Method for confirming charged particle generation in an instrument and associated instrument
阅读说明:本技术 用于确认仪器中带电粒子产生的方法及相关的仪器 (Method for confirming charged particle generation in an instrument and associated instrument ) 是由 詹姆斯·亚瑟·凡高登 于 2019-02-11 设计创作,主要内容包括:本发明提供多种用于确认一仪器中带电粒子产生的方法。一种确认一仪器中带电粒子产生的方法包括:当所述带电粒子光学系统位于一腔室时,为所述仪器的一带电粒子光学系统提供电连接。所述方法包括:将一电子部件耦合到在所述腔室内产生的带电粒子电流,所述电子部件包括一阻抗。此外,所述方法包括:通过所述电子部件测量对所述带电粒子电流的一电响应。本发明还提供多种相关的仪器。(The present invention provides various methods for confirming charged particle generation in an instrument. A method of confirming charged particle generation in an instrument comprising: providing an electrical connection to a charged particle optical system of the instrument when the charged particle optical system is in a chamber. The method comprises the following steps: an electronic component is coupled to the charged particle current generated within the chamber, the electronic component including an impedance. Further, the method comprises: an electrical response to the charged particle current is measured by the electronic component. The invention also provides a plurality of related instruments.)
1. A method for confirming charged particle production in a mass spectrometer, comprising: the method comprises the following steps: providing an electrical connection to a charged particle optical system of the mass spectrometer when the charged particle optical system is in a chamber;
coupling an electronic component to the charged particle current generated within the chamber, the electronic component comprising an impedance; and
an electrical response to the charged particle current is measured by the electronic component.
2. The method of claim 1, wherein: providing the charged particle optical system with the electrical connection comprises: grounding or applying a voltage to a plurality of adjacent ion optical screens or plates of the charged particle optical system.
3. The method of claim 2, wherein:
the electronic components include an electrical assembly located outside the chamber;
wherein the impedance comprises a resistance value of the resistor, the resistance value being between 10 kilo-ohms (k Ω) and 100 mega-ohms (M Ω);
wherein grounding or applying the voltage to a plurality of adjacent ion optical screens or plates of the charged particle optical system comprises:
grounding an extraction plate of the charged particle optical system;
connecting a first side of the resistor to a rear bias plate of the charged particle optical system when a rear bias plate is in the chamber and the resistance is outside the chamber;
connecting a power source to a second side of the resistor when the power source is outside the chamber; and applying the voltage via the power source when the power source is outside the chamber.
4. The method of claim 3, wherein: the resistance value of the resistor is between 100k Ω and 100M Ω.
5. The method of claim 3 or 4, wherein: the method further comprises the following steps: disconnecting a cable attached to a component of the charged particle optical system other than the extraction plate and the rear bias plate.
6. The method of any of claims 3 to 5, wherein: the method further comprises the following steps: emitting a laser of the mass spectrometer toward a sample plate located within the chamber to generate the charged particle current within the chamber while the first and second sides of the resistor are connected to the rear bias plate and the power supply, respectively, and the power supply applies the voltage when the extraction plate is grounded.
7. The method of claim 6, wherein:
emitting the laser light includes: emitting the laser light towards a sample located on the sample plate; and wherein the method further comprises: emitting the laser light towards a blank slide without any sample; and determining whether a measurable current generated by lasing the blank slide passes through the resistor.
8. The method of any of claims 1 to 7, wherein: the method further comprises the following steps: removing a downstream charged particle optical component of the charged particle optical system, wherein the electronic component is galvanically coupled with the charged particles when the downstream charged particle optical component is removed.
9. The method of any of claims 1 to 8, wherein: the method further comprises the following steps: determining that the mass spectrometer is not generating a signal, and wherein providing the electrical connection for the charged particle optical system comprises: providing a first state of the electrical connection in response to determining that the mass spectrometer is not generating a signal, the first state being different from a previous second state of the electrical connection.
10. The method of any of claims 1 to 9, wherein: the charged particle current comprises a measured ion current, and wherein the method further comprises: comparing the measured ion current to a predetermined value to determine an amount of ions generated by the chamber.
11. The method of any of claims 1 to 10, wherein: the charged particle current comprises a current of an electron beam generated within the chamber.
12. The method of any of claims 1 to 11, wherein:
coupling comprises emitting a laser of the mass spectrometer towards a target within the chamber, thereby generating the charged particle current; and
wherein the method further comprises: adjusting a laser energy and/or a laser focus of the laser in response to the electrical response to the charged particle current measured by the electronic component.
13. The method of any of claims 1 to 12, wherein: providing the electrical connection is performed with the chamber under vacuum pressure.
14. A method of confirming ionization in a mass spectrometer, characterized by: the method further comprises the following steps: grounding a first plate or screen of an ion optical system of the mass spectrometer while the first plate or screen is in a chamber under vacuum pressure;
connecting a first side of an electronic component comprising an impedance to a second plate or screen of the ion optical system when the second plate or screen is within the chamber;
connecting a power source to a second side of the electronic component when the power source is outside the chamber; applying a voltage via the power source when the power source is outside the chamber;
emitting a laser of the mass spectrometer toward a sample plate of the mass spectrometer while the first and second sides of the electronic component are connected to the second plate or screen and the power supply, respectively, while the power supply applies the voltage, when the first plate or screen is grounded; and
coupling the electronic component to an ion current generated by a sample on the sample plate while the sample plate is within the chamber.
15. The method of claim 14, wherein:
the electronic component comprises a resistor located outside the chamber;
the impedance comprises a resistance value of the electrical component, the resistance value being between 100k Ω and 100M Ω; the method further comprises the following steps: determining that the mass spectrometer is not producing a signal; the first plate or screen comprises an extraction plate; said second panel or screen comprises a rear biasing panel; and
connecting the first side to ground in response to determining that the mass spectrometer is not producing a signal.
16. The method of claim 14 or 15, wherein: the method further comprises the following steps:
measuring a first electrical response of the electronic component to the ion current;
emitting the laser light towards a blank slide without any sample; and
measuring a second electrical response by the electronic component, or detecting whether the second electrical response is absent, thereby emitting the laser light toward the blank slide.
17. The method of any of claims 14 to 16, wherein: the method further comprises the following steps: comparing the ion current to a predetermined value to determine a quantity of ions generated.
18. A mass spectrometer, characterized by: the mass spectrometer comprises:
a chamber, comprising:
an ion optical system comprising a first plate or screen and a second plate or screen; and
a sample plate;
a power source located outside the chamber; and
an electronic component connectable between the second plate or screen and the power source, wherein the electronic component comprises: an impedance, and the electronic components are configured to receive a current of charged particles generated by the chamber.
19. The mass spectrometer of claim 18, wherein: the electronic component includes a resistor located outside the chamber, and wherein the impedance includes a resistance value of the electrical component between 10 kilo-ohms (k Ω) and 100 mega-ohms (M Ω).
20. The mass spectrometer of claim 19, wherein: the mass spectrometer further comprises: a laser configured to emit towards the sample plate while a first side and a second side of the resistor are connected to the second plate or screen and the power supply, respectively, and the power supply applies a voltage;
wherein the resistor is configured to receive an ion current generated by a sample located on the sample plate; wherein the resistance value of the resistor comprises a predetermined value between 100 kilo-ohms (k Ω) and 100 mega-ohms (M Ω); and
wherein the first plate or screen comprises an extraction plate and the second plate or screen comprises a rear biasing plate.
21. The mass spectrometer of claim 20, wherein: the mass spectrometer further comprises: a shorting plug by which the extraction plate may be grounded, wherein the laser is configured to emit toward the sample plate when the extraction plate is grounded.
22. The mass spectrometer of claim 20 or 21, wherein: the mass spectrometer further comprises a switch by which the extraction plate is switchably grounded;
wherein the switch is located outside the chamber, an
Wherein the laser is configured to emit towards the sample plate when the extraction plate is grounded.
23. The mass spectrometer of any one of claims 20 to 22, wherein: the mass spectrometer further comprises: a switch by which the resistor is switchably connected between the rear bias plate and the power supply, wherein the switch is located outside the chamber.
24. The mass spectrometer of any one of claims 18 to 23, wherein: a deflector portion of the ion optical system is removable from the ion optical system.
Technical Field
The present invention relates to mass spectrometers and to other instruments for generating charged particles.
Background
A mass spectrometer is a device that ionizes a sample and then determines the mass-to-charge ratio of the resulting collection of ions. Time-of-flight mass spectrometry (TOFMS) is a well-known mass spectrometer in which the mass-to-charge ratio of ions depends on the time required for an ion to travel from the ion source to a detector under the influence of an electric field. The spectral quality in TOFMS reflects the initial conditions of the ion beam before it is accelerated into a field free drift region. In particular, any factor that results in ions of the same mass having different kinetic energies and/or being accelerated from different sites in space may result in a decrease in spectral resolution, resulting in a decrease in mass accuracy.
Matrix-assisted laser desorption ionization (MALDI) is a method of preparing gas phase biomolecular ions for mass spectrometry. The development of MALDI-TOF delayed extraction technology (DE) has made high resolution analysis based on MALDI instruments routine. In DE-MALDI, a short delay is added between the application of the laser triggered ionisation event and the application of the acceleration pulse to the TOF source region. Fast ions (i.e., high energy ions) travel further than slow ions, thereby converting the energy distribution at ionization to a spatial distribution at acceleration (the ionization region prior to application of the extraction pulse).
See U.S. patent nos. 5625184, 5627369, 5760393 and 9536726. See also Wiley et al, "enhanced resolution time-of-flight Mass spectrometer", journal of scientific Instrument review, Vol.26, No. 12, pp.1150 to 1157 (2004); modern MALDI time-of-flight mass spectrometry, journal of mass spectrometry, volume 44,
Disclosure of Invention
Embodiments of the present invention relate to various methods for confirming charged particle generation. According to some embodiments, a method for confirming charged particle generation in an instrument, the method comprising: providing an electrical connection to the charged particle optical system of the mass spectrometer when a charged particle optical system is located in a chamber. The method may comprise: an electronic component is coupled to the charged particle current generated within the chamber, the electronic component including an impedance. Further, the method may comprise: an electrical response to the charged particle current is measured by the electronic component.
In some embodiments, providing the electrical connection for the charged particle optical system may comprise: grounding or applying a voltage to a plurality of adjacent ion optical screens or plates of the charged particle optical system. The electronic components may include an electrical component located outside the chamber, and the impedance may include a resistance value of the resistor between 10 kilo-ohms (k Ω) and 100 mega-ohms (M Ω). Furthermore, grounding or applying the voltage to a plurality of adjacent ion optical screens or plates of the charged particle optical system may comprise: grounding an extraction plate of the charged particle optical system; connecting a first side of the resistor to a rear bias plate of the charged particle optical system when a rear bias plate is in the chamber and the resistance is outside the chamber; connecting a power source to a second side of the resistor when the power source is outside the chamber; and applying the voltage via the power source when the power source is outside the chamber.
In some embodiments, the resistance value of the resistor is between 100k Ω and 100M Ω. Additionally or alternatively, the method may comprise: disconnecting a cable attached to a component of the charged particle optical system other than the extraction plate and the rear bias plate. Further, in some embodiments, the method may comprise: emitting a laser of the instrument toward a sample plate located within the chamber to generate the charged particle current within the chamber while the first and second sides of the resistor are connected to the rear bias plate and the power supply, respectively, and the power supply applies the voltage when the extraction plate is grounded. Emitting the laser light may include: emitting the laser light towards a sample located on the sample plate; and the method may comprise: emitting the laser light towards a blank slide without any sample; and the method may comprise: determining whether a measurable current generated by lasing the blank slide passes through the resistor.
In some embodiments, the method may comprise: removing a downstream charged particle optical component of the charged particle optical system. -galvanically coupling the electronic component with the charged particles when the downstream charged particle optical component is removed.
In some embodiments, the instrument may comprise a mass spectrometer, and the method may comprise: determining that the mass spectrometer is not generating a signal. Further, wherein providing the charged particle optical system with the electrical connection may comprise: providing a first state of the electrical connection in response to determining that the mass spectrometer is not generating a signal, the first state being different from a previous second state of the electrical connection.
In some embodiments, the charged particle current may be a measured ion current, and wherein the method may comprise: comparing the measured ion current to a predetermined value to determine an amount of ions generated by the chamber. Additionally, the charged particle current may comprise a current of an electron beam generated within the chamber.
In some embodiments, coupling may include emitting a laser of the instrument toward a target within the chamber, thereby generating the charged particle current. The method may comprise: adjusting a laser energy and/or a laser focus of the laser in response to the electrical response to the charged particle current measured by the electronic component. Additionally or alternatively, providing the electrical connection is performed while the chamber is under vacuum pressure.
A method of confirming ionization in an instrument, the method comprising, according to some embodiments: grounding a first plate or screen of an ion optical system of the instrument while the first plate or screen is in a chamber under vacuum pressure. The method may comprise: connecting a first side of an electronic component comprising an impedance to a second plate or screen of the ion optical system when the second plate or screen is within the chamber. The method may comprise: connecting a power source to a second side of the electronic component when the power source is outside the chamber. The method may comprise: applying a voltage via the power source when the power source is outside the chamber. The method may comprise: emitting a laser of the instrument toward a sample plate of the instrument while the first plate or screen is grounded, while the first side and the second side of the electronic component are connected to the second plate or screen and the power supply, respectively, and the power supply applies the voltage. Further, the method may comprise: coupling the electronic component to an ion current generated by a sample on the sample plate while the sample plate is within the chamber.
In some embodiments, the instrument may comprise a mass spectrometer and the electronic component may be a resistor located outside the chamber. The impedance may be a resistance value of the electrical component, the resistance value being between 100k Ω and 100M Ω; and the method may comprise: determining that the mass spectrometer is not producing a signal. Furthermore, the first plate or screen may be an extraction plate; the second panel or screen may be a rear bias panel; and in response to determining that the mass spectrometer is not producing a signal, grounding and connecting the first side.
In some embodiments, the method may comprise: a first electrical response of the electronic component to the ion current is measured. The method may comprise: the laser was fired towards a blank slide without any sample. Further, the method may comprise: measuring a second electrical response by the electronic component, or detecting whether the second electrical response is absent, thereby emitting the laser light toward the blank slide. Additionally or alternatively, the method may comprise: comparing the ion current to a predetermined value to determine a quantity of ions generated.
According to some embodiments, an apparatus may comprise: a chamber, comprising: an ion optical system includes a first plate or screen and a second plate or screen. The chamber may also include a sample plate. The apparatus may further comprise a power source located outside the chamber; and an electronic component connectable between the second plate or screen and the power source. The electronic component may have an impedance and be configured to receive a current of charged particles generated by the chamber.
In some embodiments, the instrument may include a mass spectrometer, the electronic component may be a resistor located outside the chamber, and wherein the impedance may be a resistance value of the electrical component, the resistance value being between 10 kiloohms (k Ω) and 100 mega-ohms (M Ω). Additionally or alternatively, a deflector portion of the ion optical system is removable from the ion optical system.
In some embodiments, the instrument may comprise: a laser configured to emit towards the sample plate while a first side and a second side of the resistor are connected to the second plate or screen and the power supply, respectively, and the power supply applies a voltage. The resistor is configured to receive an ion current generated by a sample located on the sample plate. The resistance value of the resistor may comprise a predetermined value between 100k Ω and 100M Ω. Further, the first plate or screen may be an extraction plate and the second plate or screen may be a rear bias plate.
In some embodiments, the instrument may comprise: a shorting plug through which the extraction plate may be grounded. The laser is configured to emit towards the sample plate when the extraction plate is grounded. Additionally or alternatively, the apparatus may comprise a switch by which the extraction plate is switchably grounded. The switch is located outside the chamber, and the laser is configured to emit towards the sample plate when the extraction plate is grounded. Further, the apparatus may comprise: a switch by which the resistor is switchably connected between the rear bias plate and the power supply, wherein the switch is located outside the chamber.
Other features, advantages and details of the present invention will be apparent to those of ordinary skill in the art from a reading of the drawings and the following detailed description of exemplary embodiments, which is merely illustrative of the present invention.
It should be noted that although various aspects of the invention are not described with respect to one embodiment, one embodiment may be incorporated into another embodiment. That is, features of all embodiments and/or any embodiment may be combined in any manner and/or combination. The applicant reserves the right to amend any originally issued claim or to issue any new claim accordingly, including the right to be able to modify any originally issued claim to adhere to and/or combine any feature of any other claim, even though such claims are not originally claimed. These and other objects and/or aspects of the present invention are explained in detail in the specification set forth below.
Drawings
FIG. 1A is a perspective view of an instrument according to embodiments of the present invention.
FIG. 1B is a perspective view of an instrument and a light source according to embodiments of the invention.
FIG. 2A shows a schematic diagram of an instrument and light source according to an embodiment of the invention.
FIG. 2B shows a block diagram of the chamber of FIG. 2A, in an embodiment in accordance with the invention.
FIG. 2C shows a block diagram of a processor control system of the instrument of FIG. 2A, in accordance with an embodiment of the present invention.
FIG. 2D shows a block diagram of an example processor and memory that may be used in accordance with an embodiment of the invention.
Figures 3A-3E illustrate schematic diagrams of an external resistor coupled to an ion optical system of the chamber of figures 2A and 2B, in accordance with embodiments of the present invention.
Fig. 4A-4E illustrate a flow chart for confirming ionization or other charged particle generation in an instrument, in accordance with embodiments of the present invention.
Figure 5A shows an oscilloscope trace of an instrument fired on a blank slide in accordance with an embodiment of the present invention.
Figure 5B shows an oscilloscope trace of an instrument fired on a sample slide in accordance with an embodiment of the present invention.
Fig. 6 illustrates a partial cross-sectional perspective view of the chamber interior of fig. 2A and 2B, in accordance with some embodiments of the present invention.
FIG. 7 illustrates a block diagram of a resistor connected to a processor and a laser source for calibrating laser energy and/or laser focus, in accordance with some embodiments of the present invention.
Fig. 8 illustrates a flow diagram of an exemplary method for calibrating laser energy and/or laser focus, in accordance with some embodiments of the invention.
Fig. 9A illustrates a safety high pressure (SHV) feedthrough seal that may be used with an instrument in accordance with some embodiments of the present invention.
Fig. 9B illustrates an SHV patch cable that may be used with an instrument in accordance with some embodiments of the present invention.
Detailed Description
The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which illustrative embodiments of the invention are shown. Like numbers refer to like elements, and prime notation (e.g., 10 ', 10 "') used to indicate different embodiments of the same elements.
During assembly (and/or during operation) of a mass spectrometer/system, it may be advantageous to perform diagnostics to confirm the occurrence of ionization, such as: ionization occurs as a result of a MALDI process. According to an embodiment of the invention, for example: a diagnostic may be provided using existing optics of the instrument/system that acts as a charge collection plate. In addition, an external Direct Current (DC) power supply may be utilized to bias one of the plates of the ion optics.
Fig. 1A and 1B show one example of an instrument 10, for example: a mass spectrometer 10M. As shown in fig. 1A, the instrument 10 includes a housing 10h having a front wall 10f, the front wall 10f having a display 10d with a user interface. The housing 10h also has at least one sample entry port 10p, the sample entry port 10p being sized and configured to receive a slide. One or more ports 10p may be used. Each port 10p may be configured as an inlet only, an outlet only, or as an inlet and outlet for a sample slide (e.g., a
As shown in FIG. 1B, an instrument 10 may use at least one light source 20 according to embodiments of the present invention. In some embodiments, the instrument 10 can be a mass spectrometer 10M, and the housing 10h can include at least one sample entry port 10p, the sample entry port 10p configured to receive a slide for the mass spectrometer 10M. For example, the mass spectrometer 10M may be a desktop mass spectrometer, as shown via table 30. In addition, one or more portions of the instrument 10 may be pumped/evacuated to a desired pressure via a vacuum pump 60. The vacuum pump 60 and/or the light source 20 may be on board (e.g., internal) of the housing 10h, or may be provided as an external plug-in component of the instrument 10.
The at least one light source 20 may provide light to generate ions within the instrument 10. For example, the light source 20 may include a laser 20LS, with the laser 20LS providing laser light to the instrument 10. For example, the laser 20LS may be a solid state laser, such as: an Ultraviolet (UV) laser having a wavelength above 320 nanometers (nm). In some embodiments, the solid-state laser 20LS may generate a laser beam having a wavelength between about 347 nm and about 360 nm. The solid-state laser 20LS may alternatively be an infrared laser or a visible laser.
Furthermore, although the terms "light source" and "laser" are used herein to discuss examples, the light source 20 may include any type of light source that generates charged particles within the instrument 10 by supplying light/energy to a target/device located within the instrument 10. For example, the light source 20 may be configured to provide one of various types of pulses of light/energy to a sample plate 230 (FIG. 2A) in the instrument 10 to produce a pulse of charged particles. In some embodiments, the light source 20 and the
Fig. 2A shows a schematic view of an instrument 10 and a light source 20. The instrument 10 comprises: a
The ion
In addition to the ion current 230C, in some embodiments, the instrument 10 may provide photons 260P from a photon source 260 to the
Fig. 2B shows a block diagram of the
A resistor 201 and a
Although some examples herein describe a sample on a
Fig. 2C shows a block diagram of a processor control system 270C. The processor control system 270C may include one or more processors 270, and the processors 270 may be configured to communicate with the light source 20, the resistor 201, the
Fig. 2D illustrates a block diagram of an exemplary processor 270 and memory 280 that may be used in various embodiments of the invention. The processor 270 communicates with the memory 280 via an address/data bus 290. The processor 270 may be, for example, a commercially available or custom microprocessor. Further, the processor 270 may include a plurality of processors. The memory 280 represents an overall hierarchy of storage devices including software and data for implementing the various functions described herein. The memory 280 may include, but is not limited to, the following types of devices: cache memory, ROM, PROM, EPROM, EEPROM, flash memory, Static RAM (SRAM), and Dynamic RAM (DRAM).
As shown in fig. 2D, the memory 280 may store various types of software and data, such as: an operating system 283. The operating system 283 may control the operation of the instrument 10. In particular, the operating system 283 may manage the resources of the instrument 10 and may coordinate the execution of various programs by the processor 270.
Fig. 3A-3E show schematic diagrams of the resistor 201 coupled to the ion
The
The
Referring to fig. 3B, the resistor 201 may be used as a Current-viewing resistor (Current-viewing resistor). The
Fig. 3B also shows a plurality of probes 310 that can be used to measure the
In addition, the ion current 230C provided from the
Referring to fig. 3C, exemplary electrical connections external to the
Fig. 3C further shows a switch 201S, which switch 201S selects whether to connect the resistor 201 to the
The
Referring to fig. 3D, the
For example, as discussed herein with respect to fig. 3, the
Referring to fig. 3E, a
In some embodiments, the measured ion current 230C may be compared to a predetermined threshold ion current value. For example, if the instrument 10 has a predetermined threshold ion current value suitable for mass spectrometry generation, the response of the diagnostic methods described herein can be used to confirm/set ionization. As an example, for MALDI ionization, the laser pulse energy may be fixed, the size of the laser spot changed, and vice versa, until the predetermined threshold ion current value is detected by the resistor 201.
The methods described herein can be used in a mass spectrometer. However, any system/instrument that uses charged particle optics to accelerate an ion beam or electron beam may use the method. Such systems/instruments may include electron microscopes, plasma thrusters, X-ray generators, ion beams for medical use, ion implanters for semiconductor manufacturing, and the like. Thus, the term "charged particle optical system" as used herein is not limited to an optical system of ions. Similarly, the instrument 10 described herein may measure "charged particle current," which is not limited to measured ion current. In addition, a measurement may be performed to confirm "generation of charged particles", which is not limited to confirming ionization. Further, for electron beam applications, the polarity of the voltages described herein with respect to ion application will be reversed.
Fig. 4A-4E illustrate a flow chart of a method for confirming ionization or other charged particle generation in the instrument 10. In some embodiments, the memory 280 of fig. 2D may be a non-transitory computer readable storage medium, the memory 280 including computer readable program code that, when executed by the processor 270, causes the processor 270 to perform any one of the methods of fig. 4A-4E.
Referring to fig. 4A, the method may include providing/reconfiguring (block 411) the ion
Further, if the ion current 230C is measurable (block 412), the method may include determining (block 420) whether the ion 230I reaches the
If the ion 230I is arriving at the detector 250 (block 420), the method may include determining (block 430) whether the
The method may then include determining (block 422) whether a measurable ion current 230C is detected that should reach the
If the
After turning on (block 433) the UV LED, the method may include determining (block 434) whether the
If the signal gain of the
Referring again to block 411, in response to determining (block 410) that the ions 230I are not generated or are not determined to be generated, the ion
Referring to fig. 4B, the methods described herein are not limited to the use of ionization. For example, the operations of
After the providing/reconfiguring operations of block 411 ', the method may confirm the generation of charged particles in the instrument 10 by coupling (block 412') the resistor 201 outside the
The operation of fig. 4B is not limited to being performed with/at vacuum pressure in the
Referring to fig. 4C, the provide/reconfigure operations of block 411' of fig. 4B may include a variety of operations. For example, providing/reconfiguring (block 411') the electrical connections of the charged particle
After the operations of blocks 411 '-2, 411' -3, 411 '-4, which may be performed in any order, when the
In some embodiments, the providing/reconfiguring of block 411' may include: providing a first state of electrical connection to the charged particle
Referring to fig. 4D, the operations of block 412' of fig. 4B may include a variety of operations. For example, the operations may include: when the
In addition, the operations may include emitting (block 412 '-1) the laser light 20 onto a blank slide without any sample, and measuring (block 412' -2) any current generated by emitting (block 412 '-2) the laser light 20 onto the blank slide using the resistor 201 before emitting (block 412' -3) the laser light 20 toward the sample. For example, the operations of block 412' -2 may include: it is determined whether a measurable current generated by the laser light 20 emitted (block 412' -1) toward the blank slide passes through the resistor 201. In some embodiments, the measurements/operations of each of blocks 412 '-4 and 412' -2 may be compared to determine (a) the magnitude/effect of ionization of a sample relative to (b) the emission on a blank slide. For example, the operations of blocks 412 '-4 and 412' -2 may measure a first electrical response and a second electrical response (e.g., voltage response) through the resistor 201, respectively, and then the first electrical response and the second electrical response may be compared to each other and/or to a predetermined value. In the case of a blank slide, no measurable electrical response can be detected, as an electrical response may not be measurable. Further, in some embodiments, the operations of blocks 412 '-1 (and/or blocks 412' -2) may be performed after the operations of blocks 412 '-3 (and/or blocks 412' -4).
Referring to fig. 4E, the charged particles described with respect to fig. 4B may be ions 230I. As shown in fig. 4E, the operations of block 412' of fig. 4B may include: the number of ions 230I generated in the
Figure 5A shows an oscilloscope trace of the instrument fired on a blank slide. As shown in FIG. 5A, the
Fig. 5B shows an oscilloscope trace of the instrument 10 fired on the
Fig. 6 shows a perspective view of the interior of the
In some embodiments, the sample on the
Fig. 7 shows a block diagram of a resistor 201 connected to the processor 270 and the laser source 20LS for calibrating the laser energy and/or laser focus. The processor 270 may receive/process data/signals generated by the electrical response of the resistor 201 to the current generated by the light from the laser 20L, and the processor 270 may responsively control the laser 20LS to adjust its laser energy and/or laser focus. The combination/communication of the processor 270 with the laser 20LS and the resistor 201 is utilized to control the calibration of the laser 20LS, providing a laser calibration system 770C. Further, the resistor 201 may be coupled to a
Fig. 8 shows a flow diagram of an exemplary method for calibrating laser energy and/or laser focus. The method can include coupling (block 810) the resistor 201 outside the
The present invention advantageously provides for directly measuring the ion current 230C generated from a sample. In contrast, conventional systems can only provide indirect feedback of ion current based on the intensity of mass spectral peaks. Thus, in conventional systems, if a mass spectrum is not produced, it may be difficult to determine whether ions are being generated, reach the detector, and/or produce an output signal from a detector. However, when no mass spectrum is generated, the measurement of current 230C may be performed via the present invention.
The present invention also advantageously provides for measuring the ion current 230C without the need for additional hardware (e.g., additional diagnostic hardware) located within the
Fig. 9A shows a safe high pressure (SHV) vacuum feedthrough 910 that may be used with the instrument 10. For example, the SHV vacuum feedthrough 910 may be
PE4500SHV jack bulkhead sealed terminal connectors (jack bulk sealed connectors). In some embodiments, one of the feedthrough seals 910 may be an extraction pulse SHV feedthrough and the other feedthrough seal 910 may be a post-bias SHV feedthrough.Fig. 9B shows an
The following is one non-limiting example of the methods/diagnostic methods described herein. To assist in troubleshooting mass spectrometry instruments/systems, the following procedure was developed to test a sample for ionization. The basic principle of the process is to use a charge collection plate and a CVR. The present invention modifies the connection of existing instruments/systems so that a lower removable portion of the ion optics of the instrument/system can facilitate diagnosis. The diagnosis may include the following operations:
1. setting the position of the laser optics at a position specified in the instrument/system tuning program.
2. All high pressures are shut off to prevent damage to the instrument 10.
3. Venting the vacuum system.
4. Inside the
5. The
6. The door is closed and evacuation of the
7. Disconnecting the extraction pulse cable from the atmospheric side of the extraction pulse Safety High Voltage (SHV) feedthrough seal 910.
8. A shorting plug is connected to the atmospheric side of the extraction pulse SHV pass-through seal 910. This will ground the
9. Disconnecting the rear bias cable from the atmospheric side of the rear bias SHV feedthrough 910.
10. An
11. A
12. A standard 10x oscilloscope probe 310 rated for voltages greater than 300 volts is connected to either side of the resistor 201 in the measurement box. The respective channels on the oscilloscope may be Alternating Current (AC) coupled.
13. On an oscilloscope, a mathematical function was created to subtract the two probe voltages. This produces a differential voltage measurement across the resistor 201 (
14. A cable is connected to the laser synchronization output of the laser 20. This may be accomplished through test points or connectors on the circuit board. For example, a connector of a timing board may be used.
15. The oscilloscope is set to trigger at the leading edge of the laser synchronization signal. This is shown in fig. 5A as a falling edge trigger, but may be different depending on the electronic design.
16. A blank slide without a sample is inserted into the instrument 10 and then evacuated to operating pressure.
17. During collection, all high voltages in the instrument 10 are set to 0 volts to prevent damage to the instrument 10.
18. The
19. The oscilloscope was set to average 64 events. Without averaging, the signal may be very noisy. Averaging should make the signal more distinguishable from noise.
20. The laser light 20 is initiated on the slide and the grating, if possible. The laser energy on the slide should be about 5 microjoules (muj). This is achieved by using a laser power of 20 muj from the laser 20. The value of 5 microjoules is based on a measurement of 1.5 microjoules at the sample at a laser power of 6 microjoules for the laser 20. When a blank slide is used, the mathematical function representing the
21. Emission was stopped on a blank slide.
22. The blank slide was replaced with a complete slide of ATCC 8739 e.coli and evacuated to operating pressure. These samples may be from suspensions or hand-operated deposits. In some embodiments, the fresh sample may be suspended in a matrix.
23. All high voltages in the instrument 10 are set to 0 volts during collection to prevent damage to the instrument 10.
24. The
25. The oscilloscope was set to average 64 events. Without averaging, the signal may be very noisy. Averaging should make the signal more distinguishable from noise.
26. The laser light 20 is initiated on the slide and the grating, if possible. The laser energy on the sample should be about 5 microjoules (muj). This is achieved by using a laser power of 20 microjoules from the laser 20. The value of 5 microjoules is based on a measurement of 1.5 microjoules at the sample at a laser power of 6 microjoules for the laser 20. When using a slide with a sample, the mathematical function representing the
This change in voltage across the CVR 201 is proportional to the ion current 230C collected in the instrument 10 via ohm's law. In fig. 5B,
27. The emission was stopped on the E.coli sample.
28. The slide of E.coli was removed from the instrument 10.
In the drawings, certain layers, components or features may be exaggerated for clarity, and broken lines illustrate optional/removable features or operations unless stated otherwise. The terms "figure" and "drawings" are used interchangeably with the term "figure" in this application and/or the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
It will be understood that, although the terms first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a "first" element, component, region, layer or section discussed below could be termed a "second" element, component, region, layer or section without departing from the teachings of the present invention.
Spatially relative terms, such as "below," "beneath," "bottom," "below," "over," "upper," and the like, may be used herein for ease of description to describe one element or feature's relationship to another element or feature as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass devices used or operated in different orientations than those depicted in the figures. For example, if the device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the exemplary term "below" can include above, below, and rear orientations. The device may be otherwise oriented (rotated 90 or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
The term "about" refers to a number within +/-20% of the stated value.
As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises," "comprising," "includes" and/or "including," when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. It will be understood that when an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element or be connected or coupled to the other element via intermediate elements. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items. Furthermore, the symbol "/" has the same meaning as the term "and/or".
Unless defined otherwise, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of this specification and the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
In some embodiments, the mass spectrometer 10M is configured to obtain an ion signal from a sample having a mass range between 2000 to 20000 daltons.
The term "sample" refers to a substance being analyzed and can be any medium having a wide range of molecular weights. In some embodiments, the sample is being evaluated for the presence of a microorganism, such as a bacterium or a fungus. However, the sample may be assessed for the presence of other components, including: toxins or other chemicals.
The term "desktop" refers to a relatively compact unit that can be mounted on a standard desktop or counter or occupy a footprint equivalent to a desktop, e.g., a desktop having dimensions of about 1 foot in width by 6 feet in length, and typically between about 1 and 4 feet in height. In some embodiments, the instrument/system is located in a housing or casing of 28 inches to 14 inches (width) by 28 inches to 14 inches (depth) by 38 inches to 28 inches (height). The flight tube 240 has a length of about 0.8 meters (m). In some embodiments, longer or shorter lengths may be used. For example, the flight tube 240 can have a length between 0.4 meters and 1 meter.
The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the invention.
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