WO2016171042A1 - Spectrometry device - Google Patents

Abstract

A spectrometry device according to the present invention is provided with: a spectral optical system that spectrally diffracts light emitted from a sample including a plurality of liquid components or a sample including a liquid component and a particle component when the sample is irradiated with irradiation light; and a detector that detects the light spectrally diffracted by the spectral optical system. The spectrometry device is further provided with: a sample cell that has a light incidence surface and a light emittance surface each having a property of transmitting light with a transmission wavelength or an absorption wavelength specific for the liquid components; a light irradiation means that irradiates, with the irradiation light, a sample in the sample cell through the light incidence surface; a standing wave forming means that forms a standing wave in the sample housed in the sample cell by irradiating the sample with ultrasonic waves; and a measurement optical system that is arranged between the sample cell and the spectral optical system and that converts the light emitted from the sample cell into parallel light.

Description

Spectrometer

The present invention relates to a spectroscopic measurement apparatus that measures the spectral characteristics of only a liquid or only particles in a sample composed of a mixture of liquid and particles.

When glucose develops, the blood glucose concentration (blood glucose level) becomes abnormally high, so blood glucose concentration is measured in various situations such as health checkups and medical examinations for the prevention and treatment of diabetes. The blood glucose concentration is measured by various methods, one of which is a spectroscopic measurement method using the absorption wavelength and Raman shift amount inherent to glucose. In the spectroscopic measurement method, a sample to be measured is irradiated with light in a predetermined wavelength range, whereby a glucose value is obtained from a spectrum obtained by spectroscopically analyzing light emitted from the sample.

Blood (whole blood) is composed of plasma, which is a liquid component, and red blood cells, white blood cells, platelets, etc., which are cell components, and glucose is contained in plasma. All the cell components are fine particles, but when light is irradiated to whole blood, the light is scattered by cell components (particularly red blood cells) and loss (scattering loss) occurs. Since such a scattering loss cannot be distinguished from a loss due to light absorption of glucose (absorption loss), the glucose concentration cannot be measured accurately. Therefore, plasma and serum (those obtained by coagulating blood to remove cellular components and coagulation factors) are usually used for measuring the glucose concentration. However, in order to extract plasma or serum from blood, it is necessary to centrifuge blood or coagulate blood, and it takes time and labor to perform spectroscopic measurement.

The above problem also occurs when, for example, the concentration of components such as ethanol and glucose contained in sake before filtration, which is performed in the process of producing sake, is measured. The sake before filtration is called moromi, and it is made from fermented water in a tank used for brewing. Since koji is a white, cloudy, foamy, high-viscosity liquid, when measuring the spectral characteristics of ethanol and glucose contained in koji, it is affected by light scattering by fine-particle components such as fermented liquor, koji, and steamed rice. Although the influence of the above-mentioned fine particle component can be removed by removing the fine particle component from the soot, it takes time and labor to filter the soot to remove the fine particle component.

In the above description, the problem in the case of performing the spectroscopic measurement of only the component containing the fine particle component, that is, the liquid component, has been described. However, the same problem occurs in the case of performing the spectroscopic measurement of only the fine particle component. .

National Institute of Advanced Industrial Science and Technology HP “For Medical Technology and Welfare” “From Perspective to Incentive !? Manipulating Micro Objects As We Want?” [Search April 16, 2015], Internet < URL: http://www.aist.go.jp/science_town/medical/medical_02/medical_02_01.html> Satoshi Hirabayashi, “Development of Cell Separation Device Using Ultrasonic Radiation Pressure with Resin Structure”, Proceedings of the Japan Society of Mechanical Engineers, Information, Intelligence and Precision Instruments, 1103, pp. 9-12 (2007)

The problem to be solved by the present invention is to provide a spectroscopic measurement apparatus and a spectroscopic measurement method capable of selectively measuring the liquid component of a sample including a liquid component and a particle component, or the spectral characteristics of the particle component. Objective.

The first aspect of the spectroscopic measurement apparatus according to the present invention, which has been made to solve the above-mentioned problems, is a spectroscopic optical device that separates light emitted from a sample when the sample containing a plurality of liquid components is irradiated with the irradiation light. In a spectroscopic measurement apparatus comprising a system and a detector that detects light dispersed by the spectroscopic optical system,
a) a sample cell having a light incident surface and a light output surface having a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component;
b) light irradiation means for irradiating the sample in the sample cell with the irradiation light through the light incident surface;
c) standing wave forming means for forming a standing wave in the sample by irradiating the sample contained in the sample cell with ultrasonic waves;
d) A measurement optical system that is arranged between the sample cell and the spectroscopic optical system and converts the light emitted from the sample cell into parallel light.

In addition, the second aspect of the spectrometer according to the present invention is:
A spectroscopic system comprising a spectroscopic optical system that splits light emitted from the sample when the sample containing the liquid component and the particle component is irradiated with light, and a detector that detects the light dispersed by the spectroscopic optical system. In the measuring device,
a) a sample cell having a light entrance surface and a light exit surface parallel to each other, having a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component;
b) light irradiation means for irradiating the sample in the sample cell with the irradiation light through the light incident surface;
c) A constant wave is formed in the sample by irradiating the sample accommodated in the sample cell with an antinode and a node arranged in a direction parallel to the light incident surface and the light output surface. Presence wave forming means,
d) A condensing lens that collects a part of the light emitted from the sample cell, disposed between the sample cell and the spectroscopic optical system, and converts the light collected by the condensing lens into parallel light. And a measuring optical system having a collimator lens for conversion.

Furthermore, the third aspect of the spectrometer according to the present invention is:
A spectroscopic system comprising a spectroscopic optical system for spectroscopically splitting light emitted from a sample containing a liquid component and a particle component, and a detection device for detecting light split by the spectroscopic optical system. In the measuring device,
a) a sample cell having a light entrance surface and a light exit surface parallel to each other, the light having an absorption wavelength or transmission wavelength specific to the liquid component and having a property of transmitting light emitted from the particle component;
b) light irradiation means for irradiating the sample in the sample cell with the irradiation light through the light incident surface;
c) A constant wave is formed in the sample by irradiating the sample accommodated in the sample cell with an antinode and a node arranged in a direction parallel to the light incident surface and the light output surface. Presence wave forming means,
d) A collimator lens that is disposed between the sample cell and the spectroscopic optical system and converts a part of the light emitted from the sample cell into parallel light; and the light converted into parallel light by the collimator lens is predetermined. And a measuring optical system having an imaging lens for imaging on the imaging plane.

In the spectroscopic measurement apparatus according to the present invention, first, a standing wave is formed in the sample by the standing wave forming means. As a result, in the spectroscopic measurement device of the first aspect, liquid components having a large specific gravity among a plurality of liquid components are collected near the nodes of the standing wave by the acoustic radiation pressure, and light and shade are generated in the sample. In the spectroscopic measurement devices of the second and third aspects, the particle components in the sample are collected near the nodes of the standing wave by the acoustic radiation pressure, and the particle components and the liquid components in the sample are separated (non- (See Patent Documents 1 and 2). In this state, the sample is irradiated with the irradiation light from the light irradiation means through the light incident surface of the sample cell. At this time, since the concentration of the sample and the ratio of the contained liquid component and particle component are different between the vicinity of the node and the antinode of the standing wave, light having different properties is emitted near the node and the vicinity of the antinode. For example, in the first mode, the liquid component having a higher specific gravity is concentrated in the vicinity of the node than in the vicinity of the belly, and the concentration of the liquid component is increased, so that the intensity is lower than that of the light transmitted through the vicinity of the belly. Further, in the second and third aspects, scattered light is emitted from the vicinity of the node where a large amount of particle components are present, and the scattered light is emitted from the vicinity of the antinode where there are many liquid components. Light is emitted. Therefore, the measurement optical system separates the light having different properties emitted from the vicinity of the nodal and the antinodes of the standing wave formed in the sample and introduces only one of them into the spectroscopic optical system. It is possible to selectively measure the spectral characteristics of specific components.

In this case, the transmitted light emitted from the liquid component is light having a uniform direction, whereas the scattered light emitted from the particle component is light emitted in various directions. In the spectroscopic measurement device according to the aspect, the measurement optical system is disposed between the sample cell and the spectroscopic optical system, and a condensing lens that collects a part of the light emitted from the sample cell; It is emitted from a liquid component by comprising a collimator lens that converts the light collected by the condenser lens into parallel light and a pinhole that is disposed at the focal position of the condenser lens on the collimator lens side. The light (transmitted light) is selectively introduced into the spectroscopic optical system.

On the other hand, in the spectroscopic measurement device according to the third aspect, the measurement optical system is arranged such that a part of the light emitted from the sample cell disposed between the sample cell and the spectroscopic optical system is converted into parallel light. A collimator lens, an image forming lens that forms an image of light converted into parallel light by the collimator lens on a predetermined image forming surface, and the collimator disposed at a focal position of the collimator lens on the image forming lens side By comprising a light shielding plate that shields the light collected by the lens, the light (scattered light) emitted from the particle component is selectively introduced into the spectroscopic optical system.

In the spectroscopic measurement apparatus according to the second and third aspects,
The light irradiating means includes a light source, a condensing lens that condenses light from the light source, a collimator lens that shapes the light collected by the condensing lens into parallel light, a condensing lens, and a collimator lens. It is preferable to irradiate the sample in the sample cell with light having an optical axis perpendicular to the light incident surface and the light output surface of the sample cell.
According to such a configuration, most of the transmitted light emitted from the liquid component becomes parallel light having an optical axis perpendicular to the light incident surface and the light emitting surface of the sample cell, so that it is separated from the scattered light emitted from the particle component. It becomes easy to do.

In the spectroscopic measurement apparatus according to the first to third aspects,
A splitting optical system for splitting the spectroscopic optical system into a first measuring light and a second measuring light, which is light that has passed through the measuring optical system, and an optical path between the first measuring light and the second measuring light; An optical path length difference providing means for providing a length difference; an optical path length difference changing means for continuously changing the optical path length difference provided by the optical path length difference providing means; and the first measurement light and the second measurement light are interfered with each other. An interference optical system
The detector configured to detect the intensity of interference light between the first measurement light and the second measurement light formed by the interference optical system, and the optical path length difference changing means to change the optical path length difference. It is preferable to provide a processing unit that obtains an interferogram of the measurement light from the intensity change of the interference light detected by and obtains the spectrum of the measurement light by Fourier transforming the interferogram.

Further, the spectroscopic measurement method according to the present invention measures the spectral characteristics of the sample by diffusing the light emitted from the sample with a spectroscopic optical system when the sample containing the liquid component and the particle component is irradiated with the irradiation light. A spectroscopic measurement method comprising:
The sample is accommodated in a sample cell having a light incident surface and a light output surface parallel to each other, which has a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component,
By irradiating the sample in the sample cell with ultrasonic waves, a standing wave in which the antinodes and nodes are arranged in a direction parallel to or orthogonal to the light incident surface and the light emitting surface is formed in the sample.
By irradiating the sample in the sample cell with irradiation light through the light incident surface, part of the light emitted from the sample cell is converted into parallel light and introduced into the spectroscopic optical system.

Furthermore, in the spectroscopic measurement method according to the present invention, when a sample containing a liquid component and a particle component is irradiated with irradiation light, the light emitted from the sample is dispersed with a spectroscopic optical system, and the spectral characteristics of the sample are measured. A spectroscopic measurement method comprising:
The sample is accommodated in a sample cell having a light incident surface and a light output surface parallel to each other, which has a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component,
By irradiating the sample in the sample cell with ultrasonic waves, a standing wave in which the antinodes and nodes are arranged in a direction parallel to or orthogonal to the light incident surface and the light emitting surface is formed in the sample.
Irradiating the sample in the sample cell with the irradiation light through the light incident surface to form a part of the light emitted from the sample cell on a predetermined imaging surface and introducing it into the spectroscopic optical system. Features.

In the spectroscopic measurement method, the spectroscopic optical system splits the introduced light into first measurement light and second measurement light, and an optical path between the first measurement light and the second measurement light. An optical path length difference giving means for giving a length difference;
Optical path length difference changing means for continuously changing the optical path length difference provided by the optical path length difference providing means;
An interference optical system for causing the first measurement light and the second measurement light to interfere with each other;
An interferogram of the measurement light is obtained by detecting the intensity of the interference light when the optical path length difference is changed by the optical path length difference changing means, and the spectral optics is obtained by Fourier transforming the interferogram. It is good to comprise so that the spectrum of the light introduced into the system may be acquired.

According to the spectroscopic measurement apparatus and the spectroscopic measurement method of the present invention, a standing wave is formed in the sample, and the concentration of the liquid component contained in the sample and the ratio of the liquid component and the particle component are determined in the vicinity of the node of the standing wave. Since the measurement optical system separates light of different properties emitted from the region near the node and the region near the belly, a plurality of components such as liquid components and particle components contained in the sample are separated. Spectral characteristics of specific components in the sample can be selectively measured without performing pretreatment for separation.

1 is a schematic configuration diagram of a spectrometer according to an embodiment of the present invention. In FIG. 1, an enlarged configuration diagram of a portion surrounded by a two-dot chain line FIG. 2B is a configuration diagram in which an imaging optical system is used instead of the telecentric optical system in FIG. 2A. The schematic block diagram of a sample container. Explanatory drawing of the generation state of a standing wave. The measurement result of the spectroscopic characteristic when a specific sample is measured using the spectroscopic measurement apparatus according to the present embodiment is shown. When the left side does not form a standing wave, the right side shows when the standing wave is formed. Results are shown. The result of the light absorbency when a specific sample is measured using the spectroscopic measurement apparatus according to the present embodiment is shown, the left side shows no standing wave, and the right side shows the standing wave. Experimental results for confirming the effect of the telecentric optical system are shown. The left side shows the spectral characteristics when the imaging optical system is used, and the right side shows the spectral characteristics when the telecentric optical system is used. Experimental results for confirming the effect of the telecentric optical system are shown. The left side shows the absorbance when the imaging optical system is used, and the right side shows the absorbance when the telecentric optical system is used. Overall photograph of the sample storage device. An image taken by a CCD camera of a sample containing physiological saline and red blood cells in a state where ultrasonic vibration is applied. Interferogram of a node part when ultrasonic vibration is applied to a sample containing physiological saline and red blood cells. The figure which shows the spectral characteristic of the node part when the ultrasonic vibration is provided to the sample containing physiological saline and red blood cells, and the spectral characteristic of the physiological saline alone. The figure which shows the Example which integrated the spectrometer which concerns on this invention in the dialysis apparatus. It is a figure which shows the Example of the sample storage apparatus used with the spectrometer which concerns on this invention, Comprising: The figure which shows the state which measures the spectral characteristic of a liquid component. It is a figure which shows the Example of the sample storage apparatus used with the spectrometer which concerns on this invention, Comprising: The figure which shows the state which measures the spectral characteristic of a particle component.

Hereinafter, specific embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a schematic configuration diagram of a spectrometer according to an embodiment of the present invention. The spectroscopic measurement apparatus emits light at a predetermined angle among light source 10, irradiation optical system 12 that irradiates the sample storage device 11 with the light from the light source 10 as a parallel light beam, and light output from the sample storage device 11. A bilateral telecentric optical system 14 (hereinafter referred to as “telecentric optical system 14”) for allowing only light to enter the spectroscopic measurement system 13 is provided. The spectroscopic measurement system 13 includes a phase shifter 31, an imaging lens 32, a detection unit 33, a control unit 34 including a processing unit 341, a calculation unit 342, and the like that process the results detected by the detection unit 33. It is configured. Of the spectroscopic measurement system 13, the phase shifter 31 and the imaging lens 32 constitute the spectroscopic optical system and the splitting optical system of the present invention.

The detection unit 33 is composed of, for example, a 16 × 16 pixel two-dimensional CCD (Charge Coupled Device) camera, and is arranged such that the light receiving surface of the detection unit 33 is positioned on the imaging surface of the imaging lens 32.
The phase shifter 31 includes a fixed mirror unit 311, a movable mirror unit 312, and a drive mechanism 313 that moves the movable mirror unit 312. Both the fixed mirror unit 311 and the movable mirror unit 312 have a rectangular reflecting surface that is inclined at an angle of 45 ° with respect to the optical axis of the light emitted from the telecentric optical system 14. The reflecting surfaces of both mirror parts are arranged side by side with a very slight gap. The phase shifter 31 corresponds to the optical path length difference providing unit and the optical path length difference changing unit of the present invention. The fixed mirror unit 311 and the movable mirror unit 312 constitute an interference optical system.

The drive mechanism 313 is composed of, for example, a piezoelectric element including a capacitance sensor, receives a signal from the control device 34, and maintains a tilt angle of the reflecting surface with respect to the optical axis at 45 ° while the movable mirror unit 312 is moved in the direction of arrow A. With this configuration, the relative position of the movable mirror unit 312 with respect to the fixed mirror unit 311 changes, and an optical path length difference is given between the light beam reflected by the fixed mirror unit 311 and the light beam reflected by the movable mirror unit 312. The
Specifically, the moving amount of the movable mirror unit 312 in the optical axis direction is 1 / √2 of the moving amount of the movable mirror unit 312 in the arrow A direction. The optical path length difference that gives a relative phase change between the fixed light beam and the movable light beam is twice the amount of movement of the movable mirror unit 312 in the optical axis direction.

FIG. 2A is a diagram showing a configuration of the irradiation optical system 12 and the telecentric optical system 14 and a light path passing through the irradiation optical system 12, the telecentric optical system 14 and the sample storage device 11. The irradiation optical system 12 includes the light source 10, a condenser lens 121, an aperture stop 122 provided at the focal position of the condenser lens 121, and a collimator lens that shapes light that has passed through the aperture stop 122 into parallel light. 123. The telecentric optical system 14 includes a condenser lens 141, a pinhole 142 provided at the focal position of the condenser lens 141, and a collimator lens 143 that shapes the light that has passed through the pinhole 142 into parallel light. It consists of and. The sample storage device 11 is disposed between the collimator lens 123 of the irradiation optical system 12 and the condenser lens 141 of the telecentric optical system 14. With such a configuration, only the light collected from the light source by the condenser lens 121 and passed through the aperture stop 122 is incident on the collimator lens 123, and the parallel light is incident on the sample storage device 11. Subsequently, of the light emitted from the sample storage device 11, it enters the condenser lens 141, and only the component condensed at the focal position by the condenser lens 141 passes through the pinhole 142 and enters the collimator lens 143. To do. Then, after being shaped into parallel light by the collimator lens 143, it goes to the spectroscopic measurement system 13.

The light introduced into the spectroscopic measurement system 13 is reflected by the fixed mirror unit 311 and the movable mirror unit 312 of the phase shifter 31 and enters the imaging lens 32 as the first measurement light and the second measurement light, respectively, and the detection unit 33. The light is collected and imaged on the light receiving surface. At this time, the movable mirror unit 312 is driven by the drive mechanism 313, and a continuous optical path length difference, that is, a phase difference is given between the first measurement light and the second measurement light. Is formed with interference light of the first measurement light and the second measurement light. The processing unit 341 of the control device 34 obtains an interferogram from the intensity of the interference light detected by the detection unit 33, and obtains the spectral characteristic (spectrum) of the measurement light by performing arithmetic processing on the interferogram.

FIG. 3 shows a schematic configuration of the sample storage device 11. The sample storage device 11 includes a flat cubic sample cell 111 made of a transparent resin, glass, or the like through which light emitted from the light source 10 is transmitted, and a pair attached to two opposing side surfaces of the sample cell 111. Ultrasonic transducers 112 and 113, and a driving device 114 that controls the frequency (wavelength) of the ultrasonic wave irradiated to the sample in the sample cell 111 by the ultrasonic transducers 112 and 113. The sample cell 111 contains a sample containing a liquid component and a particle component (fine particle component). The light source 10 emits light having an absorption wavelength specific to the liquid component in the sample. For example, when blood is used as a sample, mid-infrared light is emitted from the light source 10, and in this case, the sample cell 111 is formed of germanium glass. The sample cell 111 has a light incident surface 111a and a light emitting surface 111b that are parallel to each other. The light incident surface 111a faces the collimator lens 123, and the light emitting surface 111b faces the condenser lens 141. . At this time, the positional relationship between the irradiation optical system 12 and the sample cell 111 is set so that the optical axis of the light shaped into parallel light by the collimator lens 123 is orthogonal to the light incident surface 111a of the sample cell 111. The light incident surface 111a of the sample cell 111 has such a size that almost all of the light from the light source 10 shaped into parallel light by the collimator lens 123 is incident.

The ultrasonic transducers 112 and 113 are attached to two side surfaces of the sample cell 111 adjacent to the light incident surface 111a and the light emitting surface 111b, and the driving device 114 is one of the ultrasonic vibration elements 112 and 113. One or both are driven to irradiate the sample in the sample cell 111 with ultrasonic waves. For example, FIG. 4 shows a case where ultrasonic waves are not irradiated (left), an ultrasonic wave is irradiated from one ultrasonic vibrating element (upper right), and an ultrasonic wave is irradiated from both ultrasonic vibrating elements (lower right). It is a figure which shows typically the mode in the sample cell 111 of (). As described above, in this embodiment, when one or both of the ultrasonic vibration elements 112 and 113 are driven with respect to the sample cell 111 in which the sample is accommodated, and ultrasonic waves are irradiated into the sample cell 111. A standing wave is formed in the sample. At this time, the length and width (thickness) of the sample cell 111, the frequency of the ultrasonic wave, etc. are set in advance so that the fine particle component is collected (captured) near the node of the standing wave by the acoustic radiation pressure, As a result, the sample accommodated in the sample cell 111 is separated into the fine particle component and the liquid component.

In this state, when light is emitted from the light source 10 and is incident on the light incident surface 111a of the sample cell 111, a part of the incident light passes through the region where the fine particle component is captured (fine particle component region), and the rest is other than that. Pass through the region (liquid component region). Incident light passing through the fine particle component region is scattered by the fine particles and then emitted from the light exit surface 111b. On the other hand, the incident light passing through the liquid component region is partially absorbed by the liquid component and then emitted from the light exit surface 111b. Of the light emitted from the light exit surface 111b, the light whose optical axis is orthogonal to the exit surface 111b is shaped into parallel light by the telecentric optical system 14 and then travels to the spectroscopic measurement system 13. That is, in this embodiment, only the light that has passed through the liquid component region out of the light emitted from the light exit surface 111b is shaped into parallel light by the telecentric optical system 14, and then introduced into the spectroscopic measurement system 13 to perform the spectroscopic measurement. The spectral characteristics are measured by the system 13. Thereby, qualitative and quantitative determination of the liquid component can be performed.

Next, specific experimental results obtained by measuring a sample using the spectral characteristic apparatus according to the present embodiment will be described.
Fig. 5 shows that a sample composed of absolute ethanol and polystyrene fine particles with a particle size of 1 µm (the proportion of polystyrene fine particles is 0.05 wt%, 0.10 wt%, 0.2 wt%, 0.3 wt%) is stored in a sample cell made of synthetic quartz. The measurement results of the spectral characteristics when a halogen lamp is used as the light source are shown. The graph on the left side of the figure shows the measurement results in a state where no standing wave is formed in the sample, and the graph on the right side of the figure shows the measurement results in a state where standing waves are formed. The left and right graphs in FIG. 6 are graphs of absorbance (relative intensity) obtained from the spectral characteristics (relative intensity) graphs on the left and right sides in FIG. 5, respectively.

As can be seen from FIGS. 5 and 6, when the standing wave was formed in the sample, the relative intensity of the spectral characteristics increased as compared with the case where the standing wave was not formed. This is presumably because the area of only the liquid component was increased and the amount of transmitted light was increased by capturing the fine particles in the antinodes of the standing wave. In addition, when the standing wave was formed in the sample, the relative intensity of the absorbance was reduced when the standing wave was formed, but the noise was reduced and the measurable wavelength range was widened. Since the measurable wavelength range when a standing wave is formed is close to the absorption wavelength range of water and ethanol (1100 nm to 1700 nm), forming a standing wave can be effective in measuring spectral characteristics. It could be confirmed.

Subsequently, in order to investigate the effect of adopting the telecentric optical system 14, a spectroscopic measurement apparatus using the imaging optical system 24 shown in FIG. The experiment was conducted using a light source and the like in a state where a standing wave was formed. As shown in FIG. 2B, the imaging optical system 24 uses a collimator lens 241 instead of the condenser lens 141 of the telecentric optical system 14, and an imaging lens 243 instead of the collimator lens 143. The imaging optical system 24 does not use pinholes. The results are shown in FIGS. 7 and 8 show the results of spectral characteristics and absorbance, respectively, and the graphs on the left and right sides of both figures show the results of the imaging optical system 24 and the telecentric optical system 14, respectively. In this experiment, the diameter of the pinhole 142 of the telecentric optical system 14 was 500 μm.

When the telecentric optical system 14 is used, the light emitted from the emission surface is limited by the pinhole 142, so that the amount of light introduced into the split optical system 13 is smaller than that in the case of the imaging optical system 24. For this reason, when the telecentric optical system 14 is used, a sample having a fine particle concentration of 0.3% could not be measured (see the graph on the right side of FIG. 7), but the spectral characteristics can be measured at other concentrations. There was less noise than the measurement result of the image optical system 24.

Next, erythrocytes are added to physiological saline contained in a sample cell having a thickness of 2 mm, and the sample cell is irradiated with light from an LED light source with ultrasonic vibration having a frequency of 1.6 MHz applied to the sample cell. The spectroscopic measurements of the samples were measured. FIG. 9 shows a photograph of the sample storage device used in the experiment. As shown in FIG. 9, in this sample storage device, ultrasonic transducers having a diameter of 30 mm are arranged on both sides of the sample cell.

FIG. 10 is an image of the sample cell when ultrasonic vibration is applied. From this image, it can be seen that red blood cells gather in a straight line near the nodes of the ultrasonic standing wave, and a striped pattern is formed.
Next, an interferogram was obtained based on the output signal of each pixel of the CCD camera corresponding to the position of the antinode of the ultrasonic standing wave. The result is shown in FIG. 11A. In this interferogram, it can be confirmed that there is a fluctuation in light intensity with a luminance value of about 15 in the baseline, which is probably due to red blood cells that were not aggregated into the nodes of the ultrasonic standing wave. is there.

FIG. 11B shows the spectral characteristics (that is, the spectral characteristics of red blood cells + saline) obtained by Fourier transforming the interferogram of FIG. 11A (curve L1). A curve L2 in FIG. 11B shows the spectral characteristics measured by placing only physiological saline in the sample cell.
Comparing the two, it can be seen that the spectral spectra of both agree not only in the vicinity of 1400 nm, which is the absorption wavelength band of water, but also in the entire wavelength range of 900-1700 nm. From this, it can be seen that by applying ultrasonic vibration and obtaining an interferogram in the vicinity of the abdomen, it is possible to obtain the spectral characteristics of only physiological saline excluding red blood cells from the sample.

A specific example in which the spectroscopic measurement device according to the above-described embodiment is incorporated in a blood circuit of a dialysis device will be described with reference to FIG.
The dialysis device includes a dialysis supply device that supplies dialysate to a dialyzer and a blood pump that guides blood out of the patient's shunt, passes it through the dialyzer, and returns it to the body. Dialysate flows through the dialysis circuit between the dialyzer and the dialysis supply, and blood flows between the shunt and the dialyzer through the blood circuit (arterial circuit and venous circuit).

患者 Patients with dialysis often suffer from kidney failure due to diabetes, and originally have a low ability to control blood sugar levels. For this reason, there are cases where hypoglycemia occurs during dialysis, which is dangerous. Therefore, in the dialysis apparatus according to the present embodiment, the above-described spectroscopic measurement devices are incorporated in the arterial blood circuit and the venous blood circuit, respectively. Thereby, the blood glucose level of the blood of the patient during dialysis can be measured with high accuracy.

13 and 14 show a sample storage device 21 used for acquiring the spectral characteristics of the liquid component or particle component contained in the sample by the ATR method (Attenuated Total Reflection). The sample storage device 21 includes a cubic sample cell 211, an ATR prism (trapezoidal prism) 216 arranged so as to be in contact with one of the six side surfaces of the sample cell 211, and the ATR prism 216 of the sample cell 211. The ultrasonic transducers 213 and 212 installed on the side surface of the sample cell 211 facing the contact surface 211a and the side surface of the ATR prism 216 facing the contact surface 211a and the ultrasonic transducers 213 and 212 are driven. A drive device (not shown) is provided. In this embodiment, the contact surface 211a of the sample cell 211 with the ATR prism 216 serves as a light incident surface and a light output surface.

In this embodiment, the light from the irradiation optical system is incident on the contact surface 211a at the angle of total reflection with respect to the sample storage device 21. Then, the incident light is repeatedly reflected in the prism 216, then exits from the prism 216, and enters the spectrometer. At this time, evanescent light (near-field light) having a thickness of about several hundred nm is generated on the surface of the prism 216. Although not described in detail, the irradiation optical system and the spectroscopic optical system of the present embodiment may be those shown in FIGS. 1 and 2A.

In the sample storage device 21, a standing wave is formed in the sample in the sample cell 211 by driving one or both of the ultrasonic transducers 212 and 213. At this time, when the antinode is located in the vicinity of the contact surface 211a (see FIG. 13), since the liquid component mainly exists in the vicinity of the contact surface 211a of the sample cell 211, the interaction between the liquid component and the evanescent light is caused. The spectral characteristics (absorption spectrum) of the liquid component can be measured. On the other hand, when the node is located in the vicinity of the contact surface 211a (see FIG. 14), since the particle component mainly exists in the vicinity of the contact surface 211a of the sample cell 211, the interaction between the particle component and the evanescent light causes the The spectral characteristics of the particle component can be measured.

It is known that absorption spectroscopy using mid-infrared light enables highly sensitive measurement because light absorption in the fundamental vibration mode of molecules is observed. However, since mid-infrared light is largely absorbed by the liquid (water), it is preferable to shorten the distance (optical path length) through which the liquid component passes as much as possible. In the present embodiment, the sample storage device 21 is configured by the sample cell 211 for storing the sample and the ATR prism 216, and the liquid component or the particle component contained in the sample is separated by the ATR method using evanescent light generated on the surface of the prism 216. Since the characteristics are acquired, the absorption of the light from the irradiation optical system by the liquid can be suppressed to a low level.

The present invention is not limited to the above-described embodiments and examples. For example, when the light emitted from the particle component out of the light emitted from the sample is selectively introduced into the spectroscopic measurement system 13, an imaging optical system 24 as shown in FIG. 2B may be used. In this case, it is preferable to install a light shielding plate at the focal position on the imaging lens 243 side of the collimator lens 241 in FIG. 2B so that transmitted light from the liquid component is not introduced into the spectroscopic measurement system 13.

In the above-described embodiments and examples, the sample including the particle component and the liquid component has been described. However, the spectroscopic measurement apparatus according to the present invention can also be applied to a sample including a plurality of liquid components. In this case, the liquid component is divided and distributed in the region near the node of the standing wave and the region near the antinode due to the difference in specific gravity. Therefore, the liquid component opens in the region where there are many target components and blocks other regions. When the slit is provided on the light exit surface of the sample cell, light emitted from the target component can be more selectively introduced into the spectroscopic measurement system 13.

Further, in the above embodiment, the light that has passed through the measurement optical system is divided into two, and the spectroscopic optical system is configured by the interference optical system that interferes with the split light. A system may be configured.

DESCRIPTION OF SYMBOLS 10 ... Light source 11, 21 ... Sample accommodation apparatus 111, 211 ... Sample cell 112, 113, 212, 213 ... Ultrasonic vibration element 114 ... Drive apparatus 216 ... ATR prism 12 ... Irradiation optical system 121 ... Condensing lens 122 ... Aperture stop 123 ... Collimator lens 13 ... Spectroscopic measurement system 14 ... Telecentric optical system 141 on both sides 141 ... Condensing lens 142 ... Pinhole 143 ... Collimator lens 24 ... Imaging optical system 241 ... Collimator lens 243 ... Imaging lens 31 ... Phase shifter 311 ... Fixed Mirror unit 312 ... Movable mirror unit 313 ... Drive mechanism 32 ... Imaging lens 33 ... Detection unit 34 ... Control device 341 ... Processing unit 342 ... Calculation unit

Claims (9)

Spectroscopic measurement comprising a spectroscopic optical system that splits light emitted from the sample when irradiated with a sample containing a plurality of liquid components, and a detector that detects the light dispersed by the spectroscopic optical system In the device
a) a sample cell having a light incident surface and a light output surface having a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component;
b) light irradiation means for irradiating the sample in the sample cell with the irradiation light through the light incident surface;
c) standing wave forming means for forming a standing wave in the sample by irradiating the sample contained in the sample cell with ultrasonic waves;
d) A spectroscopic measurement apparatus comprising: a measurement optical system that is disposed between the sample cell and the spectroscopic optical system and converts light emitted from the sample cell into parallel light. A spectroscopic system comprising a spectroscopic optical system for spectroscopically splitting light emitted from a sample containing a liquid component and a particle component, and a detection device for detecting light split by the spectroscopic optical system. In the measuring device,
a) a sample cell having a light entrance surface and a light exit surface parallel to each other, having a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component;
b) a light irradiation means for irradiating the sample in the sample cell with the irradiation light;
c) A constant wave is formed in the sample by irradiating the sample accommodated in the sample cell with an antinode and a node arranged in a direction parallel to the light incident surface and the light output surface. Presence wave forming means,
d) A condensing lens for condensing a part of light emitted from the sample cell, which is disposed between the sample cell and the spectroscopic optical system, and collimated light collected by the condensing lens. A spectroscopic measurement device comprising: a collimator lens that converts the light into a collimator lens; and a measurement optical system that includes a pinhole disposed at a focal position on the collimator lens side of the condenser lens. The measurement optical system includes a telecentric optical system on both the sample cell side and the spectroscopic optical system side having an optical axis orthogonal to the light incident surface and the light emitting surface of the sample cell. Item 3. The spectroscopic measurement device according to Item 2. A spectroscopic system comprising a spectroscopic optical system for spectroscopically splitting light emitted from a sample containing a liquid component and a particle component, and a detection device for detecting light split by the spectroscopic optical system. In the measuring device,
e) a sample cell having a light entrance surface and a light exit surface parallel to each other, having a property of transmitting light emitted from the particle component, which is light having an absorption wavelength or transmission wavelength specific to the liquid component,
f) light irradiation means for irradiating the sample in the sample cell with the irradiation light;
g) A constant wave in which antinodes and nodes are arranged in the sample along a direction parallel to the light incident surface and the light output surface by irradiating the sample contained in the sample cell with ultrasonic waves. Presence wave forming means,
h) A collimator lens disposed between the sample cell and the spectroscopic optical system for converting a part of the light emitted from the sample cell into parallel light; and light converted into parallel light by the collimator lens Measuring optics having an imaging lens that forms an image on a predetermined imaging surface, and a light shielding plate that is disposed at a focal position on the imaging lens side of the collimator lens and shields light collected by the collimator lens A spectroscopic measurement device comprising: a system. The light irradiating means includes a light source, a condensing lens that condenses light from the light source, a collimator lens that shapes the light collected by the condensing lens into parallel light, a condensing lens, and a collimator lens. An aperture stop disposed at a confocal point, and irradiating the sample in the sample cell with light having an optical axis perpendicular to the light incident surface and the light emitting surface of the sample cell. The spectroscopic measurement device according to any one of 2 to 4. A splitting optical system for dividing the measurement light, which is light that has passed through the measurement optical system, into first measurement light and second measurement light; and between the first measurement light and the second measurement light. An optical path length difference providing means for providing an optical path length difference, an optical path length difference changing means for continuously changing the optical path length difference provided by the optical path length difference providing means, the first measurement light, and the second measurement light. An interference optical system that interferes,
The detector configured to detect the intensity of interference light between the first measurement light and the second measurement light formed by the interference optical system, and the optical path length difference changing means to change the optical path length difference. 2. A processing unit that obtains an interferogram of the measurement light from an intensity change of the interference light detected by the sensor and obtains a spectrum of the measurement light by Fourier transforming the interferogram. The spectroscopic measurement device according to any one of 5. In a spectroscopic measurement method in which when a sample containing a liquid component and a particle component is irradiated with irradiation light, the light emitted from the sample is dispersed with a spectroscopic optical system and the spectral characteristics of the sample are measured.
The sample is accommodated in a sample cell having a light incident surface and a light output surface parallel to each other, which has a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component,
By irradiating the sample in the sample cell with ultrasonic waves, a standing wave in which the antinodes and nodes are arranged in a direction parallel to or orthogonal to the light incident surface and the light emitting surface is formed in the sample.
A spectroscopic measurement method comprising irradiating a sample in the sample cell with irradiation light to convert a part of the light emitted from the sample cell into parallel light and introducing the parallel light into the spectroscopic optical system. In a spectroscopic measurement method in which when a sample containing a liquid component and a particle component is irradiated with irradiation light, the light emitted from the sample is dispersed with a spectroscopic optical system and the spectral characteristics of the sample are measured.
The sample is accommodated in a sample cell having a light incident surface and a light output surface parallel to each other, which has a property of transmitting light having an absorption wavelength or transmission wavelength specific to the liquid component,
By irradiating the sample in the sample cell with ultrasonic waves, a standing wave in which the antinodes and nodes are arranged in a direction parallel to or orthogonal to the light incident surface and the light emitting surface is formed in the sample.
Spectroscopic measurement characterized by irradiating a sample in the sample cell with irradiation light to form a part of the light emitted from the sample cell on a predetermined imaging plane and introducing the image into a spectroscopic optical system. Method. The spectral optical system splits the introduced light into a first measurement light and a second measurement light, and an optical path length that gives an optical path length difference between the first measurement light and the second measurement light. Difference providing means;
Optical path length difference changing means for continuously changing the optical path length difference provided by the optical path length difference providing means;
An interference optical system for causing the first measurement light and the second measurement light to interfere with each other;
An interferogram of the measurement light is obtained by detecting the intensity of the interference light when the optical path length difference is changed by the optical path length difference changing means, and the spectral optics is obtained by Fourier transforming the interferogram. The spectroscopic measurement method according to claim 7 or 8, wherein a spectrum of light introduced into the system is acquired.

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