RU2601294C2 - Method of analyzing impurities in liquids in infiltration through track membrane with formation and transportation of analyzed ions through linear radio frequency trap into mass analyzer when exposed to supersonic gas stream with possible content of metastable atoms in it - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to chemical analysis of impurity compounds and ions in solutions. Basis of the invention is extraction of ions or their formation from a solution infiltrating into a vacuum part of a gas-dynamic interface via a track membrane under the action of atmospheric pressure and electric field in channels of the membrane. Liquid evaporation is supported by electric heating while passing current through a conductive coating on the membrane surface. Output and formation of ions are stimulated by the action of jets of a supersonic gas stream at possible content of metastable excited atoms in it formed when the stream flowing through an electronic source of ionization or a gas discharge area. Possible is a preliminary accumulation, separation and collision-induced dissociation of selected ions coming into a linear radio frequency trap of the gas-dynamic interface together with other jets of the supersonic gas flow to develop relatively small additional gas density near the axis of this trap. Trap is coupled with a mass-analyzer, for example a time-of-flight mass-spectrometer with an orthogonal ion input.

EFFECT: provided is the possibility of characterizing biomolecules in solutions by equilibrium probabilities of retention of various charge carriers with their individual ionogenic groups.

19 cl, 10 dwg

Description

FIELD OF THE INVENTION

The present invention relates to methods and techniques for chemical analysis of impurity compounds and ions in solutions, including multiply charged ions of biomolecules, when they are extracted from a liquid by the action of gas flows and electric fields. These methods may include a combination of separation of the analyzed ions according to the mass-to-charge ratios, mobility, resistance to collisional fragmentation of ions, and mass analysis of the product ions of this fragmentation. In particular, we are talking about identifying the individual components of the relaxation curves of ions, both extracted directly from the liquid and formed as a result of Penning ionization upon the action of metastable excited atoms from a supersonic gas stream on impurity molecules. Relaxation curves of selected ions can be observed when the ionization conditions change and / or when the combined action of switching electric fields and a profiled supersonic gas flow in a linear radio-frequency trap directed to its exit. Registration and analysis of molecular ions and their product ions in terms of mass-to-charge ratios can be performed using a time-of-flight mass spectrometer with orthogonal ion input (ortho-VPMS) or on some other mass analyzer. The characterization of the spatial structure of ions of biomolecules can be achieved on the basis of decomposition of the multidimensional charge distributions of their recorded ions, due to the retention of various sets of charge carriers present in the solution.

The decay or death of the analyzed ions can be caused either by heating of the ions due to their collisions with atoms or gas molecules, or by collisions of ions with metastable excited particles created in a gas discharge or in an electron ionization source and moving together with the gas stream. The use of such decays or death for the separation and identification of the analyzed compounds is one of the distinguishing features of the present invention, it greatly increases the separation ability of the method.

Among the tasks for which, in addition to sensitivity, both the separation ability and the dynamic measurement range are important, rapid analysis of microimpurities in water and other liquids as applied to security, customs and environmental control systems can be mentioned. Real-time analysis of liquid mixtures of various origins can also be important for a variety of technological, medical and other applications.

BACKGROUND

After the development and creation of the first time-of-flight mass spectrometers with orthogonal ion injection (ortho-VPMS) [1, 2] at our institute [1, 2], devices of this type were widely used in solving various analytical and structural problems [3-5]. The convenience of connecting such devices, in particular, with an ion source based on the electrospray of liquids, made them effective for studying the composition and structure of ions of various nature that were originally present in the solution. At the same time, there are important problems, including in the analysis of liquid samples, for which the applicability, sensitivity, separation ability and "information performance" of known instrument systems, including ortho-VPMS, are insufficient. To overcome these limitations, it is natural to strive to introduce alternative methods for producing ions into the mass spectrometric experiment and transport them to the vacuum part of the device, and to use additional measurement dimensions associated with controlled transformations of the studied ions and data recording during these transformations.

One of the possible methods for obtaining ions from a liquid is the field evaporation of ions. Despite the fact that the field evaporation of ions itself has been studied for a long time [6, 7], the features of the transition of ions from the liquid phase to the gas phase still remain poorly understood. In particular, this relates to the question of the effect of the charge state on the efficiency of the exit of ions from a liquid in electric fields. The bulk of the work on field evaporation of ions from a liquid is connected with the study of the mechanism of ion formation during the electrospray of polar solutions [8, 9]. However, experimental methods based on the electrospray of solutions are not direct and do not allow obtaining information on the primary ions leaving charged microdrops.

Another circumstance that stimulates interest in studying the field evaporation of ions from solutions is due to the rapid development of mass spectrometry, especially its biochemical, biological, environmental, and medical fields, which is associated with the development of new ionization methods and the creation of ion sources in which field evaporation is a key process determining the ionization efficiency of complex molecules. This mainly refers to the electrospray of solutions, which is widely used in mass spectrometry of heavy organic ions [10]. It is believed that field evaporation of ions is one of the main mechanisms responsible for the generation of simple ions by electrospray. At the same time, the mechanism of the exit of large multiply charged ions from a liquid is still the subject of discussion [11-14]. An increase in the ion charge, on the one hand, leads to an increase in the energy barrier due to an increase in the polarization energy, and, on the other hand, to its decrease due to an increase in the action of the electric field. In general, the height of the barrier increases. In this connection, the question arises of the fundamental possibility of realizing the conditions for field evaporation of multiply charged (in particular, doubly charged) ions from polar solvents.

It can be expected that for multiply charged ions having a complex structure, the question of the efficiency of field evaporation from solutions does not have such an unambiguous answer. Firstly, because in some ions the centers of localization of individual charges are spatially separated. In this case, the energy of the polarization interaction of the ion with the medium should apparently be expressed by a certain sum of the polarization energies of the individual charges that make up the multiply charged ion. Secondly, for extended multiply charged ions, for example, for denatured protonated biomolecules, the size of which can significantly exceed the region of the barrier at the phase boundary, individual parts of such an ion can appear on different sides of the barrier, which should facilitate the exit of the remaining part of the ion in the liquid.

One more important feature of the field evaporation of ions from liquids should be taken into account, namely, that the phase boundary is crossed not by an isolated ion, but by an ionic cluster, which includes several polar liquid molecules [8, 9, 15]. Therefore, the polarization energy is determined by the size of the entire ionic cluster leaving the liquid. The size of the cluster shell depends on the size of the ion charge; therefore, a more correct consideration of the issue of the efficiency of field evaporation of multiply charged ions should take this circumstance into account. The possibility of creating conditions for direct field evaporation of ions from polar solutions without spraying was first demonstrated in [16, 17]. The stabilization of the liquid surface in a strong electric field was ensured due to the fact that the solution containing ions was placed in the channels of the polymer track membrane, the diameter of which was several tens of nanometers. Prospects for the application of this method are currently recognized (see, for example, the review [18]). Subsequently, it was shown that under stationary conditions, a strong local electric field capable of stimulating the effective exit of ions from the polar liquid is created due to the charging of the surface of the dielectric membrane. This technique of extraction of ions from solutions has a number of significant drawbacks that limit its use, in particular, in analytical applications. First, in the stationary mode, the formation of an ion-extracting electric field has a number of features that greatly complicate the control of the process of ion exit from the solution. In addition, there is a problem of fluid retention in the channels of the membrane. The inability to directly control the electric field with a high probability can lead to a situation where the field strength at the end of the channel exceeds a certain critical value and the solution flows to the vacuum surface of the membrane, which will lead to a complete loss of operability of the membrane interface.

One way to overcome these difficulties is described in the RF patent for the invention [19]. The main idea of this approach is to use electric field pulses with a duration sufficient for extraction of relatively light ions from the liquid, but incapable of leading to a significant movement and leakage of liquid from the membrane channels. An important feature of the described design of the membrane ion source in this case is the coating of the membrane surface with a conductive metal film to effectively create electric fields inside the membrane channels. At the same time, a certain area around the channels remains uncovered by the metal, which is important to maintain a sufficient angle of wetting by the liquid of the membrane surface, which prevents the spreading of the liquid. These features of the proposed design of the membrane ion source can be used in some embodiments of the present invention, therefore, the described approach is taken as its prototype.

The impact on the membrane surface of a supersonic gas stream, especially when it contains metastable excited atoms, as proposed in the present invention, can also overcome the difficulties described. In addition, ions can be formed from neutral molecules of the solution, and initially ionized compounds in the solution are transformed by the action of metastable excited atoms, which can expand the analytical capabilities of this approach.

In the past 20 years, gas-filled radio frequency multipoles, devices containing a set of rods usually parallel to each other, symmetrically located around the axis of the device, have become widespread in mass spectrometry. Radio frequency voltages are most often in antiphase applied to adjacent rods. These devices are usually used as a means of focusing and efficiently transporting ions or for accumulating ions (in this case they are called linear radio frequency traps or linear ion traps) with the possible isolation of selected ions and conducting controlled dissociation and other structural transformations [20-22]. In these devices, the property of high-frequency force fields described in Mechanics of Landau and Lifshitz [23] is used to cause the particles to be pushed out in such fields to reduce the strength of these fields. More precisely, the averaged particle motion in such (electric) fields is described, to a first approximation, by the effective potential, which is directly proportional to the square of the high-frequency field intensity multiplied by the square of the particle’s charge, and inversely proportional to the particle mass. For a special case of an ideal radio-frequency quadrupole, the effective potential depends quadratically on both coordinates (in a rectangular coordinate system in a plane orthogonal to the axis of the quadrupole), reaching a minimum value on the axis of the quadrupole. The averaged free movement of ions in such a field (in the absence of other external fields, collisions with residual gas molecules, and neglecting ion-ion interactions) are independent harmonic oscillations in both coordinates. In these devices, used as ion storage rings and reactors, two important properties in this case - the ability to accumulate ions and the ability to separate these ions can conflict with each other. In order to effectively stop ions inside a multipole, a sufficiently high gas density is usually needed, and for high selectivity of isolation of selected ions or excitation of resonant ion oscillations and their heating (for fragmentation and other transformations), the gas density should be relatively low.

One of the possible approaches to overcome this contradiction by creating a slightly diverging supersonic gas flow [24] directed along the multipole axis and creating an increased gas density near this axis is described in our patents in the Russian Federation [25-27]. When using a multichannel supersonic flow directed along the generators of a slightly diverging wedge, as described in our patent application [28], the sensitivity can be noticeably higher than with a single channel of the same flow. In this case, the residence time of ions inside the flow in the multichannel case can be significantly reduced, and at the end of the quadrupole, the analyzed ions can be focused near the axis of the radio frequency quadrupole, where the gas density will be close to the residual density. Thus, the problem of the extraction of ions from the gas stream, critical for its propagation along the axis of the quadrupole, can also be practically eliminated.

The software for the analysis of experimental data should include software packages that basically implement the original methods developed by us, described in [29–33]. Among these methods, the most important are:

1. The correction method for the effects of saturation and "dead" time when using time-to-digital conversion for recording data of the VPMS [31];

2. A method for identifying exponential contributions to a registered signal from an ion ensemble that relaxes to a new stationary state after switching the ion accumulation mode [29, p. 192], by finding the roots of the characteristic polynomial using the procedure described in [33];

3. A method for identifying exponential contributions to a set of ion current curves, developed earlier for the analysis of a set of effusiometric curves [32].

Existing methods for the implementation of collision-induced ion dissociation or for kinetic mass spectrometric measurements usually require preliminary isolation of one type of ion with the loss of all the others, thereby requiring the use of a large volume of the initial sample and time-consuming experiments. One of the exceptions is the “multi-reflection” ortho-VPMS A.N. Verenchikova [34], where due to a significant increase in the effective length of the ion drift and, consequently, their flight time, it becomes possible to produce collisional dissociation of not one, but several types of selected ions, which are far enough separated by the exit time (by a time longer than the ion drift time in a secondary time-of-flight mass spectrometer). This approach is much more technically complex than in our case, of course, eliminates any kinetic measurements and produces primary ions for dissociation only in m / z.

Dynamic methods for capturing ions in a quadrupole trap, when the reverse ion output is blocked by switching on the corresponding potential (for example, at the input diaphragm of the quadrupole) until the launched ion packet returns from the pivot point, only a small part of the initial ion flow can be used if subsequent manipulations with the ions great time. The initial ion flow should be locked at this time, and the corresponding ions are usually lost.

The use of a rotational field for the selective dissociation of ions accumulated in a quadrupole linear trap in a collision with atoms or molecules of a buffer gas is described in US Pat. No. 7,351,965 B2 [35]. It is proposed that the registration of product ions, as well as the removal of unwanted ions, be made through gaps along the vertices of the main electrodes of a hyperbolic shape. It is proposed to compensate for violations of the quadrupole field near these slots with the help of thin electrodes located along the slots in the middle at the exit from them. When conducting dissociation, it is proposed to intentionally distort the quadrupole field by setting potentials on these auxiliary electrodes that are different from the potentials of the main electrodes. This is useful for shifting the resonance frequencies of strongly promoted ions to prevent their death on the quadrupole electrodes. In the considered patent [35], it is proposed to capture ions dynamically in the trap, raising the voltage at the input diaphragm, because the buffer gas pressure in the quadrupole is not enough to stop the ions reflected from the blocking potential in the last section of the quadrupole. In this case, ions remain in the trap, which have reflected from this potential and did not have time to go back through the output diaphragm of the quadrupole until a blocking voltage is established on it. In the patent [35], to ensure the capture of a sufficiently large number of analyzed ions, the use of a relatively long quadrupole (1000 mm) is assumed. This length not only increases the dimensions of the device, but also makes more stringent requirements for the parallelism of the rods of the quadrupole and other conditions for its manufacture to ensure uniformity of the resonant frequencies of free movements of ions in different places of the quadrupole. The ion accumulation method of the present invention is expected to accumulate a sufficient number of ions in a quadrupole, an order of magnitude shorter, with a comparable residual pressure of the buffer gas.

A standard method for estimating the cross sections for collisions of ions moving in a gas is one or another type of measurement of the mobility of the ion or the proportionality coefficient between the stationary velocity of the ion and the electric field strength that causes this movement. Often this movement is used for preliminary separation of ions. Since in ordinary versions of the method, the time of movement of ions in a drift tube is relatively small, the most acceptable combination of separation of ions by mobility with a time-of-flight analyzer with orthogonal ion input.

A serious problem of this combination is the provision of high ion transmission through the drift tube in the HPMC. One of the possible solutions was proposed by us in US patent No. 6992284 [36], which provides a fairly detailed overview of the work on the separation of ions by mobility. Patent 6,992,284 refers to the use of a sequence of alternating sections of a strong and a weak field in a drift tube at a gas pressure of several Torr instead of a uniform electric field. This leads to the focusing of ions to the axis of the quadrupole and allows you to slightly increase the total voltage along the pipe, which favorably affects the resolution of ion packets in mobility. 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.

In the present invention, the mobility of the ions in their separation acts indirectly. The greater the mobility of ions with a given m / z, the greater the amplitude of the ions will be under the influence of a resonant oscillating field and, therefore, will be more strongly repelled by the blocking field of the output aperture of the quadrupole, providing an increase in the characteristic relaxation time of the signal when changing the ion accumulation conditions. The determination of such characteristic times of the relaxation curves of ions with a selected value of m / z will make it possible to further separate them in accordance with different mobility values.

U.S. Patent No. 7397029 of July 8, 2008, V.D. Berkut and V.M. Doroshenko [37], a method for exciting fragmentation of ions by metastable excited particles (atoms or molecules) is described. The initial ions are extracted using a primary mass spectrometer, while they accumulate in a three-dimensional or linear ion trap or move in a transport multipole. It is possible to additionally excite the initial ions or product ions by applying an alternating electric field to produce secondary product ions due to collisional activation. All of these resulting ions are recorded by a secondary mass spectrometer. Metastable atoms and molecules are supposed to be obtained using a gas discharge. They are supposed to be introduced into the ion trap in a direction perpendicular to the axis of the trap.

The current system that implements this approach is described in [38, 39]. Experimental data are presented that demonstrate the expected dependences of the intensities of the fluxes of the initial ions and ion-products of interaction with metastable atoms of noble gases when the initial ions are in a linear quadrupole trap under the influence of a constant flow of metastable atoms.

In our case, metastable atoms or molecules are obtained in the ion source of electron ionization in a supersonic gas stream, and their density in the stream and distribution over the excitation energies can be controlled by changing the flow or energy of ionizing electrons. Moreover, when using a mixture of inert gases as a buffer gas, a change in the composition of metastable atoms can be achieved by changing the energy of the electrons, which can allow selective ionization of the components of the analyzed sample without changing the composition of the buffer gas. The primary ions under study are separated both by the values of m / z and ion mobilities, and by the degree of resistance to fragmentation of the ions “stopped” in the linear ion trap for the selected energy of ionizing electrons. Fragmentation of primary ions is organized by a joint action with controlled contributions from collisions with metastable particles and with atoms and molecules of supersonic flow and residual gas. In this case, the energy of the main components of the gas stream can be changed by setting the temperature of the capillaries of the formation of the stream.

SUMMARY OF THE INVENTION

The features of the possible implementation of the proposed methods are: The flow of the studied ions is the result of extraction of ions from a liquid sample emerging from the channels in the membrane ion source when a supersonic gas stream acts on the membrane surface. Alternatively, ions are formed from neutral molecules evaporating from this sample due to Penning ionization when interacting with metastable buffer gas atoms in a supersonic gas stream. Metastable atoms in the aforementioned stream are formed either in a high-frequency gas discharge organized at the outlet of the flow formation channels, or the stream is passed through an electron ionization source with a variable kinetic energy of electrons. A part of the supersonic flow formation channels is directed to the membrane surface, the rest - along generators orthogonal to the tip of a weakly converging wedge, the axis of symmetry of which passes through the electron ionization source and further along the radio frequency quadrupole, almost coinciding with the axis of this quadrupole. The wedge tip or the line of intersection of the generators passes near the surface of the membrane mentioned above, from the channels of which the analyzed liquid leaks. The leakage of fluid through the channels of the membrane is caused by the pressure drop between the outer and inner surfaces of the membrane and the difference in electrical potentials between these surfaces. To supply the necessary potentials, the surface of the membrane can be coated with conductive layers. When analyzing a conductive fluid, coating the outer surface of the membrane (under atmospheric pressure) with a conductive layer is optional.

The channels of supersonic flow formation on opposite planes of the wedge are displaced along the wedge tip, so that in the region of the wedge tip near the membrane, where the continuations of such channels are as close as possible, the supersonic gas flow jets emerging from them intersect only with their peripheral parts, where the density of gas atoms in the jet is at least half that of the middle of the jet. The heating of the chamber and the formation channels of the supersonic gas stream jets will ensure the efficient evaporation of liquid from the membrane channels and the release of ions and charged liquid droplets due to the increased kinetic energy of the stream atoms. To ensure reliable evaporation of charged droplets, for better collection and declusterization of the analyzed ions, a thin wire electrode is located at a small distance from the membrane and the tip of the wedge in the direction of the quadrupole, the electric field of which attracts the analyzed ions. To prevent the death of such ions on this electrode, it is either covered with a thin dielectric film, or, along with a constant, radio frequency voltage, which repels ions, is applied to it. Further, the diverging jets of a supersonic gas stream, together with ions, enter the radio-frequency quadrupole. The angle of divergence of the jets is such that the gas density in the stream near the axis of the quadrupole in its second half does not significantly exceed the average density of residual gases in the quadrupole. After leaving the quadrupole, the ion beam is introduced into the subsequent mass analyzer using a coaxial conical or wedge-shaped skimmer with an inlet or slot at its apex. In this case, most of the gas flow is scattered by the outer surface of the skimmer and enters the first stage of differential pumping

The features and advantages of the proposed approach are a consequence of the small divergence of the supersonic gas stream emerging from the relative thin and long channels with a reduced (compared to atmospheric) gas pressure at their inlet. The mean free path of the molecules of the main component of the gas stream is comparable with the diameter of the channel. The conditions for the formation of the aforementioned flow can be selected so that in the second half of the radio-frequency quadrupole the density of the gas around its axis does not practically differ from the density of the residual gases at the periphery of the radio-frequency quadrupole. This density for the effective functioning of the electron ionization source should be sufficiently low, corresponding to a pressure at room temperature of 10 ^-4 Torr or less. Thus, the movement of ions near the axis of the quadrupole will be the same as in a conventional quadrupole with the same density of residual gases. The difference will be that the relatively energetic natural vibrations of the ions in the direction perpendicular to the plane of symmetry of the wedge will be much faster offset by the gas flow along the surfaces of the wedge. Thus, more favorable conditions will be provided for recording the survey mass spectra of the sample under study in comparison with a conventional gas-filled quadrupole or with a single-channel supersonic flow along its axis.

The flow of ions leaving the membrane channels by the action of an electric field and a supersonic gas flow will gradually change the pH of the solution due to the predominant release of small H ₃ O ⁺ or OH ^- ions from the membrane channels. The direction of change in pH is determined by the sign of the detected ions. If an alkali metal salt, for example, NaCl, was added to the analyzed solution in a suitable concentration, then two-dimensional charge distributions of multiply charged ions of biomolecules by the number of protons held by these ions, and in this case sodium ions, can be observed. Using our developed method of decomposition of such charge distributions [33, 40], it is possible to determine the probabilities of holding various charge carriers by separate ionogenic groups of biomolecules. If we control the pH of the basic solution and the content of sodium ions, then having obtained the probabilities of the proton and sodium ions being retained by some sites of biomolecules, we can estimate the ratios of the corresponding equilibrium constants for these sites. The totality of such estimates can characterize the spatial structure of a biomolecule in solution and practically does not depend on changes in the composition and type of ions upon transition to the gas phase and on their various discrimination during transportation and registration.

In the analysis of neutral microimpurities, they are detected in the form of ions formed under the action of metastable atoms of a supersonic gas flow. Here, some separation of the analyzed microimpurities is possible with a change in the energy of ionizing electrons in the ion source of electron ionization. For this purpose, for example, a mixture of inert gases with close concentrations: He, Ne, Ar, Xe can be used as a buffer gas in the formation of a supersonic flow. The ionization energies of these gases and the formation of their metastable excited atoms vary in the range of about 10 eV and cover the range of possible ionization energies of most known compounds. The transition from one electron energy to another for an interval specific to a given target compound may allow the release of ions formed from this compound.

To identify biomolecules, as well as to establish the structure of molecules of ordinary chemical compounds, a detailed analysis of selected ions, including their collision-induced dissociation, may be required. Forced vibrations of ions in the plane of symmetry of the wedge in the second half of the quadrupole with the corresponding dipole excitation will occur at a gas pressure close to the residual. This can provide a sufficiently high selectivity for the elimination of undesirable components and the accumulation of selected ions differing in m / z and / or in different charge states for subsequent dissociation in collisions with atoms and / or buffer gas molecules. To ensure effective control of the movement of ions inside the quadrupole by creating suitable electric fields without violating the conditions for focusing ions outside the quadrupole, the input and output apertures of this quadrupole are multilayer with independent setting of potentials on these layers.

By creating in the first half of the quadrupole a longitudinal electric field directed against the flow (counterfield) with the practical absence of a longitudinal field in the second half of the quadrupole, the flow of some ions (with a collision cross section substantially smaller than the analyzed ions) into the second half of the quadrupole can be stopped. The ion flux with m / z less than a given one can be interrupted by applying the corresponding radio frequency voltage to the rods in the first half of the quadrupole. By applying a nonresonant oscillating field in the symmetry plane of the wedge with a frequency much lower than the resonance for the analyzed ions with a maximum value of m / z, the ions inhibited by the longitudinal antipole can be transferred to oscillating trajectories. The amplitudes of these trajectories are proportional to the magnitude of the oscillating voltage and are practically independent of the gas density. They increase with increasing m / z ion. Thus, ions with the desired value of m / z can be brought to the region of maximum accumulation due to the increasing reflection of ions from a break in the longitudinal stress in the middle of the quadrupole, uncompensated by their death on the rods of the quadrupole. In this case, ions with large m / z can accumulate to a decreasing degree as their death rapidly increases on the rods of the quadrupole with an increase in the amplitude of the oscillations.

By changing the intensity of the counterfield in the first half of the quadrupole, the ions that accumulate or reach a stationary level of accumulation can be “stopped” at various distances from the end of the first half of the quadrupole. A shift in the localization of such a “stop” will lead to a relaxation transition from one stationary number of “stopped” ions to another, which will result in the observation of the corresponding relaxation curves. The characteristic times of these curves will correspond to the average positions of stopped ions (depending on their mobility) with respect to the transition region from the first half of the quadrupole to the second.

At energies of ionizing electrons sufficient to form metastable excited particles of the main components of the gas stream, processes of transformation and death of the analyzed ions are possible inside this stream, which can occur as a result of the capture of such particles by these ions. The polarizability of metastable excited atoms is much greater than for unexcited ones (for Ar ~ 300 and ~ 1.6 A ^3, respectively). The collision frequency of the studied ions and gas atoms is proportional to the ion charge, the square root of the polarizability of the gas atom and when the mass of the ion is significantly larger than the mass of the atom, it practically does not depend on other properties of the ion. The rate of death of ions will depend on the residence time of these ions inside the gas stream and on the probability of death of these ions when they collide with metastable particles. It should be expected that this probability for different ions may be different, even if they do not significantly differ in m / z and mobility. The transfer of energy from a metastable particle to an ion does not necessarily mean its death or a change in m / z. Excessive energy can change the structure of the ion or be scattered in collisions with atoms and molecules of the gas stream. Thus, the relaxation rates of the intensities of ion peaks during an abrupt change in the conditions for the capture of metastable particles can be different for different types of ions (even at the same m / z and mobilities), and on this basis, additional ion separation is possible.

In the present case, the formation of product ions is also possible if, as a result of interaction with a metastable particle, dissociation occurs while the charge is retained by at least one fragment of the initial ion. If the initial ions are “stopped” at the end of the first half of the quadrupole, then partially arbitrary product ions can appear in the second half of the quadrupole and can be detected by the mass analyzer if their formation occurred near or inside the transition zone from the first half of the quadrupole to the second or took some time exceeding the transition time of the parent ion from the first half of the quadrupole to the second. The intensities of these product ions will relax with the same characteristic time as the parent ions. When several types of ions are superimposed, relaxing with different characteristic times, they can be separated by the methods of multidimensional separation of exponential contributions, which we described earlier [25, 32].

A more interesting possibility of such an analysis of ions can be realized in the second half of the quadrupole after preliminary isolation of the packet of ions of interest as described above in the first half of the quadrupole or without such isolation. To ensure unhindered transport of inhibited ions from the first half of the quadrupole, a practically zero longitudinal field is created along the second half of the quadrupole. This will ensure the registration of survey mass spectra of ions emerging from the first half of the quadrupole. If the output aperture of the quadrupole is chosen to pass most of the gas stream, then applying a small braking voltage to it, not exceeding the potential of the ion source, will not noticeably reduce the flow of recorded ions. This diaphragm will be able to reflect back only ions that deviate strongly enough from the axis of the quadrupole. By excitation of resonant or non-resonant oscillations of ions with a selected m / z in the plane of symmetry of a wedge containing jets of gas flow, it is possible to bring the ions of interest into the zone where they will repel from the output diaphragm. They will return to the first half of the quadrupole and accumulate there until a certain stationary level is reached, determined by the initial flow of these ions and their death rates on the rods of the quadrupole and their exit from the quadrupole for registration.

In the plane of symmetry of the wedge containing the stream jets, the gas density at the end of the quadrupole will be close to the residual density, and therefore the selectivity of the resonant vibrations of ions should be quite high. With an increase in the amplitude of the resonance oscillations, the death rate of the corresponding ions on the rods of the quadrupole should increase and at the same time the speed of their exit from the quadrupole should decrease. When these velocities coincide, the registered ion current of the oscillating ions should decrease by half compared with the case of no oscillations. The magnitude of such a death-registration rate will depend on the magnitude of the braking voltage applied to the output aperture of the quadrupole. The optimal value for subsequent measurements will be such a value when the characteristic time of establishment of the stationary recorded ion current of the oscillating ions upon a spasmodic change in any condition affecting the ion flux is in the range of 10-20 seconds. It is with this characteristic time that the recorded current of the oscillating ions will decay when the input ion stream is blocked, for example, by increasing the voltage on the external side of the input diaphragm of the quadrupole to a value exceeding the potential of the ion source.

For a homogeneous ensemble of oscillating ions, in this case, the detected ion current will decay exponentially with some characteristic time in the indicated range, at least after a certain delay, when the ion space charge will not have a noticeable effect on the transfer of ions from the quadrupole to the mass analyzer. If this ensemble includes several types of ions that differ in mobility, then each of these types will have its own oscillation amplitude (with resonance vibrations) proportional to the mobility. In this case, the braking field of the output diaphragm will prevent the exit of such ions from the quadrupole in different ways, and the death rates of such ions on the rods of the quadrupole will also differ. In accordance with its mobility, each type of ion will have its own characteristic decay time of the recorded signal, and the total recorded curve of the ion current of resonantly oscillating ions will be the sum of the exponential dependencies.

If at the moment of passage of these ions near the axis of the quadrupole to create a short pulse of the electric field in the direction orthogonal to the oscillations, then with a suitable amplitude, the ions will reach the surface of the wedge containing gas jets. When the amplitude of the oscillations does not exceed the half-width of the gas stream, the ion can pass the return point or the “stop” point and spend a relatively considerable time inside a sufficiently dense gas stream. In this case, he has a chance to collide with a metastable excited stream atom and undergo dissociation. If such pulses are periodically applied with a period significantly exceeding the relaxation time of ion oscillations in the wedge symmetry plane, a significant part of the ions will be transformed. In this case, the probability of ion death will increase, and the ion current of these ions will begin to decay. The characteristic decay time of the ion flux will depend on the nature of the ion. Along with the initial ions, their product ions will be observed, and their currents will decay with the same characteristic times as the parent ions. A similar behavior of the selected ions can also be observed after changing the direction of their oscillations, so that their “stopping point" falls inside the zone of relatively high gas density in the stream. It is also possible to superimpose oscillations in two directions in the plane of symmetry of a wedge containing jets of a gas stream and orthogonal to this plane. At the same frequency of these oscillations and a phase shift of π / 2, the ions will move along an elliptical trajectory with different intersections of the zone relative to the dense gas flow, depending on m / z and / or ion mobility. When the corresponding voltages are turned on / off, relaxation curves will be observed. In the presence of product ions, the characteristic times of their relaxation curves will coincide with the characteristic times of the initial ions. If the oscillation frequencies do not coincide in the orthogonal directions or when only one oscillating voltage is turned on / off, the relaxation curves of the product ions may differ from the relaxation curves of the initial ions. To detect the presence and estimate the concentration of the target compound in the test solution in the case of varying the amplitude of the switched off voltages, we can use the multidimensional version of the selective digital filtering method that we described earlier [48].

At the same time, the implementation of various options for the transformation of parent ions is possible. For example, this is the use of various gases to produce metastable excited particles and the change in the energy of ionizing electrons to excite a larger number of high-energy excited states or, conversely, to reduce the concentration of metastable excited particles. Secondly, this can be a significant increase in the effective temperature of the ions by a multiple increase in the amplitude of the radio frequency voltage at the moment of "stopping" the ions inside the gas stream for the period of their initial oscillations, as described in our patent of the Russian Federation [41] during ion rotation in a quadrupole. Another possibility of controlling the collisional dissociation of selected ions is their pulsed acceleration-deceleration along the gas stream during the stay of their significant fraction inside this stream. In the last two cases, the fraction of the “ordinary” collision-induced ion dissociation can exceed the contribution of ion transformation in collisions with metastable excited atoms.

BRIEF DESCRIPTION OF ILLUSTRATIONS

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

Fig. 1. General scheme of the gas-dynamic interface of the ortho-VPMS with a membrane ion source and a multichannel supersonic gas stream with axial ion removal from the gas stream to the mass analyzer.

Fig. 2. Schematic view of the cross section (AA) of the interface in the location of the ion declustering region.

Fig. 3. Schematic view of the cross-section (BB) in the first half of the radio-frequency quadrupole with forced non-resonant ion oscillations and their accumulation in the selected m / z range.

Fig. 4. Illustration for the separation of characteristic times of ion accumulation.

Fig. 5. Calculated resonance curves for rotating or oscillating ions in a quadrupole with m / z = 400 and 401 for argon buffer gas at densities corresponding to 0.3 mTorr and 30 mTorr at room temperature.

Fig. 6. Schematic view of the cross section (CC) at the end of the second half of the radio frequency quadrupole with oscillating ions in the plane of symmetry of the gas stream and in the orthogonal direction.

Fig. 7. Two examples of experimental relaxation curves of recorded ion currents when switching the accumulation modes of the corresponding ions for a biased single-channel supersonic gas flow.

Fig. 8. Illustration to the formation of multidimensional relaxation data.

от величины осциллирующего напряжения при различных модах осцилляций и сравнительные изменения токов ионов двух изотопов ксенона для вертикальных осцилляций для смещенного одноканального сверхзвукового газового потока.Fig. 9. Experimental dependences of measured ion fluxes $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

on the magnitude of the oscillating voltage for various modes of oscillations and comparative changes in the ion currents of two xenon isotopes for vertical oscillations for a displaced single-channel supersonic gas flow.

.Fig. 10. Dependence of the flow _{Qin of the} mixture of 2% Xe in Ar through the capillary on the pressure _pin at the inlet of the capillary: points — experimental data, solid curve — approximation by a quadratic function $$Q_{\mathrm{at}x}\approx a\cdot p_{\mathrm{at}\mathrm{<figure-callout\; id="2"\; label="x"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">x</figure-callout>}}^2$$

.

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 to the vacuum part of the mass spectrometer using a supersonic gas flow is described in our US patent No. 7482582 dated January 27, 2009 [42]. It was further developed to provide additional analytical capabilities due to the resonant excitation of ion rotation around a supersonic flow in our next US patent No. 7547878 of June 16, 2009 [43]. 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 our patents in the Russian Federation [25-27]. The implementation of a new version of the accumulation and isolation of the analyzed ions from the electron ionization source in the radio-frequency quadrupole, based on the use of an off-axis multichannel supersonic flow, is described in our patent application [28]. The jets of this flow are directed along the generators of the diverging wedge with the axis of symmetry directed along the axis of the radio-frequency quadrupole. In this case, in contrast to the version of the orthogonal ion output to the mass analyzer described in the RF patent [27], there is the possibility of efficient coaxial coupling of the mass analyzer with a gas-dynamic interface.

In the present invention, most of the jets of a supersonic gas stream (5) from the channels (4), Fig. 1, is directed along the generators of a converging wedge, the tip of which is localized near the midpoint of the track membrane (84), which at this point has a maximum deflection under the influence of atmospheric pressure from the outside of the membrane. The remaining stream jets from the channels (90) are directed directly to the membrane surface, or are scattered at the edges of the membrane fastening membrane (82), partially blowing around the “vacuum” membrane surface. We carry out the necessary estimates when filtering aqueous solutions through a membrane with channels with a diameter of 50 nm, a length of 10 μm and a density of 10 ⁵ channels per 1 mm ² .

The average thermal velocity of water molecules at room temperature - T _r (k is the Boltzmann constant, M _H2O - water molecules) is equal to:

- из канала 50 нм диам. Из мембраны площадью ~4 мм² общий поток пара воды будет ~2,1 см³Торр/с. Поток газа в нашей системе при остаточном давлении в интерфейсе 10^-4Торр 0,75 sccm≈9,5 см³Торр/с. (см. Рис. 10). Таким образом, поток паров воды из мембраны при комнатной температуре не сильно увеличит остаточное давление в интерфейсе. Поток жидкости (масса в секунду, Ландау Гидродинамика, стр. 82) через канал радиуса r и длины L при перепаде давления Δp (~10⁶ дн/см² для атмосферного давления) и динамической вязкости v=0.01 см²/с для воды (Ландау стр. 74):The pressure of saturated water vapor at room temperature is ~ 18 Torr, the equivalent density is n _sat , the channel radius r = 2.5 · 10 ^-6 cm. The rate of liquid evaporation is equal to the rate of condensation under equilibrium conditions: $$V_{vap}=\frac{n_{sat}}{\mathrm{four}}{V}_T\pi {\mathrm{<figure-callout\; id="2"\; label="r"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">r</figure-callout>}}^2=\frac{\mathrm{eighteen}}{\mathrm{four}}\cdot 59000\cdot 3.14\cdot {\mathrm{2,5}}^2\cdot {10}^{-12}=5.2\cdot {10}^{-6}\mathrm{from}{m}^{3}T\mathrm{about}RR/\mathrm{from}$$

- from a channel of 50 nm diam. From the membrane with an area of ~ 4 mm ^{2, the} total flow of water vapor will be ~ 2.1 cm ³ Torr / s. The gas flow in our system at a residual pressure in the interface of 10 ^-4 Torr 0.75 sccm≈9.5 cm ³ Torr / s. (see Fig. 10). Thus, the flow of water vapor from the membrane at room temperature will not greatly increase the residual pressure at the interface. Fluid flow (mass per second, Landau Hydrodynamics, p. 82) through a channel of radius r and length L at a pressure drop Δp (~ 10 ⁶ days / cm ² for atmospheric pressure) and dynamic viscosity v = 0.01 cm ² / s for water ( Landau p. 74):

. Для 4-10⁵ каналов Q=6·10^-7 г/с. 1 см³Торр/с для водяного пара при комнатной температуре - $$M_{с{м}^3}\approx \frac{18\cdot 273}{\mathrm{22,4}\cdot {10}^{3}760\cdot 293}\approx \mathrm{0,985}\cdot {10}^{-6}\approx {10}^{-6}г/с$$

. Q≈0,6 см³Торр/с. $$Q=\frac{\pi \Delta p}{8vl}{r}^{\mathrm{four}}\approx \frac{3.14\cdot {10}^6}{8\cdot 0.01\cdot {10}^{-3}}{\mathrm{2,5}}^{\mathrm{four}}\cdot {10}^{-24}\approx \mathrm{1,5}\cdot {10}^{-12}g/\mathrm{from}$$

. For 4-10 ⁵ channels, Q = 6 · 10 ^-7 g / s. 1 cm ³ Torr / s for water vapor at room temperature - $$M_{\mathrm{from}{\mathrm{<figure-callout\; id="3"\; label="m"\; filenames="00000076.png"\; state="\{\{state\}\}">m</figure-callout>}}^3}\approx \frac{\mathrm{eighteen}\cdot 273}{22.4\cdot {10}^{3}760\cdot 293}\approx 0.985\cdot {10}^{-6}\approx {10}^{-6}g/\mathrm{from}$$

. Q≈0.6 cm ³ Torr / s.

Thus, for a membrane with channels with a diameter of 50 nm and a length of 10 μm, the evaporation rate at room temperature is ~ 3.5 times the rate of water outflow. By reducing the evaporation temperature, it is possible to equalize the evaporation and discharge rates only by approaching the freezing point, because at 0 ° C, the pressure of saturated water vapor is 3.9 times less than this pressure at room temperature. It is hardly advisable to increase the diameter of the channels since at a fixed temperature, the flow of water vapor will increase. A more powerful pumping out is required in order to leave the ion source operable (4). To increase the rate of outflow of the solution from the channels, you can create an electric field inside the channels. On the other hand, if about a third of the gas stream is directed to the membrane, then at the initial gas temperature of about 100 ° Celsius the energy of gas atoms is not enough to maintain the evaporation of water from the membrane at room temperature. It may suffice for evaporation at a lower temperature, slightly higher than 0 ° C. An atomic flux of 3.5 cm ³ Torr / s with an excess energy corresponding to 100 ° can produce a water vapor stream of 0.56 cm ³ Torr / s. The evaporation rate of water from 4 · 10 ⁵ channels at 0 ° C is 0.54 cm ³ Torr / s. This means that it is desirable to have an additional supply of energy to the membrane to prevent freezing of the solution in the channels. A slight increase in the temperature of the membrane could provide heat due to the work performed by the pressure force when pushing the solution through the channels of the membrane. However, this contribution is negligible. The allocated power for one channel, since the mass flow for water numerically coincides with the volume flow, is as follows:

and for 4 · 10 ⁵ channels it will be equal to ~ 0.6 erg. Compared with the energy needed for the evaporation of water leaving the channels Q = 6 · 10 ^-7 g - 2500 · 6 erg in 1 s, 0.6 erg is 4 · 10 ^-5 fraction. Additional heating due to the flow of electric current in the channels when creating an electric field in them is about the same order of magnitude, as shown by the estimates below. Coating the "vacuum" surface of the membrane with a conductive layer will allow you to create a controlled electric field inside the channels. Its heating by passing current along a conductive coating can also be arranged.

. Эту силу нужно сложить с силой от перепада давления для расчета скорости истечения:The electric field at the outlet of the channel is equivalent to an increase in the pressure drop and increases the flow rate. An external field of intensity E = ΔU / L, in order to compensate for the field inside the conductor, creates a surface charge density σ = ΔU / (2πL) on its surface (if there is an electrolyte in the membrane channel). The total charge of the electrolyte surface in the membrane channel will be q = r ² ΔU / (2L). The force acting on a charge is $$F=0.5{\left(\frac{r\Delta U}{L}\right)}^2$$

. This force must be added to the force from the differential pressure to calculate the flow rate:

с πΔp≈3·10⁶ дн/см², т.е. $${\left(\frac{\Delta U}{L}\right)}^2=6\cdot {10}^6$$

, и $$\frac{\Delta U}{L}\approx \mathrm{2,4}\cdot {10}^3эл.ст.ед.\approx 7\cdot {10}^5В/см$$

. Для длины канала 10 мкм, падение напряжения вдоль канала должно быть 700 В. Величина заряда на поверхности жидкости в канале при таком напряжении $$q=\frac{r^2\Delta U}{2L}=\mathrm{6,25}\cdot {10}^{-12}\mathrm{2,4}\cdot \frac{{10}^3}{2}=\mathrm{0,75}\cdot {10}^{-8}эл.ст.ед.\approx 16эл.зарядов$$

. Скорость истечения в этом случае удваивается по сравнению с бесполевым случаем: Q_700B=1,2 см³Торр/с. Поскольку в массовых единицах это 1,2·10^-6 г/с, то линейная скорость истечения будетIn order for the outflow rate to become 2 times greater than without a field, and to approach the evaporation rate at ~ 10 °, a coincidence is necessary $$0.5{\left(\frac{\Delta U}{L}\right)}^2$$

with πΔp≈3 · 10 ⁶ days / cm ² , i.e. $${\left(\frac{\Delta U}{L}\right)}^2=6\cdot {10}^6$$

, and $$\frac{\Delta U}{L}\approx \mathrm{2,4}\cdot {10}^3\mathrm{uh}l.\mathrm{from}t.ed.\approx 7\cdot {10}^5\mathrm{AT}/\mathrm{from}m$$

. For a channel length of 10 μm, the voltage drop along the channel should be 700 V. The charge on the surface of the liquid in the channel at this voltage $$q=\frac{{\mathrm{<figure-callout\; id="2"\; label="r"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">r</figure-callout>}}^2\Delta U}{2L}=6.25\cdot {10}^{-12}\mathrm{2,4}\cdot \frac{{10}^3}{2}=0.75\cdot {10}^{-8}\mathrm{uh}l.\mathrm{from}t.ed.\approx 16\mathrm{uh}l.s\mathrm{but}R\mathrm{I\; am}d\mathrm{about}\mathrm{at}$$

. The flow rate in this case doubles compared with the fieldless case: Q _700B = 1.2 cm ³ Torr / s. Since in mass units it is 1.2 · 10 ^-6 g / s, the linear flow rate will be

or 3 · 10 ⁴ channel diameters per second. If we assume that with such a frequency the charges on the liquid surface in the channels are updated, then the electric current through the membrane will be: I = 16 · 4 · 10 ⁵ 3 · 10 ⁴ = 1.92 · 10 ⁹ el.zar./s = 3 · 10 ^-10 A. The allocated power is quite small: w≈2 · 10 ^-7 W. This value is comparable with the above estimate of the specific work (0.6 erg / s) for squeezing out fluid from the channels. The obtained estimate of the magnitude of the current through the membrane makes sense if the coating with a conductive layer of the membrane surface is carried out as described in the patent [19], when there are uncoated zones around the channels. This will not only prevent the spreading of liquid from the channels on the membrane surface, but also leave only one drain of charges from the channels - this is their departure together with the liquid in the form of droplets and cluster ions into the vacuum part of the device.

, где λ - теплота испарения одного г жидкости, $${М}_{с{м}^3}\approx {10}^{-6}г$$

- масса кубического сантиметра водяного пара. Для воды λ около 2500 Дж/г необходимая мощность равна:In order for the liquid to evaporate at a constant temperature, a constant supply of energy equal to the evaporation energy is necessary - $$∍=\lambda Q_{700B}{M}_{\mathrm{from}{\mathrm{<figure-callout\; id="3"\; label="m"\; filenames="00000076.png"\; state="\{\{state\}\}">m</figure-callout>}}^3}$$

where λ is the heat of vaporization of one g of liquid, $$M_{\mathrm{from}{\mathrm{<figure-callout\; id="3"\; label="m"\; filenames="00000076.png"\; state="\{\{state\}\}">m</figure-callout>}}^3}\approx {10}^{-6}g$$

- the mass of a cubic centimeter of water vapor. For water λ about 2500 J / g, the required power is:

$$∍=2500\cdot \mathrm{1,2}\cdot {10}^{-6}=3\cdot {10}^{-3}\mathrm{AT}\mathrm{but}tt.$$

This approach can be realized by applying a small voltage drop to the edges of a strip of metal sprayed onto the membrane surface. If this gold is about 10 nm thick and 2 mm wide, then the resistance of the strip will be about 6 ohms. To obtain a power of about 3 mW in this case, a current of about 22 mA is needed, for which a voltage of ~ 132 mV is enough. In fact, you need a slightly larger supply of energy, because some of it will be lost to radiation. This additional energy will be supplied by the gas flow when the capillaries of the flow formation are heated to a temperature not exceeding 100 ° C. With the formation of menisci of liquid exiting from the channels of the membrane, the energy received by the liquid will increase both by increasing the effective area of the open gas stream, and by increasing the flow of thermal radiation from the heated metal layer. Thus, the evaporation rate will also increase. With a small initial excess of the outflow velocity over the evaporation rate, when a certain average meniscus size is reached, these velocities become equal. The ions of biomolecules with solvent molecules that came out with the liquid into the meniscus and around the solvent molecules will be blown away by the gas stream after receiving a sufficient total momentum from the stream atoms entering these menisci.

In addition to the membrane heating mentioned above, additional changes are supposed to be introduced into the design of the membrane ion source described in [19]. To eliminate the effect of impurities in the laboratory air on the measurement results, the analytical zone of the source is closed, for example, with a rubber gasket (87). A liquid sample is injected through this gasket using a syringe (88). To prevent the destruction of the membrane (84), a protective mesh (83) is installed with the syringe needle, which at the same time is one of the electrodes for organizing the electric field inside the membrane channels (84). Since the ion current through the membrane is quite small in accordance with the above estimate (~ 3 · 10 ^-10 A at a voltage of 700 V), the internal resistance of the corresponding power supply module can be quite large (about 1 mOhm). Therefore, touching a syringe in contact with a solution under such a voltage does not pose a great danger, however, for complete reliability, such a voltage should be turned off for the duration of handling the syringes. Two operating modes of the membrane ion source are possible. In the first case, the syringe (88), containing a sufficient volume of the analyzed liquid sample, is left for the entire time of measurement, and the liquid from this syringe, under the influence of atmospheric pressure, enters the syringe plunger inside the analytical zone of the source, maintaining a constant volume and composition of the analyzed sample in it. In the second mode of operation, a fixed volume of the liquid sample is started with the syringe (88), the syringe (88) is removed and the syringe (89) containing an inert gas medium is inserted. This “gas” syringe is left for the entire time of measurement, and it maintains a constant (near atmospheric) pressure of the gaseous medium above the liquid sample, allowing it to be diverted by seepage through the membrane (84). If an electric field is created inside the membrane channels, then the most mobile ions predominantly escape through these channels (when analyzing positive ions in an aqueous solution, these are H ₃ O ⁺ ions), gradually changing the pH of the medium and possibly the relative content of other ions in the solution. If you control the ionic composition of the analyzed solution (the methods and equipment for this are known - http://www.shelfscientific.com/cgibin /tame/newlaz/microionn-m82.tam?ofr=16544039), then you can record the distribution of multiply charged ions of biomolecules in these changing and well-known conditions. Carrying out the decomposition of the obtained multidimensional charge distributions according to the method described by us [33], we can determine the adequacy of the probability changes of the determined probabilities of charge carrier confinement by individual ionic groups of the biomolecule to the equilibrium processes in solution. In cases of correspondence to equilibrium relations for such groups, the corresponding equilibrium holding constants of various charge carriers can be determined that are specific for particular conformations of the studied biomolecules in solution. Thus, they can be used to characterize such forms in the analyzed mixtures. If necessary, the composition of the analyzed solution can be changed more forcefully if, instead of inert gas, a buffer solution containing the desired maximum concentration of the selected charge carriers is injected using a syringe (89) under the influence of atmospheric air. Here, the problem may be the rate of establishing the acceptable uniformity of the composition over the entire volume of the solution and the correspondence of the measured concentrations of charge carriers to those that actually determine the replacement processes of these carriers for certain ionic groups of the studied biomolecules.

Charged droplets and cluster ions emerging from the membrane (84) by the electric field of the wire electrode (91) are concentrated around it and the gas stream of already diverging jets (5) is dried and declustered. The electric field (28) of the diaphragm (8) is gradually transported inside the radio frequency quadrupole (10). To ensure better focusing of charged droplets and cluster ions around the electrode (91) opposite the membrane (84) symmetrically relative to the axis (38) of the quadrupole (10), an electrode (85) imitates the working shape of the membrane (84). The electric potential of this electrode coincides with the potential of the “vacuum” surface of the membrane (84). The electrode (91) with insulators (207) is mounted on the shell (202), Fig. 2. The potential of this shell coincides with the potential of the “vacuum” surface of the membrane (84). The potential of the electrode (91) creates a field (204) and a potential well (58) in the path of ions and charged droplets. To prevent the death of ions and loss of charge by droplets on the electrode (91), this electrode is covered with a thin dielectric film, the use of which for such purposes is described in our patent of the Russian Federation [25]. Alternatively or in addition to such a coating, a radio frequency voltage similar to that of the radio frequency quadrupole (10) can be applied to the electrode (91). In this case, there is an additional opportunity to control the process of ion declustering and further transportation of declustered ions. Such a voltage will create a field (205) that repels ions (206) from the electrode (91) more strongly with a decrease in m / z during declustering and increases their kinetic energy, giving them additional heating in collisions with atoms of a gas stream. Together with a constant field (204), this radio-frequency field will repel ions (206) from the walls of the shell (202). The jets of the gas stream (203) will drag the ions diffusely emerging from the cloud (206) into the region of the focusing field (28) of the diaphragm (8), ensuring their entry into the radio-frequency quadrupole (10).

In the rest, the gas-dynamic interface is close to the variant given in the application [28], which is schematically shown in Fig. 1. A distinctive point from this application is that the gas stream (1) already does not contain the analyzed compounds that are blown through the valve (53). In this case, a mixture of inert gases (He, Ne, Ar, Kr, Xe) is formed in chamber (2) at a lower pressure than atmospheric pressure (He, Ne, Ar, Kr, Xe) at close concentrations, so that in the electron ionization source (6) it is possible to obtain various metastable atoms of said inert gases. The desired initial temperature of these gases is maintained by passing current through the windings (3) and (50). The channels (4) and (90) of the formation of the gas stream jets are drilled in the wall (54). An increased initial temperature of the gas in the flow is necessary to create optimal conditions for the evaporation of the liquid in the membrane channels (84) and the charged droplets formed at the outlet of the channels (84) and ion de-clusterization near the electrode (91).

For the entire system to function properly, the divergence of the gas stream must be such that the density of the gas stream near the axis of the quadrupole when leaving it is so small that the inlet (70) of ions with gas through the skimmer (71) does not lead to an unacceptable residual pressure inside the mass analyzer . Since the gas flow diffusely scatters (81) on the skimmer (71), pumping (75) will be less efficient than for the case of orthogonal ion removal [27]. Thus, when the mass analyzer is coaxially coupled with a gas-dynamic interface, it is necessary to use more powerful pumping, or confine oneself to the inlet of less intense gas flows to ensure the operability of the ion source (6).

, когда кинетическая энергия направленного движения его атомов становится равной половине исходной тепловой энергии этих атомов. Здесь и далее k - постоянная Больцмана, T₀ - исходная температура газа, M - масса атомов газа. Для аргона и комнатной температуры (293К) эта скорость равна: $$V_Z^{crit}=\sqrt{\frac{3\cdot \mathrm{1,38}\cdot {10}^{-16}293\cdot 6.02\cdot {10}^{23}}{2\cdot 40}}\approx \mathrm{3,02}\cdot {10}^4см/с$$

. До достижения этой скорости зависимость плотности газа n в канале радиуса r от расстояния Z от начала канала при диффузном отражении атомов газа от его стенок в первом приближении определяется выражением (решение уравнения (1) в [24]):Existing laser “drilling” technologies make it possible to create cylindrical channels with a diameter of 10-30 microns with a channel length of up to 50 times their diameter. If, for example, you have 14 channels (4) and (90) with a diameter of ~ 20 μm and a length of ~ 1 mm, then the dimensions of such channels will ensure the creation of a supersonic gas flow inside them at an initial pressure of ~ 10-fold exceeding this pressure in our experiments for one channel with a diameter of about 0.2 mm [24], i.e. about 300 Torr. For the total flow through all 14 channels to be practically the same as through one channel in our experiments, about 0.75 sccm (cm ³ per minute at atmospheric pressure and room temperature) at an initial pressure of 30 Torr, a slightly smaller initial pressure, somewhere around 280 Torr. This statement is a consequence of the proposed model for the formation of a supersonic jet [24] and the measurements taken. In this model, the critical role is played by the critical flow rate. $$V_Z^{crit}=\sqrt{\frac{3\mathrm{<figure-callout\; id="0"\; label="k\; T"\; filenames="00000077.png,00000080.png"\; state="\{\{state\}\}">k\; </figure-callout>}{T}_{}{}_0}{2M}}$$

when the kinetic energy of the directed motion of its atoms becomes equal to half the initial thermal energy of these atoms. Hereinafter, k is the Boltzmann constant, T ₀ is the initial temperature of the gas, M is the mass of gas atoms. For argon and room temperature (293K), this speed is equal to: $$V_Z^{crit}=\sqrt{\frac{3\cdot 1.38\cdot {10}^{-16}293\cdot 6.02\cdot {10}^{23}}{2\cdot 40}}\approx 3.02\cdot {10}^{\mathrm{four}}\mathrm{from}m/\mathrm{from}$$

. Before reaching this speed, the dependence of the gas density n in a channel of radius r on the distance Z from the channel beginning with diffuse reflection of gas atoms from its walls in a first approximation is determined by the expression (the solution of equation (1) in [24]):

Z(n) достигает максимального значения и далее начинает убывать, указывая на то, что упрощенная модель течения газа в канале, основанная на балансе импульсов атомов газа в тонком слое газового потока, перестает быть адекватной. Она не учитывает, например, вклад диффузии атомов газа, что принципиально важно вблизи критической точки. Введение диффузионного члена в уравнение газового потока (уравнение (3) в [24]) позволяет пройти критическую точку $$n_{crit}=f/V_Z^{crit}$$

, но требует для получения осмысленного результата фактического отсутствия или очень малого сопротивления потоку в оставшейся части канала. Это условие может быть удовлетворено, если доминирующим здесь станет зеркальное отражение атомов от стенок канала, что представляется вполне вероятным для очень малых углов столкновения атомов со стенкой (при относительно большой продольной скорости этих атомов). Для проведенных измерений с каналом с диаметром 0.215 мм и величине потока F=0,75 sccm плотность потока такова:where n ₀ is the density of the gas at the entrance to the channel, f = nV _z is the density of the gas flow in the channel, V _Z is the velocity of the gas flow. For $$n_{crit}=f/V_Z^{crit}$$

Z (n) reaches its maximum value and then begins to decrease, indicating that the simplified model of gas flow in the channel, based on the balance of momenta of gas atoms in a thin layer of a gas stream, ceases to be adequate. It does not take, for example, the contribution of the diffusion of gas atoms, which is fundamentally important near the critical point. The introduction of a diffusion term into the gas flow equation (equation (3) in [24]) allows one to pass the critical point $$n_{crit}=f/V_Z^{crit}$$

, but requires to obtain a meaningful result of the actual absence or very small resistance to flow in the remaining part of the channel. This condition can be satisfied if the mirror reflection of atoms from the channel walls becomes dominant here, which seems quite probable for very small angles of collision of atoms with the wall (at a relatively large longitudinal velocity of these atoms). For measurements with a channel with a diameter of 0.215 mm and a flux of F = 0.75 sccm, the flux density is as follows:

The distance to the critical point, based on (99), will be about 4 mm:

The relative resistance to gas flow with a mean free path comparable with the radius of the channel, which is determined mainly by the ratio of the lateral surface area (with a length of about the mean free path of gas atoms) to the cross-sectional area, is inversely proportional to this radius. Therefore, the density of the gas stream at a given initial pressure will be approximately proportional to the radius of the channel. Those. in the case under consideration, the flow through each channel with a diameter of 20 μm (proportional to the cube of the diameter) at a constant initial pressure will decrease by about 1240 times compared to a channel with a diameter of about 0.215 mm. An increase in the initial pressure by ~ 9.5 times will increase this flow by ~ 90 times, i.e. for 14 channels (⌀2О microns) the total flow will practically remain, since for each channel, the flux will be ~ 14 times smaller, and the flux density ~ 8 times greater than for the channel (⌀215 μm). Quadratic dependence (1002), Fig. 10, the flow rate from the initial pressure was confirmed by us with experimental measurements for the supersonic jet formation channel currently used in our system. These data (1001) indicate that the flow velocity at the entrance to the channel in our case is proportional to the initial pressure. Since the gas density is also proportional to pressure, this is precisely where the quadratic dependence of the flow value or flow density on pressure arises. Thus, based on (99), the distance to the critical point will decrease inversely with the initial gas pressure. This is qualitatively understandable, since the gas acceleration along the channel is proportional to the number of atomic collisions in the volume (or pressure squared) and inversely proportional to the gas density (the mass of the accelerating gas) will result in proportion to pressure. Thus, the flow velocity will reach a critical value at a distance from the channel beginning inversely proportional to the pressure. If for our channel (⌀215 μm) the critical speed was reached at a distance of about 3.6 mm from the entrance to the channel, then for channels with a diameter of 20 μm and a pressure of ~ 9.5 times greater than the critical channel, the critical length will be about 0, 4 mm. Thus, the length of such a channel of 1 mm will be quite sufficient for the development of a supersonic flow in it.

Thus, it can be expected that at the same pumping speed, the residual gas pressure in the proposed system at an initial pressure of ~ 280 Torr will be close to that in the existing gasdynamic interface - about 10 ^-4 Torr for an initial pressure of ~ 30 Torr. Since the total cross-sectional area of 14 channels in the case under consideration is ~ 8 times smaller than the cross-sectional area of one channel for the existing interface, then with the same total gas flow, the flux density for 14 channels will be ~ 8 times greater than for one ten times wider. This means that the expected temperature in the stream [24] for 10 channels will be ~ 8 less than for one channel, and the divergence of gas jets in this case will be ~ 3 times less than before. If in our experiments this divergence at the exit from the quadrupole for argon leaving one channel resulted in a mean square radius of the jet of less than 0.4 mm, then in the case under consideration this radius will be about 0.14 mm, and the standard deviation of the flux density distribution over one coordinate will be about 0.1 mm.

With such divergence of supersonic jets, their minimum distance from the axis of the quadrupole at its end is about 1.4 mm, allowing the gas flow from these channels to exit the quadrupole to have a circular zone around the axis of the quadrupole with a diameter of about 2 mm, within which less than 0.1% of the total flow. Thus, a conical skimmer (71) with an inlet with a diameter of ~ 2 mm on the axis of the quadrupole will pass an admissible gas flow into the mass analyzer to provide a pressure of less than 10 ^-7 Torr in the mass analyzer if the interface has the same pumping speed pressure is not worse than 10 ^-4 Torr. In this case, the recorded ions (20) at the end of the quadrupole should be concentrated in this zone near the axis (38) and the electric fields (31), (33) and (35) should be accelerated to the energy ϕ, and the potential distributions convex upward (55) and (76) along the axis of the quadrupole, creating a focusing distribution of the potential in the plane orthogonal to the axis, directed inward to the skimmer (71). These fields are created by an electrode system (17). The potential value ϕ (55) should be close to optimal for registration with ortho-VPMS. The increased value of the holding potential (59) at the output diaphragm (19), which creates the field (39), can be set for the accumulation of ions inside the quadrupole (10). The excitation of nonresonant oscillations (304) of ions with a frequency significantly lower than the resonant frequency of the selected ions makes it possible to limit the range m / z of the accumulated ions. Cutting off ions with relatively small m / z can be carried out by increasing the radio frequency voltage, which leads to loss of stability of motion and death of ions with m / z, less than a given value. Ions with relatively large m / z have a large amplitude of nonresonant oscillations as they approach the resonance and will more effectively die due to diffusion on the rods of the quadrupole (201).

The ion source of electron ionization (6) has an indirect heating cathode (18) (22), which provides a relatively small spread (at the level of 0.1 eV) in the controlled energy of ionizing electrons, which allows one to set the composition of metastable excited ions in gas gas with good accuracy flow and prevent significant formation of ions, the presence of which can lead to the death of metastable ions. This is how the data shown in Fig. 9.

Under the influence of electric fields (28) and (29) directed through the inlet diaphragm, consisting of conductive layers (9) with non-conductive layers (8) between them, with a round inlet (48) with a diameter exceeding the diameter (23) of the gas stream , the ions inside this stream and partially from its outside will be introduced into the radio-frequency quadrupole (10). Under the action of the radio-frequency focusing field of the quadrupole, ions (12) will be pressed against the axis of the quadrupole with a force inversely proportional to the mass of the ion and directly proportional to the square of its charge.

By creating in the first half of the quadrupole a longitudinal electric field (13) directed against the flow (5) (counterfield), the flow of some ions into the second half of the quadrupole can be stopped. First of all, these will be ions moving outside the gas flow, the kinetic energy of which, when entering the quadrupole, will not allow overcoming the voltage drop in the first half of the quadrupole (56) - (60), shown on the potential curve (57) - (27) of the gas-dynamic interface, conducted near the electrodes on which the corresponding potentials U are set. Ions (12) moving inside the gas stream will be inhibited not by a voltage drop, but by the electric field strength. In order to prevent the reverse exit of inhibited ions through the input diaphragm (9), a potential barrier (61) is created on it and nonresonant oscillations (304) of the ions are excited by applying a voltage (303) with a frequency ω _osc along with a radio frequency voltage (302) to the pair of quadrupole rods (301), symmetric with respect to the plane of symmetry of the wedge containing jets of gas flow.

Ions (308) having a “stopping point” during oscillations (304) at a distance from the axis of the quadrupole exceeding the radius of the hole (48) of the inlet diaphragm (9) of the quadrupole, in the presence of an anti-field (13), can accumulate within certain limits in the quadrupole. To do this, it is enough, as in our patent of the Russian Federation [41], to partition the inner surface of the input diaphragm (9) of the quadrupole and apply sufficient radio frequency voltage in the opposite phases to adjacent sections (46) - (47). It is also possible, as in our patent of the Russian Federation [25], to cover the inner surface of the diaphragm (9) with a thin dielectric film and pre-charge it with ions of the same sign as the detected ions. The accumulation of ions can be considered confirmed if there is a time-varying change in the current of the detected ions during a jump in the opposite field strength (13), a rapid change in the difference in radio frequency voltage between the two halves of the quadrupole, and also when the amplitude of the oscillating voltage is switched. For the time dependences of the ion current to be conveniently recorded, it is necessary that the characteristic relaxation time of the ion current be in the range of seconds or tens of seconds.

и изотопов ксенона с атомными массами 129, 131 и 132. Потоки регистрируемых ионов изменялись включением на время, показанное двойными стрелками (705) осциллирующего напряжения с частотой 50 кГц и амплитудой 0,84 В и (706) запирающего напряжения на входной диафрагме квадруполя. Возникающий при этом потенциальный барьер показан пунктиром (708). Сплошная кривая (709) грубо описывает распределение потенциала U электрического поля вдоль квадруполя. Зарегистрированные кривые ионного тока после выключения осциллирующего напряжения были удовлетворительно аппроксимированы экспонентами с различными характеристическими временами (701), (702), (703) и (704). Обращает на себя внимание отсутствие релаксации при выключении входного потока ионов (706), что кажется необъяснимым при наличии накопления ионов. Однако, представляется, что такое поведение может быть понято, если принять во внимание вероятное формирование облака основных ионов газового потока ионов аргона (710) на входе в квадруполь при радиочастотном напряжении квадруполя, превышающим порог устойчивости движения этих ионов в квадруполе. Это облако может существенно изменить распределение потенциала (709) в начале квадруполя, и при исчезновении облака (710) включением барьера (708) накопленные ионы в квадруполе правее облака (710) могут получить энергию, достаточную для их гибели на начальных секциях квадруполя (700). Повторное формирование облака (710) при выключении барьера (708) может также объяснить релаксационное убывание регистрируемого ионного тока после окончания периода (706) запирания входного потока ионов. Таким образом, влияние электростатического поля накопленных ионов оказывается важным для объяснения вида наблюдаемых кривых ионного тока.Similar curves for a displaced single-channel supersonic flow (707) in a quadrupole (700) are shown on the left side of Fig. 7 for ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

and xenon isotopes with atomic masses 129, 131, and 132. The fluxes of detected ions were changed by switching on for the time shown by the double arrows (705) of the oscillating voltage with a frequency of 50 kHz and an amplitude of 0.84 V and (706) of the blocking voltage at the input diaphragm of the quadrupole. The resulting potential barrier is shown by a dashed line (708). The solid curve (709) roughly describes the distribution of the potential U of the electric field along the quadrupole. The recorded ion current curves after switching off the oscillating voltage were satisfactorily approximated by exponents with different characteristic times (701), (702), (703) and (704). Noteworthy is the absence of relaxation when the input ion stream is switched off (706), which seems inexplicable in the presence of ion accumulation. However, it seems that this behavior can be understood if we take into account the probable formation of a cloud of the main ions of the gas stream of argon ions (710) at the entrance to the quadrupole at a radio frequency voltage of the quadrupole exceeding the stability threshold for the motion of these ions in the quadrupole. This cloud can significantly change the distribution of potential (709) at the beginning of the quadrupole, and when the cloud (710) disappears by switching on the barrier (708), the accumulated ions in the quadrupole to the right of the cloud (710) can get enough energy to die in the initial sections of the quadrupole (700) . The re-formation of the cloud (710) when the barrier is turned off (708) can also explain the relaxation decrease in the recorded ion current after the end of the period (706) of blocking the input ion flux. Thus, the influence of the electrostatic field of the accumulated ions is important for explaining the form of the observed ion current curves.

(масса 127 Да) и ¹²⁹Xe⁺ далее убывающие релаксационные кривые. Для ионов ¹³¹Xe⁺ и ¹³²Xe⁺ всплески ионных токов оказались относительно малыми, а релаксационные кривые свое поведение изменили. Для ¹³²Xe⁺ - это возрастание, а для ¹³¹Xe⁺ ионный ток оказался практически постоянным. Такое поведение может быть объяснено взаимным влиянием накопленных облаков ионов в первой половине квадруполя. Поскольку нерезонансные осцилляции с частотой 50 кГц в данном случае имеют большую амплитуду для ионов с большими m/z, а распределение потенциала (719) при приближении к стержням квадруполя имеет более резкий излом в середине квадруполя, то наиболее легкие ионы $$S{F}_5^{+}$$

имеют больше вероятность проникновения во вторую половину квадруполя, и их облако (711) локализовано в среднем правее облаков других ионов (712), (713) и (714). При включении ускоряющего напряжения во второй половине квадруполя (716) ионы $$S{F}_5^{+}$$

дополнительно ускоряются электростатическим полем других облаков ионов (712), (713) и (714). Это ускорение максимально сразу после включения (718) и далее убывает по мере «расходования» упомянутых облаков других ионов. Ионы ¹²⁹Xe⁺ наряду с ускорением от облаков (713) и (714) испытывают торможение от ионов (711). Последнее вместе увеличенной амплитудой осцилляций по сравнению с $$S{F}_5^{+}$$

приводит к более заметному накоплению ионов ¹²⁹Xe⁺. Относительная амплитуда всплеска их потока после (718) в ~8/3 раз больше, чем для ионов $$S{F}_5^{+}$$

. Облако (714) ионов ¹³²Xe⁺ отталкивается от перехода во вторую половину квадруполя облаками (713), (712) и (711). Это отталкивание уменьшается по мере выхода их ионов, что и приводит к возрастанию регистрируемого тока ионов после переключения (718). Для ионов ¹³¹Xe⁺ (713) ускорение облаком (714) и торможение облаками (712) и (711) в какой-то степени компенсируют друг друга, что и привело к практическому постоянству потока ¹³¹Xe⁺ после (717). Естественно, что при таком сильном воздействии полей накопленных ионов на процесс их выхода в масс-анализатор вряд ли возможно аналитическое описание наблюдаемых зависимостей ионного тока, как например, экспонентами (701) - (704) для кривых в левой половине Рис. 7. Экспоненциальные зависимости кривых релаксации ионных токов характерны для относительно небольших плотностей накопленных ионов, когда электростатическим полем этих ионов можно пренебречь.Such an effect is even more distinctly manifested in the relaxation curves of the ion current shown in the right part of Fig. 7. Here are presented the dependences of the recorded currents of the same ions as in the left part of Fig. 7, but for a different distribution of electric potential (719) along the axis of the quadrupole (700). At the time point (717), non-resonant oscillations were turned on, and after some time (718), the almost constant potential (715) in the second half of the quadrupole (700) switched to decreasing (716). Large enough bursts of ion currents were observed $$\mathrm{<figure-callout\; id="5"\; label="S\; F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">S\; </figure-callout>}{F}_{}^{}{}_5^{+}$$

(mass 127 Da) and ¹²⁹ Xe ⁺ further decreasing relaxation curves. For ¹³¹ Xe ⁺ and ¹³² Xe ⁺ ions, the bursts of ion currents turned out to be relatively small, and the relaxation curves changed their behavior. For ¹³² Xe ⁺ , this is an increase, while for ¹³¹ Xe ^{+ the} ion current turned out to be almost constant. This behavior can be explained by the mutual influence of the accumulated ion clouds in the first half of the quadrupole. Since nonresonant oscillations with a frequency of 50 kHz in this case have a large amplitude for ions with large m / z, and the potential distribution (719), when approaching the rods of the quadrupole, has a sharper kink in the middle of the quadrupole, the lightest ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

are more likely to penetrate into the second half of the quadrupole, and their cloud (711) is localized on the average to the right of the clouds of other ions (712), (713) and (714). When the accelerating voltage is turned on in the second half of the quadrupole (716), the ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

additionally accelerated by the electrostatic field of other clouds of ions (712), (713) and (714). This acceleration is maximally immediately after switching on (718) and then decreases as other clouds of other ions “spend” them. ¹²⁹ Xe ⁺ ions, along with acceleration from clouds (713) and (714), are inhibited by ions (711). The latter together with an increased amplitude of oscillations compared with $$\mathrm{<figure-callout\; id="5"\; label="S\; F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">S\; </figure-callout>}{F}_{}^{}{}_5^{+}$$

leads to a more noticeable accumulation of ¹²⁹ Xe ⁺ ions. The relative amplitude of the burst of their flux after (718) is ~ 8/3 times greater than for ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

. The cloud (714) of ¹³² Xe ⁺ ions is repelled from the transition to the second half of the quadrupole by clouds (713), (712) and (711). This repulsion decreases as their ions exit, which leads to an increase in the recorded ion current after switching (718). For ¹³¹ Xe ⁺ ions (713), cloud acceleration (714) and cloud deceleration (712) and (711) to some extent cancel each other, which led to the practical constancy of the ¹³¹ Xe ⁺ flux after (717). Naturally, with such a strong effect of the fields of accumulated ions on the process of their exit to the mass analyzer, it is hardly possible to analytically describe the observed dependences of the ion current, for example, by the exponents (701) - (704) for the curves in the left half of Fig. 7. The exponential dependences of the ion current relaxation curves are characteristic of relatively low densities of accumulated ions, when the electrostatic field of these ions can be neglected.

When ions accumulate at the “stop” site, the average force acting on the ions from the flow side (5) is equalized with the opposition of electric fields, or, for example, inertia forces and forces due to the gradient of the effective quadrupole potential, which occurs during oscillations, can be in equilibrium ions. In these cases, various ions (12) will actually be in potential wells, differing by their minimum position and steepness, as shown in the lower part (401), Fig. 4. Ideally, for a uniform effective field and a linear change in the mobility of ions κ _i along the flow (due to a change in the gas density in the flow), such wells will be described by parabolas. The positions of their vertices Z _i will be determined by their mobilities averaged over the possible positions of the ions inside the flow, and by the coefficients a _i at the quadratic term, proportional to the ion charge z and the effective braking field strength. The stationary 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 inversely proportional to the coefficients for the quadratic term of the corresponding parabolas and directly proportional to the effective temperature of the ions:

. При отсутствии влияния объемного заряда и возбуждающих осцилляции полей $$T_{eff}^i$$

практически равна начальной температуре газа T₀, которую он приобрел в каналах (4). При смещении ионов от оси квадруполя под действием объемного заряда или, например, осцилляций возрастает их средняя кинетическая энергия, добавка к которой оказывается равной среднему значению эффективного потенциала радиочастотного квадрупольного поля [44]. Пропорционально этой дополнительной кинетической энергии увеличивается эффективная температура ионов $$T_{eff}^i$$

[45].where k is the Boltzmann constant, effective temperature $$T_{eff}^i$$

. In the absence of the influence of the space charge and exciting field oscillations $$T_{eff}^i$$

almost equal to the initial gas temperature T ₀ , which he acquired in the channels (4). When ions are displaced from the axis of the quadrupole under the action of a space charge or, for example, oscillations, their average kinetic energy increases, the addition of which turns out to be equal to the average value of the effective potential of the radio-frequency quadrupole field [44]. In proportion to this additional kinetic energy, the effective temperature of the ions increases $$T_{eff}^i$$

[45].

или положение равновесия для соответствующих ионов определяется уравниванием передаваемого импульса p «неподвижному» иону (что точно справедливо для ионов достаточно больших масс) в единицу времени от поля с напряженностью Ј и от потока со скоростью V_f:Minimum position $$U_{pot}^i$$

or the equilibrium position for the corresponding ions is determined by equalizing the transferred momentum p to the "stationary" ion (which is exactly true for ions of sufficiently large masses) per unit time from the field with intensity Ј 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 stream, σ _i is the cross section of collisions of the ion with atoms or molecules of the gas in the stream at a relative speed V _f , M is the molecular mass of the gas. The gas flow velocity in the adiabatic approximation is determined by the initial temperature of the gas T ₀ and its molecular mass M:

For small deviations from the equilibrium position along the axis of the quadrupole Z, the total momentum transferred to the ion per unit time along this axis 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 $$\gamma =-\frac{dn}{ndZ}$$

- 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. With a field strength of 1 B / cm, γ = 0.2 (which corresponds to a decrease in the average density of the gas stream by 2 times for 5 cm between the beginning of the quadrupole and its middle), the effective temperature of singly charged $$T_{eff}^i=400K$$

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

Shown in Fig. 4 distributions along the axis of the quadrupole (38) of potential energies, ion densities and schematic images of the clouds of these ions (403), (404) and (405) demonstrate possible interconnections between them. Ions (403) and (405) have the same equilibrium positions, but differ in charges, respectively, these are singly charged and four charged ions. This leads to significantly different distribution densities in the ion penetration zone (402) into the ion transport region of the mass analyzer, 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 m / z values of these ions. The fluxes of ions leaving the accumulation zone can be estimated similarly to the molecular flux through the hole:

- линейная плотность ионов в зоне проникновения (402), 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 уменьшился, поскольку $$n_i^L$$

и, соответственно, скорость расхода ионов пропорциональна общему числу накопленных ионов в соответствующем облаке (при отсутствии влияния объемного заряда данных ионов). Альтернативно (если исходный поток ионов не упал, а, наоборот, вырос) регистрируемый поток ионов будет возрастать, экспоненциально приближаясь к новому стационарному потоку этих ионов. Выражение (105) означает, что для многозарядных ионов (при фиксированном значении m/z), например, показанных на Рис. 4 - (405), уменьшение их потока будет связано не только с очень сильным уменьшением $$n_i^L$$

, но и с двухкратным в данном случае уменьшением средней тепловой скорости этих ионов из-за вчетверо большей массы. Скорее всего, такие ионы на фоне хорошо регистрируемого потока ионов (403) в условиях, показанных на Рис. 4, в сравнимое время вообще регистрироваться не будут. Для их регистрации облако ионов и распределение (405) надо сдвинуть вправо уменьшением напряженности поля (13) до появления сигнала приемлемой интенсивности. В этом случае нестационарная часть облака ионов (403) практически полностью исчезнет, и сигнал соответствующих ионов либо не будет регистрироваться более, если исходный поток ионов был заперт входной диафрагмой (9) или их поток станет постоянным, если поток исходных ионов не прерывался.where n _i is volumetric and $$n_i^L$$

is the linear density of ions in the penetration zone (402), 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 over time if the initial ion flux decreases, since $$n_i^L$$

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 (if the initial ion flux did not fall, but, on the contrary, increased), the recorded ion flux will increase, exponentially approaching a new stationary flux of these ions. Expression (105) means that for multiply charged ions (at a fixed value of m / z), for example, shown in Fig. 4 - (405), a decrease in their flow will be associated not only with a very strong decrease $$n_i^L$$

, but also with a twofold reduction in this case of the average thermal velocity of these ions due to a fourfold larger mass. Most likely, such ions against the background of a well-recorded ion flow (403) under the conditions shown in Fig. 4, they will not be registered at all in comparable time. For their registration, the ion cloud and distribution (405) must be shifted to the right by decreasing field strength (13) until a signal of acceptable intensity appears. In this case, the non-stationary part of the ion cloud (403) 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 (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 the ortho-VPMS and a time-to-digital converter for registration of ions at 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 (402) $$n_i^L$$

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

. Для обеспечения характеристического времени падения регистрируемого сигнала около 10 сек. (при идеальной 100 процентной регистрации) нужно накопить ~10000=1000×10 ионов. При стандартном отклонении распределения ионов σ≈4 мм, локальная линейная 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 линейная плотность в 1 ион/см в этом случае достигается на удалении от максимума распределения в 4,29 σ≈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) и увеличения ширины распределения ионов и при сохранении неизменным стационарного потока 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 $$n_i^L\approx \mathrm{one}\mathrm{and}\mathrm{about}n/\mathrm{from}m$$

. To provide a characteristic time of the recorded signal fall of about 10 seconds. (at an ideal 100 percent registration) ~ 10,000 = 1,000 x 10 ions must be accumulated. With a standard deviation of the ion distribution σ≈4 mm, the local linear 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 linear density of 1 ion / cm is achieved at a distance from the distribution maximum of 4.29 σ≈1.72 cm. With a decrease in the detection efficiency, the number of accumulated ions to obtain the same results should be increased. 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) and an increase in the width of the ion distribution, while keeping the stationary flow of recorded ions unchanged.

Distributions (403) and (404) demonstrate the case of a slight excess of the cross section for the collision of ions (404) with gas atoms or molecules compared to (403) for a single ion charge and coincident masses, which leads to a weak shift of the distribution (404) to the right compared to (403) 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 zone of penetration of ions (402) into the transfer region into the mass analyzer is more than four (4.29) standard deviations away from the distribution center (403). In this case, the ratio of the distribution value (404) to the distribution value (403) in the region of ion penetration into the second half of the quadrupole (402) will be about 2.64. This means that the characteristic time of change of the signal from ions (403) is ~ 2.64 times longer than for ions (404). Thus, practically insoluble signals (403) and (404) 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 selected 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.

The recorded signal for ions of a certain type when changing the conditions for the retention of such ions will exponentially relax to a new level (if the influence of the space charge of the ions on the rate of their transition to the second half of the quadrupole is not noticeable). If there are several types of ions among those “stopped” at the end of the first half of the quadrupole, these ions, depending on their mobility, will be localized on average at different distances from the zone of transition of ions from the first half of the quadrupole to the second. In this case, the sum of exponentially relaxing curves with characteristic times greater for more distant ions will be observed. If such a total curve is divided into exponential components, then they will correspond to ions with different mobility values.

It must be borne in mind that in fact it is quite possible that for each type of “stopped” ions a whole spectrum of daughter ions will be recorded due to their interaction with metastable excited particles of the main components of the gas stream. For this, the dissociation of the initial ions should occur after they cross the conditional boundary of the penetration of (402) ions into the transfer region into the mass analyzer, otherwise product ions with m / z different from the initial ions may die on the surface of the input diaphragm (9) or on the rods of a quadrupole (10). The relaxation curves for daughter ions leaving together with the parent ions will be exponentials with the same characteristic time as for the parent ion. For several types of parent ions, these curves will be combined, for example, as shown in Fig. 8. Unique daughter ions of different origins (800) and (803) fall in their exhibitors (801) and (804), respectively. The daughter ions (805), which have contributions originating from both types of parent ions, include two exponentials in their relaxation curve. In this case, it is possible to use multidimensional methods for separating the set of relaxation curves described, for example, in our patents in the Russian Federation [25, 26]. All these possible separation methods suggest the absence of a noticeable effect of the electrostatic field of the accumulated ions on the shape of the observed relaxation curves. This, as shown by the data on the right side of Fig. 7 is not always the case. In addition, the accumulated ions can have a significant effect on the resonance behavior of forced oscillations and rotations of ions in a quadrupole. That is why when receiving the data in Fig. 7, nonresonant excitation of oscillations was used. In order to ensure the excitation of resonant oscillations in the second half of the quadrupole, it makes sense to have an almost zero longitudinal field, as shown in Fig. 7 (715) and create a potential barrier (59) on the exit diaphragm (19). In this case, slow diffusion-penetrating ions from the first half of the quadrupole will not accumulate there, but will have sufficient time (at least some of these ions) to be in the second half of the quadrupole to acquire the amplitude of resonant vibrations close to the stationary value.

The curves in Fig. Figure 5 shows the calculated selectivity of oscillations at argon densities corresponding to pressures of 30 mTorr - curves (501) and (502) and 0.3 mTorr - curves (503) and (504) at room temperature, for singly charged ions with masses 400 and 401 and s collision sections 100 A ² . Under the experimental conditions of our measurements, the residual gas pressure in the quadrupole is about 10 ^-4 Torr, and the estimate of the gas density inside the stream jets (605) corresponds to an argon pressure at room temperature of about 1 Torr.

In Fig. Figure 6 schematically shows the cross section (CC) at the end of the second half of the quadrupole (10), where the average ion density is relatively low, since the longitudinal electric field is practically absent here. Therefore, in this case, the excitation of resonant oscillations is more likely to detect a relatively higher selectivity compared with the first half of the quadrupole. The amplitude of the radio frequency voltage (602) in this case is chosen so as to ensure the stability of the movement of not only the target ions, but also their possible product ions. For a given amplitude of the oscillating voltage (603), the amplitude of the stationary oscillations of ions with a resonant value m / z is proportional to the first approximation to the mobility of these ions. Thus, with a proper choice of the voltage amplitude (603) in the second half of the quadrupole, the accumulation of ions with a given value of m / z can be organized, having mobilities in a certain range when the oscillation amplitude of these ions (615) approaches the edges of the output diaphragm (611). When the conditions for the accumulation of these ions are changed, for example, by a decrease in the potential barrier (59) to a certain acceptable level (55), it is possible to observe relaxation curves of the ion current similar to those shown in Fig. 7. These curves are similar to the relaxation curves considered above for the delayed exit of ions from the first half of the quadrupole — equations (100) - (105). The density of the gaseous medium, together with the cross section for the collision of ions with its atoms or molecules, determines the amplitude of ion oscillations, which ultimately determines the effective height and steepness of the corresponding potential barriers.

Since the influence of residual gases on oscillating ions (616) is rather small, it is possible with fairly high accuracy to apply short pulsed fields when these ions pass near the quadrupole axis (38) to transfer their return points in the region of a more probable intersection with the flow, for example , (606) or (604). The amplitude of the rectangular pulsed field E _орт , orthogonal to the plane of ion oscillations (524), and with duration τ for shifting the return point by a height h from the plane of oscillations will be determined by the relation:

where ω _res is the resonant frequency of ion oscillations of a given m / z, e is the elementary charge. A pulse along the direction of oscillations can correct the corresponding component of the ion velocity so that its return point is in the desired position relative to the edge of the flow (609). In this case, the amplitude E _{⇒ of} such a pulse will be proportional to the shift of this position x from the stationary amplitude of the Chion oscillations (615) along the oscillation direction:

If metastable excited atoms in a sufficient concentration are present in the flux, then in the position of ions (606) the formation of corresponding product ions is possible, while for position (604) there will be much less such products. The formation of product ions for multiply charged ions is more likely, although charge conservation in dissociation fragments during the capture of metastable excited atoms by singly charged ions was also observed [39]. In any case, an additional channel for the death of the initial ions opens here, which should lead to a decrease in the relaxation times of the corresponding ion currents.

In order to obtain product ions in the absence of metastable atoms in the flow, as well as to increase the yield of such products, in the general case, a technique similar to that described in our patent of the Russian Federation can be used [41]. If at the moment of “stopping” of ions (606) in the flow, we multiply (2 or 3 times) increase the amplitude of the radio frequency field for the period of resonant oscillations of the selected ions: T _osc = 2π / ω _osc , then if this does not lead to a loss of stability of the motion of ions (606), the average kinetic energy of these ions will increase quadratically (4 or 9 times). In proportion to this, the stationary internal temperature of the ions will increase, which should lead to a significant increase in the probability of dissociation. With a multiple increase in the amplitude of the radio frequency voltage, the ions during the time of this increase T _{osc will make a} multiple number of oscillations, and when the amplitude returns to the previous amplitude, the average kinetic energy of the ions will return to its previous value. For this, it is only necessary that at the moment of the amplitude return the radio-frequency voltage has an extreme value - in this case, the ions will have zero kinetic energy of motion in the radio-frequency field at the time of switching. Ions (604), brought to the “edge” (609) of the gas stream, can be processed into product ions in a relatively moderate fraction and provide, with such periodic removal, a measurable change in the characteristic relaxation time of ion currents, which is the same for the initial ions and their ions products. At the same time, ions (606), periodically transported “inside” the flow, can significantly reduce the characteristic time of their life, so that after a short time delay these ions will be practically absent in the ensemble of oscillating ions (608).

For measurements, together with the product ions, mainly only ions will remain (616). Ions with greater mobility and oscillation amplitudes greater than those of ions (616) will be more likely to die on the rods of a quadrupole (601), but are less likely to turn into product ions due to a significant decrease in the density of the gas stream at the point of their “stop” . The period between the transportations of ions “inside” the flow should be such that a stationary regime of ion oscillations has time to be established between such transportations (616). For the density of residual gases corresponding to a pressure of 10 ^-4 Torr at room temperature, this time for ions with a mass not exceeding several thousand Da will be no more than 100 ms. The periodic inclusion (with the same period) of a multiple increase in the radio frequency voltage has an important advantage over the constant use of such a voltage. With a constantly increased radio frequency voltage, product ions with m / z smaller than the initial ions can be lost for registration due to the loss of stability of their motion in a relatively strong radio frequency field. If the multiple radio frequency voltage is briefly turned on briefly, the decay of the “heated” ions will largely occur after the “heating” period already at a reduced radio frequency voltage, and the danger of death on the quadrupole rods for a significant fraction of the product ions will be eliminated.

To determine the presence in the analyzed mixture of a given target compound, this compound is first added to the gas stream in a known concentration. The blocking voltage of the output diaphragm of the quadrupole (19) and the oscillating voltage (603) are selected so that approximately half of the ions of the target compound are detected compared to the initial flux of these ions at zero voltage of the blocking diaphragm. In this case, the characteristic time of establishment of the recorded ion current of the target ions when changing the conditions of their transportation is selected in the range convenient for measurements, for example, about 10 s. To increase the accumulation time of the target ions to achieve greater sensitivity, this characteristic time can be increased. The registration of half the ion current from the initial one means that approximately half of the target ion flux dies mainly on the rods in the quadrupole and possibly further along the path to the mass analyzer. In this case, the death rate of ions with large oscillation amplitudes (in the real analyzed mixture) than the target ions will be even greater. Thus, a relative enrichment of the ensemble of recorded ions with ions having a mobility less than or equal to the mobility of the target ions will occur. the amplitude of ion oscillations at a given intensity of the oscillating field will be proportional to the mobility of the ions (at the corresponding rms velocity of the target ions in the quadrupole). Such a situation may be important for the analysis of small impurities in the presence of dominant contributions of ions with the same m / z, but with greater mobility.

For evaluation purposes, we assume that every 10 μc (oscillation frequency 50 kHz) the oscillating target ions approach the minimum distance to the rods of the quadrupole, and some of those ions that die on the tail of the spatial distribution reaching the corresponding rod. If the fraction of ions dying in this way is the same each time (under stationary conditions, this is so) and equals p, then for 10 s of such oscillations the fraction of the remaining ions will be:

Moreover, the approximate equality written out is practically accurate. This means that if, for example, at each approach to the rods of the quadrupole, a 10 ^-6 fraction of ions die, then with a 10-second average residence time of ions in the quadrupole, their real number in the oscillating ensemble will be e ^-1 ≈0.37 fraction of the total number of incoming ions in 10 seconds.

, где M - масса атома газа и m - масса иона. В рассматриваемом случае основной газ потока - аргон, и его исходная температура T_g - комнатная (~300K). T_eff будет около 1440К, что соответствует средней тепловой кинетической энергии ионов около 0,18 эВ (1,5 kT_eff) или kT_eff≈0,12 эВ.Let us estimate now what the amplitude of ion oscillations should be in order to have an acceptable (for measurement) probability of death at the nearest rod when the radius of the quadrupole r ₀ (the minimum distance from the axis of the quadrupole to the surface of the rods) is 3.65 mm. In order to be able to double (as described above) a periodic increase in the amplitude of the radio frequency voltage to obtain fragment ions and maintain the stability of the motion of the initial ions, it is necessary to excite oscillations of the target ions at relatively low radio frequency voltages. At the same time, in this case, the stability threshold of the motion of the main ions of the flow, for example argon, must be exceeded. An RF voltage V _rf close to optimal for some target ions will be such that at zero voltage of the output diaphragm (19) it will be near the first local minimum of the recorded current of these ions. Assuming that this is a consequence of local defocusing of the ion beam and its death at the exit diaphragm, (19) then, if there is a repulsive potential on it, a sufficiently large part of these ions will be reflected from this diaphragm, providing relatively favorable conditions for the accumulation of such ions. For example, for singly charged ions with a mass of about 130 Da, as measurements for the existing interface show, such a radio frequency voltage should create an effective potential of about U _eff = 2.8 (r / r ₀ ) ² V, where r is the distance from the axis of the quadrupole. When point "stop" of the ions is 1.83 mm at a distance of approximately half the quadrupole radius r _0, then their "potential" energy is equal to ~ 0.7 eV. As shown in [44], this “potential” energy will actually coincide with the kinetic energy of ion motion in the radio frequency field of the quadrupole. In the process of "oscillatory" motion, the "potential" energy passes into kinetic, which reaches a maximum near the axis of the quadrupole. In fact, however, with such a motion, the total kinetic energy of the ions remains unchanged. Because If the effective temperature of the ions as compared with the temperature of the residual gases is proportional to the kinetic energy of the ions [45], then the effective temperature of the ions T _eff = T _g + αEkin can be considered unchanged under stationary conditions of the considered ionic movements. The proportionality coefficient α for a monatomic gas is $$\frac{2M}{3m}$$

where M is the mass of the gas atom and m is the mass of the ion. In the case under consideration, the main gas of the flow is argon, and its initial temperature T _g is room temperature (~ 300 K). T _eff will be about 1440K, which corresponds to an average thermal kinetic energy of ions of about 0.18 eV (1.5 kT _eff ) or kT _eff ≈ 0.12 eV.

In the direction orthogonal to the plane of oscillations (y), the effective potential of the radio frequency field of the quadrupole creates a potential well: U _eff = 2.8 (y / r ₀ ) ² . In accordance with the Boltzmann principle, the distribution of the oscillating ion packet in the y direction (for distances measured in mm) will be proportional to:

In the direction of oscillations (x) near the “stop” point x _{0, the} kinetic energy of ion motion along the x axis goes into the “potential”, which determines the local distribution:

For a half-effective temperature of 720K, kT _eff ≈0.06 eV and the ion distribution near the corresponding stopping point x ₁ will be proportional to:

If x ₀ corresponded to half the radius of the quadrupole (about 1.83 mm), then x ₁ ≈1.1 mm. To calculate the probability p of the death of the ion upon reaching the quadrupole rod, we simplistically assume that this death occurs when the ion intersects the tangent plane to the cylindrical rod of the quadrupole, orthogonal to the oscillation plane. In this case, such a probability will be equal to the integral outside the radius of the quadrupole of the function (109) or (110) normalized to the unit area in the cases under consideration. Estimates of such integrals can be obtained, for example, using formulas (590) and (591) from [46]:

.In the first case, this probability will be about $$\exp (-1.75\times {1.83}^2)/(2\times \sqrt{\pi }\times 2.42)\times 0.91=\exp (-5.86)/9.43\approx 3.02\times {10}^{-12}$$

.

In the second, exp (-22.8) / 17.3≈7.2 × 10 ^-12 .

For the stopping point x ₂ = 1.4 mm, the effective temperature will be 980 K and the distribution of “stopped” ions is proportional to: exp (-2.57 (xx ₂ ) ² ). The corresponding probability will be: - exp (-13,02) / 13,3≈1,67 × 10 ^-7. Those. the maximum characteristic time of accumulation and death of ions at an oscillation frequency that coincides with the resonant frequency of the oscillating field in a radio frequency field with a frequency ω _rf = 2π · 0.6228 · 10 ⁶ rad / s and V _rf = 28 V [44]:

taking into account formula (108), there will be ~ 32 s in this case.

Estimating the probability of a decrease in the ensemble of oscillating ions due to exit from the quadrupole into the registration system is a much more complicated task and can be effectively solved on the basis of computer simulation. In this case, a potential distribution should be found on the conducting layers of the output diaphragm (19), which ensures the passage of an ion stream through this diaphragm that is comparable to the flow of dying ions. If these flows coincide, the characteristic time for the establishment of stationary conditions for the registration of ions will become two times less than if only the loss of ions is taken into account, i.e. in the latter case, about 16 s.

If the stream jets at the end of the quadrupole are located at a distance of about 1.4 mm from the ion oscillation plane, then the relative probability density of stopping the ions transversely oscillating at the end of the quadrupole for the average value of the 1.4 mm amplitude of vibration in the location of each of the nearest two stream jets transversely shifted from the axis of the quadrupole by ~ 1.4 mm, there will be exp (-2.57 × 1.96) ≈0.0065. For the next two pairs of jets (with a distance between them of about 0.7 mm), the relative probability densities will be around: 0.0018, 0.00004. Thus, the total relative probability density of the ion entry into all the jets of the stream at the end of the quadrupole will be about 0.0083 × 2≈0.017. For a distance from the plane of oscillations to the plane of the jets of about 1.2 mm in the middle of the quadrupole, this probability density will be approximately 0.064. Performing longitudinal vibrations in the second half of the quadrupole, the ions will spend a relatively large time near the pivot points at the end and in the middle of the quadrupole. Therefore, a fairly good estimate of the average relative probability density of ion entry into the region of the gas stream jets is the half-sum of the densities given above: (0.017 + 0.064) / 2≈0.04. The magnitude of the gas flow in a jet with an initial area of about π × 10 ^-4 mm ² and with a gas density equivalent to 5 Torr at room temperature (the density increased by ~ 8 times for our measurements of a single-channel gas flow from a capillary with a diameter of ~ 0.2 mm), will be proportional to 5 × π × 10 ^-4 mm ² Torr. In this case, the standard deviation of the distribution of gas density in the jets is significantly less than the standard deviation σ of the transverse ion distribution throughout the quadrupole. Thus, the maximum contribution of the gas flow when taking into account the normalization factor of the normal two-dimensional distribution of “stopped” 1 / (2πσ ² ) ions for the ion oscillation amplitude of 1.4 mm will be approximately 0.04 × 2.57 × 5 × 10 ^-4 ≈0.51 × 10 ^-4 Torr. If the residual gas pressure is about 10 ^-4 Torr, then the total average gas background for transverse ion oscillations will be about 1.51 × 10 ^-4 Torr. Thus, under the described conditions of gas current formation, transverse ion oscillations in the second half of the quadrupole will occur at an average gas density not much higher than the density of the residual gases. A similar estimate for the first half of the quadrupole (if we consider the distance from the axis to the plane of the jets at the beginning of the quadrupole equal to ~ 1 mm) gives: ~ 3 × 10 ^-4 Torr. That is, in this case, the selectivity of the excitation of transverse ion oscillations in the first half of the quadrupole will be approximately three times worse than it would be with the residual density of gases, if, of course, the influence of the anharmonicity of the effective potential of the quadrupole and the effects of the space charge of ions are excluded.

To estimate the average amplitude of ion oscillations, it is reasonable to consider not the motion of an individual ion, but the entire (sufficiently large) ensemble of such ions having the same charge values q = ez, m / z and mobility. In this case, despite the relative rarity of collisions of ions and gas atoms, one can reduce the influence of these collisions on the motion of the center of inertia of such an ensemble to the friction force proportional to the velocity of this center. This ultimately leads to the fulfillment of the mobility equation for such a motion at an oscillating field frequency equal to the eigenfrequency of ion vibrations in the effective potential of the radio frequency field of the quadrupole. The original equation of the motion in question, similar to equation (3) in [44], can be written as:

, $$c=\frac{q{V}_{osc}}{m{r}_0}$$

. Здесь предполагается, что время релаксации скорости τ_v не зависит от скорости центра инерции ансамбля ионов. Такое свойство является следствием совпадения «потенциальной» энергии ионов в эффективном потенциале квадруполя и их кинетической энергии колебаний в радиочастотном поле квадруполя [44]. Стационарное решение этого уравнения может быть найдено подстановкой $$x(t)=A{e}^{i{\omega }_{ost}t}$$

в уравнение (109), и A получается равным:Where $$b=\frac{2q^2{V}_{rf}^2}{{\mathrm{<figure-callout\; id="2"\; label="m"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">m</figure-callout>}}^2{\omega }_{rf}^2{\mathrm{<figure-callout\; id="0"\; label="r"\; filenames="00000077.png,00000080.png"\; state="\{\{state\}\}">r</figure-callout>}}_0^{\mathrm{four}}}$$

, $$c=\frac{q{V}_{os\mathrm{<figure-callout\; id="0"\; label="c\; m\; r"\; filenames="00000077.png,00000080.png"\; state="\{\{state\}\}">c\; </figure-callout>}}}{m{r}_{}}$$

. Here it is assumed that the relaxation time τ _v velocity does not depend on the center of mass velocity of ions ensemble. This property is a consequence of the coincidence of the “potential” energy of the ions in the effective potential of the quadrupole and their kinetic energy of vibrations in the radio frequency field of the quadrupole [44]. A stationary solution to this equation can be found by substituting $$x(t)=A{e}^{i{\omega }_{ost}t}$$

into equation (109), and A is equal to:

From this relation it can be seen that at resonance, when

Hence, the velocity of the center of inertia of the ensemble of ions at the resonant frequency of the oscillating field, as well as the amplitude of the oscillations, is proportional to the strength of this field:

where κ = τ _v q / m is the ion mobility. Equality (111) means that the average amplitude of the resonant oscillations of ions is proportional to their mobility, and the moment of passage of the center of inertia of the ion ensemble near the axis of the quadrupole coincides with the time of the maximum intensity of the oscillating field. The direction of motion of the center of inertia of the ensemble of ions coincides with the direction of the field. τ _v for not too large electric fields is proportional to the average time between collisions τ or inversely proportional to the frequency of collisions of an ion with gas atoms v = 1 / τ (see, for example, [45]):

The Langevin cross section of a collision of a gas atom with an ion is as follows [47]:

where β is the polarizability of the gas atom (for argon - 1.64A ³ ), V is the relative velocity of the ion and gas atom. The average time between Langevin collisions of a xenon ion with argon atoms at a density n corresponding to a residual gas pressure of 10 ^-4 Torr will be:

τ _v ≈ 5.1 · 10 ^-3 sec. for xenon

.and $$\kappa =\frac{{\tau }_{v}q}{m}=\frac{5.1\cdot {10}^{-3}4.8\cdot {10}^{-10}6.02\cdot {10}^{23}}{130\cdot 130}\frac{\mathrm{from}{\mathrm{<figure-callout\; id="2"\; label="m"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">m</figure-callout>}}^2}{\mathrm{from}\cdot \mathrm{AT}}=3.8\cdot {10}^7\frac{\mathrm{from}{\mathrm{<figure-callout\; id="2"\; label="m"\; filenames="00000075.png,00000083.png"\; state="\{\{state\}\}">m</figure-callout>}}^2}{\mathrm{from}\cdot \mathrm{AT}}$$

.

To ensure the amplitude of the oscillations in A = 1.4 mm, the oscillating voltage with a frequency of 89 kHz, based on (110), is equal to:

Thus, with resonant ion oscillations at a voltage with an amplitude of 0.75 mV with a period of about 11.2 μs between two opposite quadrupole rods at an argon pressure of 10 ^-4 Torr, the maximum ion accumulation time, as well as the maximum characteristic time of establishment of a stationary ion flux, will be about 32 s. Since the presence of gas jets in the described interface design leads to an approximately 50% increase in the effective density of the residual gas in the quadrupole, an oscillating voltage with an amplitude of about 1.2 mV is really necessary to ensure this level of characteristic time.

It is possible to increase the maximum ion accumulation time without changing the amplitude of the oscillating voltage and without significantly changing the relative flux of the recorded ions, by shifting the oscillation plane to the region between the rods of the quadrupole. This time will reach its maximum value when the plane of oscillations passes symmetrically between the pairs of the nearest quadrupole rods. In our case, the quadrupole rods are cylinders with a radius of about r _c = 4.15 mm, and the minimum distance from the center of the quadrupole to the rods is r ₀ = 3.65 mm. With an average ion displacement of 1.4 mm from the center of the quadrupole in the direction between the rods, the closest distance to the rods of the quadrupole will be:

. Т.е. произошло увеличение почти на 0,2 мм по сравнению с осцилляциями в направлении стержня (3,65-1,4=2,25 мм). Эффективная температура ионов при этом не изменилась (980K), распределение ионного облака около точки остановки будет, как и ранее, пропорционально: exp(-2,57r²) для расстояний, измеряемых в мм. Вероятность достижения одного из двух стержней станет равной: $$r_{sim}=\sqrt{{({\mathrm{<figure-callout\; id="0"\; label="r"\; filenames="00000077.png,00000080.png"\; state="\{\{state\}\}">r</figure-callout>}}_0+r_c)}^2-{1.4}^2-2\cdot ({\mathrm{<figure-callout\; id="0"\; label="r"\; filenames="00000077.png,00000080.png"\; state="\{\{state\}\}">r</figure-callout>}}_0+r_c)\cdot 1.4\cdot \cos \frac{\pi }{\mathrm{four}}}-4.15=\sqrt{60.84-1.96-15.4}-4.15=6.59-4.15=2.44mm$$

. Those. there was an increase of almost 0.2 mm compared to oscillations in the direction of the rod (3.65-1.4 = 2.25 mm). The effective temperature of the ions has not changed (980 K), the distribution of the ion cloud near the stopping point will, as before, be proportional to: exp (-2.57r ² ) for distances measured in mm. The probability of reaching one of the two rods will become equal:

At an ion oscillation frequency of 50 kHz, the obtained probability of death corresponds to the characteristic ion accumulation time τ _A ≈94 s. A similar calculation for the oscillation amplitude of 1.41 mm (T _eff = 990 K) leads to the probability of the death of an ion on one of the two rods of the quadrupole, equal to 8.6 · 10 ^-8 . This corresponds to the following connection of relative variations of such probability or characteristic time with a relative variation of the amplitude of the oscillations or the amplitude of the resonant oscillating voltage:

This means that a small change in the amplitude of oscillations, for example, by 1%, will cause a change in the probability of ion loss on the rods of the quadrupole by ~ 62%, which can lead to a well-measured change in the relaxation times of the corresponding ion currents. In the presence of several types of oscillating ions with mobilities differing by a few percent or even tenths of a percent, separation of relaxation ion curves is possible.

For a more reliable separation of such ions and their identification, their collision-activated dissociation can be organized in a way alternative to that described above, when the amplitude of the radio frequency voltage is multiplied by the period of the ion’s own oscillations. To do this, it suffices to move the paths of the oscillating ions, for example, (608), to the region of higher average gas density (609) with the pulses of the fields (106) and (107). If at the moment of “stopping” of the oscillating ions after a pulsed change in the trajectory of transverse vibrations a pulsed longitudinal field is created in the form of a short meander, then accelerated ions in the time interval of this meander will have a chance to collide with a gas atom, the greater the higher the average gas density in the “stop” "Ions. With a sufficient amplitude of this meander, the colliding ions are likely to produce product ions with m / z different from the m / z oscillating ions. This will lead to the concentration of such product ions near the quadrupole axis, since they come out of resonance with the oscillating field, and to their conclusion from the quadrupole with subsequent possible registration in the mass analyzer. The periodic repetition of such a procedure with a period exceeding the settling time (more than 3 ÷ 4τ _v - ~ 20 ms for a pressure of about 10 ^-4 Torr) of stationary oscillations of the target ions in the plane of symmetry of the gas flow will lead to the registration of a set of exponentially decaying peak sets of product ions. The characteristic time of such a decline will coincide for ions formed during the decay of a specific parent ion. This may make it possible to separate such sets of ions even with relatively small differences in such characteristic times, for example, using multidimensional methods for separating the set of relaxation curves described, for example, in our patents of the Russian Federation [25-27]. A similar possibility was already considered above for data of the same type obtained in a different way. An illustration for such data is shown in Fig. 8.

The rate of death or conversion of ions in the stream will depend on the residence time of these ions inside the gas stream when exposed to oscillating fields (this depends on m / z and ion mobility) and on the probability of death of these ions when they collide with metastable particles. It should be expected that this probability for different ions may be different, even if they do not significantly differ in m / z and mobility. The transfer of energy from a metastable particle to an ion does not necessarily mean its death or a change in m / z. Excessive energy can change the structure of the ion or be scattered in collisions with atoms and molecules of the gas stream. Thus, the relaxation rates of the intensities of ion peaks during an abrupt change in the density of metastable particles can be different for different types of ions (even with the same m / z and mobilities), and additional ion separation is possible on this basis. If the density of metastable atoms in the gas stream is not high enough for the processes of interaction of the analyzed ions with them to be observed at the above-described pulsed displacement of transversely oscillating ions into the stream, then it is possible to superimpose the induced oscillations of ions in the orthogonal direction (613) by applying the corresponding stresses (614) to a pair of opposing quadrupole rods. If the phase of these oscillations is shifted by π / 2 from the transverse oscillations at the same frequencies, then the ion trajectories will be elliptical, with a suitable amplitude (614) passing near the dense part of the gas jets (605). If the frequency of the transverse vibrations is shifted to the low frequency region relative to the resonance for these ions, and the orthogonal vibrations are resonant, a more complex ion path (612) will be obtained with a relatively longer ion residence time inside the flow for a suitable amplitude of these vibrations. By changing the amplitude of the corresponding oscillating voltage in both of these cases, ions with different mobility can be introduced into the flow. Thus, it becomes possible to record the mobility spectra of ions with a selected m / z, since this choice is determined by the frequency of the oscillating field. In the presence of product ions, data similar to those obtained in a chromatography-mass spectrometric experiment can be obtained, when each peak of ion mobility will contain a set of mass spectra of product ions. The advantage in this case, as well as for the classical separation of ions by mobility, is a controlled rate of information.

от величины осциллирующего напряжения для различных направлений осцилляций для одноканального сверхзвукового потока, смещенного на 2 мм в конце квадруполя в направлении между стержнями. Регистрация данных производилась через 4 секунды после включения соответствующей величины осциллирующего напряжения. Наиболее выраженная структура (901) этих зависимостей была обнаружена у осцилляций, направленных в сторону смещения газовой струи - V_vert. Колебания ионов между стержнями квадруполя (902) - V_sin и (903) - V_cos приводили к заметно меньшей вариации данных при осциллирующих напряжениях, меньших 1,5 В. Дальнейшее увеличение осциллирующего напряжения приводило ожидаемо в последних двух случаях к более быстрому затуханию сигнала, чем при осцилляциях в направлении между стержнями. Структуру (901) можно объяснить гибелью метастабильных атомов аргона внутри струи на ионах аргона, образованных в струе при прохождении ионного источника (4). На краях струи оставшиеся метастабильные атомы аргона приводят к гибели ионов $$S{F}_5^{+}$$

. Справа на Рис. 9 показаны зависимости ионных токов двух изотопов ксенона вместе с ионами $$S{F}_5^{+}$$

для осцилляций, направленных внутрь струи. Смещение локальных минимумов ионного тока (904) ионов $$S{F}_5^{+}$$

и ионов Xe⁺ (905) можно объяснить увеличением амплитуды осцилляций более тяжелых ионов ксенона при заданной амплитуде нерезонансного осциллирующего напряжения.In Fig. Figure 9 shows the registered ion dependences $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

from the magnitude of the oscillating voltage for different directions of oscillations for a single-channel supersonic flow shifted by 2 mm at the end of the quadrupole in the direction between the rods. Data was recorded 4 seconds after switching on the corresponding value of the oscillating voltage. The most pronounced structure (901) of these dependences was found for oscillations directed toward the displacement of the gas jet, V _vert . Oscillations of ions between the rods of the quadrupole (902) - V _sin and (903) - V _cos led to a noticeably smaller variation in the data at oscillating voltages less than 1.5 V. A further increase in the oscillating voltage led expectedly in the last two cases to a more rapid attenuation of the signal, than with oscillations in the direction between the rods. The structure (901) can be explained by the death of metastable argon atoms inside the jet on argon ions formed in the jet during the passage of an ion source (4). At the edges of the jet, the remaining metastable argon atoms lead to the death of ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

. To the right in Fig. Figure 9 shows the dependences of the ion currents of two xenon isotopes together with ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

for oscillations directed inside the jet. Displacement of local minima of the ion current (904) of ions $$S{\mathrm{<figure-callout\; id="5"\; label="F"\; filenames="00000074.png,00000077.png"\; state="\{\{state\}\}">F</figure-callout>}}_5^{+}$$

and Xe ⁺ ions (905) can be explained by an increase in the amplitude of oscillations of heavier xenon ions at a given amplitude of a nonresonant oscillating voltage.

In the case under consideration, relaxation curves can be recorded for each ion mobility point. When organizing resonance oscillations after they are switched on, the intensities of the corresponding product ions will relax with almost the same characteristic time as the parent ions. This property is a consequence of the exit of product ions from the resonance of forced oscillations and their exit without significant delay from the quadrupole to the mass analyzer. In the presence of several types of ions that relax with different characteristic times, they can be separated by the methods of multidimensional separation of exponential contributions, which we described earlier [25–27]. When non-resonant transverse oscillations are superimposed, the form of the relaxation curves of the product ions may differ from those expected under resonant excitations. This may be useful for more reliable determination of the presence of target compounds in complex mixtures when using the multidimensional version of selective digital filtering described in our patent of the Russian Federation [48].

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Claims (19)

1. The method of structural-chemical analysis of impurity compounds in solutions when these solutions leak into a vacuum through a track membrane under the influence of atmospheric pressure and an electric field in the membrane channels, characterized in that a supersonic buffer gas stream is directed to the membrane surface, facilitating the exit and / or formation ions of the analyzed compounds from the solution and the transportation of the mentioned ions to the mass analyzer, as well as the fact that one part of the channels forming the said gas stream is directed towards the surface of the track membrane, and the other part along generatrices orthogonal to the tip of the weakly converging wedge, the axis of symmetry of which coincides with the axis of the mentioned trap, and the channels are located around this axis on both sides of the plane of symmetry of the wedge, the tip of the wedge is located near the said membrane and parallel to its surface . 2. The method according to p. 1, characterized in that the said buffer gas stream contains a mixture of inert gases and is passed through an electron ionization source or a glow discharge zone under conditions that ensure the formation of metastable excited atoms in this stream of at least some of these gases. 3. The method according to p. 1, characterized in that it provides heating to a controlled temperature of the buffer gas at the inlet to the supersonic gas flow formation system. 4. The method according to p. 1, characterized in that the said track membrane is heated by passing an electric current through a sprayed conductive layer on its surface. 5. The method according to p. 1, characterized in that the said transportation of the analyzed ions is carried out through a radio-frequency linear trap. 6. The method according to p. 1, characterized in that a wire electrode is installed parallel to said wedge tip towards the said linear RF trap, creating a potential well for cluster ions and charged droplets by applying corresponding DC and RF voltages to this electrode with its possible coating thin dielectric film. 7. The method according to p. 5, characterized in that the linear radio frequency trap is a radio frequency quadrupole. 8. The method according to p. 7, characterized in that the rods of the radio-frequency quadrupole are partitioned, and the electrical power circuits for the first and second halves of the quadrupole are such that they allow the creation of separately controlled quasilinear longitudinal constant, radio-frequency quadrupole and independently generated oscillating fields for opposite pairs of rods. 9. The method according to p. 1, characterized in that the input and output diaphragms of the linear RF trap are multilayer with alternating conductive and dielectric layers, the outer layers of these diaphragms are conductive. 10. The method according to p. 9, characterized in that the conductive layer of said input diaphragm on the side directed toward the radio frequency trap is divided into sections to which antiphase radio frequency voltages with controlled frequency and amplitude are applied. 11. The method according to p. 1, characterized in that the linear radio frequency trap is coaxially coupled to the mass analyzer, in particular, it can be a time-of-flight mass analyzer with orthogonal ion input. 12. The method according to p. 11, characterized in that for the implementation of coaxial pairing with the mass analyzer using a conical or wedge-shaped skimmer, the inlet or inlet of which at its apex is located symmetrically along the axis of the linear radio frequency trap; the divergence of the wedge containing jets of a supersonic gas stream is such that no more than 0.001 fractions of this stream enter the skimmer, providing an acceptable level of residual gas pressure in the mass analyzer. 13. The method according to p. 11, characterized in that the series of mass spectra is recorded sequentially in a selected range of mass to charge ratios with a gradual change in the composition of charge carriers in a solution in which the presence of the studied biomolecules is assumed or organized; a change in the composition of the charge carriers in the solution is ensured either due to differences in the mobilities of the ions leaving the membrane channels at different speeds under the action of an electric field, or by replacing the part of the analyzed solution emerging through the channels with a specially selected buffer solution; the concentration of small carrier ions in the analyzed solution is determined by appropriate sensors; peaks corresponding to multiply charged ions of the studied biomolecule are detected in the mass spectra; decomposition of the resulting multidimensional charge distributions is performed for various concentrations of charge carriers in solution; from the totality of the determined probabilities of holding various charge carriers by separate ionogenic groups of the biomolecule, those that correspond to the equilibrium processes of substitution of charge carriers in solution and which give adequate estimates of the equilibrium constants of these processes are selected; the totality of such estimates is used to characterize the structure of the studied biomolecules in solution. 14. The method according to p. 11, characterized in that the energy of the ionizing electrons in the electron ionization source or the voltage in the gas discharge region is set at a level at which metastable excited particles of the main components of the gas stream can form in a significant amount; in the absence of a longitudinal electric field in the second half of the linear trap in the first half of this trap, create a longitudinal electric field directed against the gas flow (counterfield), which inhibits the ions of interest so much that the maximum recorded flux of these ions significantly decreases / increases with a characteristic time acceptable for measurements establishing the previous level of this current with a stepwise increase / decrease in the intensity of the counterfield; a non-resonant oscillating field is created in the plane of symmetry of the wedge containing jets of a gas stream, which reduces approximately twice the registered ion current of the ions of interest; when turning on / off this oscillating field, a series of survey mass spectra is recorded and analyzed with the separation of exponentially relaxing contributions to all peaks of the mass spectrum; contributions corresponding to a certain type of initial ions should exhibit coincident relaxation times. 15. The method according to p. 14, characterized in that when analyzing the ions generated in the membrane ion source from neutral molecules, the energy of the ionizing electrons in the electron ionization source is set at a level at which metastable excited atoms with an excitation energy are formed in the buffer gas sufficient to ionize the Pening of the analyzed target compound; in the first half of the linear radio-frequency trap, an extremely close radio frequency field is created, focusing the target ions around the axis of the trap and leading to the death of ions with smaller m / z on the rods of the quadrupole; they also create a non-resonant oscillating field between the quadrupole rods in the plane of symmetry of the wedge containing jets of a supersonic gas stream with a frequency significantly lower than the resonant frequency of the target ions and an amplitude that leads to a significant and increasing death of ions with m / z greater than for the target ions ; in the second half of the mentioned trap, a relatively weak radio-frequency field is created, focusing the analyzed ions to be detected, including the product ions of the dissociation of the target ions; on the inner surface of the output diaphragm of the linear trap, a voltage is set that repels the studied ions, deviating from the axis of the linear trap by a distance greater than the radius of the outlet of the diaphragm, but transmitting ions focused near the axis of the linear trap; create in the second half of the linear trap an oscillating field resonant for the target ions in the symmetry plane of the wedge containing jets of gas flow; when turning on / off the various amplitudes of the resonant oscillating voltage, measure and analyze the data according to p. 14. 16. The method according to p. 15, characterized in that in the second half of the linear radio frequency trap they also create a resonant oscillating field in the orthogonal direction to the first resonant field and phase-shifted from this first field by π / 2; when turning on / off two resonant oscillating voltages with different amplitudes, they measure and analyze data according to p. 14. 17. The method according to p. 15, characterized in that in the second half of the linear radiofrequency trap create, in the same way as in the first half of the quadrupole, a non-resonant oscillating field between the rods of the quadrupole in the plane of symmetry of the wedge, which leads to differences between relaxation curves of product ions from relaxation source ion curves; By constructing multidimensional selective digital filters for the entire data set, the concentration of the target compound in the test mixture is identified and evaluated. 18. The method according to p. 17, characterized in that instead of a resonant oscillating field when the target ions pass near the quadrupole axis under the influence of a non-resonant oscillating field, a pulsed electric field of suitable amplitude is periodically created in the direction orthogonal to the non-resonant oscillations, thereby moving the “stop” points of the oscillating target ions to a region of relatively high gas flow density; the relaxation curves of the ion current are recorded when the sequence of pulsed fields of various amplitudes is turned on / off; By constructing multidimensional selective digital filters for the entire data set, the concentration of the target compound in the test mixture is identified and evaluated. 19. The method according to p. 18, characterized in that at the “moment” of stopping the oscillating ions moved “inward” of the gas stream, they pulse sequentially accelerate and decelerate along the gas stream to conduct collision-induced dissociation of these ions.

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