JP2012210324A - Calibration system and calibration method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a calibration system capable of performing highly accurately the calibration of a blood component measuring apparatus by suppressing sedimentation of solid particles in a suspension liquid to be used as a calibration liquid, and to provide a calibration method.SOLUTION: The calibration system 10A includes: a first transmitting part 44 and a second transmitting part 46 through which infrared rays can transmit and in which a calibration liquid 26 comprising the suspension liquid including the blood component with a predetermined concentration can circulate therein; and a pump 32 supplying the calibration liquid 26 to the first transmitting part 44 and the second transmitting part 46. The pump 32 supplies the calibration liquid 26 so that the linear flow speed of the calibration liquid 26 in the first transmitting part 44 and the second transmitting part 46 becomes 0.005-4.2 cm/s.

Description

  The present invention relates to a calibration system and a calibration method used to calibrate a blood component measuring apparatus that measures a predetermined component contained in blood by transmitting infrared light through the body.

  It is recommended that diabetic patients routinely measure their own blood glucose fluctuations. For example, patients themselves have conventionally punctured their fingers to collect blood and use a measuring device to measure blood sugar levels. Measuring was done. However, since the measurement method described above imposes a great burden on the patient, in recent years, a non-invasive technique capable of measuring a blood component contained in blood by irradiating the patient with near infrared light has been used. An apparatus for measuring blood components has been developed.

  In this measurement method using the blood component measurement device, for example, glucose contained in blood absorbs a part of near-infrared light and is close to a part of a patient's body (for example, a finger). The blood glucose level (glucose concentration) is calculated by receiving near-infrared light transmitted through the body by irradiating infrared light and measuring the transmittance or absorbance. Further, when measuring this blood glucose level, it is difficult to determine whether the measured transmittance or absorbance is the glucose concentration in blood or the glucose concentration contained in body tissue. Is used to calculate the glucose concentration of blood based on the amount of glucose that periodically changes (see, for example, Patent Document 1).

  On the other hand, since the blood component measuring apparatus as described above requires measurement accuracy, calibration work is performed in order to reduce the measurement error. This calibration work is performed, for example, at the time of factory shipment of the apparatus or during regular maintenance and before blood glucose level measurement, and is performed using a predetermined calibration body. The calibration body transmits near infrared light and is filled with an aqueous solution containing a predetermined concentration of glucose inside. A blood component measurement device that transmits near-infrared light sequentially to a plurality of calibration bodies filled with aqueous glucose solutions of different concentrations and creates a calibration curve from the signal intensity obtained based on the transmittance or absorbance. In the database. By calculating the blood glucose level based on this calibration curve, the accuracy is improved in measuring the blood glucose level (see, for example, Patent Document 2).

Japanese Patent No. 3903340 JP 2000-258344 A

  In optical measurement, red blood cells that occupy 30 to 50% of blood become light scattering factors, resulting in measurement errors. In order to reduce such measurement errors, conventionally, a suspension of glucose solution in which solid particles (insoluble particles) are suspended or a suspension of standard blood (blood whose glucose concentration is known) is used as a calibration solution. There is. However, in calibration using such a suspension, solid particles in the suspension may settle. In this case, since the transmitted light intensity from the calibration body varies, there is a problem that the calibration accuracy is lowered.

  The present invention has been made in consideration of such problems, and calibration that can accurately calibrate the blood component measurement apparatus by suppressing the sedimentation of solid particles in the suspension used as the calibration liquid. An object is to provide a system and a calibration method.

  In order to achieve the above object, the present invention provides a calibration system used for calibrating a blood component measuring apparatus that measures blood components by transmitting infrared light to the body, and transmits the infrared light. A permeable portion capable of circulating a calibration liquid made of a suspension containing the blood component at a predetermined concentration and a liquid feeding mechanism for feeding the calibration liquid to the permeable portion. The liquid mechanism is characterized in that the calibration liquid is fed so that the linear flow rate of the calibration liquid in the permeation section is 0.005 to 4.2 cm / s.

  By passing the calibration liquid through the permeation part in such a flow velocity range, settling of the solid particles in the calibration liquid flowing through the permeation part is suppressed, and the solid particles are uniformly dispersed in the calibration liquid flowing through the permeation part. Therefore, the influence on the measurement accuracy due to the sedimentation of the solid particles can be eliminated. That is, since the transmitted light intensity from the transmissive body can be received without variation, the calibration accuracy can be preferably improved.

  In the calibration system, the liquid feeding mechanism may feed the calibration liquid such that a linear flow rate of the calibration liquid in the transmission unit is 0.01 to 4 cm / s. As a result, calibration can be carried out at a linear flow velocity substantially equal to the actual linear flow velocity of blood, so that the calibration accuracy can be improved more suitably.

  In the calibration system, the liquid feeding mechanism may be capable of setting a plurality of flow rates for the linear flow rate of the calibration liquid in the transmission unit. According to this configuration, by setting the flow rate according to the measurement target region, calibration can be performed at a flow rate equivalent to the actual flow rate of the measurement target region, and the calibration accuracy can be improved more effectively.

  Further, the present invention is a calibration method for calibrating a blood component measuring apparatus that measures blood components by transmitting infrared light to the body, and includes a first transmitting unit that can transmit infrared light. Receiving the infrared light transmitted through the first transmission part while circulating a calibration solution made of a suspension containing the blood component of a predetermined concentration at a linear flow rate of 0.005 to 4.2 cm / s, While obtaining a transmission spectrum, and passing the calibration liquid at a linear flow rate of 0.005 to 4.2 cm / s in a second transmission part having an optical path length of infrared light different from that of the first transmission part, the second A step of receiving infrared light transmitted through the transmission part to obtain a transmission spectrum, and calculating a signal intensity from the obtained at least two or more transmission spectra by differential analysis, and generating a calibration curve based on the signal intensity And obtaining a step.

  With such a calibration method, the transmitted light intensity from the transmissive body can be received without variation, and therefore the calibration accuracy can be suitably improved.

  According to the calibration system and the calibration method of the present invention, the blood component measuring apparatus can be accurately calibrated by suppressing the sedimentation of solid particles in the suspension used as the calibration liquid.

1 is a schematic configuration diagram illustrating a blood component measurement device and a calibration system according to a first embodiment of the present invention. It is a partial cross section side view of the blood component measuring device of FIG. It is an external appearance perspective view of the flow cell which comprises a calibration system. It is a schematic block diagram which shows the case where the main-body part of a calibration system is moved to the base end side with respect to the blood component measuring apparatus shown in FIG. It is a graph which shows the calibration curve based on the relationship between the signal intensity | strength of the near infrared light obtained using a calibration system, and the density | concentration of a calibration liquid. It is a graph which shows the calibration curve based on the relationship between the signal intensity | strength obtained using the several calibration liquid which has a different density | concentration, and the density | concentration of this calibration liquid. It is a schematic block diagram of the experimental apparatus for investigating the relationship between the linear flow rate of a calibration liquid, and the transmitted light amount. FIG. 8A is a graph showing a result of a test using the test apparatus shown in FIG. 7, and FIG. 8A is a graph showing a case where the linear flow rate of the calibration liquid is 0, 0 to 0.02 cm / s, and FIG. It is a graph which shows the case of 0.05-2.5 cm / s. FIG. 9A is a third graph showing the results of the test using the test apparatus shown in FIG. 7, and FIG. 9A is a graph showing a case where the linear flow rate of the calibration liquid is 2.8 to 4.2 cm / s, FIG. 9B is a graph showing a case where the linear flow velocity is 10 to 25 cm / s. It is a graph which shows the standard deviation of the transmitted light amount in each linear flow velocity in the experiment using the experimental apparatus shown in FIG. It is a schematic block diagram of the blood component measuring apparatus and the calibration system which concerns on 2nd Embodiment of this invention. 12A is a partially omitted perspective view of the first flow system in the calibration system shown in FIG. 11, and FIG. 12B is a partially omitted perspective view of the second flow system in the calibration system shown in FIG.

  DESCRIPTION OF EMBODIMENTS Hereinafter, preferred embodiments of a calibration system and a calibration method according to the present invention will be described with reference to the accompanying drawings.

[First Embodiment]
FIG. 1 is a schematic configuration diagram showing a blood component measuring device 12 and a calibration system according to the first embodiment of the present invention. The calibration system is a calibration structure that is used to calibrate the blood component measurement device 12. First, the blood component measuring apparatus 12 that is calibrated by the calibration system 10A will be briefly described with reference to FIGS.

  This blood component measuring device 12 measures the glucose concentration in the blood non-invasively, and is provided on the base body 14 and an upper portion on the distal end side of the base body 14 as shown in FIGS. When measuring blood components, for example, a socket 16 into which a finger of a subject is inserted, a light emitting unit 18 provided inside the base body 14 and capable of emitting light toward the socket 16 side, And a light receiving unit 20 to which light emitted from the light emitting unit 18 and transmitted through the finger is incident. The blood component measuring device 12 is integrally controlled by a computer (not shown) including the light emitting unit 18 and the light receiving unit 20.

  In FIG. 1, the upper side of blood component measuring device 12 having socket 16 is referred to as the “tip” side (arrow A direction), and the lower side of blood component measuring device 12 is referred to as the “base end” side (arrow B direction). The same applies to the other drawings.

  The upper surface of the base body 14 is formed in a planar shape. For example, the base body 14 is formed so that a finger or the like can be moved along the upper surface toward the socket 16 (arrow A direction).

  For example, the socket 16 is formed in a cover shape having a space into which the tip of a finger can be inserted, and a light receiving unit 20 is provided so as to face the space and the upper surface of the base body 14. The light receiving unit 20 is made of a photodiode, for example.

  The light emitting unit 18 includes, for example, a halogen lamp provided with a spectroscope that extracts near infrared light, or an LED capable of emitting near infrared light, and is provided at a position facing the light receiving unit 20 in the base body 14. In other words, the light emitting unit 18 and the light receiving unit 20 are disposed to face each other in the vertical direction in the base body 14 and the socket 16 through the space of the socket 16. That is, in the blood component measurement device 12, light is emitted from the light emitting unit 18 provided below in the vertical upward direction and received by the light receiving unit 20 (see FIG. 2).

  In the blood component measuring device 12, after inserting a finger (for example, an index finger) into the socket 16, the operator presses a measurement button (not shown), whereby the near infrared light emitted from the light emitting unit 18 is The light passes through the artery, vein and other tissues in the finger and is received by the light receiving unit 20. The computer receives a signal from the light receiving unit 20 during a period corresponding to a pulse, and obtains a blood glucose level through spectrum analysis and difference analysis.

  Next, the calibration system 10A will be described with reference to FIGS. As shown in FIGS. 1 to 3, the calibration system 10 </ b> A includes a main body 24 in which a light scatterer 22 is housed, and a part of the main body 24 is provided inside the main body 24 and filled with a calibration liquid 26. The flow cell 28 includes a reservoir tank 30 provided at the end of the flow cell 28 and storing the calibration liquid 26, and a pump 32 that circulates the calibration liquid 26 along the flow cell 28. As the calibration liquid 26, a suspension containing a predetermined concentration of glucose is used. Examples of such a suspension include those obtained by mixing solid particles (light scattering particles) in a glucose solution and standard blood (blood whose glucose concentration and various blood cell counts are known).

  The main body 24 is formed, for example, in the shape of an ellipse having a circular arc at the tip, imitating a finger, and is filled with agar or the like that is the light scatterer 22. That is, in the calibration system 10A, by providing the light scatterer 22 inside, the scattering generated in the living tissue around the blood vessel when near infrared light is transmitted through the finger of the subject is reproduced.

  In addition, two sets of first and second recesses 34 and 36 are spaced apart from each other at a predetermined interval along the axial direction (arrow A, B direction) of the main body 24 on the side surface along the width direction of the main body 24. Formed. The first and second recesses 34 and 36 are formed, for example, so as to be recessed in a triangular cross section. The first recess 34 is the base end side (in the direction of arrow B) of the main body 24, and the second recess 36 is the main body. 24, the inner wall surface of the socket 16 with respect to one of the first and second recesses 34, 36 when the calibration system 10A is inserted into the socket 16. The convex portion 38 having a triangular cross-section formed on is engaged. As a result, the calibration system 10 </ b> A including the main body 24 is positioned and fixed with respect to the socket 16.

  That is, the first and second concave portions 34 and 36 and the convex portion 38 function as a positioning mechanism that positions the calibration system 10 </ b> A with respect to the blood component measuring device 12.

  The flow cell 28 includes, for example, a transparent body 40 made of a transparent glass or resin material capable of transmitting near-infrared light and formed in a hollow shape, and tubes 42 respectively connected to both ends of the transparent body 40. Thus, the inside of the transmission body 40 and the tube 42 communicate with each other, and the calibration liquid 26 is filled. The transmissive body 40 is formed in a rectangular cross section, and is joined to the first transmissive portion 44 formed in a wide shape along the width direction of the main body portion 24 and the end portion of the first transmissive portion 44, and the main body portion 24. And a second transmission portion 46 formed in a wide shape along a height direction orthogonal to the width direction (see FIG. 3).

  As shown in FIG. 3, the first and second transmission parts 44 and 46 are hollow and have a rectangular cross section and are formed in substantially the same shape, and are joined so that their end parts intersect with each other at a substantially right angle at the central part. At the same time, the first transmission portion 44 is disposed on the proximal end side (in the direction of arrow B) and the second transmission portion 46 is disposed on the front end side (in the direction of arrow A). Therefore, the optical path length L2 in the second transmission part 46 is set to be longer than the optical path length L1 in the first transmission part 44 (L2> L1).

  The area of the horizontal cross section of the first transmission part 44 and the area of the vertical cross section of the second transmission part 46 viewed along the axial direction (arrow A, B direction) of the tube 42 are formed to be the same. . Here, since the first and second transmission parts 44 and 46 are formed so as to have the same volume, the flow velocity does not change when the calibration liquid 26 is circulated inside the transmission body 40. Is preferred.

  As shown in FIG. 1, the transmissive body 40 has the first transmissive portion 44 in the state where the first concave portion 34 of the main body portion 24 is engaged with the convex portion 38 of the blood component measuring device 12. In the state where the second recess 36 is engaged with the projection 38 as shown in FIG. 4, the second transmission unit 46 and the light receiving unit 18 receive the light. It is arranged at a position facing the portion 20.

  If the optical path lengths L1 and L2 of the first transmission part 44 and the second transmission part 46 are too large, it is difficult to measure the correct absorbance. Therefore, the optical path length L1 in the first transmission part 44 and the optical path length L2 in the second transmission part 46 are preferably 1.0 cm or less in order to measure accurate absorbance.

  The tube 42 includes a first conduit 48 that connects between the first transmission part 44 and the reservoir tank 30 in the transmission body 40, and a second connection that connects the second transmission part 46 and the reservoir tank 30 in the transmission body 40. The first pipe 48 extends from the first transmission part 44 toward the base end side (in the direction of arrow B) of the main body part 24, while the second pipe 50 is provided. Is extended from the second transmission part 46 toward the distal end side (arrow A direction) of the main body part 24 and then bent into a U shape and extends toward the proximal end side (arrow B direction). ing.

  A pump (liquid feeding mechanism) 32 is provided in the middle of the first conduit 48. The pump 32 circulates the calibration liquid 26 by sending the calibration liquid 26 to the permeator 40 (the first permeation part 44 and the second permeation part 46) so that the solid particles contained in the calibration liquid 26 do not settle. -It is a mechanism for fluidizing. The pump 32 according to the illustrated configuration example causes the calibration liquid 26 in the reservoir tank 30 to flow to the permeator 40 through the first conduit 48 and to circulate again to the reservoir tank 30 through the second conduit 50. Yes. That is, the flow cell 28 and the reservoir tank 30 constitute a circulation path for the calibration liquid 26.

  The pump 32 is not particularly limited as long as the calibration liquid 26 can be accurately fed at a desired flow rate. The pump 32 is a turbo type (centrifugal pump, mixed flow pump, axial flow pump) or positive displacement type (piston pump, plunger). Pumps, diaphragm pumps, roller pumps, etc.) can be applied.

  As shown in FIGS. 1 and 4, for example, another reservoir tank 30 a in which calibration solutions 26 of different concentrations are stored is provided, and a plurality of reservoir tanks 30, 30 a and a flow cell 28 are connected via switching means (not shown). The connection state may be selectively switched. In this case, in the single calibration system 10 </ b> A, it is possible to supply the calibration liquid 26 of different concentrations to the flow cell 28 and perform the calibration operation of the blood component measuring device 12.

  Here, a preferable range of the linear flow rate of the calibration liquid 26 fed to the permeate body by the pump 32 will be described. The present inventor conducted a flow experiment of the calibration solution 26 at various linear velocities in order to investigate a preferable flow rate (linear flow rate) of the calibration solution 26 when calibrating the blood component measuring device 12. FIG. 7 shows an outline of the experimental apparatus 60. The experimental apparatus 60 shown in FIG. 7 includes a calibration cell 62, a supply tube 64 and a discharge tube 66 connected to the calibration cell 62, a liquid feed pump 68 connected to the supply tube 64, and a calibration cell 62. A light projecting unit 70 and a light receiving unit 72 disposed opposite to each other are provided.

  In this experiment, standard blood with a known glucose concentration and various blood cell counts was used as the calibration liquid 26. The calibration cell 62 corresponds to the first transmission part 44 or the second transmission part 46, and is made of a transparent glass or resin material capable of transmitting near-infrared light and formed in a hollow shape. The supply tube 64 is a flow path for transferring the calibration liquid 26 from the liquid feeding pump 68 to the calibration cell 62, and the discharge tube 66 is a flow for transferring the calibration liquid 26 flowing out from the calibration cell 62 to the outside and discharging it. Road. The liquid feed pump 68 of the illustrated configuration example is configured as a syringe pump, and includes a syringe 74 filled with the calibration liquid 26 and an apparatus main body 76 to which the syringe 74 is attached. The apparatus main body 76 includes a fixing portion 76 a that holds and fixes the outer cylinder 74 a of the syringe 74, and a driving portion 76 b that presses the pusher 74 b of the syringe 74 to advance. When the drive unit 76 b of the apparatus main body 76 moves forward and presses the pusher 74 b of the syringe 74, the calibration liquid 26 in the syringe 74 is discharged and fed to the calibration cell 62 via the supply tube 64. The moving speed of the pusher 74b by the driving unit 76b is variable, and accordingly, the linear flow rate of the calibration liquid 26 in the calibration cell 62 is set to an arbitrary speed within the range of the driving capability of the driving unit 76b. Can do.

  Using such an experimental apparatus 60, the calibration liquid 26 was fed to the calibration cell 62 at various linear flow velocities, and the intensity of transmitted light (transmitted light amount) from the calibration cell 62 was measured for each linear flow speed. . The results are shown in FIGS. 8A to 9B. 8A to 9B, the horizontal axis represents the liquid passing time [min], and the vertical axis represents the transmitted light amount [count]. In FIG. 8A, a, b, c, and d indicate cases where the linear flow rates of the calibration liquid 26 are 0, 0.0005, 0.01, and 0.02 cm / s, respectively. In FIG. 8B, e, f, g, h, i, and j indicate the cases of 0.05, 0.1, 0.5, 1.0, 2.0, and 2.5 cm / s, respectively. . In FIG. 9A, k and l indicate cases where the linear flow velocity is 2.8 and 4.2 cm / s, respectively. In FIG. 9B, m, n, o, and p indicate cases where the linear flow velocities are 10, 12, 15, and 25 cm / s, respectively. In the experiment with a linear flow rate of 10 to 25 cm / s, a peristaltic pump was used instead of the liquid feeding pump 68 (syringe pump) shown in FIG.

  FIG. 10 shows the standard deviation of the amount of transmitted light at each linear flow velocity in the above-described experiment. The standard deviation is obtained by taking the standard deviation for 0 to 1 minute, 1 to 2 minutes,... 9 to 10 minutes (each 60 points) for each linear flow velocity. That is, 10 standard deviations were calculated for each type of linear flow velocity (however, only those measured up to 10 minutes). Further, in FIG. 10, in order to eliminate the standard deviation that is specifically increased due to the influence of an artificial error such as air contamination, the smallest value among the 10 standard deviations is shown.

  As understood from FIGS. 8A, 8B, and 9A, it was confirmed that at 0.005 to 4.2 cm / s, the amount of transmitted light hardly changed with time, and the amount of transmitted light was almost constant. Further, as understood from FIG. 10, the standard deviation is small at 0.005 to 4.2 cm / s, that is, the variation is small. From these results, it can be seen that when the linear flow velocity is 0.005 to 4.2 cm / s, the sedimentation of the solid particles in the calibration liquid 26 is effectively prevented.

  On the other hand, as understood from FIG. 8A and FIG. 9B, it was recognized that the amount of transmitted light changed with time in the case of 0 cm / s and 10 cm / s or more. Therefore, in the case of 0 cm / s and 10 cm / s or more, it can be understood that sedimentation of solid particles in the calibration liquid 26, hemolysis due to shear stress, turbulent flow, etc. occur, and the amount of transmitted light becomes unstable due to the influence. .

  Next, a calibration method of the blood component measurement device 12 will be described. Here, the calibration solution 26 having a glucose concentration Q is used, and the calibration solution 26 is filled in advance in the permeator 40 and the tube 42 constituting the calibration system 10A, and constantly circulates through the pump 32. It is assumed that

  First, the operator holds the calibration system 10 </ b> A in the ready state, and inserts the calibration system 10 </ b> A into the socket 16 in the blood component measuring device 12 from the distal end side of the main body 24. Then, as shown in FIG. 1, by engaging the first concave portion 34 of the main body 24 with the convex portion 38 of the socket 16, the first transmission portion 44 constituting the transmission body 40 becomes a blood component. It is positioned and fixed at a position facing the light emitting unit 18 and the light receiving unit 20 of the measuring device 12.

  Next, when the operator presses a measurement button (not shown) of the blood component measurement device 12, the near-infrared light emitted from the light-emitting unit 18 causes the main body 24 and the first transmission unit 44 in the calibration system 10A. And is received by the light receiving unit 20. At this time, since the main body 24 has the light scatterer 22, near-infrared light is scattered and included in the calibration liquid 26 when the near-infrared light passes through the first transmission part 44. A part of the near-infrared light is absorbed by glucose molecules and then received by the light receiving unit 20. Specifically, a portion of near infrared light having a unique wavelength is absorbed by glucose molecules.

  Then, an output signal based on the intensity of transmitted light received by the light receiving unit 20 is output to a computer (not shown), and a transmission spectrum PA is created through spectrum analysis performed in the computer. Specifically, in the computer, the absorbance is calculated from the intensity of light emitted from the light emitting unit 18 to the calibration system 10A and the intensity of transmitted light based on the output signal from the light receiving unit 20, and based on the absorbance. Thus, a transmission spectrum PA is created.

  In this case, in the blood component measurement device 12 according to the present embodiment, the linear flow rate of the calibration liquid 26 in the first transmission unit 44 is set to 0.005 to 4.2 cm / s, more preferably 0.01 to. It is set to 4.2 cm / s. Thereby, sedimentation of the solid particles in the calibration liquid 26 flowing in the first transmission unit 44 is suppressed, and the light receiving unit 20 can receive the transmitted light intensity from the first transmission unit 44 without variation. That is, when the solid particles in the calibration liquid 26 flowing in the first transmission part 44 are settled, the transmitted light intensity from the first transmission part 44 varies, so that the transmission spectrum PA cannot be created with high accuracy. However, since the sedimentation of the solid particles in the calibration liquid 26 is prevented, the transmission spectrum PA can be created with high accuracy.

  Next, the operator pulls the calibration system 10 </ b> A away from the socket 16 of the blood component measurement device 12, i.e., in the base end side (the direction of arrow B) of the blood component measurement device 12, whereby the first recess 34. The convex portion 38 is detached from the second concave portion 36 and engaged with the second concave portion 36 (see FIG. 4). As a result, as shown in FIG. 4, the second transmission unit 46 of the calibration system 10 </ b> A is positioned at the position where the second transmission unit 46 of the calibration system 10 </ b> A faces the light emitting unit 18 and the light receiving unit 20 of the blood component measuring device 12.

  When the operator presses the measurement button again, the near infrared light emitted from the light emitting unit 18 passes through the main body 24 and the second transmitting unit 46 of the calibration system 10A and is received by the light receiving unit 20. At this time, as shown in FIG. 3, the second transmission part 46 that transmits near-infrared light has an optical path length L2 (cross-sectional area) along the irradiation direction of the near-infrared light. Is formed larger than the optical path length L1 (cross-sectional area) (L2> L1), the distance of the near-infrared light passing through the calibration liquid 26 becomes longer.

  As a result, in the second transmission unit 46, light absorbed by the calibration liquid 26 is increased as compared with the case where near infrared light is transmitted through the first transmission unit 44, and accordingly, the light reception unit 20 receives light. The near-infrared light emitted will be reduced. That is, when transmitting near-infrared light to the calibration system 10 </ b> A, the absorbance when transmitted through the second transmission unit 46 is greater than the absorbance when transmitted through the first transmission unit 44.

  That is, the first transmission part 44 with a short optical path length L1 is for reproducing the transmission spectrum of the body when the blood vessel contracts due to pulsation and the blood volume is reduced, while the first transmission part 44 with a long optical path length L2 is used. The 2 transmission part 46 is provided in order to reproduce the transmission spectrum of the body when the blood vessel is expanded by pulsation and the blood volume is increased.

  Then, an output signal based on the intensity of the transmitted light received by the light receiving unit 20 is output again to a computer (not shown). The computer performs spectrum analysis and creates a transmission spectrum PB based on the absorbance.

  In this case, in the blood component measurement device 12 according to this embodiment, in the blood component measurement device 12 according to this embodiment, the linear flow rate of the calibration liquid 26 in the second transmission unit 46 is 0.005 to 4.2 cm / s, more preferably 0.01 to 4.2 cm / s. Thereby, sedimentation of the solid particles in the calibration liquid 26 flowing in the second transmission part 46 is prevented, and the light receiving part 20 can receive the transmitted light intensity from the second transmission part 46 without variation. That is, if the solid particles in the calibration liquid 26 flowing in the second transmission part 46 are settled, the transmitted light intensity from the transmission body varies, so the transmission spectrum PB cannot be created with high accuracy. By preventing sedimentation of solid particles in the liquid 26, the transmission spectrum PB can be created with high accuracy.

  Finally, differential analysis is performed based on the transmission spectra PA and PB obtained when the first and second transmission parts 44 and 46 in the calibration system 10A are transmitted, and the signal intensity S in the calibration liquid 26 is calculated. Thus, a linear calibration curve K based on the relationship between the signal intensity S and the concentration Q of the calibration solution 26 as shown in FIG. 5 is obtained.

  And in the blood component measuring device 12, this calibration curve K is preserve | saved as a database, A highly accurate measurement can be performed by referring when measuring a blood glucose level.

  In the above description, the case where the blood component measuring device 12 is calibrated using a single calibration solution 26 having a predetermined concentration Q has been described. For example, as shown in FIGS. The reservoir tanks 30 and 30a are provided in the calibration system 10A, and the calibration liquids 26 having different concentrations Q and Q1 to Q3 are sequentially sent to the flow cell 28 to obtain the signal strengths S and S1 to S3 in the respective calibration liquids 26. Good. In this case, as shown in FIG. 6, it is possible to create a calibration curve K1 with higher accuracy from the relationship between the signal strengths S and S1 to S3 and the concentrations Q and Q1 to Q3 of the calibration liquid 26. As a result, the blood component measurement device 12 can improve the measurement accuracy of the blood glucose level using the calibration curve K1 created with higher accuracy.

  As described above, in the first embodiment, in the calibration system 10A that calibrates the blood component measurement device 12, the calibration liquid 26 is fed by the pump 32 at a linear flow rate of 0.005 to 4.2 cm / s. In the calibration liquid 26 that flows through the first permeation part 44 and the second permeation part 46, the solid particles in the calibration liquid 26 that flow in the first permeation part 44 and the second permeation part 46 are suppressed from being settled. Since the state of being uniformly dispersed is maintained, the influence on the measurement accuracy due to the sedimentation of the solid particles can be eliminated. That is, the transmitted light intensity from the first transmission unit 44 and the second transmission unit 46 can be received without variation. Therefore, the blood component measuring device 12 can be calibrated with high accuracy.

  That is, calibration curves K and K1 are created from the signal intensities S based on the transmission spectra PA and PB obtained with high accuracy, and stored and used as a database in the blood component measuring device 12, for example. When measuring the blood glucose level of the subject with the measuring device 12, a highly accurate measurement result can be obtained. In other words, the measurement error of the blood sugar level in the blood component measuring device 12 can be further reduced.

  In the calibration system 10A, the pump 32 may send the calibration solution 26 so that the linear flow rate of the calibration solution 26 in the first transmission unit 44 and the second transmission unit 46 is 0.1 to 4 cm / s. preferable. The linear flow velocity of blood in peripheral blood vessels such as human fingers is 0.1 to 4 cm / s. Therefore, by sending the calibration liquid 26 at a linear flow rate of 0.1 to 4 cm / s, the calibration can be performed at a linear flow rate that is almost equal to the actual linear flow rate of blood. It can improve suitably.

  In the calibration system 10 </ b> A, the pump 32 may be configured so that a plurality of flow rates can be set for the linear flow rate of the calibration liquid 26 in the first transmission unit 44 and the second transmission unit 46. Since the blood flow rate differs depending on the body part, setting the flow rate according to the measurement target part enables calibration at a flow rate equivalent to the actual flow rate of the measurement target part, and makes calibration accuracy more effective. Can be improved.

[Second Embodiment]
Next, a calibration system 10B according to the second embodiment is shown in FIGS. The same components as those in the calibration system 10A according to the first embodiment described above are denoted by the same reference numerals, and detailed description thereof is omitted.

  In FIG. 11, the blood component measuring device 12 that is calibrated by the calibration system 10B is configured in the same manner as the blood component measuring device 12 shown in FIG. The calibration system 10B includes a first flow system 80 and a second flow system 82 that allow the calibration liquid 26 to flow.

  The first flow system 80 includes a first main body 84 in which the light scatterer 22 is housed, a first flow cell 86 in which a part of the first main body 84 is provided in the first main body 84 and filled with the calibration liquid 26, A first reservoir tank 88 is provided at the end of the first flow cell 86 and stores the calibration liquid 26, and a first pump 90 circulates the calibration liquid 26 along the first flow cell 86.

  The first main body 84 is formed, for example, in the shape of an ellipse in cross-section with a circular arc at the tip, similar to the main body 24 shown in FIG. In order to reproduce the scattering that occurs in the living tissue around the blood vessel when external light is transmitted, agar or the like that is the light scatterer 22 is filled inside.

  A pair of recesses 92 are formed on the left and right side surfaces in the width direction of the first main body portion 84. The concave portion 92 is formed, for example, so as to have a triangular cross section. When the first main body portion 84 is inserted into the socket 16, the convex portion 38 formed on the inner wall surface of the socket 16 with respect to the concave portion 92. Engaged. As a result, the first main body 84 is positioned and fixed with respect to the socket 16.

  FIG. 12A is a partially omitted perspective view showing the distal end portion of the first flow cell 86. As shown in FIGS. 11 and 12A, the first flow cell 86 includes, for example, a first transmission portion 94 made of a transparent glass or resin material capable of transmitting near infrared light and formed in a hollow shape, and the first flow cell 86. The first transmission part 94 has a first conduit 96 connected to one end of the first transmission part 94 and a second conduit 98 connected to the other end of the first transmission part 94. And the inside of the second pipe line 98 communicates with each other and is filled with the calibration liquid 26. The first transmission portion 94 is formed in a rectangular shape in cross section, and is formed in a wide shape along the width direction of the first main body portion 84.

  The first conduit 96 is a tube connecting the first permeation portion 94 and the first reservoir tank 88 in the permeator 40, and the first conduit 96 extends from the first permeation portion 94 to the first main body. It extends toward the base end side (arrow B direction) of the portion 84. The second conduit 98 is a tube that connects the second transmission part 108 and the first reservoir tank 88, and extends from the second transmission part 108 toward the distal end side (the direction of arrow A) of the first main body part 84. Then, it is bent in a U shape and extends toward the base end side (in the direction of arrow B).

  A first pump (liquid feeding mechanism) 90 is provided in the middle of the first pipeline 96. The first pump 90 circulates the calibration liquid 26 by sending the calibration liquid 26 to the first transmission part 94 and the second transmission part 108 so that the solid particles contained in the calibration liquid 26 do not settle. It is a mechanism for making it flow, and is configured similarly to the pump 32 shown in FIG. The first pump 90 feeds the calibration liquid 26 so that the linear flow rate of the calibration liquid 26 in the first transmission unit 94 is 0.005 to 4.2 cm / s.

  As shown in FIG. 11, the second flow system 82 includes a second main body portion 100 in which the light scatterer 22 is housed, and a part of the second main body portion 100 is provided inside the second main body portion 100 and is filled with the calibration liquid 26. The second flow cell 102, a second reservoir tank 104 provided at an end of the second flow cell 102 and storing the calibration liquid 26, and a second for circulating the calibration liquid 26 along the second flow cell 102. A pump 106. The second main body 100 is configured similarly to the first main body 84, the second reservoir tank 104 is configured similar to the first reservoir tank 88, and the second pump 106 is configured similar to the first pump 90. .

  FIG. 12B is a partially omitted perspective view showing the tip of the second flow cell 102. As shown in FIGS. 11 and 12B, the second flow cell 102 includes, for example, a second transmission part 108 made of a transparent glass or resin material that can transmit near-infrared light and formed in a hollow shape, and the second flow cell 102. The second transmission part 108 has a first conduit 110 connected to one end of the transmission part 108 and a second conduit 112 connected to the other end of the first transmission part 94, and the second transmission part 108, the first conduit 110. And the inside of the second pipe 112 communicates with each other and is filled with the calibration liquid 26. The second transmission portion 108 is formed in a rectangular shape in cross section, and is formed in a wide shape along a height direction orthogonal to the width direction of the first main body portion 84. The optical path length L4 (see FIG. 12B) in the second transmission unit 108 is set larger than the optical path length L3 (see FIG. 12A) in the first transmission unit 94 (L4> L3).

  If the optical path lengths L3 and L4 of the first transmission part 94 and the second transmission part 108 are too large, it becomes difficult to measure the correct absorbance. Therefore, the optical path length L3 in the first transmission part 94 and the optical path length L4 in the second transmission part 108 are preferably 1.0 cm or less in order to measure accurate absorbance.

  As shown in FIGS. 12A and 12B, the first transmission part 94 and the second transmission part 108 are hollow and have a rectangular cross section and are formed in substantially the same shape. In other words, the area of the horizontal section of the first transmission portion 94 viewed along the axial direction (arrow A, B direction) of the first main body portion 84 and the axial direction (arrow A, B direction of the second main body portion 100). ) Are formed so that the area of the vertical cross section of the second transmissive portion 108 is the same as seen along the line. Here, since the first transmission part 94 and the second transmission part 108 are formed so as to have the same volume, the flow rate may change when the calibration liquid 26 is circulated inside the transmission body 40. It is preferable.

  Next, a calibration method for the blood component measurement device 12 using the calibration system 10B will be described. Here, the calibration solution 26 having a glucose concentration Q is used, and the calibration solution 26 is previously provided in the first permeation unit 94, the first pipe 96, and the second pipe 98 constituting the first flow system 80. 26 is satisfied, and when the infrared light is transmitted through the first transmission part 94 to obtain a transmission spectrum, it is always in a state of being circulated through the first pump 90. Also, in the second flow system 82, the calibration liquid 26 is filled in advance in the second transmission unit 108, the first pipeline 110, and the second pipeline 112, and the second transmission unit 108 has a red color to obtain a transmission spectrum. When external light is transmitted, it is always in a state of being circulated through the second pump 106.

  First, the operator grasps the first flow system 80 and inserts the first flow system 80 into the socket 16 of the blood component measuring device 12 from the distal end side of the first main body portion 84. Then, as shown in FIG. 11, by engaging the concave portion 92 of the first main body portion 84 with the convex portion 38 of the socket 16, the first transmission portion 94 becomes the light emitting portion 18 of the blood component measuring device 12. And it is positioned and fixed at a position facing the light receiving unit 20.

  Next, when an operator presses a measurement button (not shown) of the blood component measurement device 12, the near infrared light emitted from the light emitting unit 18 is transmitted through the first main body 84 and the first transmission unit 94. Then, the light receiving unit 20 receives the light. At this time, a part of the near infrared light having a specific wavelength is absorbed by the glucose molecules.

  Then, an output signal based on the intensity of the transmitted light received by the light receiving unit 20 is output to a computer (not shown), and a transmission spectrum (hereinafter referred to as “first transmission spectrum”) is obtained through spectrum analysis performed in the computer. Created. Specifically, the computer calculates the absorbance from the intensity of light emitted from the light emitting unit 18 to the calibration system 10B and the intensity of transmitted light based on the output signal from the light receiving unit 20, and based on the absorbance. Thus, a first transmission spectrum is created.

  In this case, in this embodiment, the linear flow rate of the calibration liquid 26 in the first transmission unit 94 is set to 0.005 to 4.2 cm / s, more preferably 0.01 to 4.2 cm / s. Is done. Thereby, sedimentation of the solid particles in the calibration liquid 26 flowing in the first transmission unit 94 is prevented, and the light receiving unit 20 can receive the transmitted light intensity from the transmission body without variation, and the first transmission spectrum. Can be created with high accuracy.

  Next, the operator pulls the first main body 84 of the first flow system 80 toward the proximal end side (arrow B direction) of the blood component measurement device 12 and pulls out the first main body 84 from the socket 16. When the first main body 84 is pulled out from the socket, the operator grips the second flow system 82 and inserts the second flow system 82 into the socket 16 from the front end side of the second main body 100, so that the convex portion 38 of the socket 16 Then, the recess 92 of the second main body 100 is engaged. Accordingly, the second transmission unit 108 is positioned and fixed at a position facing the light emitting unit 18 and the light receiving unit 20 of the blood component measurement device 12.

  Then, when the operator presses the measurement button again, the near infrared light emitted from the light emitting unit 18 passes through the second main body unit 100 and the second transmission unit 108 and is received by the light receiving unit 20. At this time, the second transmission part 108 that transmits near-infrared light is formed such that the optical path length L4 along the irradiation direction of the near-infrared light is larger than the optical path length L3 in the first transmission part 94. Therefore (L4> L3), the distance of the near-infrared light passing through the calibration liquid 26 becomes longer.

  As a result, in the second transmission unit 108, the light absorbed by the calibration liquid 26 is increased as compared with the case where the near infrared light is transmitted through the first transmission unit 94, and accordingly, the light reception unit 20 receives the light. The near-infrared light emitted will be reduced. That is, when transmitting near-infrared light to the calibration system 10 </ b> B, the absorbance when transmitted through the second transmission unit 108 is greater than the absorbance when transmitted through the first transmission unit 94.

  That is, the first transmission portion 94 having a short optical path length L3 is for reproducing the transmission spectrum of the body when the blood vessel contracts due to pulsation and the blood volume is reduced, while the first transmission section 94 has a long optical path length L4. The 2 transmission part 108 is provided in order to reproduce the transmission spectrum of the body when the blood vessel is expanded by pulsation and the blood volume is increased.

  Then, an output signal based on the intensity of the transmitted light received by the light receiving unit 20 is output again to a computer (not shown). The computer performs spectrum analysis, and transmits a transmission spectrum (hereinafter referred to as “second” based on the absorbance). A transmission spectrum ”). In this case, in this embodiment, the linear flow rate of the calibration liquid 26 in the second transmission unit 108 is set to 0.005 to 4.2 cm / s, more preferably 0.01 to 4.2 cm / s. Is done. Thereby, sedimentation of the solid particles in the calibration liquid 26 flowing in the second transmission unit 108 is prevented, and the light receiving unit 20 can receive the transmitted light intensity from the transmission body without variation, and the second transmission spectrum. Can be created with high accuracy.

  Finally, differential analysis is performed based on the first and second transmission spectra obtained when the first transmission unit 94 and the second transmission unit 108 in the calibration system 10B are transmitted, and the signal intensity S in the calibration liquid 26 is detected. As shown in FIG. 5, a linear calibration curve K based on the relationship between the signal intensity S and the concentration Q of the calibration liquid 26 is obtained. And in the blood component measuring device 12, this calibration curve K is preserve | saved as a database, A highly accurate measurement can be performed by referring when measuring a blood glucose level.

  As described above, in the calibration system 10 </ b> B that calibrates the blood component measurement device 12, the calibration liquid 26 is fed into the first transmission unit 94 by the first pump 90 at a linear flow rate of 0.005 to 4.2 cm / s. By doing so, sedimentation of the solid particles in the calibration liquid 26 flowing in the first transmission part 94 is prevented, and the transmitted light intensity from the first transmission part 94 can be received without variation. In addition, the calibration liquid 26 in the second permeation section 108 is fed into the second permeation section 108 by the second pump 106 at a linear flow rate of 0.005 to 4.2 cm / s. The sedimentation of the solid particles is suppressed, and the transmitted light intensity from the second transmission part 108 can be received without variation. Therefore, the blood component measuring device 12 can be calibrated with high accuracy.

  In the calibration system 10B, the first pump 90 and the second pump 106 use the calibration liquid so that the linear flow rate of the calibration liquid 26 in the first transmission unit 94 and the second transmission unit 108 is 0.1 to 4 cm / s, respectively. More preferably, 26 is fed. The linear flow velocity of blood in peripheral blood vessels such as human fingers is 0.1 to 4 cm / s. Therefore, by sending the calibration liquid 26 at a linear flow rate of 0.1 to 4 cm / s, the calibration can be performed at a linear flow rate that is almost equal to the actual linear flow rate of blood. It can improve suitably.

  In the calibration system 10B, the first pump 90 and the second pump 106 are configured so that a plurality of flow rates can be set for the linear flow rate of the calibration liquid 26 in the first transmission unit 94 and the second transmission unit 108. Good. Since the blood flow rate differs depending on the body part, setting the flow rate according to the measurement target part enables calibration at a flow rate equivalent to the actual flow rate of the measurement target part, and makes calibration accuracy more effective. Can be improved.

  In the above description, the present invention has been described with reference to preferred embodiments. However, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the scope of the present invention. Needless to say.

DESCRIPTION OF SYMBOLS 10A, 10B ... Calibration system 12 ... Blood component measuring device 44, 94 ... 1st permeation | transmission part 46, 108 ... 2nd permeation | transmission part 30, 30a ... Reservoir tank 32 ... Pump 80 ... 1st flow system 82 ... 2nd flow system 88 ... first reservoir tank 90 ... first pump 104 ... second reservoir tank 106 ... second pump

Claims (4)

A calibration system used to calibrate a blood component measurement apparatus that measures blood components by transmitting infrared light through the body,
A transmitting part capable of transmitting the calibration liquid, which is capable of transmitting the infrared light and is made of a suspension containing the blood component at a predetermined concentration;
A liquid feeding mechanism for feeding the calibration liquid to the transmission unit;
The liquid feeding mechanism feeds the calibration liquid so that the linear flow rate of the calibration liquid in the permeation portion is 0.005 to 4.2 cm / s.
A calibration system characterized by that. The calibration system of claim 1,
The liquid feeding mechanism feeds the calibration liquid so that the linear flow rate of the calibration liquid in the transmission part is 0.01 to 4 cm / s.
A calibration system characterized by that. The calibration system of claim 1,
The liquid feeding mechanism is capable of setting a plurality of flow rates for the linear flow rate of the calibration liquid in the permeation unit.
A calibration system characterized by that. A calibration method for calibrating a blood component measuring apparatus that measures blood components by transmitting infrared light through the body,
The first transmission part is circulated at a linear flow rate of 0.005 to 4.2 cm / s through a calibration solution made of a suspension containing the blood component having a predetermined concentration in the first transmission part that can transmit infrared light. Receiving infrared light that has passed through and obtaining a transmission spectrum;
Infrared light transmitted through the second transmission part while flowing the calibration liquid at a linear flow rate of 0.005 to 4.2 cm / s in a second transmission part having an optical path length of infrared light different from that of the first transmission part. Receiving light and obtaining a transmission spectrum;
Calculating a signal intensity from the obtained at least two or more transmission spectra by differential analysis, and obtaining a calibration curve based on the signal intensity,
A calibration method characterized by the above.

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