NIST-AMD-SS25-03BRB.docx

NIST-AMD-SS25-03BRB

6640 / 334516

Primary POC: Brandon Butler (Brandon.butler@nist.gov) Secondary POC: Julie Morris (Julie.Morris@nist.gov)

Title: Aqueous size-exclusion chromatography with triple-detection – Combined Sources Sought/Notice of Intent to Sole Source

BACKGROUND

***THIS IS A COMBINED SOURCES SOUGHT NOTICE AND NOTICE OF INTENT TO SOLE SOURCE***

The National Institute of Standards and Technology (NIST) is seeking information from sources that may be capable of delivering an aqueous size-exclusion chromatography instrument for absolute molar mass characterization, inclusive of FOB Destination delivery, warranty (2-year extended), and optional purchases as detailed herein.

If no alternate sources are identified, the Government intends to issue a Sole Source Award to Waters Technologies Corporation (34 Maple St. Milford, MA 01757, UEI JFT8BGF7FKV6) under the authority of FAR 13.106-1(b)(2). The North American Industry Classification System (NAICS) code for this acquisition is 334516.

The Contractor shall provide a system that meets all technical specifications identified below.

All items must be new. Used or remanufactured equipment will not be considered for award. Experimental, prototype, or custom items will not be considered. The use of “gray market” components not authorized for sale in the U.S. by the Contractor is not acceptable. All line items shall be shipped in the original manufacturer’s packaging and include all original documentation and software, when applicable.

The Contractor shall provide one size-exclusion chromatography with triple-detection that meets the following minimum technical requirements. Procurement options are specified for manual cuvettes and automated measurements by a module containing dynamic, static and electrophoretic light scattering (DLS/SLS/ELS) and field-flow fractionation (FFF). The Contractor shall deliver the equipment as described below.

SYSTEM REQUIREMENTS:

High Pressure Liquid Chromatography (HPLC) Pump

a) The pump shall be capable of delivering aqueous and organic solvents at operating pressures up to 9,500PSI (655 bar).

b) The pump shall support flow ramping, settable from 0.01 to 30.00 minutes to gradually reach flow rates up to 5.000 mL/min.

c) The pump shall support flow rates as low as 0.001 mL/min and as high as 5.000 mL/min.

d) The pump shall have a flow accuracy of +/- 1.0%.

e) The pump shall have a flow precision of ≤0.075% RSD or +/- 0.02 min SD, whichever is greater.

f) The pump shall be capable to deliver a minimum of eleven gradient curve profiles [including linear, step (2), concave (4), and convex (4)].

g) The pump shall have a pressure pulsation of ≤1.0% or 25 psi, whichever is greater.

h) The sample compartment temperature shall be settable from 20 to 70 °C (+/- 0.1 °C).

i) The injector shall have the ability to automatically withdraw from several sample vials and dispense into a single vial.

j) The sample compartment shall be able to accommodate both HPLC Vials and/or well plates (96 / 384 well).

k) The injector precision shall be equal to or less than 1.0% RSD from 0.5 to 0.9 µL; 0.5% RSD from 1.0 to 4.9 µL; and <0.25% RSD from 5.0 to 1000.0 µL.

l) The injector linearity shall be equal to or better than 0.999 correlation coefficient over its entire injection range.

m) The column compartment shall support optional column selection, up to 3 columns.

n) The system flow path shall be compatible with a pH range of 1 to 12.5.

o) The system shall support leak sensors. Drips shall be managed through a drip tray which shall direct all leaks to either the front or rear of the instrument and then into a suitable waste container.

Multi-Angle Light Scattering (MALS) detector

p) The MALS detector shall make static light scattering measurements at 18 or more angular locations, simultaneously, to quantify molar mass of macromolecules in solution from 200 Da to 1000 MDa and rms radius from 10 nm to 500 nm.

q) The sensitivity of the MALS instrument shall support quantifying the molar mass of an injection of 10 ng of 100 kDa polyethylene glycol in aqueous mobile phase on standard SEC, to an accuracy of 5% and precision of 2%.

r) The MALS instrument shall provide thermoelectric temperature control of the read head from 20°C to 70°C, with precision and accuracy of ±0.1°C or better.

s) The MALS instrument shall be equipped with a forward laser monitor to measure the intensity of light transmitted through the flow cell, to correct the scattering signal for absorbance of the laser beam by the sample as well as diagnose the presence of bubbles or large contaminants in the flow cell.

t) The MALS instrument shall provide a means of removing particles adhering to the MALS flow cell interior surfaces so as to minimize detector noise due to light scattering from these particles, and to prolong time between manual maintenance. The device shall be remotely controlled by software and function by applying a radio frequency ultrasonic field to the flow cell’s external surface via a direct mechanical contact.

u) The MALS instrument shall have an onboard computer with a touch screen display to allow one to visualize rapidly any of the detector outputs including all light scattering, UV absorption. As well as critical status indicators such as temperature or leak detector status. Such a display allows one to confirm the system is operating properly and to diagnose problems.

v) The touch screen display shall provide a simple and intuitive indication of the system’s readiness to make good-quality measurements with high signal-to-noise ratio, low drift and no bubbles in the cell.

w) The MALS instrument shall be calibrated using a uniform fluid such as 1X phosphate buffer solution, commonly available with high quality and repeatability, rather than calibrated against a molar mass standard, because the latter technique depends on precise knowledge of concentration and refractive index increment of the standard in each specific solvent. As a consequence of the uniform fluid calibration method, absolute rather than relative results will be obtained.

x) The MALS instrument shall provide a laser driver that quenches mode-hopping potential of the diode laser light source.

y) The MALS instrument and software shall operate to prolong laser lifetime by automatically reducing laser drive current when the instrument is idle, and restoring power for measurements.

z) The MALS instrument shall allow the user to reduce its laser intensity by 1 % - 90 %, either from the front panel display or from the control software. This capability eliminates detector saturation due to very high concentrations of very large macromolecules or nanoparticles.

aa) The MALS instrument shall be field-diagnosable for failures and troubleshooting, and field-serviceable to facilitate rapid, on-site repair in case of failure.

Differential Refractometer (dRI) detector

ab) The dRI detector shall be capable of being used off-line (batch mode via sample injection into the flow cell by means of a syringe or pump) to measure the dn/dc of a sample at the same wavelength as the MALS instrument, as this value is necessary for MALS calculations.

ac) The dRI detector shall be able to measure the Absolute Refractive Index of the solution, as this value is necessary for MALS calculations.

ad) The dRI instrument shall use an array of 512 or more photodiodes (rather than 2 as in a traditional dRI instrument) in order to provide a range of at least - 0.0047 to + 0.0047 RIU (refractive index units) while providing sensitivity of 7.5·10-10 RIU or better across the entire range of detection without switching gain settings.

ae) The dRI instrument shall feature an embedded computer, front panel touch-screen display and key pad to control, configure and monitor all instrument operations. This display allows one to visualize rapidly any of the detector outputs including differential and absolute refractive index as well as critical status indicators such as temperature and leak detector status. Such a display allows one to confirm the system is operating properly and to diagnose problems.

af) The touch screen display shall provide a simple and intuitive indication of the system’s readiness to make good-quality measurements with high signal-to-noise ratio, low drift and no bubbles in the cell.

ag) The dRI instrument shall be controlled and interfaced to the same data acquisition and analysis software used for the MALS instrument.

ah) The dRI instrument shall be field-diagnosable for failures and troubleshooting, and field-serviceable to facilitate rapid, on-site repair in case of failure.

Photodiode array detector

ai) The wavelength range shall be 190 nm to 800 nm to cover the UV/Vis range with a single light source lamp not two.

aj) Detector shall autocalibrate before each run.

ak) Detector shall operate across 190 nm to 800 nm with 1.2 nm Digital and Optical Resolution.

al) Collect 8 channels of 2D data at user defined bandwidth for user optimization of 2D detection

am) Lamp optimization software to fine tune energy of lamp for the best quality, consistent spectra over the life of the lamp and to extend the lifetime of the lamp.

an) Detector software shall offer routines for plotting, detection of purity, and spectral libraries.

Software

ao) The software shall permit remote monitoring and control of the instruments. This allows users to increase productivity by working on other tasks while MALS-UV-dRI measurements are ongoing. ASTRA does so for all Wyatt instruments + UV and dRI.

ap) The software shall correct the data for interdetector band-broadening such that molar mass is displayed as being uniform across the elution volume of known monodisperse macromolecules. This feature is essential in order to obtain correct molar masses and conformations when two or more detectors are connected in series to a liquid chromatography system.

aq) The software shall provide for the determination of molar masses and sizes in the eluting macromolecules, stating with each measured value the associated uncertainties (or error bars in graphs).

ar) The software shall account for changes in all relevant solvent properties, e.g. solvent refractive index or viscosity, due to changes in temperature.

as) The software shall be capable of controlling the HPLC.

at) The software shall be capable of accepting a blank measurement and subtracting it from the sample measurement in order to eliminate gradient baselines.

au) The software shall be capable of analyzing copolymers using a three-detector method (MALS-UV-dRI).

av) The software shall be capable of analyzing macromolecular conformation by combining two properties such as size/molar mass.

aw) The software shall include an option for compliance with the requirements of FDA’s 21CFR(11) documents.

ax) The software shall be able to be installed on at least four computers without additional licenses.

OPTIONS (These are optional requirements which may or may not be exercised during the duration of the contract’s period of performance) Module with dynamic light scattering (DLS), static light scattering (SLS), and electrophoretic light scattering (ELS)

ay) Temperature Control Specifications

i) For DLS and SLS measurements, the instrument shall provide temperature control of the cuvette from at least -10 °C to +120 °C with precision and accuracy of ±0.3 °C or better, thermal stability better than 0.01 °C and programmable ramp rates in the range of 0.01 °C to 15 °C per minute.

ii) For ELS measurements, the instrument shall provide temperature control of the sample holder from at least 4 °C to 70 °C.

az) Measurement Specifications

i) The range of measurement of hydrodynamic radius by DLS in cuvettes shall cover 0.2 – 1000 nm.

ii) The range of measurement of hydrodynamic radius by DLS in a flow cell shall cover 0.2 – 500 nm.

iii) The size range for measurement of particle concentration should extend up to 225 nm.

iv) The range of measurement of molar mass by SLS shall cover 300 – 1,000,000 g/mol.

v) The range of measurement of turbidity by SLS shall cover 1 – 100 NTU.

vi) The solution conductivity range for measurement of electrophoretic mobility by ELS in a dip cell or disposable ELS cell, or in the flow cell when not pressurized, shall cover 0 – 7 mS/cm.

ba) Measurement Sensitivity

i) The sensitivity of the DLS measurement shall support quantifying the hydrodynamic radius of a purified solution of lysozyme at concentrations down to 0.1 mg/mL, with an accuracy of 5% and precision of 2%.

ii) The sensitivity of the SLS measurement shall support quantifying the molar mass of a purified solution of lysozyme at concentrations down to 0.1 mg/mL, with an accuracy of 5% and precision of 2%.

iii) The sensitivity of the SLS measurement shall support quantifying turbidity down to 1 NTU, with accuracy and reproducibility of 0.3 NTU and precision of 10%.

iv) The sensitivity of the ELS measurement shall support quantifying zeta potential and electrophoretic mobility of a purified solution of 1 g/L lysozyme in the flow cell or 1 g/L BSA.

bb) Cell pressurization specifications

i) The instrument shall support pressurization of the flow cell in order to suppress bubbles created by electrolysis of salt-containing solutions, enabling ELS measurements in solutions with conductivity up to 100 mS/cm.

ii) The instrument shall support an optional accessory for pressurizing the flow cell capable of pressurization up to 300 psi.

bc) Dynamic Range

i) The instrument shall provide a linear dynamic range for SLS measurements of at least 5 decades without attenuation of the optical signal, in order to provide maximal accuracy relative to the calibration conditions in determination of molar mass and particle concentration.

ii) The instrument shall allow the user to reduce its laser intensity by 1% - 90%, either from the front panel display or from the control software. It shall also be capable of further attenuating the light intensity reaching the DLS detector, automatically, by at least four orders of magnitude. These capabilities eliminate detector saturation due to very high concentrations of very large macromolecules or nanoparticles and protect the detector from exposure to damaging light levels.

bd) Correlator specifications

i) The instrument shall incorporate a multi-tau correlator with 512 or more bins, and a sampling time of 100 nanoseconds, that performs correlation over a large range of time scales simultaneously for optimal detection of a large range of particle sizes without the need to optimize data acquisition times.

be) Laser Specifications

i) The instrument shall utilize a near-infrared laser with wavelength longer than 750 nm in order to avoid exciting fluorescence which can overwhelm the DLS detector. The ZetaStar utilizes a laser with wavelength of 785 nm to meet this requirement.

ii) The instrument shall be equipped with a rear laser monitor that measures the intensity of the laser beam prior to entering the cuvette, in order to calculate any necessary compensation to the scattering signal for laser source intensity fluctuations and drift related to ambient temperature changes, laser device aging, dust or any other mechanism. This rear monitor ensures consistent molar mass, particle concentration and turbidity measurements over long and short periods.

iii) The instrument shall be equipped with a forward laser monitor that measures the intensity of the laser beam exiting the cuvette, in order to measure turbidity or absorbance, to assess the presence or formation of bubbles and for other diagnostic purposes.

bf) Connection to SEC-MALS instrument

i) The instrument shall connect the main MALS detector’s flow cell by means of an optical fiber between the MALS read head and the DLS-SLS detector.

ii) The fiber connection shall be software-switchable between the MALS flow cell and the DLS instrument’s cuvette measurement system. The switch shall be controlled both by the user, from the instrument’s display and main software.

iii) This capability permits efficient utilization of the DLS detector for both batch (unfractionated) and online (fractionated) analyses. The DLS/SLS/ELS instrument shall provide dynamic light scattering measurements simultaneously with MALS data acquisition.

Flow-field Fractionation (FFF) Module

bg) The FFF module shall operate with a single pump to generate all flows

bh) The FFF module shall supports flow rates up to 10 mL/min with isocratic and quaternary Agilent pumps (5 mL/min with Agilent binary pumps). Cross flow can be regulated from 0.03 – 6.67 mL/min by default. Precision of the detector flow rate is 0.1% with dilution control module.

bi) The sample shall be introduced through a third port of the channel upper plate directly on top of the focusing zone. This is the preferred method, because the sample does not have to migrate from the tip of the channel all the way to the focusing position. It saves time and reduces possible interaction of the sample with the membrane. This is specifically important for semi-preparative applications with large injection volumes.

bj) The FFF module shall be able to be configured for tip injection, which is required for hollow-fiber channels or size-exclusion columns.

bk) The FFF module and channels shall be compatible both with aqueous and with organic solvents like THF, toluene, acetone and alcohols. This adds flexibility and makes the system more versatile for possible future applications that may require different solvents compared to the initial use of the system.

bl) The FFF module shall incorporates a display monitor that provides the instrument status and method progress, and allows manual operation like flushing, switching valves, etc. directly from the instrument. This allows basic instrument control without the need to access the host PC, which might be placed in a separate room outside the laboratory.

bm) The FFF module shall use HPLC pumps, autosamplers, with control software to inject all the sample that is loaded into the injection loop; other systems require loading three times the amount that will be injected.

bn) The FFF module shall be capable of asymmetric-flow FFF measurements with a dedicated fraction collector output port for minimal band broadening with Agilent fraction collectors.

bo) Software shall be compatible with SEC-MALS measurements, refractive index and array detection,

bp) The FFF module shall incorporates a high-performance flow regulator that utilizes the Coriolis effect for mass flow measurement of the cross flow. Therefore, the system can regulate flow rates from 0.03 to 6.67 mL/min with precision independent of solvent type, pressure or temperature.

bq) Pressure transducer shall monitor the pressure in the FFF channel, for safety and system condition tracking. A second transducer below the semi-permeable channel membrane, which, together with the main channel transducer, provides the capability of measuring pressure drop across the membrane to determine if it is open or clogged. A third pressure transducer measures the inlet pressure of the flow coming from the pump. This adds the information about excessive pressure drop between the pump pressure reading and the inlet pressure, indicating whether the inline filter holder needs service.

br) Transducers shall eliminate issues associated with dead volume such as trapped air leading to pressure fluctuations, and bacterial growth.

bs) FFF modules shall control temperature stable temperature within the channels between ambient and 50°C.

bt) The FFF module shall offer dilution control. This reduces the dilution of the sample at the channel outlet and increases the concentration at the detector by a factor of up to 10 without loss of sample, and up to 5 without loss of resolution. The detector flow rate is controlled with a precision of 0.1 %, which is a critical specification to ensure exact concentration readings and reproducibility.

bu) Flows shall be automatically adjusted to obtain optimal focus of the sample above the membrane with the narrowest spatial distribution.

bv) The module shall automatically switch between FFF module and column, so that a single pump, autosampler and injector valve can be directed to either of the separation devices, and the eluent from either device can be directed to the detectors, by means of a single software control.

bw) The system shall allow the user to prevent the sequence from starting if the solvent will fall below a certain volume.

bx) The software and hardware shall provide a comprehensive measurement of the system parameters with auto diagnostic functionality. The user shall be informed about deviations from set values for flow rates and inconsistencies of flow and pressure values.

by) Software shall permit asymmetric-flow FFF method calculations based on user-entered channel flow, cross flow and gradient parameters in order to calculate optimal separations without actually running the instruments.

bz) Analysis software shall provide results of a separation run in order to determine the hydrodynamic radius from 1 – 10,000 nm of species eluting under known channel- and cross-flow conditions.

Fluorescence detector (FD)

ca) The FD shall have the ability to set the sampling/data rate and filter time constants independently to maximize resolution and sensitivity.

cb) The FD shall have standard analytical flow cell with a volume of not more than 13 μL for optimal peak dispersion

cc) The FD shall have optional flow cells for optimizing detection of a wide range of applications.

cd) The FD shall have a means to optimize lamp performance automatically and without user intervention. This compensates for lamp degradation over time without the need to frequently replace the lamp.

ce) The FD shall perform an optics and electronic diagnostic routine upon power-up.

cf) The FD flow cells shall be simple to replace in a cartridge form with finger-tight fittings.

cg) The FD shall have a wavelength range of 200 to 890 nm for the excitation wavelength and 210 to 900 nm for the emission wavelength.

ch) The FD shall have an optical bandwidth of 20 nm.

ci) The FD shall have a wavelength accuracy less than ± 3 nm.

cj) The FD shall have a wavelength repeatability of less than ± 0.25 nm.

ck) The FD shall have a Hg/Xe lamp as a higher energy source.

cl) The FD shall be able to collect 2D data, 3D data and excitation λ- emission λ plots.

cm) The FD shall be able to collect up to 4 2D data channels simultaneously with unique ex/em pairs.

cn) The FD shall have a sensitivity measured with the Raman s/n of water greater than 1000 with the noise measured at the signal (without using a dark signal as the noise reference).

INSTALLATION:

Upon receipt of the equipment, the NIST PI shall install the instrument in Building 224, Room B227, at NIST Gaithersburg, MD. The equipment will operate to manufacturer’s specifications upon installation. Installation is to occur within 60 days after delivery.

WARRANTY:

The Contractor shall provide, at a minimum, a two-year warranty for the equipment. The warranty shall cover all parts, labor and travel. The warranty shall commence after acceptance by the Government.

TRAINING:

N/A

PERIOD OF PERFORMANCE:

Two (2) Years:

Base Year plus one (1) Option Year.

DELIVERABLES:

HOW TO RESPOND TO THIS NOTICE

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QUESTIONS REGARDING THIS NOTICE

Questions regarding this notice may be submitted via email to the Primary Point of Contact and the Secondary Point of Contact listed in this notice. Questions should be submitted so that they are received by 11:00 a.m. Eastern Time on June 20, 2025. Questions will be anonymized and answered via sources sought notice amendment following the question submission deadline.

IMPORTANT NOTES

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Thank you for taking the time to submit a response to this request!