HTP-APP_Pre-Proposal Conference.pdf

M2PC Project Overview

Sam Paulsen Project Manager

Agenda

Project Schedule

Project Scope

Coordinating with Facility D/B Contractor

Contracting Approach

Scope: Key Performance Parameters (KPPs)

Description of Scope *Threshold KPP Objective KPP

Demonstrate HTP culturing of microbial isolates and consortia

Capacity to operate M2PC with 500 strain experiments per week

Capacity to operate M2PC with 2000 strain experiments per week

Capacity to operate M2PC with 100 microbiome experiments per week

Capacity to operate M2PC with 500 microbiome experiments per week

Demonstrate HTP assaying and phenotyping of microbial isolates and consortia

Capacity to operate M2PC to obtain 1,000,000 multimodal analytical measurements per month

Capacity to operate M2PC to obtain 3,000,000 multimodal analytical measurements per month

Provide capability for remote planning and operations

Demonstrate that remote users can run pre-defined EMSL protocols to be executed autonomously within M2PC across culturing, assaying, and analyses

Demonstrate that remote users can perform dynamic experimental intervention with help from EMSL staff by modifying an executed protocol during the experimental timeframe

Facility 24,500 sq. ft. 50,000 sq. ft.

Scope statement: Provide a high-throughput microbial molecular phenotyping capability and a facility that houses and supports the capability.

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P he no ty p in g P la tfo rm

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Schedule: High-Level

M2PC Acquisition Strategy (and Facility) – Procurement Lead Garrett Hyatt – Acquisition Lead Specialist

High-Throughput Automated Phenotyping Platform (HTP-APP) – Procurement Lead

Samantha Ernst – Acquisition Lead Specialist

Integration of the two procurements is key Working to a single, integrated schedule

• High-throughput phenotyping specifications include integration with design build contractor. Includes facility constraints.

• Design

• Install

• Facility specifications includes integration with the high-throughput phenotyping contractor. Defines facility constraints.

• Design

• Construction

M2PC requires two major procurements

The M2PC will be a single facility focused on microbial molecular phenotyping

It requires two major procurements to complete

Solicitations timed to support award shortly after CD 2/3

Automation laboratory facility coordination

N

Characteristic Value/Constraint Comments

Automation lab size 12,000 ft2 Open space, could have some columns

Utilities location Fed from Overhead

120V & 208V Power Defined number in P- Spec

Actual locations will be adjusted during design

Exotic power Not provided HTP-APP contractor would need to provide transformers for exotic power

CA, N2

Defined number in P- Spec

Actual locations will be defined during coordinated design

Vacuum exhaust, direct exhaust, snorkels

Defined number in P- Spec

Actual locations will be defined during coordinated design

Heat load TBD BTU/hr Verified during design

Partnering with facility contractor

• Design & schedule

• Facility requirements for the system

Automation laboratory facility coordination

Facility Contractor delivers to ~4ft of connection point.

HTP-APP contractor performs final connections.

M2PC Project R&D Technical Overview

Theva Thevuthasan Project Manager

Performance Requirements

Agenda

Various Requirements

KPPs and KPPs - Stretch Goals

System Testing and Training

Performance Requirements/ Specifications

Mission needs

Science workshop

Design Guiding Principles

Discussion w/ potential users

Conceptual design

• Key performance parameters requirements

• Science core functions

• General system requirements

• Scheduling software requirements

• Safety requirements

• Testing, training and operations

Science Core Functions

Five dynamically interconnected core scientific functions are required as foundations to formulate the concept to achieve those KPPs:

• Media

• Cultivation

• Sample preparation

• Strain engineering

• Analytical capabilities

Science Core Functions

Media

- Configurable to bulk dispense a single media type into many plates and different media type and composition to every well, every plate, and/or tubes.

Cultivation

- Create experimental diversity so that a wide range of environmentally relevant parameter space can explored, including cultivation temperatures, light exposures, humidity changes, various gas concentrations, and shaking speeds.

- Maximum number of incubators should be incorporated into automated system

- Is it possible to monitor the growth – e.g., optical density

Sample preparation

- Multiple capabilities - heating, cooling, shaking, lyophilizing, bead beating

Strain engineering

- Provide strain building capability to support the genetic diversity

Analytical capabilities

- Automated plate readers

- Microcopy, cytometry, cell sorting, sequencing, PCR, various LC and GC

- Mass Spectrometry capabilities – at least five distinct capabilities or more

- Emerging capabilities – leading technological edge

Project KPPs

KPP# KPP title KPP threshold, minimum requirement

KPP 1

Demonstrate HTP culturing of microbial isolates and consortia

(i)Capacity to operate M2PC with execution of 500 new strain experiments per week.

(ii)Capacity to operate M2PC with execution of 100 new microbiome experiments per week.

KPP 2

Demonstrate HTP assaying and phenotyping of microbial isolates and consortia.

Capacity to operate M2PC to obtain 1,000,000 multimodal analytical measurements per month.

KPP 3

Provide capability for remote planning and operations.

Demonstrate that remote users/operators can run pre-defined EMSL protocols to be executed autonomously within M2PC across culturing, assaying, and analyses.

Minimum throughputs required to meet the project scope requirements

KPP 1 Testing

Strain Experiments

•Constructing mutant plasmids to create a test panel

•Transforming plasmids to create engineered microbial strains

•Cultivating strains across different media, nutrient/metals & carbon sources, temperatures, pH, etc. - analyzing their growth

Example

•Construct 500 single or multiple gene knockout/up-regulated constructs

•Use 12 replicates of each

•Grow each in 4 media types with 2 different carbon sources

•Test growth at multiple time points

•Total of 500 “experiments” performed in 500 96-well plates at multiple time points

Microbiome Experiments

•Creating communities of one or more unique microbes in varying proportions and a variety of media/growth conditions

•Perturbations - temperature range, pH range, various metal ion concentrations, primary or secondary metabolites and different carbon and/or nitrogen sources.

KPP 2 Testing

Multimodal Analysis

• Capturing scientifically relevant data

- during the growth of microorganisms

- functional responses associated with experimental perturbations

- after sample processing/preparation

Example

• Various spectroscopy and spectrometry measurements can be carried out to characterize the growth and processed samples.

• Cell characteristics including cell size, cell count and cell cycle can be measured using spectral and image cytometry.

• Characterization using Gas chromatography (GC) or Liquid chromatography (LC) coupled with UV, fluorescence detection (FLD), mass spectrometry (MS), or refractive index detection (RID) to detect the chemical components.

• Characterization using automated microscopy.

KPP Stretch Goals Increase throughputs within the available contract cost

Stretch Goals

Stretch Requirement

#1

KPP #1(i): Provide a minimum of 625 strain experiments per week

KPP #1(ii): Provide a minimum of 125 microbiome experiments per week

KPP #2: Provide a minimum of 1,250,000 multimodal analytical measurements per month.

#2

KPP #1(i): Provide a minimum of 750 strain experiments per week

KPP #1(ii): Provide a minimum of 150 microbiome experiments per week

KPP #2: Provide a minimum of 1,500,000 multimodal analytical measurements per month

#3

KPP #1(i): Provide a minimum of 875 strain experiments per week

KPP #1(ii): Provide a minimum of 175 microbiome experiments per week

KPP #2: Provide a minimum of 1,750,000 multimodal analytical measurements per month

#4

KPP #1(i): Provide a minimum of 1000 strain experiments per week

KPP #1(ii): Provide a minimum of 200 microbiome experiments per week

KPP #2: Provide a minimum of 2,000,000 multimodal analytical measurements per month

General System Requirements Minimum requirements for the complete system

Modular

• Replace broken or old instruments

• Incorporate emerging technologies

• Minimize system downtime

Flexible

• Flexibility to move instruments

• Flexibility to move processes

Expandable

• Adaptable for future technologies

• Expand the components with minimum disturbance

Overall System

• Maximize throughput

• High efficiency

• High uptime

System Control Software Requirements

Automation System Control Software

• Parameterization of protocols

• Interleaved dynamic scheduling – protocols run in parallel

• Error recovery – location of the error and remote resolutions

• Reconfiguring - updated accordingly within the software system within minutes

• Security and Safety - accessibility by operators and different classes of users

• High uptime and Simulation – should be able to simulate a workflow

• Operable with EMSL data management and LIMS system

• Remote planning and operation

EMSL LIMS

Automation system control software needs to interact with:

• EMSL LIMS – L7 Enterprise Science Platform (L7/ESP)

• A team is working on L7/ESP – they will be interacting with contractor

• Connections - L7/ESP is equipped with a wide range of pre-built connectors

• Experimental Design – L7/ESP incorporates experiment design capabilities

• Data Processing – L7/ESP data analysis and third-party software systems, and logistics systems.

Safety and Security

Some Important Safety Considerations:

Bio Safety - BSL-2

• exposed to potentially infectious aerosols, droplets, or splashes from BSL-2 controlled organisms shall be placed within a biocontainment enclosure

Robotics Safety

• intrinsically safe per consensus standards

Electrical Safety

• NRTL, UL, CSA … certified instruments and electrical components

Cyber Security

• ensuring that all infrastructure and IoT devices comply with NIST SP 800-213

Laboratory Facility Coordination

• The system will be located in a new facility which will be built in parallel

• Collaborate and coordinate with the facility design-build contractor to locate the utilities and facility characteristics needed to house the capability

• Mechanical and electrical utilities will be provided by the facility contractor – HTP-APP contractor will make the final connections

• Facility limitations are listed in the document

Testing, training and operations

System testing

• Factory acceptance testing

• Onsite functional testing (Installed)

• KPP verification testing (Witnessed by 3rd Party Commissioning Agent and Battelle team)

Training to our staff

• At least 4 researchers

• At least 2 weeks

One-year operations

• Warranty for one year

• List of consumables for one year

Hardware redundancy

• 5%

RFP Overview

Samantha Ernst

HTP-APP RFP Package

• Request for Proposal (RFP) including Draft Contract

• Attachments 1-10

RFP is currently publicly posted to:

• SAM.gov

• PNNL’s Acquisition Supplier Portal (ASP)

M2PC HTP-APP - RFP Overview https://sam.gov/opp/3640065498e845949175b9a3bd92f8ce/view https://ebs.pnnl.gov/ViewSolicitation.aspx?SolID=1478

Acquisition Strategy & Characteristics

• Procure a fully operational system that is designed, fabricated, installed, and tested.

• System includes software, integration hardware, BSL-2 enclosure(s), OTS equipment

• HTP-APP and facility design proceeds concurrently, each informing the other throughout the design process

• Facility construction will have a “ready for equipment” milestone that triggers the ability to start installation of the

HTP-APP

• 3rd Party Commissioning Agent for HTP-APP to verify system meets capability and throughput requirements

• Procured by Battelle via separate subcontract

M2PC HTP-APP

Acquisition Strategy

Acquisition Strategy & Characteristics cont.

• Firm Fixed Price Contract with Set Price of $47M

• Minimum requirements plus stretch goals that can be met within the set contract amount are the basis for award

• Two-Step, Best Value, Source Selection

• Proposals Evaluated in accordance with an approved Source

Selection Plan (SSP) and established Evaluation Criteria in the

RFP

• 2 Phase Review and Approval required by DOE-PNSO &

DOE IRB/HCA

• Acquisition Plan & Request for Proposal - Completed

• Contract Award

M2PC HTP-APP

Acquisition Strategy

M2PC HTP-APP

Source Selection

Source Selection

Approach: Two-Step, “Best Value”, Source Selection

Step 1: Review and Evaluation of all Offerors Received Verify Mandatory Go/No-Go Requirements are Met Evaluate & Score Step 1 Technical Proposals – no conceptual design Top 3 Offerors Advance to Step 2

Step 2: Evaluation of Highest Qualified Offerors Conduct Oral Presentations/Interviews Evaluate & Score Step 2 Technical (conceptual design) and Price

Proposals Stipends to the unsuccessful Step 2 Offerors (after contract award)

Basis of Award: Best Value Contract award will be made to the Offeror with the highest evaluated proposal for Step 2 who’s determined to be the “best value"

Request for Proposal (RFP)

Key Elements and Structure Scope Overview Basis of Award o 2-Step, Source Selection o Stipends (for Step 2 Unsuccessful Offers) o Set Contract Price and Funding Profile

Information/Instructions Draft Contract o Contract Clauses & Requirements o Terms and Conditions

Attachments o Performance Specification o General Requirements o Conceptual Design Report (for Information/Reference Only) o Proposal Submission Requirements o Evaluation Criteria o Notification of Intent to Propose o Price Proposal and Milestone Worksheet o Reps and Certs o Supplement to the General Provisions o Onsite Work Hazards Form

M2PC HTP-APP

Request for Proposal

Items for Awareness - Conceptual Design Report (CDR)

The CDR is being included as part of the RFP is to mitigate conflict of interest concerns.

Ensures all potential Offerors have the same information available from the CDR development effort in order to eliminate any unequal access to information concerns.

Section 2.2.1 in the P-Spec discusses the CDR, how it was used in the process, that it is for information only.

The CDR does NOT indicate or establish requirements or criteria that are to be used as part of the offered HTP-APP system designs.

Items for Awareness - Price Proposal and Stretch Goals

Offers with a higher number of stretch goals committed to within the set firm fixed price (as part of the base) will be evaluated more favorably.

Propose price on all stretch goal options which are associated with a "No" that are in excess of the set price of $47M.

Pricing of stretch goal options is the incremental difference between each stretch goal.

Items for Awareness - Milestones

Milestone payment amounts must add up to $47,000,000 and shall be equitable for the amount of work and duration anticipated for each proposed milestone.

Milestones should align with the proposed conceptual project schedule and take into consideration the funding profile limitations, major project milestones, and coordination with the facility contractor.

Milestone payment schedule will be incorporated into the final contract award.

RFP Responses

• Thoroughly review the RFP and all accompanying attachments

• Provide proposal in accordance with Proposal Submission

Requirements and Evaluation Criteria

Submit via email to Samantha.Ernst@pnnl.gov

Questions submitted by 4:00pm Pacific Time on January 13, 2025

Intent to Propose submitted by 4:00pm Pacific Time on January 13, 2025

Step 1 Proposals due by 4:00pm Pacific Time on January 24, 2025

Step 2 Proposals due by 4:00pm Pacific Time on April 18, 2025 (for down-selected Offerors only)

RFP Response Requirements mailto:Samantha.Ernst@pnnl.gov