75N91024Q00093_DRAFT SON.pdf

STATEMENT OF NEED (SON)

1.0 TITLE

Procurement of One (1) 3i Marianas Super-Resolution Spinning Disk Confocal Microscopy System with C-Shaper

2.0 BACKGROUND

The Laboratory of Cancer Biology and Genetics (LCBG) is made up of multidisciplinary teams comprised of 12 sections conducting basic, and translational research with the goal of advancing the field of cancer research. Research programs in the LCBG are focused on human genetics, developing new cancer models, and investigating molecular mechanisms, including genetic/epigenetic regulation of gene expression, cell signaling, cell cycle, stemness, oncogene and non-oncogene addiction, and tumor cell-microenvironment interactions. The goal is to understand the mechanisms underlying cancer initiation and metastatic progression and develop new treatments while nurturing the training and development of the next generation of scientists.

The Muthuswamy lab was among the first to employ three-dimensional cell culture (organoids) to bridge the gap between growing cells as a flat monolayer and tumors growing in vivo. Dr.

Muthuswamy’s lab uses patient tumor organoids for personalizing cancer treatment, investigating metastatic cancer progression, understanding how cell polarity proteins regulate the development of drug resistance, developing new immune-oncology treatments, and identifying new biomarkers.

In 2001, the lab developed a 3-D culture platform to grow a human breast epithelial cell line, MCF- 10A, as polarized acinar structures and used it to investigate how 3-D cell architecture impacts transformation by the oncogene HER2/ErbB2. These studies led to the development of conditions to grow patient tumors as organoid cultures. Using the pancreatic cancer patient tumor-derived organoids models; the lab has demonstrated that the tumor organoids are a clinically relevant research platform because they are highly effective in modeling in vivo and clinical drug responses.

In ongoing research, the Muthuswamy Lab continues to develop organoid platforms for multiple types of cancer. It aims to use them to personalize patient treatment, to understand the basis for patient-to-patient differences in response to drugs, and mechanisms that regulate drug resistance, metastasis, and histomorphology.

The Muthuswamy Lab has also developed a method to co-culture tumor organoids with autologous peripheral blood-derived T cells. This method functions as an empirical platform for a dramatic (1000–100,000 fold) clonal expansion of cytotoxic T cells activated by antigens presented on the tumor cell surface. The organoid-primed cytotoxic T cells (opT cells) generated from co-culture create an opportunity to identify tumor-selective cytotoxic cells and T-cell receptors for use in immune-therapy applications for cancers including breast, pancreas, and head and neck.

Regulation of cell proliferation and death within an organoid in response to drugs or T cells is unknown. A methodical analysis of changes in cell proliferation and death over a period of 10-14 days is essential to begin to obtain insights into how patient tumor-derived organoids respond to treatment. A modern spinning disc confocal microscope with super-resolution capabilities is a key instrument needed to further the Muthuswamy Lab research. Multi-channel fluorescence imaging requires rapid acquisition with a high-sensitivity detector, allowing short exposure times. A spinning disc microscope with up to 200 fps imaging speed paired with a Z-piezo stage and a fast and sensitive camera are the ideal platforms for imaging organoids growing in 3D. To counter the optical aberrations intrinsic in organoid imaging, the system must be able to employ adaptive optics to correct aberrations due to unavoidable refractive index mismatches and unpredictable specimen environments. The acquisition of this spinning disk super resolution confocal microscope with adaptive optics will support the current and future imaging needs of researchers in the Muthuswamy Lab in the NCI/CCR/LCBG.

3.0 TYPE OF ORDER

This will be a Firm Fixed-Price Purchase Order.

4.0 SPECIAL ORDER REQUIREMENTS

4.1 PRODUCT FEATURES/SALIENT CHARACTERISTICS

The Muthuswamy Lab in the LCBG has identified a need for a new spinning disk confocal microscope to enable high-resolution imaging of organoids over an extended period of 10-14 days.

To meet the needs, the new system will need to possess several unique characteristics. NCI requires a 3i Marianas Spinning Disk Confocal Microscope System with Yokogawa CSU-W SoRa and C- Shaper. The system must include a fully motorized upright microscope with high NA PSF-optimized objective lenses, a Piezo Z stage for rapid 3D imaging, a fast gated White LED for transmitted illumination, a CSU-W Spinning Disk confocal with 200 fps imaging speed, 16 x 17 mm field of view, a fast and sensitive camera with pixel size optimally matched to the mag and CSU W field, and a customized LaserStack with five laser lines including 405nm, 488nm, 561nm, 640nm and 785 wavelengths. The system must include a C-Shaper adaptive optics module to correct optical aberrations while imaging live organoids in 3D. The system needs to use SlideBook software for image acquisition, control, and tight synchronization of all system hardware. Slidebook software should also allow 3D-Deconvolution, Ratio-Imaging, FRET, Particle Tracking, CellNet Pattern Recognition, and Stereology.

The following salient characteristics for the new instrument have been identified:

• Zeiss AxioObserver 7 Basic Marianas motorized research grade inverted microscope stand with harmonic focusing drive, motorized 6-position filter cube turret, motorized 6-position nosepiece, motorized epi FL shutter, manual 5-position DIC-ready condenser, transmitted light LED illuminator, binocular observation tube, 10x eyepieces, motorized left side camera port, c-mount and touch-screen controller with docking station. Includes Definite Focus 3 nosepiece and beam combiner.

• X-Cite mini+ white-light LED light source with 385nm UV LED. Must include a LED head, miniCUBE controller, speedDIAL remote, coupling flange for Zeiss AxioObserver, and accessory kit.

• Motorized X,Y Stage for Marianas with 500μm Piezo Z flat top stage with 120mm x 75mm travel, 500μm piezoelectric Z-axis, rack mount controller, joystick control and universal slide/dish holder.

• High efficiency hard coated shift free microscope filter cubes for DAPI, GFP, and mCherry for standard visual fluorescence imaging.

• Phosphorescence Blocking Filter for LED transmitted light autofluorescence to prevent UV and blue laser light from triggering inadvertent phosphorescence.

• High resolution objectives with the longest working distance possible including LCI Plan Apochromat 25x/0.8NA oil/water/silicone/glycerine immersion WD=0.57mm, Plan- Apochromat 10X/0.45 WD=2.1mm, Plan-Apochromat 20x/0.8NA FWD=0.55mm, and Alpha Plan Apochromat 100x/1.46NA Oil TIRF Immersion DIC WD=0.11mm. Objectives should include DIC prisms with polarizers.

• CSU-W1 T1 Spinning Disk Confocal, 25um disk, 1X Camera Adapter including a 10-position emission filter wheel, 3 motorized dichroic positions, a motorized aperture and optical fiber. The CSU-W1 should have an acquisition speed of 200 FPS with an effective field of view of 15mm x 16mm, and be capable of near IR Excitation of up to 785nm.

• CSU-W1 addition of SoRa Super-Resolution Disk, a magnification changer with 1x, 2.8x and 4x positions, control electronics and software. The SoRa must have an imaging speed of 200 FPS, a wavelength range of 405nm to 640nm excitation and 420nm to 680nm emission, and XY resolution of 150nm or 120nm with deconvolution, a Z Resolution of 320nm or 300nm with deconvolution. The SoRa should have a FOV of 67um x 63um with a 63x Objective and 4x Relay Magnification, or 61um x 57um with a 100x Objective and 2.8x Relay Magnification.

• C-Shaper Adaptive Optics Module for Marianas Spinning Disk Confocal Microscope System with on-the-fly dynamic optical aberration correction that increases signal-to-noise at every plane while imaging deep within a sample with negligible additional acquisition time.

• ORCA Fusion BT scientific CMOS Camera with a CoaXpress 89fps connection, 2304x2304 6.5μm pixels FOV, 95% QE, quiet scan 0.7e- read noise. Must include a CoaXpress card, CoaXpress cables and one trigger cable, must be cooled to -8C.

• CSU-W1 Near IR Illumination Port to allow input of near IR laser lines (685-785nm) via auxiliary port, including Coupler-FCP8 fiber with 685nm-785nm transmission. Must include a 660LP dichroic for combining IR and VIS illumination.

• CSU-W1 Dichroic for 405/488/561/640/785 Excitation. Single bandpass filters for 445/58nm, 525/50nm, 600/50nm, and 706/95nm.

• Five Band Emission Filter for blocking lasers for 405/488/561/640/785

• LaserStack v4 base which includes control electronics, shutter and manipulator for fiber output that can accept up to 6 lasers. 5 solid state laser lines, including a controller, beam combining optics and cleanup filter. Laser lines included: LaserStack v4 405nm 140mW;

LaserStack v4 488nm 200mW; LaserStack v4 561nm 200mW; LaserStack v4 638nm 200mW; LaserStack v4 785nm 300mW with a kineMATIX fiber mount with side panel for LaserStack v4. TTL Synchronization for SlideBook to allow for millisecond timing and trigger control of multiple devices including the LaserStack.

• Stage top incubator with Bold Line temperature controller, heater, air pump, and digital CO2 gas mixer. Includes active humidity controller 50-95% and heated chamber for ASI stages.

Includes Köhler lid.

• 1x 1"x3" Glass Slide and 2x 35mm Petri-Dish Insert for Stage Top Chambers with interchangeable plate adapter allowing to hold two chamber slides and two 35mm Petri dishes.

• An Acquisition Workstation 210-128 which includes Dual 10-Core Xeon Silver 2.4GHz processors, 128GB RAM, 16GB NVIDIA Quadro RTX A4000 workstation graphics card, 512GB OS M.2 NVMe SSD, 1300W power supply, backlit wired keyboard, Windows 10 Pro and 3-year manufacturer's NBD warranty. The system also requires 8-Port NVMe Controller (4th Generation) that supports up to 8 NVMe M.2 solid state drives as JBOD (just a bunch of disks), RAID-0, RAID-1, or RAID-10. Requires available PCIe 3.0 x16 slot. The system requires (4) 8TB NVMe M.2 Solid State Drives configured in a RAID-0 Configuration with data striped across 4 SSDs as a single volume for peak capacity and performance. Each volume mounted as an independent drive in Windows.

• The Workstation requires a 34" WQHD Curved USB-C Monitor with two (2) HDMI inputs, one DisplayPort 1.4 input, one USB-C input, one USB-C 3.2 Gen 2 port and five (5) USB 3.2 Gen 1 ports. Must have a resolutions of 1440 x 1440 (WQHD) with 109 pixels per inch.

• The microscope should include a System Master Power Control Module that includes single switch control and system power distribution for two AC input power circuits; provides AC circuit fusing and allows for power of up to 20 devices with two always-on outputs; for 110V-230V.

• The microscope needs to have a 12U Equipment Rack featuring locking casters, venting side panels and support for up to 440 lbs (200 kg). Dimensions (H x W x D) are 70 x 50 x 46 cm (27.6 x 19.7 x 18.1")

• The Acquisition Workstation needs to have SlideBook Software installed with a full Online License. SlideBook microscopy software will manage instrument control, image processing, and data analysis with a standard set of drivers to control hundreds of different kinds of microscope automation devices and cameras. Data will be acquired in a native 3D format over time, wavelength, and specimen locations in customizable experiment protocols. Data will be able to be displayed, filtered, and quantified by a wide variety of intrinsic tools and easily exported to other applications. A GPU-accelerated volume rendering engine will enhance exploration of 3D and 4D data.

• The Acquisition Workstation must have the 3D Deconvolution Module for SlideBook to allow for Nearest Neighbors rapid deblurring algorithm, Constrained Iterative quantitative restoration algorithm, point spread function (PSF) measurement guide and an optical configuration database.

• The system must include a syGlass 3D and 4D virtual reality viewing and segmenting software and include a Meta Quest 2 VR headset and charger and an Academic License.

• The microscope requires a Vibration Isolation Table CleanBench 750x1500 (30x60) with a 2" thick smooth laminated top with 1/4-20 tapped holes 1" on center, alphanumeric grid, front support bar, subshelf, casters, and OnTrak unloading system.

• All adaptors and hardware necessary for integration of the specified components

• Hardware products include one year of warranty against manufacturer defects at no additional cost.

• SlideBook software products must include one year of unlimited phone and e-mail support and one year of free access to updated program releases.

4.2 WARRANTY

In addition to the Implied warranty contained in FAR Clause 52.212-4, the Contractor is encouraged to provide express warranties. At a minimum, the Contractor shall provide a 12-month warranty from date of final installation on all equipment and associated items provided under, or as a part of this purchase order.

The warranty shall include repair and or replacement of parts, including travel, labor, and materials, at no additional cost to the Government. The warranty shall not exclude or limit the Governments rights for an Implied warranty as established in the terms and conditions of clause 52.212-4.

4.3 DELIVERY / INSTALLATION

Delivery shall be within sixteen (16) weeks of the purchase order award. All shipping/handling (including FOB Destination) and delivery/installation fees shall be included in the quote. Upon delivery, the Contractor shall notify the respective NCI Technical Point of Contact to schedule installation dates and times. Installation shall occur within fourteen (14) calendar days of delivery and shall be performed by, or under the direct supervision of, a certified operator.

The contractor shall deliver and install the equipment at the following address:

Laboratory of Cancer Biology and Genetics (LCBG) National Institutes of Health/NCI 9000 Rockville Pike Bethesda, MD 20892 Technical Point of Contact: [to be provided upon award]

4.3.1 DELIVERY GUIDANCE

The Contractors shall communicate and follow instructions from the Technical Point of Contact (TPOC) to coordinate delivery and installation.

The Contractor shall direct all courier and delivery services – including those not operated by the Contractor (e.g.

FedEx, USPS, UPS) – to follow the instructions in this section.

All companies delivering to the NIH main campus must comply with Commercial Vehicle Inspection Facility (CVIF) access procedures. Upon arrival, the CVIF will provide a list of buildings and loading docks to delivery personnel.

Deliveries will be logged in at the loading dock, and the loading dock contractor or Government personnel will attempt to contact the TPOC listed on the package. In the event that the TPOC is unable to accept the package, the delivery shall not be left at the loading dock station. The delivery must be returned to the Contractor, and the Contractor must coordinate with the TPOC to deliver on another date at no additional cost.

Deliveries can only be made between 6:00 a.m. and 4:00 p.m. EST, Monday – Friday, excluding federal holidays.

4.4 INSPECTION AND ACCEPTANCE

Pursuant to FAR Clause 52.212-4, all items to be delivered in relation to this Purchase Order are subject to final inspection and acceptance by an authorized representative of the Government. The authorized representative of the Government is the TPOC who is responsible for inspection and acceptance of all services, materials, or supplies to be provided by the Contractor.

4.5 TRAINING

The Contractor shall provide on-site training for up to 10 users. Training shall be conducted by a certified operator. The user training shall include an overview of setup approaches, instrument settings, and a demonstration of the performance. Instrument care and maintenance must also be covered and information about accessing unlimited technical support. The training shall be provided at a time specified by the Technical Point of Contact within 7 business days following installation of the device. All training expenses, including materials and/or travel expenses, shall be included in the quoted price.

5.0 PAYMENT

Payment shall be made in full after the successful delivery, installation, and acceptance of equipment by the NCI Technical Point of Contact (TPOC). Payment authorization requires submission and approval of invoices to the NCI TPOC and NIH OFM, in accordance with the payment provisions listed below:

The following clause is applicable to all Purchase Orders, Task or Delivery Orders, and Blanket Purchase Agreement (BPA) Calls: Prompt Payment (Jan 2017) FAR 52.232-25.

Highlights of this clause and NIH implementation requirements follow:

I. Invoice Requirements

A. An invoice is the Contractor's bill or written request for payment under the contract for supplies delivered or services performed. A proper invoice is an "Original" which must include the items listed in subdivisions 1 through 12, below, in addition to the requirements of FAR 32.9. If the invoice does not comply with these requirements, the Contractor will be notified of the defect within 7 days after the date the designated billing office received the invoice (3 days for meat, meat food products, or fish, and 5 days for perishable agricultural commodities, dairy products, edible fats, or oils) with a statement of the reasons why it is not a proper invoice. (See exceptions under II., below.) Untimely notification will be considered in the computation of any interest penalty owed the Contractor.

1. Vendor/Contractor: Name, Address, Point of Contact for the invoice (Name, title, telephone number, e-mail and mailing address of point of contact).

2. Remit-to address (Name and complete mailing address to send payment).

3. Remittance name must match exactly with name on original order/contract. If the

Remittance name differs from the Legal Business Name, then both names must appear on the invoice.

4. Invoice date.

5. Unique invoice #s for all invoices per vendor regardless of site.

6. NBS document number formats must be included for awards created in the NBS: Contract

Number; Purchase Order Number; Task or Delivery Order Number and Source Award Number (e.g., Indefinite Delivery Contract number; General Services Administration number); or, BPA Call Number and BPA Parent Award Number.

7. Unique Entity Identifier (UEI) which is in the System for Award Management (SAM) and replaces the Dun & Bradstreet Data Universal Numbering System (DUNS) number.

8. Federal Taxpayer Identification Number (TIN). In those rare cases where a contractor does not have a UEI number or TIN, a Vendor Identification Number (VIN) must be referenced on the invoice. The VIN is the number that appears after the contractor’s name on the face page of the award document.

9. Identify that payment is to be made using a three-way match.

10. Description of supplies/services that match the description on the award, by line billed.*

11. Freight or delivery charge must be billed as shown on the award. If it is included in the item price do not bill it separately. If identified in the award as a separate line item, it must be billed separately.

12. Quantity, Unit of Measure, Unit Price, Extended Price of supplies delivered or services performed, as applicable, and that match the line items specified in the award.*

NOTE: If your invoice must differ from the line items on the award, please contact the Contracting Officer before submitting the invoice. A modification to the order or contract may be needed before the invoice can be submitted and paid.

Shipping costs will be reimbursed only if authorized by the Contract/Purchase Order. If authorized, shipping costs must be itemized. Where shipping costs exceed $100, the invoice must be supported by a bill of lading or a paid carrier's receipt.

B. The Contractor shall submit invoices to the Department of Treasury’s Invoice Processing Platform (IPP) at https://www.ipp.gov with a copy to the approving official, as directed below.

The Contractor shall submit a copy of the electronic invoice to the following Approving Official (Technical Point of Contact):

Approving Official: Technical Point of Contact Name- Email Address-

II. Invoice Payment A. Except as indicated in paragraph B., below, the due date for making invoice payments by the designated payment office shall be the later of the following two events:

1. The 30th day after the designated billing office has received a proper invoice.

2. The 30th day after Government acceptance of supplies delivered or services performed.

B. The due date for making invoice payments for meat and meat food products, perishable agricultural commodities, dairy products, and edible fats or oils, shall be in accordance with the Prompt Payment Act, as amended.

III. Interest Penalties

A. An interest penalty shall be paid automatically, if payment is not made by the due date and the conditions listed below are met, if applicable.

1. A proper invoice was received by the designated billing office.

2. A receiving report or other Government documentation authorizing payment was processed and there was no disagreement over quantity, quality, or contractor compliance with a term or condition.

3. In the case of a final invoice for any balance of funds due the contractor for supplies delivered or services performed, the amount was not subject to further settlement actions between the Government and the Contractor.

B. Determination of interest and penalties due will be made in accordance with the provisions of the Prompt Payment Act, as amended, the Contract Disputes Act, and regulations issued by the Office of Management and Budget.

https://www.ipp.gov/

IV. PROVIDING ACCELERATED PAYMENT TO SMALL BUSINESS

SUBCONTRACTORS, FAR 52.232-40 (MAR 2023)

(a) Upon receipt of accelerated payments from the Government, the Contractor shall make accelerated payments to its small business subcontractors under this contract, to the maximum extent practicable and prior to when such payment is otherwise required under the applicable contract or subcontract, after receipt of a proper invoice and all other required documentation from the small business subcontractor.

(b) The acceleration of payments under this clause does not provide any new rights under the Prompt Payment Act.

(c) Include the substance of this clause, including this paragraph (c), in all subcontracts with small business concerns, including subcontracts with small business concerns for the acquisition of commercial products or commercial services.

(End of Clause)

V. HHSAR 352.232-71 Electronic Submission of Payment Requests (February 2, 2022)

(a) Definitions. As used in this clause—

Payment request means a bill, voucher, invoice, or request for contract financing payment with associated supporting documentation. The payment request must comply with the requirements identified in FAR 32.905(b), ‘‘Content of Invoices’’ and the applicable Payment clause included in this contract.

(b) Except as provided in paragraph (c) of this clause, the Contractor shall submit payment requests electronically using the Department of Treasury Invoice Processing Platform (IPP) or successor system. Information regarding IPP, including IPP Customer Support contact information, is available at www.ipp.gov or any successor site.

(c) The Contractor may submit payment requests using other than IPP only when the Contracting Officer authorizes alternate procedures in writing in accordance with HHS procedures.

(d) If alternate payment procedures are authorized, the Contractor shall include a copy of the Contracting Officer’s written authorization with each payment request.

(End of Clause) http://www.ipp.gov/