阅读说明：本技术 生物样品快速质谱进样装置 (Quick mass spectrum sampling device for biological samples ) 是由 郑江花 胡海俊 丁正知 于 2020-07-23 设计创作，主要内容包括：本发明公开了一种生物样品快速质谱进样装置,主要涉及一种生物样品的质谱快速进样装置,具体来说是通过超声悬浮的方式,让生物样品液滴或小颗粒呈悬浮状态放置于容器内部,无其他界面接触,能够有效的保证样品的原始状态,保证了样品以最原本的状态完成质谱分析上样,装置直接置于质谱仪的离子源和大气压接口之间,可以直接完成生物样品的快速质谱分析。本发明通过一个装置和简单对接质谱的使用方法能够大大简化生物样品的质谱分析速度,同时能够减少样品处理的损失和二次污染等问题,同时还可以通过置入容器内,完成样品的短期存储和运输,同时可以实现无污染的多次使用。(The invention discloses a rapid mass spectrum sample introduction device for a biological sample, and mainly relates to a rapid mass spectrum sample introduction device for the biological sample, which particularly enables liquid drops or small particles of the biological sample to be placed in a container in a suspension state in an ultrasonic suspension mode without other interface contact, can effectively ensure the original state of the sample, ensures that the sample is subjected to mass spectrum analysis in the most original state, and can be directly placed between an ion source and an atmospheric pressure connection port of a mass spectrometer to directly complete the rapid mass spectrum analysis of the biological sample. The invention can greatly simplify the mass spectrum analysis speed of the biological sample by a device and a simple application method of butt-joint mass spectrum, simultaneously can reduce the problems of loss of sample treatment, secondary pollution and the like, can complete short-term storage and transportation of the sample by being arranged in a container, and can realize multiple applications without pollution.)

1. Quick mass spectrum sampling device of biological sample, its characterized in that: the ultrasonic suspension device comprises a fixing device and an ultrasonic suspension device, and a biological sample is suspended and stored at a position between a transmitting end and a reflecting end of the ultrasonic suspension device.

2. The rapid mass spectrometry sample introduction device for biological samples as claimed in claim 1, wherein: the fixing device is of a structure with two open sides and is used for ionization of the ion source and entering an atmospheric pressure interface of the mass spectrometer.

3. The rapid mass spectrometry sample introduction device for biological samples as claimed in claim 1, wherein: the position and the ultrasonic frequency generated by the ultrasonic suspension device are adjustable, and the intensity is adjustable.

4. The rapid mass spectrometry sample introduction device for biological samples as claimed in claim 1, wherein: the sample storage position is the middle position between the transmitting end and the receiving end of the ultrasonic suspension device probe, and the form of the stored sample can be liquid or solid.

5. The rapid mass spectrometry sample introduction device for biological samples as claimed in claim 2, wherein: the upper end and the lower end of the fixing device are adjustable, and the fixing device can be matched with an ultrasonic suspension device to finish storage and analysis of biological samples with different sizes.

Technical Field

The invention relates to a quick mass spectrum sample introduction device for a biological sample, in particular to a quick sampling and quick butt-joint mass spectrum analysis device for a small amount of liquid biological samples without pollution.

Background

High quality biological samples are the prerequisite for successful implementation of clinical tests in omics research and personalized medical procedures. The preservation mode of the biological sample is related to the quality of the sample to be detected and the detection result. Proper handling and storage of the sample is essential for obtaining accurate measurement results, and high requirements are made for the pollution-free storage of the biological sample. Meanwhile, in recent years, the national places importance on the control of medical wastes, and the development of an environment-friendly and high-efficiency biological sample storage mode is a necessary development trend of biological sample storage in the future.

The development of high throughput technology in the field of life sciences has facilitated the study of various classes of omics such as genome, transcriptome, proteome and metabolome. Accordingly, it is necessary to obtain high quality biological samples in order to objectively, comprehensively and completely reflect the respective amounts of nucleic acids, proteins, metabolic molecules and the like and the mutual relationship between them. High quality biological samples are the prerequisite for successful implementation of clinical tests in omics research and personalized medical procedures. In the actual sample testing or research process, the phenomena of sample quality failure and false positive are often encountered, and the results brought by improper sample processing, storage and management modes are sometimes disastrous. In the actual analysis process, due to the extreme complexity of the biological system, the pretreatment process is very complicated, which may cause many problems such as exogenous pollution and insufficient recovery rate, and how to complete the accurate collection, correct labeling, pollution-free treatment, high recovery rate sample loading of the biological sample becomes very important.

The high sensitivity and high throughput analysis characteristics of the mass spectrometry technology make the mass spectrometry technology a powerful tool in the aspects of biomedical detection and clinical detection of biomarkers, and particularly, the mass spectrometry method of liquid chromatography-mass spectrometry (LC-MS) is widely applied to analysis such as neonatal disease screening, drug concentration monitoring, in-vivo hormone and nutrient detection, microorganism identification and the like, and even becomes a national standard or a laboratory standard. Because the mass spectrum itself can only detect the ion in the gas phase, and simultaneously because the particularity of organism itself, such as tissue, body fluid or cell, need pass through a large amount of preliminary treatments, mostly can only accomplish in professional laboratory, need a large amount of professional equipment such as breaker, centrifuge, nitrogen-blowing appearance simultaneously and all kinds of chemical reagent's cooperation. With the increasing application problems of field rapid inspection and public health rapid response, some mass spectrometry methods without preprocessing or simple processing have come into existence, but mainly focus on ion source technology, such as DART source and DESI source. The Direct Analysis in Real Time ion source (DART source for short) is a thermal Analysis and ionization technique, and the sample is placed on a carrying device between the DART source outlet and the ion sampling port of the LC-MS mass spectrometer for Analysis. The Desorption Electrospray Ionization (DESI) source is a novel normal pressure Ionization technology, and can directly place an unprocessed sample on the surfaces of various carrying devices. These analytical approaches eliminate the need for cumbersome sample preparation and time-consuming chromatographic separations, dramatically shorten sample analysis periods, and greatly reduce capital and personnel investments. However, in the analysis process of biomedical samples, the process of the treatment-free mass spectrometry realized by the ion source still has the processes of simple treatment, transfer to the surface of a carrying device and the like of the samples.

With the application of many modern medical detection means and the development of personalized medicine, the number of biological samples collected by basic research and clinical examination is more and more, and the transportation or the storage of the biological samples for a long time consumes a lot of resources and environmental cost. The existing storage modes of biological samples are also concentrated on the modes of low-temperature storage such as sample bags and sample bottles, or normal-temperature storage requiring special treatment such as vacuum freeze-drying, and the like, the storage needs the support of consumables, the pretreatment time and the intervention of numerous manual operations exist, certain operation experience requirements exist, how to effectively enable the collection, the transient storage and the rapid mass spectrum sample loading of the samples to be the problems to be solved, no pollution-free and reusable biological sample collection, storage and rapid mass spectrum sample loading schemes exist in China at present, along with the development of precise medicine, the dependence on biomedical detection technology is increased, and the development of pollution-free and reusable biological sample collection, storage and rapid mass spectrum sample loading schemes is also a development direction.

Disclosure of Invention

The invention aims to solve the technical problems of realizing pollution-free and reusable biological sample collection and storage and rapid mass spectrum sample loading analysis, and therefore provides a rapid mass spectrum sample introduction device for a biological sample. The method can greatly simplify the mass spectrometry speed of the biological sample, simultaneously can reduce the problems of loss of sample treatment, secondary pollution and the like, can complete short-term storage and transportation of the sample by being placed in a container, and can realize multiple uses without pollution.

The invention solves the technical problems through the following technical scheme: through the mode of supersound suspension, let biological sample liquid drop or tiny particle be suspension state and place inside the container, do not have other interface contact, can the effectual initial condition who guarantees the sample, guaranteed that the sample accomplishes mass spectrometry with the state of original most and go up the appearance, the device directly is arranged in between the ion source of mass spectrograph and the atmospheric pressure interface, can directly accomplish biological sample's quick mass spectrometry. Specifically, the device comprises a fixing device and an ultrasonic suspension device, and the biological sample can be directly placed in a position between the transmitting end and the reflecting end of the ultrasonic suspension device for suspension storage. The position of the ultrasonic suspension device, the generated ultrasonic frequency and the intensity are adjustable, and the fixing device is of a structure with two open sides and is used for ionization of an ion source and entering an atmospheric pressure interface of a mass spectrometer.

Preferably, the frequency and the intensity of the ultrasonic suspension device are adjustable, and the energy of the ultrasonic horn is adjusted according to different types and weights of samples, so that the samples can overcome the gravity and be stabilized in the air. Meanwhile, the upper position and the lower position of the reflection end are adjustable and used for adjusting the shape of the longitudinal wave, so that the sample can be finely adjusted up and down, and the sample can be stably and uniformly distributed on the central position of the ultrasonic standing wave.

The method for rapid mass spectrometry sample introduction of biological samples as claimed in claim 1, wherein the position and generation of ultrasonic frequency and intensity of the ultrasonic suspension device are adjustable.

A biological sample storage method and apparatus as claimed in claim 1, wherein: the sample storage position is the middle position between the transmitting end and the receiving end of the ultrasonic suspension device probe, and the form of the stored sample can be liquid or solid.

As stated in claim 2, the upper and lower ends of the fixing device are adjustable, and can be matched with the ultrasonic suspension device to store and analyze biological samples with different sizes.

The positive progress effects of the invention are as follows: this mode through supersound suspension lets biological sample liquid drop or tiny particle be suspension state and places inside the container, does not have other interface contact, can the effectual pristine condition who guarantees the sample, has stopped sample transfer process and the secondary pollution that probably appears after the transfer, and can also realize short duration preservation and transportation through certain packing, if need long distance long-time transportation can also effectively improve sample storage time through the mode of evacuation or leading to inert gas.

Drawings

FIG. 1 is a schematic view of the main body of the apparatus of the present invention;

FIG. 2 is a schematic diagram of the apparatus installation and use of the present invention;

FIG. 3 is a schematic diagram of the device short term storage and transport method of the present invention.

Detailed Description

The invention is further described below with reference to the accompanying drawings to illustrate the technical solutions in detail. The drawings are simplified schematic diagrams only serving as basic illustrations of the invention, and therefore only show the composition structures relevant to the invention.

The invention describes a rapid mass spectrum sample introduction device and a rapid mass spectrum sample introduction method for a biological sample, which can be a small amount of body fluid such as blood, urine and the like, and can also be a small amount of solid tissue. The following explains the present invention in detail by way of specific embodiments.

The implementation example is as follows: the device structure body of the invention comprises two parts, 1) a fixing device; 2) an ultrasonic suspension device; as shown in fig. 1, 101 is an ultrasonic horn, 102 is an ultrasonic emitting end of an ultrasonic suspension device, 103 is an ultrasonic receiving end of the ultrasonic suspension device, 104 is a position adjusting device of the receiving end, 105 is a stored biological sample, and 106 and 107 are fixing devices.

In practical application, the mass spectrometer can be directly docked to the mass spectrometer in a position intermediate the ion source and the atmospheric pressure interface. Fig. 2 shows a sample rapid mass spectrometry sampling apparatus and a method for docking a mass spectrometer, in which 108 is an ion source of the mass spectrometer, which may be various atmospheric pressure sources, such as ESI source, APCI source, APPI source, etc., or direct ionization sources, such as DART source and DESI source, etc.; 109 is the atmospheric pressure interface of the mass spectrometer. In the implementation process, the device structure body (the part in the dotted line frame in fig. 2) needs to be placed between the ion source and the atmospheric pressure connection port of the mass spectrometer, the liquid sample is placed between the transmitting end and the receiving end of the ultrasonic suspension device in a mode of an injection needle or a dropper and the like, the solid sample is placed between the transmitting end and the receiving end of the ultrasonic suspension device in a mode of tweezers or a sample spoon and the like, and ionization of the ion source is completed and then the solid sample enters the atmospheric pressure connection port to complete mass spectrometry.

Fig. 3 shows a storage and transfer mode of the sample introduction device for rapid mass spectrometry of biological samples, wherein 201 in the dashed line box is a main body part of the sample introduction device for rapid mass spectrometry of biological samples, and after the sample introduction is completed, the sample is required to be transported or stored for a short time, and the sample is required to be stored in a container. 202 is a container body portion, 203 and 204 are on-off valves for evacuating or passing an inert gas, and 205 is an openable door structure. The liquid sample is arranged at the middle position between the transmitting end and the receiving end of the ultrasonic suspension device in a mode of 209 injection needles or droppers and the like; the solid sample is arranged at the middle position of the transmitting end and the receiving end of the ultrasonic suspension device in modes of tweezers, sample spoons and the like, and after the sample is arranged, inert gases such as nitrogen, helium, argon and the like can be pumped in vacuum or flushed in vacuum, so that the internal air can be completely replaced, and the biological sample is guaranteed to be stored in a vacuum or inert environment.

The above embodiments are described in further detail to solve the technical problems, technical solutions and advantages of the present invention, and it should be understood that the above embodiments are only examples of the present invention and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.