Quantitative small molecule MALDI mass spectrometer

Abstract

The present invention provides a quantitative small molecule MALDI mass spectrometer, comprising: a box body, a box cover is arranged above the box body, and a first sponge board is arranged on the inner bottom surface of the box body. The present invention is small in volume and convenient to carry. The present invention is also provided with an automatic sampler, which samples the test sample through the automatic sampler, which can not only reduce the workload of experimental personnel, but also enhance the automation level of the entire inspection platform. And sampling through the automatic sampler can avoid manual sampling, resulting in inconsistent test samples and large errors in test results. And relevant software for instrument control and suitable for automatic processing of clinical data is compiled to further simplify the clinical application and inspection result reporting process. A variable electric field generator is arranged inside the present invention, and the electric field direction can be changed through the variable electric field generator to make ions reflect in the flight tube, which is more suitable for testing small molecule metabolites, and its mass resolution ability is greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and particularly to a quantitative small molecule MALDI mass spectrometer. Background Art

[0002] MALDI-TOF MS is a new type of soft ionization organic mass spectrometry developed in recent years and has become a powerful tool for detecting and identifying polypeptides, proteins, polysaccharides, nucleotides, glycoproteins, polymers, and various synthetic polymers in recent years. The principle is as follows: When a co-crystalline film formed by a sample and a matrix is irradiated with a laser of a certain intensity, the matrix absorbs energy from the laser, and charge transfer occurs between the matrix and the sample, causing the sample molecules to ionize. The ionized sample is accelerated through a flight tube under the action of an electric field and is detected according to the different flight times to reach the detector, that is, it is detected that the mass-to-charge ratio of the ion is proportional to the flight time of the ion. The core technology of MALDI-TOF-MS is to detect based on the different mass-to-charge ratios m / z of the samples and measure the molecular weights of the sample molecules.

[0003] Matrix-assisted laser desorption / ionization time-of-flight mass spectrometry MALDI-TOFMS is the simplest mass spectrometer to use among various mass spectrometers, with low requirements for pretreatment, high throughput, and high sensitivity, and is regarded as the most likely mass spectrometer to be popularized in clinical applications. However, due to poor reproducibility and low quantitative accuracy, traditional MALDI-TOF MS is currently only applied to qualitative applications such as microbial identification, nucleic acid analysis, and screening of food safety prohibited drugs. In medical applications, especially in the detection of metabolic small molecules with a large demand in clinical tests, there is still a bottleneck that the quantitative accuracy cannot meet the requirements. Summary of the Invention

[0004] In view of the above deficiencies in the prior art, the present invention provides a quantitative small molecule MALDI mass spectrometer.

[0005] In order to achieve the above invention purpose, the technical solution of the present invention is as follows:

[0006] A quantitative small molecule MALDI mass spectrometer, comprising: a box body, a box cover is arranged above the box body, a sponge board one is arranged on the inner bottom surface of the box body, a placement groove one is arranged above the sponge board one, a mass spectrometer body is arranged inside the placement groove one, a placement groove two is arranged above the sponge board one and close to one side of the sponge board one, an automatic sampler is arranged inside the placement groove two, a sponge board two is arranged above the inner part of the box cover, a handle is arranged above the box cover, a buckle is arranged on one side of the box cover, the box body and the box cover are connected by a hinge, and the box body and the box cover are connected by the buckle.

[0007] As an improvement, the mass spectrometer body includes: a housing, inside which a solid-state laser, a variable-voltage power supply, a flight tube, a detector, and a variable electric field generator are provided. The variable-voltage power supply is electrically connected to the solid-state laser, the detector, and the variable electric field generator, and the flight tube communicates with the detector.

[0008] As an improvement, the flight tube has a length between 0.3 meters and 0.5 meters.

[0009] As an improvement, three flight tubes are provided and are arranged in a superimposed triangular shape, and three solid-state lasers are provided and are respectively corresponding to the flight tubes.

[0010] As an improvement, the solid-state laser is an ultraviolet laser, an infrared laser, or a variable light laser.

[0011] As an improvement, the solid-state laser is an ultraviolet laser configured to emit a laser beam having a wavelength between 340 nm and 370 nm.

[0012] As an improvement, the solid-state laser is configured to input an ultraviolet laser beam having an energy measured at the target between 1 - 10 microjoules and a pulse width between 2 - 5 nanoseconds.

[0013] As an improvement, a digital converter that communicates with the detector is further included.

[0014] As an improvement, a controller is provided inside the mass spectrometer body, and an analysis module that communicates with the detector is provided inside the controller.

[0015] The beneficial effects of the present invention are as follows:

[0016] (1) The present invention is small in size and convenient to carry. The present invention is also provided with an automatic sampler, which samples the test samples through the automatic sampler. This can not only reduce the workload of experimental personnel, but also enhance the automation level of the entire inspection platform. And sampling through the automatic sampler can avoid manual sampling, resulting in inconsistent test samples and large errors in test results. And relevant software for instrument control and automated processing of clinical data is compiled to further simplify the clinical application and test result reporting process.

[0017] (2) A variable electric field generator is provided inside the present invention. By changing the electric field direction through the variable electric field generator, ions can be reflected in the flight tube, which is more suitable for testing small molecule metabolites, and its mass resolution ability is greatly improved.

[0018] (3) The interior of the present invention is provided with three flight tubes and three solid-state lasers corresponding to the three flight tubes. In this way, ions of the same detection sample enter the three flight tubes, and then are monitored by the same detector, and the data monitored by the three flight tubes are analyzed by the monitor, improving the reproducibility of the data and meeting the requirements of quantitative application of clinical small molecule metabolites. Description of the Drawings

[0019] Figure 1 is a schematic structural diagram of the present invention;

[0020] Figure 2 is a front view of the present invention;

[0021] Figure 3 is Figure 1 a block diagram of an exemplary circuit of the mass spectrometer body in

[0022] Figure 4 is Figure 1 a side view of the flight tube in

[0023] List of Reference Numerals for the Drawings:

[0024] 1, box body; 2, box cover; 3, first sponge board; 4, first placement groove; 5, mass spectrometer body; 6, second placement groove; 7, automatic sampler; 8, second sponge board; 9, handle; 10, buckle. Detailed Embodiments

[0025] In order to make the content of the present invention easier to be clearly understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. The same components are denoted by the same reference numerals. It should be noted that the terms "front", "rear", "left", "right", "upper" and "lower" used in the following description refer to the directions in the drawings, and the terms "inner" and "outer" refer to the directions towards or away from the geometric center of a specific component respectively.

[0026] As Figure 1 shown in the quantitative small molecule MALDI mass spectrometer, including: a box body 1, a box cover 2 is arranged above the box body 1, a first sponge board 3 is arranged on the inner bottom surface of the box body 1, a first placement groove 4 is arranged above the first sponge board 3, a mass spectrometer body 5 is arranged inside the first placement groove 4, a second placement groove 6 is arranged above the first sponge board 3 and close to one side of the first sponge board 3, an automatic sampler 7 is arranged inside the second placement groove 6, a second sponge board 8 is arranged above the box cover 2, a handle 9 is arranged above the box cover 2, a buckle 10 is arranged on one side of the box cover 2, the box body 1 and the box cover 2 are connected by a hinge, and the box body 1 and the box cover 2 are connected by the buckle 10.

[0027] Among them, the automatic sampler 7 is used to automatically sample the samples, so that the samples are unified. This not only reduces the workload of the testers, but also avoids the large errors in the detection data caused by manual sampling.

[0028] Reference Figure 2 , the mass spectrometer body 5 includes: a housing, inside which a solid-state laser, a variable voltage power supply, a flight tube, a detector and a variable electric field generator are provided. The variable voltage power supply is electrically connected to the solid-state laser, the detector and the variable electric field generator, and the flight tube communicates with the detector.

[0029] It should be noted that the flight tube has a length between 0.3 meters and 0.5 meters, there are three flight tubes, and they are stacked in a triangular shape. There are three solid-state lasers, and they correspond to the flight tubes respectively.

[0030] During operation, the same sample is placed on the sample plate. The same sample is irradiated by three solid-state lasers to form a co-crystalline film with the matrix. The matrix absorbs energy from the laser and transfers it to the biomolecule, and during the ionization process, protons are transferred to the biomolecule or obtained from the biomolecule, thus ionizing the biomolecule. The sample ions enter the flight tube. Under the electric field of the variable electric field generator, the sample ions are accelerated and fly in the flight tube, and the electric field is changed under the action of the variable electric field generator to reflect the flight direction of the sample ions, and finally reach the detector for detection.

[0031] It should be noted that the solid-state laser is an ultraviolet laser, an infrared laser or a variable light laser. The solid-state laser is an ultraviolet laser configured to emit a laser beam with a wavelength between 340 nm and 370 nm, and the solid-state laser is configured to input an ultraviolet laser beam with an energy measured at the target between 1 - 10 microjoules and a pulse width between 2 - 5 nanoseconds.

[0032] Reference Figure 2 , and it also includes a digital converter that communicates with the detector.

[0033] It should be noted that a controller is provided inside the mass spectrometer body 5, and an analysis module that communicates with the detector is provided inside the controller. The analysis module can analyze the data monitored by the same sample in the three flight tubes, thus improving the reproducibility of the data and meeting the requirements of clinical small molecule metabolite quantification applications.

[0034] The operating software inside the invention is self-developed software and does not need to use foreign software. This makes the operating software simple and easy to learn, reducing mistakes during the operation process during detection, thereby improving the authenticity of data. The self-developed software suitable for automatic processing of clinical data further simplifies the clinical application and the process of reporting test results.

[0035] The basic working process of the invention includes: pretreatment of clinical samples (including impurity separation, target molecule enrichment, sample concentration, additive addition, etc.), mass spectrometry sample preparation (mixing matrix, sample spotting, etc.), mass spectrometry detection and data acquisition, data processing, comparison, and report generation, etc.

[0036] Moreover, the invention improves in the application method, improving the factors that may affect reproducibility during the instrument testing process, including the pretreatment process of samples, the selection of MALDI mass spectrometry matrix, the application method of the matrix, and the sample preparation process, etc. By combining these two aspects of improvements, the invention can truly perform clinical quantitative analysis.

[0037] The above are only the preferred embodiments of the present invention for patent, and are not intended to limit the present invention for patent. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention for patent shall be included within the protection scope of the present invention for patent.

Claims

1. A quantitative small molecule MALDI mass spectrometer, characterized in that, Including: A box body (1), a box cover (2) is arranged above the box body (1), a first sponge board (3) is arranged on the inner bottom surface of the box body (1), a first placement groove (4) is arranged above the first sponge board (3), a mass spectrometer body (5) is arranged inside the first placement groove (4), a second placement groove (6) is arranged above the first sponge board (3) and close to one side of the first sponge board (3), an automatic sampler (7) is arranged inside the second placement groove (6), a second sponge board (8) is arranged above the box cover (2), a handle (9) is arranged above the box cover (2), a buckle (10) is arranged on one side of the box cover (2), the box body (1) and the box cover (2) are connected by a hinge, and the box body (1) and the box cover (2) are connected by the buckle (10); Wherein, the mass spectrometer body (5) includes: a housing, a solid-state laser, a variable voltage power supply, a flight tube, a detector and a variable electric field generator are arranged inside the housing, the variable voltage power supply is electrically connected to the solid-state laser, the detector and the variable electric field generator, and the flight tube communicates with the detector; there are three flight tubes, and they are stacked in a triangular shape, and there are three solid-state lasers, and they respectively correspond to the flight tubes.

2. The quantitative small molecule MALDI mass spectrometer according to claim 1, characterized in that, The flight tube has a length between 0.3 meters and 0.5 meters.

3. The quantitative small molecule MALDI mass spectrometer according to claim 2, characterized in that, The solid-state laser is an ultraviolet laser, an infrared laser or a variable light laser.

4. The quantitative small molecule MALDI mass spectrometer according to claim 3, characterized in that, The solid-state laser is an ultraviolet laser configured to emit a laser beam with a wavelength between 340 nm and 370 nm.

5. The quantitative small molecule MALDI mass spectrometer according to claim 4, characterized in that, The solid-state laser is configured to input an ultraviolet laser beam with an energy measured at the target between 1 - 10 microjoules and a pulse width between 2 - 5 nanoseconds.

6. The quantitative small molecule MALDI mass spectrometer according to claim 1, characterized in that, It further includes a digital converter that communicates with the detector.

7. The quantitative small molecule MALDI mass spectrometer according to claim 1, characterized in that, A controller is arranged inside the mass spectrometer body (5), and an analysis module that communicates with the detector is arranged inside the controller.

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