RU2612324C2 - Method of continuous stable electric spraying of solutions in source of ions at atmospheric pressure - Google Patents

Abstract

FIELD: electrical engineering.

SUBSTANCE: invention relates to mass-spectrometry. Method enables obtaining a continuous stable flow of charged particles by electric spraying for high volumetric speeds of analyzed substances solutions, without formation of large drops at the beginning of a new sample electric spraying, which substantially simplifies the process of obtaining a continuous and stable mono-dispersed flow of charged particles in wide range of sprayed liquid volumetric flow rates and respectively stable ion current of the analyzed substances coming into the analyzer, as well as long-term operation of the source without disassembling and cleaning. Method features are adding the liquid sample into the area of spraying without interrupting the eluent flow and drying the pumped off the gas-vapour mixture of excess not sprayed eluent and gas. Mode of continuous stable emission of charged particles (ion current) is implemented for an arbitrary long time only provided that each fed into the spraying area sample does not cause hydraulic fracturing of the liquid flow. Besides, the continuous stable mode of emission of charged particles is affected by a long-term stable pumping off the gas-vapour mixture from the area of spraying, which is quite easily achieved by drying the gas-vapour mixture from the eluent. Herewith the adjustable parameter of spraying is the value of electric voltage supplied to the counter electrode, and the flow of withdrawn gas from the coaxial channel between capillaries after setting the stable mode does not change during all time of operation of the ion source at continuous supply of the liquid sample into the area of electric spraying.

EFFECT: technical result is enabling production of continuous long-term stable current of charged particles by electric spraying in a wide range of volumetric speeds of analyzed substances solutions under normal conditions with successive introduction of a sample into the area of spraying and respectively stable ion current of the analyzed substances coming into the analyzer.

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Description

The present invention relates to the field of mass spectrometry, namely, to ion sources with a soft ionization method using electrospray of the analyzed solutions in a nonuniform constant electric field at atmospheric pressure, and will find wide application in mass spectrometry, ion mobility spectrometry in solving problems of organic and bioorganic chemistry, immunology, medicine, diagnosis of diseases, biochemical studies, pharmaceuticals, proteomics, metabolomics e and forensics: the study of proteins, including their tryptic hydrolysates (obtaining peptide maps, searching for drug candidates by the interaction of a library of ligands, synthetic or natural origin, with target proteins), trace analysis of biochemical markers, drugs and their metabolites in biological tissues and liquids.

In the process of electrospray of analyzed solutions of substances for ion sources in an inhomogeneous constant electric field at atmospheric pressure, hot satellite gas is used to obtain ions of the studied substances from charged microdrops.

A well-known method for extracting ions from solutions at atmospheric pressure [1] is that at the end of the metal capillary through which the solution of the substance flows, a meniscus of liquid is formed under the influence of a nonuniform constant electric field, from which the emission of charged microdrops evaporates under normal conditions with the formation of ions transported by an electric field or satellite gas to an ion analyzer. The flow of the analyzed solution was 0.05-5 μl / min. This method has much in common with other spray methods, which include: Aerospray [2], Electrospray [3], Ion Spray [4], Thermospray [5], Atmospheric Pressure Ionization (API) in combination with ultrasonic spray of liquid [6 ]. In all these methods, the analyzed solution is converted into a finely dispersed charged aerosol, which evaporates in the region with atmospheric gas pressure, and evaporation products, including charged ions, are taken into the chamber of the ion analyzer through a gas-dynamic conveying system. The difference in the methods used for dispersing and charging microdrops does not change the essence of the physical processes leading to the extraction of ions from an evaporating charged aerosol. This is confirmed by the similarity of mass spectra for different spray methods. All these methods are aimed at increasing the flow of sprayed liquid to match the flow of liquid from the chromatographic column, i.e. 50-200 μl / min.

As the latest examples in this direction of the development of the ion source for solutions of labile substances, one can cite [7–8]. In these devices, electrospray plays an auxiliary role, as a way of charging micro droplets of liquid sprayed by an additional stream of atomizing gas, usually nitrogen. For the greatest extraction of the charged component from the obtained microdroplets, another auxiliary stream of hot gas-evaporator began to be used. Thus, in the design of the ion source with electrospray of the solution, only the charging of the sprayed microdrops remains from the method itself, and the microdrops in the form of a “shower” are received and their evaporation occurs gasdynamically in gas flows. The main disadvantage of these methods is the non-monodispersity of the emitted charged microdrops and, accordingly, the unstable ion current, which affects the shape of the recorded spectra, as shown by the example of the ion mobility spectrum in [9].

The best characteristics in the range of the space velocity of the analyzed solution using electrospray and ion current stability were obtained in [10]. The method of spraying large volumes of the analyzed solution for ion sources of electrospray with a stable ion current, proposed in [11], is selected as a prototype in this patent.

A known method of electrospraying chromatographic flows of analyte solutions of substances for ion sources with atmospheric pressure, based on the formation of the meniscus of the analyzed liquid in a strong electric field with the emission of charged particles from the top of the meniscus, and the unsprayed solution is removed from the spraying area by countercurrent gas flow through the coaxial channel under normal conditions.

The disadvantage of this method is that it is not possible to completely avoid the appearance of large drops when entering the mode or setting up stable spraying at the beginning of the process. The consequence of this significant drawback is the need to clean the elements of the transportation system due to the deposition of non-volatile components (not become ions) from non-evaporated droplets.

The aim of the proposed method is the organization of a stable, monodisperse flow of charged microdrops by electrospray for chromatographic flows of the analyzed solutions of substances, with the elimination of the formation of large droplets during the spraying period, including when changing the injected sample solution, based on the fact that the eluent is supplied to the region the liquid sample is injected through the injector without interruption of the liquid flow, and in the pumping channel of the unsprayed eluent in the mixture with gas, the pumping pump is drained Vai gas by dehumidifier installed in front of the air micropump allows continuously and efficiently separate air pumped from the eluent under standard conditions. After entering the stable spraying mode, the settings (voltage at the counter electrode and the volume of the countercurrent of the surrounding gas through the coaxial channel) do not change when the fluid flow is continuously introduced into the supply channel to the spraying area. A mixture of water and acetonitrile with the addition of acetic or formic acid is used as an eluent.

As an example embodiment of the invention, the following actions can be considered. An electrospray ion source and a dynamic fluid flow divider [9] connects a liquid micropump to the eluent supply channel, for example, a Harvard Apparatus Sigle Syringe Pump MAI 70-2208 Model 11 Plus syringe micropump, or a microcolumn liquid chromatograph with a set value of the eluent flow. Between the ion source and the liquid micropump, an injector is installed, a three-way switch tap, which allows the sample solution to be introduced into the flow of the eluent pumped by the micropump without breaking the fluid flow. An Tomas 50200 type air micropump is connected to the pumping channel for the vapor-gas mixture from the nebulized eluent and laboratory air, a Festo LF-1/8-D-MINI 40 air dryer is installed between the air micropump and the ion source in the pumping channel, and to control the flow of the gas-vapor mixture, the same channel, the OMEGA 2317 gas flow meter is installed, it is better if it is installed between the air micropump and the air dryer. Such an embodiment of the invention makes it possible to reproduce and control the operating parameters of the entire system for continuous stable electrospray of solutions in an ion source at atmospheric pressure.

Information sources

1. Alexandrov M.L., Gal L.N., Krasnov N.V., Nikolaev V.I., Pavlenko V.A., Shkurov V.A. DAN T. 277, No. 2. Physical chemistry, p. 379-383 (1984).

2. Iribarne J.V., Thomson B.A. Int. J. Mass-spectrom. Ion phys. V. 50, p. 331 (1982).

3. Fenn J.B., Whitehouse CM., Dreyer R.N., Yamashita M. Anal. Chem. V. 57, p. 675 (1985).

4. Covey T.R., Bruins A.P., Henion J.D. Anal. Chem. V. 59, p. 2642 (1984).

5. Pilesot D., Kin H.Y., Diches D.F., Vestal M. Anal. Chem. V. 56, p. 1236 (1984).

6. Kambara H. Anal. Hem. V. 54., p. 143 (1982).

7. Shimadzu Corp. (www.Shimadzu.com).

8. Thermo Scientific (www.tectronica.com).

9. V.A. Samokish, N.V. Krasnov, M.Z. Muradymov. Electrospray ion source with dynamic fluid flow divider. // Scientific instrument making. 2012, T. 22, No. 3, S. 5-12.

10. N. Arseniev, N.V. Krasnov, M.Z. Muradymov. Investigations of electrospray stability during dynamic division of fluid flow. // Mass spectrometry, 2014, T. 11, No. 1, S. 36-38.

11. N.V. Krasnov, M.Z. Muradymov, Samokish V.A. Patent for invention No. 2530782 dated 08/15/2014. The method of electrospraying of chromatographic streams of analyzed solutions of substances for ion sources.

Claims (1)

The method of electrospraying chromatographic flows of analyte solutions of substances for ion sources with atmospheric pressure, based on the formation of the meniscus of the analyzed liquid in a strong electric field with the emission of charged particles from the top of the meniscus, oriented vertically upward, while the unsprayed eluent is removed from the spraying area by countercurrent surrounding gas through a coaxial channel under normal conditions, characterized in that a liquid sample is introduced into the eluent supply channel into the spray area the injector without interrupting the fluid flow, and in the pumping channel of the unsprayed eluent mixed with gas, the pumped gas is drained.