JP2002214198A - Microinjector and mass spectroscope - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an injector capable of suppressing the reduction in detecting sensitivity and having a long life. SOLUTION: A discharge member 21 constituting this injector is provided with a silicon substrate 1. A through-hole having an inner wall formed by a tubular silicon oxide film 15 with an inside diameter of 50 μm or less is formed in the silicon substrate 1. The silicon oxide film 15 is partially protruded to one surface of the silicon substrate 1. A silicon oxide film 17 is formed on the surface of the silicon substrate 1 where the silicon oxide film 15 is protruded. A water repellent organic thin film 19 is formed on the surface of the silicon oxide film 17. A nozzle 16 is formed by the silicon oxide film 15 of the protruded part and the silicon oxide film 17 and organic thin film 19 formed on the circumference thereof. Ten nozzles 16 are formed on one surface of the silicon substrate 1 and circumferentially arranged at equal intervals.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a microinjector provided with a discharge member for spraying a liquid sample to ionize and introduce the liquid sample into a mass spectrometer, and a mass provided with the microinjector. The present invention relates to an analyzer. Such a mass spectrometer (M
S) is connected to, for example, a high-performance liquid chromatography device (LC) or a capillary electrophoresis device (CE) as a liquid sample supply source, and is used as an LC-MS device or a CE-MS device. LC-MS devices and CE-MS devices are particularly used for separation and detection of trace components, and are widely used for trace component analysis in fields such as medicine, pharmacy, and environmental measurement.

[0002]

2. Description of the Related Art To connect LC or CE to MS, LC
In order to introduce a liquid sample containing trace components separated by CE or CE into the MS, an interface (injector) having a discharge member for spraying the liquid sample is required. As such an injector, an ESI (electron spray ionization) system is mainly used. An ESI type injector sends a liquid sample to the tip of a thin nozzle as a discharge member, and applies a high voltage to the tip of the nozzle to spray the liquid sample as charged droplets. The charged droplet sprayed from the injector is ionized as the droplet progresses due to the Coulomb repulsion of ions in the droplet. Conventionally, in injectors, a single nozzle has been used as a nozzle for spraying a liquid sample.

[0003]

The prior art has the following problems to be improved. 1. When an LC-MS device is constructed by connecting LC and MS via an ESI-type injector, the flow rate of a liquid sample (sample + solvent) separated through a normal-size LC column in LC is several hundred μL (microliter). ) / Min to 1 mL (milliliter) / min. However, when a single nozzle having an inner diameter of 50 to 100 μm, which is usually used in an ESI type injector, is used, there is a problem in that the particle size of the discharged sample varies. This leads to an increase in noise components, which is a factor of lowering the detection sensitivity.

[0004] 2. If the diameter of the nozzle is reduced by reducing the diameter of the nozzle in order to solve the above problem 1, the variation in the particle diameter of the discharged sample can be suppressed. However, as the nozzle diameter becomes smaller, the pressure loss becomes larger, so that the pressure on the delivery side of the separated liquid sample in the LC body increases, which has a problem that the LC body such as a detector may be adversely affected.

The ESI type injector having a single nozzle as a discharge member for spraying a liquid sample has the following problems. 3. The discharge performance of the ESI type injector largely depends on the shape of the tip of the nozzle as a discharge member.
In the conventional injector, since the nozzle tip is constituted by the cut surface of the glass capillary or the metal capillary, it is difficult to manufacture a discharge member with good reproducibility. 4. Since a high voltage is applied to the tip of the nozzle, when used repeatedly, the tip shape changes due to cracking, deformation, evaporation, and the like, and there is a problem that the life is short.

Accordingly, an object of the present invention is to provide an injector which can suppress a decrease in detection sensitivity, improve the reproducibility of measurement results, and has a long life, and a mass spectrometer using the same.

[0007]

A microinjector according to the present invention is a microinjector provided with a discharge member for spraying a liquid sample to ionize and introduce the liquid sample into a mass spectrometer. The discharge member includes a member having a silicon substrate as a base material and a plurality of microtubes having an inner diameter of 50 μm or less formed on one surface of silicon oxide.

[0008] By using a member formed with a plurality of fine tubes having an inner diameter of 50 µm or less as a discharge member of the microinjector, the particle size of the liquid sample to be discharged is reduced and the dispersion of the discharge particle size is reduced. it can.
Further, since a plurality of microtubes are formed, a substantial orifice diameter can be increased, so that the delivery pressure on the liquid sample supply side does not matter. Furthermore, regarding the change in the tip shape when a high voltage is applied, the effective life is increased because many normal nozzles remain even if some nozzles are deformed due to the formation of multiple fine tubes. become longer. Since micromachining technology based on semiconductor manufacturing technology is used, a plurality of microtubes can be processed in a uniform shape with submicron accuracy, and the manufacturing reproducibility is good.

[0009] The microinjector of the present invention is an ES.
In addition to the I method, the present invention can be applied to other ionization methods such as an atmospheric pressure chemical ionization (APCI) method. Here, the APCI method will be briefly described. A needle electrode is arranged in front of a thin tube for discharging a sample liquid, and the liquid sample is discharged from the thin tube while heating the liquid sample, and the liquid sample is atomized. In this method, carrier gas ions (also referred to as buffer ions) generated by corona discharge from a needle electrode to a sample droplet are chemically reacted to be ionized.

[0010] A mass spectrometer according to the present invention comprises the microinjector of the present invention and high electric field generating means for charging a liquid sample sprayed from the microinjector.

According to a method of manufacturing a discharge member for a microinjector according to the present invention, a through hole having an inner wall formed of a silicon oxide film is formed in a silicon substrate, and the silicon substrate is selectively formed from one surface side in a through direction of the through hole. To form a fine tube made of a silicon oxide film.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the microinjector according to the present invention, the discharging member further includes a conductive member at least in a portion where the fine tube is formed on the surface where the fine tube is formed, It is preferable that a voltage can be applied to the conductive member.

[0013] In the microinjector according to the present invention, the discharge member is provided on at least a portion where the fine tubes are formed, an inner surface portion of the fine tubes, or both of the surfaces on which the fine tubes are formed. It is preferable to further include an organic thin film or an inorganic thin film for controlling wettability.

[0014]

FIG. 1A is a perspective view showing a discharge member constituting a microinjector according to one embodiment, and FIG.
FIG. 4 is an enlarged sectional view showing a nozzle portion of a discharge member. FIG. 2 is a process cross-sectional view showing one embodiment of a method for manufacturing a discharge member. The structure of the ejection member will be described with reference to FIGS. 1 and 2F.

The discharge member 21 has a length and a width of 15 m.
m, a silicon substrate 1 having a thickness of 200 μm.
The silicon substrate 1 has a thickness of 0.5 μm and an inner diameter of 20 μm.
A through hole having an inner wall formed by the m-shaped tubular silicon oxide film 15 is formed. The silicon oxide film 15 is formed so as to partially protrude from one surface of the silicon substrate 1.
The outer wall and tip of the protruding silicon oxide film 15 and the silicon substrate 1 on the side where the silicon oxide film 15 protrudes.
A silicon oxide film 17 having a thickness of about 4.5 μm is formed on the surface of the substrate. On the surface of the silicon oxide film 17, a fluorocarbon-based organic thin film 19 is formed with a thickness of 70 nm. The protruding portion of the silicon oxide film 15 and the silicon oxide film 17 and the organic thin film 1 formed on the outer periphery thereof
A nozzle (fine tube) 16 is constituted by 9. The nozzle 16 has a length of 100 μm, a thickness of 5 μm, and an inner diameter of 20 μm.
μm. The nozzle 16 has 10 nozzles on the surface of the silicon substrate 1.
This is formed and arranged at equal intervals on the circumference of 0.1 mm in diameter.

An embodiment of a method for manufacturing a discharge member will be described with reference to FIG. (A) Silicon nitride films 3a and 3b are formed to a thickness of 0.1 μm on both surfaces of a silicon substrate 1 having a thickness of 200 μm washed with hydrogen fluoride by LPCVD (low pressure CVD). The conditions are as follows: film forming temperature: 800 ° C., film forming pressure: 0.2.
The deposition was performed at 5 Torr, NH ₃ flow rate: 150 sccm, SiH ₄ flow rate: 40 sccm, and a film formation time of 90 minutes. On the silicon nitride films 3a and 3b, Al (aluminum) layers 5a and 5b are formed to a thickness of 0.2 μm by sputtering. The conditions of the LPCVD method are as follows: deposition pressure: 1.5 × 10 ⁻¹
Pa, Ar flow rate: 30 sccm, power: 1 kW, film formation time: 5 minutes.

(B) A photoresist is coated on the upper Al layer 5a by a spin coating method, exposed through a photomask having a desired opening pattern by a photolithography technique, and the photoresist layer is patterned by using a developing solution. And further washing. The lower Al layer 5b is protected by a resist, and the Al layer 5a is patterned using a mixed acid aluminum solution using the patterned photoresist layer as a mask to form a circular window 7 having a diameter of 23 μm in the Al layer 5a. Thereafter, the resist is removed using an acetone solution.

(C) Using an ICP-RIE (reactive ion etching by inductively coupled plasma) apparatus,
Using the layer 5a as a mask, the silicon substrate 1 and the silicon nitride film 3a are anisotropically in the depth direction of the silicon substrate 1.
3b is etched to form a through hole 9 in the silicon nitride film 3a, a through hole 11 in the silicon substrate 1, and a silicon nitride film 3b.
Then, a through hole 13 is formed. At this time, the silicon substrate 1 is cut into a desired size.

(D) After the Al layers 5a and 5b are peeled off and the silicon substrate 1 is cleaned using a mixed solution of sulfuric acid and hydrogen peroxide, the inner surface of the through hole 11 of the silicon substrate 1 is thermally oxidized, for example. Oxidized by wet oxidation method to 0.5μ thickness
Then, a tubular silicon oxide film 15 having an inner diameter of 20 μm is formed. The surface of the silicon substrate 1 has silicon nitride films 3a, 3b
It is not oxidized because it is covered with. Conditions are oxidation temperature:
1100 ° C., oxidation time 5 hours, O ₂ flow rate: 1000 sc
cm.

(E) Using an ICP-RIE apparatus, the silicon nitride films 3a and 3b are selectively removed, and the exposed silicon substrate 1 is removed from one surface side in a direction in which the tubular silicon oxide film 15 penetrates. It is selectively removed until the thickness becomes 100 μm. As a result, the silicon oxide film 15 in the portion where the silicon substrate 1 has been removed is projected. The projecting portion of the silicon oxide film 15 is designated by reference numeral 15a. The height of the tubular silicon oxide film 15a is 100 μm, the thickness is 0.5 μm, and the inner diameter is 20 μm. Silicon oxide film 1
The height of 5a can be adjusted by the thickness of the silicon substrate 1 to be removed by etching, that is, the etching time.

(F) The outer wall and the tip of the silicon oxide film 15a and the silicon oxide film 15 are formed by LPCVD.
A silicon oxide film 17 is formed to a thickness of about 4.5 μm on the surface of the silicon substrate 1 on the side where “a” protrudes to reinforce the silicon oxide film 15a. The conditions of the LPCVD method are as follows:
Film forming temperature: 600 ° C., film forming pressure: 0.3 Torr, Si
H ₄ flow rate: 200 sccm, O ₂ flow rate: 100 sccm,
The film formation was performed for 90 minutes.

Further, PECVD (plasma-excited CV
By a method D), a fluorocarbon-based organic thin film 19 is formed in a thickness of 70 nm on the surface of the silicon oxide film 17 so as to have water repellency. The conditions of the PECVD method are as follows:
0.1 Torr, CHF ₃ flow rate: 100 sccm, power:
The film formation was performed at 50 W for 10 minutes. Thus, the discharge member 21 was formed.

In the embodiment of the method of manufacturing the ejection member shown in FIG. 2, after forming a through hole in the silicon substrate 1, the inner wall is oxidized to form the silicon oxide film 15 on the silicon substrate 1. Although the through holes are formed, the production method of the present invention is not limited to this. For example, a pore is formed from one surface side of the silicon substrate to the middle, a silicon oxide film is formed on the inner wall of the pore, and then the silicon substrate is etched from the back side until the bottom of the silicon oxide film on the inner wall of the pore is exposed. Then, by selectively removing the exposed bottom portion of the silicon oxide film, it is possible to form a through hole having an inner wall made of the silicon oxide film in the silicon substrate. Thereafter, the silicon substrate is selectively etched away from the front side or the back side, whereby a fine tube made of a silicon oxide film can be formed.

FIGS. 3 and 4 are views showing a microinjector provided with a discharge member 21. FIG. 3A is a sectional view, FIG. 3B is an exploded perspective view, and FIG. Sectional view showing a nut member, (B) is a bottom view showing a nut member, (C) is a sectional view showing a discharge member and a glass member,
(D) is a perspective view showing the discharge member and the glass member, (E)
Is a cross-sectional view showing a screw member, and (F) is a cross-sectional view showing an LC joint member. FIG. 4A is a cross-sectional view taken along the line AA in FIG.

The discharge member 21 is fixed to the upper surface 23c of the cylindrical glass member 23 with the nozzle 16 facing outward, for example, by anodic bonding. A through-hole 23a having an inner diameter of 0.125 mm is formed at the center of the cylindrical axis of the glass member 23, and the discharge member 21 is fixed such that the nozzle 16 is positioned on the through-hole 23a. A flange 23b is formed on a side wall on the lower surface 23d side of the glass member 23.

The glass member 23 is made of a SUS screw member 2.
5 and a nut member 27 for fixing. The flange portion 2 of the glass member 23 is attached to the cylindrical screw member 25.
3b, a cylindrical concave portion 25a having an inner diameter slightly larger than the outer peripheral dimension of the glass member 23 is formed.
Side, and is housed in the recess 25a. Screw member 25
A thread for fastening to the nut member 27 is formed on the outer wall on the side of the concave portion 25a. Further, the screw member 25 has an LC joint member 29 corresponding to the position of the through hole 23a when the glass member 23 is accommodated in the concave portion 25a.
Is formed. A thread for fastening the LC joint member 29 is formed on the inner wall of the through hole 25b opposite to the bottom surface 25a.

The cross section of the cylindrical nut member 27 is concave. The nut member 27 has a through hole 27 having a diameter smaller than the diameter of the upper surface 23 c of the glass member 23 at the center of the cylindrical axis and larger than the diagonal dimension of the discharge member 21.
a is formed. Bottom surface 27 inside nut member 27
In b, four grooves for accommodating the gas pipes 33 are formed at equal intervals from the center to the outer periphery, and through holes communicating with the grooves are formed on the side walls of the nut member 27, respectively. . Gas pipes 3 for jetting nebulizing gas toward the nozzle 16 are provided in these grooves and through holes.
3 are accommodated. A thread for fastening with the screw member 25 is formed on the inner wall of the nut member 27. When the screw member 25 and the nut member 27 are fastened with the glass member 23 housed in the recess 25a of the screw member 25, the bottom surface 27b of the nut member urges the outer peripheral portion of the upper surface 23c of the glass member 23 toward the screw member 25. Then, the glass member 23 is fixed.

For example, PEEK (Poly Ether Ether Keton)
In the LC joint member 29 manufactured by e), a pipe 35 having an outer diameter of 0.125 mm or less and connected to the LC is fixed.
The recess 25 of the screw member 25 is provided on the outer wall of the joint member 29.
And a screw thread for fastening. Screw member 2
In a state where the joint member 5 and the joint member 29 are fastened, the pipe 35 is disposed in the through hole 23a of the glass member 23, and the tip of the joint member 29 bites into the through hole 23a of the glass member 23, and is liquid-tight and dead space. Connection without the need to be realized.

FIG. 5 is a schematic configuration diagram showing an embodiment of an LC-MS device provided with the microinjector of the present invention. The pipe 35 from the LC unit 37 is connected to the microinjector 21 arranged in the atomization chamber 41 of the MS unit 31. A gas pipe 33 for supplying a nebulizing gas is connected to the microinjector 21. Ventilation hole 4 connected to mass spectrometer 45 in atomization chamber 41
3 are formed. Although illustration is omitted,
The atomization chamber 41 is provided with a high electric field generating means (high voltage power supply) for applying a high electric field to the sample liquid sprayed from the microinjector 21.

The liquid sample from the LC section 37 is sent to the microinjector 21 via the pipe 35. Nozzle 16 of microinjector 21 (see FIGS. 1 to 4)
, The liquid sample is charged by high-voltage generating means (not shown), and a nebulizing gas is supplied from a gas pipe 33 to expose the liquid sample to the nebulizing gas. Thereby, the solvent of the liquid sample evaporates, and the sample is ionized. The ionized sample is guided to the mass spectrometer 45 through the vent hole 43 and analyzed.

FIG. 6A is a cross-sectional view showing another embodiment of the microinjector, and FIG. 6B is an enlarged cross-sectional view showing a portion surrounded by a dashed line of FIG. FIG.
The same reference numerals are given to the same portions as (A), and description thereof will be omitted. The glass member 23 is housed in the recess 25 a of the screw member 25. The joint member 29 is fastened to the concave portion 25b of the screw member 23, and the through hole 23a of the glass member 23 is formed.
The pipe 35 is led to the.

The cylindrical nut member 47 has a concave cross section. The nut member 47 has a cylindrical shaft center,
A through hole 47a is formed so that at least an upper space of the nozzle 16 is opened. A circular step 47c having a diameter smaller than the diameter of the upper surface 23c of the glass member 23 and larger than the diagonal dimension of the discharge member 21 is formed on the bottom surface 47b inside the nut member 47. A space is formed between the step 47c and the ejection member 23. A through hole for fastening the joint member 49 is formed on a side surface of the nut member 47 at a position where a space is formed between the nut member 47 and the screw member 25. The joint member 49 is for fixing a gas pipe 51 for supplying a nebulizing gas.

A plurality of notches 47d are formed in the bottom 47b at the corners on the side of the step 47c. Gas piping 51
Is supplied to a space surrounded by the glass member 23, the screw member 25, and the nut member 47, and further guided to a space between the discharge member 21 and the nut member 47 through the notch 47d. As a result, it is ejected from the through hole 47a. In this embodiment, the nebulizing gas can be guided to the vicinity of the nozzle 16.

FIG. 7A is a perspective view showing another example of the discharge member, and FIG. 7B is an enlarged sectional view showing the nozzle portion of the discharge member. The same reference numerals are given to the same parts as those in FIG. The ejection member 21a includes the silicon substrate 1, the silicon oxide film 15, and the silicon oxide film 17, as in the embodiment of FIG. Silicon oxide film 1
7, a chemically thin metal thin film 53 made of, for example, Au or Pt and having a thickness of about several 100 nm is formed by sputtering. The organic thin film 19 is formed on the surface of the metal thin film 53. The protruding portion of the silicon oxide film 15 and the silicon sensitive film 17, the metal thin film 53 and the organic thin film 19 formed on the outer periphery thereof constitute a nozzle 16a. Organic thin film 1 on metal thin film 53
An opening 19a is formed in a part of 9 so that the metal thin film 53 is exposed and can be connected to an external power supply. In this embodiment, a liquid sample passing through the nozzle 16a can be charged by applying a voltage to the metal thin film 53.

In the above embodiment, ten nozzles 16 are arranged at equal intervals on the circumference. However, the present invention is not limited to this, and the number and arrangement of the nozzles are not limited. There may be. Further, in the above embodiment, the organic thin film 19 is formed as a film for controlling the wettability of the discharge member, but the present invention is not limited to this.
An inorganic thin film that can control the wettability of the ejection member may be used. Further, the present invention is not limited to the numerical values described in the above embodiments, and various changes can be made within the scope of the present invention described in the claims.

[0036]

The microinjector of the present invention is a member having a silicon substrate as a discharge member and a plurality of fine tubes having an inner diameter of 50 .mu.m or less formed on one surface thereof by silicon oxide. Therefore, it is possible to reduce the particle size of the liquid sample to be discharged, reduce the variation in the particle size of the discharged liquid sample, suppress the decrease in detection sensitivity, and improve the reproducibility of the measurement result. Furthermore, since a plurality of microtubes are formed, the diameter of the orifice can be substantially increased, so that the delivery pressure on the liquid sample supply side does not matter. Further, since a plurality of fine tubes are formed, many normal nozzles remain even if some of the nozzles are deformed, so that the effective life can be extended.

Since the mass spectrometer according to the present invention includes the microinjector of the present invention and a high electric field generating means for charging the liquid sample sprayed from the microinjector, the reduction in detection sensitivity is suppressed. Detection with high sensitivity.

In the method of manufacturing a discharge member of a microinjector according to the present invention, a through hole is formed in a silicon substrate, a silicon oxide film is formed in the through hole, and the silicon substrate is connected to the through hole from one surface side. Since the fine tube made of the silicon oxide film is formed by selectively etching in the penetrating direction, it is possible to form the ejection member constituting the microinjector according to the present invention. Since micromachining technology based on semiconductor manufacturing technology is used, multiple microtubes can be processed in a uniform shape with submicron accuracy, manufacturing reproducibility is good, and multiple ejection members are collectively mounted on a substrate. Since it can be manufactured, it is advantageous in terms of mass production, cost, and homogeneity.

[Brief description of the drawings]

FIG. 1A is a perspective view showing a discharge member constituting a microinjector according to one embodiment, and FIG. 1B is a cross-sectional view showing an enlarged nozzle portion of the discharge member.

FIG. 2 is a process cross-sectional view showing one embodiment of a method for manufacturing a discharge member.

FIGS. 3A and 3B are diagrams showing a microinjector of one embodiment, wherein FIG. 3A is a cross-sectional view and FIG. 3B is an exploded perspective view.

FIG. 4 is a view showing the microinjector;
4A is a sectional view showing a nut member, FIG. 4B is a bottom view showing a nut member, FIG. 4C is a sectional view showing a discharge member and a glass member, and FIG. 4D is a perspective view showing a discharge member and a glass member. FIG. 7 (E) is a sectional view showing a screw member, FIG. 7 (F) is a sectional view showing an LC joint member, and FIG. 7 (A) is a sectional view taken along the line AA in FIG.

FIG. 5 is a schematic configuration diagram showing one embodiment of an LC-MS device.

FIG. 6A is a cross-sectional view showing another embodiment of the microinjector, and FIG. 6B is an enlarged cross-sectional view showing a portion surrounded by a dashed line in FIG.

FIG. 7A is a perspective view showing another example of a discharge member, and FIG. 7B is an enlarged sectional view showing a nozzle portion of the discharge member.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Silicon substrate 15, 17 Silicon oxide film 16 Nozzle 19 Organic thin film 21 Discharge member

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hiroaki Nakanishi 1 Nishinokyo Kuwaharacho, Nakagyo-ku, Kyoto-shi, Kyoto Inside Shimadzu Corporation (72) Inventor Hiroyuki Fujita 1-9-14-1 Chikawa, Toshima-ku, Tokyo (72) Inventor Ryoichi Daito 1-1-1, Ichigaya-Kaga-cho, Shinjuku-ku, Tokyo Dai Nippon Printing Co., Ltd.

Claims (5)

[Claims] 1. A microinjector having a discharge member for spraying a liquid sample to ionize and introduce the liquid sample into a mass spectrometer, wherein the discharge member has a silicon substrate as a base material. A microinjector comprising, on one surface thereof, a plurality of fine tubes formed of silicon oxide and having an inner diameter of 50 μm or less. 2. The discharge member further includes a conductive member on at least a portion where the fine tube is formed on a surface on which the fine tube is formed, and can apply a voltage to the conductive member. The microinjector according to claim 1, wherein: 3. The liquid discharging member has a wettability with respect to a liquid sample on at least a portion where the fine tubes are formed, an inner surface portion of the fine tubes, or both of the surfaces on which the fine tubes are formed. The microinjector according to claim 1, further comprising an organic thin film or an inorganic thin film for controlling the temperature. 4. A mass spectrometer comprising: the microinjector according to claim 1; and a high electric field generating means for charging a liquid sample sprayed from the microinjector. 5. The method for manufacturing a discharge member for a microinjector according to claim 1, wherein a through hole having an inner wall made of a silicon oxide film is formed in the silicon substrate, and the silicon substrate is provided on one surface. Forming a fine tube made of a silicon oxide film by selectively etching from a side in a through direction of the through hole.