D1 PD.pdf

Purchase Description

Name of Item or Project Title:

Agilent 6546 QTOF LC-MS System with accessories (Brand-name or equal).

Statement of Need and Purpose:

The Informatics (IFX) Core Group, within the Division of Preclinical Innovation (DPI) at the

National Center for Advancing Translational Sciences (NCATS) seeks to purchase an Agilent

6546 QTOF LC-MS System with accessories (Brand-name or equal) in order to expand mass spectrometry capabilities and fulfill unmet research needs.

Background Information and Objective:

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people’s health and save lives.

NCATS is one of 27 Institutes and Centers at the NIH and its mission is to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. The NCATS DPI plans, conducts and uses both internal and contract resources to advance collaborative research projects across the preclinical phases of the translational science spectrum.

The NCATS DPI IFX enables data-driven decisions that accelerate translation by developing new or enhancing the application of existing methods that prioritize targets and therapeutic opportunities for evaluation; designing novel, fit-for-purpose chemical probes; and assessing the productivity of the translational research process.

The NCATS DPI Analytical Chemistry Core (ACC) maintains a state-of-the-art laboratory whose mission is to support translational research throughout NCATS by providing analytical chemistry services involving the isolation, purification, identification and analysis of various therapeutic modalities for targeted disease states.

Untargeted metabolomic profiling captures a detailed view of the chemical processes underlying cells and is the closest representation of a given phenotype (compared to other omics). Untargeted metabolomics thus plays a key role in translational research, from the identification of biomarkers to an enhanced understanding of the mechanisms that underlie diseases, and to the identification of targetable pathways or molecules. Importantly, untargeted approaches pinpoint specific pathways or reactions that can be monitored through high-throughput targeted assays. An ultimate goal is to automate the process of generating, analyzing, and interpreting untargeted metabolic profiles to accelerate research efforts.

The acquisition of a ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF) system dedicated to untargeted metabolomics would expand mass spectrometry capabilities within DPI providing significant benefit by enabling NCATS to meet the support demands of both internal and external collaborators. Current mass spectrometry instrumentation in the NCATS DPI ACC is primarily configured for routine targeted MS-based studies. By having access to a UPLC-MS dedicated to untargeted omics experimentation, NCATS will be able to fulfill unmet research needs. Multiple applications of this requested instrumentation at NCATS would include 1) identifying biomarkers of toxicity, treatment response, and diseases; 2) elucidating biological mechanisms underlying cellular differentiation, disease development, and treatment response; 3) narrowing down possible compounds to evaluate in assays based on metabolism features. This instrument would be part of a broader NCATS effort, that includes ACC, Early Translation Branch (ETB), Therapeutic

Development Branch (TDB), Chemical Genomics Branch (CGB), and Information Technology

Resources Branch (ITRB), to leverage metabolomics and other omics in preclinical and clinical research. It is worth noting that untargeted and targeted MS-based methods dovetail together to enable meaningful discoveries and facilitate comprehensive analysis throughout the progression of projects.

The Agilent 6546 QTOF LC-MS system (Brand-name or equal) will be located the ACC laboratory where its operation and management can be overseen by mass spectrometry staff.

Thus, without acquisition of the Agilent 6546 QTOF LC-MS system (Brand-name or equal), the

NCATS IFX and ACC groups will be unable to expand the metabolomic, and multi-omic capabilities of NCATS.

Generic Name of Product:

Liquid Chromatography High-Resolution Quadrupole Time-of-Flight (QTOF) with Tandem Mass

Spectrometer (LC-MS/MS)

Purchase Description:

For reference purposes, the Liquid Chromatography High-Resolution Quadrupole Time-of-

Flight (QTOF) with Tandem Mass Spectrometer (LC-MS/MS) that meet the need of this requirement is the Agilent 6546 Quadrupole Time-of-Flight MS Instrument with 1290 Infinity II

LC, as follows:

Line Item No.

Part No. Item Description Qty

1 G6546AA

Agilent 6546 Q-TOF LC/MS System with Agilent Jet Stream source, oil foreline pump, bundled PC, monitor, installation (44K), familiarization (44L), credits for a 4-day Agilent training class where available, and one (1) Year SW Update/Phone Assist (44W)

2 M5960AA

MassHunter Workstation Software for LC/TOF and LC/(Q)TOF with installation (44K), familiarization (44L), and one (1) Year SW Update/Phone Assist (44W). This software includes feature extraction and data quality control.

3* G7120A

1290 Infinity II High Speed Pump. Power range 1300 bar and 5ml/min flow, binary high pressure mixing, lowest delay, highest precision and accuracy. Includes Active Seal Wash, Tool Kit, Solvent Cabinet, bottles and ISET.

4* G7167B

1290 Infinity Multisampler up to 1300 bar for well plates and individual sample containers. Includes 1 sample drawer, 2x 54-vial containers, a needle flush port, 40 uL metering device, 20 uL loop. (for Dual-needle instruments metering is 100 ul and loop size is 20 ul) with installation (44K).

5* G7116B

1290 Infinity II Multicolumn Thermostat. Capacity up to 8 columns, temperature range 4 deg C. to 110 deg C. Includes 1.6uL Quick-Connect Heat Exchanger, Quick-Connect fitting and two Quick-Turn fittings, with Installation (44K).

6* G4231C 2 pos/6 port valve head, 1300 bar with installation (44K) 1

7 G3835AA

Mass Profiler Professional (MPP) as well as installation (44K), familiarization (44L), and one (1) Year SW Update/Phone Assist (44W). This software includes statistical analyses and intuitive visualization tools (e.g., uni- and multi-variate analyses, PCA, clustering, class prediction)

8 G3836AA

Pathway Features for MPP with familiarization (44L), and one (1) Year SW Update/Phone Assist (44W) This software enables pathway enrichment analyses.

9 G3874AA

MassHunter METLIN Metabolite PCDL. Personal Compound Database and Library for ~25000 endogenous metabolites, with ~ 9000 accurate mass MS/MS spectra for over 2300 compounds and RTs for 700 compounds

10 G3876CA

Standalone Forensics Tox PCDL library (contains drugs of abuse).

11 G5883CA

Standalone Mycotoxin Personal Compound Database and Library for current Agilent TOF and Q-TOF LC/MS Systems

12 G6890CA

Extractables and Leachables Accurate Mass PCDL for Agilent LC/MS systems

13 H2149A Method and Application Consulting On-site consulting for a maximum of four (4) participants for five (5) day on-site (includes travel)

14 5043-1759 Flex Bench, Floor with PS 1

15 5043-1735 Drawer for Flex Benches 1

* In addition to the item description provided above, the items listed herein have the following configuration:

Item 3: G7120A with the following configuration:

a. High Speed UCT (033)

b. Jet weaver upgrade kit (070)

c. Prooshell 120 EC-C18,2.1x50mm, 1.9 um

d. Manual DVD for 1220/1260/1290

e. Agilent Lab Advisor Advanced Software

f. Ultra Clean Tubing Kit

g. A-Line Stay Safe Cap Starter Kit

h. V380 Jet Weaver Mixer Upgrade Kit

Item 4: G7167B with the following configuration:

a. MassHunter System Driver

b. Agilent InfinityLab sample thermostat

c. Dual-height drawer kit

d. 1290 Infinity multi-wash option

Item 5: G7116B with the following configuration:

a. Quick-Conn HE ULD (064)

b. Valve drive for 1290 MCT

c. Quick-Connect HE Standard Flow

d. Quick-Connect HE Ultra Low Dispersion

e. Column ID kit for 1290 Infinity II MCT

Item 6: G4231C with the following configuration:

a. Kap kit QCHE G4231C

b. 2/6 cap kit 0.12 mm ID, incl. QC-HE

The salient characteristics of the Ultra-high Performance Liquid Chromatography (UHPLC) coupled to a Quadrupole Time-of-Flight (QTOF) Tandem Mass Spectrometer (MS/MS) are as follows:

• The UHPLC and QTOF systems must be manufactured by the same vendor to ensure seamless integration and operation, as well as ensuring compatibility from upgrades to the software and hardware. This enables service coverage to be maintained without voiding warranty.

• Must be capable of integrating with laboratory sample and data analysis processes and workflows.

• Handling and Shipping to NCATS, FOB Destination.

• Installation and Equipment familiarization on-site (NCATS).

• On-site consulting for at least four (4) participants for five (5) day (includes travel).

• Twelve (12) month warranty on the instruments.

• Ninety (90) days warranty on consumables.

• Twelve (12) months software updates and phone assistance.

QTOF System:

• Automated optimization of ion optics and full QTOF mass axis calibration, fully integrated part of the mass spectrometer (no manual adjusting of plumbing).

• Transparent and automated introduction of reference masses through a built-in calibrant delivery system with support for real-time internal reference mass correction for MS and

MS/MS operation.

• Focusing of the electrospray plume at the sampling aperture of the mass spectrometer for optimal ion sampling and peak shape.

• Utilizes an orthogonal Dual Jet Stream Thermal Focusing Technology. The 90-degree orthogonal source orientation is required to reduce noise from undesolvated droplets.

• The Time-of-Flight (TOF) tube must use INVAR alloy, which has a low coefficient of expansion, minimizing mass error caused by room temperature variations. The TOF tube must also be vacuum insulated with an outside flight tube for additional temperature stabilization so that mass error cannot be >1 ppm per 1 °C.

• A VacShield to allow routine maintenance of front ion source and ion transfer optics without venting MS system.

• Up to 5 orders of in-spectrum dynamic range within a single spectrum that contains co-eluting compounds.

• Utilize Analog-to-Digital conversion at a minimum of 10 GHz.

• Detection and enhancement signal of fragile molecules that are susceptible to fragmentation and loss within the atmospheric pressure interface of an LCMS.

• A mass range of m/z 50 – 10,000.

• An MS sensitivity (positive or negative) of >500:1 RMS in 10 replicates with a 1 pg injection of reserpine monitoring most intense product ions (174, 195, 397, and 488 m/z for positive and 152, 176, 194, and 257 m/z for negative) and maintaining maximum mass resolution.

• An MS/MS sensitivity (positive or negative) of >1,500:1 RMS in 10 replicates with a 1 pg injection of reserpine while maintaining maximum mass resolution.

• An MS mass accuracy of <2.0 ppm RMS in 10 replicates. Measured in positive mode with a product ion m/z 397.2122 (reserpine) and in negative mode with a product ion m/z

152.0353 (chloramphenicol).

• An MS/MS mass accuracy of <0.8 ppm RMS in 10 replicates. Measured in positive mode at

(M+H)+ ion m/z 609.2807 (reserpine) and in negative mode at (M+H)+ ion m/z 321.0051

(chloramphenicol).

• Maintain <1 ppm mass accuracy within a 3 °C drift/hr without need of re-tuning.

• A mass resolution in positive mode of >30,000 FWHM at 118 m/z and >60,000 FWHM at

2,722 m/z and a mass resolution in negative mode of >30,000 FWHM at 113 m/z and

>60,000 FWHM at 2,834 m/z. This is at full acquisition speed without sacrificing the sensitivity in single bend V-shaped flight path.

• An MS acquisition speed of 50 spectra/sec while maintaining maximum resolving power.

• An MS/MS acquisition speed of 50 spectra/sec while maintaining maximum resolving power.

• A polarity switching time of 1.5 sec for a complete cycle of positive and negative spectral acquisition.

• Isotopic fidelity such that the relative isotopic abundance error is <5% of the RMS for 10

ESI calibrant ions in positive polarity (RIA error (%) = 100 × (RIAexp – RIAtheo)/ RIAtheo).

• Capable of utilizing the following ion sources: APCI, APPI, combined ESI/APCI, nanoESI interface, and GC APCI source with fully integrated GC and transfer line control.

UHPLC system:

• UHPLC instrument must be come with and be compatible with a rollable Flex Bench.

• A highspeed hydraulic pump system with dual pistons in series with a servo-controlled variable stroke design. Smooth motion control for active damping and a metal microfluidic solvent mixing device to minimize delay volume.

• A pump flow range of 0.001 – 5 mL/min settable in 0.001 mL/min increments (300 pL/step increments).

• An operating range up to 130 MPa (1300 bar) at 0 – 2 mL/min and down to 80 MPa (800 bar) at 5 mL/min.

• An operational pH range of 1 to 12.5.

• Column compartment must hold a minimum of 2 columns and be upgradeable to 8 columns with a temperature range of 4 to 110 °C.

• Sample compartment has up to 8 single height drawers each having a footprint to hold 2 microtiter sample plates. Drawers are configurable for single height, double height, and triple height usage depending on plate or vial type.

• Sample capacity of up to 6,144 well-plate samples (16 x 384 shallow-well microtiter plates) or 432 2-mL vial samples (8 x 54 position 2-mL racks).

• Sample compartment temperature range of 4 to 40 °C that is settable in 1 °C increments; a maximum temp of 5 °C below ambient; ±2 °C at 4 °C set-point.

• Capable of utilizing a diode array detector (DAD), diode array detector fixed slit (DAD FS), and/or evaporative light scattering detector (ELSD) in addition to various mass spectrometers.

Software and Data Processing:

• System must be operable with OpenLab, MassHunter, Mass Profiler Professional (MPP) software.

• QTOF software must offer full native support and control for Agilent 7100 CE, 1100/1200/1290 LC systems, 1260 SFC, and RapidFire sampling system.

• Data Dependent MS/MS and Data Independent MS/MS support.

• System must contain and be compatible with the following Personal Compound and

Database Libraries (PCDLs): MassHunter METLIN metabolite, Forensics Tox, Mycotoxin, and Extractables and Leachables Accurate Mass.

• PCDLs must be curated to confirm no elemental formula errors, ensure fragment ions can be theoretically generated from parent compound, and fragment masses are corrected to display precise mass.

• PCDLs must contain MS/MS spectrums with 3 spectra/compound at different collision energies.

• Data file format compatible with 3rd party software for data analysis.

Quantity:

One (1) Liquid Chromatography High-Resolution Quadrupole Time-of-Flight (QTOF) with

Tandem Mass Spectrometer (LC-MS/MS) as described in the Purchase Description.

Delivery:

Delivery is required within three (3) weeks after receipt of order (ARO). Delivery shall be made to the below address with FOB Destination. Shipping, handling, and travel shall be included in the quote.

National Center for Advancing Translational Sciences (NCATS)

9800 Medical Center Drive

Rockville, MD 20850

Building and Room to be informed at time of award.

The installation and equipment familiarization shall be conducted on dates and times agreed upon by the vendor and the NCATS point of contact designated on the award