Brian L. Lamarche
- Courses1
- Reviews1
- School: Washington State University
- Campus: Tri
- Department: Computer Science
- Email address: Join to see
- Phone: Join to see
-
Location:
2710 Crimson Way
Richland, WA - 99354 - Dates at Washington State University: March 2013 - March 2013
- Office Hours: Join to see
Biography
Washington State University Tri - Computer Science
Vice President of Software Development at Hecate
Research
Brian
LaMarche
Richland, Washington
Experienced software engineer and architect with a demonstrated history of working in the high-tech and research industry. Skilled in developing field ready applications that stand the test of time.
Experience
Washington State University
Adjunct Faculty
Taught introductory and advanced data structures, software engineering processes, design patterns, verification and validation for upper division computer science courses. Developed robotic teaching aides that secure computer science concepts while introducing industry standard tools and presenting students with challenges not found in the typical classroom.
Hecate Software, Inc.
Vice President of Software Development
Lead software development teams to build high-quality field ready software for various research and engineering industries. Chief Architect of GreenLight, a digital pressure testing software for testing blow out preventers, choke manifolds, individual assets and other critical high-end capital equipment.
Hecate Software, Inc.
Software Engineer
Senior software engineer developing software applications for various clients. Chief architect of GreenLight, a digital pressure testing software suite for the oil and gas industry.
PNNL
Research Scientist / Software Engineer
Software engineer for the Instrument Development Laboratory.
Designed, developed, and maintained laboratory automation applications for: LC-MS, GC-MS, confocal and light field microscopy. Developed several plug-in based laboratory automation systems including deterministic finite state automaton for parallel operation of LC-MS instruments. Developed imaging software for object recognition, image registration and classification. Constructed real-time and near real time software applications for acoustic telemetry systems.
Education
Washington State University
Bachelors of Science
Computer Science
Washington State University
Adjunct Faculty
Taught introductory and advanced data structures, software engineering processes, design patterns, verification and validation for upper division computer science courses. Developed robotic teaching aides that secure computer science concepts while introducing industry standard tools and presenting students with challenges not found in the typical classroom.Washington State University Tri-Cities
Doctor of Philosophy (Ph.D.)
Computer Science - Bioinformatics
Devised and developed algorithms and software for the processing of liquid chromatography mass spectrometry data to mine label free global proteomics data for environmental applications.
Publications
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry
Molecular and Cellular Proteomics
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry
Molecular and Cellular Proteomics
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.
Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry
Analytical Chemistry
We report on the performance of Structures for Lossless Ion Manipulation (SLIM) devices as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM device, and demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central ‘rung’ electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning the RF on the rung electrodes and DC on the guard electrodes; however, both resolving power and ion transmission showed a dependence on these voltages and the best conditions for both were > 300 Vp-p RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R~58), showing that degraded resolution from a ‘racetrack’ effect from turning around a corner can be successfully avoided, and the capability also maintained for essentially lossless ion transmission.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry
Molecular and Cellular Proteomics
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.
Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry
Analytical Chemistry
We report on the performance of Structures for Lossless Ion Manipulation (SLIM) devices as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM device, and demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central ‘rung’ electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning the RF on the rung electrodes and DC on the guard electrodes; however, both resolving power and ion transmission showed a dependence on these voltages and the best conditions for both were > 300 Vp-p RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R~58), showing that degraded resolution from a ‘racetrack’ effect from turning around a corner can be successfully avoided, and the capability also maintained for essentially lossless ion transmission.
Increasing confidence of LC–MS identifications by utilizing ion mobility spectrometry
International Journal of Mass Spectrometry
Ion mobility spectrometry in conjunction with liquid chromatography separations and mass spectrometry offers a range of new possibilities for analyzing complex biological samples. To fully utilize the information obtained from these three measurement dimensions, informatics tools based on the accurate mass and time tag methodology were modified to incorporate ion mobility spectrometry drift times for peptides observed in human serum. In this work a reference human serum database was created for 12,139 peptides and populated with the monoisotopic mass, liquid chromatography normalized elution time, and ion mobility spectrometry drift time(s) for each. We demonstrate that the use of three dimensions for peak matching during the peptide identification process resulted in an increased numbers of identifications and a lower false discovery rate relative to only using the mass and normalized elution time dimensions.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry
Molecular and Cellular Proteomics
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.
Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry
Analytical Chemistry
We report on the performance of Structures for Lossless Ion Manipulation (SLIM) devices as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM device, and demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central ‘rung’ electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning the RF on the rung electrodes and DC on the guard electrodes; however, both resolving power and ion transmission showed a dependence on these voltages and the best conditions for both were > 300 Vp-p RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R~58), showing that degraded resolution from a ‘racetrack’ effect from turning around a corner can be successfully avoided, and the capability also maintained for essentially lossless ion transmission.
Increasing confidence of LC–MS identifications by utilizing ion mobility spectrometry
International Journal of Mass Spectrometry
Ion mobility spectrometry in conjunction with liquid chromatography separations and mass spectrometry offers a range of new possibilities for analyzing complex biological samples. To fully utilize the information obtained from these three measurement dimensions, informatics tools based on the accurate mass and time tag methodology were modified to incorporate ion mobility spectrometry drift times for peptides observed in human serum. In this work a reference human serum database was created for 12,139 peptides and populated with the monoisotopic mass, liquid chromatography normalized elution time, and ion mobility spectrometry drift time(s) for each. We demonstrate that the use of three dimensions for peak matching during the peptide identification process resulted in an increased numbers of identifications and a lower false discovery rate relative to only using the mass and normalized elution time dimensions.
Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry; Dynamic Switching in Structures for Lossless Ion Manipulations
Analytical Chemistry
A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows the efficient switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 Torr. In the “dynamic mode” we show that mobility-selected ions can be switched into the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. This development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key component of modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.
MultiAlign: a multiple LC-MS analysis tool for targeted omics analysis
BMC bioinformatics
MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs.
An adaptable multiple power source for mass spectrometry and other scientific instruments
Review of Scientific Instruments
An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.
A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements
Analytical Chemistry
To better understand disease conditions and environmental perturbations, multiomic studies combining proteomic, lipidomic, and metabolomic analyses are vastly increasing in popularity. In a multiomic study, a single sample is typically extracted in multiple ways, and various analyses are performed using different instruments, most often based upon mass spectrometry (MS). Thus, one sample becomes many measurements, making high throughput and reproducible evaluations a necessity. One way to address the numerous samples and varying instrumental conditions is to utilize a flow injection analysis (FIA) system for rapid sample injections. While some FIA systems have been created to address these challenges, many have limitations such as costly consumables, low pressure capabilities, limited pressure monitoring, and fixed flow rates. To address these limitations, we created an automated, customizable FIA system capable of operating at a range of flow rates (∼50 nL/min to 500 μL/min) to accommodate both low- and high-flow MS ionization sources. This system also functions at varying analytical throughputs from 24 to 1200 samples per day to enable different MS analysis approaches. Applications ranging from native protein analyses to molecular library construction were performed using the FIA system, and results showed a highly robust and reproducible platform capable of providing consistent performance over many days without carryover, as long as washing buffers specific to each molecular analysis were utilized.
Signatures for Mass Spectrometry Data Quality
Journal of Proteome Research
Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324.
A Cabled Acoustic Telemetry System for Detecting and Tracking Juvenile Salmon: Part 1. Engineering Design and Instrumentation
Sensors
In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary sensing technology, to meet the needs for monitoring the survival of juvenile salmonids through eight large hydroelectric facilities within the Federal Columbia River Power System (FCRPS). Initial development focused on coded acoustic microtransmitters and autonomous receivers that could be deployed in open reaches of the river for detection of the juvenile salmonids implanted with microtransmitters as they passed the autonomous receiver arrays. In 2006, the Pacific Northwest National Laboratory began the development of an acoustic receiver system for deployment at hydropower facilities (cabled receiver) for detecting fish tagged with microtransmitters as well as tracking them in two or three dimensions for determining route of passage and behavior as the fish passed at the facility. The additional information on route of passage, combined with survival estimates, is used by the dam operators and managers to make structural and operational changes at the hydropower facilities to improve survival of fish as they pass the facilities through the FCRPS.
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry
Molecular and Cellular Proteomics
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.
Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry
Analytical Chemistry
We report on the performance of Structures for Lossless Ion Manipulation (SLIM) devices as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM device, and demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central ‘rung’ electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning the RF on the rung electrodes and DC on the guard electrodes; however, both resolving power and ion transmission showed a dependence on these voltages and the best conditions for both were > 300 Vp-p RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R~58), showing that degraded resolution from a ‘racetrack’ effect from turning around a corner can be successfully avoided, and the capability also maintained for essentially lossless ion transmission.
Increasing confidence of LC–MS identifications by utilizing ion mobility spectrometry
International Journal of Mass Spectrometry
Ion mobility spectrometry in conjunction with liquid chromatography separations and mass spectrometry offers a range of new possibilities for analyzing complex biological samples. To fully utilize the information obtained from these three measurement dimensions, informatics tools based on the accurate mass and time tag methodology were modified to incorporate ion mobility spectrometry drift times for peptides observed in human serum. In this work a reference human serum database was created for 12,139 peptides and populated with the monoisotopic mass, liquid chromatography normalized elution time, and ion mobility spectrometry drift time(s) for each. We demonstrate that the use of three dimensions for peak matching during the peptide identification process resulted in an increased numbers of identifications and a lower false discovery rate relative to only using the mass and normalized elution time dimensions.
Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry; Dynamic Switching in Structures for Lossless Ion Manipulations
Analytical Chemistry
A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows the efficient switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 Torr. In the “dynamic mode” we show that mobility-selected ions can be switched into the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. This development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key component of modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.
LC-IMS-MS Feature Finder: detecting multidimensional liquid chromatography, ion mobility and mass spectrometry features in complex datasets
Bioinformatics
We introduce a command line software application LC-IMS-MS Feature Finder that searches for molecular ion signatures in multidimensional liquid chromatography-ion mobility spectrometry-mass spectrometry (LC-IMS-MS) data by clustering deisotoped peaks with similar monoisotopic mass, charge state, LC elution time and ion mobility drift time values. The software application includes an algorithm for detecting and quantifying co-eluting chemical species, including species that exist in multiple conformations that may have been separated in the IMS dimension.
