Quantification method

Abstract

An object of the present invention is to provide a method for more accurately quantifying a test substance in a measurement system in which the amount of the test substance increases or decreases in a measurement device during measurement of a sample.SOLUTION: A method for quantifying a test substance in a sample containing the test substance, the method comprising (1) measuring the same sample a plurality of times using a measurement device to obtain a plurality of quantitative values of the test substance in the sample, and (2) calculating, from the plurality of quantitative values, an increase or decrease amount of the test substance caused by the measurement device, and correcting at least one of the plurality of quantitative values with the increase or decrease amount to obtain a true quantitative value of the test substance.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a quantitative method for use in an assay system in which the amount of an analyte that was originally present in a sample cannot be determined because the amount of the analyte increases or decreases within the assay system during sample measurement. [Background technology]

[0002] As an example, consider a substance that is highly hydrolyzable, and when a sample comes into contact with water adsorbed on the inner walls of a cell or pipe in a measurement system during measurement, the substance is hydrolyzed.

[0003] Due to their properties, it is inevitable that such substances contain hydrolysis products as impurities. When the hydrolysis product is the test substance, when the sample is introduced into a measuring device for measurement, the test substance is generated by water adsorbed on the inner walls of the piping or container. The test substance thus generated becomes background, and the quantitative value of the test substance obtained will be higher than the amount of the test substance originally contained in the sample.

[0004] In order to accurately quantify such test substances, it is necessary to remove the water adsorbed on the inner walls of the measuring device completely or to an extent that does not affect the quantification, thereby preventing the generation of background.

[0005] Considering pressure resistance and heat resistance, metals are likely to account for the majority of components constituting a measurement system, including piping, depending on the design of the measurement device. Some literature suggests that water adsorbed to metals can be desorbed from the surface by heating the components to 120 to 150 °C (see, for example, Non-Patent Documents 1 and 2). However, it is extremely difficult to confirm that water has been completely removed or reduced to a level that does not affect quantification. Furthermore, heating components can cause mechanical changes in the measurement system, such as shifting the optical axis, which could affect the quantification results. Therefore, it is not realistic to completely remove water adsorbed to the inner walls of a measurement device or to a level that does not affect quantification to prevent background generation.

[0006] Meanwhile, methods for reducing background during measurement have also been devised. For example, Patent Documents 1 and 2 describe methods for reducing substances that cause background and are present around the light source and detector in gas spectroscopic analysis. This method is based on the premise that the test substance and the substance that causes the background exist in separate spaces. However, in the problem to be solved by the present invention, the test substance and the background exist in the same space, so if the signal derived from the background is reduced by this method, the signal derived from the test substance will also be reduced at the same time, making it impossible to quantify.

[0007] Furthermore, Patent Document 3 proposes a method for reducing background signals during gas spectroscopic analysis by applying pressure to a gas that is a test substance in order to reduce background signals during measurement. This method also requires that the test substance and the background exist in separate spaces. If the test substance and the background exist in the same space, reducing the signal from the background will also reduce the signal from the test substance, making quantification impossible. Furthermore, this method is limited to gases, and its range of application is limited. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Publication No. 9-005233 [Patent Document 2] Patent Publication No. 2011-179942 [Patent Document 3] Patent No. 4715759 [Non-patent literature]

[0009] [Non-Patent Document 1] Journal of the Vacuum Society of Japan, 2010, Vol. 53, p. 527 [Non-patent document 2] Surface and Vacuum, 2018, Vol. 61, p. 27 Summary of the Invention [Problem to be solved by the invention]

[0010] As described above, when quantifying a highly hydrolyzable test substance, measurements must be performed in a state where water is adsorbed onto the inner walls of the piping or container of the measurement device with which the sample comes into contact. If it were possible to know the amount of background generated, i.e., the amount of increase or decrease in the test substance, it would be possible to quantify the test substance originally contained in the sample by correcting the obtained quantitative value by the amount of increase or decrease. However, in reality, it is not possible to know the amount of increase or decrease, and therefore it is not possible to quantify the test substance.

[0011] Furthermore, when quantifying by liquid chromatography, there is a problem that test substances that are adsorbed to the packing material in the column cannot be accurately quantified. To accurately quantify such test substances, it is sufficient to reduce adsorption by surface treatment of the packing material, and various manufacturers have made efforts to do so. However, depending on the type of test substance, adsorption cannot be avoided and accurate quantification cannot be performed.

[0012] The present invention aims to solve the above problems and provide a method for more accurately quantifying a test substance in a measurement system in which the amount of the test substance increases or decreases within the measurement device during sample measurement. [Means for solving the problem]

[0013] In order to solve the above problems, the present invention provides: 1. A method for quantifying a test substance in a sample containing the test substance, comprising: (1) measuring the same sample multiple times using a measuring device to obtain multiple quantitative values ​​of the test substance in the sample; and (2) calculating the increase or decrease in the amount of the test substance caused by the measurement device from the plurality of quantitative values, and correcting at least one of the plurality of quantitative values ​​by the increase or decrease to obtain a true quantitative value of the test substance; The present invention provides a quantitative method comprising the steps of:

[0014] In this way, the test substance can be quantified more accurately in a measurement system in which the amount of the test substance increases or decreases within the measurement device during sample measurement.

[0015] Furthermore, the test substance in the sample can be measured using one measurement device.

[0016] Alternatively, the test substance in the sample may be measured using a plurality of measuring devices.

[0017] In the quantitative determination method of the present invention, the number of measurement devices is not limited to one, but may be multiple.

[0018] Furthermore, the test substance in the sample can be measured using a plurality of measuring devices with the same specifications.

[0019] Alternatively, the test substance in the sample may be measured using a plurality of measuring devices with different specifications.

[0020] In the quantitative determination method of the present invention, when a plurality of measuring devices are used, the specifications of each device may be the same or different.

[0021] Furthermore, the test substance in the sample can be measured using a gas cell.

[0022] Alternatively, the test substance in the sample may be measured using a liquid cell.

[0023] In the quantitative determination method of the present invention, there is no particular limitation on the form of the sample.

[0024] The step (1) can also be carried out using a plurality of columns by a chromatographic method selected from liquid chromatography, ion chromatography, and gas chromatography.

[0025] In this case, the plurality of columns can be connected in series or in parallel.

[0026] The quantitative method of the present invention can be applied to quantitative analysis using, for example, a chromatographic method. [Effects of the Invention]

[0027] The present invention makes it possible to quantify test substances more accurately in measurement systems where the test substance is altered within the measurement device during sample measurement or where the test substance is adsorbed to the packing material of column chromatography. [Brief explanation of the drawings]

[0028] [Figure 1] This is an example of the quantitative method of the present invention, in which the same cell is used for the first and second measurements. [Figure 2] This is an example of the quantitative method of the present invention, in which different cells are used for the first and second measurements. [Figure 3] This is an example of the quantitative determination method of the present invention, in which two gas cells are connected in series. [Figure 4] 1 is an example of the quantitative method of the present invention, showing an example of steps when measurement is performed using a gas cell by infrared spectroscopy. [Figure 5] This is an example of the quantitative determination method of the present invention, in which three or more gas cells are connected in series. [Figure 6] In one example of the quantitative method of the present invention, two columns of the same length are connected in series by liquid chromatography, and a detector is connected to the rear of each column. [Figure 7] In one example of the quantitative method of the present invention, two columns of different lengths are connected in series by liquid chromatography, and a detector is connected to the rear of each column. [Figure 8]In one example of the quantitative method of the present invention, two columns of different lengths are connected in parallel by liquid chromatography, and a detector is connected to the rear of each column. [Figure 9] In one example of the quantitative method of the present invention, two columns of different lengths are connected in parallel in liquid chromatography and connected to one detector via a six-way valve. DETAILED DESCRIPTION OF THE INVENTION

[0029] As described above, there has been a demand for the development of a method for more accurately quantifying a test substance in a measurement system in which the amount of the test substance increases or decreases within the measurement device during sample measurement.

[0030] In order to achieve the above-mentioned object, the inventors have conducted extensive research and devised a quantitative method in which the increase or decrease in the amount of a test substance is calculated from the difference between multiple quantitative values ​​obtained by measuring the same sample multiple times, and the quantitative value is corrected by this increase or decrease to obtain a true quantitative value.

[0031] That is, the present invention is a method for quantifying a test substance in a sample containing the test substance, comprising the steps of: (1) measuring the same sample multiple times using a measuring device to obtain multiple quantitative values ​​of the test substance in the sample; and (2) calculating the increase or decrease in the test substance caused by the measuring device from the multiple quantitative values, and correcting at least one of the multiple quantitative values ​​by the increase or decrease to obtain a true quantitative value of the test substance.

[0032] Hereinafter, embodiments of the present invention will be described with reference to the drawings, but the present invention is not limited to these.

[0033] (First aspect) In a first embodiment of the quantitative method of the present invention, the test substance in the sample is measured using a single measuring device. This embodiment is applicable to both liquid cells and gas cells.

[0034] Preliminary experiment Figure 1 shows an example of measuring a liquid sample using one liquid cell. The same liquid cell A is used for the first and second measurements, but the increase or decrease in the amount of test substance must be the same between the first and second measurements. To achieve this, the same cleaning or pretreatment of cell A that was performed before the first measurement must also be performed before the second measurement. It is also necessary to confirm the reproducibility of the measurements after that cleaning or pretreatment.

[0035] Process (1) After such a preliminary experiment, the sample is measured in cell A to obtain a quantitative value A1 of the test substance in the sample. Next, the measured sample is removed and washed or pretreated in cell A. After that, the measured sample is placed back into cell A and measured again to obtain a quantitative value A2 of the test substance in the sample. Note that the tool used to remove the measured sample is made of, for example, fluororesin or a tool with a deactivated interior surface to prevent the sample from deteriorating.

[0036] Process (2) Next, the increase or decrease in the amount of the test substance caused by the measuring device (cell A) is calculated from the multiple quantitative values ​​(quantitative values ​​A1, A2) as follows, and the quantitative values ​​A1 and / or A2 are corrected by the calculated increase or decrease to obtain the true quantitative value of the test substance.

[0037] At this time, the first quantitative value A1 is ■ Quantitative value A1 = Amount of test substance originally present in the sample + Increase / Decrease Amount... Equation (17) It is expressed as: The second quantitative value A2 is calculated as follows: ■Quantitative value A2 = Quantitative value A1 + Increase / Decrease = Amount of test substance originally present in the sample + Increase / Decrease + Increase / Decrease = Amount of test substance originally present in the sample + 2 Increase / Decrease Amount... Equation (18) It is expressed as: Subtracting equation (17) from equation (18) and swapping the left and right sides, we get ■Increase / decrease amount = Quantitative value A2 - Quantitative value A1... Equation (19) This becomes: Furthermore, by transforming equation (17), ■ Amount of test substance originally present in the sample = Quantitative value A1 - Increase / Decrease Amount... Equation (20) Substituting equation (19) into the right-hand side, ■ Amount of test substance originally present in the sample = Quantitative value A1 - (Quantitative value A2 - Quantitative value A1) = 2 Quantitative value A1 - Quantitative value A2 The amount of test substance originally present in the sample is determined.

[0038] The first aspect of the present invention can be expressed, for example, as follows.

[0039] 1. A method for quantifying a test substance in a sample containing the test substance, comprising: (1) placing the sample in a measuring device A and obtaining a quantitative value A1 of the test substance in the sample using the measuring device A; (2) placing the sample subjected to step (1) into the measuring device A again and obtaining a quantitative value A2 of the test substance in the sample using the measuring device A; and (3) calculating the difference between the quantitative value A1 and the quantitative value A2, setting the difference as the increase or decrease A of the test substance caused by the measuring device A, and correcting the quantitative value A1 and / or the quantitative value A2 by the increase or decrease A to obtain a true quantitative value of the test substance; A quantitative method comprising:

[0040] (Second aspect) In a second aspect of the quantitative method of the present invention, the measurement of the test substance in the sample is carried out using a plurality of measuring devices with different specifications. Note that this aspect is applicable to both liquid cells and gas cells.

[0041] Process (1) Figure 2 shows an example of measuring a liquid sample using two liquid cells A and B. Unlike Figure 1, liquid cell A is used for the first measurement and liquid cell B for the second. As with Figure 1, the equipment used for recovery is made of, for example, fluororesin or an equipment with a deactivated interior surface to prevent the sample from changing during recovery. Two spectroscopic analyzers may also be used, with one measuring liquid cell 1 and the other measuring liquid cell 2.

[0042] For example, if two measuring devices, liquid cells or gas cells, are designated cells A and B, a sample is first measured in cell A to obtain quantitative value 1A, and the measured sample is then measured in cell B to obtain quantitative value 1B. At this time, the increase or decrease in the amount of test substance occurring in cell A is designated increase or decrease A, and the increase or decrease in the amount of test substance occurring in cell B is designated increase or decrease B. Separately, a sample is first measured in cell B to obtain quantitative value 2B, and the measured sample is then measured in cell A to obtain quantitative value 2A. At this time, the increase or decrease in the amount of test substance occurring in cell A is designated increase or decrease A, and the increase or decrease in the amount of test substance occurring in cell B is designated increase or decrease B. Of course, cells A and B must be cleaned or pre-treated so that the increase or decrease in the amount of test substance is the same between the first and second measurements.

[0043] Process (2) Next, from the multiple quantitative values ​​(quantitative values ​​1A, 1B, 2B, 2A), the increase or decrease A and B of the test substance caused by the measuring device are calculated as follows, and each quantitative value is corrected by the calculated increase or decrease to obtain the true quantitative value of the test substance.

[0044] If measurements are taken in the order of A and B, then (A→B), and measurements are taken in the order of B and A, then (B→A), then ■ Quantitative value A (A → B) = Amount of test substance originally present in the sample + Increase / Decrease A... Equation (1) This becomes: Transforming equation (1) gives ■ Amount of test substance originally present in the sample = Quantitative value A (A → B) - Increase / decrease amount A... Equation (2) Also, ■Quantitative value B (A → B) = Quantitative value A (A → B) + Increase / Decrease B... Equation (3) Then, by transforming equation (3), ■Increase / decrease B = Quantitative value B (A → B) - Quantitative value A (A → B)... Equation (4) Therefore, the increase or decrease amount B can be determined from the results of measuring A and B in that order.

[0045] On the other hand, when measurements were taken in the order of B and A, ■ Quantitative value B (B → A) = Amount of test substance originally present in the sample + Increase / Decrease B... Equation (5) Transforming Equation 5 gives ■Amount of test substance originally present in the sample = Quantitative value B (B → A) - Increase / decrease amount B... Equation (6) By substituting the increase or decrease B calculated using equation (4) into this, the amount of test substance originally present in the sample can be calculated.

[0046] moreover ■Quantitative value A (B → A) = Quantitative value B (B → A) + Increase / Decrease A... Equation (7) Then, by transforming equation (7), ■Increase / decrease amount A = Quantitative value A (B → A) - Quantitative value B (B → A)... Equation (8) The amount of test substance originally present in the sample can also be determined by substituting the obtained increase or decrease A into equation (2).

[0047] The amount of the test substance originally present in the sample is calculated using two values, Equation (2) and Equation (6), and the reliability of the quantitative value can be confirmed by comparing these values. Furthermore, if the test substance does not change inside the measurement device during measurement, quantitative value A (A → B), quantitative value B (A → B), quantitative value A (B → A), and quantitative value B (B → A) will all be the same, and the increase / decrease amounts A and B will be zero.

[0048] The second aspect of the present invention can be expressed, for example, as follows.

[0049] 1. A method for quantifying a test substance in a sample containing the test substance, comprising: (1A) placing the sample in a measuring device A and obtaining a quantitative value 1A of the test substance in the sample using the measuring device A; (1B) placing the sample subjected to step (1A) into a measuring device B and obtaining a quantitative value 1B of the test substance in the sample using the measuring device B; (2B) a step of placing a new sample in the measurement device B, separate from the sample subjected to the steps (1A) and (1B), and obtaining a quantitative value 2B of the test substance in the sample using the measurement device B; and (3) calculating the difference between the quantitative value 1A and the quantitative value 1B, setting the difference as the increase or decrease B of the test substance caused by the measuring device B, and correcting the quantitative value 2B by the increase or decrease B to obtain a true quantitative value of the test substance; A quantitative method comprising:

[0050] It is preferable to include, after the step (2B), a step (2A) of placing the sample subjected to the step (2B) into a measuring device A and using the measuring device A to obtain a quantitative value 2A of the test substance in the sample.

[0051] In this case, in addition to the step (3), it is preferable to carry out a step (3') of calculating the difference between the quantitative value 2B and the quantitative value 2A, using this difference as the increase or decrease A of the test substance brought about by the measuring device A, and correcting the quantitative value 1A with the increase or decrease A to obtain the true quantitative value of the test substance.

[0052] (Third aspect) A third aspect of the quantification method of the present invention is a quantification method for cases where it is known that the increase or decrease obtained by measuring the same sample multiple times is the same in the first measurement as in the second or subsequent measurements (for example, when the measurement of the test substance in the sample is performed using multiple measuring devices with the same specifications). Note that this aspect is applicable to both liquid cells and gas cells.

[0053] Process (1) If preliminary experiments have shown that the increase or decrease obtained by measuring the same sample multiple times is the same for the first measurement and the second or subsequent measurements (for example, if measurement device A and measurement device B have the same specifications and the increase or decrease brought about by measurement device A is the same as the increase or decrease brought about by measurement device B), the amount of test substance originally present in the sample can be determined by one set of measurements (only A → B or B → A) without changing the measurement order, such as A → B or B → A, as in the second embodiment.

[0054] First, a sample is quantitatively measured to obtain a quantitative value 1 of the test substance. At this time, the test substance increases or decreases within the measurement system, resulting in a certain increase or decrease 1. Therefore, this quantitative value 1 is the difference between the amount of the test substance originally present in the sample and the increase or decrease 1, which is the amount of the test substance that has changed in quality within the measurement device. If the increase or decrease when the test substance increases is a positive value, then Quantitative value 1 = Amount of test substance originally present in the sample + Increase / Decrease 1... Equation (9) Transforming equation (9) gives ■ Test substance originally present in the sample = Quantitative value 1 - Increase / decrease amount 1... Equation (10) Since the quantitative value 1 is obtained, it is clear that if the increase or decrease amount 1 is known, the test substance originally present in the sample can be quantified.

[0055] Next, the sample after the first quantitative measurement is removed from the test system and measured again under the same conditions to obtain quantitative value 2. These same conditions are conditions under which it is known that the increase or decrease obtained by measuring the same sample multiple times will be the same in the first measurement as in the second or subsequent measurements (for example, conditions under which the increase or decrease brought about by measurement device A is the same as the increase or decrease brought about by measurement device B). This quantitative value 2 is the amount of the test substance present in the sample after the first measurement, i.e., quantitative value 1, plus increase or decrease 2, which is the amount of the test substance increased or decreased in the measurement device during the second measurement.

[0056] Process (2) That is, ■Quantitative value 2 = Quantitative value 1 + Increase / decrease amount 2... Equation (11) is. Here, since the increase / decrease amount 2 in the second measurement is the same as the increase / decrease amount 1 in the first measurement, ■Increase / decrease 2=Increase / decrease 1...Formula (12) Substituting this into equation (11), ■Quantitative value 2 = Quantitative value 1 + Increase / decrease amount 1... Equation (13) Furthermore, substituting equation (9) for the quantitative value 1 in equation (13) gives Quantitative value 2 = Amount of test substance originally present in the sample + Increase / Decrease 1 + Increase / Decrease 1... Equation (14) This becomes: Subtracting equation (9) from equation (14) gives ■Quantitative value 2 - quantitative value 1 = increase / decrease amount 1... Equation (15) The increase or decrease 1 can be calculated from the quantitative values ​​measured twice. By switching the right and left sides of equation (15), ■Increase / decrease amount 1 = Quantitative value 2 - Quantitative value 1... Equation (16) Substituting this into equation (10), we get ■ Test substance originally present in the sample = Quantitative Value 1 - (Quantitative Value 2 - Quantitative Value 1) = Quantitative Value 1 - Quantitative Value 2 + Quantitative Value 1 = 2 x Quantitative Value 1 - Quantitative Value 2 This becomes:

[0057] Since quantitative values ​​1 and 2 are obtained as measurement data, it is possible to quantify the amount of the test substance originally present in the sample. Furthermore, if the test substance does not change inside the measurement device during measurement, increase / decrease amount 1 and increase / decrease amount 2 will be 0, and quantitative values ​​1 and 2 will be the same value.

[0058] The third aspect of the present invention can be expressed, for example, as follows.

[0059] 1. A method for quantifying a test substance in a sample containing the test substance, comprising: (1) placing the sample in a measuring device A and obtaining a quantitative value A of the test substance in the sample using the measuring device A; (2) placing the sample subjected to step (1) in a measuring device B having the same specifications as the measuring device A, and obtaining a quantitative value B of the test substance in the sample using the measuring device B; and (3) calculating the difference between the quantitative value A and the quantitative value B, setting the difference as the increase or decrease in the amount of the test substance caused by each of the measuring devices A and B, and correcting the quantitative value A and / or the quantitative value B by the increase or decrease to obtain a true quantitative value of the test substance; A quantitative method comprising:

[0060] In the cases of Figures 1 and 2, the equipment used to handle the sample for the first measurement and the equipment used to recover the sample after the first measurement can be made of, for example, fluororesin or equipment with a deactivated interior to prevent deterioration during sample handling and recovery. However, even if deterioration cannot be avoided, the first measurement can be considered to measure a quantitative value that includes the increase or decrease in the amount of the test substance during all steps from sample handling to the first measurement, while the second measurement can be considered to measure a quantitative value that includes the increase or decrease in the amount of the substance during sample recovery after the first measurement. In this case, the equipment used to handle the sample during the first measurement and the equipment used to recover the sample after the first measurement must be the same to ensure that the increase or decrease in the amount of the substance during these steps is the same. It is also necessary to confirm the reproducibility of the quantitative values, including the recovery process.

[0061] (Fourth aspect) In the quantitative determination method of the present invention, as shown in FIG. 3, it is also possible to perform measurement by spectroscopy using two spectroscopic devices each using a gas cell connected in series.

[0062] For example, two infrared spectrometers using gas cells are connected in series as shown in Figure 3, and hydrogen chloride (test substance) in dichlorosilane (sample) is quantified according to the procedure shown in Figure 4. As shown in Figure 4, the quantification method of the present invention comprises drying the inside of the measuring device by evacuation (step 1), drying the inside of the measuring device with dry gas (step 2), introducing the sample into the measuring device (step 3), measuring absorbance (step 4), and replacing the inside of the measuring device with dry gas (step 5). Each step is described in detail below.

[0063] (Step 1: Drying the inside of the measuring device by vacuuming) Prepare a vacuum pump, connect it to the measuring device, and evacuate the inside. For example, you can evacuate the inside of the device until the vacuum level reaches minus 90 kPa (G) while heating the piping, mass flow controller, and valve to 40°C.

[0064] (Step 2: Drying the inside of the measuring device with dry gas) For example, dry nitrogen gas (Grade 3, dew point -70°C, H2O concentration 2.55 ppm) filled in a gas cylinder is introduced into the measuring device at a pressure of 200 kPa and a flow rate of 4 to 5 liters / minute, and the inside of the measuring device is dried overnight (approximately 10 hours).

[0065] (Step 3: Introducing the sample into the measuring device) Dichlorosilane gas is introduced into the measurement device, for example, at a pressure of 50 to 100 kPa and a rate of 2 to 3 liters / minute.

[0066] (Step 4: Absorbance measurement) The absorbance of hydrogen chloride in dichlorosilane gas filled in a gas cylinder is measured. For example, the absorbance of 2981 cm originating from the stretching vibration mode of H-Cl in the hydrogen chloride to be analyzed. -1 The peak of hydrogen chloride does not overlap with the infrared absorption peak of dichlorosilane and is located in its valley, so it is thought that quantification can be performed without being affected by dichlorosilane, but this peak is not the only possible one. Immediately after introducing the sample, the absorbance of the hydrogen chloride peak is measured continuously, and when it stabilizes at a constant value, that value is used for quantification.

[0067] (Step 5: Replacement of the inside of the measuring device with dry gas) After the measurement is completed, the dichlorosilane gas is removed from the measurement device. For example, after evacuating the device to -90 kPa (G), dry nitrogen gas is introduced into the measurement device at a pressure of 200 kPa and a flow rate of 4 to 5 liters / minute to replace the inside of the device with dry nitrogen gas. Immediately after introducing the dry nitrogen gas, the absorbance of the dichlorosilane peak (near 2237 cm-1) is continuously measured, and replacement is continued until this peak is no longer detected.

[0068] In this case, three or more infrared spectrometers using gas cells may be connected in series, as shown in Figure 5. The quantitative value obtained by one infrared spectrometer is subtracted from the quantitative value obtained by the previous infrared spectrometer to determine the increase or decrease, and the quantitative value is corrected by the increase or decrease, just as in the case of two spectrometers.

[0069] (Fifth aspect) Figure 6 shows an example of liquid chromatography in which two columns of the same diameter, length, and packing material are connected in series, with a detector attached to the rear of each. The quantitative value obtained by Detector 1 is subtracted from the quantitative value obtained by Detector 2 to determine the amount of increase or decrease, and the quantitative value is corrected by the amount of increase or decrease, as in the previous example. Note that refractive index (RI) detectors for liquid chromatography generally have low pressure resistance. When using this detector, the pressure resistance must be confirmed. Since the diameter, length, and packing material are the same, ideally, the amount of increase or decrease in the amount of test substance passing through the two columns will be the same. However, it is desirable to confirm this beforehand. To do this, simply connect each column separately and check the quantitative values. If the quantitative values ​​are different, it indicates that the amount of increase or decrease in the test substance is different. As previously mentioned, quantitative values ​​can be obtained by switching the order of the two columns and measuring.

[0070] Figure 7 shows an example of liquid chromatography in which two columns of the same thickness and packing material but different lengths are connected in series, with a detector connected to the rear of each. In this case, the only difference is the length, and the increase or decrease in the amount of test substance that occurs as it passes through each column is ideally proportional to the length, but it is advisable to confirm this beforehand. Here too, it is possible to connect each column individually and confirm the quantitative value.

[0071] Figure 8 shows an example of a liquid chromatography system in which two columns of the same diameter and packing material but different lengths are connected in parallel, with a detector attached to the rear of each. In this case, there is no back pressure on the detector, so there is no need to worry about the pressure resistance of the RI detector mentioned above. The only difference is the length, and the increase or decrease in the amount of test substance that occurs as it passes through each column is ideally proportional to the length, but it is advisable to confirm this beforehand. In this case, too, it is possible to connect each column individually and confirm the quantitative value. Alternatively, as shown in Figure 9, when connecting two columns of different lengths in parallel, it is also possible to connect them to a single detector via a six-way valve.

[0072] In the present invention, step (1) can also be performed using a plurality of columns by a chromatography method selected from liquid chromatography, ion chromatography, and gas chromatography. In this case, the plurality of columns can be connected in series or in parallel. [Example]

[0073] EXAMPLES The present invention will be explained in more detail below by showing examples and comparative examples of the present invention, but the present invention is not limited to these.

[0074] (Example) Two identical infrared spectrometers, designated as Apparatus A and B, were prepared. To remove moisture adsorbed on the inner walls of Apparatus A and the piping, dry nitrogen (dew point temperature -70°C, moisture content 2.55 ppm) was passed through each piping for 1 minute while heating it to 40°C, followed by 10 minutes of vacuum pumping. This cycle purge was repeated 30 times. It took approximately 5 hours for the vacuum to reach -90 kPa (G) or higher. Then, without breaking the vacuum, standard gas (nitrogen containing 0.1, 0.2, 0.5, 1.0, and 5.0 ppm hydrogen chloride) was introduced and measurements were performed, and a calibration curve was created. Dichlorosilane gas was then introduced without breaking the vacuum, and the hydrogen chloride peaks were measured over time. Once the measurements stabilized, hydrogen chloride was quantified using the calibration curve. The same procedure was performed on Apparatus B, and it was confirmed that the same quantitative values ​​were obtained using Apparatus A and B.

[0075] Next, Apparatus A and B were connected in series. To remove moisture adsorbed on the inner walls of the apparatus and piping, each piping was heated to 40°C while dry nitrogen (dew point temperature -70°C, moisture content 2.55 ppm) was passed through for 1 minute. Then, a 10-minute vacuum was applied. This cycle purge was repeated 30 times. It took approximately 5 hours for the vacuum to reach -90 kPa (G) or higher. Then, without breaking the vacuum, standard gas (nitrogen containing 0.1, 0.2, 0.5, 1.0, and 5.0 ppm hydrogen chloride) was introduced and measurements were performed. Calibration curves were created for each of Apparatus A and B. Dichlorosilane gas was then introduced without breaking the vacuum, and the hydrogen chloride peaks were measured over time. Once the measurements stabilized, hydrogen chloride was quantified using the calibration curve. The results of hydrogen chloride quantification for different lots (Runs 1–11) are shown in Table 1. The amount of hydrogen chloride varied from 0.026 ppm to 1.083 ppm for each lot, but the value of Apparatus B minus Apparatus A, i.e., the amount of hydrogen chloride generated in the system of Apparatus B during measurement (increase or decrease), was almost constant.

[0076] [Table 1]

[0077] Next, devices B and A were connected in series in this order, and the results of quantification were performed with different lots in the same manner as in the previous section (execution numbers 12 and 13) are shown in Table 2. The amount of hydrogen chloride varied from 0.463 ppm to 0.815 ppm for each lot, but the value for device A minus device B, i.e., the amount of hydrogen chloride generated in the system of device A during measurement (increase or decrease), was nearly constant and was nearly the same value as when devices A and B were connected in this order, confirming that there was no effect of the order of the devices.

[0078] [Table 2]

[0079] As described above, the quantitative method of the present invention can obtain the increase or decrease in the amount of the test substance with good reproducibility, and by correcting the quantitative value using this increase or decrease, a true quantitative value (a more accurate quantitative value) can be obtained.

[0080] (Comparative Example) In the previous example, when two infrared spectrometers were connected in series, the measurement results from the first-stage instrument, Instrument A, were considered to be the same as those from the conventional method, and therefore this data was used as the comparative example. The measurement procedure and results were the same as in the examples. However, because the amount of hydrogen chloride generated within the Instrument A system during measurement was unknown, the quantitative value of hydrogen chloride in dichlorosilane had to be directly adopted as the quantitative value of hydrogen chloride quantified by Instrument A. The amount of hydrogen chloride in dichlorosilane obtained in the comparative example, as shown in Table 3, is larger than the value obtained in Table 1 and is therefore overestimated. Furthermore, because the amount of hydrogen chloride generated within the Instrument A system could not be quantified in the comparative example, the amount of hydrogen chloride in dichlorosilane could not be quantitatively determined; it could only be determined that it was below a certain value.

[0081] [Table 3]

[0082] The present invention is not limited to the above embodiment. For example, although two infrared spectrometers are used in the example, the light source and detector may be the same for the first and second measurements in Fig. 2. That is, the light source of one infrared spectrometer may be incident on cells A and B for measurement.

[0083] Furthermore, if the results of an infrared spectrometer analysis of a test object (sample) are affected by residual moisture in the system through which the test object (sample) passes, better results can be obtained by further heating the piping and gas cell used to introduce the test object and passing high-purity dry nitrogen gas through them to thoroughly remove the moisture adsorbed on the inner walls. Although this is not possible with current technology, heating the piping and gas cell used to introduce dichlorosilane gas to 120 to 150 °C or higher and passing high-purity dry nitrogen gas through them to thoroughly remove the moisture adsorbed on the inner walls would reduce the blank value and lower the lower limit of quantitation and detection limit. When heating at high temperatures, it is preferable to insulate the detector and cell to avoid affecting the infrared spectrometer detector. Furthermore, using gas cells, piping, and window materials capable of drawing a higher vacuum would further reduce residual moisture in the system, thereby reducing blank values ​​and enabling more accurate measurements and achieving better results. This method can also be used to quantify hydrogen chloride in trichlorosilane and tetrachlorosilane, which have higher boiling points than dichlorosilane.

[0084] This specification includes the following inventions.

[0085] [1]: A method for quantifying a test substance in a sample containing the test substance, comprising: (1) measuring the same sample multiple times using a measuring device to obtain multiple quantitative values ​​of the test substance in the sample; and (2) calculating, from the multiple quantitative values, the increase or decrease in the test substance caused by the measuring device, and correcting at least one of the multiple quantitative values ​​by the increase or decrease to obtain a true quantitative value of the test substance.

[0086] [2]: The quantitative determination method according to [1] above, characterized in that the measurement of the test substance in the sample is carried out using one measuring device.

[0087] [3]: The quantitative method according to [1] above, wherein the test substance in the sample is measured using a plurality of measuring devices.

[0088] [4]: The quantitative method according to [3] above, characterized in that the measurement of the test substance in the sample is carried out using a plurality of measuring devices of the same specifications.

[0089] [5]: The quantitative method according to [3] above, characterized in that the measurement of the test substance in the sample is carried out using a plurality of measuring devices with different specifications.

[0090] [6]: The quantitative determination method according to any one of the above [1] to [5], wherein the test substance in the sample is measured using a gas cell.

[0091] [7]: The quantitative determination method according to any one of the above [1] to [5], wherein the test substance in the sample is measured using a liquid cell.

[0092] [8]: The quantitative method according to any one of [1] to [7] above, characterized in that the step (1) is carried out using a plurality of columns by a chromatographic method selected from liquid chromatography, ion chromatography, and gas chromatography.

[0093] [9]: The quantitative determination method according to [8] above, characterized in that the multiple columns are connected in series or in parallel.

[0094] The present invention is not limited to the above-described embodiments. The above-described embodiments are merely examples, and anything that has substantially the same configuration as the technical idea described in the claims of the present invention and that exhibits similar effects is included within the technical scope of the present invention.

Claims

1. 1. A method for quantifying a test substance in a sample containing the test substance, comprising: (1) measuring the same sample multiple times using a measuring device to obtain multiple quantitative values ​​of the test substance in the sample; and (2) calculating the increase or decrease in the amount of the test substance caused by the measurement device from the plurality of quantitative values, and correcting at least one of the plurality of quantitative values ​​by the increase or decrease to obtain a true quantitative value of the test substance; A quantitative method comprising:

2. 2. The quantitative determination method according to claim 1, wherein the measurement of the test substance in the sample is carried out using a single measurement device.

3. 2. The quantitative determination method according to claim 1, wherein the measurement of the test substance in the sample is carried out using a plurality of measurement devices.

4. 4. The quantitative determination method according to claim 3, wherein the measurement of the test substance in the sample is carried out using a plurality of measuring devices having the same specifications.

5. 4. The quantitative determination method according to claim 3, wherein the measurement of the test substance in the sample is carried out using a plurality of measuring devices with different specifications.

6. 2. The quantitative method according to claim 1, wherein the test substance in the sample is measured using a gas cell.

7. 2. The quantitative method according to claim 1, wherein the test substance in the sample is measured using a liquid cell.

8. 2. The method according to claim 1, wherein the step (1) is carried out using a plurality of columns by a chromatography method selected from liquid chromatography, ion chromatography, and gas chromatography.

9. The quantitative determination method according to claim 8, wherein the plurality of columns are connected in series or in parallel.

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