Patent Application
20170309461
The present disclosure relates to mass spectrometry and more particularly to remote ionization and ion transfer.
Mass spectrometers (MS) operate in a vacuum and separate ions with respect to mass-to-charge ratio. In embodiments that use a mass spectrometer, a sample, which may be solid, liquid, or gas, is ionized. The ions are separated in a mass analyzer according to mass-to-charge ratio and are detected by a device capable of detecting charged particles. The signal from the detector is then processed into the spectra of the relative abundance of ions as a function of the mass-to-charge ratio. The molecules are identified by correlating the identified masses with known masses or through a characteristic fragmentation pattern.
An ambient ionization source, an ion transfer tube assembly, a mass spectrometry system, and a method for delivering an ion stream to an ion detection device are described that include using an ion transfer tube that provides a coaxial sheath gas flow. In an implementation, an ion transfer tube assembly that employs example techniques in accordance with the present disclosure includes an ion transfer tube for delivering the ion stream, where a sheath gas flow flows through the ion transfer tube, and where the ion transfer tube receives the ion stream from a first conduit coupled to an ion source; a pump fluidly coupled to the ion transfer tube, where the pump causes the sheath gas to flow through the ion transfer tube, where the ion stream is substantially surrounded by the coaxial sheath gas flow, and where the ion stream is received by a second conduit coupled to the ion detection device.
In an implementation, a mass spectrometry system that employs example techniques in accordance with the present disclosure includes an ion source coupled to a first conduit; an ion detection device coupled to a second conduit; an ion transfer tube, where the ion transfer tube is coupled to the first conduit and the second conduit and delivers an ion stream from the ion source to the ion detection device, where an outlet of the first conduit and an inlet of the second conduit is disposed in the cross-sectional center of the ion transfer tube, and where a sheath gas flows through the ion transfer tube such that the ion stream exits the outlet of the first conduit and is substantially surrounded by the coaxial sheath gas flow; and a pump fluidly coupled to the ion transfer tube, where the pump causes the sheath gas to flow through the ion transfer tube.
In an implementation, a method for providing an ion stream to a mass spectrometry system that employs example techniques in accordance with the present disclosure includes generating the ion stream using an ion source with a first conduit; and providing the ion stream from the ion source with a first conduit to an ion detection device with a second conduit using an ion transfer tube coupled to the first conduit and the second conduit, where an outlet of the first conduit and an inlet of the second conduit is disposed in the cross-sectional center of the ion transfer tube, and where a sheath gas flows through the ion transfer tube such that the ion stream exits the outlet of the first conduit and is substantially surrounded by the coaxial sheath gas flow, and where the ion stream flows into the second conduit.
This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
The detailed description is described with reference to the accompanying figures. The use of the same reference number in different instances in the description and the figures may indicate similar or identical items.
Overview
Mass spectrometers (MS) operate in a vacuum and separate ions with respect to the mass-to-charge ratio. In some embodiments using a mass spectrometer, a sample, which may be solid, liquid, or gas, is ionized and analyzed. The ions are separated in a mass analyzer according to mass-to-charge ratio and are detected by a detector capable of detecting charged particles. The signal from the detector is then processed into the spectra of the relative abundance of ions as a function of the mass-to-charge ratio. The molecules are identified by correlating the identified masses with known masses or through a characteristic fragmentation pattern.
Ambient ionization methods can be used in an MS or ion-mobility spectrometry (IMS) system to ionize substances for real-time and in situ chemical analysis without any sample preparation. Among them are desorption electrospray ionization (DESI), direct analysis in real-time (DART), low-temperature plasma (LTP), direct atmospheric pressure chemical ionization (DAPCI) and many others. However, the application of ambient ionization for real-life problems is limited by the shortness of the distance from the sample to inlet of ion detection device. Remote sample ionization involves ion transfer to the detection system inlet using flexible tubing. However, ions from the substance which will be analyzed are frequently generated at higher pressure conditions, for example, at atmospheric pressure. A variety of direct ambient ionization methods include desorption electrospray ionization (DESI) (Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471-473), direct analysis in real time (DART) (Cody, R. B.; Laramee, J. A.; Durst, H. D. Anal. Chem. 2005, 77, 2297-2302), atmospheric pressure Dielectric Barrier Discharge Ionization (DBDI) (Na, N.; Zhao, M.; Zhang, S.; Yang, C.; Zhang, X., J Am Soc Mass Spectrom 2007, 18, 1859-1862), low-temperature plasma (LTP) (Harper, J. D.; Charipar, N. A.; Mulligan, C. C.; Zhang, X.; Cooks, R. G.; Ouyang, Z., Anal. Chem. 2008, 80, 9097-9104), etc., which are all incorporated herein by reference.
In many instances it is not feasible to place analyzed samples in front of a mass spectrometer inlet. In this case, generated ions need to be transferred over a long distance without significant loss of analyte signal.
There are significant technical challenges for providing efficient transfer of low abundance analyte ions of interest from an ionization source into ion detection system over a long distance, especially in the case of a miniature mass analyzer. The challenges are mainly related to size and weight limitations of portable systems, which severely limit the choice of vacuum pumps that can be used in such systems. Small vacuum pumps limit the intake flows into a mass spectrometer to about 0.15 L/min. The main mechanism of ion losses in long narrow tubing at ion concentration less than 108 cm−3 is radial diffusion to the walls (Lin, B.; Sunner, J., Ion transport by viscous gas flow through capillaries, J Am Soc Mass Spectrom, 1994, 5, 873-885). The change in ion concentration n with diffusion limited losses can be described by the following equation:
where D*=D/1.6 is an effective ion diffusion coefficient (to account for parabolic velocity profile inside the capillary) and t is residence time (See Sunner, J. et al.). The total residence time tf can be calculated from the value of the intake flow Q and the capillary volume V:
where factor 60 is derived from the conversion of L/min to L/s. Substituting tf for t in Equation 1 and using the relation V=πr02L, the following equation can be obtained:
where Q is the intake flow in L/min, D is the tubing diameter, and L is the capillary length in cm. However, as can be calculated from these equations, for a portable mass spectrometer (e.g., Q˜0.15 L/min) with remote sampling at L=50 cm and a typical value of diffusion coefficient D=0.04 cm2/s, only 0.01% of ions are transmitted from the ionization source to the mass analyzer.
One way to overcome this problem for remote direct ionization was proposed by R. Graham Cooks et al., in U.S. Pat. No. 8,592,756, which is incorporated herein by reference, where a gas flow, created by an additional pump at the inlet of a mass spectrometer, pulls ions produced by LTP ionization into a transfer tube with a much higher flow rate than intake flow into the MS inlet. This arrangement allows to reduce diffusion ion losses on walls of the transfer tube because of decreased ion residence time. However, in the Cooks et al. arrangement, ions are distributed over the whole internal section of large diameter tube (e.g., 6.0 mm is shown on
Accordingly, an ion transfer tube assembly, a mass spectrometry system, and a method for delivering an ion stream to an ion detection device are described that include using an ion transfer tube with a coaxial sheath gas flow. In an implementation, an ion transfer tube assembly that employs example techniques in accordance with the present disclosure includes an ion transfer tube for delivering the ion stream, where a sheath gas flows through the ion transfer tube, and where the ion transfer tube receives the ion stream from a first conduit coupled to an ion source; a pump fluidly coupled to the ion transfer tube, where the pump causes the sheath gas to flow through the ion transfer tube, where the ion stream is substantially surrounded by the coaxial sheath gas flow, and where the ion stream is received by a second conduit coupled to the ion detection device.
In an implementation, a mass spectrometry system that employs example techniques in accordance with the present disclosure includes an ion source coupled to a first conduit; an ion detection device coupled to a second conduit; an ion transfer tube, where the ion transfer tube is coupled to the first conduit and the second conduit and delivers an ion stream from the ion source to the ion detection device, where an outlet of the first conduit and an inlet of the second conduit is disposed in the cross-sectional center of the ion transfer tube, and where a sheath gas flows through the ion transfer tube such that the ion stream exits the outlet of the first conduit and is substantially surrounded by the coaxial sheath gas flow; and a pump fluidly coupled to the ion transfer tube, where the pump causes the sheath gas to flow through the ion transfer tube.
In an implementation, a method for providing an ion stream to a mass spectrometry system that employs example techniques in accordance with the present disclosure includes generating the ion stream using an ion source with a first conduit; and providing the ion stream from the ion source with a first conduit to an ion detection device with a second conduit using an ion transfer tube coupled to the first conduit and the second conduit, where an outlet of the first conduit and an inlet of the second conduit is disposed in the cross-sectional center of the ion transfer tube, and where a sheath gas flows through the ion transfer tube such that the ion stream exits the outlet of the first conduit and is substantially surrounded by the coaxial sheath gas flow, and where the ion stream flows into the second conduit.
In these implementations, after a short transfer through the first conduit, a coaxial sheath gas flow is introduced, which is created by a high flow pump or compressor. Sample ions from the sample are concentrated in a small central part of the gas transfer flow, and the gas velocity of the flow containing the ions (i.e., the ion stream) is increased hence decreasing residence time of ions in the ion transfer tube and ion losses along the walls of the ion transfer tube. Additionally, the sheath gas separates the ions from the walls, thus eliminating a possible charging of the inner tube surface in the case of nonconductive materials. Because the mass spectrometer inlet (e.g., second conduit) has a small inside diameter (e.g., 0.25-0.75 mm) the ion transfer tube described herein provides better matching of the mass spectrometer inlet with the ion stream diameter than some other technologies.
Example Implementations
In implementations, the analysis system 100 can include an ion source 102 that provides an ion stream 110 to the ion detection device 114 for analysis. The ion source 102 can receive a substance (e.g., fluid, solid, etc.) and use the substance to produce ions that are indicative of the composition of the substance to be analyzed. Some examples of an ion source 102 may include an electrospray ion source, a sonic spray ionization source, atmospheric pressure matrix-assisted laser desorption/ionization, nano-electrospray ionization, atmospheric pressure chemical ionization, desorption electrospray ionization (DESI), direct analysis in real-time (DART), direct atmospheric pressure chemical ionization (DAPCI), dielectric barrier discharge ionization, low temperature plasma desorption ionization, and electrospray-assisted laser desorption ionization, an inductively-coupled plasma, a spark ion source, a corona discharge ion source, and/or a radioactive ion source (e.g., 63Ni or 241Am), etc. In embodiments, the ion source 102 may generate ions from a sample at atmospheric pressure or other pressures (e.g., a reduced pressure, high pressure, etc.).
As shown in
The ion transfer tube 106 can be configured to deliver an ion stream 110 from the ion source 102 to an ion detection device 114 with a coaxial sheath gas flow 128. In some embodiments, the ion transfer tube 106 may include a flexible tube configured to contain a gas flow, such as a polymer flow tube, and may be selected to minimize ion losses. In some other specific embodiments, the ion transfer tube 106 may include other materials suitable for a gas flow, such as glass or metal, and may be conductive or non-conductive.
Additionally, the diameter of the first conduit 104 may be smaller than the diameter of the ion transfer tube 106 in order to facilitate a coaxial sheath gas flow 128. A coaxial sheath gas flow 128 encompasses an ion stream 110 introduced from the first conduit outlet 130 into a sheath gas flow 108 that is pumped through the ion transfer tube 106, where the sheath gas flow 108 separates the ions in the ion stream 110 from the walls of the ion transfer tube 106. The ion stream 110 is concentrated in a central portion of the cross section of the ion transfer tube 106, where the sheath gas flow 108 velocity increases the flow velocity of the ion stream 110. This coaxial sheath gas flow 128 prevents ion losses to the walls of the ion transfer tube 106, decreases residence time of the ions in the ion transfer tube 106, and minimizes possible charging of the inner surface of the ion transfer tube 106.
As illustrated in
In implementations, the ion detection device 114 may include a mass spectrometer that separates ionized masses based on charge to mass ratios and outputs the ionized masses to a detector. Some examples of an ion detection device 114 and/or mass spectrometer include a quadrupole mass analyzer, a time of flight (TOF) mass analyzer, a magnetic sector mass analyzer, an electrostatic sector mass analyzer, a quadrupole ion trap mass analyzer, etc. Some examples of a detector that can be used in the ion detection device 114 and/or mass spectrometer can include an electron multiplier, Faraday cups, and/or ion-to-photon detectors.
Additionally, pump 116 can be coupled to the ion detection device 114 as illustrated in
Referring to
Illustrated in
The processor 120 provides processing functionality for the analysis system 100 and/or controller 118 and can include any number of processors, micro-controllers, or other processing systems, and resident or external memory for storing data and other information accessed or generated by the analysis system 100 and/or controller 118. The processor 120 can execute one or more software programs that implement techniques described herein. The processor 120 is not limited by the materials from which it is formed or the processing mechanisms employed therein and, as such, can be implemented via semiconductor(s) and/or transistors (e.g., using electronic integrated circuit (IC) components), and so forth.
The controller 118 may include a memory 122. The memory 122 can be an example of tangible, computer-readable storage medium that provides storage functionality to store various data associated with operation of the analysis system 100 and/or controller 118, such as software programs and/or code segments, or other data to instruct the processor 120, and possibly other components of the analysis system 100 and/or controller 118, to perform the functionality described herein. Thus, the memory 122 can store data, such as a program of instructions for operating the analysis system 100 (including its components), and so forth. It should be noted that while a single memory 122 is described, a wide variety of types and combinations of memory (e.g., tangible, non-transitory memory) can be employed. The memory 122 can be integral with the processor 120, can comprise stand-alone memory, or can be a combination of both. In specific instances, the memory 122 may include a buffer (e.g., a region of a physical memory storage used to temporarily store data while it is being moved from one place to another) and/or datalog for storing sensor data.
The memory 122 can include, but is not necessarily limited to removable and non-removable memory components, such as random-access memory (RAM), read-only memory (ROM), flash memory (e.g., a secure digital (SD) memory card, a mini-SD memory card, and/or a micro-SD memory card), magnetic memory, optical memory, universal serial bus (USB) memory devices, hard disk memory, external memory, and so forth. In implementations, the analysis system 100 and/or the memory 122 can include removable integrated circuit card (ICC) memory, such as memory provided by a subscriber identity module (SIM) card, a universal subscriber identity module (USIM) card, a universal integrated circuit card (UICC), and so on.
The controller 118 may include a communications interface 124. The communications interface 124 can be operatively configured to communicate with components of the analysis system 100. For example, the communications interface 124 can be configured to transmit data for storage in the analysis system 100, retrieve data from storage in the analysis system 100, and so forth. The communications interface 124 can also be communicatively coupled with the processor 120 to facilitate data transfer between components of the analysis system 100 and the processor 120 (e.g., for communicating inputs to the processor 120 received from a device communicatively coupled with the analysis system 100 and/or controller 118). It should be noted that while the communications interface 124 is described as a component of an analysis system 100 and/or controller 118, one or more components of the communications interface 124 can be implemented as external components communicatively coupled to the analysis system 100 via a wired and/or wireless connection. The analysis system 100 can also include and/or connect to one or more input/output (I/O) devices (e.g., via the communications interface 124), including, but not necessarily limited to a display, a mouse, a touchpad, a keyboard, and so on.
The communications interface 124 and/or the processor 120 can be configured to communicate with a variety of different networks, including, but not necessarily limited to a wide-area cellular telephone network, such as a 3G cellular network, a 4G cellular network, or a global system for mobile communications (GSM) network; a wireless computer communications network, such as a WiFi network (e.g., a wireless local area network (WLAN) operated using IEEE 802.11 network standards); an internet; the Internet; a wide area network (WAN); a local area network (LAN); a personal area network (PAN) (e.g., a wireless personal area network (WPAN) operated using IEEE 802.15 network standards); a public telephone network; an extranet; an intranet; and so on. However, this list is provided by way of example only and is not meant to limit the present disclosure. Further, the communications interface 124 can be configured to communicate with a single network or multiple networks across different access points.
Generally, any of the functions described herein can be implemented using hardware (e.g., fixed logic circuitry such as integrated circuits), software, firmware, manual processing, and/or a combination thereof. Thus, the blocks discussed in this disclosure generally represent hardware (e.g., fixed logic circuitry such as integrated circuits), software, firmware, or a combination thereof. In the instance of a hardware configuration, the various blocks discussed in the above disclosure may be implemented as integrated circuits along with other functionality. Such integrated circuits may include all of the functions of a given block, system, or circuit, or a portion of the functions of the block, system, or circuit. Further, elements of the blocks, systems, or circuits may be implemented across multiple integrated circuits. Such integrated circuits may comprise various integrated circuits, including, but not necessarily limited to a monolithic integrated circuit, a flip chip integrated circuit, a multichip module integrated circuit, and/or a mixed signal integrated circuit. In the instance of a software implementation, the various blocks discussed in the above disclosure represent executable instructions (e.g., program code) that perform specified tasks when executed on a processor. These executable instructions can be stored in one or more tangible computer readable media. In some such instances, the entire system, block, or circuit may be implemented using its software or firmware equivalent. In other instances, one part of a given system, block, or circuit may be implemented in software or firmware, while other parts are implemented in hardware. In a specific embodiment, an analysis function or other parts and functions of the analysis system 100 can be implemented on a remote system (e.g., a server).
Further, the analysis system 100 and/or the communications interface 124 may include a user interface. In implementations, a user interface can include a device configured to display information to a user. For example, a user interface can include a display screen and/or a touch screen. In one specific embodiment, analysis system 100 and communications interface 124 includes a user interface that further includes a touch screen that is coupled to controller 118 and is configured to present sensor information to a user. In this specific embodiment, the user interface may also receive input from a user and transmit the input to controller 118.
Example Processes
Accordingly, an ion stream is provided using an ion source (Block 302). In implementations, producing an ion stream including a sample of ions can include, for example, using an ion source 102 (e.g., electrospray ionization, inductively-coupled plasma, spark ionization, a corona source, a radioactive source (e.g., 63Ni), etc.) to produce the ions and create a vapor and/or aerosol containing the ions (e.g., ion stream 110), which may subsequently be introduced into first conduit 104 and/or ion transfer tube 106. In one embodiment, producing a sample of ions includes using an ion source 102 including an electrode and a low-temperature plasma ionization process. In another embodiment, providing an ion stream 110 can include using a corona discharge ion source that utilizes a corona discharge surrounding a conductor to produce the sample of ions from an object of interest. In another embodiment, providing an ion stream can include using electrospray ionization that is used to produce the sample of ions. Electrospray ionization may include applying a high voltage to a sample through an electrospray needle, which emits the sample in the form of an aerosol. The aerosol then traverses the space between the electrospray needle and a cone while solvent evaporation occurs, which results in the formation of ions. It is contemplated that providing an ion stream may include using other types of an ion source 102.
Additionally, providing the ion stream may include using the sheath gas flow 108 in the ion transfer tube 106 to provide a vacuum (e.g., a venture configuration) that can pull ions generated from the ion source 102 into the first conduit 104 and into the ion transfer tube 106. It is contemplated that other methods may be utilized to move the ions into the first conduit 104 and/or ion transfer tube 106.
The ion stream is provided to an ion detection device using an ion transfer tube (Block 304). In implementations, providing an ion stream can include using a coaxial sheath gas flow 128 in the ion transfer tube 106 to deliver the ion stream 110 to the ion detection device 114. In these implementations, a sample of ions and/or the ion stream 110 can travel and/or move through the first conduit 104 and exit the first conduit outlet 130 generally into the cross-sectional center of the ion transfer tube 106 and sheath gas flow 108, which results in a coaxial sheath gas flow 128. The coaxial sheath gas flow 128 can include the ion stream 110 generally in the center of and/or away from the walls of the ion transfer tube 106, where the ion stream 110 is cross-sectionally linearly surrounded by the sheath gas flow 108. In a specific embodiment, the sheath gas flow 108, which may be created using a pump 126 disposed proximate to the second conduit 112 and/or the ion detection device 114, can pull ions produced by the ion source 102 into the first conduit 104 and the ion transfer tube 106 with a much higher flow rate than the intake flow of the second conduit 112 and ion detection device 114. The high flow decreases ion residence time within the ion transfer tube 106. This allows a reduction of ion diffusion and ion losses on the walls of the ion transfer tube 106 due to decreased residence time of the ions and ion stream 110 within the ion transfer tube 106 and due to minimal contact of the ion stream 110 with the walls of the ion transfer tube 106. Because the sheath gas flow 108 separates the ions and ion stream 110 from the walls of the ion transfer tube 106, possible charging of the ion transfer tube 106 is avoided when the ion transfer tube 106 includes a nonconductive material.
Once the ion stream 110 and ions enter and/or are drawn into the second conduit 112, the ions may be transported into the ion detection device 114 and/or mass spectrometer and may be analyzed to determine the composition of the object of interest associated with the ions.
Although the invention has been described in language specific to structural features and/or methodological acts, it is to be understood that the invention defined in the appended claims is not necessarily limited to the specific features or acts described. Although various configurations are discussed the apparatus, systems, subsystems, components and so forth can be constructed in a variety of ways without departing from this disclosure. Rather, the specific features and acts are disclosed as example forms of implementing the claimed invention.
