WO2000019193A1 - Dispositif d'electronebulisation a courant divergent pour spectrometrie de masse - Google Patents

Dispositif d'electronebulisation a courant divergent pour spectrometrie de masse Download PDF

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Publication number
WO2000019193A1
WO2000019193A1 PCT/US1999/022323 US9922323W WO0019193A1 WO 2000019193 A1 WO2000019193 A1 WO 2000019193A1 US 9922323 W US9922323 W US 9922323W WO 0019193 A1 WO0019193 A1 WO 0019193A1
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WO
WIPO (PCT)
Prior art keywords
electrospray
flow
conduit
main
liquid
Prior art date
Application number
PCT/US1999/022323
Other languages
English (en)
Inventor
Inc. Varian
Gregory J. Wells
Roger C. Tong
Peter P. Yee
Original Assignee
Varian Inc
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 Varian Inc filed Critical Varian Inc
Publication of WO2000019193A1 publication Critical patent/WO2000019193A1/fr

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Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • G01N30/724—Nebulising, aerosol formation or ionisation
    • G01N30/7266—Nebulising, aerosol formation or ionisation by electric field, e.g. electrospray
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0013—Miniaturised spectrometers, e.g. having smaller than usual scale, integrated conventional components
    • H01J49/0018—Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]

Definitions

  • the present invention relates to electrospray apparatus and methods, and more specifically, to a device which efficiently performs electrospray ionization at large liquid flow rates.
  • Mass spectrometers have become common tools in chemical analysis. Generally, mass spectrometers operate by separating ionized atoms or molecules based on differences in their mass-to-charge ratio (m/e). A variety of mass spectrometer devices are commonly in use, including ion traps, quadrupole mass filters, and magnetic sector mass analyzers. The general steps in performing a mass-spectrometric analysis are: (1) create gas-phase ions from a sample; (2) separate the ions in space or time based on their mass-to-charge ratio; and (3) measure the quantity of ions of each selected mass-to-charge ratio.
  • a mass spectrometer system consists of an ion source, a mass-selective analyzer, and an ion detector.
  • magnetic and electric fields may be used, either separately or in combination, to separate the ions based on their mass-to-charge ratio.
  • the mass-selective analyzer portion of a mass spectrometer system will simply be called a mass spectrometer. Ions introduced into a mass spectrometer are separated in a vacuum environment.
  • the liquid sample to be analyzed is pumped through a capillary tube or needle.
  • a potential difference (of for example, three to four thousand volts) is established between the tip of the electrospray needle and an opposing wall, capillary entrance, or similar structure.
  • the needle can be at an elevated potential and the opposing structure can then be grounded; or the needle can be at ground potential and the opposing structure can be at the elevated potential (and of opposite sign to the first case).
  • the stream of liquid issuing from the needle tip is broken up into highly charged drops by the electric field, forming the electrospray.
  • An inert drying gas such as dry nitrogen gas (for example) may also be introduced through a surrounding capillary to enhance nebulization (droplet formation) of the fluid stream.
  • the electrospray drops consist of sample compounds in a carrier liquid and are electrically charged by the electric potential as they exit the capillary needle.
  • the charged drops are accelerated in an electric field and injected into the mass spectrometer, which is maintained at a high vacuum.
  • the carrier liquid in the drops starts to evaporate giving rise to smaller, increasingly unstable drops which liberate surface ions into the vacuum for analysis.
  • the desolvated ions pass through sample cone and skimmer lenses, and after focusing by a RF lens, into the high vacuum region of the mass spectrometer, where they are separated according to mass-to-charge ratio and detected by an appropriate detector (e.g., a photo-multiplier tube).
  • electrospray method is very useful for analyzing high molecular weight dissolved samples, it does have some limitations.
  • commercially available electrospray devices utilizing only electrospray nebulization to form the spray are practically limited to liquid flow rates of 20-30 microliters/min, depending on the solvent composition. Higher liquid flow rates result in unstable and inefficient ionization of the dissolved sample. When used in conjunction with a liquid chromatograph, this acts as a limitation on the flow from the chromatograph.
  • One method of improving the performance of electrospray devices at higher liquid flow rates is to utilize a pneumatically assisted electrospray needle. As shown in Figs.
  • one example of such a needle 10 is formed from two concentric, capillary tubes (elements 14 and 22 in the figure).
  • the sample-containing liquid 12 flows through the inner tube 14 and a nebulizing gas 16 flows through the annular space between the two tubes.
  • This improves the efficiency of the ionization process by improving the ability of the electrospray needle 20 to form drops 18 from the sample liquid.
  • the drops formed are too large and degrade the performance of the mass spectrometer (by increasing the noise) if allowed to enter the device.
  • electrospray needles are still not capable of being efficiently used with a liquid chromatograph, which typically has a relatively high flow rate at its output.
  • Another conventional device utilizes a flow restrictor to control the portion of the main flow which is re-directed to a sampling needle.
  • the split ratio (the relative portion of the main fluid flow which is directed to the sampling needle) is variable, but once set it remains approximately constant over a wide range of input flow rates.
  • the fluid flow rate through the sampling needle increases proportionally. At sufficiently high fluid flow rates into the main conduit, this can cause the output of the sampling needle to be greater than the optimal value for input to a mass spectrometer.
  • the quality of the electrospray degrades as liquid flow rates increase. Pneumatic, mechanical, or thermal means are required to assist in nebulizing large liquid flow rates for electrospray. Finding the optimum operating conditions can be difficult, as the quality of electrospray is a function of multiple parameters (liquid flow rate, gas flow rate, geometry, and voltage);
  • pneumatic nebulization requires gas plumbing and hardware to provide pressure and/or flow control.
  • disposal of significant amounts of vapor and condensate are issues when large liquid flows are nebulized for electrospray.
  • the present invention is directed to an electrospray apparatus for producing gas-phase ions from a liquid sample matrix.
  • the electrospray needle of the present invention includes a main flow conduit through which the sample containing solution flows at a high flow rate (i.e., higher than which an electrospray tip can effectively ionize without nebulization assistance).
  • a sampling tube with an electrospray tip intersects the main flow conduit. In the absence of an electric field to cause droplet formation by the electrospray process, no liquid will flow through the sampling tube. In the presence of an electric field, droplets will be formed at the electrospray tip of the sampling tube.
  • the sampling tube continuously pulls in a portion of the fluid sample from the main flow conduit.
  • the flow through the sampling tube is formed into an electrospray and provided to a mass spectrometer or other instrument.
  • the inventive structure splits off a portion of the main flow prior to electrospraying, with the split flow rate being independent of the input flow rate through the main conduit. This permits setting the flow rate out of the electrospray needle to an optimized rate for input to a mass spectrometer, while permitting an input flow rate into the main flow conduit which is optimized for the output of a liquid chromatograph or other desired instrument.
  • Figs. 1 A and IB are schematic diagrams showing a cross-sectional side view (1 A) and an end view (IB) of a prior art device for forming an electrospray from a liquid sample.
  • Figs. 2A and 2B are schematic diagrams showing a cross-sectional side view (2A) and an end view 2(B) of a first embodiment of the split flow electrospray device of the present invention.
  • Fig. 3 is a schematic diagram showing a cross-sectional side view of a second embodiment of the split flow electrospray device of the present invention.
  • Fig. 4 is a schematic diagram showing a cross-sectional side view of a third embodiment of the split flow electrospray device of the present invention.
  • Fig. 5 is a schematic diagram showing a cross-sectional side view of a fourth embodiment of the split flow electrospray device of the present invention.
  • Fig. 6 is a schematic diagram showing a fifth embodiment of the split flow electrospray device of the present invention. DETAD ED DESCRIPTION OF THE INVENTION
  • the present invention is a configuration for an electrospray needle or capillary which is designed for use in situations of a relatively high flow rate of a liquid sample matrix, such as from the output of a liquid chromatograph.
  • the invention is especially useful in situations in which the flow rate is too high to obtain a satisfactory electrospray without the use of a nebulizing gas and the accompanying elements.
  • the present invention is capable of forming an acceptable electrospray for relatively high input flow rates without the use of a nebulizing gas.
  • FIGS 2A and 2B are schematic diagrams showing a side view (2A) and an end view 2(B) of a first embodiment of the split flow electrospray device 100 of the present invention.
  • the inventive electrospray device includes a main flow conduit 102 through which the liquid sample matrix (i.e., the sample compound contained in a carrier liquid or liquids) 104 flows.
  • the liquid sample matrix i.e., the sample compound contained in a carrier liquid or liquids
  • LC liquid chromatograph
  • a sampling tube 106 with an electrospray tip passes through the outer wall of main conduit 102 through which flows the sample matrix from its source, such as the output of a LC (not shown).
  • Sampling tube 106 intersects the liquid flow in the conduit 102.
  • Sampling tube 106 continuously diverts a portion of the sample liquid 104 from main flow conduit 102.
  • the flow through the sampling tube is formed into an electrospray 110 and may, therefore, be provided to a mass spectrometer or another mass-analyzing instrument.
  • the inventive arrangement results in a flow split off of the main flow, prior to electrospraying. This allows setting of the flow rate out of the electrospray needle to be made compatible with the optimized rate for input to a mass spectrometer, while permitting a higher flow rate in main conduit 102.
  • the sample liquid is pulled into electrospray needle 106 by a combination of capillary action of the needle on the fluid flow in the main conduit and pressure in the main conduit. Initiation of the flow of fluid up the needle is caused by the pressure differential between the needle and the main conduit.
  • Alternate embodiments of the present invention include electrospray needles which utilize other mechanisms to initiate and maintain the flow through the sampling tube.
  • the driving force(s) that produces flow through the tube can include any combination of capillary action, electro-osmotic flow, and pressure (which may be either actively or passively produced).
  • sampling tube angles other than normal relative to the flow direction of the main flow conduit can be used to passively change the pressure drop across the sampling tube. Such an embodiment is shown in Figure 3 (in which sampling electrospray tube 106 is oriented at an angle ⁇ with respect to the longitudinal axis of the main conduit). Similarly, back pressure in the main conduit may be adjusted by changing the resistance to the fluid flow downstream.
  • FIG. 4 shows an embodiment of the present invention in which a mixing section 200 for liquids is provided prior to removal of a portion of the mixed flow through sampling tube/electrospray needle 202 to form the electrospray 204.
  • Liquid ports 206 and 207 are used to introduce the liquid sample matrix and a desired fluid for mixing.
  • Discharge port 208 provides an exit for the fluid flow not subjected to electrospraying.
  • Multiple, parallel sampling/electrospray tubes 105 may be utilized to obtain an increased ion generation rate, or for other purposes such as providing an electrospray to multiple analysis instruments. See Figure 5, which shows an embodiment of the present invention in which multiple electrospray needles 105 are provided to extract fluid from main flow conduit 102.
  • Another embodiment of the present invention includes a reservoir 210 containing the liquid sample matrix 213, with a sampling tube/electrospray needle 212 inserted. This embodiment operates by adjusting the pressure inside reservoir 210 by means of pressure control port 214 in contrast to the flow sampling or splitting structure of the previous embodiments.
  • This embodiment is shown in Figure 6.
  • This embodiment of the invention is suited for introducing a mass calibrating fluid into a mass spectrometer without the use of a pump.
  • the calibrating fluid does not have to flow through the LC column, and therefore it is possible to draw it from the reservoir by electrospraying it from the end of the sampling tube.
  • the advantages of the present invention over prior art electrospray devices include: (1) pneumatic nebulization or mechanical (e.g.
  • ultrasonic assistance is not required to form an electrospray from large liquid flow rates;
  • the flow to the electrospray tip is only that which can be effectively electrosprayed without assistance of such nebulizing or assisting elements;
  • the device is relatively flow rate insensitive, i.e., changes in the flow rate through the main conduit have little or no effect on the electrospray flow rate;
  • excess flow that which is split off and not electrosprayed flows out of a discharge tube, and can easily be collected; and
  • the invention produces more efficient sample transfer to the mass spectrometer because of lower liquid flow rates which can be optimized to that most efficiently used by the spectrometer.
  • the sampling tube should be “primed” by some means prior to proper operation of the inventive system. Priming acts to fill the sampling tube with liquid and displace air within the tube. This is important because air bubbles within the tube will stop the electrospray process from occurring when the air is encountered. Priming can be done in several ways, e.g., temporarily increasing the restriction at the end of the main flow conduit, thus forcing liquid through the sampling tube.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

L'invention porte sur un appareil d'électronébulisation destiné à produire des ions en phase gazeuse à partir d'une matrice de prélèvement de liquides. L'aiguille d'électronébulisation (ou capillaire) (202) inclut un conduit d'écoulement principal à travers lequel la solution contenant le prélèvement s'écoule à un débit élevé (supérieur, par exemple, à celui qu'une buse d'électronébulisation peut effectivement ioniser sans assistance de nébulisation). Un tube de prélèvement muni d'une buse d'électronébulisation croise le conduit d'écoulement principal. Ce tube de prélèvement pompe en permanence une partie du prélèvement liquide à partir du conduit d'écoulement principal. L'écoulement à travers le tube de prélèvement est formé en électronébulisation (204) et distribué à un spectromètre de masse ou autre instrument. La structure de l'invention provoque une divergence d'une partie de l'écoulement principal (200) préalablement à l'électronébulisation, le débit du courant divergent étant indépendant de la vitesse du débit d'entrée à travers le conduit principal. Cela permet, d'une part de fixer le débit sortant de l'aiguille d'électronébulisation à une vitesse optimisée en vue de sa distribution dans un spectromètre de masse, d'autre part d'injecter un débit d'entrée dans le conduit d'écoulement principal, lequel est optimisé pour la sortie d'un chromatographe en phase liquide.
PCT/US1999/022323 1998-09-28 1999-09-27 Dispositif d'electronebulisation a courant divergent pour spectrometrie de masse WO2000019193A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16226098A 1998-09-28 1998-09-28
US09/162,26019980928 1998-09-28

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WO2000019193A1 true WO2000019193A1 (fr) 2000-04-06

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2370519A (en) * 2000-11-13 2002-07-03 Agilent Technologies Inc Micro-device with electro-spray emitter
EP3746760A4 (fr) * 2018-01-30 2021-10-13 UT-Battelle, LLC Sonde d'échantillonnage
US11313841B2 (en) 2015-04-09 2022-04-26 Ut-Battelle, Llc Open port sampling interface
WO2023012619A1 (fr) * 2021-08-01 2023-02-09 Dh Technologies Development Pte. Ltd. Système de transport de liquide ayant de multiples buses de nébuliseur
US11892383B2 (en) 2015-04-09 2024-02-06 Ut-Battelle, Llc Capture probe

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0655769A1 (fr) * 1993-11-17 1995-05-31 Hewlett-Packard Company Méthode et dispositif pour la préparation d'un échantillon pour source d'ions du type électrospray
EP0715337A1 (fr) * 1994-11-28 1996-06-05 Hitachi, Ltd. Spectrométric de masse pour des solutions et dispositif associé
US5595712A (en) * 1994-07-25 1997-01-21 E. I. Du Pont De Nemours And Company Chemical mixing and reaction apparatus
WO1997004297A1 (fr) * 1995-07-21 1997-02-06 Northeastern University Systeme permettant des transferts de micro-quantites de fluide
WO1998007505A1 (fr) * 1996-08-21 1998-02-26 Sheehan Edward W Procede et appareil perfectionnant l'analyse par electropulverisation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0655769A1 (fr) * 1993-11-17 1995-05-31 Hewlett-Packard Company Méthode et dispositif pour la préparation d'un échantillon pour source d'ions du type électrospray
US5595712A (en) * 1994-07-25 1997-01-21 E. I. Du Pont De Nemours And Company Chemical mixing and reaction apparatus
EP0715337A1 (fr) * 1994-11-28 1996-06-05 Hitachi, Ltd. Spectrométric de masse pour des solutions et dispositif associé
WO1997004297A1 (fr) * 1995-07-21 1997-02-06 Northeastern University Systeme permettant des transferts de micro-quantites de fluide
WO1998007505A1 (fr) * 1996-08-21 1998-02-26 Sheehan Edward W Procede et appareil perfectionnant l'analyse par electropulverisation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VANHOUTTE K ET AL: "DEVELOPMENT OF A NANOSCALE LIQUID CHROMATOGRAPHY/ELECTROSPRAY MASS SPECTROMETRY METHODOLOGY FOR THE DETECTION AND IDENTIFICATION OF DNA ADDUCTS", ANALYTICAL CHEMISTRY,US,AMERICAN CHEMICAL SOCIETY. COLUMBUS, vol. 69, no. 16, 15 August 1997 (1997-08-15), pages 3161-3168, XP000699503, ISSN: 0003-2700 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2370519A (en) * 2000-11-13 2002-07-03 Agilent Technologies Inc Micro-device with electro-spray emitter
GB2370519B (en) * 2000-11-13 2004-08-04 Agilent Technologies Inc Microdevice for handling fluid samples
US11313841B2 (en) 2015-04-09 2022-04-26 Ut-Battelle, Llc Open port sampling interface
US11585792B2 (en) 2015-04-09 2023-02-21 Ut-Battelle, Llc Open port sampling interface
US11885778B2 (en) 2015-04-09 2024-01-30 Ut-Battelle, Llc Open port sampling interface
US11892383B2 (en) 2015-04-09 2024-02-06 Ut-Battelle, Llc Capture probe
EP3746760A4 (fr) * 2018-01-30 2021-10-13 UT-Battelle, LLC Sonde d'échantillonnage
WO2023012619A1 (fr) * 2021-08-01 2023-02-09 Dh Technologies Development Pte. Ltd. Système de transport de liquide ayant de multiples buses de nébuliseur

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