GB2050686A

GB2050686A - Apparatus for Analyzing Liquid Samples with a Mass Spectrometer

Info

Publication number: GB2050686A
Application number: GB8012654A
Authority: GB
Original assignee: Hewlett Packard Co
Current assignee: HP Inc
Priority date: 1979-05-25
Filing date: 1980-04-17
Publication date: 1981-01-07
Also published as: DE3013620A1; FR2457562A1; JPS55156859A

Abstract

In apparatus for analyzing liquid samples by a mass spectrometer, a stream of liquid droplets of the sample formed by probe 11 is expelled as droplets into desolvation chamber 37, the droplets evaporated therein and the evaporated materials injected into the spectrometer source region. In some embodiments, no solvent or solute is pumped out of the desolvation chamber during transit; discrimination against highly volatile materials is thereby prevented. The apparatus may be used as an interface between a liquid chromatograph and the mass spectrometer. Temperature control is by circulating liquid 30, chamber 37 has non-reactive walls (e.g. Au), and filter 28 prevents clogging. Aperture and droplet sizes are specified. The length of chamber 37 may be variable (Fig. 2, not shown), and temperature controlled by an infra red heater. An acoustic transducer (e.g. piezo-electric) may stimulate the probe to break up the liquid stream into droplets. Tribo- electric jet-exit port reaction allows focussing by eletrostatic plates, and charging also encourages repulsion and minimises coalescence. Increase of surface charge density with desolvation also encourages the droplets to further break up and speed the evaporation process. <IMAGE>

Description

SPECIFICATION Apparatus for Analyzing Liquid Samples with a Mass Spectrometer This invention is concerned with the introduction of liquid samples into the source region of a mass spectrometer. The invention has particular applicability as an interface between the output of a liquid chromatograph (LC) and a mass spectrometer, enabling the use of the mass spectrometer as an analyzer for the LC. There has recently been much effort devoted to this problem, a summary of which is provided in the paper entitled, "On-Line Liquid Chromatography Mass Spectrometry: The monitoring of HPLC Effluents by a Quadrapole Mass Spectrometer and a Direct Liquid Inlet Interface (DLI)", published by Patrick J. Arpino, in the Instrurnental Applications in Forensic Drug Chemistry Proc. Int.

Symp., May 29-30, 1978, edited by Klein, Krugel, and Sobol.

Among methods mentioned in that article for introducing the LC effluent into the mass spectrometer are several in which the liquid leaving the LC is instantly vaporized at or near the tip of a capillary tube; the same is thereby introduced into the mass spectrometer source in gaseous form. Such a system is also described in U.S. Patent No. 3,997,298. It has been found to be a deficiency in such systems that the capillary frequently becomes plugged with residue of the sample and the solvent in which the sample is dissolved; this occurs apparently because of evaporation at the solvent-vapor interface within the capillary tip when the temperature rises about the solvent boiling point. Another prior art system in which the liquid is heated and vaporized is discussed by H. R. Udseth, R. G. Orth, and J. H.

Futrell, in a paper entitled, "An LC-MS Interface" presented at the Annual Conference on Mass Spectrometry in St. Louis, Missouri, U.S.A., in June 1978.

A different system, is discussed by Tsuge, Hirata, and Takeuchi in an article entitled, "Vacuum Nebulizing Interface for Direct Coupling of Micro-Liquid Chromatograph and Mass Spectrometer", published in Analytical Chemistry, Volume 51, No. 1, January 1979. In this system, a high velocity carrier gas streams by the liquid to form an aerosol, which is then sprayed into a pumping region, where the higher volatility solvent is pumped out. This system may prove to be disadvantageous in that it discriminates in favor of materials of low volatility, more highly volatile materials being preferentially pumped away together with the solvent.

The present invention provides apparatus for introducing a liquid solution of a solute dissolved in a solvent into the source region of a mass spectrometer, comprising probe means for forming a stream of liquid droplets of said solution and expelling said stream from said probe means; and desolvation means for evaporating said droplets after said droplets have been expelled from said probe means, and directing at least some of the evaporated materials into said source region of the mass spectrometer.

In apparatus as set forth in the last preceding paragraph, it is preferred that said desolvation means comprises a desolvation chamber adjacent said probe means, said stream of liquid droplets being expelled from said probe means into said desolvation chamber.

In apparatus as set forth in the last preceding paragraph, it is preferred that said desolvation chamber is configured to direct substantially all of said evaporated materials into said source region of the mass spectrometer.

In apparatus as set forth in any one of the last three immediately preceding paragraphs, it is preferred that said probe means comprises input means for accepting said liquid solution; and diaphragm means having an orifice therein in communication with said input means, said liquid solution being expelled from said orifice in the form of said stream of liquid droplets.

Apparatus as set forth in the last preceding paragraph may further comprise temperature control means for maintaining the temperature in said probe means below the boiling point of said liquid solution to insure that said solution emerges from said orifice in the form of said stream of liquid droplets.

In accordance with the illustrated preferred embodiments, the present invention provides an apparatus for analyzing liquid samples by a mass spectrometer. A highly directional jet of very fine liquid droplets containing the sample to be analyzed is first created. The liquid jet is evaporated prior to injection into the mass spectrometer, which, in preferred embodiments, is accomplished by spraying the jet into a desolvation chamber located upstream of the source region of the mass spectrometer. If the mass spectrometer is being utilized to analyze the effluent from a liquid chromatograph, the droplets will consist of the solute under analysis dissolved in the carrier solvent. The stream of liquid droplets evaporates as it passes through the desolvation chamber, so that a gaseous mixture of solvent and solute atoms enters the mass spectrometer source.The solvent may be selected so that the mass spectrometer will produce a chemical ionization (Cl) spectrum characteristic of the solute to be analyzed. In accordance with the invention, evaporation of the liquid droplets takes place during transit through the desolvation chamber. When used in conjunction with an LC, the present invention solves the problem of "plugging up" encountered by prior art systems, since the liquid is not vaporized at or near the tip of the LC output.

In some preferred embodiments, the system, is configured so that no solvent or solute is pumped out of the desolvation chamber during transit; discrimination against highly volatile materials is thereby prevented.

There now follows a detailed description which is to be read with reference to the accompanying drawings of apparatus according to the present invention; it is to be clearly understood that the apparatus has been selected for description to illustrate the invention by way of example and not by way of limitation.

In the accompanying drawings: Figure 1 shows a probe and desolvation chamber by means of which liquid samples can be analyzed with a mass spectrometer; and Figure 2 illustrates an embodiment of the invention in which the length of the desolvation chamber may be varied.

In Figure 1 there is shown an interface probe 11 of the general type which was disclosed by J.

Serum and A. Melera in a paper entitled, "A New LC-MS System" presented at the ASNS Meeting on June 1, 1978. A liquid sample 13 is injected into the probe 11; for example, the liquid may be the effluent output of a liquid chromatograph (LC) system. The sample 13 is transmitted through a column 1 5 into a chamber 17, which is essentially a volumetric region whose boundaries are defined by a metallic diaphragm 19 on one side and a surface 21 of a retaining element 23 on the other side. The diaphragm 1 9 includes a centrally positioned hole 20 therein with an inside diameter typically in the range of 5u--25. The diaphragm 19 is held in place by means of a cap 25 which is threaded onto the retaining element 23.The cap 25 also includes a centrally positioned hole 27 of inside diameter about .005"-.025". An O-ring 29 provides a vacuum seal. It is advantageous to include a filter to preclude clogging of the orifice 20, e.g., a thin filter element 28 may be positioned at the entrance to the orifice 20 as shown. This filter element 28 may be of a porous plastics material such as that which is commercially available under the Registered Trade Mark "Teflon".

The temperature in the chamber 1 7 is controlled to keep the liquid solution in the chamber below its boiling point, in order that the solution will emerge in liquid droplet form.

Temperature control may be accomplished by circulating a liquid 30 (for example, water) through a channel 31 into a region 33 in contact with the chamber 17 through a wall 35 of the retaining element 23. As indicated by the large arrows in Figure 1, water circulates into the apparatus through a channel 31 and back out through a larger channel, a portion of which is labelled 33.

The above-despribed probe 11 may be used as a component in an apparatus according to the present invention by selecting the size of the orifice 20 in the diaphragm 19, the flow rate of the sample 13, and the temperature of the coolant flowing in the channel 31 so that a jet of very fine liquid droplets is continuously formed and sprayed from the probe 11 through the opening 27. In a preferred embodiment, droplets of size in the range 1 Om-5Oum are produced using an orifice 20 of the size in the range of 5m--20ym, along with a sample flow rate in the range of 15y1/min- 4-0y1/min and a water temperature in the range 100C--400C. The probe 11 is brought into contact with a desolvation chamber 37.By desolvation chamber is meant a chamber in which the droplets lose their solvent under the influence of elevated temperature and low pressure as they traverse the chamber. Thus, a jet stream of liquid droplets 39 is emitted from the probe 11 into the chamber 37, which should have non-reactive walls, such as gold. The temperature and pressure in the chamber 37 are preferentially regulated so that the liquid droplets are not permitted to "freeze".

In the embodiments illustrated in Figures 1 and 2, the pressure in the chamber 37 is essentially determined by the rate of liquid flow into the chamber 37 from the probe 11 in conjunction with the rate of flow of gas out of the chamber 37 into the MS source region (labelled 45 in Figure 2). In an exemplary case of a jet stream consisting of cortisol as a solute dissolved in a solvent of acetonitrile/water in a 1:1 ratio, temperatures in the range of 2500C-3500C combined with pressures in the range 10 Torr-50 Torr are appropriate. The length of the chamber 37 is chosen to obtain an optimal desolvation pattern for droplets of different solute composition, size, or droplet frequency. For the solute and solvent described above, good results were obtained with a chamber of length about 2.0 cm.

Figure 2 illustrates an embodiment in which the length of the chamber 37 is variable by providing that the probe 11 be inserted into the chamber 37 up to a desired depth. For example, a mechanical connection such as a threaded connector between the probe 11 and the chamber 37 may be used which allows for adjustment of the insertion depth of the probe 11 into the desolvation chamber 37. Also shown in Figure 2 is a heating element 41, e.g. an infrared heater which is used to control the temperature in the chamber. An acoustic transducer 42 (such as a piezoelectric transducer) may be used to stimulate the probe 11 to break up the liquid stream into droplets of equal size. In this mode, the desolvation time for each droplet is the same as for all other droplets, so that no excess heating is required to evaporate large droplets.

It has been found, experimentally, that a triboelectrical interaction between the liquid jet and the exit port from the probe 11 can induce significant charging of the droplet stream. For example, a jet velocity of about 200 m/s produces a current of about 1 nanoamp at a liquid flow rate of 40y1/min through the orifice 20 of diameter 5,um (for the exemplary solvent described above).

This charging effect makes possible the inclusion of a set of electrostatic plates 43 to focus the particles into the mass spectrometer (MS) source 45. Another effect of the charging process is that the droplets tend to repel each other in flight, thereby minimizing particle coalescence.

Moreover, as desolvation proceeds, the surface charge density tends to increase and may exceed the surface tension area. At this point, the droplet explodes into smaller droplets, which process can be repeated again. The result is to speed up the evaporation process.

The preferred embodiments of Figures 1 and 2 illustrate another aspect of the invention; i.e., it is not required or necessary to "pump out" the desolvation chamber 37 to produce evaporation.

Thus, in these preferred embodiments, the desolvation chamber 37 provides a closed region between the probe 11 and the MS source 45.

Thus, all of the solute and solvent molecules in the jet stream may potentially be directed into the MS source 45 after desolvation has occurred, with no discrimination against the more volatile components of the jet stream.

Claims

1. Apparatus for introducing a liquid solution of a solute dissolved in a solvent into the source region of a mass spectrometer, comprising probe means for forming a stream of liquid droplets of said solution and expelling said stream from said probe means; and desolvation means for evaporating said droplets after said droplets have been expelled from said probe means, and directing at least some of the evaporated materials into said source region of the mass spectrometer.

2. Apparatus according to claim 1 wherein said desolvation means comprises a desolvation chamber adjacent said probe means, said stream of liquid droplets being expelled from said probe means into said desolvation chamber.

3. Apparatus according to claim 2 wherein said desolvation chamber is configured to direct substantially all of said evaporated materials into said source region of the mass spectrometer.

4. Apparatus according to any one of the preceding claims wherein said probe means comprises input means for accepting said liquid solution; and diaphragm means having an orifice therein in communication with said input means, said liquid solution being expelled from said orifice in the form of said stream of liquid droplets.

5. Apparatus according to claim 4 and further comprising temperature control means for maintaining the temperature in said probe means below the boiling point of said liquid solution, to insure that said solution emerges from said orifice in the form of said stream of liquid droplets.

6. Apparatus for introducing a liquid solution of a solute dissolved in a solvent into the source region of a mass spectrometer substantially as hereinbefore with reference to the accompanying drawings.