RU2420826C1 - Method for structural chemical analysis of organic and bioorganic compounds while separating ions of said compounds in supersonic gas stream directed along linear radio-frequency trap - Google Patents

Abstract

FIELD: physics. ^ SUBSTANCE: invention is based on separation of ions in a linear radio-frequency trap in a gas stream near the axis of said trap based on differences in mass, charge and mobility of ions when said ions are exposed to alternating and constant electric fields, created inside the trap, including charges of ions with relatively small m/z, focused around the axis of the trap, wherein ions can further be separated based on degree of resistance to collision-induced dissociation. The disclosed method involves detection of directed signals from rotating or oscillating ions derived from the gas stream by volume charge relative small ions or a non-resonance rotating field and also under the effect of fields, close on resonant on frequency, which excite harmonic motion of ions with selected m/z values. Recording of mass-spectra of product ions during collision-induced dissociation can also be carried out using a mass analyser interfaced with the trap, particularly time-of-flight mass analyser with an orthogonal ion input. ^ EFFECT: possibility of obtaining two mass-spectra of ions produced via dissociation activated by single or multiple collisions for analysed compounds. ^ 21 cl, 11 dwg

Description

FIELD OF THE INVENTION

The present invention relates to methods and techniques for the chemical analysis of organic and bioorganic compounds based on a combination of the separation of ions of these compounds according to the mass-to-charge ratios, mobility, charge states of ions and the degree of fragmentation resistance induced by repeated collisions with atoms and molecules of a buffer gas, from masses - spectrometric analysis of such partially separated ions and ion products of their fragmentation. In particular, we are talking about the preliminary separation of ions under the combined action of electric fields and a gas stream in a linear radio-frequency trap according to the values of masses, charges and collision cross-sections with atoms or molecules of the gas stream and, if necessary, according to the degree of resistance to monomolecular decay processes. The collision-induced fragmentation of selected ions can also be accelerated along the gas stream, and the analysis of product ions by mass-to-charge ratios can be performed using a time-of-flight mass spectrometer with orthogonal ion input (ortho-VMS) or on some other mass analyzer, paired with a linear RF trap.

The proposed approaches and methods are useful for qualitative and / or quantitative chemical and biological analysis.

BACKGROUND

After the development and creation at our institute of the first time-of-flight mass spectrometers with orthogonal ion injection (ortho-VPMS) [1, 2], devices of this type were widely used both in solving analytical problems and in studying the structure of biomolecules [3-5]. The convenience of combining such devices with various devices for preliminary separation of ions, producing a continuous or quasicontinuous ion flux, with pulsed time-of-flight mass analysis, which is record-breaking in speed among all known types of mass analyzers, has led to the high efficiency and attractiveness of such combinations for solving various analytical and structural problems . At the same time, there are important structural and analytical problems for which the separation ability and “information performance” of known instrumentation systems, including ortho-VPMS, are insufficient. To overcome these limitations, it is natural to strive to introduce additional measurement dimensions into the mass spectrometric experiment, associated, for example, with the combined action of electric fields and gas flow on the ions under study, which is essentially a specific variant of ion mobility separation.

An ion mobility spectrometer typically includes an ionization source, a drift cell, and an ion detector. The ion detector may be, for example, a Faraday cup, an electron multiplier, or a mass spectrometer. The ion mobility spectrometer (IIS) separates ions by their mobility in a drift or buffer gas based on their different equilibrium drift velocities. When gas-phase ions in the presence of a buffer gas are exposed to a constant electric field, they are accelerated until they collide with a neutral atom or molecule of a buffer gas. This acceleration and subsequent collisions are repeated many times. After some time, this microscopic scenario averages the instantaneous velocities of the ions, which leads to their constant drift velocity, which depends on the size of the ion, its charge, pressure and temperature of the buffer gas. The ratio of the ion drift velocity to the electric field strength is defined as the mobility of the ion. In other words, the ion drift velocity (V _d ) is proportional to the electric field strength (E), where the ion mobility κ = V _d / E is a function of the ion volume / charge ratio. Thus, SIP is a separation technique similar to mass spectrometry. SIP is known to have high sensitivity with moderate resolution. The separation efficiency decreases due to diffusion spreading of the “packet” of ions, leading to a temporary broadening of the curves of the detected ion current.

The resolution of measuring ion mobility for a uniform or quasihomogeneous electric field increases to a first approximation as the square root of the voltage applied along the mobility cell for a given ion charge. It would seem that there is not much freedom to increase resolution. However, the situation can be improved if the drift of ions in the gas stream is organized under the action of an electric field directed against the stream. Ions move against the gas flow only if the field strength is greater than a certain value determined by their mobility. Ions with lower mobility may be stationary or move with the gas stream. In this case, it becomes possible to control the rate of exit of ions to the detector, in contrast to the classical SIP. This leads, first, to an increase in the expected resolution of the spectra, if only because of a lower translational temperature of the ions. Secondly, it does not impose serious restrictions on the speed of the detector.

The combination of an ion mobility spectrometer (IMS) with a mass spectrometer (MS) is widely known. In 1961, Barnes and co-workers [6] were among the first to combine these two separation methods. Such devices separate and analyze ions according to their mobility and the ratio of mass to charge, which is often referred to as two-dimensional separation or two-dimensional analysis. Young and coworkers [7] first realized that a time-of-flight mass spectrometer (HPMC) is the most preferred type of MS, which is used in such a combination because of its ability to detect ions of all masses coming from an ion mobility spectrometer almost simultaneously. The combination of an ion mobility spectrometer with VPMS can be referred to as Mobility-VPMS or SIP-VPMS. This well-known device included means for producing ions, a drift cell, IMSS and a small hole for transferring ions from a mobility cell to IMSS.

In 2003, Loboda (US Patent No. 6,630,662) [8] described a method for improving ion mobility separation based on the balance of ion drift due to the influence of a constant electric field and gas flow. Using this balance, the ions are first accumulated in the RF focusing device, in particular in the quadrupole, and then, changing the electric field or gas flow, the ions are gradually removed from the quadrupole and fed to the mass spectrometer. This type of ion accumulation is limited to collecting a relatively small amount of ions due to the space charge effect. There is also some restriction on the range of mass-to-ion charge ratios (m / z), since RF focusing for a given RF voltage has less efficiency for large ions, which cannot be greatly improved by increasing this voltage due to the possibility of creating ignition conditions for a discharge at high gas pressure. Unfortunately, at a lower pressure, the influence of the gas flow on ions is less and only less efficient accumulation and separation of large ions can be achieved. A significant increase in the pressure or density of the gas stream, which also reduces the possibility of ignition of the discharge, is also impossible, because in this case, the focusing ability of the radio frequency voltage disappears. At least for these reasons, this method has significant resolution restrictions.

The separation of ions when exposed to electric fields and a supersonic gas stream, as proposed in the present invention, is free from these disadvantages. Considering the described device as a prototype of the present invention, the following main distinguishing points can be noted associated with the presence in our case of a slightly diverging relatively dense gas stream in the axial region of the radio-frequency quadrupole and a relatively low residual gas density outside the stream inside the quadrupole. The low residual density of the gas outside the stream allows the inclusion of resonant rotating fields to remove excess ions to the rods of the quadrupole with relatively high selectivity, significantly reducing the undesirable effects of space charge accumulation. There are no restrictions on the use of sufficiently high radio frequency voltages for focusing large ions, since a relatively high gas density is concentrated in a narrow near-axis region, where the quadrupole field is small.

The relatively slowly decreasing density of the gas flow along the axis of the quadrupole allows, by setting the corresponding constant quasihomogeneous electric field directed against the flow, to “stop” the analyzed ions in a desired place inside the quadrupole, so that the intensity of the flow of these ions in the ortho-VMS or other mass analyzer corresponds to the dynamic range measuring system. Using the repulsion of relatively large analytical ions by small ions focused near the axis of the quadrupole, as well as the m / z-dependent displacement of the ions from the axis by a nonresonant rotating field, it is possible to separate the ions along m / z due to different displacements of the ions by the opposite field along the axis (due to the decrease flux density with the removal of ions from the axis) along with separation by mobility. The same controlled displacement of the analyzed ions from the axis allows the use of near-optimal values of the opposite field strength to obtain a sufficiently high resolution of the ion packets in mobility with minimization of the effects of the space charge of the analyzed ions. The relatively high density of the gas stream near the axis of the quadrupole allows efficient fragmentation induced primarily by single collisions of the selected ions with atoms or molecules of the gas stream without organizing a special collision chamber. Significantly lower requirements for pumping power in our case to create a gas flow density near the axis of the quadrupole, comparable with the density of the flow in the quadrupole of the prototype, are another advantage of the proposed system.

One of the important prerequisites for the present invention is the creation by us of a technique of resonant excitation of the rotation of selected ions around the axis of the radio-frequency quadrupole and the fragmentation of these ions due to collisions with buffer gas molecules [9-11]. This technique was new, previously not proposed by anyone. In contrast to the present invention, the rotation of the ions in this case was excited during their movement along the quadrupole without stopping this movement. This provided limited opportunities for kinetic measurements and determined the relatively low ability to detun from signals of interfering ions. In addition, this method of resonant rotation imposed very strict requirements on the manufacturing quality of the quadrupole: small deviations in the diameter of the rods or in the distances between them led to significant losses in resolution, which in our case turned out to be no more than 100 when real measurements were taken.

In the proposed embodiment, the ion cloud during resonant excitation rotates in a relatively narrow zone along the length of the quadrupole (from several mm to 1-2 cm), while ions perform quasi-chaotic oscillations along this zone with an average transit time of this zone comparable to the rotation period and much shorter characteristic time of registration. Thus, the field inhomogeneities are significantly averaged, and their influence on the width of the resonance curves is weakened. In this case, the resolution of the resonant excitation for given ions and a given buffer gas will be mainly determined by the density of this gas in the region of rotation. At a reasonable residual pressure of 0.1 mTorr for helium, the expected mass resolution at half maximum peaks for organic ions with a mass of about 1000 Da will be about or even more than 5000. For other buffer gases, the resolution at a given gas pressure varies inversely with the square root of the molecular weight.

We developed a calculation model and conducted experiments on the formation of a supersonic gas stream at relatively low initial buffer gas pressures with ion transfer by this stream [12-14] and ion focusing into the stream directed along the axis of the radio-frequency quadrupole. These methods are also new, not previously known in the literature.

A gas-dynamic interface has been created for the ortho-VPMS at our disposal with a gas flow former and a sectioned radio-frequency quadrupole. This interface configuration is new. In general terms, it is described in our US patent No. 7,547,878 of June 16, 2009 [15]. Unlike the present invention, there is no “locking” diaphragm in this quadrupole, and instead of a quasihomogeneous field inside the quadrupole, a parabolic potential distribution is created with a minimum located near the beginning of the quadrupole. Preliminary experiments demonstrated the operability of this equipment, however, it was not possible to efficiently capture impurity ions in a helium buffer gas into such a trap. The excitation of non-resonant rotation or the creation of a relatively dense stream of small ions drifting along the axis of the quadrupole, as proposed in the present invention, analytical (relatively large) ions are removed from the area near the axis of the radio-frequency linear trap, which will deprive them of the possibility of return exit through the input diaphragm of the trap. This should be guaranteed to ensure effective capture of ions in the trap if measures are taken (as is done in the present invention) to prevent the death of ions on the inner surface of the inlet diaphragm. The possible replacement of the buffer gas with a heavier one and the introduction of a locking diaphragm will reduce the time of thermalization of ions in the trap.

The software for the analysis of experimental data should include software packages that basically implement the original methods developed by us that were described earlier [16–20, 29]. Among these methods, the most important are:

1. A correction method for the effects of saturation and “dead” time when using time-to-digital conversion for recording VPMS data [18, 29].

2. A method for identifying exponential contributions to a decaying induced signal from decaying ions [16, p. 192] with finding the roots of the characteristic polynomial using the procedure described in [20].

3. A method for identifying exponential contributions to a set of ion current curves, developed earlier for the analysis of many effusiometric curves [19].

Existing methods for implementing collisional ion dissociation or tandem mass spectrometry (MS / MS) usually require preliminary isolation of one type of ions with the loss of all the others, thereby requiring the use of a large volume of the initial sample and a large time-consuming experiment. One of the exceptions is the “multi-reflection” ortho-VPMS by A.N. Verenchikov [21], where due to a significant increase in the effective length of the ion drift and, therefore, their flight time, it becomes possible to produce collisional dissociation of not one, but several types of selected ions sufficiently far apart in exit time (for a time longer than the ion drift time in the secondary time-of-flight mass spectrometer). This approach, which is much more technically complex than in our case, produces primary ions for dissociation only in m / z.

Certain possibilities for collisional dissociation of several types of ions in one primary ion package are provided by the combination of SIP with HPMC and especially for HPMC with orthogonal ion input.

Shoff and Harden [22] were the first to use SIP-MS in a method similar to tandem mass spectrometry (MS / MS) for the study of organic compounds. In this method, a mobility spectrometer is used to isolate the source ion. A mass spectrometer is used to analyze ion fragments that are produced by fragmentation induced by collisions of the initial ions with atoms or molecules of a buffer gas. Below this specific technique for the operation of SIP-MS is referred to as SIP / MS, or as SIP / VPMS if the mass spectrometer is a time-of-flight mass spectrometer. Other previous instruments and methods using sequential SIP / MS analysis were described in [23–25], but none of them combines the instrumental improvements proposed in this invention. Together with the soft ionization methods and sensitivity enhancement obtained using the gas-dynamic interface disclosed here, SIP / MS systems and the corresponding methods of the present invention offer significant analytical advantages over the prior art, especially for the analysis of high molecular weight compounds such as biomolecules.

A possible approach that reduces the loss of source ions is described in the application of AV Loboda No. 20070120053 for a US patent [26]. This application proposes, after the accumulation of ions in the quadrupole at a buffer gas pressure of about 0.1 Torr, to carry out dipole excitation of ion vibrations with the selected m / z, so that these ions in the plane of the dipole excitation deviate far enough from the quadrupole axis on average. During or after this excitation, a quadrupole field that is linearly changing along the quadrupole is created in time. The potentials of this field are chosen so that in the plane of excitation of the vibrations of the selected ions, an average electric field is created that moves the ions to the exit of the quadrupole (on the axis of the quadrupole this field is zero, and in the perpendicular plane it moves the ions in the opposite direction). In this case, unexcited ions, having on average a smaller deviation from the axis of the quadrupole in this plane, will be less susceptible to the influence of this pulling field. Thus, the packet of ions of interest can be moved into the collision chamber, and the remaining ions will remain in the storage quadrupole. After completing the first packet in the same way, the next packet can be delivered to the collision chamber. This approach is quite interesting and, apparently, will work. However, its resolution should be low enough (it is unlikely to be more than 10) for several reasons. The main one is the rather high density of the buffer gas needed to trap ions in the trap. Thus, ion packets transferred to the collision chamber will contain many ions in a fairly wide mass range, and for the collisional dissociation of “individual” ions, all other ions from this packet must be removed.

The relatively high gas density in the radio frequency multipole during the accumulation of ions in existing systems either leads to low selectivity of the ions during their isolation, or requires additional time to download the "excess" gas. Another possible solution is to create complex multi-tambour systems, where the functions of accumulation, isolation, and collisional dissociation are performed in different parts of the system with very different buffer gas densities. Such a design leads to additional losses of ions and an increase in the cost of the instrument complex. It is such a construction that is proposed in the just described US patent application [26].

Dynamic methods of capturing ions in a quadrupole trap, when the reverse ion exit is blocked by switching on the corresponding potential until the launched ion packet returns from the pivot point, only a small part of the initial ion flux can be used if subsequent manipulations with the ions require a relatively long time. The initial ion flow should be locked at this time, and the corresponding ions are usually lost.

The use of resonant rotational motion of ions as well as their resonant one-dimensional vibrations in a radio-frequency quadrupole to eliminate excess ions that interfere with the measurement of less intense analytical peaks or cause saturation phenomena in the measuring system of a time-of-flight mass spectrometer is described in US patent application No. 20080149825 Kozlovsky B. AND. et al. [27]. In our case, similar goals can be achieved by appropriate resonant unwinding of the clouds of analyzed ions displaced from the quadrupole axis by the electrostatic field of the buffer gas ions, or by switching on a non-resonant rotating field in the storage part of the radio frequency quadrupole, which will increase the selectivity of such elimination in the presence of a significant gas flow along the quadrupole axis . The resonant spin around the axis of the quadrupole with a relatively small intensity of the rotating field will lead the analyzed ions to the rods of the quadrupole. Thus, in the absence of a noticeable effect of the ion space charge, a controlled decrease in the number of selected ions outside the gas stream is possible, where the buffer gas pressure is significantly lower than inside the stream, while maintaining these ions inside the stream.

A serious problem of combining the separation of mobility ions with a time-of-flight analyzer is the provision of high ion transmission through the drift tube in the VMS. One of the possible solutions was proposed by us in US patent No. 6,992,284 [28], which provides a fairly detailed overview of the work on the separation of ions by mobility. Patent No. 6,992,284 refers to the use of a sequence of alternating sections of a strong and a weak field instead of a uniform electric field in a drift tube at a pressure of several gas torr. This leads to the focusing of ions to the axis of the quadrupole and allows a slight increase in the total voltage along the tube, which favorably affects the resolution of the ion packets in mobility and allows achieving an almost 100% transmission of analytical ions along the drift tube. Nevertheless, in all realized variants of separation of ions by mobility, a sufficiently high resolution cannot be obtained. Even for ion drift at atmospheric pressure, a resolution of more than 100 is not achieved.

The repulsion of ions accumulated in a linear radio-frequency trap and the related phenomenon of stratification of ion clouds with different m / z around the axis of the trap were considered in a number of works [31, 32]. This phenomenon is associated with a decrease in the focusing ability of the effective potential of the radio-frequency quadrupole field with increasing m / z ions. The equalization of the forces of electrostatic repulsion of ions with smaller m / z focused around the axis of the quadrupole, with the compressive influence of the quadrupole radio frequency field directed to the axis of the quadrupole, leads to the formation of relatively narrow circular clouds of ions in the cross section. The distance between these clouds and the quadrupole axis increases with increasing m / z of the ions that form these clouds. In the presence of a gas stream along the axis of the quadrupole, a sufficiently high density of “small” ions around the axis of the quadrupole can push the relatively “large” analyzed ions out of the gas stream zone, thereby fulfilling the function of their non-resonant rotation, which was the basis of our patent application RF No. 2009126684 / 20 (037160), July 14, 2009 [33]. If in the case of rotation the ions are focused in the plane of rotation into a relatively small spot rotating around the axis of the quadrupole, then the electrostatic repulsion leads to a more or less uniform distribution of ions along a certain circle centered on the axis of the quadrupole. This will make it possible to work efficiently with a larger number of accumulated ions than in the case of nonresonant rotation. This can be an important advantage when analyzing multicomponent mixtures.

In 1991, Amirav and Danon (US Patent No. 5055677) [41] described a method and apparatus for analyzing samples, including: forming and introducing into a vacuum chamber a mass spectrometer of a supersonic molecular beam of a carrier gas mixed with a sample of material for analysis; ionization of the material in a supersonic molecular beam; separation of ions according to their ratio of mass to charge m / z; and registration of m / z-separated ions of the analyzed material. Ions in a supersonic molecular beam can be filtered from ions of thermal background molecules and carrier gas ions after ionization, but before registration. A system with an electron ionization source and a quadrupole mass spectrometer is described. The advantages of using a supersonic gas stream or a molecular beam to analyze chemicals as neutral impurities to this gas stream are discussed.

The presented mass spectra for the same compounds, recorded under ordinary conditions and under conditions of cooling in a supersonic gas stream, clearly demonstrate a much better quality of the data obtained for the latter case - a much lower level of chemical noise and a significant increase in the intensity of molecular peaks are achieved ( more than 100 times). Although the authors attribute the latter solely to the cooling of ions in a supersonic gas stream, it seems obvious that at least a partial increase in the intensity of molecular peaks compared to electron-ionization mass spectra with an energy of 70 eV can be explained by the recharging of helium ions with an ionization energy of 24.587 eV on molecules analyzed compounds in a supersonic gas stream.

Subsequently, practically the same technique with a supersonic gas flow was used to solve specific analytical problems (Amirav et al., US Patents No. 7345215 dated March 18, 2008 and No. 7518103 dated April 14, 2009) [42, 43]. In all these systems, the classical scheme of supersonic flow formation (nozzle-skimmer) was used and no attempts were made anywhere to pre-separate ions or organize their dissociation induced by collisions. The ion flux from the electron ionization source with a fixed electron energy (70 eV) was sent directly (except for their reflection in the electrostatic mirror) to a quadrupole mass spectrometer.

An alternative formation of a supersonic gas stream using a long glass capillary with a length of 180 mm and an inner diameter of 0.6 mm by coupling an electrospray ion source with a quadrupole mass spectrometer is described by J. Fenn in US Patent No. 6297499 of October 2, 2001 . [44]. There was also no preliminary separation or fragmentation of ions in front of the mass analyzer. In our case, when conducting experimental measurements, we used a metal capillary approximately ten times smaller in length and cross-sectional area to form a supersonic flow, and the gas pressure in the chamber at the inlet of the capillary was significantly lower than atmospheric (more than 20 times).

SUMMARY OF THE INVENTION

Features of one of the possible implementations of the proposed methods are:

At a buffer gas pressure (helium, argon, nitrogen, or other gases or a mixture of gases) of the order of several Torr or tens of Torr at the inlet and less than mTorr, a narrowly directed gas flow forms at the outlet of the cylindrical channel. A relatively small admixture of the analyzed sample in the buffer gas stream is transported in the form of a focused molecular beam to the ion source of electron ionization.

The second possibility of forming the flow of the studied ions is the transportation of ions, including multiply charged ions of biomolecules, from an electrospray source with their focusing by a system of aperture diaphragms to the input of the gas flow formation channel. To minimize the loss of ions inside the channel, it is heated - this is one of the standard methods for transferring ions from an electrospray source to the region of relatively low pressure at the entrance to the mass spectrometer. Instead of an electrospray source, this ion injection can also use any other ion source operating at relatively high pressure up to atmospheric pressure.

Ionization of gases in a molecular beam is carried out in a source of electron ionization with a variable ionization energy, allowing ionization of only the target analyzed compounds, which, as a rule, have lower ionization energies than atoms or molecules of a buffer gas. In the presence of multiply charged ions of biomolecules, for example, from an electrospray source, capture of slow electrons with subsequent dissociation processes is possible.

The accumulation, preliminary separation, controlled fragmentation and focusing of ions is carried out in a sectioned radio-frequency quadrupole, the axis of which is close to the axis of the gas flow. In the initial region of the quadrupole, limited by the input and “locking” diaphragms, by setting the corresponding voltages on the sections of the rods of the quadrupole, a relatively weak quasihomogeneous electric field is created that slows down the ions. The field between the input diaphragm and the first section of the quadrupole has the opposite direction. It accelerates ions and has sufficient tension to provide a potential barrier that prevents the neutralization of ions on the inner surface of the input diaphragm. Both diaphragms are multilayer with alternating conductive and dielectric layers, which allow creating a sufficiently strong field inside the aperture of the diaphragm, capable of stopping ions moving inside the gas flow or causing collision-induced dissociation of ions. At the same time, the outer conducting layers of the diaphragms make it possible to organize the desired distribution of electric potential outside the diaphragms.

In the positive ion mode, buffer gas ions can be obtained with increased energy of ionizing electrons in an ion source with electron ionization. To increase their density in the initial region of the quadrupole, these ions are inhibited by a gradual increase in the longitudinal electric field directed against their movement between the input and locking diaphragms. If the ionization energy of the analyzed neutral impurities in the gas stream is less than the ionization energy of the buffer gas, then in the dense cloud of buffer gas ions in the region between the inlet and the closing diaphragms, the neutral impurities will ionize due to recharging, and this can significantly increase the sensitivity of the analysis. With a fairly dense flow of buffer gas ions and in the region after the closing diaphragm, some of the analytical ions can also be formed by recharging. If necessary, these processes can be eliminated, for example, by increasing the intensity of the radio frequency field in the second half of the quadrupole, so that the light buffer gas ions lose their stability in the quadrupole and die on its rods.

In the absence of a longitudinal electric field in the quadrupole directed against the gas flow, which is hereinafter referred to as the counterfield, the ortho-VPMS or other mass analyzer coupled with the quadrupole, a survey mass spectrum of the test mixture is recorded. Since the proposed method involves at least a partial stop of the ion flow by the antipole, the most intense ion flows, especially those that are not of interest to the study, should be reduced as much as possible to prevent undesirable effects of space charge accumulation. This can be done by including resonant rotational fields for ions with corresponding m / z. These fields, with proper selection of their intensity, can provide the desired rate of death of selected groups of ions if they are in the zone of residual density of the buffer gas. To control the rate of their death and the level of their accumulation (if it is impossible to register these ions with a subsequent mass analyzer), it is desirable to have an additional channel for measuring ion currents. One of the possible methods for such a measurement can be registration of the induced signal on specially introduced electrodes between the rods of the quadrupole, as described in our patent application [33]. The description of this method will be partially repeated below and new approaches for the analysis of the obtained data are proposed.

If the recharging processes after the closing diaphragm can be neglected or their contribution is sufficiently small, then the gas flow with an increasing field strength will provide mainly the transport of ions with substantially larger cross sections and m / z than the buffer gas ions located near the quadrupole axis and the gas stream . This will happen until, under the influence of the accumulated space charge of small ions of the buffer gas, these large ions begin to shift from the axis of the quadrupole and the flow of these ions in the ortho-VMSS begins to decrease. The movement of buffer gas ions will be provided by resonant charge exchange.

With a significant decrease in the flux of registered analyzed ions with the smallest m / z value, a gradual decrease in the protofield in the quadrupole begins until the state of registration of these peaks with a minimum sufficient intensity is established. In the process and upon completion of this procedure, the ions of interest will accumulate in the trap and will be on average at some distance from the axis of the quadrupole and from the locking diaphragm.

An indicator of the accumulation of these ions will be an increase in the recorded intensity of the corresponding peak of the ion current or the sum of the intensities of several peaks due to the isotopic distribution of these ions. This increase in intensity for individual ions under the stationary influence of the space charge of all ions inside the trap will have an exponential nature of approaching the initial current intensity of the ions in question in the absence of blocking the flow of these ions by the input diaphragm. The characteristic time of this exponent will be determined by the average distance of the ions from the locking diaphragm, the dispersion of their distribution along the axis of the quadrupole, and the mass of the corresponding ions. For a given mass, this characteristic time will depend on the cross section of the ions (or their mobility) and their charge. In the presence of several types of registered ions with increasing intensity, this increase will be described by several exponentials with characteristic times specific in these conditions for each type of ion.

The selection of these exponentials will mean the actual separation of these ions, additional to their separation by m / z in a time-of-flight mass spectrometer or other subsequent mass analyzer. Since the relative differences in the characteristic times of these exponentials can be significantly larger than the corresponding differences in ion mobilities, the separation ability of the proposed method can be significantly larger than in traditional methods for separating ions by mobility, and it will ultimately be determined by the recording time. In addition, ions with different charges, even with the same mobility, can also be separated, since the dispersion of the distribution of ions along the axis of the quadrupole is directly proportional to the effective translational temperature of the ions and inversely proportional to their charge in a uniform electric field and in the linear approximation of changes in the density of the ion flux along the axis quadrupole near the equilibrium point between the effects of flow and field on the ions in question.

There is one more possibility to try to separate ions with coincident characteristic rise times of the signal from them. By including a resonant rotational voltage causing radial vibrations for stratified ions with a given m / z, these characteristic times can be changed. This change for different ions can be different due to a different change in the mobility of ions with an increase in the average rate of collision of ions with gas atoms and a related different increase in their effective translational temperature [34]. The situation is similar to the separation of ions in the known method of increment of ionic mobility or FAIMS [35, 36].

раз выше, чем резонансная частота вращающего поля в квадруполе, когда влиянием объемного заряда можно пренебречь. При сдвиге ионов от оси квадруполя нерезонансным вращающим полем изменение частоты вращений при больших раскрутках может возникнуть из-за неидеальности квадрупольного поля. Если ионы различаются по степени устойчивости к диссоциации или вероятности рекомбинации при данной амплитуде вращающего поля, они в этом случае могут быть также разделены и проанализированы, аналогично тому, как это было описано в нашей заявке на Патент РФ [33].In the absence of significant additional separation of ions at small amplitudes of the resonant rotational voltage, this voltage can be increased to values at which the death of the corresponding ions begins either due to dissociation or due to recombination on the rods of the quadrupole. Here it must be borne in mind that for a highly selective for m / z ion loss, it may be necessary to apply a rotating field with a shifted frequency compared to the resonant frequency of small oscillations or ion rotations. In the presence of repulsion of ions by a space charge, this resonance frequency turns out to be

times higher than the resonant frequency of the rotating field in the quadrupole, when the influence of the space charge can be neglected. When ions are shifted from the axis of the quadrupole by a non-resonant rotating field, a change in the rotation frequency for large spins can occur due to the non-ideal quadrupole field. If the ions differ in their degree of resistance to dissociation or in the probability of recombination at a given amplitude of the rotating field, they can then be separated and analyzed in the same way as described in our patent application [33].

The inclusion of the processes of ion death on the rods of the quadrupole when a certain limit level of the recorded ion flux is reached or when this flux is blocked can provide more favorable conditions for the signal to be separated from the (main) ions that are most localized to the closing diaphragm. The fact is that among ions with a given value of m / z, those ions that have the least mobility are most strongly shifted by the flow against a given electric field. At the same time, ions with greater mobility are more unwound by the resonant rotating field, and, therefore, they are more likely to die on the rods of the quadrupole, and the signal from them will be less than the signal from the main ions than in the absence of this death. Periodic switching on and off of such a death makes it possible to carry out measurements of ion fluxes passing through the locking diaphragm and relaxing with changing characteristic times during any desired time. With a periodic change in these characteristic times, it is possible to accumulate recorded signals and provide the desired separation efficiency of signals from different ions without increasing the influence of space charge, which would lead to direct accumulation of ions.

With a relatively low signal level from the analyzed ions, by creating a small opposite field at the entrance to the locking diaphragm, it is possible to organize the accumulation of these ions. Periodic switching on and off of this counterfield will also allow to accumulate registered signals and ensure sufficient separation efficiency.

The analyzed ions, which have larger masses than the buffer gas ions, are efficiently focused by the quadrupole at high radio frequency voltages, at which the buffer gas ions can lose stability in the quadrupole and die on its rods. Large ions can be shifted from the quadrupole axis by a non-resonant rotating field with a frequency much lower than the resonant frequency of the analyzed ions with a minimum m / z. Large ions can be accumulated at a distance from the axis of the quadrupole and without applying a rotating field, namely by creating a sufficiently dense cloud of repulsive ions with respect to light impurities, in particular, specially added to the buffer gas.

A stepwise decrease in the longitudinal field strength in the initial part of the quadrupole with a time duration of steps sufficient to determine the characteristic times of the exponentials describing the rise or fall of the signals of the observed ions, all the accumulated ions are analyzed. If necessary, the inclusion of a sufficiently strong accelerating field inside the outlet of the locking diaphragm produces collision-induced dissociation of the selected ions. In this case, the fragment ions correspond to a certain initial ion based on the coincidence of the characteristic times of the corresponding exponentials, and they can be separated even if the m / z coincidence of these fragment ions. To limit the influence of the space charge of the accumulated ions (even those that were not visible in the survey mass spectrum taken at the beginning of the measurements), unwanted ions can be unwound and removed to the quadrupole rods by switching on the corresponding resonant rotational voltages. Resonant frequencies and the control of the allowable number of ions accumulated in a quadrupole can be carried out by recording induced signals from rotating ions, similar to that described in our application [33].

Upon reaching a critical amount of the studied ions, the flow of incoming ions can be reduced by switching on the corresponding inhibitory field at the input diaphragm. When using a non-resonant rotating field to shift ions from the axis of the quadrupole, it is possible to separate the processes of accumulation and analysis of ions, completely stopping the process of ion flow through the input diaphragm by switching on a sufficiently strong inhibitory field in this diaphragm. In this case, the removal of excess ions from the quadrupole may not be required, and the organization of measurements is greatly simplified, although the possibilities for analysis of trace elements are reduced, because The accumulation of ions in the quadrupole will be limited by the influence of the space charge of the ions of the main components.

In the second half of the quadrupole, after the locking diaphragm, a weak longitudinal braking electric field is created to provide sufficient time for focusing the accelerated ions, and to prevent the death of these ions on the back surface of the locking diaphragm, the potential of this surface rises to a sufficiently high level. To prevent the main part of the gas stream from getting inside the time-of-flight mass analyzer, the axis of the gas stream is shifted so that its continuation falls outside the receiving hole of the ortho-VPMS. To remove ions from the gas stream at the end of the quadrupole, a strong short electric field is created between the last section of the quadrupole and the output diaphragm. After the output diaphragm, a decelerating electric field is created, focusing the ions on the center of the input diaphragm of the mass spectrometer and lowering the ion energy to the level optimal for registration in the ortho-VMS.

The theoretical foundations of the method of separating exponential contributions as applied to the analysis of sets of effusiometric curves were developed by us earlier [19]. The essence of the approach is based on a complete analogy between systems of differential and finite-difference linear equations with constant coefficients. This analogy for a single equation, for example, was used by us in the development of linear prediction methods for the effective estimation of the mass numbers of ions from their exit times for a magnetic static mass spectrometer [16, 30]. Having determined the coefficients of such a forecast, in particular, which is accurate for the sum of the exponential curves, the damping factors of the corresponding exponentials can be determined by finding the roots of the characteristic polynomial, as well as for the corresponding differential equation with constant coefficients. In this case, the computational procedure described by us in [20] can be used.

Based on this analogy, in the general case, the total intensity vector of product ions or induced signals for subsequent recordings can be expressed, without taking into account measurement errors, as the product of some transition matrix to a vector of such intensities for the previous registration, since this is true for linear combinations of exponentially decaying flows of product ions or induced signals recorded for different pairs of introduced electrodes and for different frequencies. The matrix elements of this transition matrix can be found by minimizing the error of such an approximation, which reduces to solving the corresponding systems of linear algebraic equations for each row of this matrix. The eigenvectors of this matrix describe, up to normalization, the intensity vector of product ions of each type of ion present in the mixture being analyzed. The eigenvalues corresponding to these vectors characterize the factors of exponential decay of the intensity of such ions. The coefficients describing the contributions of the eigenvectors of the transition matrix to the observed intensities of the product ions or induced signals are found by the least-squares method to ensure on average the minimum errors of the measured data for all registrations. The quality of approximation compared with measurement errors is a criterion for the accuracy of the analysis. Knowing the number of types of the initial ions and the characteristic times of their exponential decay, one can find the contributions of each of these exponents to all samples in the recorded mass spectra by solving the corresponding systems of linear equations. Thereby, mass spectra of product ions of each type of starting ion will be obtained, as if they were completely separated before their registration. This is important because will allow to determine the “exact” masses of all product ions, if the corresponding mass spectra were recorded on a high-resolution mass analyzer.

BRIEF DESCRIPTION OF ILLUSTRATIONS

For a more complete understanding of the present invention, the following description is related to the corresponding illustrations, in which:

Figure 1. The general scheme of the gas-dynamic interface of ortho-VPMS for preliminary separation and registration of ions.

Figure 2. Illustration for the processes of transporting ions “stopped” in a quadrupole in front of a “locking” diaphragm.

Figure 3. The cross-sectional diagram of the region of ion accumulation in the case of repulsion of large ions by small ions focused around the axis of the quadrupole.

Figure 4. Calculated resonance curves for oscillating ions for two values of gas density.

Figure 5. The cross-sectional diagram of the region of ion accumulation in the case of deviation of large ions from the axis of the quadrupole by a non-resonant rotating field.

6. Illustration for four possible types of recorded data curves.

7. Flowchart of the procedure for calculating the exponential contributions to the kinetic curve of decaying ions.

Fig. 8. Illustration for the method of separation of exponentially decaying superimposed peaks of ion-products of collisional fragmentation of the initial isobaric ions.

Fig.9. Dependence of the integrated intensity distributions of the ion beam Xe ⁺ , ³⁶ Ar ⁺ and N ₂ ⁺ and the displacement of the receiving slit with a width of s = 1 mm at the output of the quadrupole with the flow of Ar along its axis: the points are experimental data, the solid curve is the approximation by test functions.

Figure 10. Dependences of the differences between the experimental and calculated intensity distributions of ion beams Xe ⁺ , ³⁶ Ar ⁺ and N ₂ ⁺ and the ratios of these differences for pairs Xe ⁺ , N ₂ ⁺ and Xe ⁺ , ³⁶ Ar ⁺ on the displacement of the receiving gap at the exit of the quadrupole with the gas flow along it axis.

11. Illustration illustrating a possible mechanism for the formation of distributions shown in Fig.10.

All these illustrations are explanatory in nature and do not impose any restrictions on the possible implementation of the invention.

DETAILED DESCRIPTION OF THE INVENTION

A new approach for transporting ions from the high-pressure region at the exit of the mobility cell of the ion mobility spectrometer to the vacuum part of the mass spectrometer through the formation of a supersonic gas flow is described in our US patent No. 7,482,582 of January 27, 2009 [13]. It was further developed to provide additional analytical capabilities due to the resonant excitation of ion rotation around a supersonic flow in a radio frequency quadrupole at the entrance to the ortho-VPMS in our next US patent No. 7,547,878 of June 16, 2009 [15]. The specific development of these approaches to ensure effective quantitative determination of the presence of impurities in gas mixtures and structural analysis of multiply charged ions of biomolecules is described in application No. 2009126684 of July 14, 2009 for the grant of a patent of the Russian Federation [33] and in the present invention, which differs from this application by the separation of ions into the basis of the balance between the displacement of ions under the action of a supersonic flow and their drift under the influence of an oppositely directed electric field and the intentional use of the repulsive effect of lighter ions, localized around the axis of the quadrupole.

A feature of the proposed method, in contrast to the mentioned patents, is not the separation of ions from a helium stream with ions from a mobility cell, but like in application No. 2009126684 [33] the intentional formation of a gas stream, schematically shown in FIG. 1, from a buffer gas, preferably heavier than helium (1) coming from the chamber (3) into the cylindrical channel (2). A stream of atmospheric air or other gas mixture containing microimpurities and main components directly or after enrichment, for example, by adsorption-desorption on a suitable carrier, is introduced into the stream (1) or alternatively, ions of organic or bioorganic compounds from an electrospray source or other sources are introduced into the channel ( 2) together with the stream (1) a system of focusing electrodes, not shown in Fig.1. In order to prevent the adsorption of ions of biomolecules on the inner wall of the channel (2), it is heated by current through the winding (4). The pumping of gases entering the stream (1) is carried out mainly by a pump (15). The flow axis is offset relative to the axis of the quadrupole (38) by an angle corresponding to a shift (39) in the plane of the receiving slit (21) of the mass spectrometer exceeding the half-width of the slit so that only a small part of the flow enters the next differential stage through the inlet movable slot (21) pumping out the ortho-VPMS or other subsequent mass analyzer. The formation of such a relatively dense gas stream is confirmed by our experimental data, some of which are shown in Fig.9 and Fig.10. This issue will be considered in sufficient detail below.

A gas stream (5) containing (during analytical measurements) a small admixture of atmospheric air or another gas mixture or ions of organic or bioorganic compounds enters the ion source with electronic ionization (6) with a variable energy of ionizing electrons. To reduce the spread in electron energy, the source is equipped with a cathode (18), for example, of LaB ₆ with indirect heating (22). By choosing the appropriate electron energy and the composition of the gas mixture, various ionization modes can be realized, as a result of which either the formation of positive (or negative) ions of the analyzed compounds or the conversion of ions coming from other sources occurs. So, for example, at an electron energy exceeding the ionization threshold of atoms or molecules of a buffer gas, the ions of this gas, the main component in the jet, will be the main primary ions (5). Since the ionization potentials of organic compounds are usually less than the ionization potential of atoms or molecules of a buffer gas, such as Ar or N ₂ , then when the corresponding molecules collide with the ions of the buffer gas, charge transfer to these molecules will occur, and a significant fraction of these molecules will be ionized.

In contrast to our application No. 2009126684, the input and closing diaphragms are multilayer, consisting of conductive (8), (19) and dielectric (9), (14) layers, respectively. The minimum number of conductive layers, as shown in FIG. 1, is four. Functionally, these diaphragms are designed to create sufficiently strong fields inside the holes of the diaphragms, allowing not to pass ions through the input diaphragm (8) - (9), when necessary, and to produce collision-induced dissociation of ions inside the locking diaphragm (19) - (14). The external conducting layers of the diaphragms are used to create the desired electric fields outside these diaphragms, in particular, to focus the incoming ions (28), (34) and to prohibit the return of ions after passage through the diaphragms (29), (30).

Sectioning the quadrupole rods (10) and to the right of the outer layer of the locking diaphragm (19) - (14) allows optimal creation of radio-frequency and longitudinal electric fields (30) and (31) in this part of the quadrupole to ensure effective focusing of the analyzed ions (20), passing through the closing diaphragm (19) - (14), including product ions of collision-induced dissociation under the action of fields (34) and (36). For efficient registration in the ortho-VMSS, ions are removed from the gas stream (5) by a strong electric field (32) at the exit of the quadrupole (10) and are exposed to a braking electric field (33) created by electrodes (23), (17) and (21 ) The distribution of potentials of the accelerating (25) and braking potentials (26) along the axis of the quadrupole (38) is shown in the lower right part of the figure. Distribution (26) is approximated by a convex upward parabola. Since the potential of the electric field in vacuum satisfies the Laplace equation, with the cylindrical symmetry of the electrodes (23) and (17) in the orthogonal plane, the potential distribution along both coordinates will be described by parabolas convex downward with coefficients at the quadratic term equal to half of this coefficient for the parabola 26). One of these parabolas is conditionally shown by a dashed line (27). Such a potential distribution will lead to the focusing of ions to the axis of the ion-optical system and at least will not significantly increase the width of ion beams passing through the gap (21). The remaining kinetic energy of ions (37) is close to optimal for recording on the ortho-VPMS (for our device it is ~ 14 eV). To introduce ions into other types of mass analyzers, another organization of the focusing system at the output of the radio frequency quadrupole may be required (10).

Preliminary registration of all ions passing through the locking diaphragm (19) - (14), in the absence of additional electric fields inside the quadrupole, in addition to the radio frequency focusing voltage and focusing fields of the input and locking diaphragms, will provide information on the possible presence of ions of interest in the analyzed mixture and m / z ranges ions that are subject to a detailed study, as well as interfering intense peaks, the removal or attenuation of which would be useful in the analysis. In this case, for the efficient registration of ions of relatively large m / z, an increase in the radio frequency voltage may be required at which the buffer gas ions can lose their stability of motion and recombine on the rods of the quadrupole. The same can happen with other ions with relatively small m / z.

In the absence of a significant ion flux with m / z lower than that of the analyzed ions and moderate intensities of all other observed peaks, excluding the significant influence of the space charge on the dynamics of the analyzed ions at reasonable accumulation times, the following simplified version of the proposed ion separation method is possible. With a gradual increase in the intensity of the longitudinal quasihomogeneous field (13), directed against the flow (1), the maximum intensity among all the ions of interest decreases to the minimum level sufficient for measurements. With a sufficient density of the gas stream (5), this will mean a “stop” of the cloud of corresponding ions at a distance to the left of the locking diaphragm (19) - (14). At this point, the average force acting on the ions from the flow side (1), the atomic density (7) in which, despite the possible formation of clusters (24), decreases with distance from the outlet of the capillary (2), is equalized with an almost constant reaction electric field (13). With this effect of the flow (1) and field (13), various ions (12) will actually be in potential wells, differing in the position of their minimum and steepness, as shown in the lower part (201) of FIG. 2.

Ideally, for a uniform electric field and a linear change in the mobility of ions κ _i along the flow, such wells will be described by parabolas with the positions of the vertices Z _i determined by the ion mobilities averaged over possible positions inside the flow and the coefficients a _i for the quadratic term proportional to the ion charge z.

The ion distributions inside these potential wells in accordance with the Boltzmann principle will be described by Gaussian curves (100) with maxima coinciding with the minima of the potential wells and dispersions proportional to the coefficients of the quadratic term of the corresponding parabolas and inversely proportional to the effective temperature of the ions.

при отсутствии влияния объемного заряда и других возбуждающих полей кроме радиочастотного квадрупольного поля практически равна температуре газа T_g, которую он приобрел в капилляре (2). Положение минимума

или положение равновесия для соответствующих ионов определяется уравниванием передаваемого импульса «неподвижному» иону (что справедливо для ионов достаточно больших масс) в единицу времени от поля с напряженностью E и от потока со скоростью V_F:where k is the Boltzmann constant, effective temperature

in the absence of the influence of the space charge and other exciting fields, in addition to the radio-frequency quadrupole field, it is practically equal to the gas temperature T _g , which it acquired in the capillary (2). Minimum position

or the equilibrium position for the corresponding ions is determined by equalizing the transmitted momentum to a “fixed” ion (which is true for ions of sufficiently large masses) per unit time from the field with intensity E and from the stream with speed V _F :

where e is the elementary charge, n is the density of the gas stream averaged over the possible positions of the ion in the plane orthogonal to the flow, σ _i is the cross section of collisions of the ion with atoms or molecules of the gas at a relative velocity V _F , M is the molecular mass of the gas. The gas flow velocity in the adiabatic approximation is determined by the gas temperature T _g and its molecular mass M:

For small deviations from the equilibrium position along the Z axis, the total momentum transferred to the ion will be:

,

,

and the increase in the potential energy of the ions when they deviate from the position of its minimum is as follows:

,

,

в точке равновесия для данных ионов.Where

at the equilibrium point for these ions.

Thus, the coefficient a _i in the distribution (100) will be:

величина стандартного отклонения распределения этих ионов будет:and the dispersion of this distribution will be inversely proportional to the charge of the ion and the field strength that stops these ions in the stream. At a field strength of 1 V / cm, α = 0.1 (which corresponds to a halving of the gas flow density over 5 cm between the inlet and closing diaphragms of the quadrupole), the effective temperature of singly charged ions

the standard deviation of the distribution of these ions will be:

The distributions shown in FIG. 2 along the axis of the quadrupole (38) of potential energies, ion densities and schematic images of the clouds of these ions (203), (204) and (205) demonstrate possible interconnections between them. In this case, one does not need to pay attention to the different removal of ion clouds from the axis of the quadrupole (38), because this can be caused by the influence of the space charge inside and near the gas jet (5) or by the action of rotating fields, which will be considered below. Ions (203) and (204) have the same equilibrium positions, but differ in charges, respectively, these are singly charged and quadruply charged ions. This leads to significantly different distribution densities in the region of penetration (208) of ions into the region of the accelerating field created by the locking diaphragm (19) - (14), which leads to very different characteristic times of the recorded signals, allowing them to be completely separated even in the case of exactly the same values m / z of these ions. The ion fluxes through the closing diaphragm (14) can be estimated similarly to the molecular flux through the hole:

- линейная плотность ионов в области проникновения (208), V_i - средняя тепловая скорость ионов, S - эффективная площадь поперечного сечения облака ионов. Это означает, что поток ионов (105) во времени будет экспоненциально затухать, если поток исходных ионов заперт, поскольку

и, соответственно, скорость расхода ионов пропорциональна общему числу накопленных ионов в соответствующем облаке (при отсутствии влияния объемного заряда данных ионов). Альтернативно этот поток будет возрастать, экспоненциально приближаясь к исходному потоку этих ионов. Выражение (105) означает, что для многозарядных ионов, например, показанных на Фиг.2 - (205), уменьшение их потока будет связано не только с очень сильным уменьшением

, но и с двукратным в данном случае уменьшением средней тепловой скорости из-за вчетверо большей массы. Скорее всего, такие ионы на фоне хорошо регистрируемого потока ионов (203) в условиях, показанных на Фиг.2, в сравнимое время вообще регистрироваться не будут. Для их регистрации облако ионов и распределение (205) надо сдвинуть вправо уменьшением напряженности поля (13) до появления сигнала приемлемой интенсивности. В этом случае облако ионов (203) практически полностью исчезнет, и сигнал соответствующих ионов либо не будет регистрироваться более, если исходный поток ионов был заперт входной диафрагмой (8)-(9) или их поток станет постоянным, если поток исходных ионов не прерывался.where n _i is volumetric and

is the linear density of ions in the penetration region (208), V _i is the average thermal velocity of ions, S is the effective cross-sectional area of the ion cloud. This means that the ion flux (105) will decay exponentially in time if the initial ion flux is blocked, since

and, accordingly, the ion flow rate is proportional to the total number of accumulated ions in the corresponding cloud (in the absence of the influence of the space charge of these ions). Alternatively, this flux will increase, exponentially approaching the initial flux of these ions. Expression (105) means that for multiply charged ions, for example, shown in Figs. 2 - (205), a decrease in their flux will be associated not only with a very strong decrease

, but also with a twofold reduction in this case of the average thermal velocity due to a fourfold larger mass. Most likely, such ions against the background of a well-recorded ion flux (203) under the conditions shown in FIG. 2 will not be recorded at all in comparable time. To register them, the ion cloud and distribution (205) must be shifted to the right by decreasing field strength (13) until a signal of acceptable intensity appears. In this case, the ion cloud (203) will almost completely disappear, and the signal of the corresponding ions will either not be detected more if the initial ion flux was blocked by the input diaphragm (8) - (9) or their flux becomes constant if the flux of the initial ions was not interrupted.

около 0,001 иона/см. Для меньших масс - еще меньше пропорционально корню квадратному из массы.Based on expression (105), we can estimate the range of acceptable numbers of ions stopped in the quadrupole and detected. If you use ortho-VPMS with a time-to-digital converter for recording ions with a mass spectral accumulation time of 1 second (for mass spectra of a moderate mass range, up to 1000 Yes, this means, for example, for our mass spectrometer, the accumulation of 10,000 mass spectra , and for ions with masses up to 4000 Da - 5000 mass spectra) can be arbitrarily considered the minimum detected ion flux of 1 ion per second. The average thermal velocity of ions, for example, with a mass m _i = 4000 Da at room temperature will be about 40 m / s. This means that to ensure a flow of 1 ion per second, a linear ion density in the penetration region is needed (208)

about 0.001 ion / cm. For smaller masses - even less in proportion to the square root of the mass.

≈1 ион/см. Для обеспечения характеристического времени падения регистрируемого сигнала около 10 сек (при идеальной 100 процентной регистрации) нужно накопить ~10000 ионов. При стандартном отклонении распределения ионов σ≈4 мм, локальная плотность ионов в максимуме распределения будет также ~10000 ионов/см. Такая ширина распределения замечательна также тем, что она близка к вписанному радиусу квадруполя в нашем случае (3,7 мм), что приведет к существенной компенсации расталкивающего влияния объемного заряда ионов за счет притяжения ионов к зарядам-изображениям на стержнях квадруполя. Локальная плотность в 1 ион/см в этом случае достигается на удалении от максимума распределения в 4,29σ≈1,72 см. При уменьшении эффективности регистрации число накопленных ионов для получения тех же результатов должно быть увеличено. Так, например, при эффективности регистрации 0,01 должно быть накоплено около 1000000 ионов, и тогда влияние объемного заряда может стать заметным и привести к отклонениям от экспоненциального поведения регистрируемых кривых. Возможный выход - уменьшение плотности накопленных ионов за счет уменьшения напряженности противополя при некотором уменьшении радиочастотного фокусирующего напряжения для обеспечения большего удаления ионов от оси квадруполя (38) для того, чтобы сохранить прежним поток регистрируемых ионов.A well-recorded maximum value of the ion flux during the accumulation of 5000-10000 spectra in the absence of phenomena of signal saturation can be considered ~ 1000 ions per second, which corresponds to m _i = 4000 Yes

≈1 ion / cm. To provide a characteristic time of the recorded signal falling about 10 seconds (with an ideal 100 percent registration), ~ 10,000 ions must be accumulated. With a standard deviation of the ion distribution σ≈4 mm, the local ion density at the distribution maximum will also be ~ 10,000 ions / cm. This distribution width is also remarkable in that it is close to the inscribed radius of the quadrupole in our case (3.7 mm), which will lead to a significant compensation for the repulsive effect of the space charge of ions due to the attraction of ions to image charges on the rods of the quadrupole. In this case, a local density of 1 ion / cm is achieved at a distance from the distribution maximum of 4.29σ≈1.72 cm. With a decrease in the detection efficiency, the number of accumulated ions must be increased to obtain the same results. So, for example, with a detection efficiency of 0.01, about 1,000,000 ions should be accumulated, and then the influence of the space charge can become noticeable and lead to deviations from the exponential behavior of the recorded curves. A possible way out is a decrease in the density of accumulated ions due to a decrease in the antifield strength with a certain decrease in the RF focusing voltage to ensure a greater removal of ions from the axis of the quadrupole (38) in order to keep the ion flux recorded.

Distributions (203) and (204) demonstrate the case of a slight excess of the cross section for the collision of ions (204) with gas atoms or molecules compared with (203) for a single ion charge and coincident masses, which leads to a weak shift of the distribution (204) to the right compared to (203) with the same standard deviations. In this case, this shift is 1 mm, which is 25% of the standard deviation of the distribution σ = 4 mm. The region of penetration of ions (208) into the region of the accelerating field is removed from the distribution center (203) by more than four (4.29) standard deviations. In this case, the ratio of the distribution value (204) to the distribution value (203) in the region (208) will be about 2.64. This means that the characteristic time of a change in the signal from ions (203) is ~ 2.64 times longer than for ions (204). Thus, practically insoluble signals (203) and (204) for registration with a continuous decrease in field strength (13), an analogue of which is proposed, for example, in the US Patent Loboda [8], become completely separated when registering signals from ions for the chosen constant values field strength (13). Compared to the half-maximum resolution of the peaks, as is customary in the separation of ions by mobility, this means about a ten-fold increase in resolution. This gain can be increased several times, because separation of exponential contributions with comparable signal intensities for characteristic times differing by 20% or even 10% is quite realistic.

By setting a sufficiently strong field (36) inside the opening of the locking diaphragm (19) - (14), collision-induced dissociation of the analyzed ions can be carried out to produce product ions (211), (212), the flux of which will vary in the same exponents as and the corresponding starting ions (209) and (210). If, for example, all types of initial ions have unique fragments that differ in their m / z values, then these fractions, with their sufficient intensity, can be used to determine the characteristic times of the corresponding individual exponents. In general, the separation of such multidimensional data will be discussed below. We can expect a gain in resolution by several times for multidimensional data compared with the analysis of one-dimensional curves.

The decrease in the standard deviation, which at a given flux density will occur for ions with a large collision cross section, which follows from relations (100) - (104), can lead to an increase in the influence of the space charge on the quality of the recorded data. The way out here can be the controlled removal of recorded ions from the axial region of the gas stream due to the combined action of the space charge of smaller ions and a decrease in the focusing effect of the radio frequency field, for example, a decrease in the radio frequency voltage, as well as the effect of a non-resonant rotating field in the absence of the space charge of small ions. The same displacement of the ions leads to their additional separation, so ions of large m / z will deviate more strongly from the axis of the quadrupole (38) and the gas jet (5), where the density of the gas flow is less and therefore they will shift more toward the beginning of the quadrupole under the action of the field ( 13).

Thus, two situations are possible for the studied ions. In the first case, there is a flux of relatively small ions, significantly exceeding the flux of the studied ions in intensity, so that it is possible to create a space charge near the axis of the quadrupole (38), sufficient for a noticeable stratification of the ions of interest in the m / z range, which allows for their additional separation. The absence of a sufficient flow of small ions determines the second embodiment of our method, based on the excitation of nonresonant rotation of ions around the axis of the quadrupole (38).

In the absence of a sufficient stream of small ions, such a stream can be created by adding suitable impurities to the buffer gas. An excessively intense stream of small ions can be compensated by an increase in the amplitude of the radio frequency voltage, which will lead to better focusing of the studied ions and partial death of small ions that are outside a sufficiently dense gas stream (5). If this intensity is insufficient, by increasing the longitudinal field strength (13) directed against the stream (1), the speed of small ions in the stream (5) can be reduced, which will lead to an increase in the density of the space charge. An increase in field strength (13), however, is limited by a decrease in the standard deviation of the distribution of the analyzed ions, which can lead to an unacceptable increase in the influence of the space charge of these ions on the recorded data. Therefore, essentially the only way to control the average distance of the ions from the axis of the quadrupole (38) in this case is to change the amplitude of the radio frequency voltage. It should be noted that since the flux density (5) decreases with increasing distance Z from the exit from the capillary (2), the speed of small ions in the flow due to the reaction of the field (13) will decrease and, accordingly, the density of these ions in order to preserve them flow - increase. This will lead to an increase in the distance of analytical ions from the axis of the quadrupole (38) with increasing Z and to their increasing shift by the field (13) away from the locking diaphragm (19). This means a sharper decrease in the density of ions in their distributions near the locking diaphragm, which is predicted by the Gaussian distribution (100). Thus, the above estimates, showing significant ratios of the recorded ion fluxes at relatively small shifts of the distribution maxima, may turn out to be underestimated, which can provide even greater resolution of the proposed method.

квадрупольного радиочастотного поля и кулоновского отталкивания от облака малых ионов, сфокусированных в виде цилиндрического жгута вокруг оси квадруполя (38):The average radius r _{i of the} deviation from the axis of the quadrupole (38) of relatively large ions when repelled by a cloud of small ions is determined by the equality of the focusing force

quadrupole radio frequency field and Coulomb repulsion from a cloud of small ions focused in the form of a cylindrical bundle around the axis of the quadrupole (38):

where Q is the linear density of the cloud of small ions, V _rf and ω are the amplitude and angular frequency of the quadrupole radio frequency voltage, r ₀ is the inscribed radius of the quadrupole (3.7 mm for our quadrupole), m is the mass of ions. Thus, ions with large values of m / z (206) will be more removed from the gas jet (5) and more significantly shifted to the left by field (13) due to a decrease in the effect of the flux (1), compared with ions with smaller m / z (203 ), (204) and (205). Ions (207) with the same mass and close collision cross section, but with a larger charge than ions (205), although they will be displaced closer to the flow axis (1) and are subject to a stronger influence of the flow, are shown shifted to the left, because in this case, the influence of the field, proportional to the charge, may be more significant.

The value of the second derivative of the total "potential" radial energy of large ions at an equilibrium distance from the axis of the quadrupole (38) will be:

, и эта величина не зависит от линейной плотности заряда малых ионов. Это означает, что собственная частота ω_r малых радиальных колебаний больших ионов не зависит от линейной плотности расталкивающих малых ионов и в

раз больше, чем собственная частота колебаний или вращений этих же больших ионов при отсутствии их расталкивания объемным зарядом:those. this is doubled compared to the second derivative of the effective potential

, and this value does not depend on the linear charge density of small ions. This means that the natural frequency ω _{r of} small radial vibrations of large ions does not depend on the linear density of repulsing small ions and in

times greater than the natural frequency of oscillations or rotations of these same large ions in the absence of their repulsion by the space charge:

.

.

To excite such radial vibrations of large ions in a quadrupole, it is sufficient to create a rotating field (11, Figure 1) with such a frequency. Since at each point of the ring distribution of ions the rotational field can be decomposed into a radial and phase shifted by π / 2 tangential components, it is precisely the radial vibrations that will be excited. In the tangential direction, if there are any eigenfrequencies of oscillation, they are strongly shifted to lower frequencies in comparison with ω _r and the field of such a frequency will practically not be excited. The radial vibrations at each point of the ring distribution of ions will have a continuously changing phase along the ring, coinciding with the phase of the rotating field in the case of resonance, so that this ring of ions will generally rotate around the axis of quadrupole (38) with a frequency ω _r .

Schematically, such a rotating ring is shown in FIG. 3 (311) with a center offset from the center of the small ion tow (309), which are focused around the axis of the quadrupole (38). The gas jet (310) is also shown offset from the axis of the quadrupole (38). The dashed line (306) shows the conditional boundary at which the ions can lose the averaged stationary motion and recombine on the rods of the quadrupole (301) under the influence of relatively weak resonant rotating fields. One of these ions (304), on the way to recombination, is shown to rotate under the influence of a field (324), which causes resonant spinning of the ions with the chosen m / z when they diffuse beyond the boundary (306). The field untwisting the ring (311) is shown by two parallel arrows (308). The electrodes (313), (314), (312), (315), (323), (322) and (317), as in our application for the RF Patent [33], are designed to record induced voltages from moving ions. Inside the quadrupole rod images (301), radio frequency voltages (302) and two rotational voltages (303) are shown to create fields (308) and (324).

The rotation of the ring distribution (311) can noticeably increase the average kinetic energy of the analyzed ions compared to the thermal one. This will lead to an increase in the effective and internal temperature of ions [34]. The result of this may be a change in the cross section for collisions of an ion with atoms or molecules of a gas stream. Such a change for different ions can vary significantly and even have a different orientation. So, for example, for multiply charged ions, in the case when some charges in the ion are localized at a sufficient distance from each other, due to the repulsion of these charges, the ion structure at a relatively low temperature will have a more or less developed character. The collision cross section for such an ion will be increased in comparison with the structure where such repulsion is compensated to some extent by the chaotic movements of the ion fragments at elevated temperature. If the ion charges are located close enough to each other, then at a lower temperature the ion structure will be more compact due to the polarization attraction of the neutral parts of the ion to the charged center. Therefore, an increase in temperature will lead to thawing of the motions of such parts of the ion and to an increase in the collision cross section. Thus, the excitation of radial ion vibrations can lead to the separation of ions, which at room temperature had the same masses, charges and collision cross sections. The absence of new components during such excitation of the analyzed ions can be used to confirm the accuracy of the analysis. The ion cloud (204), shown in Figure 2, can be interpreted as the result of such an “unwinding” of the ion cloud (203), resulting in an increase in the average number of collisions with gas atoms (7) per unit time by ~ 1%, leading to a shift of the distribution (204) to the right by 1 mm and an increase in the effective temperature of ions by ~ 10%, which also led to a broadening of the distribution (204). In this case, the ratio of ion densities at a distance of 17 mm to the right of the distribution center (203) for distributions (204) and (203) turned out to be ~ 5.8, in contrast to the above value of ~ 2.64 for the same dispersion of distributions (203) and (204).

Rotation of the ring distributions of selected ions can be used, especially for ions with large m / z, to limit the increase in their number in order to avoid undesirable effects of space charge accumulation. If ions are located at a sufficiently large distance from the axis of the quadrupole (38), then the rotation of their annular cloud can lead to the death of ions located on the outer periphery of the ring. By changing the amplitude of the rotational voltage, it is possible to adjust the rate of such death and bring these ions to the desired stationary amount. For ions with average m / z, an increase in the voltage rotating their ring distribution may not lead to their selective death. In this case, the excitation of an additional resonant rotating field, effective in the absence of the influence of the space charge, with a frequency of:

.

.

In this case, such a field can divert the corresponding ions to the rods of the quadrupole if, due to random diffusion walks, they are in the zone where the space charge of small ions focused around the axis of the quadrupole (38) already practically does not affect them.

During the entire time of manipulation with relatively intense ion fluxes, low-intensity ionic populations can accumulate and become suitable for conducting quantitative measurements. As such populations accumulate, their further growth must also be limited either by the method just described, or by stopping the flow of ions through the input diaphragm. In the latter case, the flow of small ions along the axis of the quadrupole (38) ceases, the stratification of clouds of relatively large ions disappears, and it remains only to use a rotating field to control the position of ions in the radial directions or use stronger fields (13) to stop the studied ions in the flow (5 )

In the absence of a sufficient density of small ions to displace the studied ions from the axis of the quadrupole (38), rotational voltage is applied to the rods of the quadrupole with a frequency significantly shifted toward low frequencies from the resonance frequencies of the studied ions ω _res . The amplitude of this voltage is large enough to unwind the desired ions in the region of relatively high gas density inside the stream, so that these ions can approach or even cross the jet boundary (5). At the same time, in the region of residual gas density, the influence of this rotating field should not be enough to significantly unwind the ions and lose them in decays or on the rods of the quadrupole.

How this can be done is illustrated in FIG. 4. Shown here are the resonance curves for the relative average ion spin radii, based on formula (411), taken from our work [9]:

The curves were calculated for hypothetical ions with m / z 400 and 401 for the expected flux density in the ion spin region and 100 times lower residual gas density. The widths of these curves at half maximum, formula (412), also differ 100 times:

The characteristic relaxation time of the ion velocity τ _ν was calculated by the formula (413):

based on the mass of buffer gas atoms M = 40 Da, their average thermal velocity V (neglected ion velocities) at room temperature and a reasonable value for the collision of ions with gas atoms σ = 200 Å ² . The gas density n was calculated from the equation of state of an ideal gas at pressures of 30 mTorr for the upper wide (407) and (408) and at and 0.3 mTorr for the lower narrow curves (409) and (410), respectively. It is seen that with a sufficiently large deviation from the “resonance” point near the jet (5), the mean square radius of rotation of the ions slightly deviates from the maximum value. At the same time, the resonance curves at a residual pressure outside the zone of the gas stream fall off quite sharply, and the spin radius with a sufficient deviation from the resonance even at relatively high rotational voltages can be quite acceptable. With large deviations from resonance, the radius of rotation (414):

practically does not depend on the relaxation time of the ion velocity (413) or on the gas density.

To control the total number of accumulated rotating ions, registration of induced voltage differences across thin electrodes, for example (313) and (314) shown in Fig. 1, Fig. 3 and Fig. 5, can be used. With the symmetrical position of these electrodes relative to the nearest rods (301) of the quadrupole, the induced signal from the rotating field (303) will be largely compensated and, with careful adjustment, reduced to a value comparable to the signal from rotating ions. This signal at the frequency of the rotating field with acceptable stability of the generator of the rotating field will be almost constant in amplitude. The signal from the accumulated ions will initially increase almost linearly with time, and when a significant space charge density is reached, the signal will begin to saturate due to the death of the ions caused by their repulsion or other reasons. The presence of such saturation will signal the end of the accumulation process. The measurement of the phase shift of the registered variable signal from the signal of the rotating field will carry qualitative information on the composition of the accumulated ions - formula (415):

,

, создающих два вращающих поля, нерезонансного (508) и резонансного (524). Условная граница зоны прохода ионов через диафрагму(19)-(14) показана пунктирной линией (504). Пунктирной линией с большим шагом (507) показана граница, после которой ионы начинают сталкиваться с поверхностями стержней квадруполя. Зона между двумя этими пунктирными линиями - это область возможного нерезонансного вращения ионов (505), (506), (509) без значительной вероятности их потери либо на поверхностях стержней, либо путем переноса в орто-ВПМС или в другой используемый масс-анализатор. Усредненная траектория резонансного вращения (511) выбранных ионов вокруг центра (510), вращающегося вокруг оси квадруполя (38), показана точками.Elimination of an excessive amount of certain ions can be organized by the formation of resonant rotating electric fields corresponding to the selected m / z. This excites an additional rotation of the ions of these compounds around their position in a packet of nonresonantly rotating ions. Figure 5 schematically shows a cross section of a quadrupole in the region of rotation of the accumulated ions. Inside the image of the rods (301) of the quadrupole, expressions are given for the stresses applied to them. This is a focusing radio frequency voltage (302) with a frequency ω and amplitude V _rf and two rotational voltages (503) with frequencies ω ₁ , ω ₂ and amplitudes

,

creating two rotating fields, non-resonant (508) and resonant (524). The conditional boundary of the zone of passage of ions through the diaphragm (19) - (14) is shown by the dashed line (504). The dashed line with a large step (507) shows the boundary after which the ions begin to collide with the surfaces of the rods of the quadrupole. The area between these two dashed lines is the region of possible non-resonant rotation of ions (505), (506), (509) without a significant probability of their loss either on the surfaces of the rods, or by transfer to the ortho-VMS or to another mass analyzer used. The average trajectory of the resonant rotation (511) of the selected ions around the center (510), rotating around the axis of the quadrupole (38), is shown by dots.

Moving near the surface of introduced electrodes (312), (313), (322), (323), ions (506), (505) and (509) cause the appearance of an induced charge of the opposite sign on these electrodes. The position and shape of these electrodes should be such as to ensure, on the one hand, the highest possible level of induced signals, and, on the other hand, distortions of the quadrupole field that are inevitable when introduced, should not significantly distort the movement of the analyzed ions and lead to significant losses in resolution and sensitivity. The calculations of the induced signals and the simulation of ion motion using the Simion package [40] for calculating electric fields showed that cylindrical electrodes with a diameter of 0.2 mm located symmetrically with respect to the nearest quadrupole rods with axes at a distance of the radius of the quadrupole r ₀ from the axis of the quadrupole have acceptable characteristics (38). The paired electrodes (315), (314), (317), (316) located symmetrically with respect to the planes passing through the axes of the adjacent quadrupole rods (301) of the quadrupole are significantly less affected by the ion field, while the induced voltages from the fields of round rods quadrupoles will be almost the same for the electrodes of the corresponding pairs. This allows, similarly to ICR spectrometry, to organize registration of rotating ions by measuring the signal between the electrodes of the corresponding pairs. Moreover, in this case, such registration can be carried out through four channels - for each pair of electrodes (312) - (315), (313) - (314), (322) - (317) and (323) - (316). By simply summing the amplitudes of the signals over all four channels, the signal-to-noise ratio can be doubled. More complex processing of signals from freely rotating ions, including the fast Fourier transform, taking into account the phase shifts of the resulting complex amplitudes, can lead to a four-fold increase in the resolution of the resulting spectrum. A similar technique was proposed by E. N. Nikolayev and J. Franzen for ICR spectra during signal registration using a multi-electrode cell [37]. The resonant frequencies of the signals from the ions will be significantly less than the radio frequency ω of the ion-focusing voltage (302) and much larger than the frequency of the forced rotation (508) around the gas stream. Using amplifiers with an appropriate bandwidth connected between the electrodes (312) - (315), (313) - (314), (322) - (317) and (323) - (316), the high-frequency and low-frequency components of the recorded signal can be significantly let loose.

Rotational movements of the ring ion distributions arising, as described above, due to electrostatic repulsion of small ions from the axial tow, can also be detected by induced signals on the pairs of electrodes (312) - (315), (313) - (314), ( 322) - (317) and (323) - (316). In this case, because the analyzed ions are distributed around the axis of the quadrupole (38), upon excitation of free rotations by a short-term inclusion of a package of rotational stresses in a given frequency range, the influence of the space charge of rotating ions can be weakened, leading to the fusion or coalescence of ion clouds with close m / z, well known for ICR spectrometers [38]. We observed the same phenomenon when simulating free rotations against the background of forced ion rotations in a radio-frequency quadrupole [33]. The registration of a signal from free ion rotations with obtaining a mass spectrum based on the inverse Fourier transform is important for obtaining a survey mass spectrum of the accumulated ions and determining their resonant frequencies.

. Большая из них возбуждает радиальные колебания ионов «внутри» кольца распределения, часть из которых имеет возможность диффузионно попасть в область остаточного давления буферного газа, где отталкивание объемного заряда существенно меньше, чем фокусирующее воздействие радиочастотного квадрупольного поля. Следует заметить, что отношение этих сил убывает как третья степень расстояния от оси, поскольку отталкивание убывает обратно пропорционально расстоянию, а фокусирующая сила квадратично растет с расстоянием ионов от оси квадруполя (38).It is advisable to carry out such registration during the accumulation of ions periodically, thereby controlling the number of accumulated ions with different m / z and the rate of their accumulation. If some ions exceed the maximum permissible amount or if the expected number of these ions exceeds the limit in the expected measurement time, the corresponding rotational field is turned on to remove excess ions to the quadrupole rods. For ring distributions at relatively small distances from the axis of the quadrupole (38), for such a removal, the use of rotating fields with two frequencies differing by a factor of approximately equal

. Most of them excite radial vibrations of ions “inside” the distribution ring, some of which can diffusely fall into the region of the residual pressure of the buffer gas, where the repulsion of the space charge is much less than the focusing effect of the radio-frequency quadrupole field. It should be noted that the ratio of these forces decreases as the third power of the distance from the axis, since the repulsion decreases inversely with the distance, and the focusing force increases quadratically with the distance of the ions from the axis of the quadrupole (38).

Thus, with a tenfold increase in the distance of the ions from the axis compared to the equilibrium distance (for example, from 0.1 mm to 1 mm), the resonant frequency of rotation of the ions at this distance will be less than the resonant frequency in the absence of the influence of the space charge by ~ 1/2000 fraction. This is quite comparable with the expected resolution of the excitation of rotation at a residual pressure of such a buffer gas as argon at the level of 10 ^-4 Torr. Therefore, the use of resonant rotating fields without taking into account the influence of the space charge with sufficient intensity is quite acceptable for the effective removal of ions that are in the critical zone of the residual pressure of the buffer gas on the rods of the quadrupole. Moreover, the selectivity of such a procedure can be quite high. The probability of ions entering this critical zone can be controlled by the amplitude of the resonant rotational field, exciting the radial vibrations "inside" the corresponding ring distribution. Since the density of the buffer gas in this zone can be much higher than the residual density, the selectivity of such excitation in m / z can be significantly lower. At the same time, it can be expected that the probability of ions entering the critical zone will also be determined by their mobility, since their speed will be proportional to mobility, and the addition to the effective temperature (which diffusion depends on) will be proportional to the square of this speed.

It should be expected that the selectivity of the controlled death of excess ions in the case of their relatively small deviation from the axis of the quadrupole (38) by a non-resonant rotational field when an additional rotational field of the resonant frequency is applied will be lower compared to a similar shift of the ions by the space charge. This is a consequence of the fact that in the case of non-resonant rotation there is only one resonant frequency of excitation of oscillations or ion rotations, which, under conditions of increased gas density, necessitates the use of sufficiently large amplitudes of the rotational voltage, which can lead to the death of ions with a greater than in the previous case , spread in m / z when they reach the critical region of the residual pressure of the buffer gas. The solution here may be to use two additional rotating fields to the main non-resonant rotating field. One thing is that the amplitude is increased and the frequency shifted from the resonance by so much that it does not greatly affect the spin of the ions in question in the region of relatively high density at their equilibrium distance from the axis of the quadrupole (38), but cannot significantly spin them in the region of residual density buffer gas. The second is a relatively weak resonant rotational field, effectively spinning the ions in question to a radius larger or comparable to the radius of the quadrupole and, thereby, leading to their death in the region of the residual density of the buffer gas. Such an approach, of course, makes sense if, by chance, the first rotating field is not near the resonance of other ions, the death of which is undesirable. The same, of course, applies to fields that excite radial ion vibrations in ring distributions in the case of stratification of ion clouds in the presence of a significant space charge along the axis of the quadrupole (38).

Thus, in both cases, one can achieve a sufficiently high selectivity of ion death by the method of shifting the analyzed ions from the axis of the quadrupole (38) using relatively low intensity resonant rotational fields. Since the equilibrium radius of resonant rotation is proportional to the mobility of the ion

which follows from the definition of mobility and equation (411):

then the probability of the death of an ion at a given resonant rotational voltage V _res will depend on its mobility. To ensure the death rate of the selected ions, close to optimal, it will be necessary to conduct test measurements of the induced signals for different rotational voltages.

With such measurements, two situations are possible. If the resonant voltage V _{res is} sufficiently large, so that all ions with a given m / z that fall into the zone of the residual density of the buffer gas die quickly, then in this case the signal at the resonant frequency may be absent or extremely weak. The ion death rate in this case will be determined by their exit velocity into this zone and depend on the voltage of the spin fields or radial oscillations. When V _res determines the radius of rotation (417) noticeably smaller than the radius of the quadrupole, the death of ions can occur diffusion and rather slowly. In this case, a relatively large number of such resonantly rotating ions can provide a sufficient induced signal at the resonant frequency for its normal registration. In necessary cases, the selection of the appropriate intensity of the radio-frequency quadrupole focusing field and other necessary fields can provide a greater or lesser contribution of fragmentation processes to the total loss of ions. Thus, the separation of ions can be realized according to the degree of resistance to the processes of monomolecular decay, similarly to how it is described in our patent application [33].

This second case seems to be preferred because provides measurements at two frequencies for the same ions, which increases the reliability of the information received. Signals related to the same type of ions, in the absence of a noticeable influence of their space charge, should include exponentials with the same characteristic time. If the resonant frequency for these ions is precisely known, and the rotation frequency is slightly different from it, then, by measuring the phase shift of the induced signal with respect to the rotational voltage at these two frequencies, we can estimate, according to expression (415), two characteristic relaxation times of the ion velocity or their mobility in two regions - in the region of the residual density of the buffer gas and in the region near the axis of the quadrupole (38). The constancy (up to measurement errors) of the phase shift along the obtained exponential curves is an additional criterion for the correctness of the measurements. If the curves significantly deviate from the exponentials, and the phase shifts in different parts of these curves statistically coincide, this may be due to the influence of the space charge or to other nonlinear effects in the measurement process that must be eliminated.

An illustration of one of the possible ways to limit the influence of space charge on the recorded data using ortho-VMS at the output of the radio frequency quadrupole is shown in Fig.6. The graphs in the upper left part demonstrate the case of registration of relatively weak ion flows, when at first switching the polarity of the focusing field (34) of the locking diaphragm (19) - (14) results in the accumulation of ions. After some time, the focusing field (34) is restored, and the time-decreasing stream of ions passing through the locking diaphragm (19) - (14) is recorded, which is illustrated by curve (601). The dashed curves (602) and (603) show two exponentials with characteristic attenuation times of 5 sec and 10 sec, respectively, which together give curve (601). If necessary, these ion accumulation and registration procedures can be repeated as many times as desired. The addition of recorded curves (601) will lead to an increase in the signal-to-noise ratio with an acceptable influence of the space charge, which will allow one to obtain the desired efficiency of dividing the total curve (601) into components similar to curves (602) and (603).

In the case of a relatively large flux of analyzed ions, their accumulation during registration with the focusing field turned on (34) will lead to the registration of an increasing curve (604), which in the shown case is the sum of two exponential curves (605) and (606), approaching with increasing registration time to the fluxes of the corresponding ions, which would be recorded in the absence of an antifield (13). In the absence of stratification of the analyzed ions by the space charge of small ions and in the case of using non-resonant rotation of ions to displace them from the axis of the quadrupole (38) by blocking the flow of analyzed ions at the input diaphragm (8) - (9) at an instant in time (613), an increasing ion flux (607) ) becomes falling (608). The characteristic times of the exponential components (609), (610) and (611), 612) of the increasing branch of the ion current (607) and the decreasing branch (608) coincide in pairs. Thus, the selection of exponential components in curves (607) and (608) can provide a criterion for the adequacy of the analysis based on the coincidence of the number of found exponentials, their characteristic times and the continuity of the transition from curves (609) and (611) to curves (610) and ( 612).

Instead of blocking the input stream of the analyzed ions by turning on at the time (620) the death of these ions on the rods of the quadrupole (301) due to the resonant spinning, the increasing recorded signal (614) can also become decreasing (615). In this case, the characteristic times of exponentially falling sections of the components (617) and (619) will be significantly less than the characteristic times of the corresponding increasing sections (616) and (618). This can lead to a noticeable reduction in the analysis time if it is possible to further separate the recorded signal (614) - (615) due to differences in the mentioned characteristic times of the change of signals before and after the inclusion of the death of ions at time (620). Periodic repetition of turning on and off this death also opens up the possibility of accumulating the recorded data and increasing the efficiency of their separation. This method of data recording provides the greatest efficiency of accumulation of small components of the initial ion flux, because this flow is not interrupted during the entire measurement time.

With careful selection of the amplitude and frequency of the resonant rotating field and also, if necessary, the amplitude of the radio frequency focusing voltage, it is possible to form ion-products of fragmentation induced by multiple collisions, and on this basis, additional separation of the analyzed ions or control of the adequacy of the results of separation of the recorded ion current curves. In addition, in this case, it is possible to increase the relative content of the ions of interest, which differ from other "interfering" ions not only in m / z, but also in mobility. Ions with matching m / z, but with less mobility, are more strongly displaced by the gas flow and can relatively quickly leave the quadrupole through the locking diaphragm (19) - (14) to the mass analyzer. Ions with greater mobility will be more unwound by a resonant rotating field, will come closer to the rods of the quadrupole (301), will have a higher effective temperature and, accordingly, a greater probability of death on the rods than ions with less mobility, as illustrated in Fig. 2 for distributions ( 203) and (204) along the axis of the quadrupole, which can be transferred to the radial distributions of the corresponding ions.

As you know, the sum of the exponential curves satisfies the finite-difference equation with constant coefficients or, in other words, there is an exact linear forecast of the subsequent values of such curves from the previous ones measured with some (constant in this case) time step. Having determined the coefficients of such a forecast, for example, by the least squares method, the damping factors of the corresponding exponentials can be determined by finding the roots of the characteristic polynomial, as for the corresponding differential equation with constant coefficients. In this case, the computational procedure described by us in [22] can be used, the modified block diagram of which is shown in Fig. 7. The initial data for this procedure are the linear prediction coefficients and their number. To determine this number in this case, you can use the natural separation of the observed data at the frequency of rotation of the initial ions. Firstly, these are the curves proportional to the sinusoidal signal from the rotational voltage itself, and the curves shifted in phase from this signal by π / 2, which are caused only by rotating ions. Secondly, it can be data taken for various pairs of respective electrodes, for example, (312) - (315) and (313) - (314). By calculating the Fourier coefficients for these two sinusoids (cosine and sine transforms) for some set of time intervals, we obtain data sets for forecasting. Consistently increasing the number of coefficients of such a forecast, we find them in the first array, requiring a minimum of forecast errors. Using the found coefficients, we find the forecast error for the second array. We leave such a number of forecast coefficients N, which provides a minimum of such an error. We find N refined coefficients for both sets of Fourier coefficients {C _k }, requiring a minimum of the average forecast error for both arrays or for all available data if multichannel registration is implemented.

If we write down the condition for accurate prediction for one exponent exp (-t / τ) for equally spaced measurements with a step Δt, we obtain a characteristic equation if we introduce the notation w = exp (-Δt / τ):

Its roots (positive numbers less than 1) are equal to the damping factors of all the exponentials included in the measured data. It was the roots of the polynomial with constraints that were found using the procedure described by us in [22]. The procedure takes into account the errors of measurement or calculation of the coefficients of the polynomial, reducing the problem to finding the minimum of the functions of many variables, which describes the sum of the squares of the discrepancies of these coefficients with their calculated values through the desired roots. To increase the accuracy of finding such a minimum, a random choice of the initial descent point to a minimum is made, and the obtained search results are then averaged.

Apparently, standard procedures for finding the roots of a polynomial can be used. However, inaccuracies in setting the coefficients of the polynomial can lead to the appearance of roots that are outside the permissible range, or even complex. What to do in such cases is not entirely clear. It is better to use the method where the restrictions on the sought quantities are laid down from the very beginning. Moreover, the accuracy of the approximation of the coefficients of the polynomial through the found roots in the presence of estimates of the error in the calculation of these coefficients will be a criterion for the adequacy of the obtained exponential attenuation factors.

Knowing these factors or the characteristic decay times of all the exponentials included in the signal measured at the ion rotation frequency close to the resonant one, by solving the corresponding system of normal equations, one can find the contributions of these exponentials and find phase shifts with respect to the rotating field, the signal from which will be undamped An “exponent” with a damping factor of 1. Formula (415) allows for the measured phase shift φ (converted to the phase shift between the directions of the rotating field and the average linear velocity and new at this frequency) to define the characteristic relaxation time τ _ν speed. It is uniquely associated with the mobility of κ ions (416).

If the resonant frequency of ions dying with some characteristic time found is not exactly known, then it is possible to carry out measurements simultaneously for two close rotation frequencies. In this case, having obtained the corresponding phase shifts, we will have two equations (415) with two unknowns, of which both the resonance frequency and the characteristic relaxation time of the velocity of these ions can be found. Thus, if rotating ions significantly differ in the characteristic times of their death, then their resonant frequencies and mobilities can be determined even in cases where the corresponding ions cannot be resolved by any known method of mass analysis or ion separation by mobility.

Another possibility of separating signals from ions with the same m / z, but differing in the characteristic times of their death or transfer from the quadrupole to the ortho-VPMS or to another subsequent mass analyzer, is obtained by analyzing the entire set of multidimensional data containing signals from these ions, including mass spectra of product ions, if they were recorded. Registration of induced signals on four pairs of introduced electrodes (312) - (315), (313) - (314), (322) - (317) and (323) - (316) at two frequencies of rotational voltages used as described above , to remove excess ions with a given m / z to the quadrupole rods after calculating the sine and cosine Fourier transforms, it gives a sixteen-dimensional data set. If the number of significant types of ions with a given m / z described by different exponents is not more than 16, then in the general case each of these exponents can be obtained as a linear combination of these data, and this is the basis for their detection, which will be described in detail below. If necessary, the data dimension can be increased by introducing additional rotating fields. Their frequencies should be shifted relative to the frequencies already used. Measurement of induced signals at each frequency increases the data dimension by 8. During the formation of product ions by collision-induced dissociation, some of these additional frequencies may correspond to some product ions. To find these frequencies, periodic excitation of free ion rotations in a given frequency range and registration of induced signals with their Fourier transform can be used. In the presence of product ions of relatively small m / z, these product ions can enter the region close to the gas stream (5) and be transported to the ortho-VMS and recorded there. If the frequency of these measurements coincides with the measurements of the induced signals and their Fourier transforms, the data obtained at the ortho-VPMS are included in the general data set and can be analyzed together.

Ions with selected values of m / z and mobility, starting from lower values, can be moved to the output diaphragm (14) by the action of a gas stream (5) by decreasing the counterfield (13) or increasing the focusing RF field V _rf . A sufficiently strong field can be created inside the diaphragm (14), which ensures the formation of fragment ions of collision-induced dissociation, which in this case will be caused by strong, mostly single collisions with gas atoms or molecules. During rotation in a quadrupole, ion fragmentation is caused by ion heating as a result of repeated collisions with buffer gas atoms, and both of these fragmented mass spectra can carry complementary information on the structure of the compounds under study. The intensities of fragment ions, sequentially recorded in the second case in the ortho-VPMS or in another mass analyzer with a certain time step, are a multidimensional data set that can also be analyzed by the considered method.

Fig. 8 illustrates the idea of such an ion analysis. Here, the change in time t of the intensities J of three hypothetical peaks of the mass spectrum of the accumulated ions whose input stream is stopped is depicted. One of these peaks (800) with a minimum m / z, shown by thick lines, decays relatively slowly exponentially (801) with a characteristic time τ ₁ . The other, (803) with a maximum m / z, shown by thin lines, exponentially disappears much faster (804) with a characteristic time τ ₂ . The average peak (805) is the sum of the first two peaks and is composed respectively of two lines - thick and thin. These three peaks correspond to two hypothetical starting ions disappearing with characteristic times τ ₁ and τ ₂ , which, upon fragmentation, give two equally probable product ions, shown by thick and thin lines, respectively. These three peaks at consecutive equally spaced time instants with an interval Δt (802) can be expressed through each other using linear expressions, which are written in matrix form in (806):

In a more general case, the time-following intensities of the peaks of the mass spectrum are written as the product of the transition matrix A _kl by the vector of previous intensities - equation (807):

и собственные числа (809):Here l numbers the measured mass spectral peaks (the total number is n), k - sets the number of initial ions (no more than n), decaying with different characteristic times and producing product ions, the intensities of which form a linearly independent system of vectors. The matrix elements of the transition matrix can be calculated using the least squares method from the condition of the best in the mean-square fulfillment of equality (807) for all moments of measurement. For this, the number of recorded mass spectra (measurement times) should be no less than the number of peaks of the mass spectrum (n). By solving the eigenvalue problem (808) for the transition matrix, eigenvectors are found

and eigenvalues (809):

The eigenvectors describe the intensity distributions of the product ions for each source ion, which corresponds to an eigenvalue (809), which is an exponential decay factor of the number of these ions. So, for example, for the transition matrix in expression (806), vectors with components (1, 1, 0) and (0, 1, 1) are eigenvalues with eigenvalues equal to the first exp (-Δt / τ ₁ ) and the second exp ( −Δt / τ ₂ ) exponential decay factors. After the number of initial ions and the exponential decay or relaxation factors of the corresponding signals are found, the contributions of the mass spectra of product ions from these initial ions in all recorded samples of the initial mass spectrum to successive equally spaced time instants can be calculated by solving the corresponding systems of linear algebraic equations based on the requirement of a minimum of the standard error of the approximation. In this way, mass spectra can be obtained for each source ion, as in the case of their complete separation before measurements.

The experimental data we obtained, shown in Figs. 9 and 10, confirm the formation of a dense argon gas jet near the axis of the quadrupole (38) and the focusing of a sufficiently intense stream of argon ions around this axis, which can cause stratification of large mass ions. The data were obtained for an interface that differs from that shown in Fig. 1 by the absence of a locking diaphragm (19) - (14), the design of the input diaphragm (8) - (9), single-layer in this case, with an inlet diameter of 3 mm, and the inverse arrangement electrodes (17), which were used to form a scattering field at the exit of the quadrupole (10). The capillary (2) had a diameter of 0.215 mm and a length of 18 mm. The argon pressure in the mixture with 2% xenon in chamber (3) was about 32 Torr. The residual gas pressure in the quadrupole chamber is ~ 1.1 · 10 ^-4 Torr. The gas flow from the capillary (2) was equal to ~ 12.6 cm ³ Torr / s. The data were obtained in the absence of a longitudinal electric field inside the quadrupole during the movement of the movable gap (21) with a width of 1 mm. The pitch of the slit was 0.1 mm. A series of mass spectra were recorded on the ortho-VPMS, previously developed by our group together with the laboratory of Prof. G. Volnik from the University of Giessen, Germany.

In Fig. 9, the squares show the registered ion flux distributions for xenon (901) (2% of the argon in the stream), the ³⁶ Ar argon isotope (with a fraction of ~ 0.3% of ⁴⁰ Ar) (903), and nitrogen molecules N ₂ (902 ), the main “pollutant” of the argon we use. Continuous curves are the result of a partial approximation of experimental data by trial functions. For light ions, these functions are the result of the convolution of a rectangular “hardware” gap function and a Gaussian curve with a standard deviation of 0.25 mm for ³⁶ Ar and 0.15 mm for N ₂ . The width of the hardware function of the gap in this case turned out to be two times less than the actual width of the gap - 0.5 mm. The distribution of xenon ions (901) is approximated by a more complex function. This is the result of the convolution of the same rectangular function of a slit with a width of 0.5 mm with an annular Gussian distribution with the center shifted relative to the center of a circular hole with a diameter of 2 mm in front of the movable slit. The radius of the annular distribution is 0.65 mm, the standard deviation is 0.1 mm, the shift along the coordinate of movement of the slit is 0.24 mm and in the perpendicular direction is 0.11 mm. The ion cutting radius in front of the gap instead of 1 mm turned out to be 0.85 mm.

The two-humped form of the distribution of xenon ions, as well as a decrease in the effective slit width and the radius of the collimating hole in front of the slit, can be explained by the influence of the space charge of mainly argon ions, which repels heavier and less focused xenon ions and forms negative countercharges at the sharp edges of the slit and collimating hole . Passing near these edges, the positive recorded ions experience a rather large deviation from the initial trajectories and do not subsequently fall into the accumulation zone of the time-of-flight mass analyzer. The standard deviation of the annular distribution of xenon ions (0.1 mm) leads to an estimate of the effective temperature of xenon ions at 40 K using relations (107), (106) and (100). This estimate confirms the presence of a sufficiently dense supersonic gas flow along the axis of the quadrupole. The linear density of argon ions at the end of the quadrupole turns out to be about 100,000 ions / cm, and the radius of the ring distribution of xenon ions at the end of the quadrupole is ~ 0.6 mm. Thus, an increase in the radius of this distribution from 0.6 mm to 0.65 mm in front of the gap (21) due to the influence of the space charge and the defocusing field of the electrodes after the quadrupole turned out to be less than 10%.

The presence of additional peaks (904), to the right of the main (901), (902) and (903), shown separately in Fig. 10 (1001), most likely, can be attributed to ions inside the gas stream (5), shifted from the axis quadrupole (38), as shown in Figure 1 (39). These ions are likely to be obtained as a result of the charge exchange of scattering ⁴⁰ Ar ⁺ ions after a quadrupole on Xe, ³⁶ Ar xenon atoms and N ₂ nitrogen molecules in a jet (5). These three distributions cannot also be attributed to ions formed before the gap (21), because even if the effective width of this gap is about 0.5 mm (as in the case of the main distributions of the same ions (901), (902) and (903)), then the observed distributions (1001) must be obviously wider than it actually is , since the standard deviation of the slot function in this case will be about 0.15 mm, which is very close to the standard deviations of the distributions (1001), but these distributions are quite far from rectangular functions, which would be for very narrow ion distributions in front of the gap (21) . The passage of ions moving inside the gas stream through the gap (21) is also unlikely due to the presence of a decelerating electric field from the electrodes (17), which will inhibit ions with kinetic energy close to thermal and will not allow them to approach the gap with high efficiency ( 21).

A possible mechanism for the formation and transport of ions forming a distribution (1001) is illustrated in FIG. 11. The initial distribution of ions (1101) outside the jet and the gas distribution in the jet (1102) in front of the movable gap (21), the sharp edges of which, to preserve the zero potential of the gap when exposed to a positive space charge of ions, are negatively charged, are conventionally shown. When moving in a jet (5), atoms, for example, xenon (1103) near the upper edge of the slit (21) with the initial direction forming a small negative angle with the direction of the axis (1104) of the ion-optical system, have a chance to deviate from their initial direction (beyond due to polarization attraction to the charged edge of the gap) so as to move near the axis (1104), get a charge when recharging from an argon ion (1107) from distribution (1101), get inside the receiving gap (1105) of a time-of-flight analyzer in the form of an ion (1108) and be registered there. Because the angle of deviation of the flow from the axis (1104) of about 0.0025 rad is enough to inform the xenon atom (with a kinetic energy of ~ 0.12 eV) the energy of motion in the orthogonal direction of about 1 µeV to compensate for this angle. With a significant deviation of the ion from the jet from the axis (1104), it has no chance of getting inside the gap (1105) due to the relatively low velocity of such an ion (1106), which coincides with the gas flow rate. He will not miss an electrostatic lens (1110) - (1111) - (1112) by the action of its fields (1115), as shown for the xenon ion (1109). At the same time, ions (1113) from the distribution (1101), which have at least an order of magnitude higher velocity (1114) than the velocity of the gas flow, can be focused by the lens (1110) - (1111) - (1112) with significant deviations from the axis (1104), so that inside the gap (1105) all ions from (1101) can pass through the gap (21) without significant deviations from the original direction of motion and retain their charge in contrast to the argon atom (1116) obtained from ion (1107), which gave its charge to the xenon atom (1103).

In principle, the lower edge of the gap (21), if the gap is sufficiently displaced upward from the position shown in FIG. 11, can make some contribution to the stream of recorded ions from the gas stream (5). However, since this should be the result of diffuse reflection of ions from the surface of this lower edge, and the reflected ions must travel a significant part of the path inside the stream (5) that passed above the considered edge, which can lead to their loss for registration, the flux of such detected ions should be small. Apparently, the presence of such ions can explain the small excess of the approximation curves for the distributions (902) and (903) by the recorded signal of the right tails.

The observed distribution of ions (1001), therefore, can be represented as the product of the distributions of the corresponding atoms or molecules in the stream (5) by the probability distributions of the formation of the corresponding ions from them with the direction of their movement, leading to the passage through the gap (1105). If we assume that the second distribution is independent of the density of the corresponding ions or of the starting atoms and molecules in the flow (5) and is proportional to the same distribution for other ions formed by a similar mechanism, then the ratio of the observed distributions of such ions will characterize the flow itself and will not depend on the conditions of formation and ion transport. Bearing in mind this possibility, the ratios of the distributions of xenon ions to the distributions of nitrogen ions and ³⁶ Ar ⁺ ions were calculated and presented on the right in FIG. 10 (1002). Since ³⁶ Ar ⁺ ions, in contrast to xenon ions, are able to lose their charge as a result of resonant charge exchange on argon atoms, the corresponding ratio (1002) shown by the dashed line is apparently of no interest. At the same time, the ratio of the distributions of xenon and nitrogen ions (solid line) demonstrates a qualitative proximity to the Gaussian curve with a standard deviation of about 0.15 mm. Because Since the distribution of nitrogen ions should decrease with a deviation from the flow axis, the obtained standard deviation of the distribution ratio should be an estimate from above of the standard deviation of the distribution of xenon ions. The formation of a Gaussian distribution, in principle, can be either the result of free molecular expansion of the gas in the jet (5), or the result of a diffusion process. In the first case, the standard deviation of such a distribution will be proportional to the rms velocity of the gas in the direction perpendicular to the axis of the flow, in the second, the square root of the diffusion coefficient. The ratio of a relatively narrow Gaussian distribution to a wider one will also be a Gaussian distribution. For free-molecular expansion, the ratio of the distribution for xenon to the distribution for nitrogen will correspond to a distribution of particles with a mass of about 100 units equal to the difference in molecular weights of xenon and nitrogen. In this case, the broadening of a gas such as argon will be larger than xenon, proportional to the square root of the ratio of atomic masses. In the diffusion case, the main part of the broadening will be proportional to the square root of the ratio of the diffusion coefficients. In both cases, this increase will be less than twofold (the diffusion coefficients of argon and xenon in argon differ by no more than 30%). Thus, we can assume that the value of 0.3 mm is an upper estimate of the standard deviation of the distribution of gas density in the stream (5) in these two possible cases.

Claims (21)

1. The method of structural-chemical analysis of the ions of organic and bioorganic compounds based on the balance of the effects of a narrowly directed buffer gas stream containing the analyzed ions of these compounds and a constant electric field moving the ions towards the stream in a linear radio-frequency trap, followed by detection, characterized in that the separation of the analyzed ions is carried out by selecting constant and variable electric fields inside the mentioned trap, taking into account the possible influence of the volume charge of a series of buffer gas ions to said analyzed ions, which are localized on average in certain places along the axis of the mentioned trap with a certain average distance from the said axis, after which time-varying signals are recorded proportional to the number of selected from the analyzed ions in the trap and / or proportional to the diffusion the flow of the mentioned selected ions, gradually arriving at the detector with characteristic times specific under given measurement conditions for ions differing in eniyami collisions with atoms or molecules of the buffer gas and / or the m / z values, and / or charge states and / or in the degree of resistance to unimolecular decomposition caused by repeated collisions with the atoms or molecules of the buffer gas. 2. The method according to claim 1, characterized in that in order to provide higher selectivity for the excitation of rotations or oscillations of ions, the linear radio frequency trap is a radio frequency quadrupole. 3. The method according to claim 1, characterized in that to create an ion stream of the compounds under study into a linear radio-frequency trap, the analyzed mixture is added to the buffer gas stream, and in the form of a well-focused molecular beam, this stream is passed through an electron ionization source located in front of the linear input diaphragm radio frequency trap. 4. The method according to claim 3, characterized in that the electron ionization source is a variable ionization energy source. 5. The method according to claim 3, characterized in that a gas mixture is added to the gas stream containing ions of the analyzed compounds from an external ion source, for example, multiply charged ions of biomolecules from an electrospray ion source. 6. The method according to claim 2, characterized in that to prevent the unauthorized death of resonantly rotating or oscillating ions on the rods of the quadrupole, these rods have a circular cross-section, providing near the rods a significant deviation from the ideal quadrupole field and, accordingly, the shift of the resonant frequencies of the ions. 7. The method according to claim 1, characterized in that in order to create a longitudinal electric field in a linear radio frequency trap and possibly change the longitudinal distributions of the focusing radio frequency field and / or the rotating or oscillating field, its rods are sectioned. 8. The method according to claim 1, characterized in that the linear radiofrequency trap in its middle part contains a locking diaphragm, which forms, together with the input diaphragm, an ion accumulation and fragmentation region. 9. The method according to claim 8, characterized in that for creating the desired electric fields outside the diaphragms and in their holes, the input and locking diaphragms of the linear radio frequency trap are multilayer with alternating conductive and dielectric layers. 10. The method according to claim 1, characterized in that for detecting selected ions and their fragmentation product ions, induced primarily by single collisions under the influence of a strong accelerating field inside the opening of the locking diaphragm, a linear radio frequency trap is coupled to a mass analyzer, in particular, this can be a time-of-flight mass analyzer with orthogonal ion input. 11. The method according to claim 1, characterized in that for detecting induced signals from ions rotating or oscillating in a linear radio frequency trap, the potential difference between two extended recording electrodes placed along the trap rods is periodically measured so that the induced voltages from these rods these electrodes turn out to be close in amplitude but opposite in phase, and to a large extent cancel each other when measured at frequencies close to the natural frequencies of the tions or oscillations of the ions. 12. The method according to claim 1, characterized in that for the registration of induced signals from ions, the measurements are repeated for several pairs of the said recording electrodes located, inter alia, between the pairs of the closest rods of the linear radio-frequency trap, thereby realizing multi-channel recording. 13. The method according to claim 2, characterized in that the excitation of rotation close to resonant, ions with selected values of m / z and mobility are periodically displayed in the zone of possible contact with the rods of the quadrupole; by changing the constant longitudinal and / or amplitude of the non-resonant rotating field, the amplitude and / or frequency of the quasi-resonant rotating field, the characteristic time of ion death, which is determined under the given conditions of stationary rotation, and m / z ions by their mobility and charge, are changed. 14. The method according to item 13, wherein the selection of the amplitude of the radio frequency field and other fields that control the localization and movement of ions creates ion fragments of the selected ions as a result of their multiple collisions with atoms or molecules of a buffer gas in a linear radio frequency trap; these fragment ions for relatively small m / z are focused to the axis of the radio frequency trap and recorded by the mass analyzer. 15. The method according to claim 1, characterized in that when registering sequential mass spectra of ion-products of collisional fragmentation, as well as when obtaining a multidimensional data set based on multichannel registration of induced signals, the separation of contributions to these mass spectra and / or these data for ion-products or signals from the initial ions, differing in characteristic times of death, is based on the calculation of a statistically stable transition matrix between time-equilibrium sets of intensities peaks of mass spectra and / or multidimensional data and estimates of its eigenvalues. 16. The method according to claim 10, characterized in that to reduce the proportion of the buffer gas stream to the mass analyzer, coupled to a linear radio frequency trap, the axis of this stream is shifted relative to the axis of the specified trap so that the main part of the stream does not enter the high vacuum through the inlet aperture part of said mass analyzer. 17. The method according to claim 1, characterized in that for controlling the accumulation of rotating ions in a linear radio-frequency trap by measuring the ion flux to said detector or induced signals at a rotation frequency exceeding the detector response or said signals of predetermined levels, it is a criterion for stopping the accumulation by locking the ion flow at the entrance diaphragm of the aforementioned trap or the organization of partial death of ions with the selection of control fields leading to acceptable stationary response levels of the detector or said induced signals from said ions. 18. The method according to claim 1, characterized in that to obtain an estimate of the mobility of the selected fragmenting or dying ions at a known resonant frequency of oscillation or rotation of these ions in a linear radio frequency trap, the phase shift of the induced signal from these ions is measured, which exponentially relaxes for fragmenting or dying ions, from a signal of a rotating or oscillating field, constant in amplitude for stationary measurement conditions. 19. The method according to claim 1, characterized in that in order to simultaneously obtain estimates of the resonant frequency and mobility of the selected ions, two or more rotating or oscillating fields with frequencies close to the resonant are exposed to the ions, and phase shifts of the induced signal from the said ions are measured from the signals of these fields. 20. The method according to claim 1, characterized in that in the presence of fragmenting or dying ions with different characteristic death times in a linear radio-frequency trap, the separation of signals from them and determination of phase shifts is performed based on the construction of finite-difference equations that statistically stably describe the observed signals, and finding the roots of the corresponding characteristic equations, and on the same basis, the signals with different characteristic times obtained by the detector are separated. 21. The method according to claim 1, characterized in that to obtain a mass spectrum of ions in a selected m / z range present in a linear radio frequency trap, free rotations or ion oscillations are excited by a short wave packet in a given frequency range, and after the induced signals are recorded Within a given time, a fast Fourier transform is performed.

Images