, 41, 42(42a) and 42B are operating correctly. For example, the verification section 90 is connected to the magnetic sensors 40, 41, 42(42a), and 42b, and can determine whether the magnetic sensors 40, 41, 42(42a), and 42b are operating correctly or not from the output (magnetic value of blood) from the magnetic sensors. For example, the verification unit may be configured in the same manner as the verification unit 90 in the first embodiment.

The blood purification apparatus 1F may further include a controller 80 connected to the magnetic sensors 40, 41, 42(42a) and 42b, and determining whether or not the blood 10 contains magnetic particles based on the outputs of the magnetic sensors. The control section 80 can confirm the operation states of the magnetic sensors 40, 41, 42(42a) and 42b determined by the verification section 90. Thus, the control unit 80 as a safety circuit can check the operation states of the magnetic sensors 40, 41, 42(42a) and 42b, and as a result, can accurately determine whether or not the blood 10 contains magnetic particles.

< magnetic particles >

Examples of magnetic particles include particles exhibiting ferromagnetism or paramagnetism. At least a part of the outer peripheral portion of the magnetic particle is modified by a substance to be separated, which can capture a specific substance in blood.

The magnetic particles may include, for example, iron, cobalt, nickel, inorganic compounds thereof, organic-modified inorganic compounds in which these metals or inorganic compounds are modified with organic compounds, and the like.

The magnetic particles can capture a specific substance in blood by capturing the substance by the separated components. The specific method for capturing a specific component in blood by the component capturing substance to be separated is not particularly limited, and for example, chemical bonding, adsorption, steric structure capturing, or the like can be suitably employed. The magnetic particles may be magnetic particles to which a substance to be separated component-captured is added by coating treatment or the like, or may be magnetic particles composed of the substance to be separated component-captured itself. Further, the magnetic particles may be embedded in the particulate-formed substance captured by the separated component.

At least a part of the outer circumferential portion of the magnetic particle is preferably coated with a polymer or silica matrix depending on the component to be separated.

At least a part of the outer circumferential portion of the magnetic particle may have hydrophobicity or hydrophilicity depending on the component to be separated.

The average particle diameter of the magnetic particles may be 2nm or more. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles can be efficiently recovered by the magnetic field generating means provided in the magnetic extraction portion 30. If the particle diameter is 100nm or more, the effect is large, and if the particle diameter is 250nm or more, the effect is large.

The average particle diameter of the magnetic particles may be 1mm or less. When the average particle diameter of the magnetic particles is within the above range, the magnetic particles have high dispersibility and an enlarged specific surface area, and as a result, a specific substance in blood can be efficiently captured (e.g., adsorbed). If it is 10 μm or less, the effect is greater; if the thickness is 5 μm or less, the effect is further increased.

In the present specification, the "average particle diameter" refers to a particle diameter (also referred to as a median diameter D) having a cumulative value of 50% in a particle diameter distribution obtained by a laser diffraction/scattering method₅₀)。

The animal which can purify blood by the blood purification apparatus 1F is not particularly limited, and may be a human or non-human animal such as livestock or pets. Examples of animals other than humans include dogs, cats, monkeys, pigs, cows, horses, sheep, goats, rats, mice, white rats, birds, and the like.

As described above, the blood purification apparatus 1F can extract a specific substance from the blood to purify the blood. The blood purifying apparatus 1F may be directly connected to the animal, or may immediately purify the blood taken from the animal. Alternatively, the blood purification apparatus 1F may purify blood taken from an animal in advance without being directly connected to the animal. The purified blood may be returned to the individual animal immediately, or may be temporarily stored and then returned to the individual animal.

In the present embodiment, examples of the specific substances in blood removed by the magnetic particles include: low molecular weight compounds, proteins, nucleic acids, cells, and the like. More specifically, substances causing diseases such as urea, creatinine, uric acid, β 2 microglobulin, LDL cholesterol, abnormal antibodies in immune diseases, viruses, bacteria, fungi, cancer cells, and the like are exemplified.

The technique according to the present disclosure has been explained in detail using the above embodiments. The technique according to the present disclosure is not limited to each of the above embodiments. That is, an improved embodiment in which at least a part of the above-described embodiments is modified, changed, or improved, or one or more combinations of the above-described embodiments, or a combination of the above-described embodiments and the improved embodiment may be included in the technique according to the present disclosure within the scope of the technical idea of the present invention described in the patent claims.

Description of the reference numerals

1A: blood purification device

1B: blood purification device

1C: blood purification device

1D: blood purification device

1E: blood purification device

1F: blood purification device

2: connector (entrance)

3: connector (export)

10: blood, blood-enriching agent and method for producing the same

20: main flow path

21: main flow path

22: main flow path

23: return path

30: magnetic extraction part (magnetic extraction component)

40: magnetic sensor

41: magnetic sensor

42: magnetic sensor

42 a: magnetic sensor

42 b: magnetic sensor

50: filter

61: first channel selector (first channel selector)

62: second channel selector (second channel selector)

70: magnetic particle mixing section

80: control unit

90: a verification unit.