JPH06173A - Multiple item biochemical analyzer - Google Patents

Abstract

PURPOSE:To provide the multiple item biochemical analyzer which can simultaneously measure plural components and facilitated handling of reagents. CONSTITUTION:This multiple item biochemical analyzer is constituted by providing the analyzer with a sample component detecting section 4 consisting of an ion detecting section 1, a gas detecting section 2 and biochemical component detecting section 3 consisting of a spectroscopic means, such as IR spectroscopic means or Raman spectroscopic means. A disposable sample component detecting section including plural ion sensors, reference electrode, plural gas sensors and total reflection attenuation prism for spectroscopically detecting the biochemical components is used for analyzing the sample oozing out of the skin. As a result, the plural components are rapidly measured by using the trace samples and the number of the reagents is reduced in a wide medical treatment field and, therefore, the reduction of running costs is possible.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a multi-item biochemical analyzer, capable of simultaneously measuring a plurality of components, greatly reducing the number of reagents, and reducing the labor and running cost of reagent management. To provide an analyzer.

[0002]

In the medical field, ionic components (eg, sodium, potassium, calcium, hydrogen,
It is desirable to analyze minute amounts of samples such as chlorine and other ions), gas components (eg, carbon dioxide gas, oxygen gas, etc.), and biochemical components (urea, virubilin, uric acid, creatinine, glucose, etc.) in a short time. It is rare. On the other hand, as a method capable of measuring the components of whole blood, "Dry Chemistry" is described in "Spectrophotometric Method in Clinical Biochemical Examination" edited by N. Yoshino and Hisao Osawa, pp. 1 to 42, Academic Society Publishing Center (1984). . In dry chemistry, films for ionic components and biochemical components applicable to whole blood have been developed. On the other hand, an ion gas analyzer that incorporates an ion electrode and a gas electrode and is applicable to measurement of whole blood is on the market. Further, JP-A-56-63259 discloses an ion gas biochemical analyzer for analyzing whole blood, which incorporates an ion electrode, a gas electrode, and an enzyme electrode. Furthermore, there is a biochemical automatic analyzer for measuring serum, which is widely used in clinical laboratories.

A transcutaneous gas sensor has already been put into practical use as described in Tatsuo Togawa, "Biometrics and Sensors", Corona Publishing Co. (1986), pages 372 to 377. In addition, transcutaneous measurement by attenuated total reflection infrared spectroscopy is described in Transaction on Biomedical Engineering, BME-26 (1979) pp. 597-6.
Page 00 (Transaction on Biomedical Engineering BME-
26 (1979) pp597-600), and transdermal measurement of glucose and the like without heating. The fact that glucose contained in sweat is correlated well with blood glucose is described in Clinical Chemistry, 15 (1986), pp. 75-79.
It is described on the page.

As an ion sensor, an ion-selective field effect transistor can measure sodium, potassium, chlorine, calcium, hydrogen, etc., and as a gas sensor, a Seberinghouse-type carbon dioxide sensor and Clark-type oxygen which are miniaturized by using semiconductor technology. There are sensors, and these sensors are described in "Biometrics and Sensors" by Tatsuo Togawa, Corona Publishing Co. (1986), pages 357 to 385.

[0005]

However, the conventional apparatus has not been sufficiently considered in the point of simultaneously measuring a plurality of components in a sample. In dry chemistry, it is possible to measure ionic components up to 3 components in one film, but biochemical components are measured using a film that measures only one component, and a film that measures gas components is still under development. It has not been. Further, there is a problem that an ion gas analyzer cannot measure biochemical components, an ion gas biochemical analyzer can measure only two biochemical components, and an automatic biochemical analyzer cannot measure gas components. Moreover, conventional devices have not been fully considered in terms of analysis time. Since dry chemistry films are measured one by one, it takes a long time to measure a plurality of components in the same sample. In addition, the biochemical automatic analyzer has a problem that it cannot handle emergency tests because it takes time to obtain serum by centrifugation of whole blood. Moreover, the conventional apparatus has not been fully considered in terms of the amount of sample used for analysis. Dry chemistry and automatic biochemistry analyzers have a problem that a large amount of sample is required to measure multiple components in the same sample.

Further, the conventional apparatus has not been sufficiently considered in terms of reagent management and running cost, and in dry chemistry, the reagent is contained in the film in a dry state, so that the film is protected from deterioration of the reagent. There is a problem that storage management is complicated and running costs are high. In addition, the biochemical automatic analyzer requires a reagent for each measurement item and each measurement sample, and there is a problem that management of many kinds of reagents is complicated and running cost becomes high.
An object of the present invention is to provide a multi-item biochemical analyzer with a low running cost, which enables simultaneous measurement of a plurality of components with a small amount of sample in a short time, and easy management of reagents.

[0007]

Means for Solving the Problems The above-described object is to provide a multi-item biochemical analyzer with an ion detector for detecting an ion component, a gas detector for detecting a gas component, and an infrared spectroscope for detecting a biochemical component. Means or a biochemical component detecting section composed of a spectroscopic means such as Raman spectroscopic means is arranged in series and / or parallel to form a sample component detecting section, and only a trace amount of a liquid sample such as blood is detected as a sample component detecting section. And a plurality of components in the liquid sample are simultaneously analyzed in a short time. In addition, the blood flow is examined by heating the skin using a disposable sample component detection unit that includes multiple ion sensors, multiple gas sensors, and a total reflection attenuation prism that spectroscopically detects biochemical components. Analyze the sample that comes close to the surface of the skin and exudes from the skin with higher accuracy. That is, in a multi-item biochemical analyzer that simultaneously measures ionic components, gas components and biochemical components in a liquid sample without adding reagents to the liquid sample and reacting them, the biochemical components are attenuated by total reflection red It is measured by external spectroscopy or attenuated total reflection Raman spectroscopy.

The multi-item biochemical analyzer of the present invention comprises a biochemical component comprising an ion detecting part for detecting an ionic component in a liquid sample, a gas detecting part for detecting a gas, and a spectroscopic means for detecting the biochemical component. A sample component detection unit composed of a detection unit, an amplification unit for amplifying signals from the ion detection unit and the gas detection unit, a light source unit for making light incident on the biochemical component detection unit, and a biochemical component detection unit A light receiving part that receives the light emitted from the device, a calculating part that calculates the concentrations of ionic components, gas components, and biochemical components by calculating the output signals from the amplifying part and the light receiving part, and the sample component detection of the liquid sample It has an analysis part including a sample supply part for supplying the analysis part and a control part for controlling the analysis part. The ion detector electrochemically detects the ion component and the gas component detector electrochemically detects the gas component, respectively.
A liquid sample is brought into contact with the sample component detection unit to detect an ionic component, a gas component, and a biochemical component. In addition, the sample component detection unit is provided with a flow channel through which the liquid sample flows, and the liquid sample is introduced into the flow channel from the sample supply unit. An ion detector, a gas detector, and a biochemical component detector are arranged in series in the flow path. Alternatively, the ion detecting unit, the gas detecting unit, and the biochemical component detecting unit are divided into a plurality of groups and are arranged in parallel with the flow path interposed therebetween. The part of the flow path that comes into contact with the gas detection part is formed of a film having a high gas permeability. Instead of disposing the flow path, a sample spotting part for spotting the liquid sample is provided on the sample component detecting part, and a cover having a low gas permeability is provided on the sample spotting part.

The sample component detection unit is attached to the surface of the inspection target to measure the components in the liquid sample transdermally exuded from the inspection target, and the ion detection unit detects the components in the body fluid such as sweat and saliva of the inspection target. The ionic component, the gas detection unit uses the gas component transudatively exuded from the blood vessel to be inspected, and the biochemical component detection unit uses the transmitted light transmitted through the inspection target or the reflected light reflected from the inspection target for biochemistry Each component is measured individually. further,
The sample component detection unit is configured to be detachable from the electric circuit unit including the amplification unit, the light source unit, and the calculation unit.

At least a biochemical component detecting unit including an ion detecting unit for detecting an ionic component in a liquid sample, a gas detecting unit for detecting a gas, and a spectroscopic means for detecting a biochemical component is formed on a silicon substrate, A sample component detection unit including a first optical fiber unit that transmits incident light and emitted light that are coupled to the biochemical component detection unit, an amplification unit that amplifies signals from the ion detection unit and the gas detection unit, and a biochemical component A light source unit for making light incident on the detection unit, a light receiving unit for receiving light emitted from the biochemical component detection unit, and a second unit for transmitting incident light and emitted light
Of the liquid sample, and an electric circuit section including an optical fiber section, an arithmetic section for calculating output signals from the amplifying section and the light receiving section, and calculating respective concentrations of an ionic component, a gas component, and a biochemical component. A multi-item biochemical analyzer having an analysis unit including a sample supply unit that supplies the component detection unit and a control unit that controls this analysis unit, and the ion detection unit detects an ionic component,
The gas component detection unit electrochemically detects the gas components.

A liquid sample is brought into contact with the sample component detector to detect an ionic component, a gas component and a biochemical component. A flow path through which the liquid sample flows is provided on the surface of the sample component detection unit, and the liquid sample is introduced into the flow path from the sample supply unit, or the liquid sample is spotted on the sample component detection unit. A cover having a low gas permeability is provided on the sample component detection unit. In order to measure a large number of samples, an autosampler is arranged and a liquid sample is automatically supplied to the sample supply unit. The sample component detection unit is attached to the surface of the inspection target, and measures the components in the liquid sample transdermally exuded from the inspection target, and the ion detection unit detects the ionic components in the body fluid such as sweat or saliva of the inspection target. The gas detection unit detects gas components percutaneously exuded from the blood vessel to be inspected, and the biochemical component detection unit detects biochemical components by using transmitted light transmitted through the inspection target or reflected light reflected from the inspection target, respectively. taking measurement. The sample component detection unit is detachable from the electric circuit unit, and the sample component detection unit is disposable. The ion component detection unit consists of either an ion selective electrode or an ion selective field effect transistor, the gas component detection unit consists of a Sewering House type electrode or a Clark type electrode, the liquid sample is whole blood of an animal, Animal-derived body fluids such as urine, more specifically, liquid samples are human-derived body fluids such as human whole blood and urine.

[0012]

[Function] By bringing the liquid sample into contact with the sample component detection unit of the multi-item biochemical analyzer, the ion detection unit, the gas detection unit, and the infrared spectroscopic means or Raman spectroscopic means arranged in the sample component detection section With the biochemical component detection unit, the ion, gas, and biochemical components can be analyzed simultaneously. That is, the ion components required by various ion sensors provided in the ion detection unit, the desired gas components in various gas sensors provided in the gas detection unit, the infrared or Raman spectrum obtained from the biochemical component detection unit, etc. The target biochemical component can be measured from the analysis of. In the ion detector, for example, a reference electrode and an ion-selective electrode are placed, and various ions can be measured by changing the type of the sensitive film of the on-selective electrode. The carbon dioxide gas can be measured with the sewering house type electrode and the oxygen can be measured with the Clark type electrode. For infrared spectroscopy or Raman spectroscopy, see Seiko Tanaka, Yoshio Iida, "Instrument Analysis (Revised Edition)", Yukabo (1985), pp. 70-1.
As described on page 09, the concentration of the target component can be determined by determining the peak area in the wavelength region peculiar to each biochemical component in the measured spectrum. Infrared spectroscopy or Raman spectroscopy using an attenuated total reflection prism can obtain biochemical component information from the surface layer of the sample. The total reflection attenuating prism arranged in the biochemical component detecting portion surely contacts the sample. The total reflection attenuating prism is small and capable of measuring a plurality of components. The biochemical component having the largest number of components in the present invention can be measured in a minute region, and the amount of sample can be significantly reduced. Further, the amount of the sample can be reduced also by integrating and disposing the ion detector, the gas detector, and the biochemical component detector. According to the present invention, many ion components, gas components, and biochemical components contained in one liquid sample can be simultaneously measured in the sample component detection unit in a short time. In addition, since the biochemical component detection unit consisting of infrared spectroscopic means or Raman spectroscopic means does not require reagents, the number of reagents required for sample analysis can be greatly reduced, and the labor and running cost of reagent management can be greatly reduced. Can be reduced.

An ion detector for detecting an ionic component in a liquid sample, a gas detector for detecting a gas, and a biochemical component detector composed of a spectroscopic means for detecting a biochemical component are formed on a silicon substrate by miniaturization. Therefore, the multi-item biochemical analyzer of the present invention can be downsized, lightened, and reduced in cost, and can be easily handled.

[0014]

1 is a block diagram showing the basic concept of a multi-item biochemical analyzer of the present invention. The multi-item biochemical analyzer comprises an ion detecting section 1 for detecting ions, a gas detecting section 2 for detecting gas, and a biochemical component detecting section 3 for detecting biochemical components, such as infrared spectroscopic means or Raman spectroscopic means. A sample component detection unit 4 configured, a sample supply unit 13 that supplies a liquid sample to the sample component detection unit 4, an amplification unit 5 that amplifies the output signals of the ion detection unit 1 and the gas detection unit 2, and a biochemical sample. A light source section 7 for generating incident light 6 to the component detecting section 3 and a light receiving section 9 for receiving emitted light 8 from the biochemical sample component detecting section 3.
And an analyzing unit 11 having a storage memory, processing an output signal from the amplifying unit 5 and the light receiving unit 9 to obtain and outputting the concentration of each component in the sample, and displaying and displaying the same, and an analyzing unit 11. The control unit 12 controls each unit to be controlled based on the data input by the analyst or the data set in the memory of the arithmetic unit 10 in advance. The ion detection unit 1, the gas detection unit 2, and the biochemical sample component detection unit 3 that constitute the sample component detection unit 4 may be arranged as long as each of these detection units comes into direct or indirect contact with the sample. It may be arranged in series and / or in parallel. The ion detector 1 uses an ion selective electrode, a coated wire type ion selective sensor, an ion selective field effect transistor (ISFET) or the like as an ion sensor. Figure 1
Although omitted, a reference electrode is also arranged in a part of the ion detector 1. In addition, various ions such as sodium, potassium, chlorine, hydrogen, and calcium are measured. A plurality of ion sensors are arranged, and each ion sensor uses a sensitive film having high selectivity for a target measurement component. In the gas detection part 2, a sewering house type electrode was used as a carbon dioxide gas sensor and a Clark type electrode was used as an oxygen gas sensor. Also,
Infrared spectroscopic means or Raman spectroscopic means were used to detect the biochemical components, but the biochemical component detection unit 3 by these spectroscopic means does not require a reagent and can measure many biochemical components at the same time. It is characterized by using a total reflection attenuating prism. Further, the present invention is also characterized by biochemical analysis in a sample using Raman spectroscopy.

The multi-item biochemical analyzer of the present invention operates as follows. First, the sample supply unit 13 to the sample component detection unit 4
When a body fluid such as blood is supplied as a sample to the sample and the sample is directly or indirectly contacted with the sample component detecting unit 4, the ion detecting unit 1, the gas detecting unit 2, and the biochemical component detecting the sample component detecting unit 4 are formed. The part 3 detects the ion component, the gas component, and the biochemical component respectively, and the outputs of the ion detection part 1 and the gas detection part 2 are input to the amplification part 5, and the incident light 6 from the light source part 7 is input to the biochemical component detection part 3. Light that enters and is emitted from the biochemical component detection unit 8
Is received by the light receiving unit 9. The output signals from the amplification section 5 and the light receiving section 9 are input to the calculation section 10 and subjected to calculation processing to calculate the concentration of each component in the liquid sample. Each unit that constitutes the analysis unit 11 is controlled by the control unit 12. In the present invention, a ionic component, a gas component, and a biochemical component can be simultaneously measured for a plurality of components by using a small amount of sample, and the biochemical component is analyzed spectroscopically, so that a reagent for biochemical analysis is used. Without this, biochemical analysis can be performed at low running cost. The principle of the ion sensor and the gas sensor adopted in the present invention is well known as described in, for example, Tatsuo Togawa “Biometrics and Sensors”, Corona Publishing Co., Ltd. (1986), pages 344 to 413. To do. A method of using the attenuated total reflection prism in the infrared spectroscopy or the Raman spectroscopy will be briefly described below with reference to FIGS. 2 to 4.

FIG. 2 illustrates the principle of attenuated total reflection infrared spectroscopy. An enlarged view of the interface between the total reflection attenuating prism 21 and the sample 22 is shown in a circle in FIG. The infrared light 20 emitted from the light source unit 7 enters the total reflection attenuation prism 21, is subjected to multiple reflection in the total reflection attenuation prism, and then enters the light receiving unit 9. As the total reflection attenuating prism 21, a high refractive index material such as glass, quartz, germanium, or silicon is used, but in some cases, it is preferable to use zinc selenide having high water resistance. As shown in the enlarged view of FIG. 2, the infrared light 20 slightly permeates into the sample 22 at the interface between the total reflection attenuating prism 21 and the sample 22 and absorbs at a wavelength unique to each biochemical component in the sample. In comparison with the infrared absorption spectrum obtained by the transmission method, the infrared absorption spectrum less affected by water can be acquired. FIG. 3 is a diagram showing an infrared absorption spectrum example of a mixed aqueous solution containing a plurality of components. The sample is a mixed aqueous solution of urea, creatinine and glucose at 1 g / dl each, and an absorption spectrum having characteristic peaks due to stretching vibration and bending vibration peculiar to the functional group of each component has been obtained. Here, the absorption spectrum of water is acquired as a reference signal, and the influence of water is removed from the absorption spectrum of the mixed solution. It is known that infrared absorption spectra unique to the other biochemical components can be obtained, and many biochemical components can be measured. Also, depending on the biochemical component, characteristic peaks may overlap on the infrared absorption spectrum, but characteristic peaks that overlap with virtual peaks of a normal distribution shape may be separated or multiple characteristic peaks of the absorption spectrum of each component may be separated. Highly accurate analysis of multiple components is possible by multivariate analysis using peaks. In addition, various ultrafiltration membranes with different molecular weight cut-offs are placed at different locations on the total reflection attenuating prism, and the sample that has passed through these ultrafiltration membranes is brought into contact with the total reflection attenuating prism to remove the effect of giant molecular weight. Then, more biochemical components can be accurately measured by attenuated total reflection infrared spectroscopy.

FIG. 4 illustrates the principle of attenuated total reflection Raman spectroscopy. As in the attenuated total reflection infrared spectroscopy described with reference to FIG. 3, the excitation light 31 that has penetrated into the sample 22 from the attenuated total reflection prism 21 generates Raman scattered light 33 due to the biochemical components in the sample 22. . Raman scattering is based on the vibration and rotational motion of functional groups in principle, similar to infrared spectroscopy. Compared to ordinary Raman absorption spectra, attenuated total reflection Raman spectroscopy has the characteristics that it is possible to increase the precision because it is not affected by water and it is possible to increase the number of measurement components because it can measure in the low wavelength range. However, it also has the drawback of low sensitivity. Whether to use attenuated total reflection Raman spectroscopy or attenuated total reflection infrared spectroscopy depends on the biochemical component to be measured. The shape of the total reflection attenuation prism is hemispherical, 3
There are prisms and parallel plates, and the plane is used for the total reflection surface.
The intensity change of the total reflection light when the wavelength of the light incident on the total reflection attenuation prism at a constant angle is changed or the incident angle of the light of the constant wavelength is changed is measured.

FIG. 5 is a view showing the arrangement of an embodiment of a flow system multi-item biochemical analyzer for emergency inspection according to the present invention.
The flow system multi-item biochemical analyzer for emergency inspection is equipped with a flow channel 40.
Ion sensors 41, 42, 43, 4 arranged facing the
4, 45, an ion detecting section including the reference electrode 50, a gas detecting section including the gas sensors 60 and 61, and a sample component detecting section 4 including a biochemical component detecting section including the attenuated total reflection prism 21. Light source unit (infrared light source unit) 7, infrared light 20, light receiving unit 9, amplifying unit 5, arithmetic unit 10, flow path 40
Cleaning solution 70 for cleaning the sensor, calibration solution 7 for calibrating the sensor
1, 72, opening / closing valves 73, 74, 75 for controlling the injection of the cleaning liquid and the calibration liquid into the flow path, a switching valve 76 for switching the injection of the cleaning liquid, the calibration liquid and the sample into the flow path, and the injection of the sample. Injection cylinder 77, liquid delivery pump 7 for delivering liquid
8. A waste liquid bottle 79 for storing waste liquid, an analysis unit 11, and a control unit 12. The portion where the flow path 40 and the gas detection unit are in contact is formed of a film having a high gas permeability, for example, silicon rubber, and the gas that has passed through the film having a high gas permeability from the flow channel 40 is detected by the gas detection unit. This configuration is the same in the embodiments shown in FIGS. 6 and 9 which will be described later. The size of the flow channel is 1 mm in diameter and 50 in length.
mm. Ion sensors 41, 42, 43, 44, 4
Reference numeral 5 is an ion-selective electrode for measuring ions of sodium, potassium, chlorine, hydrogen, and calcium, respectively. A coated wire type ion-selective sensor,
Alternatively, an ion selective field effect transistor (ISFE
T) may be used. In addition, the ion-selective electrodes may be arranged in any order in the flow direction of each liquid in the flow path 40 (from left to right in FIG. 5). The gas sensors 60 and 61 are a Sewering House type carbon dioxide gas sensor and a Clark type oxygen sensor, and these may be arranged in any order with respect to the flow direction of the liquid in the flow path 40. Also, the total reflection attenuation prism 2
Although 1 uses a prism made of zinc selenide for infrared spectroscopy, a prism made of other material may be used.

The flow system multi-item biochemical analyzer for emergency inspection according to this embodiment operates as follows. In the urgent inspection, the calibration solution 71 and 72 are sequentially sent to the sample component detection unit 4 using the liquid feed pump 78 at regular time intervals so that the sample can be measured at any time, and the calibration solution 71 or 72 is detected for a fixed time during the fixed time. While calibrating the sensor while staying in part 4,
The cleaning liquid 70 is caused to flow by the liquid feed pump 78 to clean the flow path 40. In addition, the selection of the cleaning liquid 70 and the calibration liquids 71 and 72 is performed by selecting the open / close valves 73, 74 and 75 and the switching valve 7.
6 is controlled by the control unit 12. In addition, although two-point calibration is performed with two kinds of calibration solutions, one-point calibration may be sufficient.
In this way, because it is in a standby state that can be measured at any time,
A sample such as blood collected from a patient can be directly injected into the multi-item biochemical analyzer by the injection cylinder 77 or the like. When the sample is injected into the analysis unit 11, the sample is sent to the sample component detection unit 4 by the switching valve 76 and the liquid feed pump 78, and the sample is kept in the sample component detection unit 4 for a certain period of time to remove a plurality of components in the sample. taking measurement. After completion of the measurement, the flow passage 40 is washed with the liquid feed pump 78 using the washing liquid 70 each time, and the sensor is calibrated using the calibration liquids 71 and 72 at regular intervals.
Keep it in a standby state where you can measure anytime. The used cleaning liquid, calibration liquid, and sample are stored in the waste liquid bottle 79, and are collected and safely disposed before the liquid becomes full. Each unit of the analysis unit 11 is automatically controlled by the control unit 12. Although an example of analysis of biochemical components using attenuated total reflection infrared spectroscopy has been shown, total attenuated Raman spectroscopy may be used.

In FIG. 5, the biochemical component detection section, the ion detection section, and the gas detection section are arranged in series facing the flow path 40, but the ion detection section and the gas detection section are facing the flow path 40. Can be arranged in parallel to shorten the length of the flow path 40, reduce the amount of sample, and shorten the time required for analysis. In this embodiment, the ionic component, the gas component, and the biochemical component can be simultaneously urgently measured for a plurality of components, and the biochemical component is detected spectroscopically. Therefore, a reagent for biochemical component analysis is not required. FIG. 6 is a diagram showing a configuration of a sample component detection unit and its periphery, which is an embodiment of the flow-type multi-item biochemical analyzer according to the present invention. Since there is a limit to the reduction of the sample amount in the embodiment shown in FIG. 5, in this embodiment, in order to further reduce the amount of the sample, the ion sensor, the reference electrode, the gas sensor, and the total reflection are faced to the flow channel 40. Attenuating prisms were arranged in parallel to reduce the amount of sample. Thereby, the flow path 40
Since the length can be shortened, the amount of the sample can be reduced from one-third to one-half as compared with the embodiment shown in FIG. In addition,
The parallel arrangement of the sensor groups for reducing the amount of the sample is important, and the order of arranging the sensor groups in the channel may be arbitrary. The steps of calibration, sample introduction, cleaning, and waste liquid implementation are the same as those in the embodiment of FIG. In this embodiment, ionic components, gas components, and biochemical components can be measured simultaneously,
In particular, these components can be measured with a small amount of sample.

FIGS. 7 and 8 are diagrams showing the correlation of the measurement results by the analyzer according to the present invention and the conventional analyzer. These data were obtained by dividing the same whole blood sample into two and then measuring by the standard method which was generally used in the embodiment of the present invention shown in FIG. 5 and the conventional method. It is a correlation. FIG. 7 shows the concentration of each ion of sodium, potassium, chlorine and calcium, hydrogen ion shows the pH, oxygen shows the partial pressure, and FIG. 8 shows the partial pressure of carbon dioxide and the concentrations of glucose, urea, creatinine, bilirubin and uric acid. Indicates. According to the present invention, such 12 components can be measured simultaneously,
Good results showing correlation coefficient of 0.99 or more with the reference method could be obtained in all of the ion selective electrode, the gas electrode, and the attenuated total reflection infrared spectroscopy.

FIG. 9 is a diagram showing the configuration of an embodiment of a routine type flow type multi-item biochemical analyzer according to the present invention.
The flow-type multi-item biochemical analyzer for routine is the flow-type multi-item biochemical analyzer for emergency test of FIG. 5, in which the injection cylinder 77 for injecting a sample is replaced with an autosampler 80. Prepare samples in advance and batch process. The difference from the configuration of FIG. 5 is that a nozzle 85 for sucking and discharging various liquids (sample liquid, cleaning liquid, calibration liquid) and a nozzle 85 on a support rod 83 supported by supports 81, 82 are provided.
In combination with a moving part 84 for holding and moving a piston 87, a switching valve 86 for switching between suction and discharge of various liquids, a waste liquid bottle 88, a cleaning liquid bottle 89, and calibration liquid bottles 90, 9
1, to include an auto sampler 80 composed of a large number of sample bottles 92. This multi-item biochemical analyzer operates as follows. Waste bottle 8 for auto sampler 80
8. A cleaning solution bottle 89 for storing the cleaning solution, calibration solution bottles 90 and 91 for storing the calibration solution, and a sample bottle 92 for storing the sample are arranged, and a function of keeping the temperature of the sample constant is added as necessary. In addition, the moving portion 84 that holds the nozzle 85 has the support members 81, 8
2, the support rod 83 can be moved up and down, and the moving portion 8
4 can move to the left and right along the support rod 83, and the nozzle 85 fixed to the moving portion 84 can freely move up and down and left and right. Therefore, under the control of the control unit 12, the piston 87 of the auto sampler 80 and the switching valve 86 are controlled, and the nozzle 85 selects any liquid from the cleaning liquid, the calibration liquid, and the sample liquid, and sucks and discharges the liquid. First, a plurality of samples to be analyzed before starting the measurement are set in advance by the auto sampler 80.
The sample bottle 92 is held. Of course, when measuring the gas components, the sample bottle 92 is capped with a low gas permeability, not shown. Prior to analysis, the sensor is calibrated with pump 78 and then channel 40 is washed. For the calibration, two-point calibration is performed with two kinds of calibration liquids, but one-point calibration may be sufficient. After the cleaning is completed, the nozzle 85 moves under the control of the control unit 12 to suck the target sample in the sample bottle 92. Then, the sample is injected into the flow channel 40, and the sample is pumped into the flow channel 4 by the pump 78.
The ion sensors 41, 42, 4 are made to flow so as to satisfy 0.
3, 44, 45, reference electrode 50, gas sensor 60, 6
1. The flow of the sample is temporarily stopped at the position where each surface of the attenuated total reflection prism 21 is in contact with the sample,
Detects gas components and biochemical components. The detected signal is arithmetically processed to obtain the concentrations of the plurality of components.

Needless to say, the amount of sample can be reduced by arranging the sensor groups in parallel as shown in FIG. Although the control unit 12 automatically controls the analysis unit 11, it includes a function of repeating the analysis cycle described above from calibration or cleaning to data calculation processing a plurality of times as necessary. In this embodiment, the ionic component, the gas component,
It is also possible to batch-measure biochemical components for a plurality of components at the same time. FIG. 10 is a diagram showing the configuration of an embodiment of an emergency test spotting type multi-item biochemical analyzer according to the present invention. In the spotting multi-item biochemical analyzer for emergency inspection, the sample is supplied to the sample spotting unit 100 by spotting. The arrangement and configuration of various sensors provided on the sample spotting unit 100 are shown in FIG.
It is the same as the flow system multi-item biochemical analyzer for emergency inspection shown in. This spot-testing multi-item biochemical analyzer for emergency inspection operates as follows. In order to measure the sample at any time in the emergency test, the calibration solutions 71 and 72 are sequentially passed through the nozzle 104 to the sample spotting part 100 of the concave recess of the sample component detecting part 4 using the liquid sending pump 102 at regular intervals. Send the calibration solution 71 or 72 for a fixed time to the sample spotting unit 10
The sensor is calibrated by accumulating it at 0, and the washing liquid 70 is caused to flow by the liquid feeding pump 102 to wash the sample spotting portion 100.
Under the control of the control unit 12, the open / close valves 73, 74, 7
5 and the switching valve 101 are controlled, and the cleaning liquid 70 and the calibration liquids 71 and 72 are selected. The used calibrating liquid or cleaning liquid is switched to the switching valve 101 and is sent to the waste liquid bottle 79 by the pump 103 through the nozzle 104, and is safely discarded before the waste liquid becomes full. In FIG. 10, reference numeral 105 denotes a mixed liquid of various liquids being used, or a liquid surface in the sample spotting part 100 of the sample. For the calibration, two-point calibration is performed with two kinds of calibration liquids, but one-point calibration may be sufficient. Since the sample spotting unit 100 is in a standby state where a clean empty state is maintained and measurement can be performed at any time,
The sample such as blood collected from the patient can be directly injected into the multi-item biochemical analyzer by the method described in 7 above. The sample is the sample spotting part 1
00, the sample gas such as blood is not affected by the atmospheric gas and the sample is applied to the sample spotting part 100 for a short time.
Then, measure the components in the sample. Cleaning solution 7 after each measurement
The sample spotting part 100 is washed with 0, and the calibration liquids 71 and 72 are used to calibrate the sensor at regular intervals. In the same manner as described with reference to FIG. 5, the biochemical components are detected using attenuated total reflection infrared spectroscopy or attenuated total reflection Raman spectroscopy. In this embodiment, the sample is supplied by spotting, and the ionic component, the gas component, and the biochemical component can be urgently measured simultaneously for a plurality of components, and the biochemical component is detected spectroscopically. No reagents needed.

FIG. 11 is a diagram showing the structure of the sample component detecting section and its surroundings, which is an embodiment of the spotting type multi-item biochemical analyzer according to the present invention. In this example, the sample spotting part 100 of the example shown in FIG.
-A cover 110 having a low gas permeability is arranged via a ring 111 to improve the gas in the atmosphere so as not to affect the gas in the sample. The arrangement and configuration of various sensors are the same as those in the embodiment shown in FIG. is there. The operation of this embodiment is as follows. The sample is spotted in the sample spotting unit 100 through the nozzle hole 113 by switching the switching valve 114,
Alternatively, when injected, the cover 110 attached to the sample spotting part 100 is closed by the connection component 112 to confine the sample, and the gas in the atmosphere is prevented from affecting the gas in the sample. The components can be measured.
In addition, after the sample is spotted or injected into the sample spotting section 100 and the cover 110 is closed to contain the sample,
Although not shown in FIG. 11, the inside of the sample spotting part 100 can be depressurized to an appropriate condition by a depressurizing pump connected to the sample spotting part 100 to improve the gas component detection sensitivity. The steps of calibration, cleaning and waste liquid are the same as those in the embodiment of FIG. In this embodiment, the ionic component, the gas component, and the biochemical component can be simultaneously measured, and particularly the gas component can be accurately measured.

FIG. 12 is a view showing the arrangement of an embodiment of a routine spotting type multi-item biochemical analyzer according to the present invention.
The routine spotting multi-item biochemical analyzer is a combination of the spotting multi-item biochemical analyzer shown in FIG. 10 and the autosampler 80 shown in FIG. 9. A plurality of samples are prepared in advance. Every batch can be processed. This multi-item biochemical analyzer operates as follows. The auto sampler 80 performs the same operation as described with reference to FIG. The sample is spotted or injected from the nozzle 122 to the sample spotting unit 100 via the flow path 123. Various liquids are sucked from the nozzle 120 and flow path 1
It is temporarily stored in the waste liquid bottle 79 via 21. In this embodiment, it is also possible to adopt the structure in which the cover described in FIG. 11 is provided. In this embodiment, it is possible to perform batch measurement of a plurality of ionic components, gas components, and biochemical components at the same time. FIG. 13 is a diagram showing the configuration of an embodiment of a non-invasive multi-item biochemical analyzer according to the present invention. Non-invasive multi-item biochemical analyzers include ion sensors 41, 42, 4
3, 44, 45, reference electrode 50, gas sensor 60, 6
1. The sample component detection unit 4 including the total reflection attenuating prism 21 for detecting biochemical components and the optical fiber connector 134, and the skin 135 are heated by the heater 130 under the control of the temperature control circuit 131, and are generated. The percutaneous detection unit 132 for detecting skin gas, the infrared light 20 from the light source unit 7
33, skin 135 through the optical fiber connector 134
Total reflection attenuating prism 2 for detecting biochemical components in contact with the skin
1, the infrared light 20 emitted from the attenuated total reflection prism 21 is guided to the light receiving section 9 via the optical fiber connector 134 and the optical fiber 133, the biochemical component detection system, the amplifying section 5, the light receiving section 9, Calculation unit 10 and temperature control circuit 131
An electric circuit section 136, an analysis section 11, a control section 12,
Composed of. Ion sensors 41, 42, 43, 4
4, 45, the gas sensors 60, 61, and the total reflection attenuation prism 21 are the same as those used in the embodiment of FIG.

This non-invasive multi-item biochemical analyzer operates as follows. The transcutaneous detection unit 132 and the electric circuit unit 136 are connected by the optical fiber 133 and electric wiring, and the transcutaneous detection unit 132 is brought into close contact with the surface of the inspection target such as the forearm or the lip. The two-point calibration or the one-point calibration is performed on the transcutaneous detection unit 132 with the calibration liquid before the mounting. A state in which the skin is heated by the heater 130 and the temperature control circuit 131 in the transcutaneous detection unit 132, the skin thickness becomes thin, the blood flow approaches the surface of the inspection target, the gas permeability of the skin is improved, and sweating occurs. Becomes Transaction on Biomedical Engineer, BME-26 (1979) pp. 597-600.
g BME-26 (1979) pp597-600) in the conventional example,
Although transcutaneous measurement of glucose or the like is performed without heating, in this embodiment, by heating, blood flow can be brought closer to the surface of the inspection target and can be measured with higher accuracy. In the present example, the ion concentration in blood was successfully determined by measuring the ions in sweat with an ion sensor in contact with the surface of the test object. Similar to FIG. 5 and the like, each unit that constitutes the analysis unit 11 is automatically controlled by the control unit 12. In addition, the detection of biochemical components is attenuated by total internal reflection infrared spectroscopy,
Any of the attenuated total reflection Raman spectroscopy may be used.The attenuated total reflection infrared spectroscopy is capable of detecting a biochemical component by using transmitted light transmitted through the test object or reflected light reflected from the test object. it can.

The percutaneous detector 132 is suitable for long-term monitoring of blood components when it is attached to the surface of an object to be inspected, and since the operator does not directly contact the sample,
It is also effective in preventing infection of bacteria, viruses, etc. that have passed through body fluids to be tested. In the present embodiment, the ion component, the gas component, and the biochemical component can be simultaneously measured transdermally for a plurality of components, and the biochemical component is detected spectroscopically, so that a reagent for biochemical component analysis is not required. FIG. 14 is a diagram showing the configuration of an embodiment of the disposable multi-item biochemical analyzer of the sample component detecting unit according to the present invention. Sample component detection unit A disposable multi-item biochemical analyzer is used for sample 14 from skin 135.
4, the ion sensors 41, 42, 43, 44,
45, reference electrode 50, gas sensors 60, 61, total reflection attenuating prism 21 for detecting biochemical components, optical fiber connector 134, disposable sample component detecting section 140 including sample reservoir 143, light source for generating infrared light 20 Part 7,
The light receiving unit 9, the amplifying unit 5, and the electric circuit unit 142 including the calculating unit 10, the connector 141, the optical fiber 133, the analyzing unit 11, and the control unit 12. Ion sensor 4
1, 42, 43, 44, and 45 are ion-selective field-effect transistors that measure each ion of sodium, potassium, chlorine, hydrogen, and calcium, and gas sensors 60 and 61 are a sewering house type carbon dioxide sensor and a Clark type. Oxygen sensors, which are miniaturized on the same substrate using semiconductor technology. These sensors are described in "Biometrics and Sensors" by Tatsuo Togawa, Corona Publishing Co. (1986), pages 357 to 385. Further, the total reflection attenuating prism 21 for detecting a biochemical component uses silicon cut out from a silicon wafer for infrared spectroscopy as a prism. This prism can also be applied to Raman spectroscopy. The sensor and the total reflection attenuating prism are separate bodies using a silicon substrate, and can be manufactured inexpensively and in a small size. Disposable detector 1
Although 40 is connected to the electric circuit section 142 via the connection connector 141, the disposable detection section 140 can be separated by the connection connector 141.

This sample component detection part disposable multi-item biochemical analyzer operates as follows. First, before the measurement, the disposable detection unit 140 is connected to the electric circuit unit 142, and two-point calibration or one-point calibration is performed with a calibration liquid. As one form of the examination in an emergency, the disposable detection unit 1 in which the skin 135 is slightly incised and the fresh blood to be the sample 144 is miniaturized and integrated.
40 is used for measurement. The sample 144 enters into the sample reservoir 143 provided in the disposable detection unit 140 by a capillary phenomenon,
A plurality of components in the sample are measured with the sample reservoir 143 filled with the sample. The disposable detection unit 140 can be easily replaced by detaching it from the electric circuit unit 142 with the connection connector 141 in units of once or in units of one day. Analysis unit 1
Each unit constituting 1 is automatically controlled by the control unit 12 as described with reference to FIG. The biochemical component may be detected by either attenuated total reflection infrared spectroscopy or attenuated total reflection Raman spectroscopy. The disposable detection unit 140 described above
Can be manufactured at low cost by using a silicon material using semiconductor technology, and is effective in preventing the infection of bacteria, viruses, etc., which are currently problems. In the present embodiment, the sample component detection unit that can simultaneously measure the ionic component, the gas component, and the biochemical component for a plurality of components can be disposable, and a reagent for biochemical component analysis is not required. In transdermal measurement, ionic components from sweat or saliva, exuded gas components from blood vessels,
The light transmitted through the skin can be used to analyze biochemical constituents. In the above description, various sensors for measuring ions and gases, and a total reflection attenuation prism were manufactured in a small size by using a separate silicon substrate, but it is also possible to form them all on a single silicon substrate. It was possible to achieve remarkable effects by using it as a sensor in each of the embodiments of the present invention described above. This will be described below.

FIG. 15 is a perspective view of an embodiment of the integrated multi-item biochemical analysis chip according to the present invention. The integrated multi-item biochemical analysis chip 150 (hereinafter, abbreviated as an analysis chip) is an ion sensor 4 formed on a silicon substrate.
1, 42, 43, 44, 45, reference electrode 50, gas sensors 60, 61, attenuated total reflection prism 21 corresponding to a biochemical component detection unit, integrated electronic circuit unit 153 including an amplifier and a calculation unit, silicon exposed portion 154. , Silicon 151, and silicon oxide 152. The analysis chip 150 is
It is separated into an electric part 155 in which an ion sensor, a reference electrode, a gas sensor, and an integrated electronic circuit part are formed, and an optical part 156 in which an attenuated total reflection prism is formed. In this embodiment,
Although the integrated electronic circuit unit 153 is integrated with the analysis chip 150, the integrated electronic circuit unit 153 is integrated into the silicon chip 150.
Instead of forming it on the upper side, it may be installed outside the analysis chip 150 to electrically exchange the detection signal and the control signal.
The analysis chip 150 was formed by the steps described below.
First, a silicon substrate having a (100) plane is thermally oxidized to form a silicon oxide 152 layer on both sides of the silicon 151. The upper surface of the analysis chip 150 is covered, and a prefabricated etching pattern is adhered to the lower surface, and a part of the silicon oxide 152 layer on the lower surface is removed with a solution of hydrogen fluoride: ammonium fluoride 1: 6. The etching pattern is silicon oxide 15 on the lower surface of the attenuated total reflection prism 21.
It has a shape that removes two layers. Then silicon 151
Was anisotropically etched with a potassium hydroxide solution at a temperature of 90 ° C., and the silicon substrate was washed to stop the etching. As a result, the lower surface of the attenuated total reflection prism 21 could be formed. Next, the silicon exposed portion 154 is formed on the upper surface of the analysis chip 150 having the silicon oxide 152 layer. A pattern for removing the silicon oxide 152 layer of the silicon exposed portion 154 is manufactured, and hydrogen fluoride: ammonium fluoride is added. The silicon oxide 152 layer was etched and washed with a 1: 6 solution. As a result, the attenuated total reflection prism 21 could be manufactured in the analysis chip 150. Next, the ion sensor 41, 42, 43, 44, 45, the reference electrode 5
0, the gas sensors 60 and 61, and the integrated electronic circuit unit 153 are manufactured. The ion sensor, reference electrode, and gas sensor separately formed on the silicon substrate may be mounted, or the ion sensor, reference electrode, and gas sensor are integrally formed on the silicon substrate by using a technique such as etching. You may. Finally, the same number of analysis chips 150 formed on the silicon substrate are cut out, and the ion sensor, the reference electrode,
Electrical wiring is applied to the gas sensor, and the electrically conductive portion of the silicon substrate is covered with an insulator so as to maintain electrical insulation from the liquid sample.

FIG. 16 is a sectional view of an embodiment of an attenuating total reflection prism formed on an integrated multi-item biochemical analysis chip according to the present invention. This sectional view is a sectional view taken along the line aa 'in FIG. 15. FIG. 16A shows a case where infrared light is directly input to and output from an attenuating total reflection prism, and FIG. 16B shows an optical fiber. This is an embodiment of the case where infrared light enters and exits the attenuating total reflection prism. Silicon 151,
The silicon oxide 152, the silicon exposed portion 154, the attenuated total reflection prism 21, the infrared light 20, the optical fiber 133, and the optical fiber connector 134 are shown. Figure 16 (a)
As described above, the attenuated total reflection prism 21 can be easily formed by etching the silicon 151, and the biochemical component can be easily detected by combining it with the necessary optical system. Although the shortening of the optical path length due to the miniaturization of the attenuated total reflection prism 21 leads to a reduction in sensitivity, it is easy to increase the number of reflections and increase the sensitivity by reducing the thickness of the attenuated total reflection prism 21. . Furthermore, FIG.
If the optical fiber connector 134 is installed on the attenuating total reflection prism 21 as shown in (b) and the optical fiber 133 is used for the entrance and exit portions of the infrared light 20, the optical axis alignment becomes extremely easy and it is easy to remove. Anyone can do it easily. The integrated tail size of the integrated multi-item biochemical analysis chip described above can be realized at 10 mm × 10 mm (thickness <1 mm) or less, and for example, the size of the sample component detection unit in the embodiment described in FIG. 5 is 20 mm. (Width) x 50 mm (flow path length) x 50 mm
It is smaller than (height). The realization of such an integrated multi-item biochemical analysis chip enables downsizing of the analysis unit, cost reduction, and easy connection, reducing the amount of sample,
It is possible to provide an effective biochemical analyzer by downsizing and portability of the device, prevention of infection from a sample, disposable analysis chip, continuous monitoring by in-vivo indwelling, and the like. Furthermore, it goes without saying that this integrated multi-item biochemical analysis chip can be used as the sample component detection unit in each of the embodiments of FIGS. 5, 6, and 9 to 14. In the above, I explained mainly about blood analysis,
The object of analysis is not limited to this, and needless to say, it can be applied to excrements such as urine of animals including humans, various body fluids such as lymph, and body tissues.

[0031]

According to the present invention, a plurality of components in a trace amount sample can be measured at the same time, an analysis result can be obtained in a wide medical field in a short time, and the number of reagents can be reduced, so that the running cost is reduced. And has the effect of simplifying reagent handling. In addition, the realization of an integrated multi-item biochemical analysis chip enables downsizing of the analysis unit, cost reduction, and easy connection, reducing the amount of sample, downsizing and porting the device, and preventing infection from samples. Disposable analysis chips and continuous monitoring by in-vivo placement are possible.

[Brief description of drawings]

FIG. 1 is a block diagram showing the basic concept of a multi-item biochemical analyzer of the present invention.

FIG. 2 is a diagram illustrating the principle of attenuated total reflection infrared spectroscopy.

FIG. 3 is a diagram showing an infrared absorption spectrum example of a mixed aqueous solution containing a plurality of components.

FIG. 4 illustrates the principle of attenuated total reflection Raman spectroscopy.

FIG. 5 is a diagram showing the configuration of an embodiment of a flow system multi-item biochemical analyzer for emergency inspection according to the present invention.

FIG. 6 is a diagram showing a configuration of a sample component detection unit and its periphery, which is an embodiment of a flow-type multi-item biochemical analyzer according to the present invention.

FIG. 7 is a diagram showing a correlation between measurement results of the analyzer according to the present invention and the conventional analyzer.

FIG. 8 is a diagram showing a correlation between measurement results of an analyzer according to the present invention and a conventional analyzer.

FIG. 9 is a diagram showing the configuration of an embodiment of a flow-type multi-item biochemical analyzer for routine according to the present invention.

FIG. 10 is a diagram showing the configuration of an embodiment of a multipoint biochemical analyzer for spotting method for emergency inspection according to the present invention.

FIG. 11 is a diagram showing the configuration of a sample component detection unit and its surroundings, which is an embodiment of the spotting multi-item biochemical analyzer according to the present invention.

FIG. 12 is a view showing the configuration of an embodiment of a routine spotting multi-item biochemical analyzer according to the present invention.

FIG. 13 is a diagram showing the configuration of an embodiment of a non-invasive multi-item biochemical analyzer according to the present invention.

FIG. 14 is a view showing the configuration of an embodiment of a sample component detection unit disposable multi-item biochemical analyzer according to the present invention.

FIG. 15 is a perspective view showing an embodiment of an integrated multi-item biochemical analysis chip according to the present invention.

FIG. 16 is a sectional view showing an example of an attenuating total reflection prism formed on an integrated multi-item biochemical analysis chip according to the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Ion detection part, 41, 42, 43, 44, 45 ... Ion sensor, 2 ... Gas detection part, 60, 61 ... Gas sensor, 3 ... Biochemical component detection part, 4 ... Sample component detection part, 5 ...
Amplifying section, 6 ... Incident light, 7, 30 ... Light source section, 8 ... Emitted light,
9, 32 ... Light receiving part, 10 ... Calculation part, 11 ... Analysis part, 12
Control unit 13 Sample supply unit 20 Infrared light 21 Total reflection attenuating prism 50 Reference electrode 40 Flow channel 70
... washing liquid, 71, 72 ... calibration liquid, 79 ... waste liquid bottle, 8
0 ... Auto sampler, 81, 82 ... Support, 83 ... Support rod, 84 ... Moving part, 88 ... Waste liquid bottle, 89 ... Washing liquid bottle,
90, 91 ... Calibration solution bottle, 92 ... Sample bottle, 100 ... Sample spotting part, 105 ... Mixed solution or sample solution surface, 110 ...
Cover, 111 ... O-ring, 130 ... Heater, 131
... temperature control circuit, 132 ... transcutaneous detection part, 133 ... optical fiber, 134 ... optical fiber connector, 135 ... skin,
140 ... Disposable sample component detection part, 141 ... Connection connector, 142 ... Electric circuit part, 143 ... Sample reservoir, 150 ...
Integrated multi-item biochemical analysis chip, 151 ... Silicon, 1
52 ... Silicon oxide, 153 ... Integrated electronic circuit part, 15
4 ... Silicon exposed part, 155 ... Electrical part, 156 ... Optical part.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Yasuhisa Shibata 1-280, Higashi Koikeku, Kokubunji, Tokyo Inside Central Research Laboratory, Hitachi, Ltd. (72) Inoko Toshiko Fujii 1-280, Higashi Koikeku, Kokubunji, Tokyo Hitachi, Ltd. Central Research Laboratory (72) Inventor Kotaro Yamashita 1-280 Higashi Koikeku, Kokubunji, Tokyo Inside Hitachi Central Research Laboratory (72) Inventor Osamu Ozawa 1-280 Higashi Koikeku, Tokyo Kokubunji City Central Research Laboratory, Hitachi Ltd.

Claims (36)

[Claims] 1. A multi-item biochemical analyzer for simultaneously measuring an ionic component, a gas component, and a biochemical component in a liquid sample without adding a reagent to the liquid sample and reacting them, A multi-item biochemical analyzer characterized by being measured by attenuated total reflection infrared spectroscopy or attenuated total reflection Raman spectroscopy. 2. A sample comprising an ion detector for detecting an ionic component in the liquid sample, a gas detector for detecting a gas, and a biochemical component detector comprising a spectroscopic means for detecting a biochemical component. A component detection unit, an amplification unit for amplifying signals from the ion detection unit and the gas detection unit, a light source unit for making light incident on the biochemical component detection unit, and an output from the biochemical component detection unit. A light receiving section for receiving the emitted light; a computing section for computing the output signals from the amplifying section and the light receiving section to calculate the respective concentrations of the ionic component, the gas component, and the biochemical component; and the liquid sample. The multi-item biochemical analyzer according to claim 1, further comprising: an analysis unit including a sample supply unit that supplies the sample component detection unit to the sample component detection unit, and a control unit that controls the analysis unit. 3. The multi-item biochemical analyzer according to claim 2, wherein the ion detector electrochemically detects the ion component and the gas component detector electrochemically detects the gas component. . 4. The multi-item biochemical analysis according to claim 3, wherein the liquid sample is brought into contact with the sample component detection unit to detect the ionic component, the gas component, and the biochemical component. Total. 5. The multi-item raw material according to claim 4, wherein the sample component detection section is provided with a flow path through which the liquid sample flows, and the liquid sample is introduced into the flow path from the sample supply section. Chemical analyzer. 6. The multi-item biochemical analyzer according to claim 4, wherein the ion detecting section, the gas detecting section, and the biochemical component detecting section are arranged in series in the flow path. 7. The multiple ion detector according to claim 4, wherein the ion detector, the gas detector, and the biochemical component detector are divided into a plurality of groups and arranged in parallel with the flow path interposed therebetween. Item biochemical analyzer. 8. The multi-item biochemical analyzer according to claim 4, wherein a sample spotting section for spotting the liquid sample is provided on the sample component detecting section. 9. The multi-item biochemical analyzer according to claim 8, wherein the sample spotting portion is provided with a cover having a low gas permeability. 10. The multi-item biochemical analyzer according to claim 5, wherein an auto sampler is arranged to automatically supply the liquid sample to the sample supply section. . 11. The multi-item biochemical analyzer according to claim 3, further comprising a sample component detection unit mounted on the surface of the inspection target. 12. The component according to claim 3, wherein the sample component detection unit is mounted on the surface of the inspection target, and the component in the liquid sample exuded from the inspection target percutaneously is measured. Multi-item biochemical analyzer. 13. The ion detecting unit detects the ionic component in a body fluid such as sweat or saliva of the inspection target, and the gas detecting unit detects a gas component transdermally exuded from a blood vessel of the inspection target,
13. The biochemical component detection unit respectively measures the biochemical component by using transmitted light that has passed through the inspection target or reflected light that has been reflected from the inspection target. Multi-item biochemical analyzer described. 14. The sample component detection unit is detachable from an electric circuit unit including the amplification unit, the light source unit, and the calculation unit, according to any one of claims 11 to 13. Multi-item biochemical analyzer described. 15. The multi-item biochemical analyzer according to claim 14, wherein the sample component detection unit is disposable. 16. The ion component detecting section comprises any one of an ion selective electrode, a coated wire type ion selective sensor, and an ion selective field effect transistor. 15
The multi-item biochemical analyzer described in. 17. The multi-item biochemical analyzer according to claim 10, wherein the gas component detection unit is composed of a sewering house type electrode or a Clark type electrode. 18. The multi-item according to claim 10, wherein the liquid sample is a body fluid derived from an animal, such as whole blood or urine of the animal. Biochemical analyzer. 19. The multi-item according to any one of claims 10, 15, 16 and 17, wherein the liquid sample is human-derived body fluid such as human whole blood or urine. Biochemical analyzer. 20. At least a biochemical component detecting unit including an ion detecting unit for detecting an ion component in the liquid sample, a gas detecting unit for detecting a gas, and a spectroscopic means for detecting a biochemical component is formed on a silicon substrate. The multi-item biochemical analyzer according to claim 1, which is formed. 21. A silicon substrate is provided with at least a biochemical component detection unit including an ion detection unit for detecting an ion component in the liquid sample, a gas detection unit for detecting a gas, and a spectroscopic unit for detecting a biochemical component. A sample component detection unit including a first optical fiber unit that is formed and is coupled to the biochemical component detection unit and that transmits incident light and emitted light; and amplification for amplifying signals from the ion detection unit and the gas detection unit. Section, a light source section for making light incident on the biochemical component detecting section, a light receiving section for receiving light emitted from the biochemical component detecting section, and a second optical fiber for transmitting the incident light and the emitted light. Section, and an electric circuit section including an arithmetic section for calculating output signals from the amplification section and the light receiving section to calculate respective concentrations of the ionic component, the gas component, and the biochemical component, and the liquid. Test the sample An analysis unit which includes a sample supply unit for supplying the component detecting unit, multi-item biochemical analyzer according to claim 1, characterized in that a control unit for controlling the analyzer. 22. The ion detector detects the ion component,
22. The multi-item biochemical analyzer according to claim 21, wherein the gas component detection unit electrochemically detects each of the gas components. 23. The multi-item biochemical analysis according to claim 21, wherein the ionic component, the gas component, and the biochemical component are detected by bringing the liquid sample into contact with the sample component detection unit. Total. 24. The multi-component method according to claim 21, wherein a flow path through which the liquid sample flows is provided on a surface of the sample component detection section, and the liquid sample is introduced into the flow path from the sample supply section. Item biochemical analyzer. 25. The multi-item biochemical analyzer according to claim 21, wherein the liquid sample is spotted on the sample component detecting section. 26. The multi-item biochemical analyzer according to claim 21, wherein the sample component detecting section is provided with a cover having a low gas permeability. 27. The multi-item biochemical analyzer according to claim 21, wherein an auto sampler is arranged to automatically supply the liquid sample to the sample supply section. 28. The multi-item biochemical analyzer according to claim 21, wherein the sample component detection unit is mounted on the surface of the inspection target. 29. The multi-component method according to claim 21, wherein the sample component detection unit is mounted on the surface of the inspection target to measure the components in the liquid sample transdermally exuded from the inspection target. Item biochemical analyzer. 30. The ion detection unit detects the ionic component in a body fluid such as sweat or saliva of the inspection target, and the gas detection unit detects a gas component percutaneously exuded from a blood vessel of the inspection target,
30. The biochemical component detection unit respectively measures the biochemical component by using transmitted light that has passed through the inspection target or reflected light that has been reflected from the inspection target. Multi-item biochemical analyzer described. 31. The multi-item biochemical analyzer according to claim 28, wherein the sample component detection unit is detachable from the electric circuit unit. 32. The multi-item biochemical analyzer according to claim 31, wherein the sample component detection unit is disposable. 33. The multi-item according to claim 21 or 32, wherein the ion component detecting section is composed of either a coated wire type ion selective sensor or an ion selective field effect transistor. Biochemical analyzer. 34. The multi-item biochemical analyzer according to claim 21, wherein the gas component detection part is composed of a sewering house type electrode or a Clark type electrode. 35. The multi-item biochemical analyzer according to claim 21, wherein the liquid sample is animal-derived body fluid such as whole blood or urine of an animal. 36. The multi-item biochemical analyzer according to claim 21, wherein the liquid sample is a human-derived body fluid such as human whole blood or urine.