JPH04325143A - Method and device for collecting and measuring blood component - Google Patents

Abstract

PURPOSE:To facilitate operations without degrading sensitivity and responsiveness by automatically and continuously drawing and measuring the components of blood. CONSTITUTION:The blood is taken out of a vein 5 through a tube 3 for the blood by a peristaric pump 6A. A permeated liquid is sent from a reservoir 7 to a reactor 1 by another peristaric pump 6B. The blood and the permeated liquid come into contact via a permeable membrane 2 in this reactor 1 and the blood components diffuse into the permeated liquid. The blood components contained in the permeated liquid can be measured if, for example, a biosensor and optical analysis apparatus are disposed on a tube 4 for the permeated liquid. The blood discharged from the reactor 1 returns to the vein 5 to prevent the decrease of the blood in the body. Since the blood is passed through the permeable membrane 2, the protein is removed in the liquid to be measured and the measurement with good reproducibility is possible.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for collecting and measuring blood components in clinical biochemical measurements.

0002

BACKGROUND OF THE INVENTION Measuring blood components is important in clinical medicine, and many items such as glucose, urea, sodium ions, and potassium ions are measured. Currently, the measurement is performed by collecting blood and using a clinical testing device or a biochemical analyzer. In response, there is a need to automatically and continuously monitor blood components, and various attempts have been made. First, there is a method in which blood is continuously removed from the body using a catheter and blood components (glucose) are measured using an analyzer. There have also been reports of implanting a biosensor subcutaneously to continuously measure blood components (glucose). (Motosuke Shichiri, Yoshimitsu Yamazaki: "Glucose sensor - Application to artificial pancreas -" Metabolism Vol. 23 No. 8 p. 9
9-106). Furthermore, an attempt has been proposed to collect body fluid components by attaching a dialysis membrane to the wall of a metal tube, embedding it subcutaneously, and pumping dialysate into the tube (Peter
T. Kissinger: “Microdialysis”
"Sampling Probe" Proceedings of the Biosensors '90, Singapore, (Proc. of the Biosensor
s'90), p. 192-p. 195).

0003

[Problems to be Solved by the Invention] However, when blood is taken out of the body with a catheter and blood components are measured, macromolecular components such as proteins contained in the blood adhere to the measuring section, resulting in decreased sensitivity and response. However, there are drawbacks such as a decrease in performance or durability, and the need for complicated cleaning and replacement of the measuring section. Another disadvantage is that the blood volume in the body decreases because the blood that is removed is discarded as is. When a biosensor is implanted subcutaneously to measure blood components, there are drawbacks such as adsorption of proteins and other substances, as well as unstable responses due to fluctuations in the environment surrounding the sensor, such as dissolved oxygen concentration and pH buffering capacity. However, it has not reached the level of practical use. The disadvantages of subcutaneously implanting a metal tube with a dialysis membrane are that the metal tube is large and requires surgery for implantation, and that it cannot be replaced frequently even if the dialysis membrane deteriorates due to protein adsorption, etc. .

FIGS. 5A, 5B, and 5C show conventional configuration diagrams. In Figure (A), blood is taken out of the body through a catheter 15, and blood components are measured with an analyzer. In this method, the collected blood is discarded, so a reduction in blood in the body becomes a problem. Furthermore, since blood contains many proteins, when blood itself is analyzed, interference with measurement due to adsorption of proteins to the measuring section becomes a problem. Figure (B) shows a method of implanting the biosensor 20 subcutaneously and performing measurements. In this method, protein adsorption occurs on the sensor portion, which adversely affects the response, and there are also problems in that the environment surrounding the sensor, such as dissolved oxygen concentration and pH buffering capacity, is not constant, resulting in unstable response. Figure (C) is a diagram showing a method of subcutaneously embedding the metal tube 23 with the dialysis membrane 22. In the case of this method, the problems are that the metal tube 23 is large and requires surgery for implantation, and that even if the dialysis membrane 22 deteriorates due to adsorption of proteins, it cannot be replaced frequently. The present invention
This method was developed in view of these issues, and is a method for automatically and continuously measuring blood components that does not cause a decrease in sensitivity or responsiveness and can be easily performed. The purpose is to provide such equipment.

[0005]

[Means for Solving the Problems] The present invention is characterized in that desired blood components are collected into the permeate by bringing blood taken out of the body into contact with the permeate through a permeable membrane. A blood component collection method, a tube inserted into a blood vessel to collect blood, a permeate that is a diffusion medium for the collected blood components, and a permeation method that diffuses only desired blood components from the collected blood into the permeate. This is a blood component sampling device characterized by comprising a membrane. The present invention also provides a blood component measuring method and device for measuring blood components obtained by the above method using a biosensor or an optical analyzer.

[0006]

[Operation] Hemodialysis is a method in which blood is taken out of the body, diffused between it and a dialysate of a certain composition through a dialysis membrane, and the purified blood is returned to the veins.Hemodialysis is widely used as a blood purification method. (Yasuhisa Sakurai, Kiyotaka Sakai: "The latest artificial organs and future prospects" IPC). It acts as an artificial kidney for people who have lost kidney function and contains urea, nitrogen, creatinine, sodium ions, potassium ions,
Its purpose is to remove chlorine ions and other substances from the blood. Therefore, the dialysate after dialysis contains the above-mentioned blood components in proportion to the concentration in the blood, but there is no example that has focused on hemodialysis as a method for collecting blood components. Blood components that diffuse from the blood into the dialysate are determined by the molecular weight cutoff of the dialysis membrane. Therefore, the dialysate after dialysis contains low molecular weight components but does not contain high molecular weight components such as proteins.

According to the method of the present invention, by bringing a permeate into contact with blood taken out of the body through a tube inserted into a blood vessel through a permeable membrane, a substance ( proteins) can be removed, and desired blood components can be collected in the permeate. Furthermore, the blood that has come into contact with the permeable membrane can be returned to the vein, thereby preventing a decrease in blood in the body. Furthermore, when measuring blood components in the permeate with a biosensor, it is possible to keep conditions such as dissolved oxygen concentration and pH buffering capacity constant, and a response with good reproducibility can be obtained. Since the permeable membrane is located outside the body, blood can be taken out by simply inserting an injection needle into a blood vessel, and the permeable membrane can be easily replaced.

[0008]

Embodiments Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 shows a configuration diagram of a blood component collection device of the present invention, and FIG. 2 shows a plan view of the blood component collection device of the present invention, both of which correspond to claims 1 and 2. The sampling method shown in the figure is to insert an injection needle 12 into a vein 5 and take blood out of the body through a tube 3. If necessary, use a peristaltic pump 6A to increase the blood flow rate to 10 per minute.
Adjust to about 0ml. Further, the permeate is sent from the reservoir 7 by a peristaltic pump 6B. This flow rate is determined depending on the components to be sampled, but for example,
It is about 0ml. Blood and permeate are in reactor 1
The blood components come into contact with each other through the permeable membrane 2 within the permeate, and the blood components diffuse into the permeate. Blood that has passed through the reactor 1 returns to the vein 5 via the injection needle 12. The collection needle must be placed upstream of the bloodstream than the return needle. The permeate is sent to drain 8. The permeate used is, for example, a carbonate buffer solution in which ions are added to adjust the ionic strength to 0.15. When measuring ion concentrations in blood components, the permeate should be free of the ionic species. The permeable membrane 2 may be a cellulose membrane or a synthetic polymer membrane such as polyacrylonitrile or polymethyl methacrylate. The molecular weight fraction is determined by the pore size of the permeable membrane. That is, high-molecular substances in blood that are larger than the pore size cannot pass through the membrane, but low-molecular substances that are smaller than the pore size can pass through and be collected in the permeated liquid. Specifically, blood components include ions such as sodium, potassium, calcium, magnesium, and chlorine, as well as glucose,
Urea, uric acid, ammonia, creatinine, phosphoric acid, insulin, bilirubin, etc. can be automatically and continuously collected with the device according to the invention.

FIG. 3 is a block diagram showing an example of the blood component measuring device of the present invention, and FIG. 4 is a plan view of an example of the blood component measuring device of the present invention, both of which correspond to claims 3 and 4. In the figure, the blood component sampling device is the same as in FIGS. 1 and 2, but in FIG. 3, a biosensor 10 is integrated as a measuring device. The permeated liquid that came into contact with blood through the permeable membrane in the reactor 1 is sent to the cell 13, and its components are continuously measured by the biosensor 10 installed in the cell 13. The biosensor 10 is, for example, an ion-sensitive field effect transistor (ISFET) in which an enzyme membrane is formed on an ion-sensitive part. Here, if the enzyme used is glucose oxidase, it is possible to measure the glucose concentration, and if the enzyme used is urease, it is possible to measure the urea concentration. In the case of potentiometric measurements that measure potential, such as with ISFET, it is necessary that the pH and pH buffering capacity of the measurement solution be constant. Stable measurements can be achieved because a pH buffer is used as the permeate. Furthermore, amperometric measurements can also be performed using a biosensor in which an enzyme film is formed on a gold electrode. In the case of this type of biosensor, a coenzyme or an electron transfer substance may be required as a mediator, but it is also possible to add these substances to the permeate in advance. In addition, enzyme electrodes and glass electrodes can also be used in this measuring device as biosensor electrodes.

In FIGS. 3 and 4, if an optical analysis device is used instead of the biosensor, claim 5 of the present invention is achieved.
and the measuring method and specific measuring device described in 6. As an optical analyzer, for example, it is possible to continuously measure blood component concentration by measuring absorbance at a specific wavelength using a spectrophotometer. It is also possible to continuously measure blood components by adding a fluorescent substance to the permeate in advance and measuring with a fluorometer.

In the present invention, the conventional method shown in FIG.
Compared to the case shown in A), as shown in Fig. 1 or Fig. 2, the blood taken out of the body comes into contact with the permeate and is then returned to the vein, so there is no decrease in blood, and a permeable membrane is used. As a result, only low-molecular components in the blood are collected in the permeate, and high-molecular components such as proteins are not included, so that the measurement is not affected by proteins. Also, Figure 5 (
Compared to the case shown in B), the influence of proteins can be prevented by the permeable membrane as shown in Fig. 3 or 4, and conditions such as the concentration of dissolved oxygen in the permeate and the pH buffering function can be kept constant, and the sensor The response is stable and reproducible. Furthermore, compared to the case shown in Fig. 5(C), since the permeable membrane is placed outside the body as shown in Fig. 3 or 4, it is only necessary to insert an injection needle into the blood vessel, and the permeable membrane can be replaced easily. can be done.

0012

Effects of the Invention Conventionally, automatic and continuous measurement of blood components has been difficult due to the effects of adsorption of proteins in the blood.
However, this invention was not practical due to problems such as the effects of inconsistent conditions such as H and dissolved oxygen concentration, the impossibility of replacement because it is implanted subcutaneously, and the lack of blood in the body. By bringing the permeate into contact with blood taken out of the body from a tube inserted into a blood vessel through a permeable membrane, it is possible to remove substances (proteins) with molecular weights greater than the molecular weight cutoff of the permeable membrane. It is possible to collect blood components in the permeate. Furthermore, the blood that has come into contact with the permeable membrane can be returned to the vein, thereby preventing a decrease in blood in the body. Furthermore, when measuring blood components in the permeate with a biosensor, conditions such as dissolved oxygen concentration and pH buffering capacity can be kept constant, and responses with good reproducibility can be obtained. Since the permeable membrane is located outside the body, blood can be taken out by simply inserting an injection needle into a blood vessel, and the permeable membrane can be easily replaced. Therefore, according to the present invention, automatic and continuous measurement of blood components is possible. As explained above, according to the present invention, there is provided a method for collecting and measuring blood components that can be easily performed without causing a decrease in sensitivity or responsiveness when measuring blood components automatically and continuously. equipment can be provided.

[Brief explanation of drawings]

FIG. 1 is a configuration diagram of an embodiment of the present invention.

FIG. 2 is a plan view of an embodiment of the present invention.

FIG. 3 is a configuration diagram of another embodiment of the present invention.

FIG. 4 is a plan view of another embodiment of the invention.

FIG. 5 is an explanatory diagram of a conventional example.

[Explanation of symbols]

1 reactor
2 Permeable membrane 3 Blood tube
4 Permeate tube 5 Vein
6A, 6B Peristaltic pump 7 Reservoir
8 Drain 9 Power supply section
10 Biosensor 11, 18 Processor
12 Syringe needle 13 Cell
14 Arm 15 Catheter 1
6 Pump part 17 Measuring part
19 Waste liquid tank 20 Sensor part
21 Dialysate tank

Claims (6)

[Claims] 1. A method for collecting blood components, which comprises bringing blood taken out of the body into contact with the permeate through a permeable membrane, thereby collecting desired blood components into the permeate. 2. A tube inserted into a blood vessel to collect blood, a permeate that is a diffusion medium for the collected blood components, and a permeable membrane that diffuses only desired blood components from the collected blood into the permeate. A blood component sampling device comprising: 3. A blood component measuring method, comprising measuring the blood components collected by the blood component collecting method according to claim 1 with a biosensor. 4. A tube inserted into a blood vessel to collect blood, a permeate that is a diffusion medium for the collected blood components, and a permeable membrane that diffuses only desired blood components from the collected blood into the permeate. A blood component measuring device comprising: and a biosensor that measures blood components in the permeate. 5. A blood component measuring method, comprising measuring the blood components collected by the blood component collecting method according to claim 1 using an optical analyzer. 6. A tube inserted into a blood vessel to collect blood, a permeate that is a diffusion medium for collected blood components, and a permeable membrane that diffuses only desired blood components from the collected blood into the permeate. and an optical analyzer for measuring blood components in the permeated liquid.