Integrated electrospray ion source

Abstract

In one aspect, an ion source for use in a mass spectrometry system is disclosed, which comprises a housing, a first and a second ion probe coupled to said housing, and a first and a second emitter configured for coupling, respectively, to said first and second ion probes. The first ion probe is configured for receiving a sample at a flow rate in nanoflow regime and the second ion probe is configured for receiving a sample at a flow rate above the nanoflow regime. Each of the ion probes includes a discharge end (herein also referred to as the discharge tip) for ionizing at least one constituent of the received sample. In some embodiment, each ion probe receives the sample from a liquid chromatography (LC) column. Further, the ion probes can be interchangeably disposed within the housing.

Claims

1. An ion source for use in a mass spectrometry system, comprising: a housing providing first and second openings, a first ion probe accommodating sample flow rates in a nanoflow regime and a second ion probe accommodating sample flow rates above nanoflow regime, the first opening being configured for coupling the first ion probe to the housing and the second opening being configured for coupling the second ion probe to the housing, each of said ion probes comprising a discharge tip for ionizing at least a constituent of a sample received by said probe, wherein each of said probes comprises an emitter extending beyond the discharge tip of the probe by a non-adjustable length, circuitry for determining if any of said first and second openings is plugged, wherein said circuitry comprises a resistance-measuring device for measuring electrical resistance across said first and second openings, and a controller for receiving values of said measured electrical resistance and processing said received resistance values to determine if any of said first and second opening is plugged.

2. The ion source of claim 1, wherein said two openings are configured such that said first and second probes are disposed at an angle relative to one another.

3. The ion source of claim 2, wherein said angle is about 90 degrees.

4. The ion source of claim 1, wherein said housing and said probes are configured such that the probes can be interchangeably disposed in said housing.

5. The ion source of claim 1, further comprising at least one heater disposed in said housing.

6. The ion source of claim 5, wherein said at least one heater comprises a first and a second heater and said first and second heaters are disposed non-coaxially relative to a longitudinal axis of at least one of said first and second probes.

7. The ion source of claim 6, wherein said first and second heaters and said at least one of said first and second ion probe are arranged in a non-coplanar manner.

8. The ion source of claim 1, wherein said ion source is configured for interfacing with a curtain plate of a mass spectrometer, wherein said curtain plate comprises an orifice through which at least a portion of the ions generated by any of said first and second ion probes enters downstream components of the mass spectrometer.

9. The ion source of claim 8, wherein said first opening of the housing and said first probe are configured such that said first probe is positioned in the housing such that a longitudinal axis thereof is substantially co-axial with a central axis associated with said orifice of said curtain plate.

10. The ion source of claim 9, wherein said second opening of the housing and said second probe are configured for positioning said second probe in the housing such that a longitudinal axis thereof is substantially orthogonal to said orifice axis.

11. The ion source of claim 1, wherein said first and second openings of the housing are configured for positioning said first and second ion probes in the housing such that discharge tips thereof are non-adjustably disposed relative to said orifice of the curtain plate.

12. The ion source of claim 1, wherein said ion source is operable with any of said first or said second probe.

13. The ion source of claim 1, wherein said ion source is operable with at least one of said first and second ion probes.

14. The ion source of claim 1, wherein any of said first and second ion probe is an electrospray ion probe.

15. The ion source of claim 14, wherein said electrospray ion probe comprises a nebulization assist.

16. The ion source of claim 1, further comprising at least one cap having a resistive element for plugging at least one of said openings in absence of an ion probe being coupled to the opening.

17. The ion source of claim 1, wherein each of the ion probes comprises an identification electrical resistance that differs from the respective identification electrical resistance of the other ion probe.

18. The ion source of claim 17, further comprising a resistance-measuring device for measuring the electrical resistance of each of said ion probes.

19. The ion source of claim 18, further comprising a controller in communication with said resistance-measuring device to receive the measured electrical resistance associated with each of the ion probes and process said measured electrical resistances to identify each of said probes as accommodating a flow rate in the nanoflow regime or above nanoflow regime.

20. The ion source of claim 19, further comprising a power supply for providing electrical power to said ion probes, and wherein said controller is in communication with the power supply to control the power supply based on received measurements of electrical resistance of the ion probes for application of electrical power to the probes.

21. The ion source of claim 1, wherein the source housing is sealed and comprises an actively pumped exhaust for removing gaseous by-products.

22. An ion source for use in a mass spectrometry system, comprising: a housing providing first and second openings, a first ion probe accommodating sample flow rates in a nanoflow regime and a second ion probe accommodating sample flow rates above nanoflow regime, said first opening being configured for coupling the first ion probe to the housing and said second opening being configured for coupling the second ion probe to the housing, each of said ion probes comprising a discharge tip for ionizing at least a constituent of a sample received by said ion probe, wherein each of said ion probes comprises an emitter fixedly positioned relative to a discharge tip of the probe, and at least one cap having a resistive element for plugging at least one of said openings in absence of an ion probe being coupled to the opening, and wherein said circuitry is configured to measure resistance of said resistive element for determining whether said opening is plugged.

23. The ion source of claim 22, wherein said circuitry comprises a resistance-measuring device for measuring the resistance of said resistive element and a controller for receiving said measured resistance and processing said measured resistance to determine whether the opening is plugged.

24. A mass spectrometer system, comprising: an ion source for generating ions, a curtain plate having an orifice for receiving at least a portion of said ions, and one or more mass analyzers disposed downstream of said orifice of the curtain plate, wherein said ion source comprises: a housing providing first and second openings, a first ion probe accommodating sample flow rates in a nanoflow regime and a second ion probe accommodating sample flow rates above nanoflow regime, the first opening being configured for coupling the first ion probe to the housing and the second opening being configured for coupling the second ion probe to the housing, each of said probes comprising an emitter for ionizing at least one constituent of a sample flowing through the ion probe, wherein the emitter of each of said ion probes extends beyond a discharge tip of the ion probe by a non-adjustable length, circuitry for determining if any of said first and second openings is plugged, wherein said circuitry comprises a resistance-measuring device for measuring electrical resistance across said first and second openings, and a controller for receiving values of said measured electrical resistance and processing said received resistance values to determine if any of said first and second opening is plugged.

25. The mass spectrometer of claim 24, wherein said openings of the housing are configured such that said ion probes can be positioned in the housing such that the discharge tip of each probe is positioned non-adjustably relative to said orifice of the curtain plate.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1A schematically depicts an ion source according to an embodiment interfaced with a curtain plate of a mass spectrometer, where the ion source includes two electrospray ion probes configured for accommodating different sample flow rates,

(2) FIG. 1B is a schematic view of the ion source depicted in FIG. 1A showing the ion probe accommodating flow rates above the nanoflow range and two heaters disposed in the housing of the ion source,

(3) FIG. 1C is another schematic view of the ion source depicted in FIG. 1A showing the ion probe accommodating flow rates in the nanoflow range and the two heaters,

(4) FIG. 1D is a schematic perspective view of the housing of an ion source according to an embodiment, where the housing includes two openings for coupling two ion probes independently to the housing,

(5) FIG. 2A is a schematic perspective view of a probe suitable for use in an ion source according to the present teachings,

(6) FIG. 2B is a schematic cross sectional view of the probe depicted in FIG. 2A,

(7) FIG. 2C is a partial schematic cross sectional view of the probe depicted in FIGS. 2A and 2B,

(8) FIG. 2D schematically depicts an ion source according to an embodiment in which one of the ion probes is disposed in one of the openings of the housing and the other opening of the housing is plugged,

(9) FIG. 2E schematically depicts an embodiment of an ion source in which only the ion probe accommodating flow rates above the nanoflow regime is coupled to the ion source's housing and the opening for receiving the other ion probe is plugged,

(10) FIG. 3 schematically depicts a mass spectrometer in which an ion source according to the present teachings is employed,

(11) FIGS. 4A and 4B present peak area sensitivity and normalized peak area sensitivity data, respectively, for a plurality of compounds obtained using a conventional electrospray ion source having an adjustable probe and emitter and an electrospray ion source having a probe that is fixedly positioned relative to the ion source housing and an emitter that is fixedly positioned relative to an ion source's probe,

(12) FIG. 5 presents data demonstrating the effect of protrusion of an emitter of an ion probe beyond the discharge tip of the probe, and

(13) FIG. 6 schematically depicts a system for identifying which ion probe, if any, is coupled to the housing of an ion source according to an embodiment of the present teachings.

DETAILED DESCRIPTION

(14) The present teachings are generally directed to an electrospray ion source for use in a mass spectrometry system, which can accommodate a wide range of sample flow rates, such as sample flow rates in the nanoflow regime and above the nanoflow regime. As discussed in more detail below, in many embodiments, the ion source can include two ion probes disposed in a housing, where one of the ion probes is configured to accommodate sample flow rates in the nanoflow regime and the other ion probe is configured to accommodate sample flow rates above the nanoflow regime.

(15) Various terms are employed herein consistent with their customary meanings in the art. By way of further clarification, the following terms are defined:

(16) The terms “nanoflow range” or “nanoflow regime” refer to flow rates less than about 1000 nanoliters/min, e.g., in a range of about 1 nanoliter/min to about 1000 nanoliters/min.

(17) The term “about” as used herein, for example, to modify a numerical value, is intended to indicate a variation of at most 5 percent.

(18) The term “substantially” as used herein refers to a deviation of at most 5 percent relative to a complete condition and/or state.

(19) The term “fixedly positioned” as referring to an element indicates that the position of that element is not adjustable by a user.

(20) FIGS. 1A, 1B, 1C and 1D schematically depict an ion source 10 according to an embodiment of the present teachings that includes a housing 12 providing two openings or ports 12a and 12b for coupling two ion probes to the housing. In this embodiment, two ion probes 14 and 16 are disposed in the housing 12 via the ports 12a and 12b. As discussed in more detail below, in other embodiments, only one of the ion probes 14 and 16 can be coupled to the housing via one of the ports and the other port can be plugged. In other words, the ion source 10 can be configured to operate with both ion probes or with only one of the ion probes. As discussed in more detail below, one advantage of the ion source 10 is that it allows for easy removal and replacement of the ion probes such that the ion source can be configured to operate with either or both of the ion probes.

(21) The ions probes 14 and 16 are configured to generate ions via electrospray ionization. As discussed in more detail below, the ion source 10 can be incorporated in a variety of different mass spectrometers for generating ions. Further, as discussed in more detail below, the ion source 10 is configured to accommodate different flow rates of samples to be ionized, including flow rates in the nanoflow range as well as above the nanoflow range. By way of example, the flow rates above the nanoflow range can be greater than 1000 nanoliters/min to about 3 milliliters/min.

(22) Referring to FIG. 1A, in this embodiment, the ion probes 14 and 16 are positioned relative to an aperture 18 of a curtain plate 20 of a mass spectrometer in which the ion source is incorporated such that at least some of the ions generated by the probes 14/16 would pass through the aperture (orifice) 18 to reach the downstream components of a mass spectrometer, such as downstream mass analyzers. The ion probe 14 is configured to accommodate sample flow rates in the nanoflow range. For example, in embodiments in which the ion probe 14 is coupled to a liquid chromatography (LC) column to receive a sample therefrom, the rate at which the sample can be delivered to the ion probe can be in the nanoflow range.

(23) The ion probe 14 is positioned relative to the aperture 18 such that its longitudinal axis A is substantially co-axial with an axis B passing through the aperture 18 and perpendicular to a plane thereof. In this manner, the ions generated by the ion probe 14 can be readily received by the aperture 18. In other words, the aperture 18 can receive the ions generated by the probe 14 at a rate substantially equal to the rate at which those ions are generated. When operating in the nanoflow regime, additional desolvating components can be located downstream from the curtain plate aperture, as described in U.S. Pat. No. 7,098,452. Hence, the axial positioning of the ion probe 14 relative to the aperture 18 results in high sensitivity due to the passage of a large fraction of ions generated by the probe 14 to the downstream components of a mass spectrometer in which the ion source is incorporated without, or at least with minimal, adverse effects on those downstream components.

(24) With continued reference to FIGS. 1A, 1B, 1C, and 1D, the ion probe 16 is in turn positioned such that its longitudinal axis C is substantially orthogonal to the axis B that is orthogonal to the plane of the orifice 18 of the curtain plate 20. As noted above, the ion probe 16 is configured to accommodate sample flow rates higher than flow rates in the nanoflow range. The orthogonal positioning of the ion probe 16 relative to the orifice 18 of the curtain plate 20 can ensure that sufficient number of ions enter the aperture 18 while minimizing, and preferably eliminating, the passage of a large number of residual droplets through the aperture 18 to the downstream components of a mass spectrometer in which the ion source is incorporated. In some cases, a large number of solvated ions can be due to endogenous and excipient compounds present in the sample liquid stream.

(25) In this embodiment, both the ion probe 14 and the ion probe 16 are fixedly (non-adjustably) positioned relative to the orifice 18 of the curtain plate 20. In other words, the positions of the ion probes, and more specifically the positions of their nozzles (i.e., exit orifices), are not adjustable relative to the orifice 18 of the curtain plate 20. More specifically, in this embodiment, an axial distance D1 between the nozzle 14a of the probe 14 and the orifice 18 of the curtain plate 20 is fixedly (non-adjustably) set in a range of about 0 millimeters (mm) to about 7 mm, e.g., about 1.9 mm. In some embodiments, the axial distance between the nozzle 14a (herein also referred to as the discharge end) of the probe 14 and the orifice 18 of the curtain plate 20 can be set with a tolerance of about 0.1 mm.

(26) Further, in this embodiment, an axial distance D2 between discharge nozzle 16a of the probe 16 and the orifice 18 of the curtain plate 20 is fixedly (non-adjustably) set at about 5.5 mm. More generally, the axial distance D2 can be in a range of about 2 mm to about 10 mm. In some cases, the axial distance D2 is set with a tolerance of 0.1 mm. Further, in this embodiment, the orthogonal distance D3 between the nozzle 16a of the probe 16 and the axis B of orifice 18 of the curtain plate 20 can be set fixedly (non-adjustably) at about 15.9 mm. More generally, the axial distance D3 can be in a range of about 6 mm to about 25 mm.

(27) As discussed in detail below, each ion probe 14/16 includes an emitter that extends by a fixed amount beyond the nozzle of the respective probe. The probes 14/16 can be any suitable probe that can be used for electrospray ionization (ESI) according to the present teachings. By way of example and with reference to FIG. 2A an exemplary ESI probe 200 includes a probe body 201 that extends from a proximal end (PE) to a distal end (DE).

(28) Referring to FIGS. 2A, 2B and 2C, the probe body 201 includes a channel 208 that extends from the proximal end (PE) to the distal end (DE) and in which an emitter 210 can be installed. The channel 208 includes an upper segment 208a that extends to a transition segment 208b, which in turn extends to lower segments 208c and 208d. In this embodiment, the portions of the probe body forming the upper segment 208a and the transition segment 208b, and the lower segment 208c of the channel 208 can be formed of a polymer, such as PEEK (poly ether ether ketone) while the portion of the probe body forming the lower segment 208d of the channel 208 can be formed of stainless steel.

(29) The emitter 210 extends beyond the distal end (DE) of the probe body (herein also referred to as the discharge end of the probe) by a fixed (non-adjustable) amount (D). The emitter 210 includes a channel 210a (e.g., a microchannel) that extends from an entrance end 211 to an ionization discharge end 212 of the emitter. The ionization discharge end 212 of the emitter extends out of the probe by a fixed (non-adjustable) amount D relative to the distal end (DE) of the probe body. The fixed distance D can be, for example, in a range of about 0.1 mm to about 2 mm. By way of example, the fixed distance D for the probe accommodating sample flow rates in the nanoflow range can be about 0.9 mm, and the fixed distance D for the probe accommodating sample flow rates above the nanoflow range can be about 1.0 mm.

(30) Referring again to FIGS. 1A, 1B, and 1C, in this embodiment, the ion source 10 can further include two heaters 200a and 200b that are coupled to the ion source housing 12 and are configured to generate heat for causing the desolvation of the ions generated by the ion probes 14 or 16, preferably before those ions reach the orifice 18 of the curtain plate 20. In this embodiment, the heaters 200a and 200b in FIG. 1B are disposed non-coaxially relative to the probes 14/16. In particular, the longitudinal axis C of the probe 16 is not along longitudinal axes H1 and H2 of the heaters 200a and 200b. Alternatively, the heaters can also be utilized as a gas source to provide temperature control over the path taken by the sample. The heaters can act as simple gas source for cooling or a heated gas source for heating of the distal end (DE) of the probe body, discharge tip of the emitter 212 in FIG. 2B, sample path and the curtain plate 20. In some aspects, the heaters can be located in a plane parallel to the mirror plane (symmetry plane bisecting the angle between the two probes) of the two probes but offset by about 4 mm towards the higher flow probe 16 (above the nanoflow probe). The offset can offer wider control over the higher flow probe region. The heater arrangement can provide thermal control for both probes, both sample paths, and both flow regimes. It will be appreciated that the orientation of the plane containing the heaters and its location may vary to accommodate different source geometries and liquid flow regime splits to achieve a desired level of thermal control over the environment to which the sample is exposed prior to its entry to the sampling orifice of the mass spectrometer.

(31) As noted above, in some embodiments, an ion source according to the present teachings can be operated with only one of the ion probes 14 and 16. For example, FIG. 2D schematically depicts such an embodiment in which the ion probe 14 is coupled to the ion source housing 12 via the port 12b and a plug 11 is employed to close off the port 12a, which is configured to receive the ion probe 16. In this manner, the ion source 10 is configured to operate with only the ion probe 14. By way of example, such a configuration can be useful in applications in which flow rates only in the nanoflow range are needed. FIG. 2D shows an additional heated element 99 located between the curtain plate 41 and the inlet of the mass spectrometer as described in U.S. Pat. Nos. 7,098,452 and 7,462,826, which are herein incorporated by reference.

(32) FIG. 2E schematically depicts another embodiment of the ion source 10 in which the ion probe 16 is coupled to the ion source housing 12 via the port 12a and a plug 11 is employed to close off the port 12b, which is configured to receive the ion probe 14. In this manner, the ion source 10 can be configured to operate with only the ion probe 16. By way of example, such a configuration can be useful in applications in which flow rates only above the nanoflow range are needed.

(33) An ion source according to the present teachings can provide a number of advantages. In particular, the fixation of the emitter relative to the probe in which the emitter is incorporated such that the emitter extends beyond the probe's discharge tip by a fixed (non-adjustable) length can be advantageous. In conventional ion sources in which the protrusion of an emitter beyond the discharge tip of a probe can be adjusted by a user, the protrusion adjustment of the emitter can be quite tedious especially for flow rates above the nanoflow regime. In particular, in a conventional electrospray ion source, as the flow rate of a sample introduced into the ion source's probe changes, the flow rate of a nebulizer gas introduced into the probe as well as the heat generated by one or more heaters disposed in a chamber to which the ion source is coupled are adjusted to optimize ionization and desolvation of the sample. Further, the length of protrusion of the emitter beyond the discharge tip of the probe is also adjusted to further optimize the ionization of the sample. Moreover, in many such conventional systems, the position of the discharge tip of the probe relative to the heater(s) and an inlet port of the mass spectrometer in which the ion source is incorporated can also be adjusted. Significantly, in conventional ion sources, different flow rates require different protrusion lengths of the emitter beyond the discharge tip of the probe. The optimization of the ionization process via adjustment of the emitter relative to the probe's tip can be difficult and typically requires a great deal of experience to accomplish.

(34) In contrast, in an ion source according to the present teachings, different probes are employed for flow rates in and above the nanoflow regime. It has been discovered that the use of different probes for accommodating such different flow rates allows fixing the emitter of an ion source relative to its probe, and particularly fixing the length by which the emitter protrudes beyond the probe's discharge tip. The use of different ion probes accommodating different sample flow rates and each having an emitter that is fixedly positioned within the probe advantageously eliminates the need for a user to adjust the emitter's position while allowing the use of different sample flow rates.

(35) An ion source according to the present teachings can be incorporated in a variety of different mass spectrometers. By way of example, FIG. 3 schematically depicts a mass spectrometer 300 in which the ion source 10 is incorporated. As discussed above, the ion source 10 includes two ion probes 14 and 16 (not shown in this figure), one of which is configured to accommodate sample flow rates in the nanoflow regime and the other is configured to accommodate sample flow rates above the nanoflow regime.

(36) In this embodiment, the ion source 10 is coupled to two LC columns 302 and 304, one which is configured to introduce a sample into the ion probe 14 at flow rates in the nanoflow range and the other is configured to introduce a sample into the ion probe 16 at flow rates above the nanoflow range. Each of the ion probes 14/16 can generate ions corresponding to at least one constituent of the sample introduced therein.

(37) The desolvated ions are introduced into a downstream mass analyzer 306, e.g., via the orifice of a curtain plate of the analyzer as discussed above, which can analyze the ions based on their mass-to-charge (m/z) ratios. The ions passing through the mass analyzer can be detected by an ion detector 308. A variety of mass analyzers can be employed. For example, the mass analyzer 306 can be one or more quadrupole analyzers, time-of-flight analyzers, differential ion mobility analyzers, and any other mass analysis or ion mobility device. Further, the ion detector can be, for example, any combination of electron multiplier/electron multiplier-BED or other suitable detectors. In some embodiments, the mass analyzer 306 is a tandem analyzer that provides multiple stages of mass analysis. By way of example, the mass analyzer 306 can be an MS/MS analyzer having two quadrupole mass analyzers and a collision cell disposed between two quadrupole mass analyzers. In some embodiments, such an MS/NIS analyzer can be operated in a multiple reaction monitoring (MRM) mode. For example, in such a mode, the first quadrupole analyzer can be configured to select precursor ions within a specified range of m/z ratios. The selected precursor ions can enter the collision cell and be fragmented due to collisions with a background gas. The second quadrupole mass analyzer can be configured to select fragment ions within a specified range of m/z ratios. In this manner, precursor/product ion pairs can be selectively detected.

(38) In use, a sample can be introduced into one of the LC columns 302/304 and the eluant can be introduced into the ion probe that is fluidly coupled to that LC column. The ion probe can cause ionization of at least one constituent of the eluant received from the LC column. The ions can then be introduced into the downstream mass analyzer 306 to be analyzed based on their mass-to-charge (m/z) ratios. The ions passing through the mass analyzer 306 can be detected by the detector 308. In some embodiments, one probe can be attached and a plug can seal the other port.

(39) In some embodiments, the electrical resistances of the probes as well as those of the plugs employed to close off the ports in the housing in which probes are not inserted can be employed to identify which probe, if any, is coupled to the housing. Further, such identification of the probe coupled to the housing can be utilized to supply appropriate power to the probe coupled to the housing. By way of example, in some such embodiments, a plug employed to close off a non-functional port (i.e., a port in which a probe is not inserted) can provide a short circuit of vanishing (zero) resistance. Further, the probe accommodating flow rates in the nanoflow range can be provided with an identification resistance (R1), e.g., in a range of about 0 Ohms to about 50 kOhms (such as 2.43 kOhms), and the probe accommodating flow rates above the nanoflow range can be provided with a different identification resistance (R2), e.g., in a range of about 0 Ohms to about 50 kOhms (such as 1.47 kOhms). The resistances of the probes can be connected in series. If the probe accommodating flow rates in the nanoflow range is inserted in one port of the housing with the other port closed off with a plug, the measured resistance will be R1, indicating that only the probe accommodating flow rates in the nanoflow range is coupled to the housing. On the other hand, if the probe accommodating flow rate above the nanoflow range is coupled to the housing, the measured resistance will be R2, indicating that only that probe is coupled to the housing. Further, if neither probe nor plugs are coupled to the housing, the measured resistance will indicate an open circuit. In such a case, a controller in communication with a device measuring the resistances will recognize that no probe is coupled to the housing and will inhibit application of voltages intended for the probes. Probe recognition is important because the software can set reasonable default values and typical high flow settings are sufficiently severe to damage a nanospray tip.

(40) By way of example, FIG. 6 schematically depicts a system 600 for identifying which probe, if any, is coupled to the housing, and controlling the application of an appropriate voltage, if any, to the probe that is coupled to the housing. The system 600 includes a resistance-measuring device 601 for measuring the resistance across the openings in the housing 12a/12b. As noted above, if only the probe accommodating nanoflow rates is coupled to the housing with the other opening closed off with a plug, the resistance-measuring device 601 measures one resistance value (e.g., R1 as discussed above), and if the only the other probe is coupled to the housing with the other opening closed off, the resistance-measuring device 601 measures a different resistance (e.g., R2 as discussed above). Further, if neither probe nor plugs are coupled to the housing, the resistance-measuring device will measure an open circuit.

(41) With continued reference to FIG. 6, a controller 602 receives the measured resistance values for the resistance-measuring device 601. The controller in turn controls a power supply 603 for adjusting voltages applied to the probe(s). For example, if the measured resistance value received by the controller indicates that only the probe accommodating flow rates in the nanoflow range is coupled to the housing, the controller 602 can cause the power supply 603 to apply an appropriate voltage to that probe (e.g. 3500 V). On the other hand, if the measured resistance value received by the controller indicates that only the probe accommodating flow rates above the nanoflow range is coupled to the housing, the controller 602 can cause the power supply 603 to apply an appropriate voltage to that probe (5500 V). Further, if the measured resistance value received by the controller indicates either a short circuit or an open circuit, the controller 602 can inhibit the power supply 603 from applying any voltages to the probes. The controller can also set default values for source heaters and gas flow rates based upon the measured resistance.

(42) The following examples are provided to further elucidate various aspects of the present teachings, and is not intended to provide necessarily optimal ways of practicing the present teachings and/or optimal results that can be obtained.

Example 1

(43) An LC-MS triple quadrupole mass spectrometer operating in MRM mode was used with two different electrospray ion sources to obtain peak area sensitivity data for a 6-compound mixture, where one of the ion sources was a conventional ion source in which the emitter's protrusion beyond the probe's discharge end was adjustable (herein referred to as “State of Art”) and the other one was an electrospray ion source according to the present teachings in which the emitter was fixedly (non-adjustably) positioned within the ion probe. The flow rate was set at 200 μL/min.

(44) The data for the State of Art source was obtained by first varying the position of the tip of the probe relative to the entrance aperture to the mass spectrometer, and by varying the emitter protrusion beyond the probe's discharge end to determine the overall optimal positions for the 6-compound mixture. Optimized data for each compound was then subsequently obtained by varying ion source temperature, ESI electrical potential, and gas flows on a compound-by-compound basis. For the ion source with the emitter fixedly positioned according to the present teachings, optimized data for each compound was obtained by varying ion source temperature, ESI electrical potential, and gas flows on a compound-by-compound basis.

(45) FIG. 4A presents a comparison of the peak area sensitivity data for the compounds. And FIG. 4B presents the normalized peak area sensitivity for each tested compound obtained using the electrospray ion source having a fixed emitter normalized relative to the peak area sensitivity obtained using the conventional electrospray ion source having an adjustable emitter. The data presented in FIGS. 4A and 4B show that peak area sensitivity obtained using the electrospray ion source having a fixed emitter is at least equal to a respective peak area sensitivity obtained using the electrospray ion source having an adjustable emitter, and in many cases, it is enhanced relative to the peak area sensitivity obtained using the electrospray ion source having an adjustable emitter. The adjustable emitter source was optimized for compound 5.

Example 2

(46) FIG. 5 demonstrates the effect of the protrusion of an emitter beyond the discharge tip of a probe in which the emitter is incorporated, for a sample flow rate of 3 μliters/min. The infusion sensitivity for each protrusion length is normalized relative to the maximum sensitivity for the single compound in use. The infusion sensitivity rapidly increases to a peak at a protrusion length of about 0.5 mm and then decreases as the infusion length further increases. Significant sensitivity decreases are evident when the protrusion length varies by as little as 0.5 mm from the optimal length. FIG. 5 was generated with a fixed nebulizer gas setting which gave a smaller optimal protrusion than typical.

(47) Those having ordinary skill in the art will appreciate that various changes to the above embodiments can be made without departing from the scope of the invention.