EP3631434A1 - Tube de dérive pour un spectromètre de mobilité ionique à colonne multicapillaire intégrée - Google Patents

Tube de dérive pour un spectromètre de mobilité ionique à colonne multicapillaire intégrée

Info

Publication number
EP3631434A1
EP3631434A1 EP18729604.1A EP18729604A EP3631434A1 EP 3631434 A1 EP3631434 A1 EP 3631434A1 EP 18729604 A EP18729604 A EP 18729604A EP 3631434 A1 EP3631434 A1 EP 3631434A1
Authority
EP
European Patent Office
Prior art keywords
drift
capillary column
drift tube
driftröhre
ion
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP18729604.1A
Other languages
German (de)
English (en)
Inventor
Gabriele SPRAVE-BAUMBACH
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
B Braun Melsungen AG
Original Assignee
B Braun Melsungen AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by B Braun Melsungen AG filed Critical B Braun Melsungen AG
Publication of EP3631434A1 publication Critical patent/EP3631434A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G01N27/622Ion mobility spectrometry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/08Measuring devices for evaluating the respiratory organs
    • A61B5/082Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4821Determining level or depth of anaesthesia
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/497Physical analysis of biological material of gaseous biological material, e.g. breath
    • HELECTRICITY
    • H05ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
    • H05HPLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
    • H05H7/00Details of devices of the types covered by groups H05H9/00, H05H11/00, H05H13/00
    • H05H7/22Details of linear accelerators, e.g. drift tubes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02Operational features
    • A61B2560/0223Operational features of calibration, e.g. protocols for calibrating sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02Operational features
    • A61B2560/0242Operational features adapted to measure environmental factors, e.g. temperature, pollution
    • A61B2560/0247Operational features adapted to measure environmental factors, e.g. temperature, pollution for compensation or correction of the measured physiological value
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/029Humidity sensors
    • HELECTRICITY
    • H05ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
    • H05HPLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
    • H05H1/00Generating plasma; Handling plasma
    • H05H1/24Generating plasma
    • H05H1/2406Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes
    • H05H1/2443Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes the plasma fluid flowing through a dielectric tube
    • H05H1/2465Generating plasma using dielectric barrier discharges, i.e. with a dielectric interposed between the electrodes the plasma fluid flowing through a dielectric tube the plasma being activated by inductive coupling, e.g. using coiled electrodes

Definitions

  • 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.
  • An ion mobility spectrometer / ion mobility spectrometer 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,
  • 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.
  • Ion mobility spectrometry is based on the fact that under normal pressure, strictly under ambient pressure generated ions in an electric field against the
  • drift gas drift 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
  • Vdr KE (vdr ftspeed, K elonenmobiltician, 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.
  • Signal intensity of the current on the Faraday plate 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
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • the ions in the drift tube move in an axial direction toward the Faraday plate.
  • 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.
  • 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
  • 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
  • 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)
  • 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.
  • 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.
  • this so-called screening grid aperture grid
  • 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
  • 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.
  • MCC multi-capillary column
  • 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.
  • 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.
  • multicapillary columns a large number of capillaries are bundled (up to thousands), each with a diameter of
  • 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 ⁇ _ to ml_, in particular with moist samples, as in regular breathing air analyzes
  • Multi-capillary columns are known in which both components are realized separately in one device.
  • An object of the invention is therefore to provide a compact and lightweight analyzer.
  • 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.
  • 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.
  • the cylindrical body is at least one, preferably radially centered, through bore /
  • Passage opening arranged, which forms the lonisations Scheme and at least one further, preferably parallel, through-hole / passage opening to
  • the multi-capillary column has a temperature control element for controlling the temperature in the multi-capillary column.
  • a temperature control element for controlling the temperature in the multi-capillary column.
  • 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
  • the multi-capillary column is thermally insulated.
  • a thermally insulating material / insulator is mounted, preferably annular around the multi-capillary column.
  • the thermal insulation is arranged in a ring around the temperature control element of the multi-capillary column.
  • 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.
  • 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.
  • 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.
  • 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
  • Such elements include, for example, parts of the stationary phase or foreign bodies / impurities.
  • 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.
  • 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.
  • FIG. 3 Front view of a drift tube according to the invention from FIG. 3.
  • 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
  • FIG. 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
  • an ionization source 16 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
  • FIG. 3 Front view of a drift tube 1 according to the invention of Figure 3.
  • a temperature control element 24 for example a heater (Within the Driftröhrenwandung) is arranged, which in turn is surrounded by a thermal insulator 26.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Physics & Mathematics (AREA)
  • Veterinary Medicine (AREA)
  • Analytical Chemistry (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physiology (AREA)
  • Pulmonology (AREA)
  • Plasma & Fusion (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un tube de dérive conçu compact qui présente un corps cylindrique dans la paroi duquel est ménagée au moins une colonne multicapillaire, de préférence parallèlement à l'axe longitudinal, ainsi qu'un spectromètre de mobilité ionique qui est destiné à surveiller une anesthésie d'un patient lors d'une intervention médicale et est équipé d'un tel tube de dérive.
EP18729604.1A 2017-05-24 2018-05-24 Tube de dérive pour un spectromètre de mobilité ionique à colonne multicapillaire intégrée Withdrawn EP3631434A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102017111459 2017-05-24
PCT/EP2018/063723 WO2018215621A1 (fr) 2017-05-24 2018-05-24 Tube de dérive pour un spectromètre de mobilité ionique à colonne multicapillaire intégrée

Publications (1)

Publication Number Publication Date
EP3631434A1 true EP3631434A1 (fr) 2020-04-08

Family

ID=64395376

Family Applications (4)

Application Number Title Priority Date Filing Date
EP18728563.0A Withdrawn EP3631433A1 (fr) 2017-05-24 2018-05-24 Tube à dérive à qualité de surface modifiée pour une utilisation dans un spectromètre à mobilité ionique
EP18729604.1A Withdrawn EP3631434A1 (fr) 2017-05-24 2018-05-24 Tube de dérive pour un spectromètre de mobilité ionique à colonne multicapillaire intégrée
EP18728081.3A Withdrawn EP3629916A1 (fr) 2017-05-24 2018-05-24 Ensemble d'électrodes pour un tube conducteur de particules
EP18728562.2A Active EP3629917B1 (fr) 2017-05-24 2018-05-24 Dispositif d'analyse pour analyser l'air expiré

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP18728563.0A Withdrawn EP3631433A1 (fr) 2017-05-24 2018-05-24 Tube à dérive à qualité de surface modifiée pour une utilisation dans un spectromètre à mobilité ionique

Family Applications After (2)

Application Number Title Priority Date Filing Date
EP18728081.3A Withdrawn EP3629916A1 (fr) 2017-05-24 2018-05-24 Ensemble d'électrodes pour un tube conducteur de particules
EP18728562.2A Active EP3629917B1 (fr) 2017-05-24 2018-05-24 Dispositif d'analyse pour analyser l'air expiré

Country Status (6)

Country Link
US (1) US20200170571A1 (fr)
EP (4) EP3631433A1 (fr)
CN (3) CN110662959A (fr)
ES (1) ES2890574T3 (fr)
RU (1) RU2761078C2 (fr)
WO (4) WO2018215619A1 (fr)

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KR20250002226A (ko) * 2022-04-12 2025-01-07 스페이스 에이지 테크놀로지스, 엘엘씨 기체 분자와 나노 입자를 선형 운동으로 구동하기 위한 베셀 튜브

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A-E KREUDER ET AL: "Characterization of propofol in human breath of patients undergoing anesthesia", INTERNATIONAL JOURNAL FOR ION MOBILITY SPECTROMETRY, SPRINGER-VERLAG, BERLIN/HEIDELBERG, vol. 14, no. 4, 29 October 2011 (2011-10-29), pages 167 - 175, XP019985549, ISSN: 1865-4584, DOI: 10.1007/S12127-011-0080-Y *
See also references of WO2018215621A1 *

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CN110662959A (zh) 2020-01-07
ES2890574T3 (es) 2022-01-20
RU2019143086A3 (fr) 2021-07-12
EP3629917B1 (fr) 2021-07-21
US20200170571A1 (en) 2020-06-04
WO2018215619A1 (fr) 2018-11-29
CN110678121B (zh) 2022-07-26
RU2019143086A (ru) 2021-06-24
CN110662486A (zh) 2020-01-07
CN110678121A (zh) 2020-01-10
RU2761078C2 (ru) 2021-12-03
EP3629916A1 (fr) 2020-04-08
WO2018215618A1 (fr) 2018-11-29
EP3631433A1 (fr) 2020-04-08
EP3629917A1 (fr) 2020-04-08
WO2018215622A1 (fr) 2018-11-29
WO2018215621A1 (fr) 2018-11-29

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