EP3631434A1

EP3631434A1 - Drift tube for ion-mobility spectrometer with integrated multicapillary column

Info

Publication number: EP3631434A1
Application number: EP18729604.1A
Authority: EP
Inventors: Gabriele SPRAVE-BAUMBACH
Original assignee: B Braun Melsungen AG
Current assignee: B Braun Melsungen AG
Priority date: 2017-05-24
Filing date: 2018-05-24
Publication date: 2020-04-08
Also published as: CN110678121B; WO2018215618A1; WO2018215622A1; EP3629917A1; EP3631433A1; EP3629916A1; CN110662959A; RU2019143086A3; CN110678121A; WO2018215619A1; ES2890574T3; CN110662486A; EP3629917B1; RU2019143086A; WO2018215621A1; RU2761078C2; US20200170571A1

Abstract

The invention relates to a compact drift tube comprising a cylindrical body, in the wall of which there is arranged at least one multicapillary column, preferably parallel to the longitudinal axis, and to an ion-mobility spectrometer, which is used to monitor the anaesthesia of a patient during a medical intervention and comprises a drift tube of this kind.

Description

DRIVING TUBES FOR ION MOBILITY SPECTROMETERS WITH

INTEGRATED MULTI CAPILLARY COLUMN

The invention relates to an electrode arrangement for a drift tube in one

Ion mobility spectrometer, which is used to monitor anesthesia of a patient during a medical procedure, with a multi-capillary column integrated in the drift tube.

Background of the invention

An ion mobility spectrometer / ion mobility spectrometer (IMS) is a device for chemical analysis of the

Composition of gases in the trace range, preferably in the range of ng / L to pg / L or ppm _v to ppt _v ; for volatile organic compounds - preferably in air, nitrogen, carbon dioxide. Fields of application are the detection, detection,

Identify and quantify chemical agents, legal and illegal drugs, explosives and components of air, including exhaled air. The mobility of ions, rarely electrically charged atoms, usually charged molecules or molecular clusters, is dependent on the size and charge of the ions. The ionization can be carried out by means of radioactive radiation sources, preferably ⁶³ Ni or ³ H, laser, UV light, surface charges or chemical ionization.

In the IMS mainly singly charged ions are observed, with UV ionization usually M + (where M stands for the molecule or the analyte), when ionizing by means of radioactive radiation sources mostly MH ⁺ (monomer), M2H ⁺ (dimer) or M (H2O) n (N2) _m ⁺ (water cluster with N2 content). The principle of

Ion mobility spectrometry is based on the fact that under normal pressure, strictly under ambient pressure generated ions in an electric field against the

Flow direction of a so-called drift gas drift. Ions of different mass and / or structure absorb energy in the electric field and continuously lose it by collisions with the surrounding air molecules and thus reach comparatively quickly uniform, different drift velocities for each ion species and are ideally separated from one another until they are consecutively timed

Detector, usually a Faraday plate, impinge. The ratio of

Ion drift velocities to the strength of the electric field are referred to as ion mobility and a linear one results for small electric field strengths Relation Vdr = KE (vdr ftspeed, K elonenmobilität, E electric field strength). The separation of the ions of different analytes over a given distance based on the different drift velocities is referred to as ion mobility spectrometry, where ion current is measured as the time of arrival on the Faraday plate as a function of the drift time. Here is the

Signal intensity of the current on the Faraday plate (usually measured as a voltage drop across a high-impedance resistor) is a measure of the concentration of the respective analyte. The molecules are sampled in their gaseous phase by an ion source, e.g. by means of a radioactive radiation source, a photoionizer (usually 10.6 or 1 1 .8 eV UV lamps or lasers of different wavelengths) or electrical discharges

(Partial discharges or corona discharges), occasionally also ionized by electrospray or the like. The ions pass through a barrier grid / electrical switching grid (Bradbury-Nielsen grid), which can interrupt the ion current controlled and get driven by an electric field in a drift tube to a

Detection device / collecting electrode on the opposite side of the ionisationsbereiches, provided that the barrier grid for a short period of time, usually between a few s and 1 ms opens and so the electrical transverse field (between the wires of the barrier grid) no longer greater than the longitudinal electrical field of lonisations- and drift space, allowing ions to pass through the barrier. By measuring the drift time of the ions between the position of the barrier grating, which spatially separates the ionization space from the drift space, and the Faraday plate as

Detection device can its drift time and with knowledge of Driftweges (distance barrier grid to Faraday plate) and the constant electric field the

ionic mobility constant K can be calculated. Ideally, for certain analyte groups, their specific mass can be derived from mobility, which is not usually important. It is essential that different ions of different analytes are detected and in the ideal case can be characterized over the time of drift, which is usually not the case, so that

be used chromatographic Vortrennungen (eg so-called multi-capillary columns, MCC), so that the analytes in the ideal case successively reach the ionization space of an IMS and are ionized successively. To generate a constant electric field, the entire drift tube is provided with metal rings / drift rings / annular electrodes, which are usually arranged at regular intervals over the length of the drift tube. This annular

Electrodes are electrical, e.g. isolated by isolators and by means of

Resistors are connected together or are e.g. placed externally on a cylindrical drift tube at fixed intervals and then connected to electrical resistors. The electrodes connected to a high voltage source generate a linear potential gradient / field gradient across the ionization and drift space at a value of about 100 to 500 V / cm along a central axis of the drift tube. By this electric field, the ions in the drift tube move in an axial direction toward the Faraday plate. To generate a homogeneous electric field, the tubes are constructed in the form of a stack of metal and insulator rings, or electrodes are placed on cylindrical insulators at specific intervals. By means of voltage dividers, which are attached to the tube jacket, the individual metal rings receive different potentials, whereby any gradients can be set. The voltages vary between 1000 and 10000 V, so that, depending on the drift paths, electric field strengths of 100 to 500 V / cm result in the tube. The homogeneity of the electric field depends on the radius of the metal rings and their distances from one another, assuming that this applies to the region where the drift velocity is linear to the electric field strength.

The drift tube is traversed by a drift gas, in the simplest case of air, from the direction of the Faraday plate. The drift gas is introduced into the drift region to collide with the sample ions to produce a drift velocity that is ideally unique to each ion. It also prevents uncharged

Analyte molecules can pass through the barrier, since then the start position would no longer be defined for each type of ion, that is, the drift path would be different. Sometimes a side effect is that the surfaces of the drift tube from there

to be cleaned on adherent molecules. The ions attached to the

Arrived detection device, are measured according to their intensity (usually current measurements, alternatively voltage drop across a high-impedance resistor) at an arrival time. The detection device analyzes the maxima of the signal intensities to represent a motion signature (a fingerprint) for identification of the sample ions to be determined. A barrier grid separates the reaction area / ionization area / reaction space, reaction space in which all the ionization processes take place, and the

Drift region / drift region, drift space, in which the separation of the ion mixture takes place. The grid controls the inlet of the ions at certain periodic time intervals. A pulsed signal, preferably square wave signal, determines the short

Lattice opening and the longer closing time. Two different lattice types are used. While the Tyndall grating consists of two consecutive grids with parallel wires, the Bradbury-Nielsen grating is arranged in one plane, which is not significant for the basic operation. The grid is "open" when the barrier grid has the potential which prevails at the location of the tube (sloping longitudinally towards the Faraday plate)

Surrounding the grid wires, the electric field is not disturbed, so that the ions can pass through the grid unhindered. If an additional field is built up between the two sets of wires, which forms perpendicular to the existing field, the grid will "close", since then the electrical cross-field between the wires will be larger than the longitudinal field to the Faraday plate.The ions can not pass the grid Depending on their polarity, they migrate to the positive or negative part of the grid and are neutralized or they are flushed out with the drift gas until a new pulse briefly opens the grid again and allows a portion of the ion cloud to enter the drift space The shorter the pulse width at which the grating is opened, the sharper the temporal resolution of the signal, but the smaller it is the signal as such, since the total amount of ions, which by the grating passes is also smaller. On the other hand, short lattice opening times reduce the number of ions entering the drift space, and thus the sensitivity, if that depends on it and not on the detection limit itself. Normally, the barrier grid has a pulse duration of a few microseconds to milliseconds, during which the ions can enter the drift region. After this When the ions enter the drift region, the ions move in the direction of a detection device under the influence of an electric field. Due to the electric field, the ions with different mass and / or structure will reach different drift velocities and thus different

Time points of the detector registered. A recorded ion mobility spectrum thus contains time-dependent current signals.

In most spectrometers is located about 0.5 to 2 mm in front of the Faraday plate, generally in front of the detector another grating. For example, this so-called screening grid (aperture grid) likewise consists of parallel wires and is of particular importance for the formation of sharp signals. The electrometer plate connected downstream as a detector is shielded from the electric field of the incoming ions. If this grid is missing, the detector would not only register the impacting ion charges, but also the approaching ions, which would increase

stepped signals and no peaks would result.

In complex gas mixtures, the simultaneous ionization of all analytes leads to a strong overlap of the signal excursion, making qualitative identification difficult and quantitative identification virtually impossible. For this reason, a gas chromatographic column is placed in front of the IMS, and a multi-capillary column (MCC) for pre-separation of the gas mixture is also connected upstream in respiratory air examinations. This MCC consists of a large number of bundled single capillaries that retain different analytes of different lengths for the same length of time in each individual capillary. Thus, the measurement data get another dimension: the retention time, which describes the respective delay of the movement of the analytes through the gas chromatographic column. In multicapillary columns, a large number of capillaries are bundled (up to thousands), each with a diameter of

Micrometer range. Despite the large number of capillaries in the multi-capillary column, this can have a diameter of only a few mm. A multi-capillary column allows a fast and high-resolution analysis at a high flow rate, but above all it can be applied with sample volumes in the range of μΙ_ to ml_, in particular with moist samples, as in regular breathing air analyzes

occurrence. State of the art

Inn prior art are ion mobility spectrometer with drift tubes and

Multi-capillary columns (MCC) are known in which both components are realized separately in one device.

These analyzers, which use an IMS in conjunction with an MCC, are also used in the medical field where high mobility of the analyzer is required. This means that the medical device will be at different

Application sites used (operating room, intensive care unit, recovery room). An object of the invention is therefore to provide a compact and lightweight analyzer.

Brief description of the invention

Against this background, it is the object of the present invention to provide a compact ion mobility spectrometer.

This object is solved by the features of a drift tube according to claim 1 and an ion mobility spectrometer according to claim 7. Advantageous developments and embodiments are the subject of the dependent claims and / or explained below.

In a preferred embodiment, a drift tube has a cylindrical body, in the wall of which at least one multi-capillary column, preferably parallel to the longitudinal axis, is arranged / formed / inserted. In other words, a drift tube of an ion mobility spectrometer, provided and adapted for use in a medical field, preferably in a

Respiratory gas analyzer, a cylindrical body. In the cylindrical body is at least one, preferably radially centered, through bore /

Passage opening arranged, which forms the lonisationsbereich and at least one further, preferably parallel, through-hole / passage opening to

Inclusion of a multi-capillary column. In the drift tube are thus at least two

Through openings parallel arranged / integrated spatially, wherein in the at least one further passage opening a multi-capillary column is arranged / inserted. In a further optionally independently claimed embodiment, the multi-capillary column has a temperature control element for controlling the temperature in the multi-capillary column. In other words, in the passage opening in which the multi-capillary column is mounted further accommodated, preferably a ring around the temperature control element, preferably a heater

Multikapillarsäule. The temperature control element is provided and adapted to control the temperature of the multi-capillary column. A side effect here is that thereby the passage opening, in which the drift region is located, can be temperature controlled indirectly. Particularly preferred is a plurality, preferably four, of MCC having through holes around the

Through opening of the drift region arranged to this evenly

temper.

In a further embodiment, the multi-capillary column is thermally insulated. In other words, in the passage opening in which the multi-capillary column is arranged, further a thermally insulating material / insulator is mounted, preferably annular around the multi-capillary column. Particularly preferably, the thermal insulation is arranged in a ring around the temperature control element of the multi-capillary column. In a further embodiment, the multicapillary column and / or the

Temperature control element and / or the thermal insulator non-metallic

educated. In other words, both the multi-capillary column, the

Temperature control element as well as the thermal insulator to be made of a non-metallic material. Because electrodes for generating an electric field are formed on the drift tube, a metallic object can disturb this field, or an unintended eddy current can be induced in this object. In order to obtain a stable electric field in the drift region of the drift column, the components multicapillary column, the temperature control element, the thermal insulator are preferably made of a non-conductive / non-metallic

Material, particularly preferably of glass and / or plastic.

In a further embodiment, the multicapillary column has a stationary phase, preferably silica gel / alumina, and / or a mobile phase, preferably Hexane / ethyl acetate / dichloromethane / methanol, on. The stationary phase can fill the capillaries of the multicapillary columns and / or be attached to the inner wall of the capillaries. In a further embodiment, the multi-capillary column has a frit at its output end. This frit serves as a filter to prevent inadvertently introduced elements distorting the measurement or the

Damage analyzer. Such elements include, for example, parts of the stationary phase or foreign bodies / impurities.

In a further preferred embodiment, a

Ion mobility spectrometer, which is used to monitor anesthesia of a patient during a medical procedure, a drift tube according to one of the preceding embodiments.

The invention will be described with reference to the drawings, in which

Embodiment is exemplified, described in more detail.

Fig. 1 shows a schematic side view of a drift tube according to the invention.

Fig. 2 shows a schematic side cross-sectional view of a drift tube according to the invention.

Fig. 3 shows a schematic front view of a drift tube according to the invention.

4 shows an enlarged view of a partial region of the schematic

Front view of a drift tube according to the invention from FIG. 3.

figure description

FIG. 1 shows a schematic side view of a drift tube 1 according to the invention. The drift tube 1 has a first end 2 or end portion and a second end 4 or end portion, which are interconnected via a central tube 6. Both the first and second ends 2 and 4 are cylindrically shaped, but with The first and second ends 2 and 4f have an outer diameter which is larger than the outer diameter of the central tube 6. The ends 2 and 4 serve to fix the drift tube 1 to a housing (not shown). Through the first end 2, second end 4 and the central tube 6 performs a through hole 8 therethrough. On the lateral surface of the central tube 8 of the drift tube 1, preferably three ring electrodes 10 are arranged at the same distance in the present case. Parallel to the through hole 8, the

Having drift region, further through holes 12 are shown for receiving multi-capillary columns.

Figure 2 is a schematic side cross-sectional view of a drift tube 1 according to the invention. Parallel to the through hole 8, which has the drift region, the further through holes 12 are therefore shown, each having a

Have / include multi-capillary 14. In the through-hole 8, which forms the drift channel, from the one end 2 to the second end 4 in the sequence, an ionization source 16, a barrier grille 18, a shielding grid 20 and a detector 22 are introduced. The first ring electrode 10 is located at the same height of the longitudinal axis of the drift tube as the barrier grille 18. The last ring electrode 10 is located at the same height of the longitudinal axis of the drift tube as the screening grid 20 of the detector 22.

Fig. 3 shows a schematic front view of the drift tube 1 according to the invention. In this case, four more are around the through hole 8 for the drift region

Through holes 12 for receiving a multi-capillary 14 evenly distributed around them. That is, the through-holes 12 for accommodating each of a multi-capillary column 14 are arranged radially further outside than an inner wall of the through-hole 8 for the drift region and distributed in the wall of the drift tube 1 equiangularly. 4 shows an enlarged view of a partial region of the schematic

Front view of a drift tube 1 according to the invention of Figure 3. In this illustration, it is clearly seen that in the through hole 12 for the multi-capillary 14 around the multi-capillary a temperature control element 24, for example a heater (Within the Driftröhrenwandung) is arranged, which in turn is surrounded by a thermal insulator 26.

LIST OF REFERENCE NUMBERS

1 drift tube

2 First drift tube end

4 Second drift tube end

6 mean raw r

8 Through hole with drift area

10 ring electrodes

12 Through hole for multi capillary column

14 multi-capillary column

16 ionization source

18 barrier grid

22 Shielding gate

22 detector

24 temperature control element

26 thermal insulator

Claims

claims

1 . Driftröhre (1) comprising a cylindrical body, in the wall thereof

at least one Mulitkapillarsäule (14), preferably parallel to the longitudinal axis, is arranged.

2. Driftröhre (1) according to claim 1, characterized in that the

Multi-capillary column (14) has a temperature control element (24) for controlling the temperature in the multi-capillary column (14), preferably that is

Temperature control element (24) around the multi-capillary column (14) is arranged.

3. Driftröhre (1) according to any one of the preceding claims, characterized in that the multi-capillary column (14) by a thermal insulator (26) is thermally insulated.

4. Driftröhre (1) according to claim 2, characterized in that the

Multi-capillary column (14) and / or the temperature control element (24) and / or the thermal insulator (26) are non-metallic, is preferably made of glass or plastic.

5. Driftröhre (1) according to any one of the preceding claims, characterized in that the multi-capillary column (14) has a stationary phase, preferably silica gel / alumina, and / or a mobile phase, preferably hexane / ethyl acetate / dichloromethane / methanol.

6. Driftröhre (1) according to any one of the preceding claims, characterized in that the multi-capillary column (14) has a frit at its output end.

7. An ion mobility spectrometer, which is used to monitor anesthesia of a patient during a medical procedure, with a drift tube (1) according to one of the preceding claims.