WO2022004094A1

WO2022004094A1 - Micro droplet formation device and analysis device

Info

Publication number: WO2022004094A1
Application number: PCT/JP2021/015116
Authority: WO
Inventors: 徹宮坂; 亨柴田; 隆之神田; 智美疋田
Original assignee: 株式会社日立ハイテク; 本多電子株式会社
Priority date: 2020-06-30
Filing date: 2021-04-12
Publication date: 2022-01-06
Also published as: JP2022011312A; JP7457306B2

Abstract

Provided are a micro droplet formation device capable of dividing even small liquid samples, that have been separated by liquid chromatography, into micro droplets with a mean particle diameter of several µm, and an analysis device.　A micro droplet device according to the present invention is characterized by comprising: an ultrasonic vibration generation unit (8) that generates ultrasonic vibrations; an ultrasonic vibration propagation and expansion unit (9) that expands and propagates the ultrasonic vibrations generated by the ultrasonic vibration generation unit; a sample excitation vibration unit (3) that imparts vibration on a liquid sample by using the ultrasonic vibrations that have been expanded by the ultrasonic vibration propagation and expansion unit, and forms microdroplets of the liquid sample; and a sample supply unit (40) that continuously supplies the liquid sample to the sample excitation vibration unit, wherein a liquid film formation member is provided on an excitation vibration surface (A) of the sample excitation vibration unit so as to be capable of maintaining the liquid sample, supplied by the sample supply unit, in a liquid film form.

Description

Microdroplet forming device and analyzer

The present invention relates to a microdroplet forming apparatus and an analyzer.

In order to analyze a liquid sample having a sample component, a method of decomposing the liquid sample into minute droplets and introducing the liquid sample into the analysis unit is used. A liquid chromatography mass spectrometer is a typical analyzer that analyzes a liquid sample as droplets.

Liquid chromatography mass spectrometry is a chemical analysis method in which various components separated by liquid chromatography are ionized and separated and detected for each mass-to-charge ratio. In this method, a liquid sample supplied from liquid chromatography is atomized into fine droplets, charged, and vaporized by heating to generate ions of analytical components.

The average particle size of the initial droplets formed by dividing the liquid sample is required to be tens to several μm. From the viewpoint of the efficiency of ionization (charging and vaporization), it is desirable that the diameter of the liquid to be formed is small, and it is also required that the particle size does not vary.

The atmospheric pressure spray method is currently widely used in mass spectrometers as a method for dividing a liquid sample into minute droplets. The atmospheric pressure spray method is a method in which a liquid is introduced into a high-speed jet to divide the liquid into split droplets, but in order to form droplets with an average particle size of several tens to several μm, the speed of sound is used. It is necessary to use a high-speed jet close to. Therefore, the device becomes large-scale. Further, the droplets formed by the atmospheric pressure spray method have a problem that the particle size tends to be unstable and the particle size distribution is wide. The particle size of the formed droplets and the distribution of the grain system also affect the charging required for ionization and the subsequent vaporization process, thus destabilizing the state of the analytical component ions to be formed. The state of ions greatly affects the measurement accuracy of chemical analysis, which is detected separately for each mass-to-charge ratio. Therefore, there is a need for a method for making a small amount of liquid sample separated by liquid chromatography into fine droplets having an average particle size of 10 μm to several μm in a more stable manner.

On the other hand, a method using ultrasonic waves is known as another method for dividing a liquid sample into minute droplets, and is disclosed in, for example, Patent Document 1 and Patent Document 2.

Japanese Unexamined Patent Publication No. 11-051902 Japanese Unexamined Patent Publication No. 2015-301650

The droplet diameter formed by ultrasonic waves is affected by the vibration frequency of ultrasonic waves. It is known that the relationship between the vibration frequency and the droplet diameter generally follows Lang's equation (J. Acous. Soc. Amer., 1962, 34, 6). According to Lang's formula, the vibration frequency for vibrating water or alcohol to form a droplet having a diameter of about 10 μm is about 200 to 300 kHz, and the vibration for forming a droplet having a diameter of 1 to 3 μm is formed. The frequency is known to be several MHz.

In general, the vibration of an ultrasonic vibrator has a small amplitude, and it is difficult to directly separate it into liquid and droplets. Therefore, by utilizing the resonance phenomenon of a metal column or a diaphragm structure, vibration having an acceleration capable of expanding the amplitude and dividing the liquid is obtained. In a general ultrasonic vibration-based droplet forming device vibration device, the limit vibration frequency is about 200 MHz because the resonance vibration of metal is used.

Patent Document 1 discloses a method in which droplets sprayed by an air spray are attached to the surface of an ultrasonic vibrator to form fine droplets. As described above, the vibration of the ultrasonic vibrator generally has a small amplitude, and it is difficult to form droplets. Further, when metal resonance is used, the limit vibration frequency is about 200 kHz, and the diameter of the formed droplet is limited to 10 μm. It is difficult to form droplets of several μm or less by the disclosed method. Further, when a small amount of liquid is supplied to a high-frequency vibrating surface of several hundred kHz or more, the droplets are likely to be scattered at the same time as the supply, and not only the fine droplets can hardly be formed, but also large liquid balls are scattered at the same time.

Patent Document 2 is a method of forming droplets by atomizing a liquid sample by vibrating the liquid sample stored in a container with an ultrasonic vibrator. In this method, the vibrating liquid itself is used to amplify the applied vibrating force, and a part of the liquid is atomized into fine droplets, that is, atomized.
This method is different from the above method using metal resonance, and since it is possible to vibrate the liquid sample at a vibrating frequency of several MHz, it is possible to form droplets having an average particle size of about several μm. .. However, since it is necessary to store the liquid to be irradiated with ultrasonic waves in a container or the like, a certain amount of liquid is required, and it is difficult to apply it to microdroplets of an extremely small amount of liquid sample separated by liquid chromatography. .. Further, if a small amount of liquid is directly supplied to the high frequency vibration surface of several MHz without storing the liquid sample in a container, the liquid tends to scatter very easily, and stable formation of fine droplets becomes more difficult.

In view of the above circumstances, an object of the present invention is to provide a microdroplet forming apparatus and an analyzer capable of dividing even a small amount of liquid sample separated by liquid chromatography into microdroplets having an average particle size of several μm. To do.

One aspect of the microdroplet forming apparatus of the present invention for solving the above problems is
An ultrasonic vibration generating part that generates ultrasonic vibration, an ultrasonic vibration transmission expanding part that transmits the ultrasonic vibration generated in the ultrasonic vibration generating part while expanding it, and an ultrasonic wave expanded by the ultrasonic vibration transmitting expanding part. The sample is provided with a sample vibration vibration unit that vibrates the liquid sample by vibration to form minute droplets of the liquid sample, and a sample supply unit that continuously supplies the liquid sample to the sample vibration vibration unit. A liquid film forming member capable of holding the liquid sample supplied from the sample supply unit in the form of a liquid film is provided on the vibrating vibration surface of the vibration and vibration unit.

Further, the analyzer of the present invention is an analyzer provided with the above-mentioned microdroplet forming apparatus of the present invention.

A more specific configuration of the present invention is described in the claims.

According to the above configuration, it is possible to provide a microdroplet forming device and an analyzer capable of dividing even a small amount of liquid sample separated by liquid chromatography into fine droplets having an average particle size of several μm.

Issues, configurations and effects other than those described above will be clarified by the explanation of the following embodiments.

Schematic diagram showing an embodiment of the microdroplet forming apparatus of the present invention The figure which shows the detail of the part A (vibration vibration surface) of FIG. The figure which shows an example of the structure of a sample vibration vibration part. The figure which shows the other example of the structure of the sample vibration vibration part. The figure which shows the other embodiment of the structure of the microdroplet forming member. The figure which shows the other embodiment of the liquid film forming means of the microdroplet forming member. The figure which shows an Example of the analysis apparatus which used the microdroplet forming apparatus of this invention. The figure which shows the other embodiment of the analyzer using the microdroplet forming apparatus of this invention.

[Microdroplet forming device]
Hereinafter, the microdroplet forming apparatus of the present invention will be described in detail. FIG. 1 is a schematic diagram showing an embodiment of the microdroplet forming apparatus of the present invention. As shown in FIG. 1, the microdroplet forming apparatus 1 has an ultrasonic vibration generating unit 8 that generates ultrasonic vibration and an ultrasonic vibration that is transmitted while expanding the ultrasonic vibration generated by the ultrasonic vibration generating unit 8. Transmission expansion unit 9 and ultrasonic vibration Sample vibration vibration unit 3 and sample vibration vibration unit 3 that vibrate the liquid sample with the ultrasonic vibration expanded by the transmission expansion unit 9 to form minute droplets of the liquid sample. Is provided with a sample supply unit 40 for continuously supplying a liquid sample.

The microdroplet forming apparatus of the present invention forms microdroplets on the supplied liquid sample by utilizing ultrasonic vibration. In the present invention, the "fine droplet" means a droplet having an average particle size of several tens of μm to several μm. In the embodiment of the present invention shown in FIG. 1, a piezoelectric element is used as the ultrasonic vibration generator 8. In the formation of minute droplets using ultrasonic vibration, the formed droplet diameter is affected by the vibration frequency, and the relationship between the vibration frequency and the droplet diameter is generally the Lang formula (J. Acous. It is known to follow Soc. Amer., 1962, 34, 6). The relationship between the vibration frequency and the droplet diameter is also affected by the solvent type. In the liquid sample used in the analyzer of this example, water or alcohol mainly used is used as a solvent. In this case, the vibration frequency for forming a droplet having a diameter of 10 μm is about 200 to 300 kHz, and the vibration frequency for forming a droplet having a diameter of 1 to 3 μm is several MHz.

In order to perform analysis with an analyzer, it is necessary to form droplets with a droplet diameter of several tens of μm to several μm. Therefore, the vibration frequency for forming the droplets for the analyzer needs to be about several hundred kHz to 10 MHz. In this embodiment, the configuration as a microdroplet forming apparatus for a liquid chromatography mass spectrometer will be described. In the liquid chromatography mass spectrometer, samples continuously supplied from liquid chromatography are continuously analyzed by the mass spectrometer. The amount of the sample liquid, which is each sample, varies to some extent depending on the specifications of liquid chromatography. Further, it is said that it is desirable that the droplet diameter of the initial droplets formed in the atmosphere from the liquid sample is small, and it is desirable that the average particle size is about several μm. In this example, it is assumed that the liquid volume of each sample liquid is several hundreds to several tens of μL or less, and the droplet diameter of the initial droplets formed in the atmosphere is several μm. In order to make the droplet diameter of the initial droplet formed from the sample liquid several μm, the vibration frequency of the ultrasonic vibration generator 8 in this embodiment was set to 2.4 MHz.

Further, a liquid was used as the ultrasonic vibration expansion transmission unit 9 of this embodiment. As a vibration expanding means, as a method generally widely used, there is a method of utilizing a resonance phenomenon in a metal columnar member, a diaphragm structure, or the like. However, when the resonance phenomenon of the metal columnar member is used, it is necessary to shorten the length of the columnar structure to be used to resonate as the frequency increases. When the resonance of a metal columnar member is used, the limit is about several hundred kHz in a realistic dimensional range. The length of the metal columnar member for resonating at several 100 kHz is as short as 1 cm or less, and it is difficult to use it as a stable resonance member. As for the diaphragm structure, it is practically difficult to realize a resonance structure exceeding several hundred kHz.

Therefore, in this embodiment, a structure using a liquid is used to expand and transmit high-frequency vibration of 2.4 MHz. In the microdroplet forming apparatus of this embodiment, as shown in FIG. 1, the sample vibrating vibration unit 3 was arranged facing the ultrasonic vibration generating apparatus 8 and the space between them was filled with a liquid. The sample vibration vibration unit 3 was arranged at a distance where the vibration generated by the ultrasonic vibration generator 8 is transmitted through the ultrasonic vibration transmission expansion unit 9 which is a liquid and is focused, that is, at a position where the vibration expands. With such a structure, the ultrasonic vibration generated by the ultrasonic vibration generator 8 can be expanded and transmitted, and the sample vibration vibration unit 3 can be greatly ultrasonically vibrated.

Further, in the present embodiment shown in FIG. 1, a vibration transmission liquid supply pipe 6 and a vibration transmission liquid discharge pipe 7 are provided in a case portion that holds the ultrasonic vibration transmission expansion portion 9 of the liquid. The liquid is sent from the liquid supply unit 41 to the ultrasonic vibration transmission expansion unit 9 through the vibration transmission liquid supply pipe 6, and is discharged from the vibration transmission liquid discharge pipe 7.

The piezoelectric element used in the ultrasonic vibration generator 8 used to generate ultrasonic vibration in the present invention generates heat when vibration is generated. If the temperature of the piezoelectric element rises due to the generated heat, there is a risk that the exciting force will decrease or the piezoelectric element will be destroyed. Therefore, in this embodiment, the vibration transmission liquid supply pipe 6 and the vibration transmission liquid discharge pipe 7 are provided in the case portion that holds the ultrasonic vibration expansion transmission unit 9.
Then, the vibration expansion transmission liquid is circulated using the vibration transmission liquid supply pipe 6 and the vibration transmission liquid discharge pipe 7 using a liquid pump (not shown), and is cooled by using a heat exchanger (not shown). did. Since the vibration expansion transmission liquid comes into direct contact with the piezoelectric element which is an ultrasonic vibrator, it is possible to prevent the temperature rise of the piezoelectric element by cooling the vibration expansion transmission liquid.

The vibration transmission state in the liquid is affected by the viscosity, surface tension and density of the vibration expansion transmission liquid used. Therefore, it is necessary to appropriately design the distance between the ultrasonic vibration generator 8 and the sample vibration vibration unit 3 as described above according to the physical properties of the selected vibration expansion transmission liquid. Further, in this embodiment, pure water is used as the vibration expansion transmission liquid from the viewpoint of being used for cooling the piezoelectric element and safety in case of leakage. However, it goes without saying that various liquids other than pure water can also be used as the vibration expansion transmission liquid of the present invention by performing the liquid in consideration of the above and the dimensional design according to the liquid.

FIG. 2 is a diagram showing details of the A portion (vibration vibration surface) of FIG. The sample vibration vibration unit 3 of this embodiment has a diaphragm 11 constituting the sample vibration vibration unit 3 and a liquid film forming member 12a, and a flow path layer 13 to which a liquid sample is supplied is provided between the diaphragms 11 and the liquid film forming member 12a. Have. The diaphragm 11 is a diaphragm 11 that comes into contact with the vibration transmission liquid and vibrates by the ultrasonic vibration 10 transmitted in the vibration transmission liquid. The ultrasonic vibration 10 transmitted through the liquid is configured to be focused by a part of the diaphragm 11.

The liquid sample 2 supplied through the flow path layer 13 formed between the thin plates is guided to the focal position of the diaphragm 11 and is vibrated and atomized by the vibration of the diaphragm 11. A large number of holes are formed in the upper thin plate 12a at a position facing the focal position of the diaphragm, and droplets of the atomized liquid sample pass through these holes toward the upper part of the figure and are minute liquids. It becomes droplets and is atomized and ejected.

The structure of the sample vibration vibration unit 3 described above is a very important structure in the present invention.
Generally, when a small amount of liquid is directly supplied onto a vibrating surface that vibrates ultrasonically, a part of the liquid becomes minute droplets and atomizes, but most of the liquid scatters. This is a major factor that makes it difficult to use ultrasonic waves for making fine droplets of a liquid sample in an analyzer. Since the liquid sample in the analyzer is very valuable and often in a small amount, it is a big problem in forming fine droplets by ultrasonic waves.

The present invention proposes a method capable of forming a liquid film on a vibrating surface that vibrates ultrasonically even with a small amount of liquid. Then, by stably atomizing and atomizing a small amount of liquid sample using ultrasonic vibration, it is possible to provide a new microdroplet forming device that can be supplied to the analyzer and an analyzer having the new microdroplet forming device. I am aiming.

The cause of the scattering phenomenon when a small amount of liquid is supplied on the ultrasonic vibration surface is considered as follows. When the amount of liquid supplied on the vibrating surface is small, it tends to become a liquid ball due to the surface tension of the sample liquid itself. The liquid that has become a liquid ball scatters due to vibration. It has been experimentally confirmed that alcohol, which has a lower surface tension than water, scatters less. However, even a small amount of alcohol cannot completely prevent scattering.

If a liquid film can be formed on the vibrating surface that has been ultrasonically vibrated, stable atomization can be achieved even with a small amount of liquid. Focusing on this point, the present invention has been made.

As a method of forming a liquid film on the vibrating surface with a small amount of liquid, a method of hydrophilically treating the vibrating surface can be considered. According to the experimental results, a certain effect was confirmed, but it was difficult to obtain a sufficient anti-scattering effect only by the hydrophilic treatment. Therefore, in the present invention, we have devised a configuration in which the liquid film forming member is arranged close to the vibrating surface. The thin plate 12a arranged to face the diaphragm 11 of FIG. 2 corresponds to the liquid film forming member of the present invention. The thin plate 12a is provided with a multi-hole portion at a position facing the focal position of the diaphragm shown in FIG. 3, which will be described later. With such a structure, it is possible to stably form a liquid film on the diaphragm even with a small amount of liquid sample supplied on the vibrating surface.

Also, by using the above-mentioned structure, it is possible to almost completely prevent the scattering of the liquid sample. Further, since the effect of restricting the ejection direction of the formed fine droplets is also produced, the spraying direction of the atomized fine droplets is also stable. The spraying direction coincides with the vibration direction of the diaphragm. In FIGS. 1 and 2, it is ejected upward (in the direction of the arrow in FIG. 2).

FIG. 3 is a diagram showing an example of the structure of the vibrating vibration unit. The sample vibration vibration unit 3 of this embodiment is composed of three thin plate materials shown in the figure. In the figure, the lowermost thin plate is the diaphragm 11, the central thin plate is the flow path plate 16, and the uppermost thin plate is the multi-hole plate 12a. The vibrating and vibrating portion of the present invention is configured by stacking and adhering these three thin plates. As a method of adhering three thin plates, a method using an adhesive or the like can also be used, but in consideration of the influence of the adhesive and the adhesive strength, in this embodiment, each thin plate is overlapped and a high pressure is applied. However, by using a diffusion bonding method that can bond each thin plate at the atomic level by raising the temperature to a high temperature, bonding integration was performed. Further, as the material of the plate material of this example, SUS316 was used in consideration of corrosion resistance and the like. It is necessary to select an appropriate material and bonding method for the plate material to be used in consideration of the physical properties against vibration and the liquid sample to be used.

The lowermost diaphragm 11 is in contact with the vibration transmission liquid of the ultrasonic vibration expansion transmission unit 9 on the lower side, and is vibrated by the ultrasonic vibration 10 transmitted through the vibration transmission liquid. Since the diaphragm 11 is required to vibrate by the ultrasonic vibration 10 transmitted in the vibration transmission liquid, flexibility and elasticity are required. In this embodiment, the thickness of the SUS of the diaphragm 11 is reduced to 50 μm to facilitate vibration.

The portion of the diaphragm 11 that is vibrated is the portion where the ultrasonic vibration is focused. The position of the vibrating focal point and its diameter are, of course, dependent on the design conditions. In this embodiment, it is designed so as to be within the range of the alternate long and short dash line (diameter several mm) in the figure even when the assembly accuracy is taken into consideration. The diameter of the vibration focal point in this embodiment is about 1 mm. That is, the diaphragm 11 vibrates in a region having a diameter of about 1 mm at any place in the alternate long and short dash line due to the ultrasonic vibration transmitted through the vibration transmission liquid.

The central flow path plate 16 is provided with a hole having the shape shown in the figure. The round portions 19 located at both ends are a supply hole and a discharge hole for the liquid sample, and are connected to the sample supply pipe 2 and the sample discharge pipe 5, respectively. The large round portion 17 in the center coincides with the region where the diaphragm 11 may vibrate. The slit portion 18 formed so as to connect the supply hole and the discharge hole of the liquid sample is sandwiched between the diaphragm 11 and the multi-hole plate 12a at the top and bottom, so that the flow path (flow path layer 13 in FIG. 1) is formed. To form. The liquid sample 2 supplied from the supply hole is sent to the large round portion 17 in the center through this flow path, and is made into minute droplets by the vibration of the diaphragm. The excess liquid sample, which is not a minute droplet, is configured to be discharged from the discharge hole through the flow path on the opposite side. Since the cross-sectional area of the flow path is determined by the thickness as well as the opening width of the flow path plate, it is necessary to select an appropriate plate thickness. Considering the ease of handling and the cross-sectional area of the flow path, it is generally appropriate to use several tens to several hundreds of μm. In this example, a plate thickness of 100 μm was used.

The uppermost multi-hole plate 12a has a pair of round holes 15 at both ends and a region 14 having a large number of holes formed in the center. The round holes 15 at both ends are holes for supplying and discharging the liquid sample to the flow path plate 16, and are adhered so as to coincide with the round portions 19 located at both ends of the flow path plate 16. The region 14 having a large number of holes formed in the central portion coincides with the region that may vibrate, which is indicated by the alternate long and short dash line on the diaphragm 1. The liquid sample supplied to the large round portion 17 in the center of the flow path plate 16 is vibrated by the vibration of the diaphragm 11, and the formed minute droplets are discharged through the central hole of the multi-hole plate 12a. To.

In order to improve the liquid flow in the flow path and facilitate the formation of a liquid film in the multi-hole plate 12a portion, in the flow path or in the hole 14 for ejecting droplets of the multi-hole plate (liquid film forming member) 12a. It is desirable that the inner surface be treated with hydrophilicity. However, it is desirable that the outer surface of the multi-hole plate (liquid film forming means) 12a is treated with water repellent as a countermeasure against contamination.

By configuring the sample vibration vibrating unit 3 as described above, it is possible to stably form a liquid film on the diaphragm even with a small amount of liquid sample, and it is possible to realize stable formation of fine droplets.

FIG. 4 is a diagram showing another example of the structure of the vibrating vibration part. The opening does not necessarily have to be composed of a large number of circular holes 14 (a) as in FIGS. 3 and 4a), and is a slit-shaped opening hole as in FIGS. 4 (b) and 4 (c). Similar effects can be expected with the opening holes 14d having a deformed shape or a combination shape as shown in 14b and c and FIG. 4D. However, in order to form a liquid film on the diaphragm and prevent scattering, it is necessary to select an appropriate opening diameter and opening width. In the microdroplet forming apparatus 1 in the embodiment of the present invention described with reference to FIGS. 1 to 3, the diameter of the opening hole is set to 150 μm. According to the experiment, the opening diameter and opening width for preventing the scattering of water and alcohol were 1 mm or less, but it was necessary to make them several hundred μm or less in consideration of stability.

Further, if the position of the vibration focus of the diaphragm can be accurately positioned, the area of the portion 17 that widens the flow path 21 near the focus position can be reduced. Needless to say, the smaller the partial area that widens the flow path 21 near the focal position, the smaller the sample solution can be sprayed. If the design is such that the vibration focus can be completely positioned on the flow path 21, even a single slit opening as shown in FIG. 4 (e) or a single spray hole as shown in FIG. 4 (f) can be used. It is also possible to obtain the same effect.

In the embodiment described with reference to FIGS. 1 to 4, at least a part of the liquid sample supplied on the vibrating plate is atomized and sprayed into fine droplets, and the unatomized liquid sample is placed in the sample discharge pipe 5. It is configured so that it can be discharged. However, when the vibrating force of the diaphragm is sufficiently large with respect to the amount of the supplied liquid sample, it is possible to atomize all of the supplied sample liquid as fine droplets. In this case, the sample discharge pipe 5 for the surplus liquid sample becomes unnecessary. In fact, even in the microdroplet forming apparatus 1 in the embodiment of the present invention shown in FIG. 1, it was possible to atomize all the supplied sample liquid 2 so as not to discharge it to the sample discharge pipe 5. When all the sample liquid supplied to the vibrating portion is atomized and sprayed, the structure of the microdroplet forming portion of the present invention can be simplified.

FIG. 5 is a diagram showing another embodiment of the structure of the microdroplet forming member, and is the other of the liquid film forming means 12 of the present invention that can be used when all the sample liquid supplied to the vibrating portion is atomized and sprayed. It is a figure explaining the Example of. In the structure shown in the figure, a small multi-hole plate (liquid film forming member) 12b is provided at the tip of the sample liquid supply pipe 22. This is configured to be placed close to the vibration focal position of the diaphragm 11. The sample liquid supplied from the supply pipe 22 is configured to be supplied to the lower side of the multi-hole plate (liquid film forming member) 12b. The sample liquid supplied to the lower side of the multi-hole plate (liquid film forming means) 12b spreads in the minute gap region between the multi-hole plate (liquid film forming member) 12b and the diaphragm 11 by a capillary phenomenon to form a liquid film. Form. Then, it can be ejected as minute droplets from the opening hole 14 provided in the multi-hole plate (liquid film forming member) 12b by the vibration of the diaphragm 11.

Of course, the shape of the opening hole 14 in the multi-hole plate (liquid film forming member) 12b in which the liquid film is provided on the diaphragm 11 is in addition to the circular hole (FIG. 4A) as described with reference to FIG. It is also possible to use a slit shape (FIGS. 4 (b) and (c)) and various shapes obtained by deforming or combining them (FIG. 4 (d)). Further, the higher the accuracy of the focal position of the diaphragm, the smaller the area of the liquid film forming member 12 such as the multi-hole plate arranged at the tip of the sample liquid supply pipe 22, and the smaller the amount of sample liquid. It becomes possible to correspond to.

In the structure of the present invention in which the liquid film forming member 12 such as a multi-hole plate is arranged close to the diaphragm 11, the gap between the vibrating plate 11 and the liquid film forming member 12 such as the multi-hole plate is vibrated. It affects the formation state of minute droplets at the time. In particular, if the gap is wide and the liquid film becomes too thick, the efficiency of forming fine droplets drops sharply. Therefore, it is required that the minute gap formed between the liquid film forming member 12 such as the multi-hole plate and the diaphragm 11 is sufficiently narrow and stable, and the gap is constant.

In the case of the diaphragm 11 and the multi-hole plate 12a for forming a liquid film described with reference to FIGS. 1 to 4, it is easy to keep the gap between them constant because they are integrally molded. However, as in the embodiment of FIG. 5, a small multi-hole plate (liquid film forming member) 12b is provided at the tip of the sample liquid supply pipe 22, and the diaphragm 11 and the multi-hole plate (liquid film forming member) 12b are provided. It is difficult to make the gap between the two with high accuracy.

Therefore, in the case of a configuration in which a small multi-hole plate 12b is provided at the tip of the sample liquid supply pipe 22 as in the embodiment of FIG. 5, in this embodiment, the multi-hole plate (liquid film forming means) 12b is the diaphragm 11. We adopted a structure (not shown) that can be placed on top of it. The structure to be placed is a state in which the multi-hole plate (liquid film forming means) 12b and the diaphragm 11 are in contact with each other under a weak pressure. Such a structure can be easily realized as compared with the case of designing a structure that guarantees the clearance accuracy. Further, by arranging the multi-hole plate (liquid film forming means) 12b so as to imitate the diaphragm 11, the structure for maintaining the gap between the diaphragm 11 and the multi-hole plate (liquid film forming means) 12b with high accuracy. Is no longer necessary. If the structure in which the multi-hole plate (liquid film forming means) 12b is placed on the diaphragm 11 with a weak force is used, the sample liquid can be supplied between the multi-hole plate (liquid film forming means) 12b and the diaphragm 11. This makes it possible to form a minute and uniform gap between the multi-hole plate (liquid film forming means) 12b and the diaphragm 11.

FIG. 6 is a diagram showing another embodiment of the liquid film forming means of the microdroplet forming member, and is a diagram illustrating another embodiment of the liquid film forming means 12 on the diaphragm 11. As described above, by forming the sample liquid supplied on the diaphragm into a liquid film on the diaphragm 11, it is possible to prevent scattering during vibration. In the examples up to FIG. 5, a method of arranging a thin plate (liquid film forming member) 12 having holes and slits formed on the diaphragm 11 is disclosed. As the liquid film forming means 12 for forming the liquid film on the diaphragm 11, a rod-shaped member 23 such as (a) fork-shaped, (b) antenna-shaped, or (c) simple rod-shaped as shown in FIG. 6 is used as a sample liquid. Even in a configuration in which the liquid film is attached to the tip of the supply pipe 22 and arranged on the diaphragm, the same effect as that of the liquid film forming means 12 using the thin plate described in the examples up to FIG. 5 can be obtained. This method is a method of forming a liquid film by utilizing the wettability of the rod-shaped member, and the configuration can be made extremely simple. The wettability to the sample liquid is also important in the liquid film forming means on the thin plate shown in FIG. 5 and the like, but it is even more important in the liquid film forming body using the rod-shaped member of FIG. As a method of ensuring the close contact state between the rod-shaped member 23 and the diaphragm 11, the method of bringing the rod-shaped member 23 into contact with the diaphragm with a weak pressure described in the embodiment of FIG. 5 can also be used.

FIG. 7 is a diagram showing an embodiment of an analyzer using the microdroplet forming apparatus of the present invention, and FIG. 8 is a diagram showing another embodiment of the analyzer using the microdroplet forming apparatus of the present invention. Is. It is a figure explaining one Example of the analyzer using the microdroplet forming apparatus of this invention. The figure is an example for a liquid chromatography mass apparatus in which the microdroplet forming apparatus of the present invention is arranged. The configuration of the embodiment will be described below.

7 and 8 show a liquid chromatography mass spectrometer as an analyzer. The microdroplet forming apparatus 1 of the present invention, a droplet charging unit (droplet charging unit 28) that applies a charge to microdroplets to generate microcharged droplets, and drying for drying and ionizing the microcharged droplets. It is provided with an ion source (ion generation unit 33) having a unit and a detection unit (mass spectrometer 32) that introduces ions formed by the ion source and separates and detects each mass-to-charge ratio.

In the microdroplet forming apparatus 1 using the ultrasonic vibration of the present invention, the vibration transmission liquid supply pipe 6 for circulating and cooling the liquid, which is the ultrasonic vibration expansion transmission unit 9, the vibration transmission liquid discharge pipe 7, and the liquid The sample liquid supplied from the liquid chromatography is squeezed by connecting the sample liquid supply tube 2 supplied from the chromatography and the sample discharge tube 5 to discharge the surplus sample liquid and vibrating the ultrasonic vibration generator 8. Spray as fine droplets. A nitrogen supply unit 26 is arranged directly above the spray surface of the microdroplet forming apparatus 1. Nitrogen is supplied to the nitrogen supply unit 26 from the nitrogen supply pipe 24, and the microdroplets 4 sprayed from the microdroplet forming device 1 are sprayed into a pipe filled with nitrogen at a substantially atmospheric pressure. It is configured. The microdroplets 4 generated by the microdroplet forming apparatus 1 of the present invention are conveyed to the upper 34 in the figure by the spray rate and the flow of nitrogen supplied from the nitrogen supply unit 26.
The initial spray rate of the minute droplets generated by the minute droplet forming apparatus 1 of the present invention is about several m / s or less to several tens of m / s, and the amount of nitrogen supplied is also the same as the flow velocity and in the pipe. Controls the amount of nitrogen supplied so that it can maintain almost atmospheric pressure.

A droplet initial heating unit 27 is connected above the nitrogen supply unit 26. The droplet initial heating unit 27 heats the minute droplets with the heating heater 30 arranged on the wall surface, and vaporizes and removes the solvent of the minute droplets. In this embodiment, the inside of the induction tube of the minute droplets is filled with nitrogen in order to prevent combustion from occurring when the minute droplets are heated by a heater or the like. That is, a gas that can prevent combustion, such as an inert gas other than nitrogen, may be used.

A droplet charging unit 28 is connected above the droplet initial heating unit 27, and is configured to impart positive ions or electrons generated by the ion generation unit 33 to the sample droplets. As the ion generation unit 33, a general corona discharger or the like can be used.

A droplet acceleration unit 29 is configured above the droplet charging unit 28. The droplet acceleration unit 29 accelerates the velocity of the sample liquid by gradually reducing the diameter of the pipe. In the apparatus configuration of this embodiment, the tube diameter from the nitrogen supply unit 26 to the droplet charging unit 28 via the initial heating unit 27 is set to a diameter of about 25 mm. In the droplet acceleration unit 29, the tube diameter of about 25 mm in diameter is gradually narrowed by 500 μm in diameter. That is, the pipe cross-sectional area ratio between the inlet and the outlet of the droplet acceleration unit 29 is 2500: 1. As a result, the sample droplets sent at a speed of several m / s to several tens of m / s accelerate to the speed of sound or higher at once.

Above the droplet acceleration unit 29, an analyzer connection unit 31 to the mass spectrometer 32 is arranged. The analyzer connection unit 31 is an elongated thin tube having a diameter of 500 μm, and by connecting the droplet acceleration unit 29 and the mass spectrometer 32, the pressure gradient of the mass spectrometer 32 having an atmospheric pressure spray pipe and a vacuum pressure inside. Is configured to absorb and hold.

A heating heater 30 is also installed in the piping portion of the droplet acceleration unit 29 and the analyzer connection unit 31, and is configured to heat the sample droplets being transported and remove the solvent. For the sample droplets charged by the droplet charging unit 28, the solvent is removed by the droplet acceleration unit 29 and the analyzer connecting unit 31, and the sample components contained in the sample liquid are ionized to the mass analyzer 32. Will be supplied. In the mass spectrometer 32, the supplied sample ions are separated by mass, and the component features contained in the sample are identified.

The method of applying a charge to the sample droplets from which the solvent has been largely removed by heating with the droplet initial heating unit 27 is the atmospheric pressure ionization method (APCI) in the current liquid chromatography mass spectrometry method. : Atmospheric Pressure Chemical Ionization) corresponds to the method. In the current liquid chromatography mass spectrometry method, in addition to the atmospheric pressure ionization method, an electrospray ionization (ESI) method is widely known, and it is selected according to the strength of the polarity of the sample to be analyzed. Is common. In the current liquid chromatography mass analysis method, in the electrospray ionization method, when the sample liquid is made into a minute liquid by using the ultra-high speed air spray method, a voltage is applied to the nozzle of the air spray to apply an electric charge to the nozzle tip. Is a method of applying an electric charge to the torn liquid by causing the sample liquid to be torn into minute droplets in the electric field.

Even when the microdroplet forming apparatus of the present invention is used, it is possible to charge the droplets by a method corresponding to the electrospray ionization method. In order to charge the droplets by a method equivalent to the electrospray ionization method, it is necessary to generate an electric field in the region where the sample liquid is separated into the droplets. In order to realize this, it is necessary to configure either one of the liquid film forming means 12 such as the diaphragm 11 or the multi-hole plate with a conductive member. Also in the previous embodiment, since the conductive SUS316 is used as the material of the diaphragm 11 and the liquid film forming means 12, the droplets formed by applying a high voltage of about several kV to 10 kV to the conductive SUS316 are used. It is possible to add a charge to. The amount of charge applied to the formed droplets is proportional to the applied voltage level, and the polarity matches the polarity of the applied voltage. Since the amount of electric charge generated in the droplet forming portion is affected by the strength of the electric field, the position of the electrode serving as the counter electrode is important as well as the voltage applied to the diaphragm 11 and the liquid film forming means 12. In the configuration of the embodiment of FIG. 7, the mesh plate of the nitrogen spray port of the nitrogen supply unit 26 is made of metal, and by setting the installation potential, the diaphragm 11 to which a voltage is applied and the counter electrode of the liquid film forming means 12 are used. Made it work.

Next, an embodiment of a method of applying a high voltage to the diaphragm 11 and the liquid film forming means 12 of the microdroplet forming apparatus of the present invention will be described. In the embodiment of the present invention described above with reference to FIG. 1, pure water is used as the vibration transmission liquid. Since pure water has conductivity, the diaphragm 11 that comes into contact with the vibration transmission liquid and the piezoelectric element that is an ultrasonic vibration means for applying ultrasonic vibration to the vibration transmission liquid 9 are in a state of being electrically connected. ..

Therefore, a high voltage is superimposed on the base potential of the drive circuit (not shown) that generates the drive waveform of the piezoelectric element of the microdroplet forming apparatus of this embodiment. By doing so, the piezoelectric element is driven with a high voltage as a base voltage. As a result, the diaphragm 11 and the liquid film forming means 12 also have a high voltage through the pure water which is the vibration transmitting liquid 9. When the drive circuit structure of the piezoelectric element of this embodiment is used, the amount of electric charge given to the formed droplets by varying the voltage and polarity of the base potential of the drive circuit that generates the drive waveform of the piezoelectric element. And the polarity can be freely controlled.

In the above embodiment, since pure water having conductivity is used as the vibration transmission liquid, a high voltage is superimposed on the base potential of the drive circuit that generates the drive waveform of the piezoelectric element. However, in this method, the drive circuit becomes complicated, there are many parts where a high voltage is applied, and the circulated pure water itself is also given a high voltage. Therefore, from the viewpoint of ensuring insulation and safety, it is not always necessary. It is hard to say that it is a preferable high voltage application method. The following other examples are also conceivable as a method of imparting an amount of electric charge to the formed droplets.

By using an insulating liquid as the vibration transmission liquid and making the holding portion of the diaphragm 11 and the liquid film forming means 12 insulating, the portion to which a high voltage is applied is the diaphragm 11 and the liquid film forming means 12. Since it can be limited, it becomes easier to ensure safety. In addition, the drive circuit of the piezoelectric element can be made very simple as compared with the method of superimposing the high voltage base power supply of the drive circuit of the piezoelectric element.

Several insulating liquids are known, including various insulating oils used in transformers and the like. However, the transmission characteristics of ultrasonic vibration are significantly different from those of water, and it is necessary to design according to the characteristics. In addition, it is necessary to select the piezoelectric element in consideration of its function as a cooling medium, safety, and ease of handling. Pure water was selected as the vibration transmission liquid in the examples of the present invention because of its safety and ease of handling.

When the microdroplet forming apparatus of the present invention is used for a liquid chromatography mass spectrometer, etc., prevention of contamination is an important item to be considered. Hereinafter, measures for preventing contamination in the present invention and examples will be described. In the liquid chromatography mass spectrometer, the sample liquid to be analyzed by the mass spectrometer is sequentially sent from the liquid chromatography. Although it is an example of the amount and speed of the sample liquid to be sent, the liquid amount of each sample liquid is about several hundred μL to several tens of μL, and the speed of being sent is about several 100 μ / min. That is, it is required that different sample liquids are sent one after another within a few seconds to one minute, and the sample liquids are continuously made into fine droplets and sent to the analyzer. During that time, it is very important to prevent contamination between the sample liquids that are continuously sent one after another in order to carry out accurate analysis.

Even one embodiment of the present invention shown in FIG. 1 has a structure in consideration of prevention of some contamination. These will be described below.

In one embodiment of the present invention shown in FIG. 1, by providing the sample discharge tube 5 together with the sample liquid supply tube 2 from liquid chromatography, the surplus sample liquid that could not be made into fine droplets is sent out to the discharge tube side. It was configured. Further, as disclosed in FIGS. 2 and 3, thin plates are overlapped to form a flow path, so that the sample liquid is supplied through an extremely narrow flow path to prevent contamination. However, in the flow path structure shown in FIG. 3, a region 17 in which the flow path is widened is provided from the viewpoint of alignment with the focal position of ultrasonic vibration, but in order to prevent contamination, ultrasonic vibration is provided. It is important to improve the design system of the focal position and minimize the spread of the flow path. Further, it is also important to reduce the cross-sectional area of the flow path by reducing the thickness of the flow path plate 16 in FIG. 3b) in order to prevent contamination.

Furthermore, it is also possible to prevent contamination by vibrating the supplied sample liquid with sufficient margin so that all the supplied liquid can be atomized and discharged as fine liquid with a margin. It is important on the above. If the conditions under which the supplied sample liquid can be completely atomized can be realized, the sample discharge pipe 5 becomes unnecessary.

As another method for preventing contamination between continuously sent sample liquids, a method of sandwiching a known gas or liquid as a buffer between the sent samples may be used. By sandwiching a known gas or liquid as a buffer, it becomes easy to prevent contamination between liquids as known in pipes and atomized parts, and dimensional restrictions on the flow path and the like are relaxed. However, this method has problems that the efficiency of analysis is lowered by the amount of the gas or liquid used as the buffer region, and the gas or liquid used as the buffer liquid is consumed.

As another method to prevent contamination, there is also a method of providing a cleaning process for piping and spray areas. This is a method of incorporating a sequence for cleaning the supply pipe, the vibrating part, etc. for each predetermined number of analyzes and analysis time. If the cleaning sequence is performed when the device is started or stopped, the analysis efficiency can be suppressed. If necessary, a method of operating the washing sequence is also conceivable.

It is necessary to determine the cleaning timing and the level of countermeasures in consideration of the risk of contamination and the effect on analysis efficiency, including the measures against sandwiching the gas or liquid used as a buffer area between the supplied sample liquids. ..

As a method for cleaning the piping and the spray region of this embodiment, a simple method is to add a known cleaning liquid instead of the sample liquid to be analyzed and apply ultrasonic vibration. Ultrasonic vibration can be expected to be effective in cleaning pipes and the like.

Further, the tip of the supply pipe 22 shown in FIGS. 5 and 6 is compared by laminating the thin plates shown in FIG. 3 and comparing the composition ratio in which the diaphragm 11, the flow path plate 16 and the multi-hole plate 12 are integrated. The structure in which the multi-hole plate 12b for forming the liquid film and the rod-shaped member 23 are arranged is a simple structure and easy to disassemble and clean. Of course, it is also effective as a pollution control measure to periodically replace each supply pipe 22 having a liquid film formation at the tip.

Also in the case of the embodiment of the integrated structure of the diaphragm 11, the flow path plate 16, and the multi-hole plate 12 described with reference to FIGS. 1 to 3, there is a risk that clogging in a thin pipe or the like may occur along with contamination. As a countermeasure against this, it is desirable that the sample vibration vibration unit 3 of the integrated structure of the diaphragm 11, the flow path plate 16 and the multi-hole plate 12 also has a structure that is easy to replace. Further, a method of defining and operating the replacement cycle of parts that are prone to contamination or clogging is also effective as a contamination prevention measure in the microliquid machine forming means of the present invention.

In the embodiment of FIG. 7, regarding the contamination in the pipe until the sample droplet after the formation of the fine droplet is conveyed to the analyzer, the heater 30 is arranged in each part in the pipe path, and the pipe wall surface is covered. Due to the high temperature, the attached sample components are decomposed by heat. As a result, in the embodiment of the analyzer to which the microdroplet forming apparatus of the present invention shown in FIG. 7 is applied, the contamination in the transport / processing path of the sample droplet between the microdroplet forming apparatus and the analyzer is described. Careed so that it would hardly be a problem.

In the embodiment described with reference to FIG. 7, a configuration example is shown in which the droplet forming apparatus 1 of the present invention is arranged on the lower side and the droplets formed upward are sprayed. However, the spraying direction of the microdroplet forming apparatus 1 of the present invention is hardly affected by the gravitational direction. FIG. 8 is an example of an arrangement configuration up to the mass spectrometer when the microdroplet forming apparatus 1 of the present invention is arranged upside down and the microdroplets are sprayed downward.

Currently, the microdroplet formation method using high-speed air spray, which is widely used in liquid chromatography mass analyzers, produces microdroplets by applying a very high-speed air flow to the supplied sample droplets. , The flying speed of the generated droplets is very fast, and some of them reach the speed of sound. However, the flying speed of the fine droplets ejected by the fine droplet forming means of the present invention is very slow, ranging from several m / s or less to several tens of m / s. Therefore, it is possible to control the flight direction of the formed droplets by using a gentle air flow.

In the configuration of the embodiment of FIG. 8, the microdroplets sprayed from the microdroplet forming apparatus of the present invention are configured to give a nitrogen flow from the side surface. Since the sprayed minute droplets are very light, it is possible to sufficiently control the flight direction by using an air flow of about several m / s to several tens of m / s. As in FIG. 7, the minute droplet whose flight direction is changed in the horizontal direction passes through the droplet initial heating unit 27, the droplet charging unit 28, the droplet acceleration unit 29, and the analyzer connection unit 31, and is a mass analyzer. Guided to 32.

As shown in FIG. 8, when the microdroplet forming means of the present invention is arranged upside down, even if a large scattered droplet or the like is generated at the time of atomization, it falls on the mist surface of the microdroplet forming apparatus 1. There is no. Further, even if the cleaning liquid is ejected from the multi-hole plate of the microdroplet forming device for cleaning or the like, the nitrogen flow can be stopped so that the cleaning liquid can be discharged in the direction of gravity. In the embodiment shown in the figure, the water distribution pipe 35 is directed directly below the ejection direction of the microdroplet forming apparatus, and is configured to be able to collect large droplets and cleaning liquid falling from the microdroplet forming apparatus of the present invention. With such a configuration, the risk of contamination in the fine droplet forming portion of the present invention can be further reduced, and the cleaning process can be facilitated.

As described in the examples of FIG. 8, in the microdroplet forming apparatus 1 of the present invention, the microdroplets can be sprayed in any direction, and the sprayed droplets can be freely controlled by a relatively gentle air flow. Therefore, it is possible to correspond to various device configurations connected to the analyzer.

As described above, it has been shown that by using the microdroplet forming apparatus of the present invention, it is possible to stably convert a small amount of sample liquid into microdroplets of several μm with a simple structure. rice field. Further, since it is possible to apply a charge to the formed minute droplets, it can also be used as an ion source for a chromatographic mass spectrometer. Further, the microdroplet forming apparatus of the present invention can spray the microdroplets in various directions and can easily control the transport direction by using the air flow, so that the liquid sample is made into microdroplets. It can also be applied to various analyzers that require.

The present invention is not limited to the above-described embodiment, and includes various modifications.
The above-described embodiment describes the present invention in an easy-to-understand manner, and is not necessarily limited to the one having all the configurations described. Further, it is possible to replace a part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. It is also possible to add / delete / replace a part of the configuration of each embodiment with another configuration.

1 ... Microdroplet forming device, 2 ... Sample supply pipe, 3 ... Sample vibration vibration unit, 4 ... Microdroplet, 5 ... Sample discharge pipe, 6 ... Vibration transmission liquid supply pipe, 7 ... Vibration transmission liquid discharge pipe, 8 ... Ultrasonic vibration generator (piezoelectric element), 9 ... Ultrasonic vibration expansion transmission unit, 10 ... Ultrasonic vibration, 11 ... Vibrating plate, 12 ... Liquid film forming member (multi-hole plate), 13 ... Channel layer, 14 ... hole part, 15 ... round hole, 16 ... flow path plate, 17 ... flow path plate central opening, 18 ... flow path plate slit flow path, 19 ... round part, 20 ... vibration focus can be formed. Region, 21 ... lower flow path of liquid film forming means, 22 ... sample liquid supply pipe, 23 ... rod-shaped member (liquid film forming means), 24 ... (nitrogen) airflow inlet, 25 ... to analyzer Sample ion to be introduced, 26 ... Nitrogen supply unit, 27 ... Droplet initial heating unit, 28 ... Droplet charging unit, 29 ... Droplet acceleration unit, 30 ... Heating heater, 31 ... Analyzer connection unit, 32 ... Mass analysis Equipment, 33 ... ion generation unit, 34 ... transport direction of atomized droplets, 35 ... water distribution pipe.

Claims

The ultrasonic vibration generator that generates ultrasonic vibration and the ultrasonic vibration generator
An ultrasonic vibration transmission expansion unit that transmits the ultrasonic vibration generated in the ultrasonic vibration generation unit while expanding it, and an ultrasonic vibration transmission expansion unit.
A sample vibration vibration unit that vibrates a liquid sample with ultrasonic vibration enlarged by the ultrasonic vibration transmission expansion unit to form minute droplets of the liquid sample, and a sample vibration vibration unit.
The sample vibration and vibration unit is provided with a sample supply unit that continuously supplies the liquid sample.
A microdroplet forming apparatus characterized in that a liquid film forming member capable of holding a liquid sample supplied from the sample supply unit in the form of a liquid film is provided on the vibrating surface of the sample vibrating unit. ..
The liquid film forming member is composed of a plurality of rod-shaped or flat members arranged in parallel with a gap of a predetermined distance from the vibrating vibration surface, and is the vibration direction of the vibration vibration surface. The microdroplet forming apparatus according to claim 1, further comprising at least one opening in a direction perpendicular to the vibrating vibration surface.
The microdroplet forming apparatus according to claim 2, wherein the sample supply unit is configured to sequentially supply a liquid to the gap between the vibrating vibration surface and the liquid film forming member.
3. The microdroplet forming apparatus according to the above.
Any one of claims 1 to 3, wherein the ultrasonic vibration transmission enlarged portion is a columnar member having a vibration transmission length of 10 mm or less or a diaphragm-shaped structure having a thickness of several hundred μm or more. The microdroplet forming apparatus according to.
The microdroplet forming apparatus according to any one of claims 1 to 3, wherein the ultrasonic vibration transmission magnifying unit is filled with a liquid.
At least one of the vibrating vibration surface or the liquid film forming member is composed of a conductive member, and a voltage applying means for applying a voltage to the vibrating vibration surface or at least one of the liquid film forming member is provided.
The microdroplet forming apparatus according to any one of claims 1 to 3, wherein the voltage applying means is configured so that at least one of its polarity and the applied voltage value can be changed.
The drive circuit for ultrasonic excitation is configured to superimpose the excitation means drive AC waveform on the DC bias voltage, and at least one of the polarity or the voltage value of the DC bias voltage can be changed. The microdroplet forming apparatus according to any one of claims 1 to 3, wherein the device is characterized by the above.
A cleaning unit for cleaning the vibrating vibration surface and the liquid film forming member,
Cleaning operation control means for issuing a cleaning operation instruction to the cleaning unit by at least one of operation instructions after a predetermined number of sprays of the fine droplets, after a predetermined spraying time, before spraying start, when spraying is stopped, and from the outside. The microdroplet forming apparatus according to any one of claims 1 to 3, further comprising.
An analyzer comprising the microdroplet forming apparatus according to any one of claims 1 to 3.
The analyzer is a mass spectrometer, and the analyzer is a mass spectrometer.
An ion having a droplet charging portion that charges the microdroplets sprayed by the microdroplet forming device to generate microcharged droplets and a drying portion for drying and ionizing the microcharged droplets. The analyzer according to claim 10, further comprising a source and a detection unit that introduces ions formed by the ion source and separates and detects each of the mass-to-charge ratios.