Systems and methods for controlling the temperature gradient along a differential mobility spectrometer.

Abstract

A system and method are provided for controlling the temperature gradient along a differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas. The differential mobility spectrometer has an internal operating pressure, electrodes, and at least one voltage source for supplying DC and RF voltages to the electrodes to separate ions transported from the inlet to the outlet. A gas port is provided near the outlet for introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer, thereby adjusting the ion residence time. A heater is provided for controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer. A method for calibrating the differential mobility spectrometer is also disclosed.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 088,883, filed April 13, 2020, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This invention relates to differential mobility spectrometers, and more specifically to systems and methods for controlling the temperature between the inlet and outlet of a differential mobility spectrometer using heated throttle gas. Background Technology

[0004] Differential mobility spectroscopy (DMS), also known as high-field asymmetric waveform ion mobility spectroscopy (FAIMS) or field ion spectroscopy (FIS), separates and analyzes ions based on the field dependence of ion mobility. In DMS, ions are transferred between a pair of electrodes in a DMS cell using a transport gas flow, and an asymmetric RF separation waveform is applied between the electrodes in a direction perpendicular to the transport gas flow. The amplitude of the waveform is called the separation voltage (SV). Within each period of the waveform, the difference in ion mobility between the high and low fields causes ions to shift toward the electrodes. To correct for the tilt of the ion trajectory and to transfer ions through the electrodes, a weak DC potential, often called the compensation voltage (CoV), is used. For a given ion, the value of CoV changes with the SV. CoV can be fixed to a target value to allow a specific ion beam to pass through the DMS with a fixed SV; or CoV can be tilted to sequentially allow ions within a defined range of CoV to pass through the DMS.

[0005] As described in U.S. Patent 8,084,736 (Schneider et al.), a throttle gas can be introduced near the outlet of the differential mobility spectrometer (DMS) to modify the flow rate of the transport gas to control the residence time of ions within the DMS, the contents of which are incorporated herein by reference. Ion residence time is a key determinant of DMS resolution, characterized by the full width at half maximum (FWHM) of peaks in an ion map generated by a sloped CoV within a defined range with a fixed SV. With other factors such as mobility coefficient and gap height fixed, increasing the ion residence time provides narrower peak widths in the ion map, thereby improving DMS resolution.

[0006] As discussed above, the SV and CoV potentials induce RF and DC electric fields within the differential mobility spectrometer, which can be represented by a normalized gas number density (E / N), where N is the gas number density representing the number of gas molecules in a given volume. A constant E / N ratio (called a homogeneous field) along the length of the DMS electrode ensures optimal ion separation. Since the electric field strength (E) at any distance from either electrode remains substantially constant along the length of the differential mobility spectrometer, the gas number density (N) must also remain substantially constant, which requires minimizing the temperature gradient along the length of the DMS electrode.

[0007] Differential mobility spectrometers can be coupled to the inlet orifice of a mass spectrometer to supply at least a portion of the separated ions for qualitative and / or quantitative analysis of compounds of interest and isomeric and desiccant substances. High-sensitivity mass spectrometers can have a large inlet orifice size between the atmosphere and a first vacuum stage and can pump large amounts of gas during operation. Existing methods for adjustable resolution may include providing an additional gas flow behind the DMS cell, and this can lead to thermal instabilities in the coupled differential mobility spectrometer due to cooling of the transport gas or throttle gas. This results in a significant variation in the gas number density (N) along the length of the DMS electrode. As discussed above, such temperature gradients are known to be detrimental, especially when the differential mobility spectrometer is operated with chemical modifiers. Summary of the Invention

[0008] One aspect of the present invention is to provide a system and method for controlling the temperature between the inlet and outlet of a differential mobility spectrometer using heated throttle gas, and thereby controlling the temperature gradient.

[0009] In one aspect, a mass spectrometer system is provided, comprising: a differential mobility spectrometer for receiving ions from an ion source, the differential mobility spectrometer having an internal operating pressure, electrodes, and at least one voltage source for providing DC and RF voltages to the electrodes; a mass spectrometer, at least partially sealed to and fluidly communicating with the differential mobility spectrometer, for receiving ions from the differential mobility spectrometer; a vacuum chamber surrounding the mass spectrometer for maintaining the mass spectrometer at a vacuum pressure below the internal operating pressure, the vacuum chamber having a vacuum chamber inlet and operable to draw a gas stream comprising ions through the vacuum chamber inlet through the differential mobility spectrometer and into the vacuum chamber; a gas port for modifying the gas flow rate through the differential mobility spectrometer, the gas port being located between the differential mobility spectrometer and the mass spectrometer; and a heater for controlling the temperature of the gas stream from the gas port.

[0010] In some embodiments, the heater controls the temperature of the gas stream from the gas port to be approximately the same as the temperature of the gas stream passing through the differential mobility spectrometer.

[0011] In some embodiments, the mass spectrometer system further includes a controller for sensing the temperature of the gas flow at opposite ends of the differential mobility spectrometer and adjusting the temperature of the gas flow from the gas port such that the temperatures of the gas flows at the opposite ends are approximately the same.

[0012] In some embodiments, the mass spectrometer system further includes a controller for sensing the temperature of the gas stream from the gas port and the temperature of the gas stream flowing through the differential mobility spectrometer, and adjusting the temperature of the gas stream from the gas port to be approximately the same as the temperature of the gas stream flowing through the differential mobility spectrometer.

[0013] On the other hand, a mass spectrometer system is provided, comprising: a differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas, the differential mobility spectrometer having an internal operating pressure, electrodes, and at least one voltage source for providing DC and RF voltages to the electrodes to separate ions transported from the inlet to the outlet; a gas port near the outlet for introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; and a heater for controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

[0014] In some embodiments, the heater controls the temperature of the throttle gas flow from the gas port to be approximately the same as the temperature of the transport gas flow at a predetermined location in the differential mobility spectrometer.

[0015] In some embodiments, the predetermined location is at the entrance of the differential mobility spectrometer.

[0016] In some embodiments, the mass spectrometer system further includes a controller for sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

[0017] In some embodiments, the controller includes at least one regulator for controlling the flow of the transport gas and the throttle gas, and at least one heater power controller for controlling the temperature of the transport gas and the throttle gas.

[0018] In some embodiments, the mass spectrometer system further includes a gas line for delivering throttle gas to a gas port and a jacket liner surrounding the gas line, wherein the heater includes a straight-line heating element within the jacket liner.

[0019] In one aspect, a method is provided for operating a differential mobility spectrometer having an inlet and an outlet, comprising: receiving ions from an ion source via a transport gas; transporting the ions from the inlet to the outlet of the differential mobility spectrometer; providing DC and RF electric fields within the differential mobility spectrometer for separating ions based on mobility as the ions are transported from the inlet to the outlet; introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; and controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

[0020] In some embodiments, the temperature of the throttle gas at the outlet of the differential mobility spectrometer is controlled to be approximately the same as the temperature of the transport gas at a predetermined location within the differential mobility spectrometer.

[0021] In some embodiments, the predetermined location is near the entrance of the differential mobility spectrometer.

[0022] In some embodiments, the temperature of the gas at the inlet and outlet of the differential mobility spectrometer is controlled within the range of 75°C to 300°C.

[0023] In some embodiments, the temperature of the throttle gas is controlled to approximately 100-200°C.

[0024] In some embodiments, the method further includes sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer, and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

[0025] In some embodiments, the method further includes regulating the flow of the transport gas and the throttle gas.

[0026] In some embodiments, the method further includes controlling the temperature of the transport gas.

[0027] In one aspect, a method for calibrating a differential mobility spectrometer having an inlet and an outlet is provided, comprising: receiving ions from an ion source via a transport gas; transporting the ions from the inlet to the outlet of the differential mobility spectrometer; providing DC and RF electric fields within the differential mobility spectrometer for separating ions based on mobility as the ions are transported from the inlet to the outlet; detecting a first value of the field-dependent mobility of the ions; introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; detecting a second value of the field-dependent mobility of the ions after the introduction of the throttle gas; and controlling the heat of the throttle gas until the second value equals the first value.

[0028] In an embodiment, detecting a second value of the field-dependent mobility of ions includes observing peak CoV shift while increasing the throttle gas flow and automatically adjusting the temperature of the throttle gas until the peak CoV after the introduction of the throttle gas becomes the same as the peak CoV when no throttle gas is applied.

[0029] In an embodiment, the method further includes automatically controlling the heating of the throttle gas until optimal peak height and peak width are achieved, which indicates that the temperature gradient along the length of the differential mobility spectrometer is minimized, thereby enabling automatic tuning of the DMS resolution optimization.

[0030] In one aspect, a mass spectrometer system is provided, comprising: a differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas, the differential mobility spectrometer having an internal operating pressure, electrodes, and at least one voltage source for providing DC and RF voltages to the electrodes to separate ions transported from the inlet to the outlet; a mass spectrometer, at least partially sealed to and in fluid communication with the differential mobility spectrometer, for receiving ions from the differential mobility spectrometer; a vacuum chamber for maintaining the mass spectrometer at a vacuum pressure below the internal operating pressure of the differential mobility spectrometer, the vacuum chamber having a vacuum chamber inlet and operable to draw a gas stream comprising ions from the inlet of the differential mobility spectrometer to the outlet and into the vacuum chamber via the vacuum chamber inlet; a gas port, adjacent to the outlet of the differential mobility spectrometer, for introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; and a heater for controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

[0031] In one embodiment, the heater controls the temperature of the throttle gas stream from the gas port to be approximately the same as the temperature of the transport gas stream at a predetermined location in the differential mobility spectrometer.

[0032] In this embodiment, the predetermined location is at the entrance of the differential mobility spectrometer.

[0033] In one embodiment, the mass spectrometer system further includes a controller for sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

[0034] In one embodiment, the controller includes at least one regulator for controlling the flow of the transport gas and the throttle gas, and at least one heater power controller for controlling the temperature of the transport gas and the throttle gas.

[0035] In one embodiment, the mass spectrometer system further includes a gas line for delivering throttle gas to a gas port and a jacket liner surrounding the gas line, wherein the heater includes a straight-line heating element within the jacket liner.

[0036] In various embodiments, any mass spectrometer system according to this teaching further includes: a curtain plate including apertures for receiving ions and defining a curtain chamber containing a differential mobility spectrometer; and a curtain gas supply for supplying curtain gas into the curtain chamber to provide a transport gas flow through the differential mobility spectrometer and a curtain gas outflow exiting the curtain chamber. In various embodiments, the mass spectrometer system further includes a heat exchanger in the curtain plate for heating the curtain gas. In various embodiments, the heat exchanger is surrounded by ceramic beads through which the curtain gas flows and is thereby heated. In various embodiments, the heater controls the temperature of the throttle gas such that the temperature at the location where the mass spectrometer is at least partially sealed to and in fluid communication with the differential mobility spectrometer is in the range of 75°C to 300°C.

[0037] These, and other aspects and advantages that will become clear thereafter, are contained in the details of the construction and operation which are described and claimed more fully below, with reference to the accompanying drawings which form part of the description, wherein the same reference numerals throughout the text denote the same parts. Attached Figure Description

[0038] Figure 1 This is a schematic representation of a differential mobility spectrometer / mass spectrometer system.

[0039] Figure 2 This is an ion map of the compound analyzed by a differential mobility spectrometer / mass spectrometer system, showing the shift between operation with and without throttle gas flow.

[0040] Figure 3 An exemplary differential mobility spectrometer / mass spectrometer system according to an embodiment is shown.

[0041] Figure 4 yes Figure 3 A schematic representation of an exemplary differential mobility spectrometer / mass spectrometer system, suitable for temperature control of at least the throttle gas flow.

[0042] Figure 5 A method for operating a differential mobility spectrometer according to an embodiment is shown.

[0043] Figure 6 A method for operating or calibrating a differential mobility spectrometer according to another embodiment is shown. Detailed Implementation

[0044] Figure 1A differential mobility spectrometer / mass spectrometer system 100 according to an embodiment is shown. The differential mobility spectrometer / mass spectrometer system 100 includes a differential mobility spectrometer 102 and a first vacuum lens element 104 of a mass spectrometer (hereinafter collectively referred to as mass spectrometer 104). Mass spectrometer 104 also includes a mass analyzer element 104a downstream of a vacuum chamber 127. Ions can be transported through the vacuum chamber 127 due to the pressure maintained by a vacuum pump 130, and can be transported through one or more additional differential pumping vacuum stages preceding the mass analyzer element 104a. For example, in one embodiment, a triple quadrupole mass spectrometer may include three differential pumping vacuum stages. The third vacuum stage may contain a detector and two quadrupole mass analyzers, with a collision cell located between the two quadrupole mass analyzers. Alternatively, there may be four or more differential pumping vacuum stages. It will be apparent to those skilled in the art that other ion optics, not described, may be present in the system. This example is not intended to be limiting, as it will be clear to those skilled in the art that the described differential mobility spectrometer / mass spectrometer coupling can also be applied to many mass spectrometer systems that sample ions from an elevated pressure source. These may include time-of-flight (TOF), ion traps, quadrupoles, or other mass analyzers known in the art.

[0045] The differential mobility spectrometer 102 includes a plate 106 and an electrical insulator 107 along the outer side of the plate 106. The plate 106 surrounds a transport gas 108 drifting from an inlet orifice 110 to an outlet 112 of the differential mobility spectrometer 102. The insulator 107 supports electrodes and isolates them from other conductive elements. The outlet 112 of the differential mobility spectrometer 102 releases the transport gas into a junction chamber 114, which defines the ion travel path between the differential mobility spectrometer 102 and the mass spectrometer 104. In some embodiments, the outlet 112 of the differential mobility spectrometer 102 is aligned with the inlet of the mass spectrometer 104 to define the ion travel path between them.

[0046] The differential mobility spectrometer 102 and the junction chamber 114 are both contained within a curtain chamber 118, which is defined by a curtain plate (boundary member) 119 and supplied with curtain gas from a nitrogen supply 120. The nitrogen supply 120 supplies curtain gas into the interior of the curtain chamber 118. Ions 122 are provided from an ion source (not shown) and emitted into the curtain chamber 118 through apertures in the curtain plate 119. The pressure of the curtain gas within the curtain chamber 118 provides both the curtain gas outflow 126 exiting the curtain chamber 118 and the transport gas 108 carrying ions 122 through the differential mobility spectrometer 102 and into the junction chamber 114. The curtain plate 119 can be connected to a power source to provide it with an adjustable DC potential.

[0047] like Figure 1As shown, the first vacuum lens element 104 of the mass spectrometer is contained within a vacuum chamber 127, which can be maintained at a pressure much lower than that of the curtain chamber 118 by means of a vacuum pump 130. Due to the significant pressure difference between the curtain chamber 118 and the vacuum chamber 127, the transport gas 108 is drawn through the differential mobility spectrometer 102, the junction chamber 114, and into the vacuum chamber 127 and the first vacuum lens element 104 via the vacuum chamber inlet 129. As shown, the mass spectrometer 104 can be sealed to (or at least partially sealed to) and fluidly communicated with the differential mobility spectrometer via the junction chamber 114 to receive ions 122 from the differential mobility spectrometer 102.

[0048] As shown in the figure, a gas port 132 is provided to allow throttle gas to enter the junction chamber 114. Within the junction chamber 114, a nitrogen supply provides throttle gas 133, which throttles back the flow of transport gas 108 in the differential mobility spectrometer 102. Specifically, the throttle gas flow 133 within the junction chamber 114 modifies the flow rate of both the transport gas 108 within and entering the differential mobility spectrometer 102, thereby controlling the residence time of ions 122 within the differential mobility spectrometer 102. By controlling the residence time of ions 122 within the differential mobility spectrometer 102, resolution and sensitivity can be adjusted. That is, increasing the residence time of ions 122 within the differential mobility spectrometer 102 can increase resolution, but may also lead to additional ion loss, thereby reducing the sensitivity detected in the mass spectrometer. Therefore, in some embodiments, it is desirable to be able to precisely control the amount of throttle gas added to the junction chamber 114 to provide a degree of control over the gas flow rate through the differential mobility spectrometer 102, thereby controlling the trade-off between sensitivity and selectivity. Figure 1 In some embodiments, the throttle gas flow 133 can be controlled in a variety of ways, including controlled leakage size, pressurized gas line with an adjustable valve, or a series of restrictive orifices, or any other method known in the art.

[0049] Gas port 132 can be oriented to disperse throttle gas flow 133 throughout the junction chamber 114. In one embodiment, gas port 132 introduces throttle gas without disrupting the gas flow lines between differential mobility spectrometer 102 and mass spectrometer inlet 129.

[0050] As described above and as is known in the art, an RF voltage, often referred to as the separation voltage (SV), can be applied perpendicularly to the direction of the transport gas flow 108 across the ion transport chamber of the differential mobility spectrometer. The RF voltage can be applied to one or both of the DMS electrodes, including the differential mobility spectrometer. The tendency of ions to migrate towards the wall and leave the DMS path can be corrected by a DC potential, often referred to as the compensation voltage (CoV). The compensation voltage can be generated by applying a DC potential to one or both of the DMS electrodes, including the differential mobility spectrometer. As is known in the art, a DMS voltage source (not shown) can provide both the RF SV and DC CoV voltages. Alternatively, multiple voltage sources can be provided.

[0051] In some embodiments, a single nitrogen supply unit may be used to provide both curtain gas and throttle gas flow. In other embodiments, multiple gas supplies may be used. Figure 1 An embodiment with a single nitrogen supply 120 is shown. A regulator with a valve can be used to control the flow rate of throttle gas into the junction chamber 114 via gas line 120c. The nitrogen supply 120 supplies a flow 131 (referred to as the curtain gas flow or total curtain gas flow) to the curtain chamber 119 via regulator 120a. The nitrogen supply 120 also flows to a chemical modifier supplier 125 via regulator 120d, which is in fluid communication with the curtain gas supply, to add the modifier to the total curtain gas flow 131. The flow through the differential mobility spectrometer and the junction chamber is ultimately maintained in the vacuum chamber 127 and drawn into the mass spectrometer orifice inlet 129, represented by the curtain inflow 128. Therefore, the curtain gas outflow 126 = (total curtain gas flow 131 + throttle gas flow 133) - curtain gas inflow 128. In some embodiments, the curtain gas flow 131 can be heated, for example using a heat exchanger discussed in more detail below.

[0052] As discussed above, the high-sensitivity mass spectrometer 104, with a large inlet 129 aperture size between the atmosphere and the first vacuum stage 127, can draw in large quantities of gas during operation. This requires a high throttle gas flow to adjust the peak resolution. Cooling of the unheated throttle gas in the transport gas can lead to a larger thermal gradient, particularly at the rear end of the DMS, and significant thermal instabilities in the differential mobility spectrometer 102, even though a heat exchanger is included to heat the curtain gas flow 131.

[0053] Under typical operating conditions, the curtain gas inflow 128 can be on the order of 16 L / min, the total curtain gas flow 131 can be on the order of 18 L / min, and the throttle gas flow 133 can be varied to control the ion residence time, as discussed above. Therefore, when increased resolution is required, the throttle gas flow 133 can be increased, for example, from the order of 0 L / min to 15 L / min. This, in turn, increases the curtain gas outflow 126 from approximately 2 L / min to approximately 17 L / min, resulting in a reduction in the signal for the ions of interest. To minimize this signal loss, the curtain gas flow 131 can be reduced while increasing the throttle gas flow 133 to maintain a constant outflow 126.

[0054] The inventors have discovered that variations in the throttle gas flow 133 cause a shift in the DMS ion peak. Specifically, when operating the differential mobility spectrometer 102 without chemical modifiers, introducing cold throttle gas or nitrogen into the junction chamber 114 may cause the DMS ion peak to shift to a lower CoV value. Using a higher throttle gas flow to achieve higher DMS resolution exacerbates this effect. Figure 2 Through Figure 1 The ion map of the adrenaline blocker reserpine was analyzed by mass spectrometer 104, with throttle gas flow 133 turned off (200) and throttle gas flow 133 set to 14 L / min (210). In this example, as throttle gas flow 133 increases from 0 to 14 L / min, curtain gas flow 131 decreases, resulting in a total gas flow (total curtain flow 131 + throttle gas flow 133) of 18 L / min, with 16 L / min of inhalation flow (curtain gas inflow 128) and 2 L / min (curtain gas outflow 126) flowing out in the opposite direction from curtain 119. Vertical line 220 shows the optimal CoV measured when throttle gas flow 133 is turned off. It should be noted that when the throttle gas flow 133 is switched on to 14 L / min, the full width at half maximum (FWHM) measurement of the DMS resolution of ion plot 210 decreases to ~0.5 V, while the CoV shift decreases to ~0.7 V. This is a sufficiently large peak shift to reduce the measured signal of the compound of interest (reserpine in this example) to 0 counts per second (cps) when the target CoV value is fixed during the data acquisition period.

[0055] Figure 2The ~0.7V peak shift is caused by the cooling effect of the introduced unheated throttle gas. As the throttle gas flow 133 increases, the curtain gas flow 131 decreases by the same amount to maintain the outflow 126 through the curtain 119 constant at ~2 L / min. As mentioned above, the curtain gas flow 131 can be heated by a heat exchanger as it passes through the curtain chamber, but for a high-sensitivity mass spectrometer with a large inlet orifice size, the throttle gas flow 133 is high enough to cause significant cooling of the transport gas 108 as it passes through the differential mobility spectrometer 102, especially at the rear end of the DMS, which can lead to a thermal gradient. Such changes in the temperature profile can also affect the separation of modifiers (see Schneider et al., Mass Spec. Rev., 2015). Table 1 shows the results in an exemplary differential mobility spectrometer 302 (e.g., Figure 3 The exemplary differential mobility spectrometer 302, which measures the temperature at its inlet 110 and outlet 112 (as shown in the figure and described below), is coupled to a high-sensitivity mass spectrometer 304 with a large inlet 329 aperture size of ID = 1.55 mm.

[0056] Table 1

[0057]

[0058] exist Figure 3 In the exemplary differential mobility spectrometer / mass spectrometer system 300, the cooling effect that occurs when throttle gas is introduced into the differential mobility spectrometer 302 coupled to and sealed to the mass spectrometer 304 is mitigated by providing an orifice heater 307 deployed near the outlet 312 and a throttle gas heater 305. The curtain 319 may also be provided with a heater exchanger 350. In an embodiment, the heater exchanger 350 may be surrounded by ceramic beads. In an embodiment, the curtain gas 331 may be heated to approximately 105-200°C as it flows through the heated beads, enters the inlet 310, passes through the differential mobility spectrometer 302 to reach the outlet 312, and enters the vacuum chamber inlet 329. The throttle gas heater 305 may be a jacket liner surrounding the throttle gas flow 333, wherein the heater includes a straight-line heating element within the jacket liner. In an embodiment, the jacket liner may be made of polytetrafluoroethylene (PTFE). Those skilled in the art will know that, in addition to jacket linings, there are many different methods that can be used to heat gas flows.

[0059] Figure 4 According to the embodiments Figure 3 A schematic representation of an exemplary differential mobility spectrometer / mass spectrometer system, suitable for temperature control of at least the throttle gas flow 333.

[0060] exist Figure 3 and Figure 4 In, with Figure 1Elements appearing in the figure are identified by similar reference numerals, but with the prefix "3", for example... Figure 3 and Figure 4 The "300" in the text indicates that it is related to... Figure 1 Similar to the "100" in the text.

[0061] Return to Figure 4 The controller 400 is shown as controlling the throttle gas heater 305 and the curtain gas heat exchanger 350 based on temperature inputs from a sensor 340 for measuring the temperature of the throttle gas flow 333 and an internal sensor (not shown) within the heat exchanger 350 for measuring the temperature of 331. The sensor 340 may be positioned, for example, along a gas line near a line heater adjacent to the throttle gas heater 305. Alternatively, the controller 400 may be connected to multiple sensors embedded in a non-conductive DMS retainer, such as a ceramic retainer.

[0062] The controller 400 can also be connected to regulators 320a and 320b to control the total curtain gas flow 331 (including any modifier gas) and the throttle gas flow 333. The controller 400 may include at least one heater power controller to control the temperature of the transport gas and the throttle gas.

[0063] according to Figure 5 In the steps described, controller 400 may be operable to sense the temperature of the gas flow at sensor 340 and adjust the temperature of the throttle gas flow 333 to normalize the temperature difference between the inlet 310 and outlet 312 of differential mobility spectrometer 302. However, in some embodiments, mass spectrometry data from mass spectrometer 304 may be used as adjustment parameters, as discussed below, rather than temperature measurements, for example, in cases where the high electric field generated between a pair of electrodes 306 at the location of interest for temperature measurement would cause interference with the operation of sensor 340.

[0064] Figure 5A method of operating a differential mobility spectrometer 302 according to an embodiment is illustrated. At 500, ions of a sample are received at the inlet 310 of the differential mobility spectrometer 302. At 510, ions are transported from the inlet 310 to the outlet 312 via a transport gas flow 308 through the differential mobility spectrometer. At 520, DC and RF electric fields are generated between a pair of electrodes 306 for separating ions based on mobility as they transport from the inlet 310 to the outlet 312. At step 525, the operator or controller 400 determines whether the resolution is sufficient for DMS separation of molecules. If not, then at step 530, the throttle gas flow 333 is adjusted to control the flow rate of the transport gas through the differential mobility spectrometer 302, and at 540, the temperature of the throttle gas flow 333 is controlled via a heater 305 to minimize the temperature gradient between the inlet 310 and the outlet 312 of the differential mobility spectrometer 302. If the resolution is determined to be sufficient for molecular separation at step 525, then the DMS data is acquired at step 545.

[0065] Throttle gas heater 305 can, for example, be configured to provide throttle gas at approximately 100-200°C, such that the temperature of the throttle gas stream 333 is approximately the same as the temperature of the transport gas stream 308 at a predetermined location in the differential mobility spectrometer, such as at inlet 310 or outlet 312. For example, in an embodiment, the gas temperature at inlet 310 and outlet 312 can be controlled to approximately 105°C by heating the throttle gas stream 333 to any required temperature, or by adjusting the preheater and throttle line heater to provide a similar gas temperature.

[0066] Optionally, the flow of transport gas 308 and throttle gas 333 can be regulated by controller 400 controlling regulators 320a and 320b.

[0067] Figure 6A method for operating or calibrating a differential mobility spectrometer 302 according to another embodiment is illustrated. At 600, ions from a sample (or calibration solution) are received at the inlet 310 of the differential mobility spectrometer 302. At 610, ions are transported from the inlet 310 to the outlet 312 via a transport gas flow 308 through the differential mobility spectrometer. At 620, DC and RF electric fields are generated between a pair of electrodes 306 for separating ions based on mobility as they transport from the inlet 310 to the outlet 312. At step 625, the controller 400 determines whether the resolution is sufficient for DMS separation of molecules. If not, then at step 630, the throttle gas flow 333 is adjusted to control the flow rate of the transport gas through the differential mobility spectrometer 302. At 640, the operator or controller 400 determines whether the DMS performance is optimal. If so, then DMS data is acquired at 645. If not, then at 650, the temperature of the throttle gas flow 333 is controlled via heater 305 to minimize the temperature gradient between the inlet 310 and outlet 312 of the differential mobility spectrometer 302. If at 625 the operator or controller 400 determines that the resolution is sufficient for molecular separation, and if at 655 the operator or controller 400 determines that the DMS performance is optimal, then DMS data is acquired at step 645. If at 655 the operator or controller 400 determines that the DMS performance is suboptimal, then the temperature of the throttle gas flow 333 is controlled at 650 until the target ions exhibit the optimal performance achieved under conditions without applied throttle gas (620), after which the process cycles back to 600. Optimal performance can be characterized by peak width, peak height, and peak CoV position.

[0068] Figure 6 The calibration method can be implemented iteratively, for example by tuning CoV based on the rate of transport gas flow 308 without applying throttle gas, observing the signal peak in the mass spectrometry data provided by mass spectrometer 304, introducing throttle gas flow 333, and then adjusting the heater power level to center the peak to the expected CoV.

[0069] In other embodiments, throttle gas heating can be adjusted to shift the peak to a specific position consistent with the position when no throttle gas is applied. In still other embodiments, throttle gas heating is adjusted to achieve an optimized peak width, particularly when a modifier gas is applied and the temperature gradient has been shown to have a significant effect on changing the peak width.

[0070] Many features and advantages of the invention are apparent from the detailed description; therefore, the appended claims are intended to cover all such features and advantages of the invention that fall within the scope of the claims. Furthermore, since many modifications and alterations will readily occur to those skilled in the art, it is not intended to limit the invention to the exact construction and operation shown and described, and thus all suitable modifications and equivalents may be invoked within the scope of the claims.

Claims

1. A mass spectrometer system, comprising: A differential mobility spectrometer for receiving ions from an ion source, the differential mobility spectrometer being configured to have an internal operating pressure, the differential mobility spectrometer having electrodes and at least one voltage source for providing DC and RF voltages to the electrodes; A mass spectrometer, at least partially sealed to and in fluid communication with a differential mobility spectrometer, for receiving ions from the differential mobility spectrometer; A vacuum chamber surrounding the mass spectrometer is used to maintain the mass spectrometer at a vacuum pressure below the internal operating pressure. The vacuum chamber has a vacuum chamber inlet and is operable to draw a gas stream, including ions, through the differential mobility spectrometer into the vacuum chamber via the vacuum chamber inlet. A heater is used to heat and control the temperature of the gas flow through the throttle valve; as well as A gas port, located between the differential mobility spectrometer and the mass spectrometer, is used to introduce a heated throttle gas flow to modify the gas flow rate through the differential mobility spectrometer.

2. The mass spectrometer system as described in claim 1, wherein, The heater is configured to control the temperature of the throttle gas flow to be approximately the same as the temperature of the gas flow passing through the differential mobility spectrometer.

3. The mass spectrometer system of claim 1 further includes a controller for sensing the temperature of the gas flow at opposite ends of the differential mobility spectrometer and adjusting the temperature of the throttle gas flow so that the temperatures of the gas flows at opposite ends are approximately the same.

4. The mass spectrometer system of claim 1 further includes a controller for sensing the temperature of the throttle gas flow and the temperature of the gas flow passing through the differential mobility spectrometer, and adjusting the temperature of the throttle gas flow to be approximately the same as the temperature of the gas flow passing through the differential mobility spectrometer.

5. A mass spectrometer system, comprising: A differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas, the differential mobility spectrometer having an internal operating pressure, electrodes, and at least one voltage source for supplying DC and RF voltages to the electrodes to separate ions transported from the inlet to the outlet. The gas port near the outlet is used to introduce throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; and A heater is used to control the temperature of the throttle gas in order to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

6. The mass spectrometer system as described in claim 5, wherein, The heater controls the temperature of the throttle gas flow from the gas port to be approximately the same as the temperature of the transport gas flow at a predetermined location in the differential mobility spectrometer.

7. The mass spectrometer system as described in claim 6, wherein, The intended location is at the entrance of the differential mobility spectrometer.

8. The mass spectrometer system of claim 5 further includes a controller for sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

9. The mass spectrometer system as described in claim 8, wherein, The controller includes at least one regulator for controlling the flow of the transport gas and the throttle gas, and at least one heater power controller for controlling the temperature of the transport gas and the throttle gas.

10. The mass spectrometer system of claim 5, further comprising a gas line for delivering throttle gas to a gas port and a jacketed liner surrounding the gas line, wherein the heater comprises a straight-line heating element within the jacketed liner.

11. A mass spectrometer system, comprising: A differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas, the differential mobility spectrometer having an internal operating pressure, electrodes, and at least one voltage source for supplying DC and RF voltages to the electrodes to separate ions transported from the inlet to the outlet. A mass spectrometer, at least partially sealed to and in fluid communication with a differential mobility spectrometer, for receiving ions from the differential mobility spectrometer; A vacuum chamber is used to maintain the mass spectrometer at a vacuum pressure lower than the internal operating pressure of the differential mobility spectrometer. The vacuum chamber has a vacuum chamber inlet and is operable to draw a gas stream, including ions, from the inlet of the differential mobility spectrometer to the outlet and into the vacuum chamber via the vacuum chamber inlet. A gas port, near the outlet of the differential mobility spectrometer, is used to introduce throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer; and A heater is used to control the temperature of the throttle gas in order to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

12. The mass spectrometer system of claim 11, wherein, The heater controls the temperature of the throttle gas flow from the gas port to be approximately the same as the temperature of the transport gas flow at a predetermined location in the differential mobility spectrometer.

13. The mass spectrometer system of claim 12, wherein, The intended location is at the entrance of the differential mobility spectrometer.

14. The mass spectrometer system of claim 11, further comprising a controller for sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

15. The mass spectrometer system of claim 14, wherein, The controller includes at least one regulator for controlling the flow of the transport gas and the throttle gas, and at least one heater power controller for controlling the temperature of the transport gas and the throttle gas.

16. The mass spectrometer system of claim 11, further comprising a gas line for delivering throttle gas to a gas port and a jacketed liner surrounding the gas line, wherein the heater comprises a straight-line heating element within the jacketed liner.

17. The mass spectrometer system according to any one of claims 1, 5, or 11, further comprising: A curtain panel, including apertures for receiving ions and defining a curtain chamber containing a differential mobility spectrometer; A curtain gas supply unit is used to supply curtain gas into a curtain chamber to provide a transport gas flow through the differential mobility spectrometer and a curtain gas outflow leaving the curtain chamber.

18. The mass spectrometer system of claim 17, further comprising a heat exchanger in the curtain for heating the curtain gas.

19. The mass spectrometer system of claim 18, wherein, The heat exchanger is surrounded by ceramic beads, through which curtain gas flows and is heated.

20. The mass spectrometer system of claim 11, wherein, The heater controls the temperature of the throttle gas so that the temperature at the location where the mass spectrometer is at least partially sealed to and in fluid communication with the differential mobility spectrometer is in the range of 75°C to 300°C.

21. A method for operating a differential mobility spectrometer having an inlet and an outlet, comprising: Ions are received from an ion source by transporting gas; Transporting ions from the inlet to the outlet of the differential mobility spectrometer; DC and RF electric fields are provided within the differential mobility spectrometer to separate ions based on mobility as they are transported from the inlet to the outlet. Throttle gas is introduced near the outlet to control the flow rate of the transport gas through the differential mobility spectrometer; and The temperature of the throttle gas is controlled to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.

22. The method of claim 21, wherein, The temperature of the throttle gas at the outlet of the differential mobility spectrometer is controlled to be approximately the same as the temperature of the transport gas at a predetermined location within the differential mobility spectrometer.

23. The method of claim 22, wherein, The intended location is near the entrance of the differential mobility spectrometer.

24. The method of claim 21, wherein, The temperature of the gas at the inlet and outlet of the differential mobility spectrometer is controlled within the range of 75°C to 300°C.

25. The method of claim 21, wherein, The temperature of the gas at the throttle valve is controlled to be approximately 100-200°C.

26. The method of claim 21, further comprising sensing the temperature of a gas flow near at least one of the inlet and outlet of the differential mobility spectrometer, and adjusting the temperature of the throttle gas flow to normalize the temperature difference between the inlet and outlet of the differential mobility spectrometer.

27. The method of claim 21, further comprising regulating the flow of the transport gas and the throttle gas.

28. The method of claim 21, further comprising controlling the temperature of the transport gas.

29. A method for calibrating a differential mobility spectrometer having an inlet and an outlet, comprising: Ions are received from an ion source by transporting gas; Transporting ions from the inlet to the outlet of the differential mobility spectrometer; DC and RF electric fields are provided within the differential mobility spectrometer to separate ions based on mobility as they are transported from the inlet to the outlet. The first value of the field-dependent mobility of detected ions; Throttle gas is introduced near the outlet to control the flow rate of the transport gas through the differential mobility spectrometer; and The second value of the field-dependent mobility of ions was detected after the introduction of throttle gas; and Control the heat of the gas in the throttle valve until the second value equals the first value.

30. The method of claim 29, wherein, The second value for detecting the field-dependent mobility of ions includes observing peak CoV shift while increasing the throttle gas flow, and automatically adjusting the temperature of the throttle gas until the peak CoV after the introduction of the throttle gas becomes the same as the peak CoV when no throttle gas is applied.

31. The method of claim 30, further comprising automatically controlling throttle gas heating until optimal peak height and peak width are achieved, which indicates that the temperature gradient along the length of the differential mobility spectrometer is minimized, thereby enabling automatic tuning of DMS resolution optimization.

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