SOW for RFQ.pdf

Request for Quotation Number 1333ND20QNB640494

Statement of Work

BACKGROUND

New programmatic areas in the Biosystems and Biomaterials Division (644), Biomolecular Measurement

Division (645) and Chemical Sciences Division (646) within the Materials Measurement Laboratory (MML) of the National Institute of Standards and Technology (NIST), are expanding beyond targeted mass spectral measurements that aim to generate quantitative values or reference spectra to non-targeted analyses (NTA). The aim of NTA is to provide a chemical fingerprint of complex samples and to generate mass spectra of unknown analytes with sufficient resolution for determining molecular formulas.

The shift to NTA requires high-resolution hybrid mass spectrometers that provide enhanced sensitivity, specificity, and reproducibility compared to unit resolution mass spectrometers. One such system is a liquid chromatograph (LC) and gas chromatograph (GC) coupled to a quadrupole-ion mobility-time of flight mass spectrometer (QTOF). This LC/APGC-QTOF system will afford Division 646 and its partners the ability to use either LC or GC on a single mass spectrometer, a unique capability for MML.

This system employs a single data-processing tool for both LC-amenable (low-volatility, polar, semi-polar) and

GC-amenable (volatile-as accessed through SPME, nonpolar) compounds, which covers most of the organic chemical measurement space. In addition, the system is equipped with an internal ion mobility spectrometry

(IMS) component, which allows MML to use the collisional cross section (CCS) property of both the intact compounds and fragment compounds to produce an additional orthogonal dimension of data and lead to faster and more accurate compound identification. Finally, the QTOF provides high-resolution mass spectral data

(albeit lower resolution than an Orbitrap), with a significantly faster scan rate than an Orbitrap system. This will complement MML’s existing Orbitrap systems and resemble cutting-edge systems that are now becoming more common in national and academic laboratories.

Currently, the three Divisions are involved in multiple cross-divisional programmatic areas that require this technology. Specifically, the area of microbiome community measurements, which aim to measure cooperative or emerging behaviors of complex microbial communities (microbiomes) as it relates to human health, agricultural productivity, biodefense, water and food safety, waste remediation, and infrastructure corrosion.

The development of microbiome standards is needed to accelerate the availability of microbiome diagnostics and to enable manufacturing of microbiome therapeutics. These efforts rely on high-resolution mass spectral analytical tools to measure the metabolic cross-talk between microbes, and for the most part, these metabolomic measurements are rather new and not fully validated. Division 644 has developed the NIST Living

Measurement Systems Foundry and other laboratory automation tools to facilitate high throughput engineering of complex microbial systems with the end goal of assessing how community structure relates to its function

(structure-function). To complement this capability, the procurement of a LC/APGC-QTOF system will allow for high-throughput multiomic measurements, leveraging the MS-based metabolomics, lipidomics and proteomics expertise in Divisions 645 and 646.

This instrumentation will be an integral part of NIST’s response to the COVID-19 pandemic, as it will be able to provide definitive methods and protocols for robust high-resolution clinical validation. These measurements and standards will aid in validating infectious disease diagnostics, an area that has demonstrated a large demand for standardization amid the COVID-19 pandemic. Additionally, this instrument will be an integral component to the rapid development of a human fecal (gut microbiome) reference material—an effort in which Divisions

644, 645, and 646 are committed to achieving and actively working with stakeholders to develop. Finally, Divisions 645 and 646 are actively engaged in supporting Division 644 and the community-at-large through reference material and data libraries development that will enable federal, academic, and industry labs to reliably reproduce and advance each other's results.

Additional cross-divisional MML programmatic areas in need of this technology include, but are not limited to:

(1) Metabolomics for Precision Medicine: metabolic profiling of a new class of cellular reference materials that are rapidly produced for on-demand harmonization;

(2) Food and Natural Product Safety: identification of natural toxins and levels of adulteration, characterization of biochemical profiles related to authenticity, and molecular fingerprinting of components;

(3) Forensics and Food Defense: identification of exogenic toxins in various foodstuffs and characterization of designer illicit drugs and database development;

(4) Environmental Sciences: characterization and better understanding of pervasiveness of per- and polyfluoroalkyl substances in the environment and subsequent human exposure;

(5) Mass Spectral Libraries: expand the NIST MS Library to include HR-MS spectra and undertake first steps to expand the MS Library to include CCS values obtained through IMS.

Both Divisions 645 and 646 have been instrumental in providing support for these MML programmatic areas, but current high-resolution mass spectrometry instrumentation was obtained for and is currently limited to more targeted measurement science applications. Since MML is expanding the scientific areas in which it will be applying non-targeted analyses/profiling, it is dire that MML acquires additional high-resolution mass spectrometric instrumentation. The application of the advanced capabilities of the proposed instrumentation will leverage the current non-targeted/untargeted analysis expertise.The instrument purchase and operation create a cross-divisional, highly-capable resource for the identification of unknown chemical compounds, broad chemical characterization of materials, and chemoinformatic data production and analysis.

Although there are many types of instrumentation available from various manufacturers, not all of them provide multiple chromatographic interfaces for LC and GC with respective ionization mechanisms, capable of post-quadrupole IMS separation, and high-resolution accurate-mass (HRAM) mass spectrometry with high scan-rate.

Existing HRMS instrumentation lacks nearly all these capabilities.

The multiple chromatograph formats (LC and GC) are necessary to cover a broad range of compounds in the chemical space, including volatile/non-volatile and polar/semi-polar/non-polar compounds. The mass spectrometer must have a high resolution (greater than or equal to 10,000 resolving power) and accurate mass

(less than or equal to 10 ppm mass error) capabilities with a fast scanning rate, which can only be performed with a time-of-flight mass spectrometer. Finally, many MS instruments offer ion mobility/differential mobility spectrometers that are installed post-ionization source and pre-quadrupole mass analyzer, these types of instruments cannot provide CCS information about the collision-cell ion fragments, a necessary component to the identification of unknown compounds. The IMS must be post-quadrupole in order to provide this valuable information.

To provide the greatest functionality and ease of use, both the LC and GC, with the mass spectrometry instrument, must work together independently (LC-HRMS and GC-HRMS) using one instrument control software package with combined analysis methods. The data system, for instrument control and data analysis, must also be included with the LC, GC and HRMS instruments.

BRAND NAME JUSTIFICATION

The statement of work identifies several projects that MML is currently engaged in or can be engaged in when this equipment is purchased. In order to carry out these projects, NIST must expand its capacity in high resolution mass spectrometry with both LC and GC separations. The functionalities of the Waters SYNAPT system are specifically necessary for NIST to carry out its mission relevant to the projects identified. The ion mobility introduces a new dimension of analysis to help with discovery in non-target analysis.

The functionality of this instrument allows NIST to gain insight into the widest array of chemical compounds, as it employs both APGC and LC separations. The instrument is also well suited for unknown compound elucidation through its MS/MS capabilities and high-resolution mass analysis. The ion mobility cell will serve to help distinguish compounds which have the same chemical formulas but differing chemical structures, thus further helping to elucidate compound identities - which is necessary for all of NIST’s ongoing projects. The benefit in procuring a whole system is the seamless integration of the instrument and the data analysis.

Procuring this one instrument takes the place of at least two other large instrument procurements which would be much more costly.

Only the Waters SYNAPT XS system meets the Government’s requirements of GC and LC sources, interchangeable LC/GC interface, IMS capabilities, metabolomics software platform, and post-quadrupole IMS capability. No other vendor produces a mass spectrometer with an ion mobility cell that can be coupled to an

APGC and LC.

NIST could not foresee a situation where a vendor would modify their instrument to meet the Government’s requirements.

SPECIFICATIONS

The Contractor shall provide a Liquid Chromatograph, Gas Chromatograph Coupled with Hybrid Quadrupole-

Time of Flight Mass Spectrometer with Ion Mobility, SYNAPT XS HDMS 4k System, Product #176850035, manufactured by Waters Corporation, including all of the following components and meeting all of the requirements herein:

-Liquid Chromatograph

-Gas Chromatograph

-Mass Spectrometer (MS)

-Software

Liquid Chromatograph (LC):

• Must be a benchtop LC instrument

• Must be able to perform chromatography with flow range 0.001 to 2.000 mL/min

• Capable of pressure limits of up to 18,000 psi

• Must have a binary solvent pump with high pressure mixing, with up to four solvent lines and vacuum degasser

• Flow accuracy and precision shall be 1.0 % and ≤ 0.075 % RSD, respectively

• The total system dwell volume <95 μL

• Composition accuracy must be ± 0.5 %

• Sample management system must hold at least 48 2-mL vials

• Injection volume range must be at least 0.1 to 10.0 µL, with injection volume accuracy of 0.2 µL and precision of ≤ 0.25 %

• The pump shall have the capability to Start the gradient “At injection (default), “Before the injection"

(pre-volume) or “After Injection” (gradient delay)

• Sample temperature control with temperature range of 4.0 - 40 °C with temperature stability of 1 °C.

• The sample manager shall have a rotary tray mechanism that rotates the samples into position reducing the distance to the injection port and hence reduces volume and dispersion.

• Injection needle wash system.

• The sample manager carryover must be less than 0.001% from sample to sample.

• Column management system for up to two LC columns

• Column temperature control of 4.0 – 90 °C with stability of ±0.5 °C.

• Must be controllable by software listed in specifications below.

Gas Chromatograph (GC):

• Must be a benchtop GC instrument

• An atmospheric pressure GC interface must be available

• Automatic sample tray that can hold at least 100 2.0-mL vials

• Include an autoinjector with split/splitless injection capabilities and injector size range of at least 10 nl to

50 µL.

• Injector pressure range from 0 to 100 psi

• Maximum injection split ratio of 250:1

• Maximum injector operating temperature of 400 °C

• Column oven temperature range of 8 °C above ambient to 425 °C, with temperature resolution of 1 °C.

• Flow adjustable range of 0 to 500 mL/min He

• Must possess an autosampler capable of headspace and SPME injections

• Must be controllable by software listed in specifications below.

Mass Spectrometer (MS):

• The instrument must be floor-standing in design, having a footprint no bigger than 1500 mm x 720 mm x 1710 mm (H x W x D).

• Electrospray Ionization (ESI) source with LC connection capabilities

• The instrument must be equipped with an atmospheric pressure ionization (API) interface that includes the source and spraying elements. Samples may be introduced by direct infusion or the system may be interfaced directly to either a LC system or a GC system.

• The instrument must be equipped with a stepwave, a T –Wave based ion optics with 2 offline T-wave design must be provided to maximize ion sensitivity while maintaining system robustness.

• Time-of-Flight mass resolution of at least 60,000 (determined at FWHM)

• Calibrated mass accuracy with targeted analysis of less than 1 ppm error, and over dynamic range of less than 3 ppm error

• Mass dynamic range of 5 orders of magnitude

• Scan rate of up to 30 scans per second

• The instrument shall be capable of MSE data acquisitions whereby high and low collision energy data is acquired simultaneously to provide fragmentation data for all detectable molecular ions.

• Ion mobility spectrometry (IMS) capabilities with the Ion mobility cell must be in between the quadrupole and time-of-flight regions of the mass spectrometer with two collision cells on either side of the ion mobility cell o For analytes that are detected by both LC and GC MS, collisional cross section values determined in both data types will agree within an average of 2% of the absolute CCS value.

o The IMS device shall incorporate the ability to use multiple IMS gases as standard

• Ion mobility resolution of 40 Ω/ΔΩ

• Nitrogen generation system to accommodate lack of gas plumbing to the house nitrogen distribution system in the laboratory that can produce producing analytical grade nitrogen gas up to 99.5% purity up to 35

L/min up to 116 psi

• Maintenance free, oil free, roots vacuum backing pump

Software Requirements:

• Software that can fully control the LC, GC, and MS and perform general data analysis of measured data within the manufacturer’s data format

▪ Software provided must be intuitive graphic-based package, and not rely on user scrips as a means of operating

▪ Communication between LC and MS and GC and MS must be performed with no manipulation of communication cables

▪ System must arrive standard with a quantitative data analysis package with the ability perform calibrations and compound values assignment and to view processed results simultaneously with chromatographic data.

• Non-targeted/metabolomics software platform that can perform data analysis of measured data within the manufacturer’s data format

▪ Must include peak-peaking algorithm for identification of compound ions, normalization of ions, and quantification of ions.

▪ Retention time alignment of identify compound ions

▪ Compound search methods within software libraries

▪ Compound search methods within online database resources such as ChemSpider

▪ Compound identification using exact mass, MS/MS fragments, isotopic distribution, retention time, and collisional cross section (CCS).

▪ Data visualization tools for data independent and data dependent analyses

▪ Perform multivariate statistics of data including principal component analysis (PCA) and correlation analysis

▪ Perform statistical tests, such as false discovery rate

• Mass spectral data library access for METLIN MS/MS spectral data

• The instrument must have implementation of Intelligent Data Capture (IDC) which employs advanced signal processing algorithms during data acquisition to isolate and store only statistically significant and analytically relevant information. The result is substantially reduced file sizes, alongside lower demands on data storage and processing, while maintaining data fidelity.

• The software shall provide an automated route to calibrating the ion mobility dimension to enable the generation of accurate collision cross section (CCS) measurements in positive or negative ion mode, for routine

LC/MS and LC/MS/MS analysis. The software shall also include the ability to use the collision cross section of a reference compound (Lock CCS) at regular intervals to ensure accurate CCS measurement with high precision, irrespective of chromatographic gradient length or the number of samples being analyzed.

DELAYED MANUFACTURING/DELAYED DELIVERY

Due to COVID-19, the National Institute of Standards and Technology is currently closed with the exception of mission-critical staff. The Contractor shall contact the NIST Contracting Officer’s Representative (COR) and

Technical Point of Contact (TPOC), to be identified at the time of award, upon award, to discuss the delivery timeline.

The Contractor may be required to delay manufacturing/shipping for a period of time that may be as short as one month from the date of award up to six months from the date of award. The TPOC will communicate with the Contractor regarding the status of NIST operations and provide written notification to the Contractor when delivery can be completed.

If the Contractor chooses to manufacture the equipment upon award, the Contractor shall be responsible for storing the equipment, at their sole expense, until such time that NIST can accept delivery of the equipment.

Installation:

The Contractor shall install the instrument in Building 227, Room B147 at NIST Gaithersburg, MD.

Installation shall include, at a minimum, uncrating/unpacking of all equipment, set-up and hook-up of all equipment, start-up, demonstration of all minimum specifications, and removal of all trash.

Installation must be discussed and scheduled in advance, with the NIST Contracting Officer’s Representative

(COR) and the NIST Technical Point of Contact (TPOC).

Installation must take place during normal business hours, between 8:30 am and 5:00 pm Eastern Time, Monday through Friday except Federal Holidays. Installation must be completed not later than 60 days after the

Contractor is authorized to manufacture the equipment.

Warranty:

The Contractor shall provide, at a minimum, a one-year warranty for the equipment. The warranty shall cover all parts, labor and travel. The warranty shall commence upon successful completion of delivery, installation, training and demonstration of all required specifications.

Service Agreement

The Contractor shall provide an additional two years of maintenance and repair service beyond the one-year warranty, for a total of three years of service. During this three-year period, two preventative maintenance visits must be performed; One at the end of year 2 and one at the end of year 3.

The Contractor shall provide 24/7 telephone support, labor, all parts, shipping and travel related expenses throughout the period of performance. The Contractor shall reply to a service call within 24 hours. In the case that on-site maintenance is required, the Contractor shall initiate on-site services within 10 business days.

For any services performed, the Contractor must provide the NIST Technical Point of Contact with a service ticket that contains the following information:

Service Ticket:

- Model number.

- Serial number.

- Date and time of arrival to NIST.

- Description of service performed.

- Name and quantity of any parts that were repaired.

- Name and quantity of any parts that were replaced.

- Date and time of departure from NIST.

- Diagnostic test results or narrative summary demonstrating that the instrument is meeting the manufacturer’s performance standards.

- Any additional comments or recommendations.

- Printed name and signature of service technician. Signature block for NIST personnel accepting the services rendered.

PERIOD OF PERFORMANCE

Delivery of equipment, installation and training must be completed not later than 90 calendar days after the

COR/TPOC advise the Contractor to commence with manufacturing.

The one-year warranty shall begin after successful completion of delivery, installation, demonstration of all required specifications and training and NIST’s acceptance of the equipment.

Two-year maintenance service period shall begin the day following the expiration date of the warranty.

PLACE OF PERFORMANCE

All work shall be completed at the Contractor’s facility. Installation of the instrument and training shall be accomplished at NIST, Gaithersburg, Maryland. Normal duty hours are Monday through Friday, 8:30 a.m. to

5:00 p.m. with the exception of Federal holidays.

DELIVERABLES

Description Quantity Due Date

Delivery and installation of the analytical instrument

One (1) 90 days after the Contractor is advised that manufacturing can commence

Operations and maintenance manual for the analytical instrument

One (1) Upon completion of delivery and installation

Training of NIST personnel at NIST, Gaithersburg, MD

Once Not later than 10 days after installation.

GENERAL INFORMATION

Safety: The Contractor employee shall be responsible for knowing and complying with commercial installation safety prevention regulations. Such regulations include, but are not limited to, general safety, fire prevention, and waste disposal.

Security: NIST is a restricted campus. An identification badge is required for access for entry into buildings and also is shown to the armed Security Police when entering the campus.

Identification Badges: Contractor employees shall comply with NIST identification and access requirements.

The Contractor shall provide the name and citizenship information of employees for on-site visits to the NIST

Technical Point of Contact (TPOC) prior to arrival. The TPOC will submit the name(s) and citizenship information to the NIST Office of Security in order for a given Contractor employee to enter the NIST campus.

The Contractor employee is responsible for absences due to missing or expired identification and access documents. Each Contractor employee shall wear a visible identification badge provided by the NIST Security

Office.

Protocols for Mitigating COVID-19 Exposure on NIST Campuses

The Contractor shall review and adhere to the requirements of Attachment I titled NIST Visitor and Contractor

Protocols for Mitigating COVID-19 Exposure on NIST Campuses. Contractor personnel performing work in

NIST workspaces, must provide all information required by Attachment I, in advance of and throughout the period of performance of the contract. This document is subject to change and must be monitored by the

Contractor. Reference www.NIST.gov.

While working on the NIST campus, the Contracting Officer's Representative and/or Technical Point of Contact will ensure that Contractor personnel comply with the requirements in place to mitigate COVID-19 exposure.

The Government reserves the right to require that Contractor personnel attend a 1-2 hour training session dedicated to COVID-19 protocols.