Patent Grant
11791150
The teachings herein relate to an ion detection system for a time-of-flight (TOF) mass analyzer or mass spectrometer. More particularly, the teachings herein relate to a multichannel ion detection system that uses the signal intensity detected in the highest resolution channels for qualitative analysis but uses the signal intensity of the highest resolution channels and lower resolution channels for quantitative analysis.
The systems and methods disclosed herein are also performed in conjunction with a processor, controller, microcontroller, or computer system, such as the computer system of
Currently, some conventional TOF mass analyzers use ion detection systems that include four-channel digitizers. A four-channel digitizer can include either a time-to-digital converter (TDC) or an analog-to-digital converter (ADC), for example. Multichannel ion detection systems provide two main benefits: enhanced dynamic range and improved resolution through independent calibration of channels (also known as channel alignment).
The use of analog detection can in principle replace the need for multiple channels from a dynamic range aspect, which may also result in better timing resolution of an ADC. However, the channel alignment benefit would disappear. This can be partially compensated for by various means of tilting either the ion packet or detector itself, but it does not remove the adverse effect of the ion packet curvature on resolution. Therefore, four-channel ADCs have conventionally been used.
Resolution on a TOF mass analyzer is a key driver of instrument performance. In a TOF ion detection system, resolution essentially refers to how well the distance between ion packets can be measured. In other words, the highest resolution would be the minimum distance between two ion packets where those two different ion packets could still be resolved.
Unfortunately, over time, the resolution of a TOF mass analyzer can degrade until it is no longer acceptable for a customer. For a multichannel TOF mass analyzer, the resolution of some channels can degrade faster and greater than other channels. For example, in a four-channel TOF mass analyzer, the resolutions measured by the two channels receiving data from the two outermost electrodes typically degrade faster than the resolutions measured by the two channels receiving data from the two innermost electrodes.
Simply discarding data from any channel with a degraded resolution may appear, at first, to be a solution to this problem. However, discarding the signal of even a single channel can reduce the overall sensitivity of the TOF mass analyzer and defeat the original purpose of using a multichannel ion detection system.
As a result, additional systems and methods are needed to address the problem of degraded resolution in some channels of a multichannel ion detection system of a TOF mass analyzer.
A system, method, and computer program product are disclosed for maintaining the resolution of a TOF mass analyzer despite a loss of resolution in one or more channels of a multichannel ion detection system of the TOF mass analyzer. The system includes a multichannel detector and electron multiplier, a multichannel digitizer, and a processor.
The multichannel detector and electron multiplier is impacted by ion packets of a TOF mass analyzer. Ion packets impact a first side of the multichannel detector and electron multiplier. The multichannel detector and electron multiplier converts the impacts into multiplied electrons and emits the multiplied electrons from two or more segmented electrodes on a second side of the multichannel detector and electron multiplier. Each electrode of the two or more segmented electrodes corresponds to and emits electrons based on impacts in a different region across a length of the first side.
A multichannel digitizer is electrically connected to the two or more segmented electrodes. The multichannel digitizer converts the electrons received from each electrode of the two or more segmented electrodes for each ion packet of the ion packets into digital values in a channel of the multichannel digitizer.
The processor receives digital values from at least two or more channels of the multichannel digitizer. The processor calculates qualitative information about the ion packets using digital values of a predetermined subset of one or more channels of the at least two or more channels. The predetermined subset of one or more channels is known to provide the highest resolution of the at least two or more channels. The processor can further calculate quantitative information about the ion packets using digital values of the at least two or more channels.
These and other features of the applicant's teachings are set forth herein.
The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
Before one or more embodiments of the present teachings are described in detail, one skilled in the art will appreciate that the present teachings are not limited in their application to the details of construction, the arrangements of components, and the arrangement of steps set forth in the following detailed description or illustrated in the drawings. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
Computer-Implemented System
Computer system 100 may be coupled via bus 102 to a display 112, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 114, including alphanumeric and other keys, is coupled to bus 102 for communicating information and command selections to processor 104. Another type of user input device is cursor control 116, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 104 and for controlling cursor movement on display 112. This input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), that allows the device to specify positions in a plane.
A computer system 100 can perform the present teachings. Consistent with certain implementations of the present teachings, results are provided by computer system 100 in response to processor 104 executing one or more sequences of one or more instructions contained in memory 106. Such instructions may be read into memory 106 from another computer-readable medium, such as storage device 110. Execution of the sequences of instructions contained in memory 106 causes processor 104 to perform the process described herein. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement the present teachings Thus implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.
In various embodiments, computer system 100 can be connected to one or more other computer systems, like computer system 100, across a network to form a networked system. The network can include a private network or a public network such as the Internet. In the networked system, one or more computer systems can store and serve the data to other computer systems. The one or more computer systems that store and serve the data can be referred to as servers or the cloud, in a cloud computing scenario. The one or more computer systems can include one or more web servers, for example. The other computer systems that send and receive data to and from the servers or the cloud can be referred to as client or cloud devices, for example.
The term “computer-readable medium” as used herein refers to any media that participates in providing instructions to processor 104 for execution. Such a medium may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, optical or magnetic disks, such as storage device 110. Volatile media includes dynamic memory, such as memory 106. Transmission media includes coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 102.
Common forms of computer-readable media or computer program products include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, digital video disc (DVD), a Blu-ray Disc, any other optical medium, a thumb drive, a memory card, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, or any other tangible medium from which a computer can read.
Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 104 for execution. For example, the instructions may initially be carried on the magnetic disk of a remote computer. The remote computer can load the instructions into its dynamic memory and send the instructions over a telephone line using a modem. A modem local to computer system 100 can receive the data on the telephone line and use an infra-red transmitter to convert the data to an infra-red signal. An infra-red detector coupled to bus 102 can receive the data carried in the infra-red signal and place the data on bus 102. Bus 102 carries the data to memory 106, from which processor 104 retrieves and executes the instructions. The instructions received by memory 106 may optionally be stored on storage device 110 either before or after execution by processor 104.
In accordance with various embodiments, instructions configured to be executed by a processor to perform a method are stored on a computer-readable medium. The computer-readable medium can be a device that stores digital information. For example, a computer-readable medium includes a compact disc read-only memory (CD-ROM) as is known in the art for storing software. The computer-readable medium is accessed by a processor suitable for executing instructions configured to be executed.
The following descriptions of various implementations of the present teachings have been presented for purposes of illustration and description. It is not exhaustive and does not limit the present teachings to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practicing of the present teachings. Additionally, the described implementation includes software, but the present teachings may be implemented as a combination of hardware and software or in hardware alone. The present teachings may be implemented with both object-oriented and non-object-oriented programming systems.
Using Fewer Channels for Qualitative Analysis
As described above, some conventional time-of-flight (TOF) mass analyzers use ion detection systems that include four-channel digitizers. A four-channel digitizer can include either a time-to-digital converter (TDC) or an analog-to-digital converter (ADC), for example. Multichannel ion detection systems provide two main benefits: enhanced dynamic range and improved resolution through independent calibration of channels (also known as channel alignment).
Resolution on a TOF mass analyzer is a key driver of instrument performance. Unfortunately, over time, the resolution of a TOF mass analyzer can degrade until it is no longer acceptable for a customer.
For a multichannel TOF mass analyzer, the resolution of some channels can degrade faster and greater than other channels. For example, in a four-channel TOF mass analyzer, the resolutions measured by the two channels receiving data from the two outermost electrodes typically degrade faster than the resolutions measured by the two channels receiving data from the two innermost electrodes.
Simply discarding data from any channel with a degraded resolution may appear, at first, to be a solution to this problem. However, discarding the signal of even a single channel can reduce the overall sensitivity of the TOF mass analyzer and defeat the original purpose of using a multichannel ion detection system.
As a result, additional systems and methods are needed to address the problem of degraded resolution in some channels of a multichannel ion detection system of a TOF mass analyzer.
One of ordinary skill in the art can appreciate that the terms “mass analyzer” and “mass spectrometer” can be used interchangeably. Generally, a mass analyzer refers to a device at one or more stages of a mass spectrometer. In other words, the mass analyzer is typically just one component of a mass spectrometer. However, it is common in industry practice to refer to an entire mass spectrometer in terms of its mass analyzer. For example, a mass spectrometer that includes a TOF mass analyzer is often referred to as a TOF mass spectrometer even though the TOF mass analyzer is just one component.
Resolution and Channel Alignment
One of the benefits of a multichannel ion detection system is improved resolution through independent calibration of channels, called channel alignment. Channel alignment is needed due to the non-ideal way in which ion packets are shaped when they impact the detector.
The shapes of ion packets 201 and 202 are ideal with respect to MCP 210 of
The orientations of ion packets 201 and 202 are ideal with respect to MCP 210 because they are essentially parallel to MCP 210. Again, this orientation allows all of the ions of ion packet 201 to strike MCP 210 at the same time and all of the ions of ion packet 202 to strike MCP 210 at the same time.
The shape and orientation of ion packets are important because they affect the resolution of a TOF ion detection system. Again, in a TOF ion detection system, resolution essentially refers to how well the distance between ion packets can be measured. In other words, the highest resolution would be the minimum distance between two ion packets where those two different ion packets could still be resolved.
The ideal shape and ideal orientation of ion packets 201 and 202 in
This decrease in resolution can be seen by determining if ion packets 301 and 302 can be placed closer together and still be distinguished at MCP 210. If ion packet 301 is placed closer to ion packet 302 its leading edge immediately starts to overlap the trailing edge of ion packet 302. If these edges overlap, the ion packets cannot be distinguished at MCP 210. This means that ion packets 301 and 302 cannot be placed much closer together. Therefore, a comparison of
In practice, it is common for TOF mass analyzers to produce ion packets with tilted or non-ideal orientations. Fortunately, however, there is a conventional remedy to this problem. In order to compensate for the tilted packets, the MCP can be correspondingly tilted in a calibration step to account for ion packets with tilted or non-ideal orientations. Non-ideal ion packet shape can also degrade resolution.
This convex shape reduces the resolution of the ion detection system. Like ion packets 301 and 302 of
Four-Channel Digitizer
Conventional TOF ion detection systems have compensated for the loss of resolution caused by the convex shape of ion packets and the convex shape of an MCP by using four electrodes and a four-channel digitizer.
Four-channel digitizer 530 is, for example, an ADC or a TDC. Each of anode electrode plates 521, 522, 523, and 524 can also be electrically connected to four-channel digitizer 530 through a four-channel preamplifier (not shown), for example. A four-channel preamplifier amplifies the electrical signal received from the electrode plates.
MCPs 510 essentially translate an ion impact image on one side to a corresponding electron emission image on the other side. Although ion packets 301 and 302 have convex shapes, their images on either side of MCPs 510 have a rectangular pattern or shape.
Each of anode electrode plates 521, 522, 523, and 524 is able to detect a different part of the rectangular pattern 305 over time. Note that the rectangular pattern is most convex along the length of the rectangular pattern because the rectangular pattern is much longer than it is wide. By detecting different parts of rectangular pattern 305 over time, the convex shape of each ion packet is detected.
Returning to
In
In timing diagram 860 of
Note that in
However, because multiple channels are used to measure different parts of the convex shape of an ion packet, it is possible to compensate for the spreading out of intensities. This is shown in timing diagram 870. Essentially, peaks 861 and 862 for ion packet 302 of
Timing diagram 870 of
In timing diagram 1060 of
Note in
However, because multiple channels are used to measure different parts of the convex shape of an ion packet, it is possible to compensate for this overlap. This is shown in timing diagram 1070. Essentially, peaks 1061 and 1062 for ion packet 902 of
Poor Resolution of Some Channels Degrades Overall Resolution
As described above, for a multichannel TOF mass analyzer, the resolution of some channels can degrade faster and greater than other channels. For example, in a four-channel TOF mass analyzer, the resolutions measured by the two channels receiving data from the two outermost electrodes typically degrade faster than the resolutions measured by the two channels receiving data from the two innermost electrodes. Returning to
In
Again, in timing diagram 1160 of
Note that in
However, because multiple channels are used to measure different parts of the convex shape of an ion packet, it is possible to compensate for the spreading out of intensities. This is shown in timing diagram 1170. Essentially, peaks 1161 and 1162 for ion packet 302 of
Timing diagram 1170 of
Use only Highest Resolution Channels for Qualitative Analysis
In various embodiments, the problem of degraded resolution in some channels of a multichannel ion detection system of a TOF mass analyzer degrading the overall resolution is solved by separately using the signal intensity detected in the highest resolution channels for qualitative analysis and using the signal intensity of the highest resolution channels and lower resolution channels for quantitative analysis. Returning to
In various embodiments, for quantitative analysis, at each bin (m/z), one approach is to only include the intensity from channels 531 and 534, if there is also signal in channels 532 and 533 at this same bin (m/z). This approach ignores a small part the signal that comes from the wider, poorly resolved portions of channels 531 and 534, but still captures most of the signal and keeps the resolution from the channels 532 and 533.
Again, in
For qualitative analysis, therefore, only the intensities 1222 and 1221 of timing diagram 1252 and intensities 1232 and 1231 of timing diagram 1253 are combined in timing diagram 1260, producing intensities 1262 and 1264. Timing diagram 1260 shows that the higher resolutions of timing diagrams 1252 and 1253 are preserved using this combination.
For quantitative analysis, intensities 1212 and 1211 of timing diagram 1251 and of intensities 1241 and 1242 of timing diagram 1254 are combined into intensities 1261 and 1263 of timing diagram 1270. However, only portions of intensities 1261 and 1263 are used for quantitative analysis. For example, intensities 1262 and 1264 are aligned with intensities 1261 and 1263. Only those portions of intensities 1261 and 1263 that overlap in time bins or m/z bins with intensities 1262 and 1264 are used for quantitative analysis.
One of skill in the art understands that bins are ranges of time or m/z value that are used to combine intensities. Timing diagram 1270 depicts bins 1271. Bins 1271 show that intensity 1261 overlaps with intensity 1262 in four bins and intensity 1263 overlaps with intensity 1264 in four bins. The intensities for four bins of intensity 1261 and the intensities for the four bins of intensity 1263 are then combined with the intensities 1262 and 1264 for quantitative analysis.
In various embodiments, peak finding is performed for each channel Channels 532 and 533 of
In an alternative embodiment, for example, only one channel with the highest resolution is used for qualitative analysis and the other 3 channels are only used additionally for intensity only quantitative analysis. For example, the digital values of channel 532 are used to get the signal intensity and resolution for qualitative analysis. However, for quantitative analysis (intensity only), the digital values of channels 531, 533, and 534 of digitizer 530 are used in addition to the digital values of channel 532.
Multichannel Ion Detection System
Multichannel detector and electron multiplier 1305 is impacted by ion packets 1301 of a TOF mass analyzer (not shown). Ion packets 1301 impact a first side of multichannel detector and electron multiplier 1305. Multichannel detector and electron multiplier 1305 converts the impacts into multiplied electrons and emits the multiplied electrons from two or more segmented electrodes 1320 on a second side of multichannel detector and electron multiplier 1305. Each electrode of two or more segmented electrodes 1320 corresponds to and emits electrons based on impacts in a different region across a length of the first side.
Multichannel digitizer 1330 can be, but is not limited to, a multichannel ADC or a multichannel TDC. Multichannel digitizer 1330 is electrically connected to two or more segmented electrodes 1320. Multichannel digitizer 1330 converts the electrons received from each electrode of two or more segmented electrodes 1320 for each ion packet of ion packets 1301 into digital values in a channel of multichannel digitizer 1330. Multichannel digitizer 1330 is, for example, a four-channel device as shown in
Processor 1340 can be a separate device as shown in
Processor 1340 receives digital values from at least two or more channels of multichannel digitizer 1330. Processor 1340 calculates qualitative information about the ion packets using digital values of a predetermined subset of one or more channels of the at least two or more channels. The predetermined subset of one or more channels is known to provide the highest resolution of the at least two or more channels. Qualitative information includes, but is not limited to, m/z peak shape.
For example, the at least two or more channels of
Returning to
In various embodiments, multichannel detector and electron multiplier 1305 can be an electrical system or a photo-electrical system, for example. As shown in
Series of one or more microchannel plates 1310 is impacted by ion packets 1301 of a TOF mass analyzer (not shown). Ion packets 1301 impact series of one or more microchannel plates 1310 on a first side of series of one or more microchannel plates 1310. Series of one or more microchannel plates 1310 converts the impacts into multiplied electrons emitted from a second side of series of one or more microchannel plates 1310.
Plurality of segmented anode electrode plates 1320 receive the emitted electrons from series of one or more microchannel plates 1310. Plurality of segmented anode electrode plates 1320 is arranged in a plane parallel with series of one or more microchannel plates 1310 and positioned next to series of one or more microchannel plates 1310.
Multichannel detector and electron multiplier 1305 can also be a photo-electrical system, for example.
In various embodiments, two-channel digitizer 1450 is a two-channel analog-to-digital converter (ADC). In various embodiments, two-channel digitizer 1450 is a two-channel time-to-digital converter (TDC).
The first one of series of one or more microchannel plates 1410 is impacted by ion packets 1401 in a rectangular pattern on a first side 1411 of series of one or more microchannel plates 1410. Series of one or more microchannel plates 1410 converts the impacts into multiplied electrons emitted in the rectangular pattern on a second side 1412 of series of one or more microchannel plates 1410. A longer side of the rectangular pattern is the length and a shorter side of the rectangular pattern is the width. Due to the convex shape of ion packet 1401, for example, ions of each packet impact a central inner area of the rectangular pattern before impacting two outer areas at each end of the rectangular pattern.
Scintillator 1420 is positioned in parallel with series of one or more microchannel plates 1410 and next to series of one or more microchannel plates 1410. Scintillator 1420 receives the emitted electrons in the rectangular pattern on a first side 1421 of scintillator 1420 from second side 1412 of series of one or more microchannel plates 1410. Scintillator 1420 converts the electrons into photons emitted in the rectangular pattern on a second side 1422 of scintillator 1420.
Two or more segmented light pipes 1431, 1432, 1433, and 1434 are connected to second side 1422 of scintillator 1420 to receive the photons from second side 1422 of scintillator 1420. Two or more segmented light pipes 1431, 1432, 1433, and 1434 together have an area large enough to receive photons from the rectangular pattern. Two or more light pipes 1431, 1432, 1433, and 1434 include one or more inner light pipes 1432 and 1433 positioned to receive photons from the central inner area of the rectangular pattern. Two or more light pipes 1431, 1432, 1433, and 1434 include one or more outer light pipes 1431 and 1434 positioned to receive photons from the two outer areas at each end of the rectangular pattern.
First photo-multiplier tube 1441 is connected to one or more inner light pipes 1432 and 1433 and converts the photons received by one or more inner light pipes 1432 and 1433 into first multiplied electrons for each packet. Second photo-multiplier tube 1442 is connected to one or more outer light pipes 1431 and 1434 and converts the photons received by one or more outer light pipes 1431 and 1434 into second multiplied electrons for each packet.
Two-channel digitizer 1450 includes a first channel 1451 electrically connected to first photo-multiplier tube 1441 that converts the first multiplied electrons for each ion packet into a first digital value. Two-channel digitizer 1450 includes a second channel 1452 electrically connected to second photo-multiplier tube 1442 that converts the second multiplied electrons for each ion packet into a second digital value.
First channel 1451 and second channel 1452 are independently calibrated to align the first digital value and the second digital value in time and account for the convex shape of the ion impacts of each ion packet.
Returning to
In various embodiments, processor 1340 calculates quantitative information about the ion packets by performing m/z peak finding on the digital values of each of the at least two or more channels after all of ion packets 1301 are received, using intensities of the digital values of the predetermined subset to build the best resolution m/z peak shape, and using intensities of the digital values of the at least two or more channels to calculate a summed intensity for each m/z peak.
In various embodiments, the predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution is determined during an auto-tune resolution procedure of the TOF mass analyzer. The auto-tune resolution procedure of a TOF mass analyzer is typically run by customers once a week or once a month, for example.
In various embodiments, the predetermined subset includes one channel
In various embodiments, for a four-channel digitizer, as shown in
In various embodiments, multichannel digitizer 1330 is electrically connected to the plurality of segmented anode electrode plates to provide a channel for each plate.
In various embodiments, multichannel digitizer 1330 is electrically connected to the plurality of segmented anode electrode plates to provide a channel for two or more plates. U.S. Provisional Application No. 62/470,486, for example, describes a multichannel ion detection system where a multichannel digitizer provides a channel for two segmented anode electrode plates.
Multichannel Ion Detection Method
In step 1510 of method 1500, impacts by ion packets of a TOF mass analyzer on a first side of a multichannel detector and electron multiplier are converted into multiplied electrons and the multiplied electrons are emitted from two or more segmented electrodes on a second side of the multichannel detector and electron multiplier using the multichannel detector and electron multiplier. Each electrode of the two or more segmented electrodes corresponds to and emits electrons based on impacts in a different region across a length of the first side.
In step 1520, the electrons received by each electrode of the two or more segmented electrodes for each ion packet of the ion packets are converted into digital values in a channel of a multichannel digitizer using the multichannel digitizer.
In step 1530, digital values from at least two or more channels of the multichannel digitizer are received and qualitative information about the ion packets is calculated using digital values of a predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution of the at least two or more channels using a processor.
Multichannel Ion Detection Computer Program Product
In various embodiments, computer program products include a tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for maintaining a resolution of a TOF mass analyzer despite a loss of resolution in one or more channels of a multichannel ion detection system of the TOF mass analyzer. This method is performed by a system that includes one or more distinct software modules.
Measurement module 1610 instructs a multichannel detector and electron multiplier to convert impacts by ion packets of a TOF mass analyzer on a first side of the multichannel detector and electron multiplier into multiplied electrons and emit the multiplied electrons from two or more segmented electrodes on a second side of the multichannel detector and electron multiplier. Each electrode of the two or more segmented electrodes corresponds to and emits electrons based on impacts in a different region across a length of the first side.
Measurement module 1610 instructs a multichannel digitizer to convert the electrons received by each electrode of the two or more segmented electrodes for each ion packet of the ion packets into digital values in a channel of the multichannel digitizer.
Analysis module 1620 receives digital values from at least two or more channels of the multichannel digitizer. Analysis module 1620 calculates qualitative information about the ion packets using digital values of a predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution of the at least two or more channels.
While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.
Further, in describing various embodiments, the specification may have presented a method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/834,234, filed on Apr. 15, 2019, the content of which is incorporated by reference herein in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2020/053540 | 4/15/2020 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2020/212856 | 10/22/2020 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 20030111597 | Gonin | Jun 2003 | A1 |
| 20050006577 | Fuhrer | Jan 2005 | A1 |
| 20060289747 | Schultz et al. | Dec 2006 | A1 |
| 20090189072 | Egan | Jul 2009 | A1 |
| 20110024620 | Hidalgo | Feb 2011 | A1 |
| 20110147578 | Schultz et al. | Jun 2011 | A1 |
| 20110186727 | Loboda | Aug 2011 | A1 |
| Number | Date | Country |
|---|---|---|
| 2005010799 | Feb 2005 | WO |
| 2017158534 | Sep 2017 | WO |
| Entry |
|---|
| International Search Report and Written Opinion for PCT/IB2020/053540, dated Jul. 23, 2020. |
| Number | Date | Country | |
|---|---|---|---|
| 20220199390 A1 | Jun 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62834234 | Apr 2019 | US |
