JP6344783B1 - Evaluation system based on gas analysis - Google Patents

Abstract

An object of the present invention is to provide an evaluation system capable of executing a presence of a specific substance or whether a disease or disorder has developed on the basis of breath analysis quickly and with high accuracy. An electric field in which a phase change is caused by applying a means for ionizing a gas injected into a vacuum vessel and a voltage in which a DC voltage and a high frequency voltage having a frequency equal to or higher than a predetermined value are applied to electrodes in the vacuum vessel. A means for adjusting a voltage applied by setting a reference point for a DC voltage and a high-frequency voltage at which the ionized gas stably oscillates in the formed electric field, and a content of ion molecules specific to the gas A means for generating a spectral pattern for the above, a related pattern extracting means for searching for a correlated pattern among the spectral patterns whose analysis results have been confirmed, and the presence or absence of a specific substance associated with the searched spectral pattern Determination means for determining that a disease or disorder has developed. [Selection] Figure 1

Description

  In the present invention, component analysis of exhaled gas exhaled mainly from animals including humans (particularly mammals) is performed, and whether the normal range or transition value is shown from the component analysis of exhaled gas during normal activity It is related with judging.

  Records that athletes achieve in competitions are sometimes canceled. A typical example is a case in which a positive reaction of a prohibited substance is confirmed, and it is presumed that an attempt was made to improve competitiveness by ingesting the prohibited substance into the body. This is generally referred to as doping. In addition, there are cases where it is ingested without knowing that it is a food or drink or medicine containing prohibited substances. Even if it is due to such negligence, if the test result is positive, the determination of doping is made. Doping is an action that goes against the spirit of fair play, and it also affects athletes' health and adversely affects society. Therefore, in accordance with the provisions of the World Anti-Doping Agency (WADA), the entire world, especially in the sports world. The use of strict rules is prohibited.

Prohibited substances refer to various prohibited drugs that have the effect of enhancing competitiveness, but there is also doping using substances other than drugs. For example, what is called blood doping is a method of self-transfusion in which one's own blood is drawn in advance and stored frozen and then returned to the body immediately before the match. Hemoglobin in blood has the property of binding to oxygen molecules and plays the role of transporting oxygen from the lungs to the whole body. Therefore, when blood is transfused, the oxygen transport capacity is improved. Athletes have appeared to intentionally use this to improve endurance.
Furthermore, it has been pointed out a method for improving competitiveness by adjusting cells, genes, genetic factors and the like using recent science and technology. In addition to such artificial processing aimed at improving performance, the act of replacing the collected urine and blood with that of another person is naturally subject to doping as a prohibited method.

  In the following, sports doping will be described as an example of taking prohibited drugs to increase muscle strength and endurance. Prohibited drugs are defined in the Prohibited List of the World Anti-Doping Code and are updated at least on January 1 each year. It has been specified in a wide variety and is said to have at least several hundred types. Many of these prohibited drugs are classified into several categories such as volatile drugs, hardly volatile drugs, anabolic steroids, diuretics, peptide hormones, etc. It is determined whether or not a prohibited drug is contained in the sample. When the analyzer extracts the same molecular component as a prohibited drug that has been positively doped in the past, the analyzer can immediately make a positive determination of doping.

  On the other hand, for example, an anabolic steroid having a muscle-enhancing action (pharmaceutical example: testosterone) may be used after generating a new substance by slightly changing its molecular structure. This is an intentional operation to prevent detection by a doping test. In spite of the fact that a new drug is originally positive for doping, there is a problem that it often passes through the test. For this reason, WADA expects that a positive diagnosis can be made or screened with the progress of various detection technologies including analyzers in the future even if doping positive cannot be detected when collecting urine or blood samples, For example, it is taken to keep for 10 years.

In addition, for example, a peptide hormone (drug example: erythropoietin (EPO)) is one of the hematopoietic factors that promote the production of red blood cells. Originally, EPO concentration in blood is examined and used for differentiation of anemia and erythrocytosis. However, since EPO has an effect of increasing red blood cells, it has been used for doping in long-distance sports, particularly for the purpose of increasing the amount of oxygen supplied to muscles and improving endurance. Since EPO is a substance originally present in the body, it is difficult to make a definitive diagnosis as to whether it is a doping act by intentionally ingesting EPO because EPO is included in the analysis results.
For this reason, in EPO doping positive determination, screening is often performed using hematocrit (volume ratio of blood cells in the blood), hemoglobin, reticulocyte count, and the like. In addition, genetically modified EPO is detected by electrophoresis in urine.

  Further, in connection with the analysis technique, there is a patent application for analyzing the content of a chemical substance contained in exhaled gas particles (for example, refer to the following patent document).

Japanese Patent No. 5270788

So far, a doping test, that is, a test of prohibited drugs in urine and blood has been performed under a strict test organization, but has various problems.
First, when collecting urine or blood as a specimen from an athlete, if you receive a test notification from a notifier called a chaperone, you are required to act within the reach of the chaperone until you enter the laboratory. . And if the specimen is urine, the same sex doping control officer (DCO) must be present in the toilet and collect urine in a state where the DCO can be confirmed. If it is a blood sample, it will be necessary for a health care worker (a doctor, a nurse, etc.) to be present for blood collection. As a price to guarantee the cleanliness of drug-free use of athletes, privacy was lacking and actual collection was laborious. Further, as described above, even if the doping is negative, the collected specimen needs to be stored for a long period of time.

  Next, as a big problem, in the case of a conventional doping test, a so-called pretreatment must be performed before applying to an analysis apparatus. For example, Shimadzu Application News, No.M243 (published in the first edition of March 2007) has a pretreatment flow for non-volatile drugs (drug example: cocaine metabolite). In the case of "Add 5M hydrochloric acid to 5ml of urine, hydrolyze by heating at 105 ° C for 30 minutes, wash with diethyl ether, then add 2-methyl-2-propanol and internal standard substance to the aqueous phase After checking the pH to 9.6 ± 0.1, extract with diethyl ether.The extract is dried with pure nitrogen gas, methyl orange / acetonitrile / TFA mixed solution is added, then MSTFA is turned yellow. Add to the plate and heat at 80 ° C for 5 minutes, add MBTFA to it, and heat at 80 ° C for 10 minutes to derivatize N-TFA-O-TMS. " is there. After a derivatized sample is finally created through a plurality of laborious pretreatments, it becomes possible to identify prohibited drugs by using a GC / MS (Scan) analyzer, which is an analyzer.

  As described above, since it is necessary to perform a pretreatment that requires a lot of time and cost, even if the time required for producing the result of the derivatized sample with the analyzer is short, the time required for the analysis becomes long after all. It will end up. In addition, the fact that pretreatment differs depending on the classification of prohibited drugs means that it is necessary to identify prohibited drugs to some extent before analysis, but the validity of existing pretreatments to analyze completely unknown prohibited drugs Therefore, many studies including the optimality of pretreatment will be required before a positive diagnosis of doping positive. This is why, for example, the news that an athlete sample collected immediately after winning the Olympics had a positive reaction to doping had passed six months after the end of the Olympics.

  Moreover, although the cited document 1 discloses an analysis technique using exhaled gas that is not urine or blood, the object of analysis is arbitrary particles contained in the exhaled gas, and the gas state as in the present invention It is essentially different in that it does not target the specimen.

  In order to solve the various problems described above, the present invention provides a gas (exhalation gas) indicating whether a specific substance has been ingested by an animal including a human being or a disease or disorder has occurred in an animal. An object of the present invention is to provide an evaluation system that can be executed quickly and with high resolution based on analysis.

  In order to achieve the above object, an evaluation system according to the present invention comprises means for ionizing a gas injected into a vacuum vessel, and a high frequency voltage having a DC voltage and a frequency equal to or higher than a predetermined value at an electrode in the vacuum vessel. Means for forming an electric field in which a phase change is generated by applying a voltage superimposed thereon, and a reference point for a DC voltage and a high-frequency voltage at which the ionized gas stably oscillates in the formed electric field, and the reference point A means for adjusting the voltage to be applied in the electric field while maintaining a constant ratio of the direct-current voltage and the high-frequency voltage, and after detecting the gas separated into ion molecules under the voltage condition, A means for generating a spectral pattern relating to the content of ionic molecules unique to the gas among the ionic molecules contained in the gas, and a spectral pattern in which an analysis result has been determined, The related pattern extraction means for searching for a correlation with the generated spectrum pattern, and when the related pattern extraction means searches for a spectrum pattern with the correlation, it is associated with the searched spectrum pattern. Determining means for determining the presence of a specific substance or the presence of a disease or disorder.

  In addition, when the related pattern extraction unit does not search for a correlation with the generated spectrum pattern, the determination unit further stores the past spectrum pattern related to the injected gas. With reference to series data, if the content of each ion molecule in the generated spectral pattern deviates from the range or threshold estimated from the time series data, the presence of the specific substance or disease or It is estimated that it corresponds to a state where a disorder has developed, and is selected as a screening selection candidate.

  According to the evaluation system of the present invention, after a gas is ionized in a vacuum environment, only ions having a specific mass-to-charge ratio among the ions oscillating in an electric field under specific conditions are stably vibrated. It will be in a state, will advance inside a vacuum vessel, will reach a detection part, and will be detected. Therefore, it is possible to obtain a spectrum pattern for molecules analyzed with high sensitivity, with the components contained in the gas being much smaller than the particle size of aerosols, etc., that is, detection sensitivity is on the order of ppm. Become. In addition, the gas can be directly injected into the vacuum vessel in the analytical instrument without requiring any pre-treatment for actual analysis, and the large amount of man-hours and time required for the pre-treatment effort so far. Is not required, and the time to obtain the analysis result can be remarkably shortened.

  In addition, a correlation pattern is searched by comparing with a spectrum pattern whose analysis result has been confirmed. Since the searched spectrum pattern identifies the components in the gas, it is possible to immediately identify the components of the gas that is the object of analysis this time, and quickly determine the presence of a specific substance or the occurrence of a disease or disorder. can do.

  Furthermore, even if the confirmed spectrum pattern is not searched, and therefore the gas to be analyzed this time cannot be definitively diagnosed from the already obtained analysis result, the analysis result and pattern correlation at the past measurement of the measured object If it is determined that the characteristics of the subject are small or greatly deviated based on the time-series data of the analysis results, there is an abnormality that cannot occur in the body of the measured body from the past transition, It can be detected easily and in a short time. This is because, as in the conventional definitive diagnosis method based on whether or not there is a match between the components, the gas contains an unknown substance (unknown substance) whose component analysis has not yet been determined. This is effective for cases where, for example, it has been determined to be negative for topping so far because it does not match the data. Even if it is not possible to specifically and accurately identify what the components of the contained substance are, it is possible to realize a screening that reliably picks up sample cases that are suspected of being abnormal or cannot be estimated as normal. The significance of the present invention is very large.

It is the figure which showed the outline of one Embodiment of the expiration gas evaluation system of this invention. It is a flowchart which shows one Embodiment of an analysis procedure. It is a schematic diagram of quadrupole mass spectrometry according to an embodiment of the present invention. It is a figure which shows an example of a breath collection container. It is a figure which shows the other example of a breath collection container. It is a figure for demonstrating the voltage stable area | region when using a quadrupole-type mass spectrometer. It is a figure for demonstrating the algorithm which determines a scan line. It is a flowchart of a scan line determination algorithm. It is the figure which showed an example of the mass spectrum showing the detection intensity | strength of each molecule | numerator obtained by a quadrupole-type mass spectrometer. It is a flowchart which shows the outline of a determination procedure. It is a figure which shows an example of the feature-value of expiration gas. It is a flowchart which shows the determination procedure using time series data. It is the figure which showed the example of a mass spectrum for demonstrating the determination procedure shown in FIG. It is a figure which shows an example of a moving average line and deviation. It is a figure which shows an example of the exhalation inhalation port of an exhalation collection container.

The evaluation system based on the breath gas analysis according to the present invention will be described below with reference to the drawings.
The present invention mainly evaluates the state of the measured body from a pharmacological or medical viewpoint by analyzing the exhaled gas exhaled by the measured body, but the measured body is not necessarily limited to humans. Not including all mammals. However, in the following embodiments, human breath gas will be described as an example.

FIG. 1 is a schematic diagram showing an embodiment of an analysis evaluation system. FIG. 2 is a flowchart illustrating an embodiment of the analysis procedure.
The analysis evaluation system 100 is roughly composed of a mass spectrometer 10 and an information processing device 6. About 80% of commercially available mass spectrometers are said to be gas chromatography (GC / MS) mass spectrometers, but GC / MS mass spectrometers are generally not very high in boiling point of the compounds to be analyzed. Is used when the characteristics of a compound can be understood to some extent, such as organic substances that vaporize at 300 ° C or less, have a molecular weight of about 1000, and are mainly composed of carbon, hydrogen, oxygen, and nitrogen. The For example, a compound having a molecular weight greatly exceeding 1000, a compound having a high boiling point and hardly vaporized, or a compound having a strong polarity is excluded from the analysis target of the GC / MS mass spectrometer. In addition, GC / MS is not suitable for analysis of unknown compounds because GC / MS uses the adsorbing power of the adsorbent to analyze the compounds roughly in advance. On the other hand, the characteristics of doping inspection are required to be applicable to the situation where new substances that have not been known so far are included in the analysis target, so that the analysis target using a general GC / MS mass spectrometer May not be in the range. Therefore, the mass spectrometer 10 of the present embodiment has a special structure, that is, details will be described later, but ion detection of exhaled gas is performed in an ultrahigh vacuum state that is not used in a general GC / MS mass spectrometer. It is configured.

  The mass spectrometer 10 of the present embodiment uses a quadrupole type (QP). The quadrupole mass spectrometer 10 is an apparatus that electrically analyzes information about mass. The main components include a sample introduction unit 1, an ionization unit 2, a mass separation unit 3, and a detection unit 4. In the analysis, it is first necessary to ionize the sample so as to have a charge, and the breath gas in the breath collection container is injected by the sample introduction unit 1, and ions in the ionization unit 2 of the quadrupole mass spectrometer 10 are injected. It flows into the source and ionizes.

An example of the breath collection container is shown in FIG. A sample 11 made of polyethylene material or the like filled with exhaled gas exhaled by the body to be measured is stabbed with a syringe 11 with an injection needle, the syringe inner cylinder 16 is pulled out and the exhaled gas is sucked into the syringe 11, and the sample introduction unit 1 The syringe 11 is set in Since the syringe 11 has one or more stoppers, the expiratory gas in the syringe 11 can be injected by opening the stopper toward the ionization unit 2.
Further, as shown in FIG. 15, a cap 18 is put on the end of the exhalation air inlet 17 in order to prevent the exhaled gas from leaking out from the exhalation air inlet 17 of the sample bag 15. Since the cap 18 may come off if the tube length of the exhalation air inlet 17 is short, the cap 18 is put on after inserting the sealing plug 19 made of silicon or rubber into the end of the exhalation air inlet 17. Good. Further, in order to increase the degree of adhesion between the sealing plug 19 and the cap 18, the cap 18 may be provided with an air hole 20.

  In this embodiment, the sample bag 15 containing exhaled gas is delivered to the place of the mass spectrometer 10 and the exhaled gas analysis is performed after the exhaled gas is transferred to the syringe 11 by the method described above. However, carbon dioxide or the like may escape from the sample bag 15 during transportation, and accurate analysis may not be possible. Therefore, when the transportation time is long, a syringe 12 including a holder 13 and a vacuum sampling tube 14 as shown in FIG. 5 is used. After inserting the holder 13 with the injection needle into the sample bag 15 and inserting the vacuum collection tube 14 into the holder 13, the expired gas in the sample bag 15 moves to the vacuum collection tube 14. Therefore, after pulling out the vacuum tube 14 from the holder 13, the vacuum tube 14 may be delivered to the place of the mass spectrometer 10 instead of the sample bag 15. Since it is the vacuum sampling tube 14, the carbon dioxide gas does not escape to the outside. The vacuum sampling tube 14 delivered to the home is set in the sample introduction unit 1 in the same manner as the syringe 11 shown in FIG. 4, and then exhaled gas is injected into the ionization unit 2 through an open valve.

  In addition, what is injected into the sample introduction unit 1 is “gas” as described as exhalation gas, and even if an atmospheric gas is added for analysis, it is only a gas component. Not included. For example, a gas mixed with particles such as saliva or sputum formed in the respiratory tract when exhaling is out of the scope of the exhaled gas of the present invention. Therefore, it is desirable to attach a filter or the like to the sample bag 15 or the exhalation-breathing port 17 so that when exhaling, the filter excludes substances other than gas and only gas is collected.

  It should be noted here that the quadrupole mass spectrometer 10 of the present embodiment does not require preprocessing performed by many existing analyzers. The ability to start the analysis process simply by injecting a fixed amount of exhaled gas into the sample introduction unit 1 has the effect of reducing labor and time.

Next, the ions ionized by the ion source are incident on the mass separation unit 3 of the quadrupole mass spectrometer 10 with an acceleration voltage as low as several tens of volts, for example. As shown in FIGS. 1 and 3, the mass separation unit 3 has four rods (metal rod electrodes) having a predetermined length (for example, about 20 cm) in a vacuumed container. In this structure, two are arranged in parallel at a predetermined interval across the central axis (referred to as the z-axis). Moreover, the voltage of the following conditions is applied to each rod.
(1) An RF voltage (= Vcos (ωt)) and a DC voltage (U) having the same polarity are applied to the opposing rods (a, c) in a superimposed manner. Note that ω is a predetermined high-frequency frequency (ω = 2πf), and V is the maximum value of the alternating current.
(2) Applying RF voltage (= Vcos (ωt)) and DC voltage (U) of the same strength as the above (1) to the adjacent rods (b, d) with opposite polarity. To do.

  That is, a voltage I = U + Vcos (ωt) obtained by superimposing direct current and high frequency alternating current is applied to the four rods with either positive or negative polarity. Therefore, in the space where the quadrupole composed of four rods in the mass separation unit 3 exists, an electric field whose phase changes at high speed is generated, and ions (charge z, mass) led to the mass separation unit 3 are generated. m) moves along the longitudinal direction (z direction in FIG. 3) of the quadrupole electrode 3 while oscillating vertically and horizontally (x direction and y direction in FIG. 3) by this electric field, and reaches the detection unit 4. . In this way, the quadrupole electrode 3 has a structure in which the ionization unit 2 is provided at one end and the detection unit 4 is once present.

  A characteristic of the quadrupole mass spectrometer 10 is that only a specific mass-to-charge ratio m / z (mass m, charge z) corresponding to each value of two voltages U and V (and high frequency frequency ω) is an electric field space. It passes through the rod while oscillating stably and reaches the detector 4. On the other hand, ions having other m / z values start to move in an unstable amplitude, and when the amplitude increases, they diverge and collide with the rod, the wall of the vacuum vessel, or other parts. It jumps out of the multipole electrode 3 and cannot reach the detector 4 (see FIG. 1).

In order to prevent the trajectory from being bent or the ions themselves from disappearing in the middle of reaching the detector 4, it is desirable that the ions do not collide with molecules such as air and water as much as possible. This is because the lower the pressure is, the longer the mean free path, which is the average distance that ions can move without colliding, and it becomes easier to reach the detector 4. Therefore, in the case of the present embodiment, the quadrupole electrode 3 is arranged in a vacuum vessel whose pressure is reduced to an extremely low pressure state (for example, a maximum of 10 ⁻⁷ Pa).

  In this embodiment, breath gas analysis is performed. However, in the case of analyzing halides (for example, explosives and agricultural chemicals) in other embodiments, negative ions such as chlorine are contained. Therefore, if the mass spectrometer 10 is configured not to be connected to the ground, negative ions can be measured.

It is known that the vibrational motion of each ion follows the differential equation called Mathieu's equation shown below, regardless of whether it is a positive ion or a negative ion.

  When ion motion follows Mathieu's equation, this equation forms a region that can be divided into a stable solution where the ion oscillates in a stable orbit and an unstable solution where the amplitude increases with time and becomes unstable and diverges. To do. Regarding the relationship between a and q in Mathieu's equation, that is, the DC voltage (U) and high-frequency voltage (Vcos (ωt)) applied to the rod, the region (stable region) that gives a stable solution on the two-dimensional (XY) plane The shaded area in FIG. 6A is shown in FIG. The region that is not the shaded region is a region where at least one of the DC voltage (U) and the high-frequency voltage (Vcos (ωt)) is unstable, and does not become a stable ion orbit under this condition. Therefore, the mass separator 3 creates the above-described stable region (step S20).

  It should be noted that the stable region when ions make a stable vibration motion is not limited to the region shown in FIG. For example, when the DC voltage (U) is adjusted to increase the U / V gradient ratio and detection is to be performed with high resolution, there is another stable region farther from the origin O. However, the stable region in which such a high resolution is possible has an extremely narrow range in which the voltage setting can be adjusted compared to the stable region shown in FIG. For this reason, it is required to perform advanced fine adjustment each time due to the problem of stable circuit reliability and temperature drift. In practice, a stable region near the origin O as shown in FIG. Is used. Also in this embodiment, the stable region near the origin O shown in FIG. 6A is used. However, in another embodiment, another stable region may be used for the purpose of high-resolution detection.

By the way, if an electrode which is a rod is applied at a voltage with a U / V ratio in the stable region, ions having a mass-to-charge ratio (m / z) will oscillate stably, but especially at the tip (P) of the stable region. When a U / V ratio (ie, U _P / V _P ) is set, a high resolution spectrum can be obtained. In actual use, the slope of the U / V ratio can be increased mainly by adjusting the value of the DC voltage (U), thereby increasing the resolution, so that the tip portion where the value of the DC voltage (U) is large (P) is advantageous from the viewpoint of resolution. Therefore, the voltage ratio of the tip portion among stable region _{(P) (U P / V} P) is selected, the voltage ratio (U _P / V _P) is constant as adjusted while the DC voltage (U) and the high-frequency voltage If (Vcos (ωt)) is continuously changed, ions of different masses also reach the detector 4 with stable amplitude motion.

  Therefore, by controlling the DC voltage (U) and the high-frequency voltage (Vcos (ωt)) so as to pass on the scan line connecting the origin (O) and the tip (P), different masses are obtained. Ions pass through the electric field generated by the quadrupole electrode 3 and reach the detector 4. This means that a stable region for each ion of the mass-to-charge ratio (m / z) is set in sequence, and a high-resolution mass spectrum (that is, the mass / m-z value on the horizontal axis, This means that a spectrum having the detected intensity on the axis is obtained.

However, in order to improve the resolution, it is preferable to specify the tip position (P). However, if the influence of temperature drift is small, the tip position (P) fluctuates and is stable every time even if the same exhalation gas is measured. You can get out of the area. Therefore, the voltage ratio (U _P / V _P) point of the gradient is less stable region than at the tip portion (P) (e.g., a point R in FIG. 6 (b)) if, always fits in the stable region Experience has shown that the probability increases. However, when the point R is used as a reference for forming the scan line, the gradient of the voltage ratio becomes small as described above, and thus the inconvenience that the resolution is lowered is unavoidable.

  Therefore, it is desirable to set the scan line reference point (Q) with a small probability of going out of the stable region while increasing the gradient of the voltage ratio (U / V) as much as possible (step S21). Conventionally, the setting of the scan line reference point (Q) has been adjusted by trial and error based on experience and intuition, but an example of an algorithm for automatically calculating the optimum scan line reference point (Q) is as follows: I'll mention it.

The algorithm will be described below.
As described above, even in the same exhaled gas, a deviation occurs in the stable region calculated due to the influence of temperature drift or the like. FIG. 7A shows an example of each stable region when the same expiratory gas is measured m times at predetermined time intervals. For convenience of explanation, FIGS. 7A and 7B are drawn as m = 5 times, and the drawn triangle approximates a stable area represented by a free curve by a straight triangle area. A related flowchart is shown in FIG.

  First, even if there is a deviation in the stable region at each measurement, it is specified to what extent the deviation is expected. This is also an index representing the reproducibility of the stable region, and is selected from reproducibility (low), reproducibility (medium), and reproducibility (high). When reproducibility (low) is set, instead of making the scan line reference point (Q) as high as possible at the tip position (P), the measurement also includes a scan line reference point (Q) that deviates from the stable region. Means. On the other hand, when reproducibility (high) is set, the scan line reference point (Q) is not at a low height away from the tip position (P), but from a stable region in all or most of the multiple measurements. This means that the scan line reference point (Q) that deviates is not included. Therefore, as shown in the flowchart of FIG. 8, the above-described reproducibility level (high / medium / low) is designated in advance (step S80).

Next, the highest tip portion is extracted from each stable region (step S81).
For the measurement shown in FIG. 7 (a), since the highest tip portion of the third measurement to the base when calculating scan line reference point extracting P ₃ a (Q). Instead of P ₃ , the average value or median value of the heights of the tip positions of all measurements may be used.
Next, the height (denoted as level 1) obtained by reducing Δh from the extracted P _{3 is} set as the first candidate for the determination line for determining the final scan line reference point (Q) (step S82). As shown in FIG. 7A, when a determination line of level 1 is drawn in each stable region, there are P _{1 to} P ₃ above the determination line and P ₄ and P ₅ below. The sum of the maximum number of vertices existing above and below the determination line is calculated (step S83).

Next, for example, when the reproducibility level is designated as low, it is determined whether the tip portion (P) located above the level 1 determination line is equal to or higher than a predetermined ratio (for example, 70%) ( Step S84). In the case of FIG. 7A, since it is 3/5 and does not exceed it, the process returns to step S82 for further lowering Δh, and the lowered height is set to the next level. On the other hand, if it exceeds, level 1 is adopted as the DC voltage (U) of the scan line reference point (Q) (step S85). When the scan line reference point (Q) is set on the judgment line of level 1 and the scan line connecting the origin O and the point Q is created, P ₄ and P ₅ are not taken into consideration, so all sampling measurements There is a high possibility that it will not be an optimal scan line for the user. However, when it is desired to increase the slope of the scan line, the DC voltage (U) indicated by the level 1 determination line is used by setting the reproducibility level low.

As described above, if the scan line reference point (Q) is set on the determination line of level 1, the scan line reference that should be excluded from being originally outside the stable region due to a variation factor such as temperature drift. There is a high possibility that it was created using points. In order to avoid this, it is only necessary to further lower the determination line to level 2 below P ₄ and P _5, and the tip portion created by the fourth and fifth measurement can be taken into consideration. .

If you have set high reproducibility level, will further reduce the Δh min judgment line from the level 1 of the decision line, the judgment line when contains P _i in all the sampling measurement, the scan line reference point ( Adopted as the DC voltage (U) of Q). In addition, not all P _i are included, and it may be determined that the condition is satisfied when P _i of a predetermined ratio (for example, 90% or more) or more is included, and the determination line may be used. In the case of the sampling measurement shown in FIG. 7 (a), level 2 is the DC voltage (U) since P _i (i = 1 to 5) in all sampling measurements is positioned above level 2 at level 2. However, for example, if P ₅ is positioned below level 2, the determination line further divided by Δh is repeatedly examined, and the voltage U of the determination line finally determined is adopted ( Step S85).

Next, the high-frequency voltage (Vcos (ωt)) on the horizontal axis is determined as follows.
FIG. 7B shows an average of the voltages V _i (where i = 1 to m, where m = 5) at the tip (P _i ) at each measurement using a normal distribution. It is the figure which showed how much it deviates from voltage _Vmicro . It is determined which range of ± σ, ± 2σ, ± 3σ with respect to the average voltage V _μ includes the voltage V of the point P (step S86). In the present embodiment, the reproducibility levels (high / medium / low) designated in step S80 correspond to the ± σ, ± 2σ, and ± 3σ, respectively.

As shown in FIG. 7B, the voltages V _i (where i = 1 to 4) at P _{1 to} P ₄ are within ± σ of the normal distribution function. In contrast, it can be seen that P ₅ exists within ± 2σ. That is, the fifth sampling measurement is the voltage V ₅ that deviates from the range of ± σ from the average voltage V _μ and can occur at a rate of about 30% on the normal distribution. Such a voltage value is processed in relation to the reproducibility level designated in step S80. Specifically, when the designated reproducibility level is high (ie, ± σ), P ₅ is excluded because it requires that all of the measurement data is within ± σ (step S87). The remaining average voltage value Vave (1-4) of P _{1 to} P ₄ is employed as the high-frequency voltage (Vcos (ωt)) at the scan line reference point (Q) (step S88). Two voltage values for the scan line reference point (Q) are determined by combining with the DC voltage (U) by the level 2 determination line described above (step S89).

On the other hand, if the reproducibility level is specified as low (ie, ± 3σ) or medium (ie, ± 2σ), P ₅ is included in the range, so the average voltage including P ₅ The value Vave (1-5) is adopted as the high frequency voltage (Vcos (ωt)) of the scan line reference point (Q). Since ± 3σ in the normal distribution function is about 99.7%, when the reproducibility level (low) is specified, almost all voltages of sampling measurement are excluded without excluding voltage V at the time of specific sampling measurement. It can be seen that the average using the value is the voltage (V) for the scanline reference point (Q).

Therefore, even if there are subtle differences in the measurement environment each time, if you want to create a scan line using a scan line reference point based on a stable area that is always created with a high reproducibility level, use the scan line reference point. (Q ₂ or Q ₂ ′ in the right diagram of FIG. 7A is used. As a result, a scan line based on the scan line reference point Q ₂ or Q ₂ ′ having a slightly lower gradient is generated, and a stable region is generated. The extraction of ion molecules with a slightly lower resolution is possible, while the reproducibility is not so high and rather high resolution analysis is desired as described above. , The DC voltage (U) on the judgment line of level 1 and the average voltage value Vave (1-3) of P _{1 to} P ₃ are used, so the scan line gradient based on the scan line reference point Q ₁ is High In the. Above may be, to generate a scan line (OQ) (step S22 in FIG. 2).
The determination of the scan line reference point (Q) described above is merely an example, and the present invention is not necessarily limited to this. The user of the quadrupole mass spectrometer may set it appropriately.

  Returning to the flowchart of FIG. 2, the mass separator 3 of the quadrupole mass spectrometer performs voltage control along the scan line (OQ) while mainly adjusting the DC voltage (U) (step S23). As a result, each ion molecule that has passed under each voltage reaches the detection unit 4. In other words, there is a stable region that settles in a stable state for ions of each mass m, so that the voltage is passed through each stable region while keeping the ratio of the DC voltage (U) and the AC voltage (V) of a predetermined frequency constant. By performing the adjustment of changing, it becomes possible to analyze each component in the exhaled gas in a lump.

The detector 4 (for example, a secondary electron multiplier) that has received ions of each m / z separated according to the ratio of the mass m to the charge z in the mass separator 3 is incident on the secondary electron emission surface. When ions are converted into electrical signals, the signals are further amplified using an amplifier circuit and then measured. For example, the detected intensity value is plotted on a calibration curve in which the value at which the maximum value is shown is created in advance to determine the content of each ion in the expiration gas (step S24), and a mass spectrum is generated (step S25). ). A plurality of mass spectra may be generated repeatedly, an average for each ion component may be taken, or a specific mass spectrum may be selected as a base, and the ion content in the exhaled gas may be determined based on the magnitude of each detected intensity from the base.
In addition, although the example using the secondary electron multiplier 5 was shown, it is not necessarily limited to this, and the structure or type of the secondary electron multiplier (continuous dynode / discontinuous dynode, etc.) It may be arbitrary.

  The amplified electrical signal is supplied to, for example, an oscilloscope, an electromagnetic oscillograph, etc., displayed on a monitor, and transmitted to the information processing device 6. The information processing apparatus 6 determines whether or not the measured object can be determined as positively doped based on the electrical signal value proportional to the detected amount of each ion in the following procedure. Although some functions of the information processing apparatus 6 may be executed by the quadrupole mass spectrometer 10, in the present embodiment, the information processing apparatus 6 performs data analysis described later.

FIG. 10 shows a detailed procedure for generating a mass spectrum based on the content of each ion molecule in the expiration gas by the information processing device 6 (step S25). An example of the mass spectrum is shown in FIG.
In the present embodiment, as shown in FIG. 9, in addition to the mass spectrum of the exhaled breath gas that is actually exhaled, a mass spectrum of atmospheric components is also created (step S100 in FIG. 10). Note that FIG. 9 is a graph in which the values of both mass spectra are displayed together, and it should be noted that the scale of the vertical axis changes midway.
Therefore, a plurality of exhalation collection containers (sample bag 15 or vacuum collection tube 14) are prepared, and the exhalation collection container different from the exhalation collection container containing the exhalation gas is sealed with the atmosphere of the collection location, Each is analyzed by a quadrupole mass spectrometer 10.

Next, the mass spectrum A of the atmospheric component and the mass spectrum B of the expiratory gas component are compared to calculate a feature amount (step S101). The feature amount here is expressed as a difference when two mass spectra are compared (see FIG. 11). Specifically, by subtracting the spectrum value of each corresponding molecular ion in the mass spectrum A from the spectral value (content) of each molecular ion in the mass spectrum B, the types of contained molecular ions derived only from the exhaled gas The content (that is, the detected intensity of the difference) is specified. For example, oxygen (O ₂ ) and water (H ₂ O) exist in the atmosphere and exhaled gas, and their mass-to-charge ratio (m / z) (that is, molecular weight) is 32 and 18, respectively. As shown in FIG. 9, O ₂ ions and water ions corresponding to m / z values of 32 and 18 have predetermined spectral values. Next, by canceling out the contents of each mass-to-charge ratio (m / z) existing as ionic molecules in the atmosphere from the exhaled gas, the influence under the measurement environment is eliminated as much as possible, and the ionic molecules unique to the measured object (Mass-to-charge ratio) will be identified. The above-described comparison of mass spectra and calculation of feature values may be performed by an analyst's visual observation or manual calculation, but may also be performed by automatic determination using an arbitrary pattern comparison algorithm.

  Next, the calculated feature amount is compared with the standard data to determine whether or not there is a significant difference (steps S102 and 103). Although standard statistical data may be used as the standard data, it is preferable that the race, age, gender, country, life, exercise environment, or the like is based on statistical data similar to the measurement object. Since the degree of deviation from the average value other than the object to be measured can be obtained by comparison with the standard data, first stage screening can be performed. If the exhaled gas contains only a component having a characteristic amount that does not greatly deviate from the standard data, it can be determined that the possibility of negative doping is high (step S111).

  By the way, in the voltage control of the quadrupole mass spectrometer 10, when trying to pinpoint the optimum scan line reference point, specific molecules that match the reference point are extracted with high sensitivity. Extraction of other molecules becomes low in sensitivity, and even if it is to be amplified by a secondary electron multiplier thereafter, the influence of noise is too great and the S / N ratio may be deteriorated. Therefore, extraction of ion molecules may be performed by performing voltage control suitable for a plurality of ion molecules included in a certain range.

This leads to a decrease in sensitivity in order to increase the detection accuracy, but there are cases where a certain molecular weight ion on the obtained mass spectrum relates to a plurality of molecules. For example, N _{2 has} a molecular weight (m / z value) of 28, but CO has a molecular weight (m / z value) of 28. Therefore, it cannot be determined by this alone whether the m / z value 28 on the horizontal axis in the mass spectrum is N ₂ or CO.

However, considering that it is known that N ₂ is decomposed into N and N, CO is C and O, for example, due to the strength of the molecular binding force, the molecular weights of a plurality of substances are the same m Even in the case of the / z value, it can be discriminated by checking whether the detection intensity of the small molecular weight of the related mass m is detected. For example, if the ionization conditions are constant ( _i ), the intensity ratio of the mass to charge ratio (m _i / z) as the parent signal and the mass to charge ratio (m _j / z) as the child signal is always constant, ( ii) The stable isotope ratio of ions in nature is always constant. Since (i) and (ii) are tables, the amount of individual ions can be determined by solving simultaneous equations using (i) and (ii).

As in the above example, it is determined whether or not the feature value obtained in step S101 is decomposed into molecules having smaller m / z values (step S104). The detected intensity of the z value is further confirmed (step S105). Thus, there is a limit to the molecular weight that can be analyzed by the quadrupole mass spectrometer 10, and even if it is not possible to directly extract a large molecular weight, if the m / z value is specified by the two-step process described above, Extraction of ion molecules can be realized with high accuracy (step S106, step S26 in FIG. 2).
It should be noted that since a feature value with a large value has a large influence, it is desirable to analyze from a molecular weight of a feature value with a large value when it has a plurality of feature amounts.

As the next processing, the mass spectrum of each ion molecule obtained in step S106 is considered as one pattern. The mass spectrum in FIG. 11 is the pattern referred to here. The pattern of ion molecules related to positive doping in the past is registered in advance in a database (for example, the database 7 or another database) in advance. The information processing device 6 searches the database for the same pattern as the current exhalation gas pattern and compares it (step S107). When there are patterns that are identical or highly correlated (Yes in step S108), it is possible to make a determination that the doping is positive (step S110).
Even if the absolute content of each molecule in the pattern registered in the database is different from the detection intensity of each molecule in the current analysis pattern, the detection intensity ratio of each ion molecule is almost the same. This would be the same pattern and be positive for doping.

  The reason why a positive determination of doping is made by the above pattern comparison is that it matches the pattern of molecules constituting the chemical substances of prohibited drugs. This is a case where the molecular ion of the prohibited drug component itself is contained in the exhaled gas. However, the doping test analyzes a metabolite excreted from the human body as a specimen. Therefore, the ingested prohibited chemical substance undergoes a chemical reaction in the body, and the metabolite after being converted or synthesized into another chemical substance is analyzed. In practice, it is difficult to make a definitive diagnosis in that the components of the exhalation gas do not always contain molecules of the doping chemical substance itself.

  In the case of the evaluation according to the present embodiment, even if it is determined that the molecular pattern indicating the prohibited drug in the database is not the same (No in step S108), the measurement object measures the expiratory gas in the past and accumulates it as a mass spectrum. It is characterized in that a reasonable doping determination can be made using certain data (detailed determination routine in step S109).

FIG. 12 is a flowchart showing the details of the detailed determination routine in step S109.
A feature of the detailed determination routine is that the breath gas analysis result of each player is stored in a database (for example, database 7), and the presence or absence of doping is estimated using this.
The breath gas of each player is collected not only at the time of the game but also at the time of practice (for example, every month, every other week, every other day, etc.) and is collected by the quadrupole mass spectrometer 10. Analyze and store in the database 7.

As shown in FIG. 13, the types and contents of the components in the breath gas are different for each player (for example, when masses m ₄ and m ₅ are compared between player A and player B, there is a large difference in the detected intensity value. ). Even with the same athlete, more or less transitions occur when viewed in time series. In other words, the A4 player's m ₄ actually increases gradually and has a high value at the time of measurement in December, although it showed a low value in January.

  In order to determine the doping based on the conventional idea, it is common that the doping is positive when the content of the prohibited substance contained in the exhaled gas exceeds or falls below a predetermined threshold. In other words, whether or not the detection of a specific component at each measurement simply exceeds a uniform threshold is a criterion for positive doping. However, depending on factors such as race, sex, region, and age, for example, there is a tendency that the content of a certain ion molecule of a specific race is higher than that of other races. In such a case, if a uniform determination is made as to whether or not the content of a specific ion molecule exceeds a predetermined threshold amount, an erroneous result may be caused. Don't be.

  In addition, it is known that a specific ion component increases or decreases when performance is improved by repeated practice, but the conventional doping determination does not consider this. For example, it is said that athletes with endurance exercise, such as long distances, increase their maximum oxygen consumption as their physical abilities increase, but this is also greatly influenced by each athlete's heart shape and myocardium. Judging by simply comparing with the average value of all players is also inaccurate. For each player, there is a demand for a doping determination after determining what kind of transition exists from the measured values at an arbitrary point in the past including normal life.

  Therefore, in the case of this embodiment, in addition to the determination based on the average data as in the conventional case, the past mass spectrum of the player stored in the database 7 is read for each ion molecule in the mass spectrum (step of FIG. 12). S120), it is checked how the time series changes. Compared to the pattern measured and accumulated in the past for each player (step S121), if the correlation (similarity) of the pattern is extremely low in spite of the breath gas of the same person, before the current measurement timing This may be the basis for the determination that the doping has been performed (step S128). Note that the determination of correlation includes both manual judgment by a pattern analyst and automatic judgment using an arbitrary statistical method and algorithm.

  Furthermore, even if there is a correlation with the past pattern, an accurate judgment may not be made for the gradual change, which is a little change, so it is expressed as the value of the detected intensity of the spectrum next. A moving average line (MA) of the content of ion molecules is created (step S123). Since the moving average line smoothes the time series data, it is possible to clearly show the transition of the molecular weight accumulated sequentially. Moreover, since there are various types of moving average lines such as a simple moving average line, a weighted moving average line, and an exponential moving average line, they may be adopted as appropriate. For example, the exponential moving average is an exponentially decreasing weight, and it can be said that emphasis is on the data near the latest, and older data is less important (not completely zero). Therefore, it can be expected to enable more realistic data analysis.

  Further, the moving average deviation rate (RD) is calculated (step S124). The moving average deviation rate is an index obtained by quantifying how far the moving average deviation value is from the above moving average line. FIG. 13 shows an example in which a 52-week moving average line relating to the detection intensity of a molecular ion having a certain m / z value is plotted in a mass spectrum obtained by an athlete collecting weekly exhalation gas and analyzing the exhalation. It is possible to grasp how far it is from the 52-week moving average line of one year.

Therefore, it is determined whether or not the moving average deviation rate (RD) is within a range of ± α% (α is set as appropriate, and the + range and the − range do not have to be the same as shown in the figure) (step) This is repeated for each ion molecule in the mass spectrum (step S126). The period used for the moving average line (MA) may be determined as appropriate. For example, when exhaled gas is collected at least in each week, it is determined whether it falls within a predetermined range (for example, ± 10%) from the average value of the past one year using a moving average line for 52 weeks. In addition, an arbitrary long and short moving average line such as 6 months (24 weeks) or 3 months (90 days) may be used.
As a result, even if the content of a certain ion molecule exceeds a predetermined uniform threshold based on the average data when compared with the average data of other players or ordinary people other than the players, Since the deviation rate (RD) based on the moving average for the player is within a predetermined range (eg, ± 10%), it is determined that it is not sufficient as a sign of an obvious abnormal value indicating positive doping. Is also possible (step S127).

On the other hand, it is assumed that the deviation rate exceeds the deviation of a predetermined range (for example, ± 10%) based on the moving average line (MA) of the player. If it is considered that deviating from the predetermined range from the life or practice so far is considered to deviate unexpectedly, it may be determined that the suspicion of doping positive is high (step S128).
In this way, even if it is not judged to be the same as the spectrum pattern of the molecules constituting the chemical substance of the prohibited drug and a positive diagnosis cannot be made, it is based on the spectrum pattern and the data value measured by each athlete in the past. A second stage screening diagnosis can be performed to determine whether or not doping is suspected. The major technical significance of the evaluation system according to the present invention is that when an unknown substance (unknown substance) that has not yet been confirmed as a prohibited drug is ingested, a conventional case where a definitive diagnosis could not be made and the doping test passed. It can be solved. Even if it is truly a prohibited drug to be doped or what the component is, it can be found that there is a component that has not been extracted from the past breath gas of the same person, If there is a value that shows a significant difference when referring to time-series data collected from past breath data analysis results, or if it is known that the divergence rate exceeds a predetermined range or threshold, it should be estimated as a false positive Is based on rationality. A final diagnosis of the presence or absence of doping will be made while conducting other tests, but the evaluation according to the present invention ensures a sample case that is suspected of being abnormal or cannot be estimated as normal. Since it will be picked up, it will demonstrate the deterrent to the doping act by athletes.

  Note that if the athlete has been taking prohibited drugs in small amounts over a long period of time, the change in the moving average line (MA) is small, and therefore the deviation rate (RD) may be within a predetermined range. In such a case, if there is a concern that it is determined that doping is negative, the possibility is low because comparison is made with the standard data in step S102 of FIG. In other words, if a prohibited drug is ingested even if it is a trace amount, if a characteristic amount different from the component analysis of the breath gas of a normal person who has not ingested is repeated, it will become apparent as an abnormal value at some point. Therefore, it is difficult to avoid the doping test by intentionally controlling the intake of the prohibited drug so as not to deviate from the moving average line.

  Furthermore, as shown in FIG. 1, the information processing device 6 is connected to a remote control device 9 via a network 8 so as to be communicable. The remote control device 9 creates alert information based on the analysis result output from the information processing device 6 while remotely monitoring the operating state of the analysis evaluation system 100, or transmits the analysis result and alert information to a doctor or the like. Request a doping decision.

  As described so far, the conventional doping test requires a great deal of labor and time because urine or blood is collected from an athlete as a specimen and is tested to determine whether it is positive or not. As a method for solving this, as previously indicated, Patent Document 1 (Patent No. 5258892) using expiratory gas as in the present invention has been proposed, but the difference from this method is shown. deep.

Patent Document 1 analyzes “particles” in exhaled air instead of urine and blood to analyze the chemical substance content of the particles. For example, paragraph [0007] has the following description. “Recently, a new method of collecting exhaled breath condensate (EBC) has been introduced. This is a condensate of exhaled water vapor at a low temperature, both volatile and non-volatile. Both compounds have been identified and the non-volatile compounds found in EBC are thought to be due to particles formed in the airways, which can cause breathing, talking and coughing. Have been studied to date, mainly because they are thought to be produced in the respiratory system and act as a medium for transmitting infectious substances. It is not yet known how it is formed, but a possible mechanism is turbulence of expiratory air in the middle of the airway where the bronchial cross-sectional area is significantly reduced. Opens at the edge of the lungs At the same time, particles are formed from RTLF. "
That is, the analysis target is not the exhaled gas itself but “particles” in the exhaled gas. It is described that the exhaled gas itself is discharged from the outlet 10.

In addition, solid and liquid particles called atmospheric aerosol particles are suspended in the air, and millions of atmospheric aerosol particles enter the lungs and a part of them is taken into the body. Patent Document 1 classifies atmospheric aerosol particles contained in exhaled air based on the size distribution of the aerosol. The size of the breath aerosol particles is from a few millimeters of visible dust to a few nanometers, so we are analyzing even the smallest of a few nanometers.
In addition, since the exhaled gas contains a large amount of water vapor, it becomes an adsorptive gas, but it is easily adsorbed on the tube wall and electrodes of the mass spectrometer, and this influence causes a decrease in detection sensitivity.

On the other hand, the mass spectrometer of the present embodiment is disposed in a pressure state that is much lower than the atmospheric pressure that is reduced to a maximum of 10 ⁻⁷ Pa, and heats the inside of the vacuum vessel to a maximum of about 200 ° C. To do. Because it is such a use environment, when the breath “gas” is ionized by the ion source, detection in the order of ppm at a molecular level far smaller than a few nanometers is performed, and the amount of each component is specified. There is one feature in the point to do.
With the method according to Patent Document 1, it is impossible to achieve a detection sensitivity equivalent to that of the present invention.

  Moreover, the amount of exhaled gas to be input to the mass spectrometer for use in the measurement is only about 0.2 ml (maximum of about 0.5 to 10 ml) as shown in the syringe of FIG. 4 and FIG. It is not necessary to inject continuously for several tens of minutes as in Document 1.

<Industrial application field of the present invention>
In the above-described embodiment, the content of examining the doping positive reaction using the gas analysis evaluation method of the present invention has been described, but the present invention is not intended only for doping. For example, when a boxing player suffers a blow and develops concussion, the doctor or the like may observe the athlete's condition and make a doctor stop because there is a possibility that a sequelae may remain. This decision is a qualitative judgment and not an objective or quantitative judgment based on the results of analyzing samples from athletes. Therefore, an objective evaluation based on some quantitative index is desired. It was. It is said that a certain tau protein is expressed when blood test is performed on a person who develops concussion, so when analyzing the exhaled gas at the onset of concussion, specific ionic molecules different from normal can be extracted. The content may change significantly. For this reason, the evaluation system based on the breath gas analysis of the present invention has a great potential to assist in the objective evaluation of concussion. The present invention is used as a quantitative index for judgment by a doctor or the like at the time when any medical illness or disorder develops or is likely to occur, not limited to concussion.
In addition, it cannot be overemphasized that persons other than the player demonstrated by this embodiment are included as a subject of analysis of exhaled gas.

  In addition, trained so-called drug dogs are used for luggage inspection to check whether drugs etc. are hidden in baggage at the airport. Narcotic dogs detect their presence by sensing the unique smell of drugs, because they contain certain components in the atmosphere. For example, since the air in a narrow space where baggage is passed through a predetermined gate is considered to be essentially the same as the exhaled gas in the above-described embodiment, the present invention is applied even if the exhaled gas is not from a mammal or the like. obtain. The drug dog identifies only the presence of narcotics, but does not inform the quantitative test results as in the present invention, and therefore can provide precise test results. Moreover, although it is not an expiration gas, it can apply also to the component analysis of the odor generated from the corpse of the animal including a human. Furthermore, from the viewpoint that the present invention is intended for component analysis in the atmosphere, the present invention can be applied, for example, to inspect whether there are residual agricultural chemicals in plants such as vegetables. Especially applicable to inspection of imported vegetables.

  Each process executed by the information processing apparatus 6 of the present embodiment is performed by downloading through various recording media such as an optical disk such as a CD-ROM, a magnetic disk, and a semiconductor memory, or via a communication network. The programs installed or loaded on the computer and these storage media are included in the scope of the invention.

DESCRIPTION OF SYMBOLS 1 Sample introduction part 2 Ionization part 3 Mass separation part 4 Detection part 5 Secondary electron multiplier 6 Information processing apparatus 7 Database 8 Network 9 Remote control apparatus 10 Mass spectrometer 11 Syringe 12 Syringe comprised of holder and vacuum tube 13 Holder 14 Vacuum collection tube 15 Sample bag 16 Syringe inner cylinder 17 Exhalation inlet 18 Cap 19 Seal plug 20 Air hole

Claims (3)

Means for ionizing the gas injected into the vacuum vessel;
Means for applying an electric field in which a phase change occurs by applying a voltage in which a DC voltage and a high-frequency voltage having a frequency equal to or higher than a predetermined value are applied to electrodes in the vacuum vessel;
A reference point of a DC voltage and a high-frequency voltage at which the ionized gas stably oscillates in the formed electric field is set, and the electric field is maintained while maintaining a constant ratio of the DC voltage and the high-frequency voltage based on the reference point. Means for adjusting the voltage applied within,
Means for generating a spectral pattern relating to the content of ionic molecules unique to the gas among the ionic molecules contained in the gas after detecting the gas separated into ionic molecules under the voltage condition;
A related pattern extracting means for searching for one having correlation with the generated spectrum pattern from among the spectrum patterns whose analysis results have been confirmed;
A determination unit that determines that there is a state of occurrence of a specific substance or a disease or disorder associated with the searched spectrum pattern when a correlated spectrum pattern is searched by the related pattern extraction unit; ,
Equipped with a,
When the related pattern extraction unit does not search for a correlation with the generated spectrum pattern, the determination unit includes:
With reference to time series data that is an accumulation of past spectral patterns for the injected gas,
When the content of each ion molecule in the generated spectral pattern deviates from the range or threshold estimated from the time series data, the presence of the specific substance or a state in which a disease or disorder has developed An evaluation system that assumes that it is equivalent and makes it a candidate for screening . Determining whether or not the range or threshold estimated from the time series data deviates includes determining based on the correlation of the spectrum pattern in the time series data or the deviation rate from the moving average line of each ion molecule. The evaluation system according to claim 1 . The gas is an exhaled gas;
The determination means, the object to be measured in the expired gas is determined whether the doping positive or concussion condition evaluation system according to claim 1 or 2.

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