The instant invention relates generally to the field of mass spectrometry, and more particularly to a multi-stage ion transfer tube assembly for transferring ions from an ionization chamber of an ionization source to a lower pressure chamber of a mass spectrometer system.
A number of atmospheric pressure ionization (API) sources have been developed for producing ions from a sample at atmospheric pressure. One well-known and important example is the electrospray ionization (ESI) source. The electrospray ionization technique, and more specifically electrospray ionization sources interfaced to mass spectrometers, has opened a new era of study for the molecular weight determination of labile and involatile biological compounds. In electrospray ionization, singly or multiply charged ions in the gas phase are produced from a solution at atmospheric pressure. The mass-to-charge (m/z) ratio of the ions that are produced by electrospray ionization depends on the molecular weight of the analyte and the solution chemistry conditions. Fenn et al. in U.S. Pat. No. 5,130,538 describes extensively the production of singly and multiply charged ions by electrospray ionization at atmospheric pressure.
Briefly, the electrospray process consists of flowing a sample liquid through a small tube or needle, which is maintained at a high voltage relative to a nearby surface. The voltage gradient at the tip of the needle causes the liquid to be dispersed into fine electrically charged droplets. Under appropriate conditions the electrospray resembles a symmetrical cone consisting of a very fine mist of droplets of ca. 1 μm in diameter. Excellent sensitivity and ion current stability is obtained if a fine mist is produced. Unfortunately, the electrospray “quality” is highly dependent on the bulk properties of the solution that is being analyzed, such as for instance surface tension and conductivity. The ionization mechanism involves desorption at atmospheric pressure of ions from the fine electrically charged particles. In many cases a heated gas is flowed to enhance desolvation of the electrosprayed droplets. The ions created by the electrospray process are then mass analyzed using a mass analyzer.
In electrospray ionization the ions are formed in an ionizing region, which is generally maintained at atmospheric pressure, and are drawn through an orifice or ion transfer tube into a low-pressure region where they undergo a free jet expansion. U.S. Pat. No. 4,542,293 describes the use of an ion transfer tube for conducting ions between the ionizing electrospray region at atmospheric pressure and a low-pressure region. A glass, metal or quartz capillary is suitable for this purpose. Ions and gas are caused to flow from the ionization region through the ion transfer tube into the low-pressure region where the free jet expansion occurs. A conducting skimmer is disposed adjacent the end of the tube and is maintained in a field which causes further acceleration of the ions through a skimmer orifice and into a lower pressure region including focusing lenses and analyzing apparatus. Alternatively, the skimmer can be maintained at ground. The skimmer orifice samples a portion of the gas expanding in the free jet, effectively serving to separate the higher-pressure viscous gas flow of the free jet that is found in the first vacuum pumping stage from subsequent vacuum pumping stages, which are maintained at lower background pressure relative to the first pumping stage. Once ions pass through the skimmer orifice, they may be required to pass through one or more additional pumping stages before entering the mass analyzer.
For practical and cost reasons, limited pumping speeds are employed in mass spectrometer instrumentation. Consequently, only a small amount of the ion laden atmospheric pressure gas is “leaked” into vacuum through the ion transfer tube. This has the unfortunate effect of limiting the sensitivity of the mass spectrometer, thereby requiring higher concentration of analyte in the sample solution for detection by the mass spectrometer. One way to augment the sensitivity of a mass spectrometer, such that lower concentrations of analyte can be detected, is to increase the amount of analyte containing vapor that is transferred from the ionization region into the vacuum region of the mass spectrometer. This is accomplished by increasing the throughput of the ion transfer tube, either by increasing the tube diameter or by reducing the tube length. Unfortunately, the resulting increased gas load causes the pressures in the vacuum chambers to increase as well. Since it is necessary to maintain the mass analyzer and detector region under high vacuum conditions, the increase in pressure must be counteracted by increasing the number of vacuum pumps employed and/or increasing the pumping capacity of the vacuum pumps. Of course, increasing the number and/or capacity of the vacuum pumps also increases the cost of the mass spectrometer, as well as the power requirements, shipping weight and cost, and bench space requirements.
There is a need for a system that increases the throughput of the ion transfer tube interface and that does not require additional vacuum pumps or increased pumping capacity of the vacuum pumps.
According to an aspect of the instant invention there is provided a multi-stage ion transfer tube assembly for supporting fluid communication between an ionization chamber of an ionization source and a low-pressure chamber of a mass spectrometer system, the multi-stage ion transfer tube assembly comprising: N ion transfer tubes disposed in a consecutive fashion one relative to another and extending between the ionization chamber and the lower pressure chamber of the mass spectrometer system, each of the N ion transfer tubes having an inlet end and an outlet end and an axial channel extending therebetween, wherein N>1; and, N−1 distinct intermediate pressure chambers, each distinct intermediate pressure chamber enclosing the outlet end of one of the N ion transfer tubes and the inlet end of an adjacent one of the N ion transfer tubes.
According to an aspect of the instant invention, provided is an ion source comprising: an ionization chamber for producing ions from a sample; a multi-stage ion transfer tube assembly comprising a first ion transfer tube having an inlet end and an outlet end, a second ion transfer tube having an inlet end and an outlet end, and a first intermediate pressure chamber enclosing the outlet end of the first ion transfer tube and the inlet end of the second ion transfer tube, the inlet end of the second ion transfer tube in fluid communication with the outlet end of the first ion transfer tube such that ions and gas exiting the outlet end of the first ion transfer tube are sampled into the inlet end of the second ion transfer tube; a plate having an orifice defined therethrough, the orifice spaced-apart from the outlet end of the second ion transfer tube; a low-pressure chamber enclosing the outlet end of the second ion transfer tube and the plate, the low-pressure chamber in fluid communication with the ionization chamber via the multi-stage ion transfer tube assembly; and, at least a vacuum pump in fluid communication with the low-pressure chamber for establishing a pressure gradient between the ionization chamber and the low-pressure chamber.
According to an aspect of the instant invention, provided is a mass spectrometer system comprising: a multi-stage vacuum chamber for establishing a progressively reduced pressure from a front stage to a back stage, via a middle stage, the multi-stage vacuum chamber comprising a plate that is disposed between the front stage and the middle stage, the plate having an orifice defined therethrough for sampling ions from the front stage into the middle stage of the multi-stage vacuum chamber; an ionization source for producing ions from a sample in the liquid phase and at a pressure substantially higher than that of the front stage of the vacuum chamber, the ionization source comprising a multi-stage ion transfer tube assembly for introducing the ions into the front stage of the multi-stage vacuum chamber via at least one intermediate pressure chamber that encloses facing ends of two separate ion transfer tubes of the multi-stage ion transfer tube assembly; and, a mass analyzer disposed within the back stage of the multi-stage vacuum chamber for analyzing ions that are received from the middle stage of the multi-stage vacuum chamber.
According to an aspect of the instant invention, provided is a method for introducing ions into a vacuum chamber of a mass spectrometer, comprising: producing ions in an ionization chamber of an ionization source; sampling the ions from the ionization chamber into an intermediate pressure chamber via a first ion transfer tube, the pressure within the intermediate pressure chamber being maintained at a value that exceeds a maximum pressure for being sampled into the vacuum chamber of the mass spectrometer; sampling some of the ions from the intermediate pressure chamber via at least a second ion transfer tube, the at least a second ion transfer tube having an outlet end that is in communication with a low-pressure chamber, the pressure within the low-pressure chamber being maintained at a value that is less than a maximum pressure for being sampled into the vacuum chamber of the mass spectrometer; and, sampling some of the ions from the low-pressure chamber into the vacuum chamber of the mass spectrometer.
Exemplary embodiments of the invention will now be described in conjunction with the following drawings, in which similar reference numerals designate similar items:
a is an enlarged view of a multi-stage ion transfer tube assembly according to an embodiment of the instant invention;
b is an enlarged view of a one-stage ion transfer tube;
a is a simplified schematic diagram showing two consecutive ion transfer tubes of equal diameter;
b is a simplified schematic diagram showing two consecutive ion transfer tubes, wherein the first ion transfer tube has a smaller diameter than the second ion transfer tube;
c is a simplified schematic diagram showing two consecutive ion transfer tubes, wherein the first ion transfer tube has a larger diameter than the second ion transfer tube;
a is a simplified schematic diagram showing two consecutive ion transfer tubes in a spaced-apart end-to-end arrangement, with an inter-tube spacing (L) greater than zero;
b is a simplified schematic diagram showing two consecutive ion transfer tubes in an overlapping end-to-end arrangement, with an inter-tube spacing (L) less than zero;
c is a simplified schematic diagram showing two consecutive ion transfer tubes in a flush-mounted end-to-end arrangement, with an inter-tube spacing (L) equal to zero;
a is a simplified schematic diagram showing two consecutive ion transfer tubes, the axis of one ion transfer tube being offset with respect to the axis of the next ion transfer tube;
b is a simplified schematic diagram showing two consecutive ion transfer tubes, the angle between the longitudinal axes of the two consecutive ion transfer tubes being greater than 0° but less than 180°;
The following description is presented to enable a person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the disclosed embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments and applications without departing from the spirit and the scope of the invention. Thus, the present invention is not intended to be limited to the embodiments disclosed, but is to be accorded the widest scope consistent with the principles and features disclosed herein. Throughout the detailed description and in the claims that follow, it is to be understood that the term mass spectrometer is intended to include any kind of mass spectrometer or a hybrid combination of such mass spectrometers. Examples include but are not limited to: triple quadrupole, linear ion trap, cylindrical ion trap, 3D ion trap, Fourier transform ion cyclotron resonance, electrostatic ion traps, Fourier transform electrostatic ion trap, time of flight, and quadrupole time of flight. It is also to be understood that the term API probe is intended to include, by way of several non-limiting examples, an electrospray ionization (ESI) probe, a heated electrospray ionization (H-ESI) probe, an atmospheric pressure chemical ionization (APCI) probe, an atmospheric pressure photoionization (APPI) probe, and an atmospheric pressure laser ionization (APLI) probe. Furthermore, the term API probe is intended to include a “multi-mode” probe combining a plurality of the above-mentioned probe types. In general, the term API probe is intended to include any device that is capable of producing charged droplets or ions from a liquid or gas introduced into an API source.
Referring to
In the discussion that follows, it has been assumed that ion transfer tube 106 is a metallic ion transfer tube and that potentially, an electric field is established between the ion transfer tube and preceding or consecutive ion optical elements. Accordingly, ions that are entrained in the background gas of the ionization chamber 102 travel through the ion transfer tube 106 entrained in the gas flow, as explained in U.S. Pat. No. 4,977,320 and U.S. Pat. No. 5,245,186. Ions exit the outlet end 112 of ion transfer tube 106, enter into the low-pressure chamber 104, and are focused through orifice 116 of plate 118 (which can take the form of a skimmer) into a lower pressure chamber 120 of a not illustrated mass analyzer by the application of a suitable potential to a tube lens 122. Operation of tube lens 122 is well known, for instance as taught in U.S. Pat. No. 5,157,260, and the details are omitted from this description for the sake of improved clarity.
By way of a specific and non-limiting example, the length of ion transfer tube 106 is about 10 cm and the inside diameter is about 580 μm. When the ionization chamber 102 is maintained at 760 torr and the low-pressure chamber 104 is maintained at about 0.98 torr using two 30 m3/hour pumps, then the inflow from the ionization chamber 102 into ion transfer tube 106 is about 1.29 liters per minute.
Referring now to
Ions that are entrained in the background gas of the ionization chamber 202 travel inside the first ion transfer tube 206 due to the pressure differential that is established between its two opposite ends. Ions exit the outlet end 224 of the first ion transfer tube 206, enter into the intermediate pressure chamber 212, and are sampled into the second ion transfer tube 214 via an inlet end 226 thereof by the application of a suitable potential to a tube lens 228 that is adjacent the outlet end 224 of the first ion transfer tube 206. Similarly, ions travel through the second ion transfer tube 214, entrained in the gas flow. Ions exit the outlet end 230 of the second ion transfer tube 214, enter into the low-pressure chamber 204, and are focused through orifice 232 of skimmer 234 into a lower pressure chamber 236 of a not illustrated mass analyzer by the application of a suitable potential to a tube lens 238.
By way of a specific and non-limiting example, the length of the first ion transfer tube 206 is about 5 cm and its inside diameter is about 580 μm, and the length of the second ion transfer tube 214 is about 5 cm and its inside diameter is about 580 μm. When the ionization chamber 202 is maintained at about 760 torr, the intermediate pressure chamber 212 is maintained at about 3.8 torr using a first 30 m3/hour pump, and the low-pressure chamber 204 is maintained at about 0.98 torr using a second 30 m3/hour pump, then the inflow from the ionization chamber 202 into the first ion transfer tube 206 is about 2.56 liters per minute.
Referring now to
Ions that are entrained in the background gas of the ionization chamber 302 travel inside the first ion transfer tube 306 due to the pressure differential that is established between its two opposite ends. Ions exit the outlet end 334 of the first ion transfer tube 306, enter into the first intermediate pressure chamber 312, and are sampled into the second ion transfer tube 314 via an inlet end 336 thereof by the application of a suitable potential to a tube lens 338 that is adjacent the outlet end 334 of the first ion transfer tube 306. Similarly, ions travel inside the second ion transfer tube 314 due to the pressure differential that is established between its two opposite ends. Ions exit the outlet end 340 of the second ion transfer tube 314, enter into the second intermediate pressure chamber 320, and are sampled into the third ion transfer tube 322 via an inlet end 342 thereof by the application of a suitable potential to a tube lens 344 that is adjacent the outlet end 340 of the second ion transfer tube 314. Ions travel inside through the third ion transfer tube 322, entrained in the gas flow. Ions exit the outlet end 346 of the third ion transfer tube 322, enter low-pressure chamber 304, and are focused through orifice 348 of plate 350 (which can take the form of a skimmer) into a lower pressure chamber 352 of a not illustrated mass analyzer by the application of a suitable potential to a tube lens 354.
In more general terms an embodiment of the instant invention includes a multi-stage ion transfer tube assembly, which assembly includes N consecutive ion transfer tubes (N>1). Each additional ion transfer tube communicates the ions through a partition between two separate chambers, such that there are N−1 additional vacuum stages compared to the single-stage ion transfer tube system shown in
Since the inflow amount of gas is increased in the multi-stage ion transfer tube assembly system, the absolute number of ions being sampled also is increased compared to the single-stage ion transfer tube system. Transferring the ions from one ion transfer tube to a consecutive ion transfer tube via an intermediate pressure chamber has the effect of increasing the ion to background gas ratio in the gas that is eventually passed through to the low-pressure region immediately in front of the skimmer. This pre-concentration effect is considered further in the following sections.
Referring now to
The following relationships may be written for the case of the two-stage ion transfer tube assembly that is illustrated in
O2≅S2 (1)
C
2
=O
2
*P
f (2)
I
2
=C
2
/P
i (3)
O
1
=S
1
+I
2 (4)
C
1
=O
1
*P
i (5)
I
1
=C
1
/P
o (6)
Similarly, the following relationships may be written for the case of the one-stage ion transfer tube assembly that is illustrated in
Os≅Ss (7)
C
s
=O
s
*P
f (8)
I
s
=C
s
/P
o (9)
In equations (1) and (7) it has been assumed that Os≅Ss and that O2≅S2, which does not take into account a small leak rate through the skimmer orifice into the lower pressure chamber that houses the mass analyzer and detector. However, the small leak rate is negligible compared to the pumping capacity in both cases, and does not affect the current discussion in any meaningful way.
Equations (7), (8) and (9) may be rearranged in a straight forward manner to obtain:
I
s
=S
s
*P
f
/P
o (10)
With only slightly more effort, equations (1) through (6) may be rearranged to obtain:
I
1
=S
1
*P
i
/P
o
+S
2
*P
f
/P
o (11)
As stated above, it is assumed that Ss=S1+S2. It now will be further assumed that S1=S2=½Ss. Accordingly:
I
1
=S
s
*P
i/2Po+Ss*Pf/2Po (12)
But since Pi>Pf, therefore it may be determined from an inspection of equations (10) and (12) that I1>Is. In other words, the amount of ions per unit time that is sampled from the API source is always greater in the situation that is illustrated in
I
1
/I
s
=[S
1
*P
i
/S
s
*P
f
]+[S
2
/S
s] (13)
By substituting the relationship S2=Ss−S1 into equation (13), the following is obtained:
I
1
/I
s=1+(S1/Ss)[(Pi/Pf)−1] (14)
Since Pi/Pf>1, then I1/Is>1, or more succinctly I1>Is.
By increasing the inflow I1 of the first ion transfer tube with respect to the single stage ion transfer tube inflow Is, an increased volume rate of sample is let in from the API source into the mass spectrometer instrument. As discussed supra the charged particles are pre-concentrated from the other inflowing gas in the intermediate pressure chamber, and still the pressure in the analyzer region of the mass spectrometer instrument is limited to the usual value by restricting the throughput of the second ion transfer tube. The pre-concentration effect, which increases the analyte ion to background gas ratio and also the analyte ion to solvent cluster ion ratio, may occur for several reasons, including (but not limited to): (1) flyout/scattering of lighter particles such as background gas, e.g. nitrogen and oxygen, so sampling of the core of the expansion from the previous ion transfer tube by the subsequent ion transfer tube increases concentration of analyte ions on the center line; (2) electric field applied to focus analyte ions but not background neutrals and also to focus ions dependent on mass; and, (3) collisions, the frequency of which is dependent on pressure Pi in the intermediate pressure chamber, that break up solvent clusters.
Of course, a number of modifications to the multi-ion transfer tube assembly shown generally at
Further optionally, a focusing or deflecting electric field may be applied between the outlet end of a first ion transfer tube and the inlet end of a second ion transfer tube that is adjacent the first ion transfer tube. In
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
Optionally, a focusing or deflecting electric field is applied between the facing ends of the two consecutive ion transfer tubes in
It should be noted, that in referring to
A benefit of using ion transfer tubes of different diameters is that the tube lens can be removed so as to permit the first ion transfer tube to slide inside the second ion transfer tube, or vice versa. This is possible when the inside diameter of one ion transfer tube is bigger than the outside diameter of the other ion transfer tube. This concept could be used in order to discriminate heavier/larger particulates with respect to lighter/smaller particulates since during the expansion occurring between the ion transfer tubes lighter particulates are scattered away from the center axis with a wider angle compared to the heavier ones. Since the lighter particulates include small solvent clusters or laboratory air molecules such as nitrogen and oxygen, it is beneficial to decrease their concentration in the ions sampled from the ion source.
Optionally, the ion transfer tubes include those having a length in the range of about 0.13 mm (0.005″) to about 2.0 mm (0.080″), and therefore the entrance orifice coincides with the exit orifice such that the ion transfer tube in effect becomes an orifice. Further optionally, the ion transfer tubes and/or orifices can have a cross section that is other than circular. Further optionally, the ion transfer tubes are of different lengths one compared to another. In general and by way of non-limiting example, each ion transfer tube has a length of between about 2.5 cm (1.0″) and about 25 cm (10.0″), with a length of between about 2.5 cm (1.0″) and about 7.5 cm (3.0″) being a typical value for many applications. Furthermore, in general and by way of non-limiting example, each ion transfer tube has a diameter of between about 150 μm (0.006″) and about 8 mm (0.31″).
Referring now to
Referring now to
Numerous other embodiments may be envisaged without departing from the spirit and scope of the invention.