WO2014014742A1

WO2014014742A1 - System for and techniques of manufacturing a monolithic analytical instrument

Info

Publication number: WO2014014742A1
Application number: PCT/US2013/050141
Authority: WO
Inventors: David Phillip FERGENSON
Original assignee: Fergenson David Phillip
Priority date: 2012-07-17
Filing date: 2013-07-11
Publication date: 2014-01-23
Also published as: WO2014014742A4

Abstract

An analytical instrument exemplified by a time-of-flight mass spectrometer that includes the monolithic construction of multiple electrodes in a single structure where the points at which the voltage is imparted are connected resistively. The substrate on which the resistive surface is deposited is not only insulative but also, optionally, has characteristics that allow it to be used as the vacuum containment vessel. Because there is no separation between electrodes of different voltages and because the vacuum vessel is insulative, there is a significantly reduced possibility of unexpected electrical discharge which can damage an analytical instrument.

Description

SYSTEM FOR AND TECHNIQUES OF MANUFACTURING A MONOLITHIC

ANALYTICAL INSTRUMENT

Cross-Reference to Related Application

[0001] This application claims the benefit and priority from U. S. Application Provisional

Application 61/672,715, filed 17 July 2012, the contents and disclosure of which are incorporated herein by reference for all purposes.

Background

Field

[0002] The invention relates to analytical instrumentation in general and mass spectrometry in particular.

Background

[0003] Many analytical instruments must be operated within a vacuum. Many of these instruments operate by applying electric fields which must be constructed within the vacuum chamber using electrodes operated at different voltages. An example of these instruments, in general, includes mass spectrometers, an old, broad and very powerful class of analytical instruments.

[0004] While different general approaches to mass spectrometry exist, all produce the same fundamental information: the determination of the mass-to-charge ratios of ions produced from a chemical sample. Typically, a mass spectrometer will determine the relative concentration of ions of various mass-to-charge ratios from a single sample. Many different approaches to the ionization of the chemical sample exist and, in some cases, other analytical technologies are implemented either upstream or downstream of the mass spectrometer. An example of an upstream technology is the use of a gas chromatograph prior to analysis by a mass spectrometer (a GC-MS) and an example of a downstream analysis is the reanalysis of mass peaks by a second mass spectrometer (MS-MS) as in a triple quadrupole mass spectrometer. Needless to say, mass spectrometers have been implemented across a very broad variety of scientific and technological applications and are integral to many industries. A particularly useful variety of mass spectrometer is the time-of-flight mass spectrometer (TOFMS).

[0005] Since first viable time-of-flight mass spectrometer was reported in the literature in 1955, all TOFMS systems have been constructed using the same technologies. A vacuum housing, typically made of either aluminum or stainless steel, is machined and/or welded. High voltage feedthroughs are installed in the housing. Inside of this housing, annular metal electrodes are mounted on insulators and connected to the high voltage sources, usually using high voltage wire. As discussed below, In the case of a reflectron, the ion mirror is made of a series of annular electrodes connected to one another via resistors with different voltages applied to the first and last of the electrodes.

Summary

[0006] The present invention is in one embodiment a time-of-flight mass spectrometer that is far easier to manufacture, less expensive, eliminates many long lead-time parts, eliminates a common failure mode of such systems and produces closer to ideal electric fields. The invention includes the monolithic construction of multiple electrodes in a single structure where the points at which the voltage is imparted are connected resistively. In its preferred embodiment, the substrate on which the resistive surface is deposited is not only insulative but also, optionally, has characteristics that allow it to be used as the vacuum containment vessel as well. Because there is no separation between electrodes of different voltages and the vacuum vessel is insulative, there is a significantly reduced possibility of unexpected electrical discharge which can damage an analytical instrument. While described embodiments focus on time-of- flight instruments, the invention may be generalized to all other mass spectrometers or any analytical instrument that combines vacuum and an electric field.

Brief Description of the Drawings

[0007] The Figures represent embodiments of the invention and are not intended to be limiting of the scope of the invention. [0008] FIGURE 1 is a schematic I diagram of a typical time-of-flight mass spectrometer constructed using current technology.

[0009] FIGURE 2 is a schematic I diagram of an embodiment of our monolithic mass spectrometer.

[0010] FIGURE 3 is a schematic diagram of another em bodiment of our monolithic mass spectrometer.

Detailed Description

[0011] The invention in broad scope relies on a novel general approach to designing and manufacturing analytical instruments such as a mass spectrometer of an advanced design and for a method of manufacturing such analytical instruments. One embodiment comprises a mass spectrometer device in which the electrodes are integrated into the surfaces of a structure which, optionally, may serve as a vacuum chamber and where the vacuum chamber is insulative. Alternatively, an embodiment is a mass spectrometer device manufactured monolithically with multiple voltage and voltage changing domains integrated into the same structural body. The invention also encompasses, inter alia, alternate methods of manufacturing the mass spectrometer embodiments described above. Advantages of the device include reductions in weight and size, and the removal of a common failure mode and the possibility of a device that more closely approaches ideal designs. Advantages of the embodiment of a method of manufacturing the device include a significantly reduced number of parts, reduced cost of the parts themselves, and possible automated production and assembly, resulting in a significantly reduced product cost.

[0012] A time-of-flight mass spectrometer (TOFMS), first made practical by Wiley and McLaren in 1955, is the conceptually simplest form of mass spectrometer, though not the least expensive to manufacture. I n a TOFMS, ions are generated in or transported to the space between two annular electrodes that are maintained at different voltages (Wiley, W.C. and McLaren, I.H., Rev. Sci. Inst., 26 (1955) 1150-1157). The electric field gradient imparts kinetic energy into sample ions that equals the difference in voltage between their point of origin and the exit of the acceleration region multiplied by the number of charges on the ions (typically one). For any particular quantity of kinetic energy imparted into an ion, that ions velocity is inversely proportional to the square of its velocity; therefore, by measuring that velocity, one can compute the mass-to-charge ratio. The simplest TOFMS measures those velocities by synchronizing the ions' time and place of origin and determining their time of arrival at an ion detector, typically a micro channel plate, maintained a fixed distance away from the acceleration electrodes. A source of unpredictable behavior of a TOFMS, leading to a reduction in resolution, is the addition of kinetic energy to the sample ions through processes unrelated to the electric field acceleration.

[0013] In 1978, B.A. Mamyrin and colleagues patented an improved TOFMS which he termed the "reflectron" though that term is often erroneously used to refer to the distinguishing component of his design which he, himself, had termed an ion mirror (Mamyrin, Boris Alexandrovich, Karataev, Valery Ivanovich, and Shmikk, Dmitry Viktorovich. 1976. TIME-OF- FLIGHT MASS SPECTROMETER. US Patent 4,072,862, filed June 14, 1976, and issued February 7, 1978.). In a reflectron, ions are accelerated as in a standard TOFMS but, upon arriving at the end of a flight tube where they would normally encounter the detector, they instead encounter an area of increasing electrical potential of their own polarity. This electric field ramp halts their motion and redirects them back down the field free drift region until they arrive at an ion detector. A common variation on this design is the use of an annular detector through which the ions are projected on their outward journey and which they strike on their return. The advantage of the reflectron is that it introduces a slight delay for the ions that is a function of their initial kinetic energies. When properly designed and implemented, the ion mirror can mitigate variations in the times of arrival of ions of the same mass-to-charge ratio, ideally ensuring that all ions of a given mass-to-charge ratio ultimately arrive at the detector at the same time.

[0014] Since the creation of the Wiley and McLaren TOFMS in 1955, all TOFMS systems have been constructed using the same technologies. A vacuum housing, typically made of either aluminum or stainless steel, is machined and/or welded with flanges integrated into the housing to allow it to be sealed once the mass spectrometer has been installed. High voltage feedthroughs are installed elsewhere in the housing. Inside of this housing, annular metal electrodes are mounted on insulators and connected to the high voltage sources, usually using vacuum-compatible high voltage wire. In the case of a reflectron, the ion mirror is made of a series of annular electrodes connected to one another via resistors with different voltages applied to the first and last of the electrodes. Photonis, Inc., disclosed the use of a resistive glass tube to be implemented in place of the annular metal rings in 2006, though their TOFMS was conventional in all other respects. They elaborated on this in a patent describing the use of resistive glass as electrodes in scientific instruments. Even though there were significant advantages gained by the use of resistive glass, again, only the use of the glass in place of metal electrodes was disclosed (Laprade, B.N., 2011, RESISTIVE GLASS STRUCTURES USED TO SHAPE ELECTRIC FIELDS IN ANALYTICAL INSTRUMENTS, filed December 22, 2009, and issued December 27, 2011).

[0015] The present invention is a device and method that is far easier to manufacture, less expensive, eliminates many long lead-time parts, eliminates a common failure mode of such systems and produces closer to ideal electric fields versus previous designs. The invention comprises the monolithic construction of multiple electrodes in a single structure where the points at which the voltage is imparted are connected resistively. The monolithic construction may originate from segments that are permanently attached, preferably by a vacuum- compatible epoxy or a thermal bonding process. In its preferred embodiment, the substrate on which the resistive surface is deposited is not only insulative but also has characteristics that allow it to be used as the vacuum containment vessel as well. Because there is no separation between electrodes of different voltages, there is a dramatically reduced probability of electrical discharge occurring between the electrodes themselves or between an electrode and a grounded, conductive vacuum vessel.

[0016] Two general designs serve to illustrate embodiments of the invention. The two require an understanding of several materials, components and processes that are discussed following. MicroPen Technologies Corporation manufactures resistors made to specification under the brand name OhmCraft™ by depositing a trace of varying width, thickness and linear resistivity in an arbitrary pattern using a computer-controlled syringe combined with the robotic manipulation of the substrate. Vacuum compatible epoxies exist, with Varian Vacuum's Torr Seal or its equivalents including Henkel Hysol H1C being the most popular class. These epoxies are electrically insulative and bond to metal, glass or ceramic. Compact high voltage power supplies, such as those available from HVM Technology, Inc., have been developed for night vision goggles and meet the performance specifications required for TOFMS systems but are less than 0.25 cubic inches in volume and are available as integrated circuits. Photonis USA, Inc. manufactures a resistive glass product whose surface can be made variably resistive or, alternatively, insulative. The product is available as sheets or tubing. Many ceramic tubes of various widths, lengths or tolerances are available from a variety of manufacturers. Some ceramic tubes have integrated flanges. Photonis has produced a demonstration version of an ion detector which is both floated at high voltage, coaxial and impedance-matched to 50 ohms, though other approaches to creating an annular ion detector exist (Laprade, B., 2006, DETECTOR FOR A CO-AXIAL BIPOLAR TIME-OF-FLIGHT MASS SPECTROMETER, filed May 15, 2005, and issued November 28, 2006).

[0017] One embodiment of the present invention is thus: A resistive glass tube is fabricated with holes which accommodate pins through which high voltage can be passed. The holes are sealed with Torr Seal epoxy or similar. Annular MicroPen traces of negligible resistance ensure that the voltage is distributed evenly at any meridian of the tube where high voltage is being introduced. The pins intersect the traces to impart voltage to the annulus. The pins are shaped such that they will contact the interior surface of the resistive glass under tension. A Photonis Corporation annular ion detector (or equivalent) is centered on the axis of the tubing at the edge of the ion source region of the mass spectrometer and pointed towards the ion mirror. HVM Technology high voltage transformers (or equivalents) are mounted on the exterior surface of the tube. Non-resistive MicroPen traces lay out a circuit board on the exterior of the glass, conducting the power, ground, control, and sense lines to those transformers while the high voltage pin from each transformer is connected directly to a feedthrough pin which penetrates the epoxy. In this manner, the entire mass spectrometer can be produced from a single, monolithic tube. Vacuum pumping and gauging can be mounted at either end of the mass spectrometer on flanges that are connected to or integrated with the housing.

[0018] Another embodiment is similar to the above but does not use resistive glass. Rather, the housing is made of ceramic with flanges either connected to or integrated with the housing. The interior of the TOFMS is inscribed by a MicroPen process on the interior of a ceramic or glass tube with different zones of resistivity able to mediate the different rates of voltage change in, for example, the source region and the ion mirror. Because a change in resistance can be adjusted during inscription, it is possible to efficiently manufacture a mass spectrometer with non-linear electric fields, focusing the generated ions in a manner that more closely parallels the ideal case. As in the case of the resistive glass tubing, the high voltage power supplies may be mounted directly on the exterior of the mass spectrometer with the power, control and sense lines being distributed from their point of introduction to the power supplies via a trace laid down by MicroPen.

[0019] In still another embodiment, a resistive coating is applied to the interior of a ceramic housing with MicroPen traces at meridians along the coating communicating the high voltages which are introduced in a manner similar to the embodiment above.

[0020] Other embodiments exist that are derivatives of these concepts. For example, the tubing may be manufactured from polycarbonate, fused silica or normal glass, rather than ceramic, with the transparent materials accepting laser light for analyte ionization. Flanges may be constructed integrally to the tubing by additive manufacturing to allow the connection of additional components. The high voltage power supplies may be located remotely with their power being distributed on traces along the surface of the mass spectrometer or else via wires routed to feedthrough pins directly. Or, while it would eliminate some of the benefits, the mass spectrometer structure may be mounted within a vacuum chamber but would still retain some benefits relating to the simplicity of its manufacture and resistance to electrical arcing and would serve as its own insulator.

[0021] Figure 1 illustrates the prior state of the art for mass spectrometers while Figures 2 and 3 describe the embodiments of our invention. In Figure 1, High Voltage Power Supply Module, 101, houses many individual high voltage transformers. High voltage cable, 102, carries the individual voltages to an Electrical Feedthrough, 103 which introduces those voltages into vacuum through a Vacuum Chamber, 104. High Voltage Wires, 105, carry the high voltage electricity to Electrodes, 106, which are mounted on Insulative Mounts, 107. When voltages need to be varied systematically along an axis, Resistors, 108, are used to connected annular electrodes where the first and last electrodes are operated at different voltages, with the resistors determining the voltages of the intermediate electrodes. In an alternate embodiment, the ion mirror is manufactured from resistive glass rather than from annular metal rings connected by resistors.

[0022] Figure 2 discloses one preferred embodiment of the invention. Individual High Voltage Transformers, 201, are mounted directly to a Vacuum Housing, 202, which is made of glass with a Resistive Interior, 203, and an insulative exterior. The High Voltage Transformers' low voltage power and control circuitry is routed on the exterior of that housing. The high voltage is communicated through holes, 204, that are sealed against vacuum with Epoxy, 205. The holes are aligned with the locations of annular conductive traces, 206, that distribute the voltage longitudinally. Note that no machined electrodes, insulative mounts, exterior high voltage cable or interior high voltage wires are necessary. Due to the insulative nature of the housing and the fact that the electrical potential adjacent to the point of introduction on the interior is similar to that at the point of introduction itself, the expensive feedthroughs of the prior art devices are replaced by far simpler pins introduced through very small holes and either sealed with Epoxy or sealed by brazing.

[0023] Figure 3 illustrates another preferred embodiment of the invention. As in Figure 2, individual High Voltage Transformers, 301, are connected to Conductive Points, 302, on the interior of the Insulative Housing, 304, through Pins, 303, introduced through holes and sealed with epoxy. Conductive traces, 305, laid down by a MicroPen (or equivalent) fabrication technique, communicate the voltages along meridians on the interior of the mass spectrometer. A resistive coating, 306, ensures a monotonous change in voltage between the conductive traces as in current TOFMS designs. A minor variation on this embodiment involves the axial variation in resistance of the coating, allowing higher order voltage curves consistent with the more ideal electric fields as in, for example, a curved field reflectron. As in the general design disclosed in Figure 2, low voltage traces on the exterior of the mass spectrometer can power and control the high voltage transformers. An additional advantage of this construction methodology is that it is compatible with any insulative surface including a surface manufactured from an inexpensive material or from a material capable of conducting light for laser desorption/ionization mass spectrometry.

[0024] The technology of this invention is distinct from all other mass spectrometers and techniques used to manufacture them. Agilent (as Hewlett-Packard) pioneered the use of metalized glass electrodes in their quadrupole mass spectrometers (Kernan, Jeffrey T., Johnson, Donald A., and Russ, Charles W., IV. 1994. Multilayer multipole. US Patent 5,298,745, filed December 2, 1992, and issued March 29, 1994). However, while these electrodes were easier to manufacture in a shape that was ideal for quadrupole mass spectrometry, they nonetheless remained fairly conventional electrodes in that they were mounted in a metal vacuum chamber, were powered by feedthroughs, and could only have a single high voltage domain in a single metalized area. Photonis has demonstrated the manufacture of an ion mirror using their resistive glass. However, this also remains a conventional mass spectrometer with the exception that the resistive glass displaces the need for individual annular electrodes and resistors. It must still be mounted on insulators and powered conventionally.

[0025] While the invention has been particularly shown and described in particular embodiments above, those skilled in the art will understand that changes in form and detail may be made without departing from the spirit and scope of the invention. Particularly, while the invention indicates the use of these design methodologies to produce a time-of-flight mass spectrometer, any analytical instrument requiring electric fields to be applied under vacuum could be improved in a similar manner.

Claims

1. An analytical instrument comprising a plurality of resistive or conductive domains or a combination of resistive and conductive domains serving as electrodes integrated with the walls of an insulator structure.

2. The analytical instrument of claim 1 wherein the resistive or conductive domains derive their resistive or conductive properties from inherent properties of the surface of the insulator structure.

3. The analytical instrument of claim 2 wherein the insulator structure is configured to serve as a vacuum chamber.

4. The analytical instrument of claim 3 wherein the analytical instrument is a mass spectrometer.

5. The analytical instrument of claim 4 wherein the mass spectrometer is a time-of-flight mass spectrometer.

6. The analytical instrument of claim 1 wherein the resistive or conductive domains are created by applying a coating or a pattern of coatings to the interior of the insulator structure.

7. The analytical instrument of claim 6 wherein the insulator structure is configured to serve as a vacuum chamber.

8. The analytical instrument of claim 7 wherein the instrument is a mass spectrometer.

9. The analytical instrument of claim 8 wherein the mass spectrometer is a time-of-flight mass spectrometer.

10. A method of manufacturing an analytical instrument whereby a plurality of electrodes is created by integrating a plurality of resistive or conductive domains or a combination of resistive and conductive domains with the walls of an insulator structure.

11. The method of manufacturing an analytical instrument of claim 10 wherein the resistive or conductive domains derive their resistive or conductive properties from the inherent properties of the surface of the insulator structure.

12. The method of manufacturing an analytical instrument of claim 11 wherein the insulator structure also serves as a vacuum chamber.

13. The method of manufacturing an analytical instrument of claim 12 wherein the analytical instrument is a mass spectrometer.

14. The method of manufacturing an analytical instrument of claim 13 wherein the mass spectrometer is a time-of-flight mass spectrometer.

15. The method of manufacturing an analytical instrument of claim 10 wherein the resistive or conductive domains are created by applying a coating or a pattern of coatings to the interior of the insulator structure.

16. The method of manufacturing an analytical instrument of claim 15 wherein the insulator structure also serves as a vacuum chamber.

17. The method of manufacturing an analytical instrument of claim 16 wherein the instrument is a mass spectrometer.

18. The method of manufacturing an analytical instrument of claim 17 wherein the mass spectrometer is a time-of-flight mass spectrometer.