BACKGROUND:
Notice is hereby given by the University of Ottawa of the intent to enter into a contract with Agilent Technologies to procure a suite of mass-spectrometers. This cutting edge-metabolomics suite is required in order to design metabolic strategies for the diagnostic/treatment of breast cancers that are associated with poor patient outcomes. Cancer cells display metabolic reorganization that fuels their elevated proliferation. There are currently intense efforts to elucidate the molecular events driving metabolic changes in cancer. In the coming years the main focus will be to assess metabolic adaptations of cancer cells as they evolve during tumor progression and the development of therapeutic resistance. The aim is to identify metabolic networks that drive the progression of poor outcome cancers in order to develop potential cancer metabolic therapies that could be used either alone or in combination with other anti-cancer drugs.
PROCESS:
Suppliers who consider their equipment functional, successfully tested, readily available and fully compliant to the ACAN minimum requirements may submit in writing a statement of specifications to the contact person identified in this Notice, on or before the closing date of this Notice. In the statement of specifications, the supplier must unequivocally demonstrate how their equipment, at minimum, equals, or exceeds the stated requirements.
If no other supplier submits a statement of specifications, on or before the closing date of this Notice, the competitive requirements of the University of Ottawa will be considered having been met.
Following notification to suppliers not successful in unequivocally demonstrating that their statement of specifications equals or exceeds the requirements set out in this Notice, the contract may then be awarded to the pre-identified supplier.
Date of issue: March 28, 2018
Closing Date: April 23, 2018, at 3:00:00 P.M. Eastern Standard Time
INTENDED USE:
The instruments being purchased consist of an accurate-mass Q-TOF LC/MS 6545 (Quadrupole-Time of flight; liquid chromatography/mass spectrometry) system, a QQQ LC/MS 6470 (Triple Quadrupole; liquid chromatography/mass spectrometry), a gas chromatograph mass spectrometry (GC/MS 5977B/7890B) system, as well as MassHunter and Mass Profiler Professional software. The suite of mass spectrometers will be stand alone and generate data as an integrated system to study metabolomics using the MassHunter acquisition software. This system will support cutting-edge research being conducted in one of the University of Ottawa’s lab to further understand and study the metabolic reprogramming of breast cancer cells. The data gathered using this system will permit novel discoveries in the broad field of metabolism with the goal of developing new and improved therapies/treatments for metabolic diseases and cancer.
This metabolomics suite is to perform metabolite profiling and stable isotope tracer analyses. Data analysis is the main bottleneck in metabolomics studies. The metabolomics suite must have validated and integrated data analysis softwares and publications in scientific journals should be available for reference. These analytical tools must be able to integrate gene expression data to generate metabolic maps. Specifically, the suite of mass-spectometers must include a software chemometrics platform designed to exploit the high information content of MS data and has to be useable in any MS-based differential analysis to determine relationships among two or more sample groups and variables. The software should be able to integrate all MS data types (LCMS and GCMS) using the same format. The main data analysis tool that is required is for qualitative and quantitative flux analysis measure labeling incorporation. All data should be also directly compatible with GeneSpring software.
The system consists of three main equipment and their components:
i) LC/QQQ: 1290/6470
- Electrospray ion source (ESI) should be an orthogonal single-deflection source of 90-degree ions, and include thermal focusing beam collimation to minimize preventative maintenance while maximizing system sensitivity.
- Covered mass range should be 5-3,000 m/z.
- Minimum Multiple Reaction Monitoring (MRM) dwell time should be 0.5 ms or less.
- Polarity switching should be 25ms or less.
- Instrument should be able to perform 4,000 MRM transitions per method in dynamic mode (based on retention time) and trigger up to 10 MRM transitions (primary and secondary) per analyte for library search and compound confirmation.
- Instrument should have a scan rate of at least 17,000 Da/s.
- Instrument should have a MRM acquisition rate of at least 500 MRMs/s
ii) LC/Q-TOF: 1290/6545
- Autotune algorithm should allow for simultaneous multi-variate optimization. The autotune algorithm should also have a fragile molecule tune for delicate molecules such as phosphorylated metabolites. Special optimized tunes for optimizing low m/z molecules (50-250 m/z) and mid-range (100-750 m/z) should be provided.
- ESI source should be an orthogonal single-deflection source of 90-degree ions, and include thermal focusing beam collimation to minimize preventative maintenance while maximizing system sensitivity.
- Given the capacity of the laboratory ventilation system where the QTOF will be installed, flight tube should be constructed of a proprietary alloy with low dimensional changes (contraction/expansion) with changes in temperature. The inner flight tube should be insulated from the outer flight tube by a vacuum (thermos design). The system should allow for exceptionally good tolerance to changes in environmental conditions to provide consistent high performance. The range of operation should be 15-35 °C. The system must be able to maintain a mass accuracy of 2 ppm, despite a change in ambient temperature of 3 degrees °C since the last calibration.
- Internal reference mass system should include a separate dedicated sprayer. The eluent HPLC sprayer must be separated from the sprayer from the internal reference mass solution to avoid any chemical interaction between the two solutions. Mass accuracy in MS mode measured at the (M+H) ion of reserpine (m/z 609.2807) should be 0.8 ppm or better when using an internal mass reference. Mass accuracy in MS/MS mode (measured from 10 repeat injections) for the product ion of reserpine (m/z 397) should be 2 ppm or better.
- Sensitivity in MS mode: at 400 μL/min HPLC flow rate, signal to noise ratio should be greater than 500:1 RMS on ion m/z 609.2807 while maintaining a resolution of 40,000 at m/z 2,722 in 4 GHZ mode, for injection of 1 pg. of reserpine.
- Sensitivity in MS/MS mode: at 400 μL/min HPLC flow rate, signal to noise ratio should be greater than 1,500:1 RMS on most intense product ions (m/z 174, 195, 397 and 448) while maintaining a resolution of 40,000 at m/z 2,722 in 4 GHZ mode, for injection of 1 pg. of reserpine.
- Linear dynamic range should cover up to 5 decades.
iii) GC/MS: 5977B/7890B
- The mass spectrometer must use an ion source where the metallic parts are constructed from inert material. Ion source temperature should be controllable from 150 – 350 °C. Stainless steel is NOT acceptable nor is coating the metallic parts with an inert material.
- Mass Spectrometer must utilize a Quadrupole Mass Filter consisting of a monolithic quartz structure. A quadrupole consisting of 4 separate rods is NOT acceptable. The rods must have a true hyperbolic shape in keeping with quadrupole theory. The Quadrupole should be independently heated and its temperature should be user-selectable from 106 – 200˚C.
- The mass spectrometer’s electronics must have the efficiency to support synchronous SIM/Scan. Synchronous SIM/Scan is a mode of operation that enables collection of both SIM data and full scan data in the same acquisition cycle. Fast electronics of the GC/MS system should provide very fast and flexible SIM and Scan. SIM dwell times should be set in 1 msec increments from higher than 100 msec to as low as 1 msec dwell, allowing rapid analysis with more compounds and more samples.
- The Mass Spectrometer must have a Gain Normalized Autotune which optimizes the electron multiplier’s (EM) gain to ensure the optimal balance between ion count, linearity and EM life expectancy.
- The mass spectrometer data system must have an integrated retention time-locking module for analyzing target compounds in complex matrices. The software module must provide the creation of custom compound databases as well as the utilization of vendor provided databases. Vendor databases should include the Fiehn GC/MS Metabolomics RTL Library and NIST 2014.
Justification of Pre-Selected Supplier:
Supplier: Agilent Technologies
Justification:
The University's research program is strictly dependent on a suite of cutting-edge metabolomics equipment. The integration of these technologies permits a global understanding of the metabolic state of cells, tissues and tumours in the context of poor-outcome breast cancers. The Researcher will use these mass spectrometry (GC/MS and LC/MS) to perform metabolomics studies, which requires an integrated system that includes powerful data analysis softwares. Data analysis is the rate limiting step in metabolomics research. We wish to acquire the Agilent suite of mass spectrometers. These systems have validated and integrated data mining capabilities including MassHunter and Profinder, notably Vistaflux that performs data alignment and automatic display of tracer analysis graphs that are already corrected based on isotopes natural abundance. Specifically, Agilent MassHunter VistaFlux enables targeted qualitative flux analysis by reducing the difficulty of data processing. VistaFlux incorporates easy creation of a targeted metabolite list, a sophisticated isotopologue extraction algorithm, and flexible pathway visualization tools. VistaFlux extends metabolomics research by capturing the fluidity of metabolism, thus increasing biological understanding. Furthermore, the Agilent Mass Profiler Professional statistical package allows for high-level statistics. The ability to integrate gene expression data with metabolomics data is of paramount importance.
Specifically:
- Agilent Q-TOF 6545 is the sole LC/MS system available to have validated and integrated stable isotope tracer analysis software (Vistaflux).
- Agilent 1290 Infinity Series UHPLC coupled to Agilent 6470 triple quadrupole (QQQ) LC/MS is the only system available that provide a validated and integrated method and software (MassHunter) to rapidly profile 215 central carbon metabolites.
- Agilent GC/MS 5977B: This instrument is compatible with the Agilent suite of mass spectrometers and integrated Mass Hunter software work across the 3 platforms.
