WO2021143078A1

WO2021143078A1 - Pulse electrospray ion source, pulse sample injection method, and mass spectrum detection system

Info

Publication number: WO2021143078A1
Application number: PCT/CN2020/102134
Authority: WO
Inventors: 余泉; 张乾; 王晓浩
Original assignee: 清华大学深圳国际研究生院
Priority date: 2020-01-17
Filing date: 2020-07-15
Publication date: 2021-07-22
Also published as: CN111243936A

Abstract

A pulse electrospray ion source, a pulse sample injection method, and a mass spectrum detection system. The ion source comprises a sample supply device, a sample injection capillary tube, and an electrode; a sample solution provided by the sample supply device enters from a sample injection end of the sample injection capillary tube and is output from an output end of the sample injection capillary tube; the electrode electrifies the sample solution to provide voltage required for forming electrospray. The ion source also comprises a moving device coupled to the sample supply device or the sample injection capillary tube. During sample injection, the sample supply device and the sample injection capillary tube intermittently move relative to each other according to a set pulse time sequence, so that a sample in the sample supply device is intermittently in contact with the sample injection end of the sample injection capillary tube, thereby realizing pulse-type electrospray sample injection. The present invention realizes synchronous execution of pulse sample injection and ionization, and improves the sample utilization rate.

Description

Pulse electrospray ion source, pulse sampling method and mass spectrometry detection system

Technical field

The invention relates to the field of analytical instruments, in particular to a pulsed electrospray ion source and a pulsed sampling method.

Background technique

The mass spectrometer has a history of more than one hundred years since its invention. Because of its high sensitivity, high accuracy, fast analysis speed, and strong qualitative ability, it has been widely used. The ion source is one of the core components of the mass spectrometer, which determines the detection range and sensitivity of the instrument. Among them, the electrospray ion source is the most widely used ion source, and its technology has won the Nobel Prize.

The working process of electrospray can be simply described as: the sample solution passes through the capillary at a low flow rate. A high voltage is connected to the capillary. The sign of the voltage depends on the nature of the object to be measured. The voltage provides the electric field gradient required for charge separation on the liquid surface. Under the action of the electric field, the liquid forms a "Taylor cone" at the tip of the capillary. As the solvent evaporates, the droplet shrinks, and the repulsive force between the charges in the droplet increases. The droplet will undergo a Coulomb explosion and reciprocate to obtain gas phase ions, which are finally detected by the mass analyzer.

Traditional electrospray has always produced gas phase ions, and the mass spectrometer pulsed sampling to detect ions, so only a part of the ions produced by the ion source are detected by the mass spectrometer, causing waste. Therefore, the application of pulsed electrospray ion source was born. At present, most of the existing pulse electrospray ion sources generate pulse electrospray by loading pulsed high-voltage electricity and alternating high-voltage electricity. These methods are all based on the improvement of the power-up method. In specific operations, it is necessary to use pipettes, syringe pumps and other auxiliary devices to inject samples, and then pulsed for ionization. That is, sample injection and ionization are asynchronous processes, and the sample utilization rate is not high.

Summary of the invention

The main purpose of the present invention is to overcome the above technical defects, provide a pulsed electrospray ion source and a pulsed sampling method, realize the synchronization of pulsed sampling and ionization, and improve sample utilization.

In order to achieve the above objectives, the present invention adopts the following technical solutions:

A pulsed electrospray ion source includes a sample supply device, a sample injection capillary, and an electrode. The sample solution provided by the sample supply device enters the sample injection capillary from the sample injection end of the sample injection capillary, and enters from the sample injection capillary. The output end of the sample capillary is output, and the electrode is used to contact or non-contact electrify the sample solution to provide the voltage required to form an electrospray, wherein the pulse electrospray ion source also includes a coupling To the sample supply device or the moving device of the sample injection capillary, the moving device makes the sample supply device and the sample injection capillary intermittently move relative to each other according to the set pulse sequence during sample injection, so that The sample in the sample supply appliance intermittently contacts the sample injection end of the sample injection capillary, thereby realizing pulsed electrospray injection.

further:

The sample supply device is a centrifuge tube or a sample plate, and the electrode is inserted into the sample solution in the centrifuge tube, or the electrode is placed under the sample plate.

The moving device includes a moving table, the sample supply device is arranged on the moving table, and the sample supply device is carried by the moving table during sample injection to move intermittently with respect to the sampling capillary.

The mobile table has a table surface arranged in a horizontal direction and is arranged to move in a vertical direction, the sample supply device is arranged on the horizontal surface of the mobile table, and the sample injection capillary is vertically arranged above the mobile table. Orientation straight.

The moving device includes a capillary moving device, the sample injection capillary is fixed on the capillary moving device, and the capillary is driven by the capillary moving device to move intermittently relative to the sample supplier during sample injection.

The capillary moving device is a capillary lifting device, the sample supply device is arranged horizontally, and the capillary lifting device controls the sample injection capillary to move up and down relative to the sample supply device.

The output end of the injection capillary is connected to a low-pressure cavity, which is a low-pressure cavity of the mass spectrometer, or is additionally provided between the output end of the injection capillary and the injection port of the mass spectrometer. Preferably, the air pressure of the low-pressure cavity is 10 ^-4 -10 ⁵ Pa.

It also includes a carrier gas passage through which the sample injection capillary passes, and the outlet of the carrier gas passage extends to the output end of the sample injection capillary. Preferably, the control carrier gas and the injection have the same pulse timing.

The sample injection capillary has an inner diameter of 10-150 μm, and the outer surface is coated with a polyamide coating.

A pulsed sampling method, using the pulsed electrospray ion source for pulsed electrospray sampling, the method comprising: during sampling, according to a set pulse sequence, the sample is made by the moving device The supply device and the sampling capillary intermittently move relative to each other, so that the sample in the sample supply device intermittently contacts the sampling end of the sampling capillary, and the sample solution passes through the sampling of the sampling capillary. End into the sampling capillary and output from the output end of the sampling capillary. At the same time, the sample solution is contacted or non-contact energized through the electrode, so that the sample solution is The output end of the capillary tube forms electrospray, thereby realizing pulsed electrospray injection.

A mass spectrometry detection system includes an electrospray ion source and a mass spectrometer, wherein the electrospray ion source is the pulsed electrospray ion source.

The present invention has the following beneficial effects:

The pulse electrospray ion source of the present invention realizes the simultaneous sampling and ionization in the pulse electrospray process, improves the utilization rate of the sample compared with the traditional pulse sampling method, and simplifies the structure of the instrument, and has small sample consumption, The obvious advantage of short response time.

In a preferred embodiment, the ion source of the present invention does not need an auxiliary sample injection device, uses self-priming sample injection, and adopts non-contact power-up to avoid dead volume and sample contamination in the sample injection channel.

Description of the drawings

Fig. 1 is a schematic structural diagram of a pulsed electrospray ion source according to an embodiment of the present invention;

Fig. 2 is a schematic structural diagram of a pulsed electrospray ion source and a small-scale mass spectrometry detection system according to another embodiment of the present invention.

Detailed ways

The embodiments of the present invention will be described in detail below. It should be emphasized that the following description is only exemplary, and is not intended to limit the scope of the present invention and its application.

It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element. In addition, the connection can be used for fixing or for coupling or connecting.

It should be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top" , "Bottom", "Inner", "Outer", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the embodiments of the present invention and simplifying the description, rather than indicating or implying what is meant. The device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present invention.

Fig. 1 is a schematic structural diagram of a pulsed electrospray ion source according to an embodiment of the present invention. Fig. 2 is a schematic structural diagram of a pulse electrospray ion source and a mass spectrometry detection system according to another embodiment of the present invention. 1 and 2, an embodiment of the present invention provides a pulsed electrospray ion source, which includes a sample supply device (such as a centrifuge tube 3 or a sample plate 3'), a sampling capillary 4, and an electrode 2. The sample supply device The provided sample solution enters the sampling capillary 4 from the sampling end of the sampling capillary 4, and is output from the output end of the sampling capillary 4, and the electrode 2 is used for contacting the sample solution. Or non-contact energization to provide the voltage required to form electrospray, wherein the pulsed electrospray ion source further includes a moving device (such as a lifting platform) coupled to the sample supply device or the sampling capillary 4 1) During sample injection, based on a preset pulse sequence, the moving device makes the sample supply device and the sample injection capillary 4 intermittently move relative to each other, so that the sample in the sample supply device is intermittent Sexually contact with the sampling end of the sampling capillary 4, thereby realizing pulsed electrospray sampling.

In a preferred embodiment, the pulsed electrospray ion source further includes a carrier gas passage 5, the sampling capillary 4 passes through the carrier gas passage 5, and the outlet of the carrier gas passage 5 extends to the inlet Sample at the output end of the capillary 4. More preferably, the carrier gas and the sample injection are controlled to have a consistent pulse sequence, and pulse carrier gas is generated at the output end of the sample injection capillary 4 immediately after the sample is sampled to promote the electrospray desolventization process and improve the sample utilization rate.

In some embodiments, pulsed power-on may be performed at a timing consistent with the pulse timing. However, the present invention does not limit the pulse mode for power-on, as long as it is ensured that there is a voltage required to generate electrospray when the sample solution is injected into the sampling capillary 4.

In another embodiment, a pulsed sampling method uses the pulsed electrospray ion source of any one of the foregoing embodiments to perform pulsed electrospray sampling. The method includes: during sampling, according to a set pulse In time sequence, the sample supply device and the sampling capillary 4 are intermittently moved relative to each other by the moving device, so that the sample in the sample supply device intermittently and the sampling end of the sampling capillary 4 Contact, the sample solution enters the sampling capillary 4 through the sampling end of the sampling capillary 4, and is output from the output end of the sampling capillary 4, and at the same time, contacts the sample solution through the electrode 2 The power is applied in a manner or a non-contact manner, so that the sample solution forms an electrospray at the output end of the sampling capillary 4, thereby realizing a pulsed electrospray injection.

In another embodiment, a mass spectrometry detection system includes an electrospray ion source and a mass spectrometer, wherein the electrospray ion source is the pulsed electrospray ion source of any of the foregoing embodiments.

The pulse electrospray ion source of the embodiment of the present invention realizes the simultaneous sampling and ionization in the pulse electrospray process, improves the sample utilization rate compared with the traditional pulse sampling method, and simplifies the structure of the instrument, and has a small sample consumption , The obvious advantage of short response time.

The features and advantages of specific embodiments of the present invention will be further described below in conjunction with the accompanying drawings.

A specific embodiment of the pulse electrospray ion source includes a sampling capillary 4, a carrier gas path 5, a lifting platform 1, an electrode 2, a centrifuge tube 3 or a sample plate 3', a low-pressure chamber 6, and the sampling capillary 4 One end is used as the sampling end, and the other end is placed in the low-pressure chamber 6, the pressure of the low-pressure chamber 6 is 10 ^-4 -10 ⁵ Pa; the sampling capillary 4 passes through the carrier gas passage 5; the electrode 2 is placed under the sample plate 3'or inserted into the sample solution in the centrifuge tube 3; the electrode 2 can be placed on the lifting platform 1 together with the centrifuge tube 3 or the sample plate 3', so The lifting platform 1 can move up and down or three-dimensionally; the other end of the low-pressure cavity 6 is connected to the injection port of the mass spectrometer. In addition, the sampling capillary 4 can be installed on the lifting platform 1, and the capillary sampling end can also move intermittently relative to the centrifuge tube 3 or the sample plate 3'. In all of the above, the sample injection capillary 4 intermittently contacts the sample and realizes pulsed sample injection. The lifting platform 1 can be replaced by other forms of mobile platforms, and the relative movement direction is not limited to vertical movement.

Preferably, the inner diameter of the sample injection capillary 4 is 10-150 μm, and the material is a capillary coated with polyamide coating.

Preferably, the air pressure in the low-pressure chamber 6 is 10 ^-4 -10 ⁵ Pa, which can be achieved by using the suction of the inlet of the mass spectrometer to reduce the air pressure, or by connecting an air pump to evacuate.

In some embodiments, the low-pressure cavity 6 may be the low-pressure cavity 6 that comes with the mass spectrometer, or it may be an independent sealed low-pressure cavity 6.

In some embodiments, the carrier gas passage 5 can be continuously fed with gas, or can be fed with gas intermittently. The gas introduced into the carrier gas passage 5 can be air, nitrogen, hydrogen, helium, and other gases.

In some embodiments, the electrode 2 is loaded with high-voltage direct current, and the electrode 2 and the sample in the centrifuge tube 3 or the sample plate 3'are powered on in a non-contact manner. As an alternative, the electrode 2 is loaded with a high-voltage direct current, and the electrode 2 is in contact with the sample on the centrifuge tube 3 or the sample plate 3'to realize contact powering.

In some embodiments, when the carrier gas path 5 can be intermittently fed with gas, the timing adopted is synchronized with the timing of pulse injection.

In various embodiments of the present invention, the way to power up the liquid sample can be that the electrode 2 is directly in contact with the sample for powering; or the high-voltage electrode 2 and the sample are not in contact, and the positive and negative charges in the sample are separated by high-voltage electric field induction, and the solution is polarized. , To avoid sample contamination caused by the contact between the solution and the electrode 2. The pressure difference between the two ends of the capillary tube can be used to realize self-priming sample injection without auxiliary equipment. The sampling capillary 4 can be intermittently contacted with the sample liquid provided by the centrifuge tube 3 or the sample plate 3'to realize pulsed sampling of charged droplets, which can effectively increase the transmission speed of the liquid in the centrifuge tube 3 and improve the response time. More preferably, the pulse carrier gas and the sampling timing are controlled, and the pulse carrier gas is generated at the end of the sampling capillary 4 immediately after the sample is injected, so as to promote the electrospray desolventization process and improve the sample utilization rate. Fourth, to achieve simultaneous sampling and ionization, real-time monitoring of chemical reactions can be achieved.

Example 1

As shown in FIG. 1, it is a schematic diagram of the structure of the pulse electrospray ion source in this specific embodiment. Including the sampling capillary 4, the carrier gas path 5, the lifting platform 1, the electrode 2, the centrifuge tube 3, and the low pressure chamber 6.

One end of the sample injection capillary 4 serves as the sample injection end, and the other end is placed in the low pressure chamber 6; the sample injection capillary 4 passes through the carrier gas passage 5; the electrode 2 is inserted into the solution in the centrifuge tube 3; The electrode 2 and the centrifuge tube 3 are placed on the lifting platform 1 together; the lifting platform 1 can move up and down or three-dimensionally; the other end of the low pressure cavity 6 is connected to the inlet of the mass spectrometer. The capillary tube 4 pulses in contact with the sample to be tested and self-priming sample injection, which can generate pulsed electrospray in the low-pressure cavity 6 so that the sample ion signal is detected by the mass spectrometer.

Example 2

As shown in Figure 2, it includes a sample injection capillary 4, a carrier gas path 5, a gas path valve 7, a lifting platform 1, an electrode 2, a sample plate 3', and a mass spectrometer cavity 6'.

One end of the sampling capillary 4 is used as a sampling end, and the other end is placed in the mass spectrometer cavity 6', the sampling capillary 4 passes through the carrier gas passage 5; the electrode 2 is placed under the sample plate 3, The droplet to be tested 8 is placed on the sample plate 3'; the electrode 2 and the sample plate 3'are placed on the lifting platform 1 together; the lifting platform 1 can move up and down or three-dimensionally; the gas path valve 7 is intermittent The capillary tube 4 pulses in contact with the sample to be tested. When the droplet to be tested is transferred to the end of the capillary tube 4, the gas valve 7 is opened instantaneously to promote the desolvation process of the electrospray, and the sample is finally detected by the mass spectrometer. Ion signal.

The background part of the present invention may contain background information about the problem or environment of the present invention, and does not necessarily describe the prior art. Therefore, the content contained in the background technology part is not the applicant's recognition of the prior art.

The above content is a further detailed description of the present invention in combination with specific/preferred embodiments, and it cannot be considered that the specific implementation of the present invention is limited to these descriptions. For those of ordinary skill in the technical field to which the present invention belongs, without departing from the concept of the present invention, they can also make several substitutions or modifications to the described embodiments, and these substitutions or modifications should be regarded as It belongs to the protection scope of the present invention. In the description of this specification, reference to the description of the terms "one embodiment", "some embodiments", "preferred embodiment", "examples", "specific examples", or "some examples" etc. means to incorporate the implementation The specific features, structures, materials or characteristics described by the examples or examples are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics can be combined in any one or more embodiments or examples in a suitable manner. If there is no conflict with each other, those skilled in the art can combine and combine the different embodiments or examples and the features of the different embodiments or examples described in this specification. Although the embodiments of the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the scope of protection of the patent application.

Claims

A pulsed electrospray ion source includes a sample supply device, a sample injection capillary, and an electrode. The sample solution provided by the sample supply device enters the sample injection capillary from the sample injection end of the sample injection capillary and enters the sample The output end of the sample capillary is output, and the electrode is used to contact or non-contact power up the sample solution to provide the voltage required to form an electrospray. The electrode is characterized in that it also includes a coupling to the sample supply The device or the moving device of the sample injection capillary, the moving device makes the sample supply device and the sample injection capillary intermittently move relative to each other according to the set pulse sequence during sample injection, so that the sample supply device The sample inside is intermittently in contact with the sample injection end of the sample injection capillary, thereby realizing pulsed electrospray injection.
The pulse electrospray ion source according to claim 1, wherein the sample supply device is a centrifuge tube or a sample plate, the electrode is inserted into the sample solution in the centrifuge tube, or the electrode is placed in the Under the sample plate.
The pulse electrospray ion source according to claim 1 or 2, wherein the moving device comprises a moving table, the sample supply device is arranged on the moving table, and the sample supply device is carried by the moving table during sample injection. The sample supplier moves intermittently with respect to the sampling capillary.
The pulsed electrospray ion source according to claim 3, wherein the moving table has a table surface arranged in a horizontal direction and is arranged to move in a vertical direction, and the sample supply device is arranged on the horizontal of the moving table. On the table surface, the sample injection capillary is positioned in a vertical direction above the moving table.
The pulsed electrospray ion source according to claim 1 or 2, wherein the moving device comprises a capillary moving device, the sample injection capillary is fixed on the capillary moving device, and the capillary moves during sample injection. The device drives the capillary tube to move intermittently relative to the sample supply.
The pulse electrospray ion source according to claim 5, wherein the capillary moving device is a capillary lifting device, the sample supply device is arranged horizontally, and the capillary lifting device controls the injection capillary relative to the The sample supply device moves up and down.
The pulsed electrospray ion source according to any one of claims 1 to 6, wherein the output end of the sampling capillary is connected to a low-pressure cavity, and the low-pressure cavity is a low-pressure cavity of a mass spectrometer, or A sealed low-pressure cavity additionally provided between the output end of the sampling capillary and the injection port of the mass spectrometer, preferably, the pressure of the low-pressure cavity is 10 -4 -10 5 Pa.
The pulsed electrospray ion source according to any one of claims 1 to 7, which preferably further comprises a carrier gas passage, the sample injection capillary passes through the carrier gas passage, and the carrier gas passage The outlet extends to the output end of the injection capillary. More preferably, the carrier gas and the injection are controlled to have a consistent pulse timing; preferably, the injection capillary has an inner diameter of 10-150 μm, and the outer surface is coated with polyamide coating. Floor.
A pulsed sampling method, characterized in that the pulsed electrospray ion source according to any one of claims 1 to 8 is used for pulsed electrospray sampling, and the method comprises: The pulse timing of the sample supply device and the sample injection capillary are intermittently moved by the moving device, so that the sample in the sample supply device intermittently interacts with the sample injection capillary. End contact, the sample solution enters the sampling capillary through the sampling end of the sampling capillary, and is output from the output end of the sampling capillary. At the same time, the sample solution is contacted or non-contacted through the electrode. The contact-type electrification causes the sample solution to form electrospray at the output end of the sample injection capillary, thereby realizing pulsed electrospray injection.
A mass spectrometry detection system, comprising an electrospray ion source and a mass spectrometer, wherein the electrospray ion source is the pulsed electrospray ion source according to any one of claims 1 to 8.