Time-of-flight mass analyzer

Abstract

The present invention relates to mass spectrometers, and more particularly to time-of-flight mass spectrometry. A time-of-flight mass analyzer is characterized in that it contains a vacuum chamber, an ion source, an ion detector and an ion flight region, wherein the ion flight region contains a system of sequentially arranged ion optical elements in the form of electrostatic sector spaces and drift spaces which provide for chromatic and spatial focusing for a spread of initial ion parameters, as well as forming a closed ion beam flight path in the shape of lobes arranged in relation to the centre of the system. The technical result of the invention consists in achieving: periodic space focusing of ions in the XY plane, which reduces ion loss and increases sensitivity; second-order time (chromatic) focusing for a spread of initial ion parameters in terms of angle, coordinate and energies, which makes it possible to achieve a high m / z resolution for a wider spread of initial ion parameters; and, in addition thereto, greater stability of the ion path with a slight variation of the mutual arrangement of the electrodes of the analyzer, resulting in increased sensitivity and m / z resolution.

Description

[0001] TIME-OF-FLIGHT MASS ANALYZER

[0002] Field of technology to which the invention relates

[0003] The present invention relates to mass spectrometers and, in particular, to time-of-flight mass spectrometry.

[0004] State of the art

[0005] Time-of-flight mass spectrometry is based on the method of separating ions by their speed as they move in drift space. For particles with similar starting energies, this leads to their sorting by M / z ratio.

[0006] The main characteristics of a mass analyzer (MA) are its resolving power in terms of the M / z ratio and the level of ion losses as they pass through the MA. Achieving high resolution for time-of-flight mass analyzers (TOFMA) requires increasing the ion flight length and, accordingly, increasing the dimensions.

[0007] One of the factors influencing the widespread use of the WPMA was the high level of ion losses caused by the duty cycle of the WPMA. To achieve high sensitivity, it is necessary to increase the number of ions in the starting ion packet. But with a large number of ions in the packet passing through the MA, a number of negative effects arise associated with the space charge, leading to a loss of resolution and errors in the accurate measurement of M / z.

[0008] A known MA is presented by the group of authors Yavor et al. in patent US10950425B2, 03 / 16 / 2021, which discloses a multi-pass mass analyzer that uses electrostatic sectors assembled into cells to change the direction of the ion beam. The disadvantages of this solution are high ion losses and low sensitivity, low M / z resolution, and low stability of the ion trajectory.

[0009] Thus, there is a need to develop multi-pass mass analyzers based on sector electrostatic fields, which, firstly, would have improved characteristics, could provide high-order isochronism, secondly, would be structurally simple, and thirdly, would have small dimensions.

[0010] The present invention provides an improved mass analyzer.

[0011] The essence of the invention

[0012] The technical task is to create a device for separating ions by mass-to-charge ratio, which has a high resolution with small dimensions, ensuring the achievement of periodic spatial focusing of ions in the XY plane, allowing to reduce ion losses and increase sensitivity, ensuring the achievement of second-order time (chromatic) focusing for the spread of initial ion parameters by angle, coordinate and energy, which allows to achieve high resolution by M / z for a wider spread of initial ion parameters, achieving better stability of the ion trajectory with a small variation in the mutual arrangement of the analyzer electrodes.

[0013] The technical result of the invention consists in achieving periodic spatial focusing of ions in the XY plane, which reduces ion losses and increases sensitivity; in achieving second-order time (chromatic) focusing for the spread of initial ion parameters by angle, coordinate and energy, which makes it possible to achieve high resolution by M / z for a wider spread of initial ion parameters; at the same time, better stability of the ion trajectory is achieved with a small variation in the mutual arrangement of the analyzer electrodes and, thus, an increase in sensitivity and resolution by M / z is achieved.

[0014] The technical result is achieved due to the fact that the time-of-flight mass analyzer contains a vacuum chamber, an ion source, an ion detector and an ion flight region, wherein the ion flight region contains a system of successively arranged ion-optical elements, which are intervals of electrostatic sectors and drift intervals, forming chromatic and spatial focusing for the spread of the initial parameters of the ions, and also forming a closed trajectory of the ion beam flight in the form of petals, located relative to the center of the said system.

[0015] In addition, the ion-optical elements are arranged and configured in such a way that the ion beam has a closed flight path in the form of a figure eight in the (x-y) plane or another similar figure with several petals.

[0016] In addition, chromatic focusing is designed to occur at intermediate points on the trajectory every 2nd revolution.

[0017] In addition, the ion-optical elements are arranged and configured in such a way that the ion beam passes through the entire system, thereby making one or more complete revolutions.

[0018] In addition, the ion-optical elements that form the trajectory deviation in the petal region contain one or more electrostatic sectors that have at least two different deflection radii.

[0019] In addition, the ion-optical elements are arranged and configured into a system, after several complete passes of which the second-order focusing of the ion beam flight time is ensured simultaneously by the energy and spatial (in the x-y plane) spreads.

[0020] In addition, the electrostatic sectors are made cylindrical. In addition, a pulsed ion source of the MALDI type is used as an ion source.

[0021] In addition, it additionally contains a pulsed ion accelerator, designed with the possibility of forming short ion packets at the input to the mass analyzer, for example, such as an orthogonal ion accelerator, or an ion packet former based on a radio frequency ion trap.

[0022] Brief description of the drawings

[0023] Fig. 1 - Ion-optical diagram of the prior art solution US10950425B2, in which the ions essentially follow an oval trajectory;

[0024] Fig. 2 - Variant of the symmetrical "eight" type geometry with three different sectors (1, 2, 3) and field-free intervals (4, 5, 6, 7);

[0025] Fig. 3 - Variant of geometry of the asymmetrical "eight" type with six different sectors (1, 2, 3, 4, 5, 6) and field-free intervals (7, 8, 9, 10, 11, 12);

[0026] Fig. 4 - Variant of the symmetrical "eight" type geometry with two different sectors (1, 2) and field-free intervals (3, 4);

[0027] Fig.5 - Variant of geometry of the asymmetrical "eight" type with four different sectors (1, 2, 3, 4) and field-free intervals (5, 6, 7, 8);

[0028] Fig. 6 - Preferred embodiment of the invention. Symmetrical figure-eight geometry with two different sectors (1, 2) and field-free intervals (3, 4); A) - 30-view, B) - XY-plane; C) - View of trajectories on the 1st revolution for ions with an initial spread in energies. The arrow indicates the focal point;

[0029] Fig. 7 - Model peak obtained for the preferred embodiment of the invention shown in Fig. 6. The peak is obtained for 12 revolutions for the total spread of the initial ion parameters with a Gaussian distribution with parameters at half-maximum: 1 / gDE=280 eV, 1 Da=1° by radial angle, 1 / 2Аг=2.5 mm - along the radial coordinate;

[0030] Fig. 8 - Dependence of the time of flight on the energy spread of ions for the preferred embodiment of the invention shown in Fig. 6;

[0031] Fig. 9 - Dependence of the time of flight on the angular spread of ions for the preferred embodiment of the invention shown in Fig. 6;

[0032] Fig. 10 - View of the trajectories of the 1st and 2nd revolutions for different spreads of the initial parameters of the ions: DE - by energy, Da - by radial angle;

[0033] Fig. 11 - View of time fronts for different revolutions and for different spreads of initial ion parameters: DE - by energy, Da - by radial angle, Dg - by radial coordinate; Fig. 12 Cylindrical coordinate system for describing the motion of charged particles in electrostatic sectors.

[0034] Implementation of the invention

[0035] A time-of-flight mass analyzer is usually part of a mass spectrometer, which includes, in addition to the mass analyzer, a vacuum chamber, an ion source, and an ion detector. The claimed time-of-flight mass analyzer contains an ion flight region, wherein the ion flight region contains a system of successively arranged ion-optical elements, which are intervals of electrostatic sectors and drift intervals, forming chromatic and spatial focusing for the spread of the initial parameters of the ions, and also forming a closed trajectory of the ion flight in the form of petals, located relative to the center of the said system.

[0036] In this case, the ion-optical elements can be arranged and configured so that the ion beam has a closed flight path, for example, in the form of a figure eight in the (x-y) plane or another similar figure with 4, 6, etc. petals.

[0037] Chromatic focusing can occur at intermediate points along the trajectory, for example, every 2nd revolution.

[0038] The ion-optical elements can be arranged and configured in such a way that the ion beam will pass through the entire system, thereby making one or more complete revolutions.

[0039] A group of ion-optical elements that forms a trajectory deviation in the petal region may contain two or more electrostatic sectors that have at least two different deflection radii.

[0040] A group of ion-optical elements that forms a trajectory deviation in the petal region may contain electrostatic sectors that have different deflection radii in different petals.

[0041] Ion-optical elements can be arranged and configured into a system, after several complete passes of which the focusing of the second or more orders of the ion beam flight time is ensured simultaneously by energy and spatial (in the x-y plane) spreads.

[0042] The resulting focusing on the spread of the initial ion parameters can have a different order for different parameters of the ion beam flight time simultaneously on the energy and spatial (in the x-y plane) spreads.

[0043] Electrostatic sectors can be made as cylindrical sectors.

[0044] Obtaining chromatic and spatial focusing can be achieved by optimizing the geometry and power supply modes of the electrodes of the ion-optical system MA, increased stability of ion trajectories can be achieved by constructing the configuration of the ion-optical system MA in such a way that the chromatic and spatial deviations of ions that occur during the passage of half a revolution are compensated during the passage of the second half of the revolution. For example, such a configuration occurs for the geometry of the ion-optical system, which forms a characteristic type of trajectories in the form of a figure eight. Compensation for chromatic and spatial deviations is carried out in this case due to mirroring, where the deviation that occurs will have the opposite sign on the next revolution.

[0045] Further, for brevity, the term spatial and chromatic focusing of the N-th order for the spread of the initial parameters of ions by angle, coordinate and energy will be replaced by the term multiple focusing.

[0046] As a result of modeling the preferred embodiment of the invention, presented in Fig. 2, for 12 flight revolutions, a model peak (see Fig. 4) was obtained for the total spread of the initial ion parameters with a Gaussian distribution. The distribution parameters at half-height are as follows: %DE=280 eV, 1 / гДа=1° by radial angle, %Дг=2.5 MM - by radial coordinate. Parameters of ion distribution correspond to the characteristic initial set of ion parameters at the entrance to MA. The obtained resolution R~78000 corresponds to the aberration limit of MA in this configuration.

[0047] It is preferable to use an orthogonal ion accelerator (OA) as an ion packet former.

[0048] To achieve the technical result of the invention, it is necessary to calculate the configuration or geometry of the ion-optical system in such a way that in the plane of the detector there is a temporary focusing of the 2nd and higher order for the spread of the initial parameters of the ions by energy and spatial spread (angle and coordinate). This focusing can also occur at intermediate points on the trajectory, for example, every 2nd revolution.

[0049] To implement the invention and to calculate it, the alternating sequence of sector fields and field-free (drift) intervals is conveniently arranged in groups that can be located symmetrically relative to the central plane ZY or relative to the central point. Alternatively, these groups can be located around the central point, providing movement of trajectories in the form of petals, in particular in the form of a figure eight.

[0050] Unlike the prototype (Fig. 1), the present invention does not require that the ion-optical elements in each ion-optical cell be configured in such a way as to achieve such focusing of ions as stated in the formula of the prototype (paragraph 3 of the independent claim), namely, going parallel at the point of entry of the ion of the cell, to the point at the point of exit of the ions of the cell, and vice versa. Also, the prototype declares symmetry (paragraph 6 of the independent claim), which in the present invention is not mandatory for the presence of second-order focusing in MA by sector fields. Also, in the method of searching for the optimal configuration of the system in the prototype, the condition of the presence of first-order focusing in each cell is imposed, however, in the approach of the present invention this condition is not imposed, which gives additional scope for searching for convenient configurations.

[0051] The power expansion approach is convenient for describing beams of charged particles confined to some main path. Most devices that generate static fields to separate charged particles (in time or space) work with such beams. This approach is similar to light optics and forms the general "language" of aberration theory.

[0052] A beam of charged particles is considered, limited by some main path, this path is called the optical axis and is the trajectory of some reference particle with certain mass, charge and energy. Then local Cartesian coordinates (x, y) are introduced into each plane of the profile. Then an arbitrary particle will be characterized in each plane of the profile by the following parameters:

[0053] Coordinates x, y

[0054] Angular coordinates

[0055] Deviation of the length of the flight path between the particle under consideration and the reference particle Z = (T - TQ)V0, where T is the flight time of an arbitrary particle, T0, v0 are the flight time and speed of the reference particle

[0056] The relative deviation of kinetic energy 5=(U-Uo) / Uo, where U is the kinetic energy of ions in the XY deflection plane, and Uo is the kinetic energy for ions moving along the ion-optical axis.

[0057] Relative deviation of mass y

[0058] Thus, the motion of a particle is described by its position vector. Assuming that the initial deviations (x0, a0, y0, b0, y, 30, 10) are small, we can represent the functions as a power series (called an aberration expansion) in these initial parameters. The coefficients of the first-order terms are called paraxial (linear) coefficients, and the coefficients of the higher terms are called aberration coefficients. These coefficients are conveniently written in matrix form. In this case, the new position vector in an arbitrary profile plane is related to the initial position vector using the so-called transfer matrix. The form of the transfer matrix in the case of first-order approximation is given below.

[0059] The transfer matrix for each optical component of the system can be calculated numerically if its physical parameters are given. If the system consists of several ion-optical components, such as electric sectors, quadrupole lenses, and drift spaces, the full transfer matrix can be obtained by multiplying the transfer matrices of the individual elements:

[0060] R = R n * R n -i * ... * R2 * Ri (1)

[0061] To facilitate the search for an optimal system that will achieve the required optical properties, symmetric geometries are introduced. That is, by introducing symmetry into the arrangement of ion-optical components, with a specially selected ratio of the parameters of a given system, it is possible to achieve conditions for multiple focusing. As a rule, a symmetric system consists of two main units (cells). For example, a system consisting of four elements can be understood as a doubly symmetric system of two cells.

[0062] It is possible to derive a plane-symmetric matrix and a point-symmetric matrix from the transfer matrix based on the concept of the inverse matrix. Each of these symmetries may or may not have an intermediate image.

[0063] In a cylindrical electrostatic sector, an arc of radius r0, which corresponds to the zero equipotential, is chosen as the optical axis. The ion-optical axis is the trajectory of a particle with mass m0, charge z0, and kinetic energy U o , respectively 1 / the speed of such a particle v0= (2U0 / m0) / 2 . A cylindrical coordinate system (r0+ x, a>, y) is used, shown in Fig. 12. The optical axis corresponds to the arc of a circle with x = 0, y = 0. The trajectory of an arbitrary particle with charge e, mass m = m0(1 + y) е / С() and kinetic energy U = Y о (1 + 5) e / eQ described by the coordinates x(t) and y(y) as functions of y. 6 and y are the relative deviations of energy and mass, respectively.

[0064] As is known, the electric potential of a cylindrical capacitor is proportional to log g. The expression for it can be written as:

[0065] Using the Taylor series expansion, formula (2) can be represented as:

[0066] The path length deviation for a cylindrical sector can be written as follows:

[0067] 1 = [ -ds - r o a) (4)

[0068] Jo v

[0069] In cylindrical coordinates, the differential element ds can be represented as:

[0070] Where the dot denotes d / dw. Using the expressions for the entry angles of the support particle

[0071] (tg(a0) = r0+x and tg(p0) = r0+x), we can rewrite expression (5) as follows: ds = (r0+ x)[tg

[0072] The equation for the velocity of a particle can be obtained from the law of conservation of energy: 2 (U - еср)1 1 / 2

[0073] The equation for the deviation of the path length (4) is expressed through the functions x(ω), y(ω), tg(a o ),tg(|3o), 5 and y, the expressions for which can be obtained by solving the equations of motion for a charged particle in a cylindrical capacitor. Detailed expressions are given for a toroidal capacitor and can be modified for a cylindrical one. (T. Sakurai, T. Matsuo, and H. Matsuda, Int. J. Mass Spectrom. Ion Process, vol. 68, no. 1-2, pp. 127-154, 1986)

[0074] The previous section discussed the calculation of the ion flight time through electrostatic sectors. It is worth noting that this reasoning is valid in the region of an ideal field, i.e. it is assumed that the sector field boundary coincides with the geometric boundary. In reality, an ion passing through an electrostatic sector flies through the input and output edge fields. In these regions, the intensity gradually decreases from the value inside the sector to zero outside. This leads to the ion trajectory deviating from the ideal one.

[0075] In order to limit this transition region, so-called field-setting (edge) electrodes are usually used. One of these electrodes is the Herzog shunt. It defines the effective boundary where it can be assumed that the field is sharply cut off if we are talking about first-order optical properties. The Herzog shunt does not eliminate second-order effects associated with image aberrations. When calculating trajectories with an accuracy of 2nd order and higher, it is necessary to include the effect of edge fields in the calculation. To find the geometry in which focusing is achieved, the problem of minimizing a function of the following type is solved: where x is the vector of system parameters (length of field-free intervals, angles and radii of sectors), R(x)j,i is the element of the final transfer matrix of the system with indices j and i.

[0076] To find the minimum of this function, two methods are used: Differential evolution and Dual Annealing. The geometric parameters of the system are subject to constraints that link these parameters in such a way that the central trajectory closes in one revolution.

[0077] It is important to emphasize that the method of searching for multiple focusing in the ion-optical system of the mass analyzer is based on the fact that the focusing optimum is sought after the complete passage of several revolutions. The optimization algorithm does not include conditions for achieving geometric focusing after the ions have passed half of a whole revolution or after passing one ion-optical cell, as is required in the prototype. The absence of intermediate focusing can be seen by looking at Fig. 10. Thus, the desired ion-optical properties of the system are obtained here after passing one or several full revolutions, as set in the calculation.

[0078] It is also important to note that the presence of symmetries and the presence of identical cells in the ion-optical system is not a necessary condition for achieving the technical result, i.e. the presence of multiple focusing of the N-th order on the detector. The presence of symmetries significantly simplifies and accelerates the calculation of the trajectory parameters, which is important for such problems of multiparameter optimization, but is not necessary. The final goal of optimization is the condition of achieving multiple focusing of the N-th order precisely on the detector after the required number of revolutions through the system. The number of revolutions is selected based on the condition of achieving the required resolution by M / z in order to achieve the required time of flight with the available final duration of the ion packet on the detector, due to the initial duration of the ion packet, the blurring of the ion packet in the detector and the level of time aberrations of the mass analyzer.

[0079] In addition, to find the optimal configuration of the ion-optical system, the condition of mandatory presence of 1st order focusing during the flight of each cell is not imposed. 1st order focusing may occur during the flight of a part of the cell or during the flight of a group of cells. In this case, 1st order focusing may take place inside the cell, not necessarily at the input or output of it. An important condition for finding the optimal configuration of the ion-optical system of the mass analyzer is the presence of a sufficient number of variable parameters in the system that affect the occurrence of aberration deviations and their compensation. For example, in the system shown in Fig. 1 (prototype) there are six variable parameters, in the system of Fig. 2 (the presented invention) - eight variable parameters.

[0080] In the above approach, which was used to calculate the parameters of the system for implementing the present invention, the choice of the cell, which plays the role of the calculation unit in calculating the parameters of the ion trajectories using the transfer matrices M (N) =[M (1) ] N , more lenient requirements are imposed. The cell, in this sense, acquires a rather conditional character, their use only accelerates the search for optimal system parameters. In our case, a cell can be, for example, a whole turn of the trajectory or several turns, on which multiple focusing appears. Recall that in the prototype, in patent US10950425B2, a group of sectors is taken as a cell, which provides parallel point spatial focusing, and also, when passing the cell, focusing of the 1st order is achieved.

[0081] Thus, the above-described approach to finding the optimal parameters of the ion-optical system of the mass analyzer, which was used to calculate the parameters of the system for implementing the present invention, is more flexible and makes it possible to find a wide variety of geometries of mass analyzers that meet the conditions for the presence of multiple focusing. Fig. 2-6 shows some embodiments of the invention. One of the features of these embodiments is the type of trajectory in the form of an 8 with 2 petals or a figure with 4, six, etc. petals that form the trajectories.

[0082] Another feature is that in a conventional cell or on one revolution, there are sector fields with different intensity on the average trajectory, which are formed by several cylindrical electrostatic sectors with different radii and different angles of the solution for changing the direction of the ion beam in the XY plane, as well as a number of field-free intervals. Their combination, i.e. the sequence of sector fields of their radii and angles of the solution, as well as field-free intervals and their length, are built in such a way that the ion trajectories are closed after one or several revolutions.

[0083] The analyzer may include a pulsed ion source, such as the MALDL type.

[0084] The analyzer may include a pulsed ion accelerator that forms short ion packets at the input of the mass analyzer, such as, for example, an orthogonal ion accelerator, or an ion packet former based on a radio frequency ion trap. The claimed analyzer, made in the manner described above, allows achieving periodic spatial focusing of ions in the XY plane, which reduces ion losses and increases sensitivity; achieving time focusing (chromatic) of the second or more orders for the spread of the initial ion parameters by angle, coordinate and energy, which allows achieving high resolution by M / z for a wider spread of the initial ion parameters; at the same time, ensuring better stability of the ion trajectory with a small variation in the mutual arrangement of the analyzer electrodes, as well as reducing the costs of manufacturing the mass analyzer due to more lenient requirements for the accuracy of manufacturing and assembly of the mass analyzer.

Claims

CLAUSE OF INVENTION 1. A time-of-flight mass analyzer characterized by the fact that it contains an ion flight region, wherein the ion flight region contains a system of sequentially arranged ion-optical elements, which are intervals of electrostatic sectors and drift intervals, forming chromatic and spatial focusing for the spread of the initial parameters of the ions, and also forming a closed trajectory of the ion beam flight in the form of petals located relative to the center of the said system.

2. A time-of-flight mass analyzer according to claim 1, characterized in that the ion-optical elements are arranged and configured in such a way that the ion beam has a closed flight path in the form of a figure eight in the (x-y) plane or another similar figure with several petals.

3. A time-of-flight mass analyzer according to item 1, characterized in that the chromatic focusing is designed with the possibility of occurring at intermediate points on the trajectory every 1st, 2nd, etc. revolution.

4. A time-of-flight mass analyzer according to claim 1, characterized in that the ion-optical elements are arranged and configured in such a way that the ion beam passes through the entire system, thereby making one or more complete revolutions.

5. A time-of-flight mass analyzer according to claim 1, characterized in that the ion-optical elements that form the trajectory deviation in the lobe region contain two or more electrostatic sectors that have at least two different deflection radii.

6. A time-of-flight mass analyzer according to claim 1, characterized in that the ion-optical elements are arranged and configured into a system, after several complete passes of which focusing of the second and more orders of the ion beam flight time is ensured simultaneously by energy and spatial (in the x-y plane) spreads.

7. A time-of-flight mass analyzer according to item 1, characterized in that the electrostatic sectors are made cylindrical.

8. A time-of-flight mass analyzer according to claim 1, characterized in that a pulsed ion source of the MALDI type is used as the ion source.

9. A time-of-flight mass analyzer according to claim 1, characterized in that it additionally contains a pulsed ion accelerator, designed with the possibility of forming short ion packets at the input to the mass analyzer. 12 SUBSTITUTE SHEET (RULE 26)

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