Analytical device equipped with ion mobility separation section

Abstract

Analyzer, which includes the following: an ion source (1); an ion mobility separation element (7) containing a pair of opposing electrodes (3, 4) to which a high-frequency voltage (13) and a direct current voltage (14) are applied; and a shielding electrode (2, 42, 43, 46) which is provided between the ion source (1) and the ion mobility separation part (7) and to which a DC voltage (12, 70) is applied, wherein the shielding electrode (2, 42, 43, 46) has an ion flow path (8, 41, 45, 47, 49) which connects an inlet (60), from which ions are introduced from the ion source (1), with an outlet (62), from which the ions are released, and the ion flow path (8, 41, 45, 47, 49) includes a cylindrical section which is bent in its middle so that the outlet (36) cannot be seen from the inlet (60).

Description

Technical field

[0001] This document refers to an analyzer with an ion mobility separation section. State of the art

[0002] An ion mobility separator (or ion mobility device), which separates and detects ions according to their ion mobility, is widely used as a point-of-care measuring device for environmental analysis, explosives detection, illicit drug detection, chemical detection, and similar applications due to its ability to operate even at atmospheric pressure without the need for a vacuum pump. The ion mobility separator separates ions in a gas phase at atmospheric pressure by exploiting the fact that the velocity of ions in the gas phase varies depending on the three-dimensional structure of a molecular ion. Therefore, this separation method differs significantly from a mass spectrometer, which separates molecular ions in an electric or magnetic field at reduced pressure.The expected result is that, using an ion mobility separator, isomeric ions with the same mass-to-charge ratio (m / z) can be separated, which are difficult to separate using a mass spectrometer. Field asymmetric ion mobility separators (FAIMS) and differential ion mobility spectrometers (DMS) are among the methods frequently used for ion mobility separation in recent years.

[0003] A mass spectrometer (MS) exhibits high selectivity because it can separate ions according to their mass-to-charge ratio (m / z) of molecular ions under reduced pressure, enabling the separation and detection of ions with high sensitivity and accuracy. A mass spectrometer is commonly used as a detector for liquid chromatography (LC) and gas chromatography (GC), and analytical techniques known as liquid chromatography-mass spectrometry (LC / MS) and gas chromatography-mass spectrometry (GC / MS) are widely employed. High sensitivity and high resolution are achieved through the temporal separation of samples, impurities, and other components by LC and GC.

[0004] Additionally, tandem mass spectrometry is used in mass spectrometers. This technique breaks down target ions and measures the fragmented ions to separate them from other impurity ions. This results in high mass resolution. Furthermore, the technology for highly sensitive measurements, such as high-resolution mass spectrometers like time-of-flight mass spectrometers (TOF / MS), Fourier transform mass spectrometers (FT / MS), Fourier transform ion cyclotron resonance mass spectrometers (FTICR / MS), and Orbitrap mass spectrometers, as well as triple quadrupole and quadrupole mass spectrometers, has advanced, and mass spectrometers are increasingly used, particularly in the fields of biology and medicine.

[0005] As described above, an ion mobility separator exhibits a separation efficiency different from that of a mass analyzer, and therefore a measurement method combining a mass analyzer and an ion mobility separator has also been reported. PTL 1 and 2 disclose examples of a device in which an ion source, a FAIMS, and a mass spectrometer are combined. The FAIMS is located in a stage downstream of the ion source and in a stage upstream of the mass spectrometer. PTL 3 discloses an example of a mass spectrometer. Ion flow paths are bent in the stage downstream of the ion source and in the stage upstream of the mass spectrometer. List of patent documents PTL 1: US 2009 / 0294650 A1 PTL 2: WO 2015 / 111311 A1 PTL 3: US 5756994 A PTL 4: US 2014 / 0 034 828 A1 PTL 5: DE 10 2014 222 380 A1 PTL 6: US 2011 / 0 101 214 A1 PTL 7: US 2003 / 0155498 A1 Summary of the invention: Technical problem

[0006] In an ion mobility separator, the technology for detecting ions with high sensitivity and throughput after the separation of ions generated by an ion source is crucial for further broadening the application and reducing false detections. However, the ion mobility separator (FAIMS or DMS), which separates and detects ions according to their ion mobility, currently faces the following challenges.

[0007] In PTL 1, a device is configured in the sequence of an ion source, a curtain plate, a FAIMS, and a mass spectrometer, and noise components are removed using a curtain gas. A gas stream is generated from the MS side toward the ion source side by directing the curtain gas to a section of the curtain plate. This gas reduces the entry of noise components (or contaminants) such as charged droplets, neutral molecules, clusters, and the like, generated by the ion source, into the mass spectrometer. As a result, the contamination of the FAIMS and the mass spectrometer is reduced. However, the noise component cannot be completely eliminated by the curtain gas alone. This is because the FAIMS, located immediately downstream of the ion source, is likely to become heavily contaminated due to the continuous spraying of samples and pretreated blood from the ion source.If the FAIMS is contaminated, problems arise because sensitivity decreases and separation efficiency deteriorates due to disturbance of the electric field, and the FAIMS's isolated voltage tends to discharge when contaminated with ions and conductive substances. Since the FAIMS is located immediately downstream of the ion source, it is easily contaminated by droplets and neutral molecules sprayed from the ion source, as described above. Therefore, the durability and robustness of the FAIMS are a significant concern.

[0008] In PTL 2, a configuration is disclosed in which ions generated by an ion source pass through a counter electrode in a stage preceding an MS, enter between an electrode of the preceding stage and an electrode of the subsequent stage, and then describe a 90-degree arc to strike the MS. According to this configuration, droplets and neutral molecules are reduced at the electrode of the preceding stage and the electrode of the subsequent stage, thus reducing contamination of the MS. In PTL 3, a configuration is described in which ions emitted by an ion source enter the MS, and other gases and noise flow to a disposal port. Although PTL 2 and 3 can prevent contamination of a mass analyzer and improve its durability, there is no description of an ion mobility separator. Therefore, the problem remains...to apply the configuration to the ion mobility separator, which is an object of the invention. PTL 4 relates to an ion transport device for a mass or ion mobility spectrometer comprising: (a) a plurality of strip electrodes arranged in a row on a solid substrate; (b) an ion outlet opening in the substrate, arranged adjacent to a first of the plurality of strip electrodes; (c) a cage electrode, which at least partially encloses the plurality of strip electrodes and the ion outlet opening; (d) a high-frequency (HF) voltage generator, which is operable to supply an HF phase difference between each pair of adjacent electrodes; and (e) at least one DC voltage source, which can be operated to supply a first and a second DC voltage to the cage electrode and an extraction electrode, and to supply each of the plurality of electrodes with a corresponding bias DC voltage.wherein the electrode strip widths of a series of the plurality of electrodes progressively increase from the first of the plurality of electrodes away from the first of the plurality of electrodes. PTL 5 relates to an air pressure interface (LD interface) for a spectrometer comprising a wall for separating an ionization chamber from a pressure-reduced region of the spectrometer, an ion inlet defining an ion path from the ionization chamber to the pressure-reduced region, and a passage defining a gas path from the ionization chamber to a gas outlet located outside the pressure-reduced region. The passage may have a higher gas conductance than the ion inlet, so that most of the gas flows into the passage and not into the ion inlet. An interface device is configured to apply a static electric field effective in such a manner as toPTL 6 relates to a device and a system for sample analysis comprising an ion inlet, an ion detector, and an ion focusing arrangement for converging a plurality of ion streams from the ion inlet into at least one focused ion stream. PTL 7 relates to a mass spectrometer system comprising two ion sources of opposite polarity, an ion deflector for the combined introduction of the ions into an ion trap mass spectrometer with ring and end cap electrodes, and a detector for detecting the emitted ions. The ions from both sources are mixed in the mass spectrometer, and reaction ions can be supplied to enable ion / ion reactions.

[0009] In view of such circumstances, the invention creates an ion mobility separator that can operate stably for a long time by improving the durability and robustness of the ion mobility spectrometer. Solution to the problem

[0010] The aforementioned problem is solved by the invention according to the independent claims. Further preferred embodiments are described in the dependent claims. Advantageous effects of the invention

[0011] According to the invention, the durability and robustness of an ion mobility separator are improved.

[0012] Further features relating to the invention will become apparent from the description and accompanying drawings of this document. Furthermore, the problems, configurations, and effects that differ from those described above will be clarified by the description of the following embodiments. Brief description of the drawings Fig. Figure 1 is a schematic representation showing a general configuration of a FAIMS. Fig. Figure 2 is a representation showing a waveform of a separation voltage in the FAIMS. Fig. Figure 3 is a schematic cross-sectional view showing an example of an analyzer in which an ion mobility separation part and a detector are combined. Fig. Figure 4 is a schematic representation showing details of an electrospray ion source. Fig. Figure 5 is a schematic cross-sectional view showing an example of the shape of an ion flow path of a shielding electrode. Fig. Figure 6 is a schematic perspective view of an arrangement example of the shielding electrode and the FAIMS. Fig. Figure 7 is a schematic cross-sectional view of the FAIMS. Fig. Figure 8 is a schematic cross-sectional view showing an example of the FAIMS, which consists of cylindrical electrodes. Fig. Figure 9 is a representation showing an example arrangement of an analyzer using the FAIMS. Fig. Figure 10 is a schematic cross-sectional view showing an analyzer in which an ion mobility separation part and a mass spectrometer are combined. Fig. Figure 11 is a view describing an arrangement example of an analyzer that uses a FAIMS and a mass spectrometer. Fig. Figure 12 is a schematic cross-sectional view of part of an analyzer. Fig. Figure 13 is a schematic cross-sectional view of part of an analyzer. Fig. Figure 14 is a schematic cross-sectional view of part of an analyzer. Fig. Figure 15 is a schematic cross-sectional view of part of an analyzer. Fig. Figure 16 is a schematic cross-sectional view of part of an analyzer. Fig. Figure 17 is a schematic cross-sectional view showing another arrangement example of a shielding electrode. Fig. Figure 18 is a schematic view of part of an analyzer. Description of embodiments

[0013] The following describes embodiments of the invention with reference to the accompanying drawings. The accompanying drawings show specific embodiments according to the principles of the invention; however, they serve to aid understanding of the invention and are not intended to be used for its interpretation in a limited way.

[0014] Fig. Figure 1 is a schematic representation showing a general configuration of a FAIMS. A FAIMS 50 comprises two flat-plate electrodes 51 and 52 made of a conductor such as a metal. The distance between these two flat-plate electrodes is approximately 0.1 mm to several mm, and ions fly through an ion-pass region between them. Both the width and length of the flat-plate electrodes are approximately several mm to several dozen mm, corresponding to the width and distance of the flying ions. In addition, FAIMS with a further miniaturized structure have become available in recent years, and there are structures in which the distance between the electrodes is reduced to approximately several dozen micrometers.

[0015] The FAIMS comprises an AC power supply 53, a DC power supply 54, and a DC power supply 57. In the FAIMS, a separation voltage (or a dispersion voltage), obtained by superimposing a high-frequency voltage, is applied to the flat-plate electrodes 51 via the AC power supply 53 such that a high-frequency electric field is established between the flat-plate electrode 51 and the flat-plate electrode 52. As in the example of the separation voltage described in Fig. As shown in Figure 2, the isolation voltage is applied such that a high voltage (positive voltage) and a low voltage (negative voltage) are repeatedly applied for a specific duration, such that their time average is zero. The voltage amplitude, which is the difference between the maximum and minimum values ​​of the isolation voltage, is at most approximately 5 kV. Additionally, by applying a compensation voltage (or correction voltage), generated by the DC power supply 54, to the flat-plate electrode 52, the ion motion trajectory 56 of a specific ion 55 is corrected so that only the specific ion 55 can pass through and other ions are excluded. This compensation voltage is approximately -100 V to +100 V and is varied according to the ions that are to be allowed to pass through.

[0016] Unlike the example shown in the drawings, it is possible to separate ions even when a separation voltage generated by the AC power supply 53 is applied to the flat-plate electrode 52. In this case, the DC power supply 54 can be applied to the flat-plate electrode 52, as shown in the drawing, or to the flat-plate electrode 51. However, depending on the flat-plate electrode to which the voltage is applied, the positive and negative signs of the compensation voltage are reversed.Additionally, if the measurement target is positive ions, the same positive DC voltage is applied to the flat plate electrode 51 and the flat plate electrode 52 by the DC power supply 57, and the positive voltage, which is less than or equal to that of an electrode located in a preceding stage of the FAIMS 50 and greater than or equal to that of an electrode in a subsequent stage of the FAIMS 50, is applied in such a way that ions coming from the preceding stage are efficiently introduced into the FAIMS and efficiently discharged into the subsequent stage.

[0017] The invention provides a shielding electrode for blocking droplets and neutral molecules as contaminated materials between an ion source and the FAIMS as an ion mobility separator. The shielding electrode significantly reduces contamination of the FAIMS, improves its durability, and enables stable data acquisition over extended periods. [First embodiment]

[0018] A first embodiment is described. Fig. Figure 3 is a schematic cross-sectional view showing an example of an analyzer in which an ion mobility separation part of the embodiment and a detector are combined. Fig. Figure 4 is a schematic representation showing details of an electrospray ion source as an example ion source 1.

[0019] In this embodiment, a shielding electrode 2, comprising an L-shaped ion flow path bent at nearly a right angle, is inserted between the ion source 1 and a FAIMS 7 as an ion mobility separation element. Components of the analyzer include the ion source 1, the shielding electrode 2, the FAIMS 7 (consisting of flat-plate electrodes 3 and 4), and a detector 32. Ions 25 generated by the ion source 1 are attracted by electric fields and gas currents to an electrode 29 along an ion current 18 on the analyzer. The ions then traverse an ion flow path 8 of the shielding electrode 2 along an ion current 19 and enter an ion pass-through region, which is the space between the flat-plate electrodes 3 and 4 that form the FAIMS 7. After the ions have been separated by the FAIMS 7, only ions that have passed through the ion passband are detected by the detector 32.

[0020] The FAIMS 7 consists of flat-plate electrodes 3 and 4 as separating electrodes. An AC voltage and a DC voltage are applied to flat-plate electrode 3 by an AC power supply 13 and a DC power supply 14, respectively. The same DC voltage as that applied to flat-plate electrode 3 is applied to flat-plate electrode 4 by the DC power supply 14. Furthermore, a compensation voltage is applied separately to flat-plate electrode 4 by a DC power supply 15. By changing this compensation voltage, it is possible to select which ions are allowed to pass through, and a differential mobility spectrum can be achieved by sampling the compensation voltage.

[0021] The electrode 29 includes a gas control unit 17 and generates a gas stream 30 that blows gas supplied by the gas control unit 17 toward the side of the ion source 1, thus eliminating noise components such as droplets and neutral molecules generated by the ion source. This makes it difficult for noise components to penetrate the FAIMS 7. As described above, this gas stream 30 reduces the contamination of the FAIMS and the detector, but it is not sufficient. Therefore, in this embodiment, the shielding electrode 2 is also used to remove and reduce noise components such as droplets.

[0022] As in Fig. Figure 4 shows a liquid sample traveling through the inner section of a tube 27 in an electrospray ion source, which is the ion source 1, and being sprayed. A high voltage of approximately 1 kV to 5 kV is applied to the tube 27 by a DC power supply 11, generating an electric field between the tube 27 and the electrode 29. A voltage of several hundred volts is applied to the electrode 29. A spray is generated by electrostatic spraying through the electric field, atomizing the liquid sample to produce ions 25 by charge repulsion. During spraying, a gas 26, such as an atomizing gas or a heat gas, is caused to flow between a tube 28 and the tube 27 to promote desolvation and trimming of the liquid. Hydrogen gas and air are often used as gases 26 and 30, respectively.For tube 27, a glass tube, a glass capillary, a metal capillary, and the like are used.

[0023] The shielding electrode 2 of the embodiment is made of a conductor such as metal, and the ion flow path 8 thereof comprises a section bent at a substantially right angle, i.e., a section bent by 90 degrees ± 10 degrees. In the example shown in the drawing, there is an ion inlet and an ion outlet. That is, in the inner section of the shielding electrode of the embodiment, an ion flow path is provided that connects an inlet, from which ions are introduced from the ion source, and an outlet, from which ions are released, and the ion flow path is bent such that the outlet cannot be seen from the inlet.By bending the ion flow path by 90 degrees, noise components such as heavy droplets and neutral molecules collide with a collision section 9 in the flow path in such a way that it is possible to reduce contamination of the flat plate electrodes 3 and 4 due to noise, with the flat plate electrodes forming the FAIMS 7 in a subsequent stage.

[0024] Fig. Figure 5 is a schematic cross-sectional view showing an example of the shape of an ion flow path of the shielding electrode 2. The shape of the ion flow path of the shielding electrode 2 is cylindrical, and its cross-sectional shape is typically circular with a diameter of approximately 0.01 mm to 10 mm. The shape of the ion flow path can be a rectangular tube, and its cross-section can be a square or a rectangle with a side of approximately 0.01 mm to 10 mm. Furthermore, the cross-sectional shape of the ion flow path can be elliptical, polygonal, or a similar shape.

[0025] A DC voltage is applied to the shielding electrode 2 by a DC voltage current source 12. Additionally, a DC voltage is applied to each electrode of electrode 29, flat plate electrode 3, and flat plate electrode 4 such that the ions generated by the ion source 1 flow freely towards the detector 32. To apply different voltages to multiple electrodes, insulators 21, 22, and 23 are inserted between the electrodes as spacers. Typically, if the electrodes to be detected are positive electrodes, the voltage is set to decrease in the sequence of electrode 29, shielding electrode 2, flat plate electrode 3, and flat plate electrode 4, with a voltage between 0 V and 1000 V applied to each electrode.The shielding electrode 2 of this embodiment is a conductor, and only a DC voltage is applied by the DC power source 12. Therefore, the entire shielding electrode 2 is at the same potential, and no electric field is generated in the ion flow path 8. However, if dirt accumulates in the collision section 9, a potential that fluctuates to a certain extent (approximately several volts) is applied to the collision section 9 due to the accumulated dirt, sample ions, and contaminated ions. However, since the ion flow within the shielding electrode 2 is guided by the gas flow, the potential of the collision section 9 is rarely generated, and thus the ions can pass through the shielding electrode 2 without losses.

[0026] Next, a method for removing noise components such as droplets, clusters, and neutral molecules using the shielding electrode 2 is described. For example, the gas flow rate of the ion flow path 8 within the shielding electrode is approximately 0.1 L / min to 10 L / min. The cross-sectional area of ​​the shielding electrode 2 is approximately 0.1 mm². 2 up to 100 mm 2 The mass of the ion is approximately 10 Da to 1000 Da, the mass of the droplet is approximately 1 million Da to 10 million Da, and the ratio of the droplet mass to the ion mass is 10 to 1 million. The ion collision cross-sectional area is approximately 10 -18 m 2 , the droplet collision cross-sectional area is approximately 10 -16 m 2 and the ratio of the cross-sectional area of ​​the droplet to the cross-sectional area of ​​the ion is 100.

[0027] A resistance force F that a substance receives from an airflow caused by a gas flow can be expressed as follows using a constant A, a mass m of the substance and a cross-sectional area S of the substance. F=A×S / m

[0028] A resistance force F2 of the ion relative to the resistance force F1 of the droplet is expressed by the following equation using a mass m1 of the droplet, a cross-sectional area S1, a mass m2 of the ion and a cross-sectional area S2. F2 / F1=(S2*m1) / (S1*m2)=10~10000

[0029] This result shows that ions have approximately 10 to 10000 times the resistance per unit mass compared to droplets.

[0030] This means that the ions tend to be bent by 90 degrees along an airflow of the gas to be introduced into the FAIMS and the detector without colliding with the inner wall of the flow path of the shielding electrode 2. In contrast, noise components such as droplets are less likely to be bent, so the probability of collision with the inner wall of the ion flow path of the shielding electrode near the collision section 9 is high, and thus the noise components are not introduced into the FAIMS or the detector. Therefore, the FAIMS and the detector are less likely to be contaminated, and thus durability and robustness are improved.

[0031] The shielding electrode 2 is heated to approximately 100°C to 200°C, causing the solvent of any liquid sample that collided with the collision section 9 of the shielding electrode 2 to evaporate rapidly. Contaminants adhere to the collision section 9 of the shielding electrode 2 as dirt and gradually evaporate as the shielding electrode 2 is heated. Even if evaporated contaminants are introduced into the FAIMS or the detector, there is a difference in the introduction time compared to the ions, so this does not interfere with the analysis of the ions.

[0032] The insulators 21, 22, and 23 are inserted between the electrodes, such as electrode 29, shielding electrode 2, and flat-plate electrodes 3 and 4, to which voltages are applied, and between the detector 32 and the electrodes. This is necessary because different voltages are applied to the respective electrodes. In particular, the AC power supply 13 applies an AC voltage to the flat-plate electrode 3 of the FAIMS 7. However, a high voltage of approximately 1 kVpp to 5 kVpp is applied to this AC voltage, and therefore it is necessary to prevent discharge to the surrounding electrodes. For example, the distance between the electrodes to be discharged can be determined from the voltage, which can be identified according to the relationship (Paschen's law) between pressure, distance, and the voltage that can be applied.For example, if it is desired to apply a voltage of approximately 3 kV to 5 kV at 1 atm, it is understood that the distance between the electrodes can be set to about 1 mm. In the case of applying an alternating voltage, as with the FAIMS, discharge occurs even more readily, and therefore it is necessary to set the distance between the electrodes to 1.5 mm or so for greater reliability. That is, it is necessary to provide a distance of approximately 1.5 mm between the shielding electrode 2 and the flat-plate electrode 3. As the distance between the electrodes increases, the probability that the ions will diffuse orbitally and collide with the electrodes, causing the ions to collapse and disappear, also increases, and the probability of a decrease in sensitivity increases. Therefore, it is desirable to shorten the distance between the electrodes as much as possible.Therefore, it is preferred that the distance between the shielding electrode 2 and the flat-plate electrode 3 is greater than a discharge limit distance and as short as possible, and the thickness of the insulator 22 is preferably about 1.5 mm, which is the distance between the electrodes that are not discharged. The distance between the flat-plate electrode 3 and the detector 32 in the subsequent stage can likewise be taken into account, and the thickness of the insulator 23 is preferably about 1.5 mm.

[0033] Next, the positional relationship between an outlet of the shielding electrode 2 and the flat plate electrodes 3 and 4 is described. Fig. Figure 6 is a schematic perspective view showing an arrangement example of the shielding electrode 2 and the FAIMS 7, and Fig. 7 is a schematic cross-sectional view of the FAIMS in a Fig. As shown in Figure 6, an outlet 36 of the shielding electrode 2 must be arranged within a cross-section 37 formed between the flat plate electrodes 3 and 4. That is, the outlet of the ion flow path provided within the shielding electrode must be located in the ion transmission region between a pair of facing electrodes of the FAIMS (ion mobility separation section). This is because the space for separating ions in the FAIMS 7 is the region of the cross-section 37, so that the outlet 36 of the shielding electrode 2 is located within the cross-section 37, and thus ions are efficiently introduced from the shielding electrode 2 into the FAIMS 7 without losses.

[0034] It is preferred that the material of the shielding electrode 2 be a conductor, such as a metal. This is because if the shielding electrode 2 is an insulator, it will become charged due to ions, charged droplets, or the like, and ion transmission will be difficult due to charge repulsion. The material of the shielding electrode 2 can be a metal, such as stainless steel, iron, gold, copper, aluminum, or any other conductor. Furthermore, the shielding electrode 2 may not be made entirely of metal, and the main body may be made of an insulator, such as plastic, ceramic, or Vespel, or a material with low electrical conductivity. Additionally, the inner surface of the ion flow path 8 in the shielding electrode 2 may be coated or plated with a conductor, such as a metal, to provide conductivity.In this way, it is sufficient for the shielding electrode 2 if at least the inner surface of the ion flow path 8, through which the ions pass, consists of a conductor.

[0035] Although the FAIMS is described using the example of two flat plate electrodes arranged so that they face each other, it is also possible to separate ions in a section between two facing cylindrical electrodes. Fig. Figure 8 is a schematic cross-sectional view illustrating an example of the FAIMS consisting of cylindrical electrodes. The FAIMS comprises an electrode 39 and an electrode 40 arranged coaxially within the electrode 39, and includes an AC power supply 13, a DC power supply 14, and a DC power supply 15. The voltage application procedure and operation are the same as those in the example of [reference missing]. Fig. 3. In the illustrated example, electrode 39 consists of a hollow cylindrical electrode and electrode 40 consists of a solid cylindrical electrode 21, but electrode 40 can also consist of a hollow cylindrical electrode. This embodiment can likewise be applied to a FAIMS containing such a cylindrical electrode or to other known FAIMS.

[0036] The ionization method implemented in ion source 1 is an ionization method commonly used in a mass spectrometer, such as electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), matrix-assisted laser desorption ionization (MALDI), desorption electrospray ionization (DESI), and atmospheric pressure photoionization (APPI).

[0037] Fig. Figure 9 is a diagram illustrating an arrangement example of an analyzer that uses the FAIMS 7 as an ion mobility separation unit. Ions generated by the ion source 1 are ion-separated in the FAIMS 7, and the ions are then ion-detected by a detector. A control unit 35 controls each component of the FAIMS 7 and consists of an information processing device, such as a PC. The control unit 35 contains a central processing unit, a main memory unit, and an auxiliary memory unit, and is connected to an input unit 34 and a display unit 33. The central processing unit consists of a processor (also called an arithmetic logic unit), such as a CPU. The auxiliary memory unit is, for example, a hard disk, and the main memory unit is a storage device.The display unit 33 is a display or similar device that shows analysis spectra, results, and analysis conditions. The input unit 34 is a keyboard, a pointing device (mouse or similar), or similar device that can input analysis conditions and the like.

[0038] As described above, a shielding electrode, which incorporates an ion flow path and is bent so that the outlet is not visible from the inlet, is installed upstream of the FAIMS. This allows for the removal and reduction of noise components such as droplets, clusters, and neutral molecules that are not used for analysis. It also significantly reduces contamination of the ion mobility separation component, such as the FAIMS, and any detector in a subsequent stage, and further improves the durability and robustness of the FAIMS. As a result, problems of reduced sensitivity, decreased resolution of the ion mobility separation component, and discharge of the ion mobility separator are resolved, and long-term maintenance is eliminated. [Second embodiment]

[0039] A second embodiment is described. Fig. Figure 10 is a schematic cross-sectional view representing an analyzer in which an ion mobility separation part and a mass spectrometer of the embodiment are combined.

[0040] The difference from the first embodiment is that the ion 25 passes through the FAIMS 7 and then through a first porous electrode 5, which is a vacuum partition to maintain the interior of the mass spectrometer 10 at vacuum pressure, along the ion stream 20, and enters a mass spectrometry section 6. In the mass spectrometry section 6, ions are separated by an ion separation analysis unit 31 and detected by the detector 32. A DC voltage is applied to the first porous electrode 5 by a DC power source 16. Insulators 23 and 24 are arranged between the flat-plate electrodes 3 and 4 of the FAIMS 7 and the first porous electrode 5, and between the first porous electrode 5 and the mass spectrometry section 6.

[0041] An ion mobility separation section comprising a FAIMS and a DMS can operate at atmospheric or sub-atmospheric pressure. Parts of the shielding electrode 2 and the FAIMS 7 are highly sensitive to gas to maintain high sensitivity. Therefore, the atmospheric pressure of the FAIMS 7 section is determined by the conductivity of an ion flow path of the shielding electrode 2, the conductivity of an ion flow path of the first pore electrode 5, and the pumping rate of a vacuum pump of the mass spectrometry section 6. For example, to operate the ion mobility separation section at atmospheric or sub-atmospheric pressure, it is preferred that the conductivity of the ion flow path 8 of the shielding electrode 2 be approximately five times or more than the conductivity of the ion flow path of the first pore electrode 5.

[0042] The mass spectrometer 10 can be any known mass spectrometer. For example, it could be an ion trap mass spectrometer such as a three-dimensional ion trap or a linear ion trap, a quadrupole filter, a triple quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform ion cyclotron resonance mass spectrometer, an Orbitrap mass spectrometer, a magnetic field mass spectrometer, or the like. Furthermore, a different known mass spectrometer than the one described above can be used.

[0043] Fig. Figure 11 is a view describing an arrangement example of an analyzer that uses the FAIMS 7 as an ion mobility separation unit and the mass spectrometer 10. The ions generated by the ion source 1 are ion-separated by the FAIMS 7 as the ion mobility separation unit, and then the ions are separated and analyzed in the mass spectrometer 10, and the ions are ion-detected. The control unit 35 controls each component of the FAIMS 7 and the mass spectrometer and consists of an information processing device such as a PC. The configurations of the control unit 35, the display unit 33, and the input unit 34 are the same as those of the first embodiment, and their exact description is not repeated. [Third embodiment]

[0044] A third embodiment is described. Fig. Figure 12 is a schematic cross-sectional view of part of an analyzer of the embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so that the illustration and description thereof are not repeated.

[0045] This embodiment differs from the first embodiment in the shape of a shielding electrode 42. The shielding electrode 42 of this embodiment is a tubular electrode bent into an L-shape, as shown in the drawing. The shielding electrode 42 is arranged between the ion source 1 and the FAIMS 7, which consists of the flat-plate electrodes 3 and 4. The inlet, outlet, and ion flow path of the shielding electrode 42 are the same as those of the shielding electrode 2 described in the first embodiment, and the ion flow path is bent such that the outlet from which the ions are released cannot be seen from the inlet from which the ions are introduced. In this embodiment, the ion flow path includes a section 26 that is bent substantially at a right angle in the middle.The shielding electrode 42 of the embodiment consists, for example, of a metal tube or a ceramic tube whose inner surface is coated with metal.

[0046] However, the configuration of the shielding electrode of the embodiment is not limited to that shown in the drawings, and other known configurations and shapes can be used as long as the inner surface of the ion flow path is coated with a conductor.

[0047] The flow path shape, cross-sectional shape, size and the like of the other ion flow paths are the same as those of the preceding embodiments. [Fourth embodiment]

[0048] Other forms of the shielding electrode are described in the following embodiments. Fig. Figure 13 is a schematic cross-sectional view of part of an analyzer of a fourth embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so their illustration and description are not repeated.

[0049] This embodiment differs from the previous embodiments in that the ion flow path 41 formed within a shielding electrode 43 is not a combination of straight lines, but a curve. The curved ion flow path 41 is so bent that it is not possible to see the outlet from which ions are released from the inlet from which the ions are introduced. The ion flow path is formed into a curved shape without corners, and therefore, in contrast to the previous embodiments, ion turbulence is expected to be less likely to occur, thus improving the ion transmission efficiency.

[0050] The flow path shape, cross-sectional shape, size and the like of the other ion flow paths are the same as those of the preceding embodiments. [Fifth embodiment]

[0051] A fifth embodiment is described. Fig. Figure 14 is a schematic cross-sectional view of part of an analyzer of the fifth embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so their illustration and description are not repeated.

[0052] This embodiment differs from previous embodiments in that the collision section 9 of a droplet within an ion flow path 45, formed within a shielding electrode 44, is recessed in a concave shape. That is, the ion flow path 45 is curved so that an outlet cannot be seen from an inlet, and furthermore, the curved section is recessed in a concave shape. Because the collision section 9 of a droplet is recessed in a concave shape, the influence on the ion current and charge repulsion with ions is reduced, even if impurities contained in the droplet accumulate in the recessed section. Therefore, the durability of the shielding electrode 44 is expected to be improved. The depth of the concave recess can be 0.1 mm or more.

[0053] The flow path shape, cross-sectional shape, size and the like of the ion flow path are the same as those of the previous embodiments, except that the collision section 9 of the droplet is recessed in a concave shape. [Sixth embodiment]

[0054] A sixth embodiment is described. Fig. Figure 15 is a schematic cross-sectional view of part of an analyzer of the sixth embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so their illustration and description are not repeated.

[0055] This embodiment differs from the previous embodiment in that an ion flow path 47, formed within a shielding electrode 46, is bent twice at nearly right angles. That is, the ion flow path 47 is bent twice so that the outlet cannot be seen from the inlet. It is expected that by bending the ion flow path twice, many droplets can be removed, thus further improving the durability of the FAIMS. The number of times the ion flow path is bent can be two or more. Furthermore, the corner of the flow path can be curved.

[0056] The flow cross-sectional shape, the cross-sectional shape, the size and the like of the ion flow path, with the exception of the number of bends, are the same as those of the previous embodiments. [Seventh embodiment]

[0057] A seventh embodiment is described. Fig. Figure 16 is a schematic cross-sectional view of part of an analyzer of the seventh embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so their illustration and description are not repeated.

[0058] This embodiment differs from the previous embodiment in that an ion flow path 49, formed within a shielding electrode 48, has a first outlet 36 at a position where the outlet cannot be seen from an inlet 60, and an outlet 62 that just pierces the inlet 60; that is, a second outlet 62 is provided at a position where the outlet can be seen from the inlet 60. During the analysis, the second outlet 62 is blocked by a removable plate element 63. In this embodiment, droplets introduced from the inlet of the ion flow path 49 travel straight and are removed by movement in one direction towards the second outlet 62. The droplet traveling towards the second outlet collides with the plate element 63, which blocks the second outlet 62, and contaminates the plate element 63.The plate element 63 is a separate and removable element from the shielding electrode 48 and can therefore be regularly removed and cleaned. On the other side, the ions flow along the airflow towards the first outlet 36, and it is possible for the ions to reach the FAIMS 7 and the detector or the mass spectrometer. The plate element 63 can be made of a material that makes it easy to wash away surface contamination, such as metal, plastic, glass, ceramic, or the like.

[0059] Fig. Figure 17 is a schematic cross-sectional view illustrating another arrangement of the shielding electrode 48. An electrode 61 is newly provided at a position facing the first outlet 36 of the ion flow path 49 provided in the shielding electrode 48. If the ions to be detected are positive ions, applying a voltage of approximately a few volts to several hundred volts to the electrode 61 from a DC power source 70 pushes the ions entering from the inlet 60 towards the first outlet 36, thus improving sensitivity. If the ions to be detected are negative ions, the polarity of the voltage applied to the electrode 61 from the DC power source 70 is reversed, and a voltage of approximately a few volts to several hundred volts is applied.

[0060] The flow path shape, cross-sectional shape, size and the like of the other ion flow paths are the same as those of the previous embodiments. [Eighth embodiment]

[0061] An eighth embodiment is described. Fig. Figure 18 is a schematic cross-sectional view of part of an analyzer of this embodiment. An ion source in a preceding stage and a FAIMS, a detector, or a mass spectrometer in a subsequent stage may have the same configuration and operation as those of the first or second embodiment, so their illustration and description are not repeated.

[0062] This embodiment differs from the previous embodiment in that an ion flow path formed within a shielding electrode 64 has two inlets, consisting of a first inlet 67 and a second inlet 68, and an outlet 69. The ion flow path has a curved shape, and thus the outlet 69 cannot be seen from either the first inlet 67 or the second inlet 68. Additionally, an ion flow path originating from the first inlet 67 and an ion flow path originating from the second inlet 68 merge in the middle to form a single flow path that terminates at the outlet 69. The analyzer comprises two ion sources, a first ion source 65 and a second ion source 66, and it is possible to introduce ions from the first inlet 67 or the second inlet 68. On the other hand, the ions exit the common outlet 69 and move towards the FAIMS 7.According to this embodiment, it is possible to measure ions generated by two different ion sources 65 and 66.

[0063] The ionization method implemented in the first ion source 65 and the second ion source 66 is a well-known ionization method commonly used in mass spectrometers, such as electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), matrix-assisted laser desorption ionization (MALDI), desorption electrospray ionization (DESI), and atmospheric pressure photoionization (APPI). Although not shown, when the analysis is performed using the first ion source 65, it is preferable for the inlet 67 to be open and the inlet 68 of the unused second ion source 66 to be closed. When the second ion source 66 is used, the inlet 68 is open and the inlet 67 is closed. The inlet closure is achieved, for example, by a valve.

[0064] The flow path shape, cross-sectional shape, size and the like of the other ion flow paths are the same as those of the preceding embodiments.

[0065] The invention is not limited to the embodiments described above and includes various modified examples. For instance, the embodiments described above are explained in detail to clarify the invention and are not necessarily limited to those that have all the described configurations. Furthermore, a part of the configuration of one embodiment can be replaced by the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. Additionally, it is possible to add, remove, and replace other configurations with respect to a part of the configuration of each embodiment. Reference symbol list 1 ion source 2 Shielding electrode 3, 4 flat plate electrode 5 First pore electrode 6 Mass Spectrometry Section 7 FAIMS 8 Ion flow path 9 Collision section 10 mass spectrometers 17 Gas control unit 21, 22, 23, 24 Insulator 32 Detector

Claims

[1] Analyzer comprising the following: an ion source (1); an ion mobility separation element (7) containing a pair of opposing electrodes (3, 4) to which a high-frequency voltage (13) and a direct current voltage (14) are applied; and a shielding electrode (2, 42, 43, 46) which is provided between the ion source (1) and the ion mobility separation part (7) and to which a DC voltage (12, 70) is applied, wherein the shielding electrode (2, 42, 43, 46) has an ion flow path (8, 41, 45, 47, 49) which connects an inlet (60), from which ions are introduced from the ion source (1), with an outlet (62), from which the ions are released, and the ion flow path (8, 41, 45, 47, 49) includes a cylindrical section which is bent in its middle so that the outlet (36) cannot be seen from the inlet (60). [2] Analyzer according to claim 1, wherein the ion flow path (8, 41, 45, 47, 49) comprises a section bent at a right angle. [3] Analyzer according to claim 1, wherein a distance between the outlet (36) of the shielding electrode (2, 42, 43, 46) and the pair of mutually facing electrodes (3, 4) is longer than a discharge limit distance. [4] Analyzer according to claim 1, wherein the outlet (36) of the shielding electrode (2, 42, 43, 46) is arranged within an ion pass-through area between the pair of mutually facing electrodes (3, 4) of the ion mobility separation part (7). [5] Analyzer according to claim 1, wherein at least one inner surface of the ion flow path (8, 41, 45, 47, 49) of the shielding electrode (2, 42, 43, 46) has conductivity. [6] Analyzer according to claim 1, wherein the ion flow path (8, 41, 45, 47, 49) is designed such that the curved section is recessed in a concave shape. [7] Analyzer according to claim 1, wherein a mass spectrometer (10) is connected to a subsequent stage of the ion mobility separation part (7). [8] Analyzer according to claim 7, wherein the mass spectrometer (10) has a first pore electrode (5) facing the ion mobility separation part (7) to maintain an interior of the mass spectrometer (10) in a vacuum state, and the conductivity of the shielding electrode (2, 42, 43, 46) is greater than that of the first pore electrode (5). [9] Analyzer according to claim 1, wherein the ion flow path (8, 41, 45, 47, 49) has a second outlet (62) at a position where the second outlet (62) can be seen from the inlet (60), and the analyzer further comprises a removable plate (63) that closes the second outlet (62). [10] Analyzer according to claim 9, wherein the ion flow path (8, 41, 45, 47, 49) is provided with an electrode (61) at the position where the outlet (36) can be seen. [11] Analyzer comprising the following: a first ion source (65) and a second ion source (66); an ion mobility separation part (7) containing a pair of opposing electrodes (3, 4) to which a high-frequency voltage and a direct current voltage are applied; a shielding electrode (64) which is provided between the first and second ion source (65, 66) and the ion mobility separation part (7), to which a DC voltage is applied and which has a first inlet (67) which is associated with the first ion source (65) and a second inlet (68) which is associated with the second ion source (66), and an outlet (69), wherein An ion flow path starting from the first inlet (67) and an ion flow path starting from the second inlet (68) merge at the center of the shielding electrode (64) to form a single flow path ending at the outlet (69), the ion flow path comprising a cylindrical section which is bent in its center so that the outlet (69) cannot be seen from the first inlet (67) and the second inlet (68).

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