TW201310495A - Thermal desorption ionization device, mass spectrometer, and method for mass spectrometry - Google Patents

Abstract

The present invention provides a thermal desorption ionization device, which carries out desorption process of a sample and causes the desorption sample to travel to an entry of a mass spectrometry for spectrometry analysis. The device comprises a charge producing unit, a heating unit, and a sampling unit. A probe of the sampling unit is utilized to touch the solid or liquid sample, and pass the probe through the heating unit to instantly vaporize the sample, the vaporized sample is then ionized by the charge producing unit for further spectrometry analysis. The present invention can dramatically shorten the analyzing time. The present invention also provides a mass spectrometer system including a mass spectrometer, and the thermal desorption ionization device. The present invention also provides a method for mass spectrometry.

Description

Thermal desorption free device, mass spectrometry system, and mass spectrometry

This invention relates to a free device, and more particularly to a thermal desorption free device. The invention also relates to a mass spectrometry system comprising the thermal desorption free device, and a mass spectrometry method.

By mass spectrometry, one can know the molecular weight of the analytes in a sample, and then cooperate with further comparison to confirm the true identity of the analyte. Therefore, since the early 20th century, the mass spectrometry was performed. The technical mass spectrometer has become an identification tool widely used in various fields because of its advantages of easy operation and quick detection results.

In 1997, the applicant connected a seven-tube multi-channel electrospray free device with a gas chromatograph (GC) to separate and detect seven ester mixtures with different molecular weights. Paper: CS Wang, J. Shiea J. Mass Spectrom . 1997; 32: 247.

To analyze the protein component by electrospray free method, the protein in a tissue section is first extracted and a protein solution is obtained, and then a mass spectrometer 1 containing an electrospray ion source 11 as shown in FIG. Hereinafter referred to as ESI-MS) for protein analysis. Related art can be found in the following papers: Yamashita, M., Fenn, JB J. Phys. Chem . 1984; 88 , 4451., Fenn, JB et al. Science 1989; 246 , 64., Fenn, JB et al. Mass Spectrom Rev. 1990; 9 , 37.

The electrospray ionization source 11 of the mass spectrometer 1 is used to perform an electrospray ionization (ESI) procedure to free proteins. The free source 11 includes a capillary 112 having an open end 111 facing the inlet 121 of the mass analyzer 12. In use, an electric field is established between the open end 111 and the inlet 121, for example, a voltage of 2-5 kV is formed therebetween. difference. Thereafter, the protein solution to be tested flows in the capillary 112 toward the open end 111, and the solution at the open end 111 forms a Taylor cone with a charge due to the traction of the electric field and the surface tension of the liquid surface ( Taylor cone) 2, when the electric field force can overcome the surface tension of the liquid, droplets with multivalent charges and containing protein molecules are formed and sprayed toward the mass analyzer 12, and then by the inlet 121 Enter the mass analyzer 12.

Referring to Figure 2, a desorption electrospray ionization (DESI) is performed by desorption electrospray free mass spectrometry (DESI-MS) 3 and mass spectrometry is performed. This method can detect a wide range of molecular weights. And a variety of compounds, can also directly detect the mass spectrometry of a moving tissue section 4 protein.

The desorption electrospray free mass spectrometer 3 comprises a desorption electrospray ion source 31, which is an electrospray ion source 11 similar to that shown in Fig. 1, except that the desorption electrospray ion source 31 is a The orientation is set toward the tissue slice 4, and there is a flow supply member 312 that surrounds the capillary 112 and is capable of ejecting a high pressure gas stream 311. The desorption electrospray free source 31 is an electrospraying process by pouring an electrospray media 32 into the capillary 112 and applying a high voltage. When starting, a plurality of charged droplets 321 are sprayed from the open end 111 in the same direction. The high-pressure airflow 311 and the high-pressure airflow 311 strikes a tissue section 4, so that the object to be tested in the tissue section 4 is desorbed by force, and the desorbed analyte is charged with the droplet 321 to be charged. An ionic state is formed which is then received by the inlet 33 of the mass analyzer and subjected to subsequent mass spectrometry.

However, the high-pressure airflow 311 is not easily concentrated after being ejected, and it is difficult to precisely control the area to be struck, the precise protein space analysis of the tissue section 4 cannot be performed, and the desorption energy of the tissue section 4 is bombarded with the charged droplet 321 and Not enough to efficiently desorb the protein molecules bound to it.

In 2002, the applicant again proposed Fused Droplet Electrospray Ionization (FD-ESI), or two-step Electrospray Ionization, and the subsequent development of various free forms. method. Different from the general electrospray ionization mass spectrometry, the two-stage electrospray ionization method is to pre-process the analyte, directly push the pump through a capillary applying a high voltage, and generate an electric spray free analyte at the end. The method is to first atomize the analyte solution by atomizer (ultrasonic atomizer or pneumatic atomizer, etc.) to produce tiny droplets with a size of about 10-30 μm. The charged droplet fusion reaction generated by spraying generates charged analyte ions. At this time, the electrospray free source design changes from multi-channel to single capillary for electric spraying, and becomes the main basis for the subsequent free source design. See the following paper: DY Chang, CC Lee, J. Shiea, Anal. Chem. 2002 , 74, 2465.; CC Lee, DY Chang, JY Jeng, J. Shiea, J. Mass Spectrom. 2002 , 37, 115.

In 2005, the applicant developed the Electrospray-Assisted Pyrolysis Mass Spectrometry (ESA-Py/MS) technique for the analysis of macromolecules, including soluble and insoluble synthetic highs. Rapid identification of molecular and natural high molecular substances including rapid analysis of crude oil, amber and humic substances. Related techniques can be found in the following papers: HJ Hsu, TL Kuo, SH Wu, JN Oung, J. Shiea, Anal. Chem. 2005, 77, 7744.; HJ Hsu, JN Oung, TL Kuo, SH Wu, J. Shiea, Rapid Commun. Mass Spectrom. 2007. 21, 375.

However, the above experimental devices are too bulky and take up considerable space. In addition, sample injection is quite cumbersome. It is necessary to send the sample to a high temperature furnace and heat it to a set temperature to form a gaseous state. Then, the carrier gas is mixed with the gaseous sample and guided to the free area via a conduit, which is inconvenient and time consuming. And the sample will remain in the tube wall during the transfer process, resulting in sample loss.

Accordingly, a first object of the present invention is to provide a thermal desorption free device for rapid sampling and analysis.

Thus, the thermal desorption free device of the present invention is for desorbing a test object and moving toward an inlet of a mass spectrometer for mass spectrometry, the thermal desorption free device comprising a charge generating unit, a heating unit, and a sampling unit.

The charge generating unit is a solvent droplet that is spaced from the mass spectrometer and that produces a charge toward the inlet of the mass spectrometer. The heating unit includes a heating body, and a passage through the heating body, the passage has an inlet, and an outlet opposite to the inlet, the outlet is directed between the charge generating unit and the mass spectrometer, And the extending direction of the outlet is intersecting with the extending direction of the charge generating unit. The sampling unit includes a probe that can be detached from the passage of the heating unit, and the probe is used for scraping or adhering the object to be tested, so that part of the object to be tested is attached to the probe.

A second object of the present invention is to provide a mass spectrometry system comprising a mass spectrometer having an inlet, and a thermal desorption free device of the first object of the present invention. A third object of the present invention is to provide a mass spectrometry method comprising a sampling step, a desorption step, a charge generation step, and an analysis step.

The sampling step is to scrape or adhere a test object with a probe to attach a portion of the test object to the probe; the desorption step is to extend the probe into a passage through a heating body. And causing the analyte on the probe to be desorbed by the heating body to form a gas phase analyte to leave the channel; the charge generating step causes a charge generating unit to generate a charged solvent droplet toward the entrance of a mass spectrometer And the gas phase analyte is fused with the solvent droplet to form a charged analyte ion; the analysis step is to pass the analyte ion into the mass spectrometer through the inlet, and analyze the mass spectrometer to generate a mass spectrometry. Figure.

The efficacy of the thermal desorption free device, the mass spectrometry system and the mass spectrometry method of the present invention is that the probe can be directly scraped or adhered to the solid and liquid analytes, and the probe is passed through the channel when the probe is The analysis of the analyte to be instantaneously vaporized for free and mass spectrometry can greatly shorten the analysis time of the analyte.

The foregoing and other objects, features, and advantages of the invention are set forth in the <RTIgt;

Referring to Figure 3, a preferred embodiment of the mass spectrometry system 5 of the present invention comprises a mass spectrometer 6 having an inlet 61 and a thermal desorption free device 7. The structure of the mass spectrometer 6 is understood by those skilled in the art and will not be described again. The thermal desorption free device 7 includes a charge generating unit 71, a heating unit 72, and a sampling unit 73.

The charge generating unit 71 is spaced apart from the mass spectrometer 6 and produces charged solvent droplets toward the inlet 61 of the mass spectrometer 6. It should be noted that, in this embodiment, the charge generating unit generates a charged solvent droplet by spraying, and the spraying method may be selected from one of the following methods: electrospray ionization, Nanospray, Sonic spray, or Thermal spray. In addition, the charge generating unit can also generate charged solvent droplets in a discharge manner, and the discharge is selected from one of the following methods: corona discharge, glow discharge, or dielectric. Dielectric barrier discharge.

The heating unit 72 includes a heating body 721 and a passage 722 extending through the heating body 721. The heating body 721 has a heating temperature ranging from 40 to 1500 ° C. The passage 722 has an inlet 723, and a The outlet 724 of the inlet 723 is oriented between the charge generating unit 71 and the mass spectrometer 6, and the extending direction of the outlet 724 is intersected with the extending direction of the charge generating unit 71.

The sampling unit 73 includes a probe 731 that can be drawn away from the passage 722 of the heating unit 72, and a grip portion 732 connected to one end of the probe 731. The probe 731 is used for scraping or adhering a solid or liquid object to be tested (not shown), and a part of the object to be tested is attached to the probe 731. The grip portion 732 has a connection. The needle 731 faces the joint surface 733 of the inlet 723, and the area of the joint surface 733 is larger than the cross section of the inlet 723.

Referring to FIG. 4, a preferred embodiment of the mass spectrometry method of the present invention is a method for analyzing an analyte to be analyzed by the mass spectrometry system 5 described above, comprising a sampling step 81, a desorption step 82, and a charge generation step. 83, and an analysis step 84, the steps of performing the mass spectrometry method using the mass spectrometry system 5 are described below with reference to Figs.

The sampling step 81 is to scrape or adhere the test object 731 to partially attach the test object to the probe 731; the desorption step 82 is to extend the probe 731 from the injection port 723. The channel 722 is inserted into the channel 722, and the object to be tested on the probe 731 is heated and desorbed by the heating body 721 to form a gas phase analyte to be separated from the channel 722 by the outlet 724. The operator can adjust the heating temperature of the heating body 721 according to different properties of the object to be tested to ensure that the object to be tested is heated to form a gas phase and exit the channel 722. The design of the grip portion 732 can be easily operated by the operator, and the area of the connecting surface 733 of the grip portion 732 is larger than the cross section of the inlet 723, so that the probe 731 can be prevented from extending into the passage 722. The entire time falls into the channel 722.

The charge generating step 83 causes the charge generating unit 71 to generate charged solvent droplets toward the inlet 61 of the mass spectrometer 6, and the gas phase analyte will fuse with the solvent droplets to form charged analyte ions, resulting in a strip. The method of the solvent droplet of the charge is as described above, and is not described herein again; the analysis step 84 is such that the analyte ion enters the mass spectrometer 6 via the inlet 61 and is analyzed by the mass spectrometer 6 to generate a mass spectrometry. Figure.

It should be particularly noted that, in this embodiment, the heating temperature of the heating body 721 ranges from 40 to 800 ° C, and the temperature range is only the operating conditions exemplified in the embodiment, and may of course be heated according to actual operation conditions. More than 800 ° C, even up to 1500 ° C or so, not limited by the disclosure of this embodiment.

5 to 13 are experimental examples tested by the apparatus and method of the present invention, which are all tested by the mass spectrometry system 5 shown in FIG. 3 and the analysis step 84 shown in FIG. 4, each of which shows selective ions. The chromatogram and mass spectrum, related structures and steps are as described above, and will not be described in the following description.

As shown in Fig. 5 and Fig. 6, the probe 731 is used to test the surface of the puffer tablet and the heart rhyme ingot respectively. From the results of Figs. 5 and 6, it is confirmed that the present invention can directly analyze the composition of the solid sample. And the active ingredient contained in the solid sample was detected.

As shown in Figs. 7 and 8, the ecstasy powder and the heroin powder were mixed in a commercially available flour to simulate a drug powder, and the probe 731 was adhered to the mixed powder and tested. From the results of Figures 7 and 8, it was confirmed that the presence of ecstasy and heroin could be detected, and it was confirmed that the present invention can directly analyze the components of the powdery sample.

As shown in Figs. 9 and 10, ketamine was added to the urine, and melamine was added to the milk, and the probe 731 was adhered to the mixed liquid and tested. From the results of Figures 9 and 10, it is indeed possible to detect the presence of K and melamine, and it is confirmed that the present invention can directly analyze the composition of the liquid sample.

As shown in Figures 11 to 13, it is a test for daily necessities such as toys, enema bags, and erasers containing plasticizers. The probe 731 was scraped or punctured, respectively, and tested, and from the results of Figs. 11 to 13, it was confirmed that the present invention can surely detect the plasticizer component in the solid sample.

As shown in Figures 14-16, the pesticide residues on the surface of fruits and vegetables are tested separately. Figures 14 to 16 are used to scrape the surface of green pepper, tomato and lotus fog with probe 731, and test whether the pesticide remains. From the results of Figs. 14 to 16, it was confirmed that the present invention can surely detect pesticide residues on the surface of agricultural products.

In summary, the present invention utilizes the above-described apparatus and method to directly scrape or adhere the solid and liquid analytes by the probe 731, and allows the probe 731 to pass through the channel 722 to receive the heating body 721. The heating action causes the analyte on the probe 731 to be vaporized instantaneously for free and mass spectrometry, which not only can quickly obtain the test result (the test result can be produced on average 3-5 seconds), and the analyte is replaced. And the sampling is quite fast, which can greatly shorten the analysis time of the analyte, and can be applied to the detection of a large number of samples, and the analyte does not need to be pre-treated, and can be operated under normal temperature and pressure conditions, and the operation procedure is simple. Therefore, the object of the present invention can be achieved.

The above is only the preferred embodiment of the present invention, and the scope of the invention is not limited thereto, that is, the simple equivalent changes and modifications made by the scope of the invention and the description of the invention are All remain within the scope of the invention patent.

5. . . Mass spectrometry system

6. . . Mass spectrometer

61. . . Entrance

7. . . Thermal desorption free device

71. . . Charge generation unit

72. . . Heating unit

721. . . Heating the body

722. . . aisle

723. . . Inlet

724. . . Export

73. . . Sampling unit

731. . . Probe

732. . . Grip

733. . . Connection surface

81. . . Sampling step

82. . . Desorption step

83. . . Charge generation step

84. . . Analysis step

Figure 1 is a schematic view showing the relative positions and modes of action of various components of an electrospray free mass spectrometer (ESI-MS);

Figure 2 is a schematic view showing the relative positions and modes of action of the major components of a desorption electrospray free mass spectrometer (DESI-MS);

Figure 3 is a schematic view showing a preferred embodiment of the mass spectrometry system of the present invention;

Figure 4 is a flow chart showing a preferred embodiment of the mass spectrometry method of the present invention;

5 to 13 are selected ion chromatograms and mass spectra, illustrating the analysis results of the respective experimental examples of the present invention.

5. . . Mass spectrometry system

6. . . Mass spectrometer

61. . . Entrance

7. . . Thermal desorption free device

71. . . Charge generation unit

72. . . Heating unit

721. . . Heating the body

722. . . aisle

723. . . Inlet

724. . . Export

73. . . Sampling unit

731. . . Probe

732. . . Grip

733. . . Connection surface

Claims (12)

A thermal desorption free device for desorbing a sample to be tested and moving toward an inlet of a mass spectrometer for mass spectrometry, the thermal desorption free device comprising: a charge generating unit, and the mass spectrum The device is spaced apart and faces the entrance of the mass spectrometer to generate charged solvent droplets; a heating unit includes a heating body, and a passage through the heating body, the channel has an inlet, and a reverse An outlet of the sample port, the outlet is oriented between the charge generating unit and the mass spectrometer, and the outlet extends in a direction intersecting the extending direction of the charge generating unit; and a sampling unit includes an extractable extension a probe for the passage of the heating unit, the probe is used to scrape or adhere the test object, and a part of the test object is attached to the probe; when the test object on the probe follows the The probe passes through the passage of the heating unit through the inlet, and is heated and desorbed by the heating body to form a gas phase analyte, and after exiting from the outlet, fuses with the solvent droplets generated by the charge generating unit to form a belt. Electric charge Analyte ions, and into the inlet of the mass spectrometer for analysis. The thermal desorption free device of claim 1, wherein the sampling unit further comprises a grip connected to one end of the probe, the grip having a connection to the probe and facing the injection The joint surface of the mouth, the area of the joint surface is larger than the section of the inlet. The thermal desorption free device according to claim 1, wherein the charge generating unit generates a charged solvent droplet by spraying, and the spraying method is one selected from the following methods: electrospraying free Method, nano spray free method, ultrasonic spray free method, or hot spray free method. The thermal desorption free device according to claim 1, wherein the charge generating unit generates a charged solvent droplet in a discharge manner, and the discharging is performed by one of the following methods: tip discharge, Glow discharge, or dielectric discharge. The thermal desorption free device according to claim 1, wherein the heating unit of the heating unit has a heating temperature ranging from 40 to 1500 °C. A mass spectrometry system for performing mass spectrometry on a sample to be tested, the mass spectrometry system comprising: a mass spectrometer having an inlet for receiving and analyzing ions of the analyte to be desorbed free; and a thermal desorption free The device comprises: a charge generating unit disposed at a distance from the mass spectrometer and generating a charged solvent droplet toward an inlet of the mass spectrometer; a heating unit comprising a heating body and a passage through the heating body, the channel Having an inlet, and an outlet opposite to the inlet, the outlet is oriented between the charge generating unit and the mass spectrometer, and the outlet extends in a direction intersecting the direction in which the charge generating unit extends; a sampling unit includes a probe that can be detached from the passage of the heating unit, and the probe is used for scraping or adhering the object to be tested, so that a part of the sample molecules of the object to be tested are attached to the sample On the probe; when the analyte on the probe passes through the channel of the heating unit through the inlet, the substrate is heated and desorbed to form a gas phase analyte and exits from the outlet. , Solvent droplets and the charge generating unit generating fusion form analyte ions charged into the inlet of the mass spectrometer for analysis. The mass spectrometry system of claim 6, wherein the sampling unit further comprises a grip connected to one end of the probe, the grip having a connection connecting the probe and facing the inlet The area of the joint surface is larger than the cross section of the inlet. The mass spectrometry system according to claim 6, wherein the charge generating unit generates a charged solvent droplet by spraying, and the spraying method is one selected from the following methods: electrospray free method, nai Rice spray free method, ultrasonic spray free method, or hot spray free method. The mass spectrometry system of claim 6, wherein the charge generating unit generates a charged solvent droplet in a discharge manner, and the discharging is performed by one of the following methods: tip discharge, glow discharge, Or dielectric discharge. The mass spectrometry system of claim 6, wherein the heating body of the heating unit has a heating temperature ranging from 40 to 1500 °C. A method for mass spectrometry comprises: a sampling step of scraping or adhering a test object with a probe to attach a portion of the test object to the probe; and a desorption step, extending the probe into the probe Heating a channel of the body, and heating the object to be tested on the probe to be desorbed by the heating body to form a gas phase analyte and leaving the channel; a charge generating step to direct a charge generating unit toward a mass spectrometer The inlet generates a charged solvent droplet, and the vapor phase analyte is fused with the solvent droplet to form a charged analyte ion; and an analysis step, the analyte ion enters the mass spectrometer through the inlet, and A mass spectrogram is generated after analysis by the mass spectrometer. The mass spectrometry method according to claim 11, wherein the heating unit of the heating unit has a heating temperature ranging from 40 to 1500 °C.