Statement of Work Q0216.docx

Statement of Work Thermo Electron Orbitrap IQ-X, Vanquish Flex Binary Package (Liquid Chromatography-High Resolution Mass Spectrometer)

General Information

1.0 Scope of Work

Vendor is to deliver and install a new Thermo Electron Orbitrap IQ-X, Vanquish Flex Binary Package. Vendor will also provide training on the use and maintenance of the instrument and associated software.

2.0 Background

The Orbitrap IQ-X, Vanquish Flex Binary Package is an Ultra-High-Pressure Liquid Chromatography System connected to a Tribrid High-Resolution Mass Spectrometry system used to analyze complex samples to identify and quantify chemical components within the sample. Ultra-High Pressure Liquid Chromatography allows for better separations in short times, increasing throughput. The tribrid system is designed to detect and fragment (for identification of unknown components) analyte ions by two separate mechanisms (collisional-induced dissociation and higher-energy collisional dissociation modes) providing complementary fragment ions allowing for confident structural determination. The high-resolution Orbitrap mass analyzer allows for confident identification of molecular and fragment ions. The USDA Agricultural Research Service (ARS) in Peoria, Illinois has a need to replace an HPLC Orbitrap-Discovery purchased in 2010. The Orbitrap IQ-X, Vanquish Flex Binary Package is required to meet the minimum technical requirements for anticipated use and allows for the ability to compare historical data and developed methods from the Orbitrap-Discovery with experiments using the Orbitrap IQ-X, Vanquish Flex Binary Package. Experimental requirements are small molecule (mass ≤ 2000 m/z) analyses with the need for ultra-low level quantification of both known (targeted) organic chemicals, as well as identification and quantification of unknown (non-targeted) chemicals in a variety of sample matrices.

Contractor Requirements

3.0 Technical Requirements / Tasks

A Thermo Electron Orbitrap IQ-X, Vanquish Flex Binary Package is required for Ultra-High Pressure Liquid Separations with High-resolution mass spectral detection of: intact; collisional-induced dissociation fragments; and higher-energy collisional dissociation fragment ions.

Technical Requirements

1. The liquid chromatograph (LC) must be an ultra-high-pressure liquid chromatograph (UHPLC) capable of rapid resolution chromatography.

2. The UHPLC must be controlled by the Mass Spectrometer (MS) software.

3. The tribrid MS must have two independent mass spectrometers: (1) linear ion trap and (2) High Resolution/Accurate Mass (HR/AM) Orbitrap.

4. The mass spectrometers must be able to operate independently or in concert with the other.

5. The MS must consist of three functioning mass analyzers: (1) quadrupole mass filter (2) linear ion trap and (3) Orbitrap.

6. Each mass analyzer must be able to work sequentially or in parallel with the other.

7. On-Line Uninterruptible Power System with Built-in Power Conditioner

8. 5.2 kVa power conditioner with Uninterruptible Power System (UPS) with minimum battery runtime of 6-8 minutes at full load

9. Uninterruptible Power System must provide electrical power and proper electrical outlets for all components of the UHPLC-Orbitrap Tribrid MS system.

10. Sensitivity: Ion Trap Full Scan MS/MS HESI (heated electrospray ionization)- 2 μL of 50 fg/μL reserpine injected at a flow of 500 μL/min must produce a minimum signal-to-noise ratio of 100:1, for the transition of the isolated protonated molecular ion at m/z 609 to the two largest product ions, while the MS is operated at unit resolution in full scan MS/MS mode, scanning the product ion spectrum from m/z 165-615.

11. Ion Trap MSn Full Scan MS/MS HESI-2 μL of 50 fg/μL reserpine injected at a flow of 500 μL/min must produce a minimum signal-to-noise ratio of 25:1, for the transition of the isolated protonated molecular ion at m/z 609 to the product ion at m/z 397 which is further fragmented to the product ion m/z 365, while the MS is operated at unit resolution in full scan MS/MS mode, scanning the product ion spectrum from m/z 165-615.

12. Mass Resolution (Orbitrap)-The mass spectrometer must have a mass resolution of 240,000 (FWHM) at m/z 200 with a spectrum repetition rate of 1.5 Hz, to ensure isotopic fidelity.

13. The mass spectrometer must be able to obtain mass resolution up to 500,000 at m/z 200 in full scan mode.

14. Mass Accuracy- The mass spectrometer must provide mass accuracies of less than 3 ppm RMS with external calibration over 24h and without any kind of mass recalibration (under defined conditions)

15. The mass spectrometer must provide mass accuracies of less than 1 ppm RMS with internal calibration.

16. Dynamic Range- The mass spectrometer must have a dynamic range of greater than 5000:1 within one spectrum (single transient acquisition) while maintaining specified mass accuracy.

17. Mass Range-The mass spectrometer must operate in the mass range of 50 - 2000 Da.

18. Polarity Switching-The mass spectrometer, set at a mass resolution of 30,000, must be able to switch between positive and negative ionization during successive scans in one full cycle (1.1 sec)

19. Scan Functions- The mass spectrometer must be capable of the following scan functions: Full Scan MS; Single Ion Monitoring (SIM); Full Scan MS/MS; MSn multistage MS experiments, n = 1-10: Enhanced Scan to determine 3+ charge state ions at 10,000 amu/s

20. Advanced Functions: The mass spectrometer must have the following advanced functions: - Automatic Gain Control (AGC) to automatically control ion injection time for optimized ion current across the entire chromatographic peak; predictive ACG algorithm to determine the ion injection time without carrying out a prescan event; Data Dependent Decision Tree logic to determine the optimal fragmentation technique and mass analyzer during the liquid chromatography run.

21. Dynamic Exclusion capability to temporarily exclude an ion while allowing acquisition of MS/MS or MSn spectra to increase the selectivity of co-eluting compounds and enhance the signal of selected compound. Capability to perform data dependent MSn scan based on information obtained from earlier MSn scan. Scan Rate. The mass spectrometer, operated with Orbitrap mass analyzer at MSn, must have a scan rate up to 30 Hz, under defined conditions. The mass spectrometer, operated with linear Ion trap at MSn, must have a scan rate up to 40 Hz.

22. Ion Source: The mass spectrometer must have an ion source with a HESI (heated electrospray ionization) probe and an option for atmospheric pressure chemical ionization (APCI) probe. The ion source must be capable of rapid switchover between the ESI and the APCI probe without breaking vacuum. The HESI and APCI probes must include a feed-back-controlled heater capable of operating up to 500 °C to vaporize the solvent and analyte. The HESI probe must operate at flow rates ranging from 1 μL/min to 2 mL/min, using 100% water without splitting. Optional APCI probe must operate at flow rates ranging from 50 μL/min to 2 ml/min using 100% water, without splitting. The HESI and APCI probe needles must be moveable relative to the sampling orifice or optimal tuning. The source must have an automatic tuning program to optimize all ion focusing voltages. The source must incorporate a safety interlock switch to shutoff voltages when the probe is removed. The source must incorporate Sweep Gas to reduce chemical noise. The source control must include high-voltage dual-polarity power supply, sheath gas flow control, and auxiliary gas flow control to accommodate a wide variety of applications. The ion transfer tube (ITT) must be capable of replacement without system venting.

23. Ion Optics: The mass spectrometer must have a progressively space stacked-ring ion guide (S-Lens) to captures and focus ions into a tight beam and minimize in-source dissociation. The mass spectrometer must have a 90 ° bent square RF active beam guide with an axial field along the length of the rods for robust and high ion transmission while reducing noise by preventing neutrals and high-velocity clusters from entering the quadrupole mass filter.

24. Ion Routing Multipole and Mass Analyzers: The tribrid mass spectrometer must consist of three functioning mass analyzers: (1) quadrupole mass filter (2) linear ion trap and (3) Orbitrap. Each mass analyzer must be able to work sequentially or in parallel with the other and be operated using Dynamic Scan Management. All three mass analyzers must be capable of real-time mass analysis and the Orbitrap and Ion trap must be capable of real time detection and data processing to enable a high spectrum repetition rate. The mass spectrometer must perform parallel detection; in 1 minute it must be able to acquire at minimum of 30 full scans (resolution 120,000, m/z 200) detected with Orbitrap and 1200 data dependent MS/MS scans of parent ions isolated with quadrupole, fragmented in ion routing multipole and detected with ion trap. The quadrupole mass filter must be capable of isolating masses at a 0.4 Da width. The mass spectrometer must have an Ion-Routing Multiple device for ion accumulation, fragmentation and routing to the Orbitrap or the linear ion trap mass analyzers. The Ion Routing Multipole must be able to multiplex up to 10 precursors per scan using the quadrupole mass filter for targeted MS2 and SIM. The mass spectrometer must be capable of Collision Induced Dissociation (CID) and Higher Collision Dissociation (HCD) at any MSn stage with fragmentation detection in either the linear ion trap or Orbitrap. The mass spectrometer must be capable of isolating ions down to 0.2 Da for up to m/z 1000 and 1 Da isolation for up to m/z 2000. The mass spectrometer must have a gas filled C-trap as intermediate storage device to the mass analyzers.

25. The mass spectrometer must have an electrostatic orbital trap as one of its mass analyzing devices. The mass spectrometer must have a dual-pressure linear ion trap as one of its mass analyzing devices. The mass spectrometer must perform automated synchronous precursor selection for up to 20 precursors at MS3 using the linear ion trap.

MS Vacuum System: The mass spectrometer must have a spilt-flow turbomolecular pump with regulated vacuum in multiple regions providing multiple stages of differential pumping between the C-trap and the Orbitrap. The mass spectrometer must have rotary pumps as fore vacuum pumps. The mass spectrometer must have pumps that maintain pressure of better than 4x10-10 Torr in the Orbitrap analyzer region.

26. MS Divert Valve: The mass spectrometer must have a divert valve to allow the user to divert the HPLC column flow during any portion of the run to waste or to the MS source. The divert valve must be under fully automated data system control.

27. MS Syringe Pump: The mass spectrometer must have a syringe pump for automated infusion under data system control.

28. Instrument Control and Application Specific Software: The mass spectrometer must support Xcalibur software for instrument control, tuning, system calibration and diagnostics, automated and manual data acquisition, and data processing including Freestyle, Qual, and Quan Browser. Xcalibur MS software must control the UHPLC. The mass spectrometer must have Method Editor software with small molecule application-specific templates to facilitate method development. The mass spectrometer must have Compound Discoverer software for small molecule identification.

29. Training- 3-day on-site training.

30. Computer, Minitower. 3.4 GHz Processor; 32 GB Memory; 1 TB Hard Drive; Windows 10, 64-bit; Monitor

31. Ultra High-Pressure Liquid Chromatograph (UHPLC)Pump. The UHPLC must have a binary pump that meets the following specifications: Solvent selection valve to select a binary mixture from a minimum of 4 separate independent solvent bottles. Flow range of 0.0001 to 5 mL/min, in 1 μL/min increments. Flow accuracy of ±0.1%. Pressure range of 5 to 151 MPa (50-1517 bar).

32. Fully automated Compressibility Compensation that is independent of mobile phase composition. Flow precision of <0.05% RSD or <0.01 min SD, whichever is greater. Capable of high-pressure gradient formation with a high accuracy and precision. Mixer volume of 25μL. Biocompatible, pH range of 2 to 12 with buffer and/or ≤ 1 mol/L chloride. Integrated degassing unit. Leak detection and excess pressure monitoring

33. Auto-Sampler: The UHPLC must have an autosampler with a thermostatically controlled sample compartment that meets the following specifications: Operate using split-loop injection. Injection volume from 0.01 to 25 μL, minimum step of 0.01 μL. Operating pressure from 5 to 151 MPa (50 to 1517 bar). Injection volume precision of <0.25% RSD for 1 μL of caffeine in water. Injection volume accuracy of ±0.5% for 10 μL of water. Minimum sample requirement of 2 μL at a 1 μL injection. Carry over must be <0.004% with Chlorhexidine or <0.0004% with caffeine. Must have a needle wash. Temperature range of 4 to 40°C and temperature accuracy of -2 °C/+4°C and temperature stability of ±1 °C. Temperature controlled sample compartment must have a low dwell volume, ≤ 110 μL with 25 μL sample loop. Sample tray must function with a variety of standard chromatography HPLC vials and well-plates. Leak detection capability Biocompatible, pH range of 2 to12 and ≤ 1 mol/L chloride

34. Column Chamber: The UHPLC must have a thermostatically controlled column chamber that meets the following specifications: Operates using still and forced air and have an active pre-heater and a passive post-column cooler. Temperature range 5 to 120 °C, in 0.1 °C increments. Temperature stability ±0.05 K. Temperature accuracy ±0.05 K (up to 80 °C). Heating performance <15 min, 20 to 50 °C, ±1 K. Cooling performance <15 min, 50 to 20 °C, ±1 K. Pressure range of 5 to 151 MPa (50 to 1517 bar). Minimum capacity for 2 chromatography columns. Humidity and fluid leak detection. Biocompatible, pH range of 2 to12, with buffer and/or ≤ 1 mol/L chloride.

35. UHPLC-MS Connection Kit: The UHPLC must have a Mass Spectrometer connection kit.

36. Additional Minimum Requirements: Tribrid Architecture: The Government requires a mass spectrometer system built on a mass spectrometer architecture that includes a quadrupole mass filter and two separate mass analyzers, an Orbitrap analyzer and a linear ion trap analyzer. The quadrupole can isolate select ions for transmission to the ion routing multipole. The ion-routing multipole features a higher-energy dissociation (HCD) collision cell, enabling ion storage with or without fragmentation, which then transmits ions to the selected mass analyzer or between the two analyzers. This unique architecture allows for parallelization (simultaneous precursor isolation, fragmentation, and data acquisition), increased scan rates, and ultimately increases the versatility of the instrument. The architecture also allows for MSn experiments using either the linear ion trap or Orbitrap as the mass analyzer at each MS stage.

37. High-Resolution Accurate-Mass Capabilities: requires a mass spectrometer system with a mass resolution up to 500,000 at m/z 200.Confident compound identification relies on measuring the accurate mass of a compound to determine molecular weight and subsequently identify the chemical formula of an unknown. This increased resolution provides the resolving power to separate compounds with very similar masses (isobars), which in turn increases the certainty of a chemical formula for the identified accurate mass. Lower mass resolution instruments may not be able to separate isobaric compounds, leading to incorrect chemical formula assignments and a reduction in the ability to identify unknowns. The Government also requires a very low mass error of <1 PPM when using internal calibration. Low mass error is equally important for identifying the exact mass of unknowns, for the same reasons noted above.

38. MSn Analysis: The Government requires a mass spectrometer system that is capable of MS/MS measurements, including MSn (n ≤ 10). Even with very high mass resolution, isomeric compounds cannot be distinguished by exact mass alone since they have the same chemical formula. To fully elucidate the structure of an unknown, MS/MS and MSn analysis is critical. For some isomers, only MSn experiments can provide the spectral details required to elucidate structural differences among isomers or isobar. The Government requires a high-resolution instrument identified capable of generating MSn precursor and product ion full scan mass spectra, allowing for optimal unknown identification and structural elucidation.

39. Refurbished or remanufactured units are not acceptable.

40. The system must come with at least a 1-year warranty.

4.0 Deliverables / Schedule

Key Deliverables

None.