JP5965151B2 - Bioparticle counter for dialysis, bioparticle counting method for dialysis, and dialysate monitoring system - Google Patents

Description

  The present invention relates to a bioparticle counter for dialysis for detecting in real time particles derived from organisms in the dialysate (hereinafter referred to as bioparticles), a bioparticle counting method for dialysis, and a dialysis equipped with a bioparticle counter for dialysis. The present invention relates to a liquid monitoring system.

  Conventionally, dialysate administered to the human body is processed so that there is no problem even if it enters the human body by filtration of biological particles using a filter, etc., and the dialysate is put into the dialysate by inspection such as culture method (official method) or fluorescent dye method. Inspected for the presence of biological particles. In hemodialysis, the dialysate is circulated to a specific medical device, and the hemodialyzed blood is administered to the human body. Therefore, the dialysate is also filtered and manufactured and managed. Inspection is being conducted.

  In the inspection by the culture method, the biological particles in the dialysate are cultured on the culture ground under conditions such as low temperature and long time (several days to one week), and the biological particles are confirmed by checking whether colonies are formed. Whether or not exists is being examined. In the fluorescent dye method, a specific staining reagent is dropped into the dialysate and stained for several minutes, then irradiated with light, photographed with a CCD camera, etc., and biological particles are present by counting the points emitted. Whether or not to do so and counting of the number of biological particles are performed (for example, see Patent Document 1).

JP 2007-300840 A

  Here, when the dialysate test by the fluorescent dye method in the prior art of Patent Document 1 is performed, the dialysate is moved to a place different from the place where hemodialysis is performed at each test, and staining with a specific staining reagent is performed. It was necessary to count the number of biological particles after processing and photographing with a CCD camera. In addition, it took about 20 minutes to confirm the result of the dialysate test. Therefore, the test could not be performed in real time during hemodialysis.

  Therefore, the present invention can test the dialysate administered to the human body in real time, detect the biological particles in the dialysate, count the number, and notify the result on the spot based on the desired conditions. The technology that can be provided.

In order to solve the above problems, the present invention employs the following solutions.
Solution 1: The bioparticle counter for dialysis of the present invention includes a liquid circulation means for circulating a dialysate for hemodialysis or blood filtration, and one of the dialysate that has been passed by the liquid circulation means and passed through the filter. A liquid diverting means for diverting a part before being administered to a human body, a light emitting means for irradiating light of a predetermined wavelength from one light source toward the dialysate diverted by the liquid diverting means, and the dialysate Among the light emitted by the interaction between the target object to be emitted and the light emitted by the light emitting means, it is determined whether or not the target object contained in the dialysate is a biological particle based on autofluorescence A biological particle counter for dialysis comprising biological particle determination means.

The counting of biological particles by the biological particle counter for dialysis of the present invention has, for example, the following characteristics and proceeds according to a predetermined procedure.
(1) A blood purification device for artificially purifying blood, for example, dialysate before flowing into a dialyzer where hemodialysis or hemofiltration dialysis is performed, or before being mixed into blood that has undergone blood filtration In order to test whether or not biological particles are present in the dialysate, a part of the dialysate before being administered to the human body (before being used for hemodialysis) is collected. Then, the collected dialysate is irradiated with light having a specific wavelength. For example, laser light with a single wavelength is emitted from a laser diode. Here, the dialysate necessary for hemodialysis and blood filtration contains components that are lacking in the human body, but since almost all of it is composed of water, the dialysate will be described below as water. In addition, the target object included in the dialysate (water) to be detected is biological particles, non-biological particles, or the like.

(2) When laser light is irradiated according to (1) above, light is emitted by the interaction between the laser light and the object. The main light that is specifically emitted is scattered light emitted by reflection with biological particles, autofluorescence that is absorbed by biological particles and emitted using the energy, non-biological particles and Scattered light emitted by reflection of the light.

(3) Based on the autofluorescence from the biological particles according to (2) above, it is determined whether or not the object contained in the water is a biological particle. And when it determines with it being a biological particle in the determination, the number of biological particles will be counted by counting the number.

  Thus, according to this solution, the bioparticle is detected by detecting the autofluorescence from the autofluorescent substance as an index with respect to the dialysate before hemodialysis or the dialysate before administration to the human body. Can be determined in real time. In addition, since it can be confirmed in real time that bioparticles are present in the dialysate at the site where hemodialysis is being performed, the dialysate can be put into the dialysate before it becomes abnormal (counting a large number of bioparticles). Since it can cope, the influence with respect to a patient can be suppressed as much as possible.

  Solution 2: The bioparticle counter for dialysis of the present invention transmits the light emitted by the interaction between the object or the dialysate and the light emitted by the light emitting means in the solution 1. The apparatus further comprises autofluorescence selection optical means for reducing Raman scattered light emitted from the dialysate and transmitting autofluorescence emitted from the object, and the biological particle determination means is the autofluorescence selection optical means. Based on the light after the Raman scattered light has been reduced by the above, it is determined whether or not the object contained in the dialysate is a biological particle, and the light emitting means emits the autofluorescence emitted after irradiation The dialysis biological particle counter is characterized by irradiating the light having the predetermined wavelength that makes the peak wavelength of the Raman scattering light different from the peak wavelength of the Raman scattered light.

The counting of biological particles by the dialysis biological particle counter of the present solution has, for example, the following characteristics and proceeds according to a predetermined procedure.
(4) When laser light is irradiated according to (1) above, light is emitted by the interaction between the laser light and water in addition to the light due to the interaction between the laser light of (2) and the object. Become. Therefore, the main light that is specifically emitted is scattered light emitted by reflection with biological particles, autofluorescence that is absorbed by biological particles and emitted using the energy, non-biological particles and Scattered light emitted by the reflection of light and Raman scattered light emitted by converting the wavelength of light incident on water (molecules). In addition, the wavelength of the laser beam to be irradiated is set so that the peak wavelength of the autofluorescence spectrum is different from the peak wavelength of the scattered light and the Raman scattered light.

(5) The wavelengths of the light emitted by the above (4) are different from each other. For example, the scattered light from biological particles and non-biological particles is approximately the same as the wavelength of the laser light, but Raman scattered light or The wavelength of light such as autofluorescence is longer than the wavelength of the laser light. In addition, for the wavelength of Raman scattered light and autofluorescence, the respective wavelength distribution regions may overlap. For example, the peak value of the wavelength distribution (peak wavelength) in autofluorescence is the peak value of the wavelength distribution of Raman scattered light. The wavelength may be longer than (peak wavelength). Here, by using the fact that the peak wavelengths of autofluorescence and Raman scattered light differ depending on the setting of the wavelength of the laser light to be irradiated, an optical separator based on a specific wavelength (cut-off wavelength) is used. The amount of scattered light can be reduced from the amount of autofluorescence. For example, using a long-pass filter or a band-pass filter with a specific wavelength as a reference, Raman scattered light is reduced, and almost all autofluorescence is transmitted.

(6) Based on the light transmitted by the above (5), that is, the autofluorescence from the biological particles, it is determined whether or not the object contained in the water is a biological particle. And when it determines with it being a biological particle in the determination, the number of biological particles will be counted by counting the number.

  As described above, according to the present solution, the dialysis solution before hemodialysis or blood filtration uses irradiation light that makes the Raman scattered light by water different from the peak wavelength of autofluorescence, and optically analyzes the Raman scattered light. By suppressing the effect and further reducing the influence, it is possible to efficiently detect autofluorescence from the autofluorescent substance as an index, and to determine in real time whether or not biological particles are present. In addition, since it can be confirmed in real time that bioparticles are present in the dialysate at the site where hemodialysis is being performed, the dialysate can be put into the dialysate before it becomes abnormal (counting a large number of bioparticles). Since it can cope, the influence with respect to a patient can be suppressed as much as possible.

  Solution 3: The bioparticle counter for dialysis according to the present invention is the selection of scattered light that reflects scattered light emitted from the object and transmits light including the autofluorescence and the Raman scattered light. The biological particle determination means further comprises an optical means, and the biological particle determination means determines whether the object contained in the dialysate is a biological particle based on the light after passing through the scattered light selection optical means and the autofluorescence selection optical means. It is a biological particle counter for dialysis characterized by determining whether or not.

The counting of biological particles by the dialysis biological particle counter of the present solution has, for example, the following characteristics and proceeds according to a predetermined procedure.
(7) According to the above (5), the wavelength of the light emitted by the above (4) is similar to the wavelength of the laser light while the scattered light from the biological particles and non-biological particles is comparable to the wavelength of Raman. The wavelength of light such as scattered light and autofluorescence was longer than the wavelength of the laser light. Therefore, the wavelength of scattered light from biological particles and non-biological particles is shorter than Raman scattered light and autofluorescence. Using this wavelength relationship, scattered light from biological particles or non-biological particles can be selected using an optical separator based on a specific wavelength. For example, it is possible to transmit only scattered light from biological particles or non-biological particles using a short-pass filter based on a specific wavelength (cutoff wavelength). In addition, by using a dichroic mirror that separates based on the cutoff wavelength, scattered light from biological and non-biological particles with wavelengths shorter than the separation wavelength is reflected, and light with a wavelength longer than the separation wavelength ( Raman scattered light and autofluorescence) can be transmitted.

(8) Included in water based on the correlation between the light separated by (5) (autofluorescence) and the light separated by (7) (scattered light from biological or non-biological particles) It is determined whether the target object is a biological particle. And when it is determined that it is a biological particle in the determination, the number of biological particles is counted by counting the number, and when it is determined that it is a non-biological particle, the number is also counted. Also good.

(9) Here, the long pass filter of (5) may be installed on the transmission side downstream of the dichroic mirror of (4). Regarding the light separation by the above (5) and (7), first, the separation by the above (5) may be performed, and the separation by the above (5) may be performed on the light after the separation. Specifically, first, the scattered light from biological or non-biological particles shorter than the cutoff wavelength is reflected by the separation according to (7) above, and light including Raman scattered light or autofluorescence longer than the cutoff wavelength. Next, the separation according to the above (5) is performed on the light including the Raman scattered light or the autofluorescence that has been transmitted, and the light including the autofluorescence longer than the cutoff wavelength is transmitted.

(10) Correlation between light (autofluorescence) finally separated (transmitted) by (9) above and light (scattered light from biological or non-biological particles) separated (reflected) in the middle Based on the relationship, it is determined whether the object contained in the water is a biological particle. And when it is determined that it is a biological particle in the determination, the number of biological particles is counted by counting the number, and when it is determined that it is a non-biological particle, the number is also counted. Also good.

  Thus, according to the present solution, since the transmission of the Raman scattered light is suppressed and the autofluorescence from the biological particles is transmitted, the correlation with the scattered light from the target object is caused. It can be determined whether or not the object contained in the water is a biological particle. For example, when there is scattered light and transmitted light, it is determined that the object is a biological particle. When there is only scattered light, it is determined that the object is a non-biological particle that is not a biological particle, and there is transmitted light. Can be determined to be Raman scattered light by water. Thereby, the counting accuracy with respect to the biological particles can be further improved. Also, the use of optical separators such as dichroic mirrors, long pass filters, band pass filters, and short pass filters can be selected according to the installation environment (conditions).

  Solution 4: The bioparticle counter for dialysis according to the present invention is a solution of the first light having a size corresponding to the amount of light at the time of receiving the light after passing through the autofluorescence selection optical means. Autofluorescence light receiving means for outputting a signal, light after passing through the scattered light selecting optical means, and a scattered light receiving means for outputting a second signal having a magnitude corresponding to the amount of light when received. When the magnitude of the second signal output by the scattered light receiving means is greater than or equal to a predetermined threshold, the scattered light that outputs a detection signal as detecting scattered light emitted from the object contained in the dialysate A detection signal output means, and a light-shielding wall that prevents light incident from other than the optical path from entering the optical path from the scattered light selection optical means to the autofluorescence light receiving means through the autofluorescence selection optical means, The biological particles The determining means is a case where the detection signal is output by the scattered light detection signal output means, and the scattered light emitted from the object contained in the dialysate is received by the scattered light receiving means. Light is received by the autofluorescence light receiving means at the same time as the time, and the magnitude of the first signal corresponding to the light received by the autofluorescence light receiving means at the same time as the time is greater than or equal to a predetermined threshold value In this case, the biological particle counter for dialysis is characterized in that the object contained in the dialysate corresponding to the detection signal output by the scattered light detection signal output means is determined as a biological particle.

The counting of biological particles by the dialysis biological particle counter of the present solution has, for example, the following characteristics and proceeds according to a predetermined procedure.
(11) The light (autofluorescence) transmitted in (7) is received, and a first signal having a magnitude corresponding to the received light amount is output. For example, a first signal corresponding to the amount of received light is output by a light detection device such as a photomultitube or a photodiode.

(12) Receives the light reflected by (7) (scattered light of the object) or the light reflected by (7) (scattered light of the object), and the size according to the received light quantity The second signal is output. For example, a second signal corresponding to the amount of received light is output by a photodetector such as a photodiode.

(13) It is determined whether or not the magnitude of the second signal output in (12) is greater than or equal to a predetermined threshold, and if the result of determination is that it is greater than or equal to the threshold, scattering from the object A detection signal (for example, a detection flag) indicating that light has been detected is output.

(14) When the detection signal is output in (13) above, the signal is separated in (5) at the time corresponding to the detection signal, that is, at the same time as the light reception in (12) above. Alternatively, when the light transmitted in (10) is received and the first signal is output, it is determined in the determination in (6) that the object is a biological particle. In addition, when the detection signal is output and the 1st signal is not output, you may determine with a target object being a non-living particle. And when it is determined that it is a biological particle in the determination, the number of biological particles is counted by counting the number, and when it is determined that it is a non-biological particle, the number is also counted. Also good. Further, the size of the biological particles (or non-biological particles) may be determined based on the size of the second signal.

  As described above, according to this solution, a predetermined threshold value is provided for the scattered light with the object, so that a signal larger than the threshold value can be determined as the scattered light of the object.

  Solution 5: The bioparticle counter for dialysis according to the present invention is the self-propagation counter according to any one of Solution 2 to Solution 4, wherein the predetermined wavelength of light emitted by the light-emitting means is 375 nm to 420 nm. The dialysis biological particle counter is characterized in that a cutoff wavelength which is a reference for transmitting light by the fluorescence selective optical means is 450 nm to 490 nm.

The counting of biological particles by the dialysis biological particle counter of the present solution has, for example, the following characteristics and proceeds according to a predetermined procedure.
(15) The wavelength of the laser beam irradiated according to (1) above is set to 375 nm to 420 nm, and the cutoff wavelength that reduces Raman scattered light due to water according to (5) or (10) and transmits autofluorescence is 450 nm. Set to a predetermined wavelength between ˜490 nm.

  Thus, according to this solution, for example, by irradiating laser light of 405 nm and using autofluorescence from intracellular riboflavin of biological particles in water as an index, the energy state of riboflavin can be easily excited. Furthermore, since the peak wavelength of the auto-fluorescence is about 520 nm, the peak wavelength of the Raman scattered light of water is about 465 nm, so that the cut-off used as a reference for the auto-fluorescence selection optical means (long-pass filter) If the wavelength is set to 490 nm, the separation can be efficiently performed, so that the counting accuracy with respect to the biological particles can be further improved.

  Solution 6: A dialysate monitoring system according to the present invention is a dialysate monitoring system including the bioparticle counter for dialysis according to any one of Solution 1 to Solution 5, wherein the dialysate is used by a plurality of people. A multi-person dialysate supply means for supplying a multi-person, a multi-person liquid distribution means for distributing and distributing the dialysate supplied by the multi-person dialysate supply means to each dialysis monitoring device, and the dialysis Informing means for informing the determination result by the biological particle counter, wherein the biological particle counter for dialysis is at least one of the dialysis fluid supply means for multiple persons or the plurality of dialysis monitoring devices. For the dialysis fluid that is connected and circulates to the dialysis fluid supply means for multiple people or the dialysis fluid that is diverted to the dialysis monitoring device, it is determined whether or not the object contained in the dialysis fluid is a biological particle. Do A dialysate monitoring system characterized and.

The inspection of biological particles in the dialysate by the dialysate monitoring system of the present invention has the following features, for example, and proceeds according to a predetermined procedure.
(16) For example, since hemodialysis usually takes several hours, hemodialysis of a plurality of people is performed at one time. Therefore, in order to supply dialysate for a plurality of people, a multi-person dialysate supply device for storing a large amount of dialysate in advance is provided.

(17) The dialysate supplied from the multi-person dialysate supply device according to (16) above circulates the piping to the place where hemodialysis is performed. Note that the piping is branched in the middle, and the dialysate that has flowed through the branched piping is used for hemodialysis, and hemodialysis is performed on a plurality of patients at the same time. It is to be noted that hemodialysis is monitored for each patient by a dialysis monitoring device, and dialysate is first sent from the multi-person dialysate supply device to the dialysis monitoring device, and the patient's hemodialysis is performed through the dialysis monitoring device. Become.

(18) Here, in the above (17), before hemodialysis is performed on each patient with the dialysate, a part of the dialysate is divided and collected, and each bioparticle counter for dialysis is used. A determination is made whether biological particles are present.

(19) The result of the determination as to whether or not there is a biological particle using the biological particle counter for dialysis according to the above (18) is displayed on the screen by the biological particle counter for dialysis or the dialysis monitoring device or an alarm sound. Or may be collected and managed by a central monitoring and control device.

  Thus, according to this solution, when hemodialysis is simultaneously performed on a plurality of patients, it can be confirmed that biological particles are present in the dialysate in real time. In addition, the result is displayed on the screen by a biological particle counter for dialysis or a dialysis monitoring device or informed by a warning sound. Therefore, the influence on the patient can be suppressed as much as possible.

  Solution 7: A dialysate monitoring system according to the present invention is the dialysate monitoring system including the bioparticle counter for dialysis according to Solution 6, wherein the bioparticle counter for dialysis is the dialysis monitor. It is a dialysate monitoring system characterized by being provided for each.

The inspection of biological particles in the dialysate by the dialysate monitoring system of the present invention has the following features, for example, and proceeds according to a predetermined procedure.
(20) Since the dialysis monitoring device according to (17) above is provided with a bioparticle counter for dialysis, biological particles are present in the dialysate in real time on the spot for hemodialysis performed at a plurality of locations. Can be confirmed. Accordingly, early treatment of the dialysate can be performed, so that the influence on the patient can be suppressed as much as possible.

  According to the biological particle counter for dialysis, the biological particle counting method for dialysis, and the dialysis fluid monitoring system of the present invention, the dialysis fluid used for the dialysis fluid is lighted even while the patient is performing hemodialysis or blood filtration. Can be determined using the detection of autofluorescence by biological particles as an index, and whether the dialysate is contaminated with biological particles in real time.

It is a figure explaining the system regarding the dialysate test | inspection in hemodialysis. It is a schematic block diagram which shows one Embodiment of the bioparticle counter for dialysis. It is a figure which shows an example of the excitation absorption spectrum of riboflavin which is an example of an autofluorescent substance, and NAD (P) H, and the autofluorescence spectrum from the substance. It is a figure which shows an example of the Raman scattered light spectrum by water at the time of irradiating the light whose wavelength is 405 nm. It is a figure which shows an example of the time change intensity distribution of the Raman scattered light by the water before optical filter entrance. It is a figure which shows an example of the time change intensity distribution of the Raman scattered light by the water after permeation | transmission of an optical filter. It is a figure which shows an example of the time change intensity distribution of all the lights before an optical filter incident. It is a figure which shows an example of the time change intensity distribution of all the lights after optical filter transmission. It is a flowchart which shows the example of a procedure of an autofluorescence count process. It is a flowchart which shows the example of a procedure of a data collection process. It is a flowchart which shows the example of a procedure of a data analysis process. It is a flowchart which shows the example of a procedure of an analysis process. It is a figure which shows an example of the output signal from the light-receiving device for fluorescence and the light-receiving device for scattering. It is a flowchart which shows the example of a procedure of an analysis result output process. It is a flowchart which shows the example of a procedure of alerting | reporting process. It is a figure which shows an example of the alerting | reporting of the count result of a biological particle. It is a figure explaining the system of the artificial dialysis apparatus for many people.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a diagram illustrating a system related to a dialysate test in hemodialysis.
As shown in FIG. 1, hemodialysis of a patient is performed by a hemodialysis apparatus 700. Determination of whether or not biological particles are present in the dialysate used for the hemodialysis and counting the number of biological particles are performed by dialysis. This is performed by the biological particle counter 77. The hemodialyzer 700 and the bioparticle counter 77 for dialysis will be specifically described. The present invention is not limited to hemodialyzers, but can be used for the dialysate in blood filter devices.

[Hemodialyzer]
The hemodialysis apparatus 700 is insufficient while discharging waste products in the blood, a dialysis monitoring apparatus 710 that monitors and adjusts patient information and the flow of blood and dialysate, and the like. The blood purifier 770 diffuses from the dialysate into the blood, and the dialysate supply device 730 that supplies the dialysate.

[Dialysis monitoring device]
The dialysis monitoring device 710 includes a control monitoring unit 740 and a flow adjustment unit 750. The control monitoring unit 740 is, for example, a device that controls and monitors overall hemodialysis, and adjusts the flow of blood collected from a patient and blood administered after hemodialysis, and dialysis sent from the dialysate supply device 730 to the blood purifier 770. Control and monitoring device 743 that adjusts the temperature and flow of the fluid, monitors the patient's physical condition (for example, blood pressure and electrocardiogram information), flows and monitors the dialysate before and after hemodialysis, and various information, progress, and input data And the like, and a display unit 745 (notification means) for displaying the above and an operation unit 747 for accepting an operation from the outside (for example, a medical worker).

  Specifically, the control monitoring device 743 is a device that includes a CPU that executes various processes, a ROM that stores processing contents (programs and data), a RAM that stores various information, and the like. The display unit 745 is a display and displays information output from the control monitoring device 747. The operation unit 747 includes, for example, a plurality of input buttons, and can receive various processes and input / output various information by pressing a predetermined operation button by a medical worker. Moreover, although not shown in figure, you may provide the external connection terminal which receives the control signal from the outside (central control apparatus), or outputs various information.

[Distribution Coordination Department]
The flow adjustment unit 750 includes, for example, a blood pump 753 for adjusting and circulating the blood flow collected from the patient, a dialysate adjustment valve 755 for adjusting the flow rate of the dialysate supplied from the dialysate supply device 730, blood It comprises a discharge device 757 for discharging the dialysate discharged from the purifier 770. These blood pump 753, dialysate adjustment valve 755, and discharge device 757 are controlled by the control monitoring device 747. Note that the dialysate discharged from the discharge device 757 to the outside of the dialysis monitoring device 710 is flowed to the waste liquid processing unit 759 and then subjected to waste liquid treatment.

[Distribution circuit]
The circulation circuit 720 includes blood circuits 721, 722, 727 and dialysate circuits 723, 724, 725, 727, 728.

[Blood circuit]
The blood circuit 721 connects between the patient's artery and the blood inlet of the blood pump 753, and flows blood collected from the patient to the blood pump 753. The blood circuit 722 connects between the blood outlet and the blood inlet of the blood purifier 770, and flows the blood pumped out by the blood pump 753 to the blood purifier 770. The blood circuit 727 connects between the blood outlet of the blood purifier 770 and the patient's vein, and administers blood hemodialyzed by the blood purifier 770 to the patient's vein. The flow rate of blood flowing through these blood circuits 721, 722, and 727 is adjusted by a blood pump 753, and for example, blood with a flow rate of about 200 ml / min circulates.

[Dialyzed fluid circuit (liquid distribution means, liquid distribution process)]
The dialysate circuit 723 flows dialysate supplied from the dialysate supply device 730. In the middle of the dialysate circuit 723, a dialysate valve 755 for adjusting the flow rate of the dialysate is provided. The dialysate flowing through the dialysate circuit 723 is diverted by the dialysate diverter 725b (liquid diverting means) in order to count biological particles in the dialysate before flowing into the dialysate inlet of the blood purifier 770. . Specifically, a part of the dialysate flowing through the dialysate circuit 723 is flowed to the dialysate circuit 725 after the diversion, and then sent to the bioparticle counter 77 for dialysis. On the other hand, most of the dialysate flowing through the dialysate circuit 723 is supplied to the dialysate circuit 724 and then to the dialysate inlet of the blood purifier 770. The dialysate circuit 726 flows the dialysate after the detection and counting process of the bioparticles in the dialyzing bioparticle counter 77 to the waste liquid treatment device 78, and the dialysate is subjected to waste liquid treatment in the waste liquid treatment device 78. The dialysate circuit 728 flows dialysate sent out from the dialysate outlet of the blood purifier 770. In the middle of the dialysate circuit 728, a discharge device 757 for discharging to the waste liquid treatment device 759 is provided. The flow rate of the dialysate flowing through these dialysate circuits 723, 724, 725, 726, and 728 is adjusted by the dialysate adjustment valve 755 and the bioparticle counter 77 for dialysis, for example, the dialysate having a flow rate of about 500 ml / min. Is flowed into the blood purifier 770, and the dialysate having a flow rate of about 10 ml / min is flowed into the bioparticle counter 77 for dialysis.

[Dialyzed fluid supply device]
The dialysate supply device 730 is a device that supplies dialysate. For example, the dialysate is stored in a tank, and the dialysate adjustment valve 755 in the dialysis monitoring device 710 is operated to supply the dialysate. The blood can be supplied to the blood purifier 770 or the biological particle counter 77 for dialysis. Further, a filter 735 is installed between the dialysate supply device 730 and the blood purifier 770, and final purification of the dialysate before flowing into the blood purifier 770 is performed.

[Blood Purifier]
The blood purifier 770 is a device that purifies blood collected from a patient, for example, and is specifically a hemodialyzer (dialyzer). In the case of a blood filtration device, a blood filter (hemofilter) is used. In the present embodiment, description will be made assuming that a hemodialyzer dialyzer 770 is used as a blood purifier.

  The dialyzer 770 includes a blood inlet, a blood outlet, a dialysate inlet, and a dialysate outlet, a blood circuit 722 is a blood inlet, a blood circuit 727 is a blood outlet, a dialysate circuit 724 is a dialysate inlet, The dialysate circuit 728 is connected to the dialysate outlet. In addition, a plurality of hollow fiber membranes (for example, thousands) capable of circulating blood inside are provided, and blood flowing from the blood circuit 722 via the blood inlet is divided into thousands of hollow fiber membranes. The hemodialyzed blood is discharged from the blood outlet to the blood circuit 727. Further, the dialysate flowing from the dialysate circuit 724 through the dialysate inflow port is caused to flow around the hollow fiber membranes in the opposite direction to the blood, and the dialyzed dialysate is dialyzed from the dialysate outlet. It flows out to the liquid circuit 728. Inside the dialyzer 770, diffusion occurs such that waste in the blood moves into the dialysate outside the hollow fiber membrane, and components deficient in the blood move from the dialysate through the hollow fiber membrane into the blood. ing.

[Biological particle counter for dialysate]
The bioparticle counter 77 for dialysis irradiates the object with light, detects the scattered light and autofluorescence from the object, and the number of autofluorescence based on the signal output from the light detection system 1. It is comprised from the autofluorescence counting system 2 which counts, the operation parts 72 and 74, and the alerting | reporting display 76 (notification means). The operation units 72 and 74 are constituted by, for example, a plurality of types of buttons 72 and a controller 74, and can accept an operation of the bioparticle counter for dialysis 77 by a medical worker. The notification display 76 can display input information, operation information, a counting result, and the like, for example.

  Note that a suction pump or a flow rate adjustment valve 726b may be provided inside the dialysis particle counter 77 or in the dialysate circuit 726. For example, by providing the particle counter 77 for dialysis, it is possible to easily adjust the dialysate supply amount of the dialysate supply device 730 when the dialysate supply amount is not sufficiently adjusted.

  Hereinafter, the components of the dialysis biological particle counter 77, the determination of the presence or absence of biological particles in the dialysate, the counting of biological particles, and the like will be specifically described.

FIG. 2 is a schematic configuration diagram showing an embodiment of a bioparticle counter for dialysis.
As shown in FIG. 2, the biological particle counter system irradiates light on an object, detects light scattered from the object and autofluorescence, and outputs a signal output from the light detection system 1. The autofluorescence counting system 2 is configured to count the autofluorescence number based on the autofluorescence count. With these systems, it is possible to detect and count biological particles (hereinafter referred to as biological particles) among objects in water. The bioparticles that can be detected (counted) in the present embodiment are, for example, bioparticles having a size of 0.1 μm to several hundreds of μm, and specifically, bacteria, yeasts, molds, and the like. The light irradiated to the biological particles is a laser beam in the ultraviolet region, and is a substance necessary for metabolism (riboflavin, NAD (P) H (nicotinamide adenine dinucleotide (phosphorus) in the body (cells) of the biological particles). The autofluorescence emitted from the acid))) is detected as an index.

[Light detection system]
The light detection system 1 includes, for example, a light emitting device 10, an irradiation optical lens system 20, a target flow device 30, a first condensing optical lens system 40, a light shielding device 50, a scattered light selection optical device 60, a light shielding wall 65, and autofluorescence selection. The optical device 70 includes a second condensing optical lens system 80, a fluorescence light receiving device 90, a third condensing optical lens system 100, and a scattering light receiving device 110. With these components, the object can be irradiated with light, and scattered light and autofluorescence from the object can be detected. Hereinafter, each component will be specifically described.

[Light emitting device (light emitting means, light emitting process)]
The light emitting device 10 includes, for example, a semiconductor laser diode (including a semiconductor LED element; hereinafter referred to as a laser diode). Laser light is oscillated by the laser diode 10 and applied to the dialysate (water) containing biological particles. The wavelength of the laser light oscillated by the laser diode 10 is determined corresponding to a substance that can emit autofluorescence existing in the cells of the biological particles (hereinafter referred to as autofluorescent substance). Here, the autofluorescent material has an excitation wavelength that easily absorbs the energy of the irradiated light and is excited to an excited state. The excitation wavelength differs depending on the substance, and the wavelength of the autofluorescence emitted when returning from the excited state to the ground state also differs depending on the autofluorescent substance. The excitation wavelength and autofluorescence wavelength of the autofluorescent material will be described with specific examples.

[Excitation wavelength and autofluorescence wavelength]
FIG. 3 is a diagram showing an example of an excitation absorption spectrum of riboflavin and NAD (P) H, which is an example of an autofluorescent substance, and an autofluorescence spectrum from the substance.
As shown in FIG. 3, each distribution shows an excitation wavelength spectrum of NAD (P) H, an excitation wavelength spectrum of riboflavin, an autofluorescence spectrum from NAD (P) H, and an autofluorescence spectrum from riboflavin. For example, the excitation wavelength spectrum of NAD (P) H has a distribution with a peak at a wavelength of about 340 nm. Moreover, the excitation wavelength spectrum of riboflavin has a distribution with a peak at a wavelength of about 375 nm, and expresses that it is suitable to irradiate laser light having a wavelength of 375 nm to 420 nm in order to facilitate excitation of riboflavin. ing.

  Therefore, in order to release a lot of autofluorescence from the biological particles, the wavelength of the laser light oscillated from the laser diode 10 corresponds to the excitation wavelength of NAD (P) H or riboflavin present in the cells of the biological particles. It is determined. In the present embodiment, it is assumed that laser light having a wavelength of 405 nm is oscillated from the laser diode 10. By irradiating the laser beam having a wavelength of 405 nm, autofluorescence due to riboflavin is released from the biological particles.

[Irradiation optical lens system]
The irradiation optical lens system 20 is composed of, for example, a plurality of types of optical lenses. For example, it is composed of a collimator lens, a biconvex lens, and a cylindrical lens, and the laser beam oscillated from the laser diode 10 is adjusted to a parallel light beam and irradiated onto the object.

[Target flow equipment]
The target flow device 30 (flow cell 30) is composed of, for example, a hollow quadrangular cylinder portion 32 made of synthetic quartz, sapphire, or the like, and includes an object (biological particles 35 or non-biological particles 37). The dialysate (water) 33 is structured to flow from top to bottom. The laser beam 31 oscillated from the laser diode 10 is irradiated to the hollow region where the dialysate (water) in the cylindrical portion 32 flows to form a detection region.

  In this detection region, the laser beam 31 interacts with water (water molecules) of the dialysate (water) 33 flowing through the flow cell 30 and the target (biological particles 35 or non-biological particles 37).

  Since the wavelength of the laser beam 31 incident on the biological particle 35 is 405 nm, the scattered light from the biological particle 35 is also emitted at a wavelength of 405 nm. As shown in FIG. 3, when the laser beam 31 is absorbed by the riboflavin in the cells of the biological particles 35, the wavelength has a distribution with a peak at about 520 nm. Here, the scattered light or autofluorescence emitted from the biological particles 35 is emitted to the surroundings.

  Further, the scattered light by the laser light 31 incident on the non-biological particle 37 is the same as the scattered light emitted from the biological particle 35.

  As described above, when the biological particles 35 and the non-biological particles 37 interact with the laser light 31, the scattered light from the biological particles 35 and the non-biological particles 37 or the autofluorescence from the biological particles 35 is emitted. . These lights are detected by the light receiving device through a plurality of condensing lens systems and wavelength selection optical devices. The intensity of the scattered light, that is, the amount of scattered light depends on the size of the biological particles 35 and the non-biological particles 37, and the larger the amount, the larger the amount of light. Here, autofluorescence from the biological particle 35 depends on the amount of riboflavin in the cell of the biological particle 35. Further, depending on the amount of light (intensity) of the laser beam 31, if the laser output is increased and the flow cell 30 is irradiated with a large amount of the laser beam 31, the scattered light from the biological particles 35 and the non-biological particles 37, the biological particles 35. Autofluorescence from will also increase. However, scattered light from biological particles 35 and non-biological particles 37 and light other than autofluorescence from biological particles 35 also increase, and specifically, light due to the interaction (Raman scattering) between laser light 31 and water 33. (Raman scattered light) will also increase. Next, the Raman scattered light by water is demonstrated concretely.

[Raman scattering by water]
FIG. 4 is a diagram illustrating an example of a Raman scattered light spectrum by water when light having a wavelength of 405 nm is irradiated. As shown in FIG. 4, when water is irradiated with laser light 31 with a wavelength of 405 nm, Raman scattered light having a wavelength distribution with a peak at a wavelength of about 465 nm is emitted by the interaction between water and the laser light 31.

[Shading device]
The light shielding device 50 is composed of, for example, a laser trap. The laser trap 50 oscillates from the laser diode 10 and shields the laser beam 31 that has passed through the flow cell 30 without causing interaction. By shielding the light, the laser beam 31 that has passed therethrough is prevented from being reflected at various places and the like to become noise in detecting scattered light from the biological particles 35 and autofluorescence.

[First condensing optical lens system]
The 1st condensing optical lens system 40 is comprised from the some optical lens, for example. The first condensing optical lens system 40 is installed at a position at an angle of about 90 degrees with respect to the traveling direction (optical axis) of the laser light 31. The first condensing optical lens system 40 collects the scattered light from the biological particles 35 and the non-biological particles 37 in the flow cell 30 and the autofluorescence from the biological particles 35. In order to collect as much side scattered light and autofluorescence as possible from these biological particles 35, it is preferable that the lens aperture is large, and a detection device that detects scattered light and autofluorescence from the biological particles 35 is provided. It is determined corresponding to the position (distance).

[Scattered light selection optical device (scattered light selection optical means, scattered light selection optical process)]
The scattered light selection optical device 60 is composed of, for example, a dichroic mirror. The dichroic mirror 60 of the present embodiment transmits light having a wavelength longer than 410 nm and reflects light having a wavelength shorter than 410 nm. A specific wavelength that serves as a reference for separation based on the wavelength of light is referred to as a cutoff wavelength. Therefore, since the wavelength of the scattered light from the biological particles 35 and the non-biological particles 37 scattered by the laser beam 31 of 405 nm in the flow cell 30 is mainly 405 nm, the biological particles 35 and the non-biological particles are caused by the dichroic mirror 60. The scattered light from 37 can be reflected. The scattered light from the reflected biological particles 35 and non-biological particles 37 is then condensed on the third condensing optical lens system 100 and imaged on the scattering light receiving device 110.

  On the other hand, the autofluorescence emitted from the biological particles 35 flowing in the flow cell 30 has a wavelength distribution with a peak at about 520 nm, as shown in FIG. 3, so that it is not reflected by the dichroic mirror 60. Almost everything will be transmitted. Similarly, as shown in FIG. 4, the Raman scattered light due to water has a wavelength distribution with a peak at about 465 nm, and a wavelength longer than the cut-off wavelength of 410 nm occupies the most part. Most of the light passes through the dichroic mirror 60 except for. The transmitted autofluorescence and the Raman scattered light due to water then proceed to the autofluorescence selection optical device.

  In addition, the cutoff wavelength used as the reference | standard of the dichroic mirror 60 is not limited to 410 nm, the scattered light from the biological particle 35 or the non-biological particle 37 scattered by the laser beam 31 is reflected, and autofluorescence is reflected from the biological particle 35. Any wavelength can be used as long as it is transmitted.

[Auto fluorescence selection optical device (auto fluorescence selection optical means, auto fluorescence selection optical process)]
The autofluorescence selection optical device 70 is composed of, for example, an optical filter. In the present embodiment, a long pass filter 70 that transmits light having a wavelength longer than a wavelength of 490 nm (cutoff wavelength) is provided.

  On the other hand, as shown in FIG. 4, most of the Raman scattered light by water has a wavelength shorter than the cut-off wavelength of 490 nm and can be reduced by about 90%.

[Intensity distribution change of Raman scattering light of water by long pass filter]
FIG. 5 is a diagram showing an example of a time-varying intensity distribution of Raman scattered light due to water before entering the long-pass filter, and FIG. 6 is an example of a time-varying intensity distribution of Raman scattered light due to water after passing through the long-pass filter. FIG. 5 and 6, it is shown that the intensity distribution of the Raman scattered light 33s due to water is changed by the long pass filter.

[Intensity distribution of Raman scattered light by water before entering the long pass filter]
As shown in FIG. 5, the Raman scattered light 33s due to water has a distribution in which random increase and decrease are repeated, with the horizontal axis representing time and the vertical axis representing an arbitrary unit of light. For example, there is a distribution in which the intensity of Raman scattered light 33s due to water has a peak of 0.5, there is also a distribution in which 0.3 is the peak, and a large amount of Raman scattered light 33s due to water may be incident. It may be incident in a small amount, and is incident randomly regardless of time.

[Distribution of Raman scattered light in water after passing through long-pass filter]
Further, as shown in FIG. 6, the Raman scattered light 33 s by water after passing through the long pass filter 70 with the horizontal axis representing time and the vertical axis representing intensity in arbitrary units of light is due to the water shown in FIG. 5. It shows that the magnitude is changed to about 1/10 with respect to the temporal change distribution of the Raman scattered light 33s.

  Next, not only the Raman scattered light 33s caused by water but also the light Lt that passes through the dichroic mirror, that is, the light Lt that is a total of the Raman scattered light 33s caused by water and the autofluorescence 35e emitted from the biological particles 35 will be described.

[Change of light intensity distribution by long pass filter]
FIG. 7 is a diagram illustrating an example of a time variation distribution of all light before incidence of the optical filter, and FIG. 8 is a diagram illustrating an example of a temporal variation distribution of all light after transmission through the optical filter. 7 and 8, it is shown that the intensity distribution of all the light Lt transmitted through the dichroic mirror 60 is separated by the long pass filter 70.

[Intensity distribution of light before entering the long pass filter]
As shown in FIG. 7, with the horizontal axis representing time and the vertical axis representing the relative intensity of light, the distribution of light incident on the long pass filter 70 is the distribution of Raman scattered light 33s and autofluorescence 35e due to water. It consists of the distribution by the combined (total) light Lt. For example, from a certain time to a time Δt, Raman scattered light 33s with water having a distribution with a relative intensity peaking at 0.5 and light intensity having a distribution with a relative intensity peaking at 0.2 Assuming that the self-fluorescent light 35e is incident, during the time Δt, the amount of light Lt synthesized from these amounts of light is incident, and the relative intensity distribution due to the light Lt peaks at 0.7. Distribution.

[Intensity distribution of light after passing through long pass filter]
Further, as shown in FIG. 8, the temporal change distribution of all the transmitted light Lt is almost the same as the temporal change intensity distribution of the amount of Raman scattered light 33s of water, which is about 10% of the incident time, and the incident time. This represents a distribution obtained by combining the time-varying intensity distribution of the light amount of the autofluorescence 35e that has not changed. For example, from a certain time to a time Δt, Raman scattered light 33s with water having a distribution with a relative intensity peaking at 0.05 and light intensity having a distribution with a relative intensity peaking at 0.2 Assuming that the self-fluorescent light 35e is transmitted, during the time Δt, the amount of light Lt synthesized is transmitted, and the relative intensity distribution by the light Lt peaks at 0.25. Distribution.

  The wavelength of the light that is separated by the autofluorescence selection optical device 70 is selected so that the Raman scattered light 33s due to water is smaller than the autofluorescence 35e emitted from the biological particles 35. Specifically, the cutoff wavelength is not limited to 490 nm, and may be a wavelength having a value of 450 nm to 520 nm, preferably 450 nm to 490 nm. Further, the present invention is not limited to a long pass filter that transmits a wavelength longer than 490 nm, and a band pass filter that transmits light in a wavelength region of 490 nm to 600 nm may be provided.

  Here, as the autofluorescence selection optical device 70, in order to use the autofluorescence 35e from the riboflavin in the cells of the biological particles 35 as an index, a long-pass filter based on the cutoff wavelength (for example, 490 nm) is provided. However, when the intracellular NAD (P) H of the biological particle 35 is used as an index, a long path such that any wavelength from 410 nm to 470 nm (for example, 450 nm) is set as a cutoff wavelength and light having a longer wavelength is transmitted. A filter or a bandpass filter that transmits light in a wavelength range of 450 nm to 600 nm as a cutoff wavelength may be provided. This is because when the laser beam 31 of about 350 nm is irradiated, the Raman scattered light 33s due to water has a distribution with a peak at 400 nm, and the detection of the autofluorescence 35e from riboflavin is performed with a long-pass filter based on 450 nm as an index. This is because most of the Raman scattered light 33s of water can be shielded in the same manner as in the above case.

[Second condensing optical lens system: see FIG. 2]
The second condensing optical lens system 80 is composed of, for example, a plurality of optical lenses.
The second condensing optical lens system 80 is installed on the traveling direction (optical axis) of the light transmitted through the long pass filter 70. By the second condensing optical lens system 80, the auto-fluorescence 35e transmitted through the long pass filter 70 and the Raman scattered light 33s by water are condensed and imaged on the incident surface of the fluorescence light receiving device 90.

[Light receiving device for fluorescence (autofluorescence light receiving means, autofluorescence light receiving process)]
The fluorescence light receiving device 90 includes, for example, a semiconductor light receiving element (photodiode Photo Diode: PD) or a photomultiplier tube (Photo Multiplier Tube: PMT) having higher sensitivity than the photodiode. These photodiodes and photomultiplier tubes (hereinafter referred to as photomultipliers) use the received light as a current, and output a current corresponding to the received light quantity. Note that the magnitude of the output current varies depending on the amount of received light, and the greater the amount of received light, the greater the current. Note that the electrical signal output from the photomultiplier 90 is then input to the autofluorescence counting system 2.

[Shading wall]
The light shielding wall 65 is composed of a cylindrical structure that surrounds the optical path from the transmission side of the dichroic mirror 60 to the photomultiplier 90. The light shielding wall 65 can prevent light other than the light (autofluorescence 35e) transmitted through the dichroic mirror 60 from entering the photomultiplier 90. For example, the Raman scattered light 33 s and the scattered light 35 s and 37 s from the object are reflected in the light detection system 1 and can be shielded from entering the optical path. Although not shown, a light shielding wall may be similarly provided on the optical path from the reflection side of the dichroic mirror 60 to the light receiving device 110 for scattering.

[Third condensing optical lens system]
The third condensing optical lens system 100 is composed of, for example, a plurality of optical lenses. The third condensing optical lens system 100 is installed on the traveling direction (optical axis) of the light reflected by the dichroic mirror 60.

[Light receiving device for scattering (scattered light receiving means, scattered light receiving process)]
The scattering light receiving device 110 is composed of, for example, a photodiode or a photomultiplier. Here, the light incident on the scattering light receiving device 110 is light having a wavelength shorter than 410 nm reflected by the dichroic mirror 60, and specifically, biological particles 35 and non-biological particles 37 that flow in the flow cell 30. Scattered light scattered by. Since the scattered light from these biological particles 35 and non-biological particles 37 has a larger amount of light than the autofluorescence 35e emitted from the biological particles 35, it can be sufficiently detected not by a photomultiplier but also by an inexpensive photodiode. In the present embodiment, this photodiode 110 is provided, and the scattered light from the biological particles 35 and the non-biological particles 37 reflected by the dichroic mirror 60 is received. The light received by the photodiode 110 is converted into an electric signal corresponding to the light amount, and the electric signal is output from the photodiode 110. The output signal from the photodiode 110 is then input to the autofluorescence counting system 2.

[Autofluorescence counting system (biological particle determination means, biological particle determination step): see FIG. 2]
The autofluorescence counting system 2 includes, for example, a detection signal processing unit 200, a data processing unit 300, and a notification unit 400. FIG. 9 is a flowchart showing an example of the procedure of the autofluorescence counting process.

  For example, the detection signal processing unit 200 receives an output signal from the light detection system 1, that is, an output signal from the fluorescence light receiving device (photomal) 90 and an output signal from the scattering light receiving device photodiode 110. Then, the received signal is amplified and AD conversion from an analog signal to a digital signal is performed (data collection processing step S200 in FIG. 9).

  For example, the data processing unit 300 receives and stores the autofluorescence signal (signal A) and the scattered light signal (signal B) subjected to AD conversion processing by the detection signal processing unit 200 (data analysis processing step S300 in FIG. 9). From the stored signals A and B, it is determined whether or not a signal derived from the biological particles 35 in the dialysate (water), that is, a signal due to the autofluorescence 35e is included, and the determination result is output (FIG. 5). Step analysis result output processing S400) in No. 9 is performed.

For example, the notification unit 400 notifies the result determined by the data processing unit 300 to the outside or outputs a notification signal to the outside (notification processing step S500 in FIG. 9).
Hereinafter, each component and its process are demonstrated concretely.

[Detection signal processor]
The detection signal processing unit 200 includes, for example, a fluorescence output signal processing device 210 and a scattering output signal processing device 220. Further, the fluorescence output signal processing device 210 includes, for example, a first amplifier 212 and a first analog / digital converter 214, and the scattering output signal processing device 220 includes, for example, a second amplifier 222, a second analog / digital converter. It consists of a digital converter 224.

[Data collection processing]
FIG. 10 is a flowchart illustrating an exemplary procedure of data collection processing.
First, when the fluorescence output signal processing device 210 receives an output signal from the fluorescence light receiving device (photomultiplier) 90 (output signal reception processing step S210), the first amplifier 212 outputs the output signal output from the photomultiplier 90. (Output signal amplification processing step S220). Then, the first analog / digital converter 214 converts the analog signal amplified by the first amplifier 212 into a digital signal (signal A) (output signal A / D conversion processing step S230).

  Similarly, when the output signal processing device for scattering 220 receives the output signal from the light receiving device for scattering (photodiode) 110 (output signal reception processing step S210), the output output from the photodiode 110 by the second amplifier 222 is output. The signal is amplified (output signal amplification processing step S220). Then, the second analog / digital converter 224 converts the analog signal amplified by the second amplifier 222 into a digital signal (signal B) (output signal A / D conversion processing step S230).

  Thereafter, the signals A and B converted into digital signals are output from the fluorescence output signal processing device 210 and the scattering output signal processing device 220 (converted signal output processing step S240). The output signals A and B are input to the data processing unit 300 next.

[Data processing section]
The data processing unit 300 includes, for example, a data collection device 310, a data analysis device 320, and an analysis result output device 330. In addition, the data collection device 310 includes, for example, a memory (RAM) 310 that stores data.

[Data analysis processing]
FIG. 11 is a flowchart illustrating an exemplary procedure of data analysis processing.
First, the data processing unit 300 receives the signals A and B output from the fluorescence output signal processing device 210 and the scattering output signal processing device 220 (conversion signal reception processing step S310). The received signals A and B are stored in the storage area of the memory 310 as they are.

  When the storage of the signal A and the signal B in the memory 310 is completed, an analysis process (analysis process step S340) is performed using the signal A and the signal B.

[Data analysis device (biological particle determination means, scattered light detection signal output means)]
The data analysis device 320 prestores (saves), for example, a calculation circuit (for example, the CPU 322) that analyzes the data (signal A and signal B) stored in the memory 310, calculation processing contents (program, threshold data), and the like. It consists of a memory 324 (ROM).

[Analysis processing (biological particle determination process, scattered light detection signal output process)]
FIG. 12 is a flowchart illustrating an exemplary procedure of analysis processing.
First, the signal B stored in the memory 310 is compared with threshold data (voltage value) stored in the memory 324 in advance by the CPU 322. Specifically, it is determined whether or not the voltage value of the stored signal B is greater than or equal to a threshold value B (V _thB ) (step S342). As a result of this determination, when it is determined that the voltage value of the signal B is greater than or equal to the threshold value B (step S342: Yes), the scattered light from the biological particle 35 or the non-biological particle 37 is incident on the light receiving photodiode 110 for scattering. This means that it has been detected. Here, a process of turning on a scattered light detection flag indicating that scattered light from the biological particles 35 or the non-biological particles 37 has been detected may be performed.

Next, the signal A stored in the memory 310 is compared with threshold data (voltage value) stored in the memory 324 in advance by the CPU 322. Specifically, it is determined whether or not the voltage value of the stored signal A is equal to or greater than a threshold value A (V _thA ) (step S344). As a result of this determination, when it is determined that the voltage value of the signal A is greater than or equal to the threshold value A (step S344: Yes), the autofluorescence 35e emitted from the biological particle 35 is incident on the fluorescence light receiving device Photomal 90 and detected. It represents that it was done. And the process which turns ON the detection flag which shows that the autofluorescence 35e was detected is performed (step S346). This detection flag (ON) is then transmitted as a flag signal to the analysis result output processing device 330.

  On the other hand, as a result of these determinations, when it is determined that the voltage value of the signal B is not equal to or greater than the threshold value B (step S342: No), or when it is determined that the voltage value of the signal A is not equal to or greater than the threshold value A ( Step S344: No), a process of turning off the detection flag is performed (Step S348), indicating that the autofluorescence 35e has not been detected. Here, when the scattered light detection flag is ON and the detection flag is OFF, a process of turning ON the non-biological detection flag indicating that the non-biological particle 37 that is not the biological particle 35 has been detected. It may be done. This detection flag (OFF) is then transmitted as a flag signal to the analysis result output processing device 330. Also, an abiotic detection flag may be transmitted.

  The analysis process will be specifically described with reference to the diagrams of the signals A and B corresponding to the output signals output from the respective light receiving devices.

[Example of output signals from fluorescent light receiving device and scattering light receiving device]
FIG. 13 is a diagram illustrating an example of output signals from the fluorescence light-receiving device and the scattering light-receiving device.
The upper signal in FIG. 13 is the time variation distribution of the signal A corresponding to the detection signal output from the photomultiplier 90 of the fluorescence light receiving device, and the lower signal in FIG. 13 is output from the photodiode 110 of the scattering light receiving device. The time change distribution of the signal B corresponding to the detected signal is shown. Here, it is assumed that the distribution of the signals A and B shown in the upper and lower stages in FIG. 13 is a timing-adjusted distribution. Moreover, about the time of a horizontal axis, it has shown that time has passed in order of time t1, t2, t3, ....

For example, at time t1, the threshold _{B (in V thB} (Figure _{V THB1))} and the voltage value of the large signal B than is input to the data processing unit 300, CPU 322 is a voltage value of the signal B is equal to or greater than the threshold B It is determined that there is (step S342: Yes). That is, it represents that the scattered light from the biological particle 35 or the non-biological particle 37 is incident on the light-receiving device photodiode 110 for scattering and detected at time t1.

Then, the threshold value A (V _thA ) stored in the memory 324 in advance by the CPU ₃₂₂ is compared with the voltage value of the signal A (step S344). Since the signal A at the time t1 is not a signal larger than the threshold value A (step S344: No), the signal B at the time t1 becomes scattered light from the non-living particles 37, and the detection flag is set to OFF (step) S348).

  Next, at time t2, the CPU 322 determines that the voltage value of the signal B is greater than or equal to the threshold value B (step S342: Yes).

Then, the CPU 322 compares the threshold value A (V _thA ) with the voltage value of the signal A (step S344), and as a result, the CPU 322 determines that the voltage value of the signal A is equal to or greater than the threshold value A (step S344: Yes). . Therefore, the signal A and the signal B at the time t2 represent the autofluorescence 35e and the scattered light from the biological particle 35, and the detection flag is set to ON (step S346).

  As described above, the result of the presence / absence of the biological particle 35 is obtained in real time. Here, the magnitude of the signal A or the signal B depends on the amount of light incident on the fluorescence light receiving device photomultiplier 90 or the scattering light receiving device photodiode 110, and further, the magnitude of the scattered light depends on the biological particles 35 or the non-living matter. It depends on the size of the particles 37. Therefore, not only the presence / absence of the biological particle 35 but also the size of the biological particle 35 or the non-biological particle 37 can be measured based on the magnitudes of the signal A and the signal B.

Here, a plurality of threshold values B corresponding to the sizes (0.1 μm to 0.3 μm, 0.3 μm to 0.5 μm, 0.5 μm to 1.0 μm,...) Of the biological particles 35 are previously stored in the memory 324 (V It is assumed that _thB1 , _VthB2 , _VthB3 , _VthB4,. For example, for the signal B at time _t2, since less than larger _{V THB2} than _{V THB1,} the size of the biological particles 35 can be determined to be 0.1Myuemu～0.3Myuemu. A plurality of threshold values B corresponding to the size (0.1 μm or more, 0.2 μm or more,...) Of the biological particles 35 may be stored, and these threshold values B may be determined as desired.

  In this embodiment, the analysis processing S340 is performed on the data stored in the signal storage processing step S310, but the biological particles 35 or the non-biological particles 37 are detected by sequentially comparing with the threshold values B and A without storing them. Alternatively, the peak of the signal B may be detected in real time to determine the particle size classification. Further, since the magnitude of the signal A corresponding to the light amount of the autofluorescence 35e also corresponds to the type and the active state of the biological particles, even if the information is obtained by detecting the peak of the signal A. Good.

  As described above, the presence / absence of the biological particles 35 can be detected in real time by the signals A and B, and the size of the biological particles 35 can also be measured. When the detection flag is set to ON by detecting the presence / absence of the biological particle 35, the biological particle 35 is counted in an analysis result output processing step S400.

[Analysis result output device (biological particle counting means)]
The analysis result output device 330 is a device that counts the number of biological particles 35 analyzed by the data analysis device 320 and transmits the count value to the notification unit 400.

[Analysis result output processing (biological particle counting process)]
FIG. 14 is a flowchart illustrating a procedure example of the analysis result output process.
First, the analysis result output device 330 receives a flag signal (detection flag) from the data analysis device 320. Then, it is determined whether or not the detection flag is set to ON (step S410). As a result, when the detection flag is ON (step S410: Yes), the biological particle 35 is detected, and the count number is incremented by 1, and the count value is calculated (step S420). And a count value (count number) is transmitted to the alerting | reporting part 400 (step S430). Although not shown here, when a reset button (not shown) is pressed or when a start button (not shown) is pressed, a process of resetting the count is executed before step S410. May be. Further, the number of biological particles 35 may be counted according to the size of the biological particles 35 based on the received flag signal (size flag).

[Notification Department]
For example, the notification unit 400 (notification unit) includes a display device 410 and a speaker 420.

[Notification processing]
FIG. 15 is a flowchart illustrating a procedure example of the notification process.
First, the notification unit 400 receives the count value transmitted by the analysis result output device 330 of the data processing unit 300 (step S510). Next, the display device 410 updates the received count value and displays the number of detected biological particles 35 (step S520). In addition, a notification sound is output from the speaker (step S530). Here, the number of biological particles 35 detected for each size of the biological particles 35 may be displayed on the display device 410. Further, a display form in which the count is incremented by 1 in real time may be used, or the updated count value may be displayed after a predetermined time (for example, every 5 seconds).

  For the notification sound, the output mode (the number of output of the notification sound, the level of the notification sound) may be changed in accordance with the increasing frequency of the count value. Moreover, you may change the output aspect of an alerting sound according to the magnitude | size of the biological particle 35. FIG. For example, when the count value of the biological particles 35 of 0.2 μm or more per unit time is 1 to 9, a single sound such as “pi!” Is output once, and when the count value is 10 to 99, “ A single sound such as “Pi! Pi!” May be output twice, and if the counted value is 100 or more, a single sound such as “Pi! Pi! Pi!” May be output three times.

  FIG. 16 is a diagram illustrating an example of a display device and a speaker that notify the counting result of the biological particles 35. As a display device, there are provided a display panel 410 for notifying the counting result according to the size of the biological particles 35 and a speaker 420 for notifying that the biological particles 35 are detected. For example, the display panel 410 displays “Size (μm)” indicating the size reference of the biological particle 35 and “Count” indicating the number (count value) of the detected biological particles 35 corresponding to each size. The display part. For example, three values “0.2”, “1.0”, and “5.0” are displayed in advance on the display portion of “Size (μm)” that indicates a reference for the size of the biological particle 35. Regarding each value, for “0.2”, the size of the biological particle 35 of 0.2 μm or more, for “1.0”, for the size of the biological particle 35 of 1.0 μm or more, for “5.0” Corresponds to the size of the biological particle 35 of 5.0 μm or more. Or, for “0.2”, the size of the biological particle 35 of 0.2 μm to 1.0 μm, for “1.0”, the size of the biological particle 35 of 1.0 μm to 5.0 μm, “5.0” "May be displayed so as to correspond to the size of each of the biological particles 35 of 5.0 µm ~, and the display may be determined as desired.

  Here, 321 biological particles 35 having a size of 0.2 μm or more, 7 biological particles 35 having a size of 1.0 μm or more, and 0 biological particles 35 having a size of 5.0 μm or more are counted. It represents that it was done.

  As described above, the notification unit 400 can notify the count value of the biological particles 35 from the display device 410 in real time, and can output a notification sound when the biological particles 35 are detected from the speaker 420. In addition, the notification unit 400 may include an external output terminal, and may output data to another device through the terminal.

  Note that the autofluorescence selection optical device of the light detection system 1 is not limited to the long pass filter 70, and may be composed of a dichroic mirror. For example, by providing a dichroic mirror that transmits light having a wavelength longer than the cutoff wavelength 490 nm and reflects light having a wavelength shorter than the cutoff wavelength 490 nm, light having a wavelength shorter than 410 nm (mainly biological particles 35 and (Scattered light from the biological particles 37) is received by the light receiving photodiode 110 for scattering, and light having a wavelength longer than 490 nm (mainly autofluorescence 35e from the biological particles 35) is received by the fluorescent light receiving device photomultitube 90. Will be.

In addition, for the scattered light selection optical device and the autofluorescence selection optical device of the light detection system 1,
Do not install an autofluorescence selection optical device behind the scattered light selection optical device, but install the scattered light selection optical device and the autofluorescence selection optical device in parallel so that the optical path of the scattered light and the autofluorescence is in a separate system. Also good. In this case, a short pass filter that transmits only light having a wavelength shorter than the cutoff wavelength of 410 nm is used as the scattered light selection optical device. A condensing lens optical system for condensing scattered light from the flow cell and autofluorescence 35e before and after each optical device, a light receiving device for scattering 110, and a light receiving device for fluorescence 90 are provided in each optical device. Install against. Thereby, for example, from the biological particles 35 and the non-biological particles 37 mainly by the scattered light selection optical device (short pass filter) based on 410 nm installed at a position 90 degrees (horizontal plane) from the optical axis of the laser light 31. Light can be detected by the light receiving photodiode 110 for scattering, and is an auto-fluorescence selection optical device (cut-off wavelength of 490 nm, which is installed at a position (vertical surface) 90 degrees from the optical axis of the laser light 31). The self-fluorescence 35e mainly from the biological particles 35 can be detected by the fluorescence light receiving device Photomal 90 by the long pass filter.

  In addition, the laser light 31 having a wavelength corresponding to the autofluorescent material is irradiated, the dichroic mirror for reflecting the scattered light from the object, and the Raman scattered light 33s due to water or the like are reduced, and the autofluorescence 35e from the biological particles 35 is reduced. By providing a long-pass filter that passes through, the counting accuracy with respect to the biological particles 35 can be improved.

  Note that the liquid to be tested is not limited to dialysate for hemodialysis or blood filtration. For example, the liquid is mostly composed of water, such as an infusion solution administered to the human body. It is also possible to detect and count the presence or absence of biological particles in real time.

  As described above, according to the present embodiment, by using the biological particle counter 77 for dialysis, the dialysis fluid, such as riboflavin and NAD (P) H in the cells of the biological particles 35 to be detected (measured). Whether or not the biological particles 35 are present can be determined in real time using the detection of the autofluorescence 35e from the autofluorescent substance necessary for metabolism of the life activity performed in the body as an index. Therefore, as a result of counting by the dialysis biological particle counter 77, when it is confirmed that a predetermined number or more of the biological particles 35 are present in the counted dialysis fluid, the dialysis biological particle counter 77 serves as a notification means. Can output a notification sound from the speaker provided on the display or display it on the display display 745 of the dialysis monitoring device 710 or the central monitoring and control device 640. Early treatment is possible, and the influence on the patient can be suppressed as much as possible.

  Next, a dialysate monitoring system equipped with the dialysis biological particle counter 77 will be described.

[Dialyzed fluid monitoring system with biological particle counter for dialysis]
FIG. 17 is a diagram illustrating a multi-person artificial dialysis device system.
As shown in FIG. 17, the multi-person artificial dialysis apparatus system includes a system for performing hemodialysis of a plurality of patients at the same time using one multi-person dialysate supply apparatus 630, and biodialysis counts for dialysis at various locations. It is composed of a dialysate monitoring system in which a vessel 77 is installed to determine the presence or absence of biological particles in the dialysate.

  A dialysate used in a multi-person artificial dialyzer system is manufactured through a plurality of steps. First, the water of the raw water supply device 600 (for example, tap water) was purified by RO water (reverse osmosis membrane (RO membrane: Reverse Osmosis membrane)) purified by removing ions and other organic substances in the RO water generation device 610. Water, so-called pure water) is produced. And the A dilution solution for dialysis is manufactured by the A powder dissolution device 623 and the B dilution solution for dialysis is manufactured by the B powder dissolution device 624 using RO water. Finally, the RO water purified by the first filter 621, the dialysis A diluted solution purified by the second filter 623, and the dialysis B diluted solution purified by the third filter 625 are mixed together to dialysate Is manufactured. The produced dialysate is stored in the multi-person dialysate supply device 630 (multi-person dialysate supply means) (multi-person dialysate supply step).

  The dialysate stored in the multi-person dialysate supply device 630 is, for example, distributed through a dialysis water distribution pipe (multi-person liquid distribution means), the first dialysis monitoring device 710a, the second dialysis monitoring device 710b, and the third dialysis. The flow is divided into the monitoring devices 710c, ... (liquid distribution process for a large number of people). Then, the dialysate flows into the dialyzers 770a, 770b, 770c connected to the dialysis monitoring devices 710a, 710b, 710c. Further, blood collected from patients A, B, and C is hemodialyzed in dialyzers 770a, 770b, and 770c, and then purified blood is administered to the patient.

  Here, it is assumed that hemodialysis for a plurality of patients is monitored by the central monitoring control device 640 (multi-person bioparticle determination result collecting means). Specifically, each dialysis monitoring device 710a, 710b is assumed to be monitored. , Information from 710c is transmitted to the central monitoring and control device 640 in real time via the network 650 and monitored (multi-person bioparticle determination result collecting step).

  In this embodiment, the presence or absence of biological particles in the dialysate is determined by the dialysis biological particle counter 77 installed at various locations. For example, biological particles are present in the dialysate before hemodialyzed blood using dialysate is administered to patients A, B, and C, ie, before flowing into dialyzer 770a, 770b, 770c. In order to determine whether or not they are present, dialysis biological particle counters 77a, 77b and 77c are provided between the dialysis monitoring devices 710a, 710b and 710c and the dialyzers 770a, 770b and 770c. The count results of the dialysis biological particle counters 77a, 77b, and 77c are transmitted to the dialysis monitoring devices 710a, 710b, and 710c, and the central monitoring control is performed from the dialysis monitoring devices 710a, 710b, and 710c via the network 650. Transmitted to the device 640. Therefore, when it is confirmed as a result of counting by any of the dialysis biological particle counters 77 that a predetermined number or more of biological particles are present in the dialyzed liquid, the dialysis biological particle counter 77 A notification sound is output from the provided speaker, or a display indicating the state of the dialysate is displayed on the display display 745 (notification means) of the dialysis monitoring device 710 or the central monitoring control device 640. As a result, the presence of biological particles in the dialysate can be confirmed in real time at the site where hemodialysis is being performed, so that early treatment of the dialysate is possible before contamination by biological particles proceeds. Can be suppressed as much as possible.

  In addition, in order to directly check the dialysate distributed from the multi-person dialysate supply device 630, the dialysate supply device 630 for multi-user or the dialysis water supply pipe (dialysis fluid distribution means for multi-person) is used for dialysis. A biological particle counter 77 can be installed. Although not shown, the bioparticle counter for dialysis is placed before and after the RO water generating device 610, the A powder dissolving device 623, the B powder dissolving device 624, the first filter 621, the second filter 623, and the third filter 625. By including 77, it is possible to confirm which device or which piping between the devices is contaminated with biological particles.

DESCRIPTION OF SYMBOLS 1 Light detection system 2 Auto-fluorescence counting system 10 Light-emitting device 20 Irradiation optical lens system 30 Target flow apparatus 40 1st condensing optical lens system 50 Light-shielding device 60 Scattered light selection optical device 65 Light-shielding wall 70 Auto-fluorescence selection optical device 80 2nd Condensing optical lens system 90 Fluorescent light receiving device 100 Third condensing optical lens system 110 Scattering light receiving device 200 Detection signal processing unit 300 Data processing unit 400 Notification unit 700 Hemodialysis device 710 Dialysis monitoring device 720 Distribution circuit 730 Dialysate supply Device 740 Control monitoring unit 750 Flow adjusting unit 770 Blood purifier

Claims (12)

Liquid distribution means for distributing dialysate for hemodialysis or blood filtration;
A liquid diverting means for diverting a portion of the dialysate that has been circulated by the liquid circulating means and passed through a filter before being administered to the human body;
A light emitting means for irradiating light of a predetermined wavelength from one light source toward the dialysate diverted by the liquid diverting means;
Of the light emitted by the interaction between the object contained in the dialysate and the light irradiated by the light emitting means, is the object contained in the dialysate a biological particle based on autofluorescence? A bioparticle counter for dialysis comprising biological particle determination means for determining whether or not. The bioparticle counter for dialysis according to claim 1,
Among the light emitted by the interaction between the object or the dialysate and the light irradiated by the light emitting means, the Raman scattered light emitted from the dialysate that is transmitted is reduced, and from the object Further comprising autofluorescence selection optical means for transmitting the emitted autofluorescence,
The biological particle determination means determines whether the object contained in the dialysate is a biological particle based on the light after the Raman scattered light is reduced by the autofluorescence selection optical means,
The bioparticle counter for dialysis, wherein the light emitting means irradiates light having a predetermined wavelength that makes a peak wavelength of the autofluorescence emitted after irradiation different from a peak wavelength of the Raman scattered light. The bioparticle counter for dialysis according to claim 2,
Scattered light selecting optical means for reflecting scattered light emitted from the object and transmitting light including the autofluorescence and the Raman scattered light is further provided,
The biological particle determination means includes
A dialysis organism characterized by determining whether or not the object contained in the dialysis fluid is a biological particle based on the light after passing through the scattered light selection optical means and the autofluorescence selection optical means. Particle counter. The biological particle counter for dialysis according to claim 3,
Autofluorescence light receiving means for receiving the light after passing through the autofluorescence selection optical means and outputting a first signal having a magnitude corresponding to the amount of light when the light is received;
Scattered light receiving means for receiving light after passing through the scattered light selecting optical means and outputting a second signal having a magnitude corresponding to the amount of light when received.
When the magnitude of the second signal output by the scattered light receiving means is greater than or equal to a predetermined threshold, the scattered light that outputs a detection signal as detecting scattered light emitted from the object contained in the dialysate Detection signal output means;
A light-shielding wall that prevents light incident from other than the optical path from entering the optical path from the scattered light selecting optical means to the autofluorescent light receiving means through the autofluorescence selecting optical means,
The biological particle determination means includes
When the detection signal is output by the scattered light detection signal output means and at the same time as the scattered light emitted from the object contained in the dialysate is received by the scattered light receiving means. When light is received by the autofluorescence light receiving means, and the magnitude of the first signal corresponding to the light received by the autofluorescence light receiving means at the same time as the time is greater than or equal to a predetermined threshold, the scattering A biological particle counter for dialysis, wherein the object contained in the dialysate corresponding to the detection signal output by the light detection signal output means is determined to be a biological particle. The bioparticle counter for dialysis according to any one of claims 2 to 4,
The predetermined wavelength of light irradiated by the light emitting means is 375 nm to 420 nm;
The bioparticle counter for dialysis is characterized in that a cut-off wavelength serving as a reference for transmitting light by the autofluorescence selective optical means is 450 nm to 490 nm. A liquid distribution step for distributing dialysate for hemodialysis or blood filtration;
A liquid diversion step for diverting a portion of the dialysate that has been circulated by the liquid flow step and passed through the filter before being administered to the human body;
A light emitting step of irradiating light of a predetermined wavelength from one light source toward the dialysate diverted by the liquid diverting step;
Of the light emitted by the interaction between the object contained in the dialysate and the light emitted in the light emitting step, is the object contained in the dialysate a biological particle based on autofluorescence? A bioparticle counting method for dialysis comprising a bioparticle determination step of determining whether or not. In the dialysis king organism particle counting method according to claim 6,
Among the light emitted by the interaction between the object or the dialysate and the light irradiated in the light emitting step, the Raman scattered light emitted from the dialysate that is transmitted is reduced, and from the object Further comprising an autofluorescence selective optical step of transmitting the emitted autofluorescence,
The biological particle determination step determines whether or not the object contained in the dialysate is a biological particle, based on the light after the Raman scattered light is reduced by the autofluorescence selection optical step,
The method for counting biological particles for dialysis, wherein the light emitting step irradiates light having a wavelength different from a peak wavelength of the autofluorescence emitted after irradiation and a peak wavelength of the Raman scattered light. The dialysis biological particle counting method according to claim 7,
The method further comprises a scattered light selecting optical step of reflecting scattered light emitted from the object and transmitting light including the autofluorescence and the Raman scattered light,
The biological particle determination step includes
A dialysis organism characterized by determining whether or not the object contained in the dialysis solution is a biological particle based on the light after passing through the scattered light selection optical step and the autofluorescence selection optical step. Particle counting method. The dialysis biological particle counting method according to claim 8,
Receiving the light after passing through the autofluorescence selection optical process, and outputting a first signal having a magnitude corresponding to the amount of light when the light is received;
A scattered light receiving step of receiving the light after passing through the scattered light selecting optical step, and outputting a second signal having a magnitude corresponding to the amount of light when the light is received;
If the magnitude of the second signal output by the scattered light receiving step is greater than or equal to a predetermined threshold value, the scattered light that outputs a detection signal as detecting the scattered light emitted from the object contained in the dialysate A detection signal output step;
A light shielding step for preventing light entering from other than the optical path from entering the optical path from the scattered light selection optical step to the autofluorescence light receiving step through the autofluorescence selection optical step,
The biological particle determination step includes
When the detection signal is output by the scattered light detection signal output step and at the same time as the scattered light emitted from the object contained in the dialysate is received by the scattered light reception step. If the light is received by the autofluorescence light receiving step and the magnitude of the first signal corresponding to the light received by the autofluorescence light receiving step is equal to or greater than a predetermined threshold at the same time as the time point, the scattering A bioparticle counting method for dialysis, wherein the object contained in the dialysate corresponding to the detection signal output in the light detection signal output step is determined to be a bioparticle. The bioparticle counting method for dialysis according to any one of claims 7 to 9,
The predetermined wavelength of the light irradiated by the light emitting step is 375 nm to 420 nm,
The bioparticle counting method for dialysis, wherein a cutoff wavelength serving as a reference for transmitting light in the autofluorescence selective optical step is 450 nm to 490 nm. A dialysate monitoring system comprising the bioparticle counter for dialysis according to any one of claims 1 to 5,
A multi-person dialysate supply means for supplying the dialysate for a plurality of people;
Multi-person liquid circulation means for diverting the dialysis liquid supplied by the multi-person dialysis liquid supply means to the respective dialysis monitoring devices;
Informing means for informing the determination result by the bioparticle counter for dialysis,
The bioparticle counter for dialysis is:
At least one of the dialysis fluid supply means for a large number of people or a plurality of the dialysis monitoring devices is provided, and is divided into the dialysis fluid or the dialysis monitoring device that circulates in the dialysis fluid supply means for a large number of people. Further, the dialysate monitoring system for determining whether or not the object contained in the dialysate is a biological particle. The dialysate monitoring system according to claim 11,
The dialysis fluid monitoring system, wherein the dialysis biological particle counter is provided for each dialysis monitoring device.